ijN,-i,:ivj,?^' i:i-ii:S:i?;;^;^S3i3^^ Xibrat^ OF THE IRew l^orl? State Deterinari? College Cornell University Library The original of tiiis book is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924000313829 PREVENTIVE MEDICINE AND HYGIENE PREVENTIVE MEDICINE AND HYGIENE BY MILTON J. ROSENAU PROFESSOR OF PREVENTIVE MEDICINE AND HYGIENE, HARVARD; FORMERLY DIRECTOR OF THE HYGIENIC LABORATORY, U. S. PUBLIC HEALTH SERVICE WITH CHAPTERS UPON SEWAGE AND GARBAGE, BY GEORGE C. WHIPPIJE, PROFESSOR OF SANITARY ENGINEERING, HARVARD VITAL STATISTICS, BY CRESST L. WILBUR, CHIEF STATISTICIAN, BUREAU OF THE CENSUS, DEPARTMENT OF COMMERCE AND LABOR THE PREVENTION OF MENTAL DISEASES, BY THOMAS W. SALMON, DIRECTOR OF SPECIAL STUDIES, NATIONAL COMMITTEE FOR MENTAL HYGIENE, ETC. NEW YORK AND LONDQN i.>^^ D. APPLETON AND COMPANY 1914 Copyright, 1913, by D. APPLETON AND COMPANY £61 Printed in the United States of America TO MY WIFE PREFACE This book has been written in response to a demand for a treatise based upon modern progress in hygiene and sanitation. The work is planned to include those fields of the medical and related sciences which form the foundation of public health work. So far as I know^ no other book on the subject covers the broad field considered in this volume. The progress in hygiene and sanitation has been so rapid that the subject of preventive medicine has become a specialty, and its scope has become so broad that the question throughout the making of this book has been rather what to leave out than what to include. The facts here brought together are widely scattered in the literature and many of them are difficult of access; they have been collected for the convenience of the student of medicine and the physician, as well as those engaged in sanitary engineering or public health work. During twenty-three years of varied experience in public health work it has been my good fortune to have served as quarantine officer, in epidemic campaigns, in epidemiological investigations, and in public health laboratories, at home, on the Continent, and in the tropics. The fruits of these experiences are reflected in this book, which may be taken as representing my personal views gained in the field, in the laboratory, in the classroom, and in administrative offices. It is wellnigh impossible to prevent or suppress a communicable disease without a knowledge of its mode of transmission. This is the most important single fact for successful personal prophylaxis, as well as in the general warfare against infection; therefore, the com- municable diseases have been grouped in accordance with their modes of transference. Each one of the important communicable diseases is dis- cussed separately in order to bring out the salient points upon which prevention is based. The classification adopted is believed to be unique and should prove helpful to those who are especially concerned in the prevention of infection. vii viii PEEFACE The book may be considered in two parts, namely, that which deals with the person (liygiene) and that which deals with the environ- ment (sanitation). The first part includes the prevention of the communicable diseases, venereal prophylaxis, heredity, immunity, eu- genics, and similar subjects. The second part deals with our environ- ment in its relation to health and disease and includes a discussion of food, water, air, soil, disposal of wastes, vital statistics, diseases of occu- pation, industrial hygiene, school hygiene, disinfection, quarantine, isola- tion, and other topics of sanitary importance, as well as subjects of interest to health officers. All the important methods used in public health laboratories are described. To have made this book in monographic style with references to authorities for every statement would have resulted in an unwieldy work of impractical size and form. The textbook style has therefore been adopted and citation of authorities for facts that are now well estab- lished has been regarded as unnecessary. In this respect it may seem that I have given scant credit to many workers from whose writings I have borrowed results, thoughts, and sometimes words or even sen- tences. At the end of each chapter will be found a list of references to articles or books that I have especially drawn upon, and I desire to acknowledge my obligations to these sources as well as to refer the reader to them for further study of particular subjects. I have also drawn freely upon my own previous writings and those of my co-workers in compiling this book. The chapter on "Disinfection" is based upon my book entitled: "Disinfection and Disinfectants," published by P. Blaki- ston's Sons & Co., Philadelphia, 1902. I have received generous help from a number of friends and it is a pleasure here to acknowledge especially my obligation to Dr. David L. Edsall for reading and correcting the chapter on "Diseases of Occupa- tion," to Dr. John F. Anderson and Dr. Joseph Goldberger for re- vising the chapters upon "Measles" and "Typhus Fever," to Prof. George C. Whipple for reading and improving the chapter upon "Water," to Charles T. Brues for many suggestions in the section upon insect-borne diseases, and to Prof. W. E. Castle for a similar service with the section on "Heredity." Dr. Charles Wardell Stiles- has kindly furnished infor- mation concerning the relation of parasites to soil. I also desire to express my obligations to Prof. Arthur I, Kendall, Dr. Harold L. Amoss, PEEFACB ix Dr. Lewis W. Hackett, Prof. William D. Frost, and Miss Emily G. Philpotts. It has been my object to give in this volume the scientific basis upon which the prevention of disease and the maintenance of health must rest. Exact knowledge has taken the place of fads and fancies in hygiene and sanitation ; the capable health officer now possesses facts concerning infections which permit their prevention and even their suppression in some instances. Many of these problems are complicated with economic and social difficulties, which are given due consideration, for preventive medicine has become a basic factor in sociology. CONTENTS SECTION I PREVENTION OF THE COMMUNICABLE DISEASES PAGS I. — ^Diseases Having Specific or Special Prophylactic Measures 1 Smallpox and Vaccination : Historical Note, 1 ; Vaccination, 3 ; Vaccine Virus, 3; Methods of Vaccination, 8; Indices of a Suc- cessful Vaccination, 11; The Immunity, 14; Revaccination, 15; Claims for Vaccination, 17; Vaccination of Exposed Persons, 17; Dangers and Complications, 19; Government Control of Vaccine Virus, 21; The Unity of Cowpox and Smallpox, 21; Compulsory Vaeeination, 22; Inoculation or Variola Inoculata, 23; Prevalence of Smallpox, 25; Epidemiology, 27; Modes of Infection, 27; Re- sistance of the Virus, 28; Smallpox in the Vaccinated and Un- vaccinated, 29; Result of Vaeeination in Germany, 33; Isolation and Disinfection, 33. Rabies: General Considerations, 36; Period of Incubation, 38; Entrance and Exit of the Virus, 38; Relative Danger of Bites, 38; Viability, 39; Prophylaxis, 39; Local Treatment of the Wound, 40; Pasteur Prophylactic Treatment, 41. The Venereal Diseases : Syphilis, 50 ; Gonorrhea, 53. Venereal Prophylaxis and Hygiene of Sex: Attitude, 55; Education, 55; Registration of Cases, 57; Continence, 57; Per- sonal Hygiene, 58; Prostitution, 58; Medical Prophylaxis, 58; Segregation, 59. Preventable Blindness : Ophthalmia Neonatorum, 61 ; Preva- lence, 62; Prevention, 63. Tetanus: Etiology, 66; Incubation, 70; Resistance, 70; Prophy- laxis, 72. II. — Diseases Spread Largely Through the Alvine Discharges 74 Typhoid Eever: General Considerations, 74; Prevalence, 75; Channels of Entrance and Exit, 80 ; Diagnosis, 80 ; Bacillus Car- riers, 83; Resistance of the Virus, 83; Typhoid Bacillus in Na- ture, 84; Modes of Spread, 86; Preventive Typhoid Inoculations, 94; Management of a Case so as to Prevent Spread, 98; Sum- mary — Personal Prophylaxis, 100. xi xii CONTENTS Cholera: General Considerations, 101; Cause and Contributing Causes of Cholera, 102; Diagnosis, 103; Modes of Transmission, 104; Immunity and Prophylactic Inoculations, 108; Quarantine, 109; Personal Prophylaxis, 110; Summary — Prevention, 110. Dysentery: Classification, 111; Modes of Transmission, 112; Resistance, 113; Immunity, 113; Personal Prophylaxis, 113. Hookworm Disease: Distribution, 114; Varieties of Hookwonm, 115; Modes of Transmission, 115; The Parasite, 116; Immlunity, 118; Resistance of the Parasite, 118; Prevention, 119; Collateral Benefits, 121. III. — Diseases Spread Largely Through Discharges prom the Mouth and Nose 122 Tuberculosis : General Considerations, 122 ; Difference between the Human and the Bovine Tubercle Bacilli, 123; Bovine Tuber- culosis in Man, 124; Modes of Infection, 129; Immunity, 135; Resistance of the Virus, 137; Prevention, 138. Diphtheria : General Considerations, 143 ; Modes of Transmis- sion, 144; Resistance, 149; Immunity, 149; Prevention, 149; Pre- vention of Post-diphtheritic Paralysis, 151; Prevention of Serum Sickness, 152; Historical Note, 153. Measles : General Considerations, 154 ; Immunity, 155 ; Resis- tance of the Virus, 156; Modes of Transmission, 156; Preven- tion, 158. Scarlet Tever: Modes of Transmission, 160; Immunity, 163; Prophylaxis, 163. Whooping Cough : Mode of Transmission, 166 ; Immunity, 166 ; Prevention, 167; Mortality, 167. Mumps, 168. Lobar Pneumonia: General Considerations, 168; Modes of Transmission, 169 : Resistance of the Virus, 169 ; Immunity, 170 ; Prevention, 170. Influenza: Immunity, 172; Modes of Transmission, 172; Pro- phylaxis, 173. Common Colds : General Considerations, 173 ; Prevention, 175. Cerebrospinal Fever: General Considerations, 176; Preven- tion, 179. IV. — Insect-borne Diseases 181 General Considerations, 181. Insecticides: Preparation of the Room for Tumigation, 187; The Relative Efficiency of Insecticides, 188; Sulphur, 190; For- maldehyde, 191; Pyrethrum, 192; Phenol-camphor, 193; Hydro- CONTENTS xiii PAGE cyanic Acid Gas, 194; Bisulphid of Carbon, 195; Petroleum, 196, Arsenic, 197. Mosquitoes: Life History and Habits, 200; Destruction of Mos- quitoes, 202; Malaria, 207; Yellow Fever, 212; Dengue, 220; Filariasis, 222. Flies: General Considerations, 223; Life History of the Musca Domestica, 224; Life History of Stomoxys Caleitrans, 226; Flies as Mechanical Carriers of Infection, 226; Suppression, 230; Sleeping Sickness, 232; Pappataei Fever, 237. Fleas: General Considerations, 237; Pulicides, 240; Relation of Plague to Rats and Fleas, 240. Eats and Other Rodents : General Considerations, 242 ; Breed- ing and Prevalence, 243; Migration, 244; On Vessels, 245; Food, 245; Habits, 245; Plague in Rats, 246; Rat Leprosy, 248; Trichi- nosis, 248; Other Parasites, 248; Economic Importance, 248; Suppression, 249; Squirrels, 253; Plague, 254. Ticks: General Considerations, 261; Texas Fever, 263; Rocky Mountain Spotted Fever, 263; Relapsing Fever, 266; South African Tick Fever, 267. Lice: General Considerations, 268; Typhus Fever, 269. Bedbugs: General Considerations, 272; Suppression of Bedbugs, 273; Kala-azar, 274. References, 274. V. — Miscellaneous Diseases 275 Infantile Paralysis : General Considerations, 275 ; Resistance of the Virus, 277; Immunity, 277; Modes of Transmission, 277. Chickenpox, 280. Glanders: Diagnosis, 281; Prevention, 284. Anthrax: Resistance, 285; Immunity, 285. Foot-and-Mouth Disease, 286. Malta Fever: Modes of Transmission, 288; Goats' Milk and Malta Fever, 290 ; Resistance, 291 ; Prevention, 291. Leprosy : General Considerations, 292 ; Immunity, 293 ; Rat Leprosy, 293; Modes of Transmission, 294; Prevention, 296; Specific Prevention, 297. Mental Diseases (By Thomas W. Salmon, M. D.) : General Considerations, 298; Infectious Diseases Which Cause Insanity, 299; Acute and Chronic Poisonings Which Cause Insanity, 301; Head Injuries and Insanity, 304; Heredity and Insanity, 304; Psychical Causes, 306; Economic Factors, 306; Immigration, 307; Agencies Available for the Application of Preventive Measures, 308. xiv CONTENTS PAGE VI. — Some General Considerations 313 Sources of Infection, 313 ; Modes of Transference, 314 ; Carriers, 315; Missed Cases, 316; Channels of Infection, 316; "Contagious" and "Infectious," 317; Epidemic, Endemic, Pandemic, and Proso- demic, 317; The Management of an Epidemic Campaign, 319. Quarantine: General Considerations, 321; Maritime Quaran- tine, 322; Quarantine Procedures, 326; The Bill of Health, 327; Equipment of a Quarantine Station, 328; Qualifications of a Quarantine Officer, 328; Disinfection of Ships, 329; Cargo, 332; Ballast, 332; Foreign Inspection Service, 333; National versus State Quarantine, 333; Interstate Quarantine, 334. Isolation, 334. SECTION II IMMUNITY, HEREDITY AND EUGENICS I. — Immunity 337 General Considerations, 337; Mechanism of Immunity — Theories of Immunity, 338; Natural Immunity, 341; Acquired Immunity, 343; Mixed Immunity, 343; How Immunity May Be Acquired, 343; Specificity, 346; Local and General Immunity, 347; Bacillus Carriers or Immunitas Non Sterilans, 348 ; Latency, 350 ; Lowered Resistance, 351; Ehrlich's Side-chain Theory of Immunity, 355; Antitoxic Immunity, 360. Toxines, 360. Antitoxins: General Considerations, 365; Gibson's Method of Concentrating Diphtheria Antitoxin, 370; Dried Antitoxin, 370; Mode of Action, 371. Endotoxins, 372. Tetanus Toxine: General Considerations, 373; Mode of Ac- tion, 376. Tetanus Antitoxin, 377. Standardization op Antitoxic Sera: Standardization of Diph- theria Antitoxin, 378; Standardization of Tetanus Antitoxin, 380. Phagocytosis, 384. Opsonins: The Opsonic Index, 388. Lysins : General Considerations, 388 ; Pf eiffer's Phenomenon, 389. Hemolysis, 392. Cytotoxins, 393. The Bordet-Gengou Phenomenon — Fixation of Comple- ment, 394. CONTENTS XV PAGE The Nbisseb-Wechsberg Phenomenon or Deviation of the Complement, 395. isohemolysins, 396. Peecipitins: General Considerations, 396; Tests for Blood, 399. Agglutinins, 400. Anaphylaxis: General Considerations, 403; Examples of Ana- phylaxis, 404; Experimental Serum Anaphylaxis, 404; Specificity, 406; Sensitization by Feeding, 408; Maternal Transmission, 408; Serum Anaphylaxis in Man, or Serum Sickness, 408; Hypersus- ceptibility and Immunity Produced by Bacterial Proteins, 411; Relation of Anaphylaxis to Protein Metabolism, 411 ; Relation of Anaphylaxis to Endotoxins, 412; Relation of Anaphylaxis to Tuberculosis, 412; Relation of Anaphylaxis to Vaccination, 413; Other Practical Relations of Anaphylaxis, 413. References, 414. II. — Heredity and Eugenics 415 General Considerations, 415 ; Prevention of Propagation of Defec- tives, 416 ; Statistics of Defectives, 418 ; Degenerate Eamilies, 419. Eugenics, 423. Principles op Heredity : Variation, 425 ; Darwin's Theory, 425 ; Mutation, 426; De Vries^Discontinuous Evolution, 427; Weis- mann's Views, 427; Mendel's Law, 428; Atavism and Reversion, 432; Galton's Law of Filial Regression, 433. The Cell in Heredity, 434. Biometry, 436. Heredity versus Environment, 440. Immunity Gained Through Inheritance, 440. III. — The Hereditary Transmission of Disease .... 442 General Considerations, 442; The Mierobic Diseases, 445; Hered- itary Transmission of a Tendency to a Disease, 445; Tubercu- losis, 446; Syphilis, 446; Cancer, 448; Leprosy, 448; Deaf- mutism, 448; Albinism, 448; Color-blindness or Daltonism, 449; Hemophilia, 450; Gout, 451; Brachydactylism, 451; Polydac- tylism, 451; Myopia, 451; Cataract, 451; Retinitis Pigmentosa, 451; Diabetes Mellitus, 452; Orthostatic Albuminuria, 453; Al- coholism, 453; Epilepsy, 453; Huntington's Chorea, 454; Fried- reich's Disease — Hereditary Ataxia, 455; Imbecility, Defectives and Delinquents, 455; Insanity, 455. Eepeeences, 457, xvi CONTENTS SECTION III FOODS PAGE I. — General Consideeations 458 The Uses of Food, 460. Classification of Foods, 461. Amount of Food: Excessive Amounts, 462; Insufficient Food, 463; Unbalanced Diets, 464. Adulteration of Food, 465. Decomposed Foods: General Considerations, 468; Fermentation and Putrefaction, 469; "Ptomaine'' Poisoning, 469. Preservation of Foods : General Considerations, 473 ; Cold, 474 ; Drying, 477; Salting and Pickling, 479; Jellies and Preserves, 480; Smoking, 481; Canning, 481; Chemical Preservatives, 483. Preparation of Food: Cooking, 491; Methods of Cooking, 492. II. — Animal Foods : Milk . - 494 General Considerations, 494; Composition, 495; Milk Standards, 499; Ferments or "Life" in Milk, 500 ; "Leukocytes" in Milk, 502; Excretion of Drugs in Milk, 503 ; Differences between Cow's Milk and Woman's Milk, 503; Classification of Milk, 504; Decomposi- tion of Milk, 506; Bitter Milk, 508; Colored Milk, 508; Adul- terations of Milk, 509 ; Dirty Milk— The Dirt Test, 509 ; Bacteria in Milk, 509; Germicidal Property of Milk, 511; Diseases Spread by Milk,' 512; Character of Milk-borne Epidemics, 516; Fresh Milk Products, 517; Inspection, 518; Pasteurization, 518; Effect of Heat Upon Milk, 522. Bacteriological Examination of Milk: Number of Bacteria, 523 ; Kinds of Bacteria, 524. Microscopic Examination: The Stewart-Slack Method, 525; The Doane-Buckley Method, 526 ; The Prescott-Breed Method, 526. Chemical Analysis of Milk: Total Solids, 527; Determination of Total Solids, 527; Determination of Fats, 528; Determination of Milk Sugar, 531 ; Determination of Proteins, 532 ; Water, 532 ; Reaction, 533; Specific Gravity, 534; Heated Milk, 535; Tests for Enzymes and Their Significance, 535. References, 537. III. — Animal Foods : Meat, Fish, Eggs, Etc -538 Meat: Structure and Composition of Meats, 538; Nutritive Value of Meat, 539 ; Sources of Meat, 540 ; Recognition of Spoiled Meat, 540; Prevention, 541; Meat Preservatives, 541; Meat In- spection, 542; Meat Poisoning, 552, CONTENTS xvii PAGE Fish: Physiological Fish Poisoning, 564; Bacterial Poisons, 564; Fish Tapeworm, 565. Shellfish: General Considerations, 565; Mussel Poisoning, 567; Miscellaneous, 567. Bob Veal, 567. Eggs, 568. IV.— Plant Foods 571 Poisoning from Plant Foods: Ergotism, 571; Lathyrism, 572; Mushroom Poisoning, 572 ; Potato Poisoning, 573 ; Beri-beri, 574 ; Pellagra, 577. SECTION IV AIR I. — Composition op the Air 582 General Considerations, 582; Oxygen, 584; Nitrogen, 585; Argon, 585; Ozone, 585; Hydrogen Peroxid, 586; Ammonia, 586; Min- eral Acids, 587; Carbon Dioxid, 587; COj as an Index of Vitia- tion, 588; Methods for Determining Carbon Dioxid, 590. II. — Pressure, Temperature, and Humidity 598 Pressure: Normal Atmospheric Pressure, 598; Diminished At- mospheric Pressure, 598; Increased Atmospheric Pressure, 600; Barometers, 601. Movements op the Atmosphere, 602. Temperature op the Air : General Considerations, 603 ; Methods of Recording Temperature, 604. Humidity: Aqueous Vapor, 605; Methods of Determining Hu- midity in the Air, 610; Relation of Humidity and Temperature to Health, 613 ; Effects of Warm, Moist Air, 616 ; Effects of Cold, Damp Air, 616 ; Effects of "Warm, Dry Air, 617. III. — Miscellaneous 619 Odors, 619; Light, 620; Electricity, 621; Radioactivity, 622; Smoke, 622; Fog, 625; Dust, 625; Dust and Disease, 627; Meth- ods for Examining Dust, 628. IV. — ^Bacteria and Poisonous Gases in the Air .... 630 Bacteria in the Air: General Considerations, 630; Method for Determining Bacteria in the Air, 631 ; Air and Infection, 632. Poisonous Gases in the Air: Carbon Monoxid, 635; Illumi- nating Gas, 636 ; Other Gases in the Air, 638. Sewer Gas : General Considerations, 638 ; Bacteria in Sewer Air, 639; Ventilation of Sewers, 640, 3 xviii CONTENTS PAGE V. — Fresh and Vitiated Air 641 Benefits of Fresh Air, 641. Effects of Vitiated Air: General Considerations, 641; The Effects of Increased Carbon Dioxid and Diminished Oxygen, 643; Poisons in the Expired Breath, 644; Physical Changes in the Air, 647. Summary, 649. VI. — Ventilation and Heating 651 Ventilation : General Considerations, 651 ; Vitiation by Respira- tion, 653; The Amount of Air Eequired, 654; Standards of Purity — EfBciency of Ventilation, 656; The Size and Shape of the Room, 657; Inlets and Outlets, 659; External Ventilation, 661; Natural Ventilation, 661 ; Mechanical Ventilation, 665. Heating: General Considerations, 665; Open Fires, 666; Frank- lin Stoves, 667; Open Gas Heaters, 667; Hot-air Furnaces, 667; Hot-water and Steam Pipes, 668; Electric Heating, 668; Cooling of Rooms, 668. SECTION V SOIL I. — General Considerations 670 Classification of Soils, 671; Surface Configuration, 671; Compo- sition of the Soil, 672; Soil Air, 674; Soil Water, 675; The Nitrogen Cycle, 676; The Carbon Cycle, 680. II. — The Soil and Its Relation to Disease 681 Bacteria in Soil, 681; Pollution of the Soil, 682; Dirt, 683; Cleanliness, 684; Influence of Soil Upon Health, 684; Diseases Associated with the Soil, 685. SECTION VI WATER I. — General Considerations 691 Composition, 692; Classification of Water, 692; Properties of Water, 693; Uses of Water in the Body, 693; Amount of Water Used and Wasted, 694; Double Water Supplies, 697. Sources op Water: Rain Water, 698; Surface Waters, 702; Ground Water, 708. Sources and Nature op Water Pollution and Infection : General Considerations, 717; Simple Tests to Determine Sources of Pollution, 718; Interstate Pollution of Streams, 719; Care of Catchment AreaS; 720, CONTENTS xix PAGE II. — Sanitaey Analysis of Watee 722 Standard Methods, 722. Odoes and Tastes: General Considerations, 723; Method of Determining Odor, 726; Prevention and Removal of Tastes and Odors, 727. Color: General Considerations, 728; Method for Estimating Color, 729. Ttjebidity : General Considerations, 729 ; Methods for Estimating Turbidity, 731. Reaction, 731. Total Solids: General Considerations, 732; Methods for Esti- mating Total Solids, 733. Hardness: General Considerations, 733; Methods for Determin- ing Hardness, 735. Organic Matter: Tree Ammonia, 736; Albuminoid Ammonia, 739; Nitrites, 741; Nitrates, 742. Chlorin: General Considerations, 744; Determination of Chlo- rin, 745. Oxygen: Oxygen Consumed, 746; Dissolved Oxygen, 748. Iron: General Considerations, 749; Iron Pipes, 750. Lead: Tests, 751. Expression or Chemical Results, 751. III. — MiCEOScoPiCAL Examination op Water 753 Methods of Microscopical Examination, 753; Significance of the Examination, 754. Bacteriological Examination: General Considerations, 754; Number of Bacteria in Water, 755; Kinds of Bacteria in Water, 758; Colon Bacillus, 759; Sewage Streptococci, 761; Typhoid Bacillus, 761; Cholera, 761. IV. — Inteepretation op Sanitaey Watee Analysis .... 763 General Considerations, 763; Allowable Limits, 764; Illustrative Analyses Interpreted, 765. V. — The Pueipication op Watee 776 Natuee's Method op Puripying Watee : General Considerations, 776; Evaporation and Condensation, 777; Self -purification of Streams, 777; Storage in Lakes and Ponds, 779; Sunlight, 779. XX CONTENTS FAQE Distilled Water, 780. Boiled Water, 780. Filters: Slow Sand Filters, 781; Mechanical Filters, 788; Household Filters, 792; Scrubbing or Roughing- Filters, 793; Screening, 793. Storage, 793. Sedimentation, 794. Chemical Methods of Puripying Water: Ozone, 794; Chlo- rinated Lime Bleaching Powder, 797; Permanganate of Potash, 798; Alum or Sulphate of Aluminum, 799; Metallic Iron: The Anderson Process, 800; Copper Sulphate, 800. Ultra-violet Rays, 801. VI. — Water and Its Relation to Disease 803 General Considerations, 803. The Mills-Reincke Phenomenon, 804. Non-specific Diseases Dub to Water: General Considerations, 806; Goiter, 807; Lead Poisoning, 810. Specific Diseases Dub to Water: General Considerations, 813; Cholera, 815; Typhoid Fever, 822; Dysentery, 834; Diarrhea, 835; Malaria, 836; Yellow Fever, 837; Animal Parasites, 837. . Ice: General Considerations, 837; Natural Ice, 838; Manufac- tured Ice, 839; Properties of Ice, 840; Ice and Disease, 840. References, 842. SECTION VII SEWAGE DISPOSAL Bt George C. Whipple General Considerations: Importance of Speedy Removal of Fecal Matter, 843 ; Dry Earth System, 844 ; Water Carriage Sys- tem, 844; Separate and Combined Systems, 845; Quantity of Sewage, 846; Composition of Sewage, 846; Ventilation and Flushing of Sewers, 848. Stream Pollution : Sewage Disposal by Dilution, 848 ; Hygienic Aspects of Stream Pollution, 850; Protection Against Pollution, 851; Water Filtration, 851; Treatment of Sewage, 851. Cooperative Sanitation, 863. The Rural Problem op Sewage Disposal, 864. References, 868. CONTENTS xxi SECTION VIII REFUSE DISPOSAL By George C. Whipple PAGE General Considerations, 870; Incineration Plants, 872; Reduction Plants, 872; Feeding Garbage to Hogs, 873; Collection of Gar- bage, 873; References, 873. SECTION IX VITAL STATISTICS By Ceessy L. Wilbur, M. D. General Considerations, 874; Necessity of Vital Statistics in Public Health Work, 875 ; Neglected Condition of Vital Statistics in the United States, 876; Collection of Vital Statistics, 878; Population, 888; Vital Rates, 888; Specific and Corrected Death Rates, 901; Classification of Causes of Death, 905; References to Sources and General Precautions in Use of Statistical Data, 908. SECTION X INDUSTRIAL HYGIENE AND DISEASES OF OCCUPATION General Considerations, 911. Some Fundamental Considerations in Prevention: General Considerations, 915; Hours of Work, 916; Fatigue, 916; Children, 917; Women, 918; Factory Inspection, 919; Pre- ventable Accidents, 920; Sedentary Occupations, 921. Diseases of Occupation: Classification of the Occupational Diseases, 921; Lead, 922; Phosphorus, 930; Arsenic, 934; Mer- cury, 935; Carbon Monoxid, 936; Hydrogen Sulphid, 937; Dusty Trades, 938; The Textile Industries, 939; Wood Dust, 941; Min- ing, 941; Effects of Heat, -942; Parasites, 943; Caisson Disease, 944. References, 944. SECTION XI SCHOOLS General Considerations, 945; School Building, 947; The School- room, 948; School Furniture, 949; Posture, 952; Lighting, 953; xxii CONTENTS Ventilation and Heating, 954; Water-closets and Urinals, 955; Cloak-rooms, 955; Cleanliness, 956; Medical Inspection of Schools, 956; The Communicable Diseases of Childhood, 959; The Eyes, 959; The Ears, 961; The Teeth, 961; Nose and Throat, 961; Diseases of the Skin, 962;- Nervous Diseases and Mental Defects, 963; Vaccination, 964; References, 964. SECTION xn DISINFECTION I. — Geneeal Considerations 966 Definitions, 966 ; Nature's Disinfecting Agencies, 967 ; Cleanliness, 968 ; Symbiosis, 968 ; When and Where to Disinfect, 969 ; Qualifi- cations of the Disinfector, 969; Controls, 969; Disinfection Must Be in Excess of Requirements, 970; The Ideal Disinfectant, 970; Terminal Disinfection, 970 ; Standardization of Disinfectants, 971. II. — Physical Agents op Disinfection 979 Sunlight, 979; Ultra-violet Rays, 979; Electricity, 980; Burning, 980; Dry Heat, 980; Boiling, 981; Steam, 982. III. — Chemical Agents of Disinfection 992 Gaseous Disinfectants: Preparation of the Room, 992; For- maldehyd Gas, 993; Sulphur Dioxid, 997; Hydrocyanic Acid Gas, 1004; Chlorin, 1004; Oxygen, 1005; Ozone, 1005. Liquid Disinfectants : General Considerations, 1006 ; Methods of Using Chemical Solutions, 1008; Biehlorid of Mercury, 1009; Carbolic Acid, 1011; The Cresols, 1013; Formalin, 1014; Potas- sium Permanganate, 1015; Lime, 1016; The Hypochlorites, 1019; Antiformin, 1020; Bromin and lodin, 1021; Ferrous Sulphate, 1021; Sulphate of Copper, 1021; Chlorid of Zinc, 1021. Acids, 1021. Soaps, 1022. Convenient Formula for Disinfecting Solutions: Biehlorid of Mercury — CoiTosive Sublimate, 1023; Formalin, 1023; Milk of Lime, 1024; Carbolic Acid, 1024; Chlorinated Lime, 1024. IV. — ^Methods op Disinfection 1025 Air, 1025; Rooms, 1026; Stables, 1027; Railroad Cars, 1028; Feces, 1030 ; Bed and Body Linen, 1032 ; Books, 1033 ; Cadavers, 1034; Thermometers, 1034; Wells and Cisterns, 1034. LIST OF ILLUSTRATIONS FIGURE 1. — Vaccinia. Course of the eruption from the fourth to the ninth day ........ 2. — Vaccinia. Course of the eruption from the tenth day 3. — Course of vaccination and revaccination 4.^Eatio of mortality of variola for 10,000 of the population, in Boston, from 1841 to 1911, inclusive 5. — Smallpox mortality per 100,000 of population in Breslau 6. — Smallpox mortality per 100,000 of population in Vienna 7. — Smallpox mortality per 100,000 of population in Prussia 8. — Smallpox mortality per 100,000 of population in Austria 9. — Chart showing relation of enforcement of muzzling law to prevalence of rabies in Great Britain . 10. — Curve showing death rate from typhoid fever in Albany before and after filtration of water .... 11. — Influence of public water supplies on the typhoid fever death rate ........ 12. — Immediate and striking effect of purifying a badly infected water supply upon the typhoid situation . 13. — Abrupt reduction in death rates from typhoid fever inci- dent to water purification in four American cities 14. — Hookworms, natural size ...... 15. — Hookworm embryo ....... 16. — Chart computed from the United States census report to show how the opening of schools in autumn increases diphtheria 17. — A South African blood-sucking fly (Pangonia), illustrat- ing long proboscis to pierce heavy fur of certain animals . 18. — Example of sealing doors for purpose of fumigation 19. — Anopheles punctipenis . 20. — Stegomyia calopus (female) . 21. — Head of stegomyia calopus (male) 22. — Eggs of stegomyia calopus . 23. — Larva of stegomyia calopus . 24. — Pupa of stegomyia calopus . 12 13 16 26 30 31 34 35 40 79 85 87 89 115 115 144 183 188 209 214 215 216 216 217 XXlll xxiv LIST OF ILLUSTRATIONS FIGURE PAGE 25. — House fly, showing proboscis in the act of eating sugar . 224 26. — Eggs of house fly, as laid in a mass .... 224 27.— Eggs of house fly 225 28. — Larvse of house fly ...... . 225 29. — Puparium of house fly . . . . . . . 226 30.— Stable fly 226 31. — Head, showing proboscis, stomoxys ealeitrans . . 227 32.— Wing of stable fly 227 33.— The "little house fly" 228 34. — ^Wing of house fly, showing how it carries dust particles 229 35. — The Hodge fly trap on a garbage can . . . 231 36.— Tsetse fly 233 37. — Various gnats ........ 235 38.— The Indian rat flea 238 39. — The common rat flea of Europe and North America . 239 40.— The human flea 239 41. — A squirrel flea 241 42. — General scheme for testing plague rat infection, city of Manila 259 43. — Isolated plague-infested center, Manila, P. I. . . . 260 44.— The Texas fever tick 263 45. — Rocky Mountain spotted fever tick .... 264 46.— The bedbug 272 47. — A device for preventing rats traveling along hawsers . 325 48. — The cell with its various combining groups, or side chains, known as receptors ....... 357 49. — The toxin molecule, showing the haptaphore (combining) group, and the toxaphore (poison) group . . . 357 50. — The first stage of antitoxin formation : a toxin molecule an- chored to a receptor ....... 357 51. — The second stage: continued stimulation causes a repro- duction of receptors ....... 358 52. — Third stage: the receptors beginning to leave the cell . 358 53. — Fourth stage: the receptors have left the cell and float free in the blood — antitoxin ..... 358 54. — The neutralization of a toxin by antitoxin: the free re- ceptors in the blood have united with the toxin = anti- toxic immunity ....... 359 55. — The second order of immunity, showing complement and immune body ....... 359 56. — The third order of immunity, showing an immune body having two affinities ...... 359 57. — History of the family Zero ...... 420 LIST OF ILLUSTRATIONS xxv PIGTJBE PAGE 58. — History (condensed and incomplete) of three markedly able families ........ 423 59. — Wilson's theory of inheritance modified by Locke . . 428 60. — Diagram showing the course of color heredity in the Andalusian fowl, in which one color does not com- pletely dominate another ..... 430 61. — Diagram showing the course of color heredity in the guinea-pig, in which one color completely dominates another ......... 431 62. — Model to illustrate the law of probability or ' ' chance ' ' . 437 63. — Normal heredity curve ....... 438 64. — Family history showing deaf-mutism .... 448 65. — Family history showing polydactylism .... 452 66. — Family history showing Huntington's chorea . . . 454 67. — Family history showing feeble-mindedness . . . 456 68. — Unsanitary surroundings of a cow-barn .... 506 69. — Conditions under which it is difficult to cleanse and disin- fect milk bottles and milk pails . ... 510 70. — A dark, poorly ventilated cow shed, difficult to keep clean 517 71. — Automatic temperature recorder for pasteurizers . . 520 72. — Straus home pasteurizer ...... 521 73. — Trichinella spiralis ....... 560 74. — Tenia solium, the pork or measly tapeworm . . 563 75. — Beef tapeworm ........ 563 76. — Dibothriocephalus latus, the fish tapeworm . ■ . . 565 77. — Portable Haldane apparatus for small percentages of car- bon dioxid ........ 591 78. — Petterson-Palmquist apparatus ..... 594 79.— Fitz air-tester 596 80. — ^Wolpert's air-tester ....... 596 81. — Dewing Co. apparatus ....... 596 82. — ^Diagram showing absolute humidity in grains at different temperatures ........ 607 83. — Sling psychrometer . . . . . . .610 84. — Relative humidity table ...... 611 85. — Dew-point apparatus ....... 612 86. — Table showing the density of smoke, in accordance with the Ringelmann chart, which may be emitted from the various classes of stacks in Boston, Mass., and the dura- tion of such emission ...... 624 87. — Magnus aspirator ....... 632 88. — Double aspirator ..,,..., 632 xxvi LIST OF ILLUSTRATIONS FIGUBE PAGE 89. — The position of inlets and outlets, and their relation to the air currents in a room . . . . .660 90. — Window ventilator ....... 663 91. — Diagrammatic sketch of various provisions for ventila- tion 664 92. — The nitrogen cycle ....... 677 93. — The nitrogen cycle in diagrammatic vertical section . 678 94.— Ground water 708 95. — Usual method of pollution and even infection of wells 712 96. — Proper construction of a well ..... 713 97. — ^Popular idea of how wells become infected from surface pollution 714 98. — Depression of the ground water level by pumping and ten- dency to draw nearby pollution from the soil or cesspool 715 99. — In a limestone formation it is difSeult to tell anything about the source of water obtained from a well . 715 100. — Spring exposed to contamination from surface washings from the hill above. Spring protected from surface washings, and with bucket which can be filled without contaminating the flow ...... 717 101. — Algas: uroglena; spirogyra; resting spores of spirogyra: chlamydomonas showing resting condition and repro- ductive bodies ........ 724 102. — Algffi: clathroeystis ; anabajna; oscillatoria ; asterionella ; navicula showing structure of diatom . . . 725 103. — The oil droplets in a diatom ...... 726 104. — Diagram illustrating the character of the ground water in relation to soil pollution, to assist the interpretation of a sanitary analysis ....... 765 105. — Diagram showing the location of samples . . . 775 106.— Section of an English filter bed 782 107. — The arrangement of a slow sand filter .... 783 108.— Diagram illustrating "loss of head" . . . .786 109. — Asiatic cholera and the Broad Street pump, London, 1854 816 110. — Asiatic cholera and the Broad Street well, London, 1854 819 111. — Map showing Hamburg water supply .... 821 112. — Change in water supply ...... 824 113. — Mean death rates from typhoid fever, 1902 to 1906, in 66 American cities and 7 foreign cities . . . 825 114.— Map of Plymouth, Penn., in 1885 828 115. — Map showing water supply of Ashland, Wis. . . 830 116. — Typical section of an Imhoff tank .... 853 LIST OF ILLUSTRATIONS xxvii FIGURE PAGE 117. — Imhoff tanks and sludge drying beds, Emscher District, Germany ........ 854 118. — Chemical precipitation plant at Worcester, Mass., inlet . 855 119. — Chemical precipitation plant at Worcester, Mass., outlet 855 120. — Triple contact beds at Hampton, England . . . 856 121. — Inclined screen, operated by water wheel, Birmingham, England 857 122. — Trickling filters and final settling basin and roughing filter at Hyde, England 858 123. — Trickling filter at Birmingham, England . . . 859 121. — Eemoving sludge from a septic tank at Manchester, England 861 125. — Septic tank and chemical precipitation tanks at Rochdale, England 862 126. — Burying sludge from hydrolytic tank at Hampton, Eng- land 863 127. — Chemical precipitation tanks at Glasgow, Scotland. Lower end 865 128. — Chemical precipitation tanks at Glasgow, Scotland. Upper end ......... 865 129. — Intermittent sand filtration bed at Brockton, Mass. . 866 130. — Filter bed with sand ridged for winter operation at Brockton, Mass 867 131. — Discharge of sewage upon a filter bed at Brockton, Mass. 868 132. — Red oxid of lead and litharge, being mixed in the manu- facture of storage batteries ..... 913 133. — An effective dust-removing system in the boot and shoe industry ......... 917 134. — System of hoods and ventilators to carry ofE the fumes from the furnaces in a foundry ..... 921 135. — A worker with lead oxid, showing respirator to protect himself against the poisonous dust .... 925 136.— The stone industry 929 137. — Workman exposed to zinc fumes in brass casting, causing a condition known as "brass-founders' ague" . 933 138. — Drum with nails which combs out the small pieces of broom corn ........" 938 139.— Faulty posture 950 140.— The Heusinger desk 951 141. — Boston school-desk and chair ...... 952 142. — Device for determining carbolic coefficients . . . 973 143. — Hot air sterilizer ....... 981 144. — Section through Arnold steam sterilizer .... 983 xxviii LIST OF ILLUSTRATIONS FIGURE PAGE 145. — Section through autoclave ...... 984 146. — Bramwell-Deane steam sterilizer ..... 984 147. — Cross section through steam disinfecting chamber . . 985 148. — Longitudinal section througli steam disinfecting chamber 986 149. — Kinyoun-Francis steam disinfecting chamber . . . 988 150. — Automatic thermometer ...... 989 151. — Plan showing the method of installing the double-ended steam chambers at a national quarantine station . . 990 152. — Chart showing application of steam under pressure . 991 153. — Flaring top tin bucket for generating formaldehyd by the permanganate method ....... 996 154. — The pot method of burning sulphur .... 999 155. — Large stack burner for sulphur, with 15 of the 18 pans removed to show construction ..... 1000 156. — Liquefied sulphur dioxid in tin can .... 1001 157. — Section through sulphur furnace ..... 1003 PKEYENTIYE MEDICINE SECTION I PREVENTION OF THE COMMUNICABLE DISEASES CHAPTEE I DISEASES HAVING SPECIFIC OR SPECIAL PROPHYLACTIC MEASURES SMALLPOX AND VACCINATION The prevention of smallpox depends primarily iipcn vaccination, sec- ondarily npon isolation and disinfection. Vaccination v?as the first specific prophylactic measure given to man; it produces an active im- munity to smallpox (variola) . On account of its importance and great practical value this subject vpill be considered in some detail, for much of the antivaccination sentiment is due to ignorance or misconstruction of the facts. Historical Note. — The credit of giving vaccination to the world is due to Jenner, who proved through carefully planned experiments that cowpox protects against smallpox. This fact had been familiar to the farmers and folk of England as a vague tradition for a long time. A young girl who sought medical advice of Jenner, when a student at Sudbury, said, "I cannot take smallpox because I have had cowpox'" ; this remark made a strong impression upon the young medical student. Benjamin Jesty, a Dorchestershire farmer, in 1774 successfully vac- cinated his wife and two sons. Plett, in Holstein, in 1791 also success- fully vaccinated three children. It was Jenner, however, who through logical and scientific methods proved that a person who has had the mild disease, cowpox, enjoys protection against the serious and often fatal disease, smallpox. Waterhouse and others soon repeated and cor- roborated Jenner's experiments and helped to establish the soundness of his conclusions. Jenner made his crucial experiments in 179G, when he transferred the vaccine matter from the hand of a dairy maid (Sarah Nelms) to the arm of a boy about 8 years old — name not given. Sarah Nelms 1 2 SPECIFIC PEOPHYLACTIC MEASUEES scratched her hand with a thorn and "was infected with the cowpox from her master's cows, in May, 1796." Jenner transferred the vaccine virus from the eruption upon the hand of Sarah Nelms to the arm of the 8-year-old boy on May 14, 1796. A typical take followed. "In order to ascertain whether the boy, after feeling so slight an affection of the system from the cowpox virus, was secure from the contagion of the smallpox, he was inoculated the first of July following with variolous matter, immediately taken from a pustule. Several slight punctures and incisions were made on both arms, and the matter was carefully in- serted, but no disease followed. The same appearances were observable on the arm as we commonly see when a patient has had variolous mat- ter applied, after having either the cowpox or the smallpox. Several months afterward he was again inoculated with variolous matter, but no sensible effect was produced on the constitution." In addition to such direct experimental proof, Jenner inoculated smallpox matter into ten persons who had at some previous time con- tracted cowpox. Date of Inoculation Ascertained to with Smallpox Name Have Had Cowpox 1. 1778 Mrs. H. Wien very young 2. 1791 Mary Barge 31 years previously 3. 1792 Sarah Portlock 27 years previously *• [ 1795 ■ I Joseph Merret i William Smith 25 years previously 1, 5, 15 years previously 6. r Elizabeth Wynne 10 months previously 7. i 1797 ) Sarah Wynne 9 months previou.sly 8.^ ( William Kodway 38 years previously 9. After 1782 Simon Nichols Some years previously 10. Not stated John Phillips 53 years previously In Justification of such human experimentation it should be re- membered that at that time the inoculation of smallpox matter into healthy individuals was an acknowledged method of preventing that disease. Jenner himself was inoculated when a boy. The question of "inoculation" (with smallpox) as contrasted with "vaccination" (with cowpox) will be discussed presently. With such proof as this Jenner put a popular belief upon a scien- tific basis. He demonstrated that cowpox is a local and trivial disease in man, that it may be readily transferred from man to man, and that it protects against smallpox. The chain of evidence was complete, but he first proved his thesis to his own satisfaction before he gave it to the world. He said himself : "T placed it on a rock where I knew it would be immovable before I invited the public to take a look at it." Jenner presented the results of his observations to the Eoyal Society, of which he was a Fellow, but the paper was refused. He then published SMALLPOX AND VACCINATION 3 it in 1798 as a book, modestly entitled, "An Inquiry Into the Causes and Effects of the Variolse YaccinEB, a Disease Discovered in Some of the Western Counties of England, Particularly Gloucestershire, and Known by the Name of the Cowpox." Every student of preventive medicine should read this brief "inquiry" in the original. It may be taken as a model of accurate observation and logical presentation, showing great self-restraint and moderation of an observant, imaginative, and judicial mind. Dr. Benjamin Waterhouse, the first professor of Theory and Prac- tice of Physic in the Harvard iledical School, early became convinced of the value of Jenner's demonstration and obtained some vaccine virus from abroad. On July 8, 1800, he vaccinated his son, Daniel Oliver Waterhouse, then five years old. This was the first person vaccinated in America, so far as existing records show. Thomas Jefferson helped materially to spread the new doctrine in this country, and, in 1806, in writing to Jenner, said: "Future nations will know by history only that the loathsome smallpox has existed and by you has been extir- pated." This prophecy has not yet been fulfilled — though eminently possible. VACCINATION Vaccination may be defined as the transference of the virus from the skin eruption of an animal having vaccinia or cowpox into the skin of another animal. For over one hundred years vaccination (from vacca — a cow) was a specific term limited to the introduction of the virus of cowpox into the skin, in order to induce vaccinia and prevent variola. In recent years, however, the term has been used in a generic sense to include the introduction of many different substances in many difierent ways and for many different purposes. Thus we speak of attenuated or killed bacterial cultures as bacterial vaccines; and the subcutaneous inoculation of organic substances of diverse origin and nature is often spoken of as vaccination. We hear of typhoid vaccines, anthrax vaccines, staphylococcus vaccines, and we read in the litera- ture of animals "vaccinated" with extracts of cancer and other organic substances. For distinction between a vaccine and a virus, see page 344. VACCINE VIBXJS Vaccine virus is the specific principle in the matter obtained from the skin eruption of animals having a disease known as "vaccinia" or "cowpox." Vaccine virus is obtained from calves, man, the buffalo, sometimes the camel, and other animals. Cowpox, or vaccinia, is an acute specific disease to which many animals are susceptible, namely, man, cattle, camels, rabbits, monkeys, 4 SPECIFIC PEOPHYLACTIC MBASUEES guinea-pigs, rats, etc. The disease runs practically the same clinical course in all susceptible species. The eruption is always^ local and confined to the site of the vaccinated area; the constitutional symptoms are always benign and usually slight. Vaccinia or cowpox is a benign disease ; when uncomplicated, it has never been known to cause death or leave any unpleasant sequelae. After an incubation period of from three to four days the local eruption begins as a papule which soon develops into a vesicle, and later into an umbilicated pustule. Surrounding the vesicle is a red- dened, inflamed, and tender areola. The neighboring lymph glands are swollen and tender, and there is slight fever lasting several days. The pustule dries, leaving a crust or scab, which comes away, disclosing a typical foveated or pitted scar. Human and Bovine Vaccine Virus. — Vaccine virus may be obtained either from bovine or human sources. Human virus is now seldom used, for the reason that the supply would not be sufficient. Upon the appearance of a smallpox outbreak it is sometimes necessary to have enough virus to vaccinate from one hundred thousand to a million people. Such large quantities evidently could not be obtained from man at any desired time. Another objec- tion to the use of human virus is the possibility, although small, of transmitting syphilis, and perhaps other diseases. When human seed is used the virus may be transferred directly from arm to arm; or the virus may be preserved dry in the scab; or the contents of the vesicle may be kept in either a dried or moist state, as described below for bovine virus. Arm to arm vaccination is still practiced in several parts of the world, particularly in Mexico, where it is claimed that it has the advantage of producing a better take; that the results are surer in that there are fewer unsuccessful vaccinations; and, finally, it is stated that the human virus affords a better immunity, but as to this there is no proof and some doubt. Bovine virus has been used more or less since the time of Jenner, but especially since Copeman showed in 1891 how to purify it with glycerin. It has the great advantage of being readily obtained in any amount and when desired. It further totally eliminates the danger of conveying syphilis and other diseases peculiar to man. Forms of Vaccine Virus. —Vaccine virus may be used in one of three forms: (1) fresh, (2) dry, (3) glycerinated. The fresh virus may be taken from the eruption of the calf or man and transferred directly. Thus the Institut Vaccinale at Paris still prefers to use the fresh virus. The vesicle is squeezed at its base be- tween the blades of forceps, and some of the contents are transferred 'Bare exceptions to this statement will be noted later. SMALLPOX AND VACCINATION 5 directly from the calf to the skin of the arm by means of a thumb lancet or any similar instrument. The vaccinal matter may be dried, and the virus remains potent in this state a very long time, especially if kept cold and protected from the light. The virus may be dried upon a splinter of ivory or other substance. Formerly physicians preserved the dried crust from a typi- cal take. Small portions of this crust were ground, moistened, and then inserted into the skin. Grlycerinated virus consists of vaccine pulp treated with 60 per cent, pure glycerin. This purifies it and hence is preferable. Before taking up the question of glycerination, we must understand the difference be- tween vaccine lymph and vaccine pulp. Vaccine Pulp and Vaccine Lymph. — A distinction is drawn between the pulp and the lymph. The jndp consists of the entire vesicle with its contents, which is scraped from the skin, and is composed of epi- thelium, leukocytes, bacteria, products of inflammatory reaction, the fluid content of the vesicle, debris, etc. The lymph is the serous fluid contained in the vesicle or which often exudes from the broken vesicle. When the eruption is produced on the skin of a calf in a large con- fluent area, the surface of the eruption is scraped away and the exuding lymph is placed upon points by dipping or brushing. Most of the active principle of vaccine virus is contained in the epithelial cells, and this portion is largely lost when only the lymph is used. The pulp, which includes the lymph, therefore contains the virus in greater concentration, and is almost exclusively used in this country at the present time. Dry Points Versus Glycerinated Vaccine Virus. — The old-fashioned dry points were prepared by dipping splinters of. ivory into the vaccine lymph. Later the lymph was collected upon a brush and thus trans- ferred to the ivory point. Bone or glass may be substituted for ivory. Bone is undesirable because it is exceedingly difficult to sterilize. The only advantage of the dry point is its convenience in vaccinating. Its disadvantage is that the virus dried upon such points cannot be purifled as is the case with glycerinated pulp. Further, the points are used as scarifiers and the method of scarification favors irritation and infection of the wound. The dry points practically always contain more bacteria than the glycerinated virus. For these reasons dry points are no longer permitted in interstate traffic in accordance with the federal regulations. The superiority of the glycerinated virus will be evident from a study of the ripening or purification of vaccine virus with glycerin (see below) . The old-fashioned dry points must not be confused with the points now placed on the market by manufacturers containing a drop of glycer- inated lymph. There is no special objection t© these, except that it encourages vaccination by the method of scarification. Some manufac- 3 6 SPECIFIC PEOPHYLACTIC MEASURES turers imitate the old-fashioned dry point by removing most of the glycerin from the ripened pulp by pressing it between blotting papers. The remaining pulp is then attached to the points with sterile dextrose, blood serum, or some other gummy substance. The Process of Ripening. — ^When the vaccine virus is fresh it is said to be "green." Glycerin is added to the green pulp, and after it has acted a certain period of time the virus is said to be "ripe." The use of glycerin for this purpose was introduced by Moncton Copeman in 1891 for the purpose of preserving and purifying the virus. The glycer- in acts as a differential germicide, that is, it preserves ^ the active principle in the vaccine virus, but destroys the frail non-spore-bearing bacteria. In time the virus itself succumbs. Vaccine virus must, there- fore, not be used while green nor when too old. Manufacturers usually date their products as "not reliable after" or "return after" 4 to 6 weeks in the summer time and 3 months during the cold season. Sixty per cent, glycerin of the best quality is used. I have shown that no growth of bacteria, yeasts, or molds takes place in this percen- tage. Two to four parts of 60 per cent, glycerin are added to 1 part of the pulp by weight. The mixture is then thoroughly ground with a mortar and pestle by hand, or between glass rollers in a special mill driven by machinery. The pulp should be thoroughly broken up and a uniform suspension obtained. The amount of glycerin added depends upon the consistency and character of the pulp. The only objection to adding more glycerin would be the greater dilution of the virus, and, therefore, a larger proportion of negative takes. A higher percentage than 60 per cent, of glycerin soon renders the virus inert. The glycerin probably destroys the bacteria by virtue of its dehydrating action. The time required for the virus to ripen depends upon the temperature. Most of the non-spore-bearing bacteria perish in 30 days at 15° to 20° C. Approximately the same effect may be obtained at 37° C. in from 24 to 48 hours. At low temperatures the glycerin has practically no bactericidal effect. The process must always be controlled bacterio- logically. Substances other than glycerin are used for the purpose of purifying vaccine virus. Carbolic acid (0.5 to 1.0 per cent.) is used with success in Japan, and to some extent in this country. Potassium cyanid, chloro- form, chlorobutanol, etc., have been tried, with less success in practice. Bacteria in Vaccine Virus.— Vaccine virus always contains bacteria. There is no such thing as aseptic vaccine virus. The active principle has not been grown in pure cultures. However, the bacteria which con- taminate vaccine virus are, for the most part, harmless to man. They are commonly those that are found on and in the skin of the calf. The 'Glycerin also serves as a preservative for other filterable viruses as foot and mouth disease, anterior poliomyelitis, rabies, etc. ' SMALLPOX AND VACCINATION 7 non-spore-bearing varieties are largely eliminated by the process of ripening. There are fewer bacteria in the typical unbroken vesicle than in a broken, crusty, inflamed eruption. Green virus may contain from a few thousand to over a million bacteria per cubic centimeter. The ripened, glycerinated virus contains comparatively much fewer, and these mostly spores of the hay bacillus, common molds, and other harmless saprophytes. The number of such bacteria in the ripened virus may be taken as an indication of the care and cleanliness with which the virus has been prepared. Staphylococci, streptococci, members of the hemorrhagic septicemic group, and, in a few instances, tetanus spores and the gas bacillus have been found in vaccine virus. Seed Vaccine, — The seed virus may be obtained (1) from cowpox, (2) from smallpox, (3) by retrovaccination. Spontaneous or casual cowpox occasionally occurs, that is to say, the disease appears to arise spontaneously because its origin cannot be traced. Casual cowpox comes either from another case of cowpox or from a case of smallpox. Cattle are not subject to smallpox, but, when small- pox virus is introduced into the skin of a calf, it produces cowpox. When smallpox is thus converted into cowpox, it remains fixed as such, and never reverts to smallpox.^ In several instances in England, Ger- many, and this country the seed virus has been obtained by starting cowpox through the inoculation of smallpox virus. Such virus should not be used until several transfers from calf to calf have been made, for the reason that some of the smallpox virus may be carried over unaltered, during the first few transfers. Eetrovaccination consists in carrying the vaccine virus back from child to calf. By this method its virulence is maintained. Instead of calves, monkeys or rabbits may be used for the purposes of retrovaccination; Propagation. — In the propagation of bovine virus young calves are preferred, because they are more manageable, the skin is more tender, and the eruption is therefore more abundant and typical. With young animals a milk diet may be used, which simplifies the problem of dust contamination from dry feed. If hay or fodder is used, it must first be autoclaved. Either heifers or bull calves are suitable. The animals are held in quarantine for seven days, under observa- tion, to determine the absence of infections such as tuberculosis, glan- ders, foot-and-mouth disease, tetanus, and skin eruptions of any kind. Before vaccinating the calf it is carefully cleaned, and the site of the inoculation is shaved and prepared surgically, but without the use of germicidal solutions. Germicides are not suitable for the reason that they are apt to destroy the vaccine virus. Cleanliness and asepsis are the watchwords. The area selected is usually the abdominal wall be- 'It is highly significant that casual cowpox was formerly much more com- mon when smallpox was much more prevalent. 8 SPECIFIC PEOPHYLACTIC MEASUKES tween the tip of the sternum and the groin, sometimes including the inner side of the thigh. The usual method is to make long, superficial incisions in the skin ahout one inch apart, and the seed virus is gently rubbed into these incisions. The calves must then be kept rigidly iso- lated in a special room, moderately lighted, free from dust, and screened to keep out insects. The temperature of the animal is taken several times daily, and the eruption at each stage of the disease is closely watched and recorded. The virus is usually taken from the animal between the fifth and the eighth day. It is an advantage to take the virus as early as prac- ticable, in order to avoid contaminating infections which may occur when the vesicles suppurate. Only typical and entirely characteristic vesicles should be removed. Before the virus is removed, the animal is killed to avoid pain, and an autopsy is done as soon as the virus is re- moved. If the autopsy shows any lesions indicating infections other than vaccinia, the virus is discarded. It is not wise in propagating vaccine virus to vaccinate too large an area. This favors infections by lowering resistance; less typical eruptions are obtained than when the area vaccinated is moderate in extent. A yield of from twenty to forty grams of pulp from one calf should satisfy the propagator. Before the virus is taken the animal is placed upon a special table, the site of the vaccination exposed and given a very thorough washing and prolonged scrubbing with soap, and an abundant flushing with sterile water. The pulp is usually obtained by scraping the vesicles with a sharp spoon curette. Glycerin (60 per cent.) in proper proportion is added at once to the pulp, and this, is ground to a state of fine and uniform subdivision in a Doring lymph mill, or simply by hand with a mortar and pestle. This glycerinated pulp is then allowed to ripen, and when ripe it is hermetically sealed in capillary tubes, or placed in small vials, or upon glass or ivory points, for the market. METHODS OF VACCINATION Vaccination consists in transferring the virus from one animal to the skin of another animal. The operation may be compared to the transfer of a culture in a bacteriologic laboratory. Precisely similar precautions to prevent contamination must be used in both cases. Vac- cination must be regarded as a surgical operation. No person unfamiliar with surgical cleanliness should be permitted to perform this "little" operation. The vaccine virus may be introduced in one of three ways: (1) by puncture, .(2) by incision, or (3) by scarification. SMALLPOX AND VACCINATION 9 Jenner used punctures or short incisions. Later blisters were raised upon the skin and* the virus placed upon the abraded surface. The incisions were then increased in number, and finally cross scratchings were made. Puncture.— The simplest and best method is puncture with a needle, for there is least chance of contamination and the eruption is typical. The disadvantage is that the virus now used is diluted with glycerin, and therefore somewhat attenuated, so that a few simple punctures are less apt to take. Incision. — The method advised and recommended is that of incision. Incision is the only method of vaccination permitted by the laws of Germany, and recommended by the Local Government Board of Eng- land. Incision, if not too deep, consists really of a series of punctures, and serves the same purpose. Incisions may be made with the point of a scalpel. I prefer to use a needle. The incision or scratch should not be deep enough to draw blood, but a few drops do no harm. It is rather difficult to control the depth of the incision with a scalpel, espe- cially if it is sharp. Scratching with a needle is much more easily controlled. The incisions should be about three-quarters of an inch long and about an inch apart. The vaccine virus is then placed upon the abraded surface, and gently rubbed, not ground, in. It is impor- tant not to cause any unnecessary irritation so as to avoid attracting infections. Scarification. — Scarification or cross-scratching is prohibited in Ger- many by ministerial decree of March 31, 1897, which was incorporated into the revised rules of the Bundesrath, July 28, 1898. The objec- tion to scarification is that this method produces an abraded surface which is soon covered by a crust of serum and blood, through which the eruption cannot pierce. The vesicles form a ring around the scarified area, leaving a central irritated wound, inviting infection. It is be- lieved that most of the cases of tetanus complicating vaccination oc- curred in cases in which scarification was used. In this method fa- vorable anaerobic conditions are produced under the crust or scab which forms over the abraded surface. The Point of Election. — The outer surface of the left arm at about the insertion of the deltoid is the most convenient for the operator and the patient. This is the original site selected by Jenner, and is less liable to severe glandular complications than other points. Flachs recommends the side of the chest at about the level of the sixth rib, in the axilla. Here the scar is not visible; there is little mo- tion, and it is easily bandaged, but this site is open to the disadvantage of greater heat and moisture and there is, therefore, greater ^danger of complications. The leg is sometimes selected to avoid disfigurement. The vaccina- 10 SPECIFIC PEOPHYLACTIC MEASUEES tion scar should not be regarded as a deformity. To the sanitarian a typical vaccine scar is a sanitary dimple. The leg is more exposed than the arm to traumatism, and, therefore, to complications. Dock refuses to vaccinate on the leg unless the patient will stay in bed until the vesicle heals. With babies in diapers and with young children it is exceedingly difficult to keep these parts clean. If the leg is selected, the vaccination should be done on the calf below the head of the fibula, and not on the outer surface of the thigh. Number of Incisions. — This has an important bearing upon the probability of the take, as well as the protection. It is not wise to de- pend upon one. The relation of the numljer of vesicles and the amount of reaction to the degree and length of the immunity has not been worked out. The German regulations of 1899 require at least four in- cisions, each one centimeter long, and two centimeters apart. The Local Government Board of England directs that four vesicles should be produced, and that the total area of the vesicle formation shall not be less than one-half a square inch. My own practice follows that of Dock, who makes not less than two incisions about an inch long and an inch apart; but in case of exposure to smallpox three or four such incisions are advisable. The Operation. — The skin at the site of the operation must be sur- gically clean, but need not necessarily be treated with antiseptics. If such are used, they must be carefully washed away in order not to destroy the activity of the virus. A thorough scrubbing with soap and water is necessary for a dirty skin. Washing with warm water followed by alcohol is usually enough. The alcohol should be permitted to evap- orate before the incision is made. In general, the. less the skin is irri- tated the less is the danger of complications. Needles are particularly handy, as they may be flamed just before the operation, and are con- venient in saving time when many people are to be vaccinated. The vaccine virus is gently rubbed into the incision, not ground in, and then allowed to dry. No dressing is necessary at the beginning, but several layers of dry sterile gauze held in place by adhesive plaster do no harm, and serve as a protection. Pads, plasters, and shields of any sort are unwise, because by retaining heat and moisture they cause a soften- ing and breaking down ; in other words, they act like a poultice. Bath- ing need not be omitted, nor any of the ordinary occupations, but un- necessary use of the arm must be guarded against, as this increases the congestion, inflammation, and the chances of infection. Schamberg and Kolmer ^ have recently advised the use of a 4 per cent, alcoholic solution of picric acid on the vaccinated area 48 hours after the insertion of the lymph. This apparently does not interfere with the success of the vaccination. Schamberg and Kolmer believe ''Lancet, Nov. 8, 1911, CLXXXI, No. 4603. SMALLPOX AND VACCINATION 11 that the picric acid lessens the degree of the local inflammatory reaction and that the patients are not so apt to exhibit constitutional disturb- ances. It also decreases the liability of extraneous bacterial infection. INDICES OF A SUCCESSFUL VACCINATION The take must be typical and the clinical course characteristic, other- wise we have no assurance that the individual is protected against small- pox. The best indices of a successful take are: (1) the course of the eruption, (2) the general symptoms, and (3) the sear. The importance of knowing the skin lesions of vaccinia were in- sisted upon by Jenner. Every vesicle, scab, ulcer, or irritated wound is net vaccinia. No confidence should be placed in doubtful or atypical takes. The typical features of vaccination are singularly alike. The clinical course of a primary vaccination is as follows: Course of the Eruption. — The primary wound soon heals. Appar- ently nothing occurs for 3 to 4 days, which is the period of incubation. Then one or more small papiiles appear upon the skin where the vac- cine virus was introduced. The papule is small, round, fiat, bright red, hard, but superficial. About the fifth day the summit of the papule becomes vesicular. The vesicle is at first clear and pearl-like. Umbilication soon develops as the vesicle enlarges. A deep, red, and swollen areola surrounds the vesicle and grows wider as the lesion ad- vances. This gives the picture of the "pearl upon the rose leaf" which constitutes the true Jennerian vesicle. By the seventh day the vesicle is full size, round or oval, fiat on top, umbilicated, and contents clear. It is multilocular ; if pricked with a pin or accidentally opened only that portion of the lymph contained in the compartment opened will exude. By the eighth day it turns yellowish, the middle is fuller, fol- lowing which the so-called second umbilication develops. Meanwhile the areola deepens, widens, and may be swollen. The skin feels hot, is painful, and the axillary glands become enlarged and tender. About the ninth day the areola begins to fade and the swelling subsides. By the eleventh or twelfth day the vesicle rapidly dries, leaving a brown, wrinkled scab, which finally drops off. It should never be removed, as it forms the best bandage. The scar is at first red, finally turns white, with the pits or fovea- tions so characteristic of true cowpox. General Symptoms. — The general symptoms vary. There are malaise, loss of appetite, sometimes nausea and vomiting, headache, pain in the muscles of the back, and other indications of a mild febrile reaction. The temperature may go to 38° or 38.5° C. between the third and seventh days. The febrile reaction bears no special relation to the size and number of the vesicles pr to the areola, The nitrogen eliminatipn Fourth Day Sixth Day Fifth Day h '^ ' # Iw-t * %^- ^# '^^^'mL. '^" ^- Eighth Day Ninth Day FiO. 1. — Vaccinia. Course of the Ebuption from the Fourth to the Ninth Dat. 12 Fourteenth Day Scar— Sixth Week Fig. 2. — Vaccinia. Course op the Ebuption from the Tenth Day. 13 14 SPECIFIC PROPHYLACTIC MEASURES increases about the tenth day for a short time. The blood changes re- semble those of smallpox, an early leukopenia and secondary leukocy- tosis. Secondary vaccinations often run an accelerated, milder, or modified course with shortened periods of incubation (see revaccination). THE IMMUNITY The immunity appears about the eighth day of the vaccination. Layet puts the point of safety at the ninth day, Burckhard at the elev- enth. These data are based upon the early work with variolation, when persons were inoculated with smallpox at various periods following vac- cination. Sacco got only local eruption by inoculating smallpox on the eighth to the eleventh days, and none after that. Vaccination protects not only against smallpox, but also against vaccinia. Curiously enough, the degree and length of immunity ap- pear to be greater against smallpox than against itself. It is irra- tional to attempt to fix a definite time for the duration of the immu- nity. This varies as in other infectious processes. It is known through experiment and experience that the immunity gradually wears off. Defi- nite protection on the average lasts about seven years. The degree of protection is usually absolute for some years, and then gradually fades. In this, as in other diseases, immunity is a relative term. Smallpox itself does not always protect against smallpox. Some people have two and even three attacks of smallpox. Such cases, however, are excep- tional, and it is also exceptional to have smallpox occur in an individual who has been properly vaccinated. Careful statistics collected in Japan since 1879 show quite definitely the gradual diminution of the immunity, beginning with the second year after vaccination. Kitasato's table,^ based on 951 cases, is as follows: SUCCESSFUL REVACCINATION AFTER: 1 year 13.6 per cent. 2 years 32.9 3 years 46.6 4 years 57.3 5 years 51.1 6 years 63.8 Weil, in 1899, reported 72.5 per cent, of successful revaccinations after seven years, 80 per cent, after eight years, 85 per cent, after nine years, and 88.6 per cent, after ten years. It is a fallacy to state that, if a revaccination takes, the subject was therefore susceptible. While this is usually true, it does not necessarily 'Journal A. M. A., March 25, 1911, p. 889. SMALLPOX AND VACCINATION 15 follow. It is a still greater fallacy to state that, if a vaccination fails, the subject is therefore immune. This view may result in real harm. Vaccination may fail for many reasons — the operation may not have been properly done, or the virus may have been inert. Sometimes per- sons are unsuccessfully vaccinated three, four, or more times before a typical take is obtained. The nature of the changes in the body which produce the immunity are not understood. In this sense vaccination is still an empiric pro- cedure. We now know of many analogous instances, however, where an active acquired immunity is induced by means of an attenuated virus. The immunity produced by vaccine virus does not depend upon an anti- toxin. The blood, however, contains specific antibodies, shown by the fact that equal parts of blood serum from a calf two weeks after suc- cessful vaccination' mixed with vaccine virus destroy its activity. EEVACCINATION The fact that the immunity wears off after a number of years makes it necessary to practice revaccination in order to afford a continuous protection. There is some difference of opinion as to just when it is best to vaccinate the second time. Ten years is too long a period, prob- ably, to depend upon in individual cases. One year — advised by some — - is shorter than necessary in most cases. The five-year interval of Japan is good in many respects, but probably not better than revaccination in the twelfth year obligatory in Germany. The best time to vaccinate is in the first year before the second sum- mer, again at from ten to thirteen years. After this it is usually un- necessary to vaccinate again, unless there is particular danger of expo- sure to smallpox. All persons exposed directly or indirectly to smallpox should at once be vaccinated — unless they have had the disease or have recently been successfully vaccinated. There are no contraindications to vaccinating babies immediately after birth. The clinical picture of secondary vaccinations may be quite different from the typical take following a primary vaccination. These altered reactions were known in the time of Jenner, but were lost sight of until recently rediscovered, and their significance realized from studies in anaphylaxis. Eevaccinations may be divided into three groups: (1) they may run an unaltered course resembling primary takes in all respects, showing that immunity to cowpox has disappeared; (2) they may run a slightly more rapid course in which the period of incubation is shortened and in which the height of the pustular stage occurs about the sixth day (this is known as the accelerated reaction); or (3) they may run a m cO cvl m ® ® ® ^ii »i (J >43 a: q: < a 111 •a: f^ ■ a o % < o -1 H a o a H o pi « o W O I > a H O £j O o 2 a ° T 1 f-^ o tf rt ^ <^ m d Q CO Q 16 SMALLPOX AND VACCINATION 17 very much shortened, milder, and rapid course. The eruption may be only a small papule or an almost imperceptible erythema which soon disappears; the period of incubation is less than 24 hours. This is known as the immediate reaction and resembles a cutaneous tuberculin reaction in many respects. These altered reactions have been studied especially by Von Pirquet and are shown graphically in Fig. 3. The immediate reaction may be put to practical use in order to dis- tinguish smallpox from chickenpox. Thus, Tieche has shown that small- pox virus introduced into the skin of a person immunized by vaccination will show the typical immediate reaction; whereas the virus of chicken- pox is invariably negative. This test can be freed of all possible danger by heating the virus to 60° C. for 30 minutes, which does not seem to affect the reaction. CLAIMS FOE VACCINATION 1. If successful, it protects the individual against smallpox for a period which has not been determined mathematically for the individual, but which averages about seven years. 2. The protection may be renewed by a second vaccination. 3. Persons successfully vaccinated on two occasions are usually immune against smallpox for life. 4. Vaccination and revaccination systematically and generally car- ried out confer complete protection to a community or a nation. In other words, while the individual protection is not always perfect, the communal protection is absolute. 5. A person vaccinated once and at a later time contracting small- pox as a rule has the disease in a less serious form than unvaccinated persons (varioloid).^ The degree of favorable modification of smallpox is in inverse proportion to the period of time elapsing between the vac- cination and the attack of smallpox. 6. The beneficial effects of vaccination are most pronounced in those in whom the vaccine aSection has run its most typical and perfect course. VACCINATION OF EXPOSED PERSONS The question frequently arises whether persons exposed to smallpox should be vaccinated. The effect of vaccination during the period of incubation of smallpox is very interesting, and may be summed up as follows : The term varioloid was introduced by Thompson in 1820 to describe the mild and modified form of smallpox occurring after vaccination. The eruption in varioloid disappears more rapidly than in variola. Yolfert, Dornbleuth, and Harden showed that one vaccination was not sufficient protection against small- pox for a lifetime, that revaccination was necessary and that the clinical mani- festations of this vaccination are as different from those of the first vaccination as varioloid is from variola. 18 SPECIFIC PROPHYLACTIC MEASURES 1. Vaccination just before or during the primary fever of small- pox does not influence the disease, nor does the vaccination take.^ 2. If the vaccination is done during the last stage of the period of incubation of smallpox, the two infections run their course side by side without influencing each other. 3. If it is done about the sixth or eighth day of the period of in- cubation the vaccination takes and may modify the severity of the smallpox. 4. Vaccination done at the beginning of the incubation period m time to have the vaccine eruption reach maturity before the smallpox begins will prevent or abort the disease. This is shown in the follow- ing diagrana : THE EFFECT OF VACCINATION DURING THE PERIOD OF INCUBATION OF SMALLPOX Toward the During the Early in the Middle of the end of the Primary On the Incubation Incubation Incubation Fever, or First Period Period Period Preemption Day 2nd to 6th days 6th to 8th days 9th to 14th days Stage - Variola Prevent Smallpox is Varioloid or Smallpox not Smallpox not Bmallpox aborted mild case influenced influenced 1 1 1 1 1 1 1 1 1 1 II 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 1 1 12 3 1 Period of Incubation of Smallpox — in Days 1 1 1 1 1 II 1 1 1 1 1 Primary Fever 1 1- 1 Eruption The vaccina- The vaccination The vaccina- The vaccination The vaccination tion takes. takes. tion takes 2 or 4 days before primary fever. takes and both af- fections run side by side. does not take (?) To produce the best results the vac- - Vaccinia cination should precede this period, so as to reach maturity before the onset of the primary fever. The vaccine vesicle reaches maturity about the 8th day. - As we can never be quite sure just what stage in the period of in- cubation a given case may be in, it is always advisable to vaccinate exposed persons. Furthermore, little harm will be done if it is too late and the vaccine eruption is added to the smallpox. Indeed, Hanna, ^ presents claims to the effect that there is abundant evidence in mitigat- ing the severity of smallpox when vaccination is performed at any time after infection up to the day of onset and even afterward. ^Public Health, July, 1910, XXIII, No. 10, p. 351. SMALLPOX AND VACCINATION 19 DANGERS AND COMPLICATIONS The alleged danger from vaccination has been greatly magnified by the antivaccinationists. However, vaccination is not always a harmless procedure; it must be looked upon as the production of an acute infec- tious disease, and, although the disease is always mild and trivial, it must not be treated as trifling. The chief danger lies in the fa^t that we have produced an open wound, which is subject to the complications of any wound. Even a pin prick or a razor scratch may result in death. While the aggregate number of deaths resulting from the complications of vaccination may be considerable, the aggregate of the individual risk is so small as to be disregarded, especially when proper precautions are talien. Many of the infections after vaccination occur in those in whom the regard for cleanliness is slight, and who neglect the site of the wound. In recent years, owing to the improved quality of the vaccine virus and the introduction of aseptic methods, a had sore arm is a rare occurrence, and serious complications still rarer. In any case, the danger connected with vaccination is infinitesimal when compared with the benefit con- ferred. The important complications are : Auto Vaccination. — This is usually due to scratching the virus into the finger, the nose; the mouth, the mucous membranes, or any part of the skin. When carried into the eye it may cause blindness. Physicians sometimes vaccinate their lips by blowing into vaccine tubes. In vac- cine establishments accidental vaccination of the hand is common. Generalized Vaccination. — This is sometimes reported, but is usu- ally a mistaken diagnosis. A generalized eruption of cowpox- is ex- ceedingly rare, if it ever occurs. I have seen it in the calf after intra- venous injection of a large amount of the virus, in which case there is a prolonged period of incubation. Wound infections, such as ulcers, gangrene, erysipelas, abscesses, lymphangitis, suppuration of the axillary glands, and other septic infec- tions are now exceedingly rare, and should be treated with the usual measures to prevent their occurrence. Impetigo contagiosa occasionally occurs and may be a serious com- plication of vaccination, especially the bullous impetigo or pemphigoid forms, which presumably have their origin in cattle. Syphilis, tuberculosis, and leprosy are sometimes feared, but these are practically impossible with the use of bovine virus. In any case it is doubtful whether tuberculosis or leprosy could be so transferred. Tetanus deserves a special word. Several outbreaks have been re- ported in this country after the use of certain viruses. Willson in 1903 found tetanus spores in the vaccine virus used in a New Jersey out- break. Glycerin does not destroy the tetanus spore. Many hundreds of 20 SPECIFIC PEOPHYLACTIC MEASUEES examinations made in the Hygienic Laboratory at Washington have failed to discover a tetanus spore in a single vaccine point or tube. The occasional danger cannot be denied. It is probable, however, that the infection in some of these cases conies from outside sources. The occurrence of occasional stray spores in vaccine virus was demon- strated by Carini.^ Such vaccine, however, had proved entirely harm- less in thousands of cases. It is more than probable that the actual danger would begin if such occasional stray spores were allowed to ger- minate in the vaccine pulp through some serious fault in manipulation. It is conceivable that the vaccine pulp after removal from the calf or heifer, if not at once chilled, or if not at once mixed with glycerin, may form a very rich medium for anaerobic bacteria. Some carelessness or neglect Just at this stage might prove disastrous if tetanus spores ac- cidentally present should multiply. The epidemic in this country in 1902 reported by Willson ^ and MacFarland ^ may have been the result of some such occurrence. On the other hand, neglected vaccination wounds or those in which proper bandages or shields favor anaerobiosis may stimulate the germination of spores coming from without and lead to the occasional reported sporadic cases following vaccination. To prevent tetanus complications it is important to avoid scarification and irritation, also to avoid the use of shields and bandages which favor anaerobic conditions; to practice strict cleanliness, and to use vaccine virus that has been properly prepared and tested. Special tests for tetanus are now required by federal regulations of every lot of vaccine virus before it is placed upon the market. Foot and Mouth Disease.— The infection of foot and mouth disease has in one instance been demonstrated as a contamination of vaccine virus.* It is, however, impossible to convey foot and mouth disease to man through cutaneous inoculation. While no harm has been done to man, the contamination is undesirable, and special federal regulations now require vaccine virus to be tested from time to time to assure its freedom from this infection. As an illustration of how seldom complications are caused by vac- cination we have the results of Germany, where in thirteen years (1885- 1893) 32,166,619 children were vaccinated. Of these 115 died within a few weeks or months after the operation, presumably of injuries in- cidental thereto. Of these at least 48 probably did not die as a direct result of the vaccination. The figures of recent years are still better, for it is' now exceedingly rare for a death to be recorded as directly due to vaccination. For '■Centralbl. f. Balct., Orig. 1904, XXXVII, p. 1147. 'Jour. A. M. A., 1902, XXXVIII, p. 1147. 'Jour. Med. Research, 1902, n. s. II, p. 474. * MoMer and Eosenau, U. S. Dept. of Agriculture, B. A, I. Circular 147 June 16, 1909. ' SMALLPOX AND VACCINATION 21 example, in the Philippine Islands in the past few years the United States authorities vaccinated 3,515,000 persons without a single death or any serious post-vaccinal complications. THE GOVERNMENT CONTROL OF VACCINE VIRUS By the law of July 1, 1902, the vaccine virus sold in interstate traf- fic in the United States must come from a licensed manufacturer. These licenses are issued by the Secretary of the Treasury only after a careful inspection of the plant, personnel, and product by a competent government officer. The licenses are good for one year only, and are reissued only after reinspection. The government regulations require each lot of vaccine virus to be examined carefully by modern bacterio- logical methods to determine the number of bacteria, and special tests must be made to determine the absence of pathogenic microorganisms. These tests include animal inoculations, as well as cultural methods. Special tests for each lot of vaccine must be made to determine the presence or absence of streptococci, tetanus spores, foot and mouth infec- tions, etc. The government does not guarantee the purity and potency of each package of vaccine virus, but through its inspections and frequent examinations of the virus on the market every confidence may now be had in the vaccine virus propagated by licensed manufacturers in this country. THE UNITY OF COWPOX AND SMALLPOX The unity or duality of these two diseases has been the subject of much contention. Jenner originally considered cowpox to be a modified smallpox. The successful experiments in Germany, England, and this country, in which smallpox has actually been modified by passing variolous matter through calves has proved positively that we are dealing with two forms of one disease. Much of the vaccine virus used during the past hundred jears was originally obtained from cases of casual cowpox. This virus has been shown by experience and experiments to protect against smallpox, which makes it highly probable that we are dealing with one disease. The parasite Cytorrhyctes variolce, discovered by Councilman, BrinekerhofE, and Tyzzer, gives a probable explanation of how smallpox may, under certain circumstances, become attenuated. The life cycle of this parasite interpreted by Calkins indicates that the mild disease, cowpox or vaccinia, is due to the asexual phase in the life cycle of the parasite which lives and multiplies in the cytoplasm of the epithelial cell; smallpox is caused by the combined asexual and sexual cycle of the same parasite, the latter phase occurring in the nucleus of the epithelial cell. When the Cytorrhyctes variolce loses its power to gen- erate by sexual division it never again regains it; that is, while small- 4 S3 SPECIFIC PKOPHYLACTIC MEASUKES pox may be modified into cowpox, cowpox has never been returned to smallpox. It seems plain that much of the so-called casual cowpox probably has its origin from smallpox through accidental inoculation in milking or handling these animals by persons having or recovering from variola. Once started, the propagation of the modified virus from cow to cow would be comparatively simple. COMPULSOEY VACCINATION Vaccination affords a high degree of immunity to the individual, and a well-nigh perfect protection to the community. To remain unvac- cinated is selfish in that such persons steal a certain measure of pro- tection from the community on account of the barrier of vaccinated persons around them. The laws ' and regulations relating to vaccination in the several states of the United States show marked lack of uniformity. Compulsory general vaccination can be said to exist by law only in Kentucky, Ehode Island, and Porto Eico.' Arizona, Hawaii, Maryland, New Mexico, North Dakota have laws requiring vaccination of children. In recent years smallpox has been so mild in the United States that the case death rate has been as low as 0.3 per cent., or 1 death in 500 cases. Decisions in the various courts in the United States have held com- pulsory vaccination to be legal. A decision of the Supreme Court of the United States (Henning Jacobson vs. The Commonwealth of Massa- chusetts, April 1, 1905) upheld in every respect the statute, the validity of which was questioned under the Constitution. The liberty secured by the Constitution of the United States .... does not impart an absolute right in each person to be, at all times, and in all circumstances, wholly freed from restraint. Real liberty for all could not exist under the operation of a principle which recognizes the right of each individual person to use his own, whether in respect to his person or his property, regardless of the injury that may be done to others. Theoretically it would be ideal if all persons submitted to vaccina- tion and revaccination voluntarily. But experience has shown that this is impractical, and, wherever tried, has failed. The best results have always been obtained where vaccination has been compulsory, and, in my judg- ment, this is the only present means by which smallpox may be eliminated. The world may learn a valuable, lesson from the splendid results obtained in Germany through compulsory vaccination and revaccina- ^Kerr, J. W., "Vaccination, and Analysis of the Laws and Eegulations Re- lating Thereto in Force in the United States," Puilic Health Bull. 52. ' Massachusetts, in 1809, was the first state to enact legislation relative to vaccination, SMALLPOX AND VACCINATION 23 tion. In England the "conscience clause" allows many persons to re- main iinvaccinated and thereby seriously diminishes the effects of the vaccination laws of that land. In Minnesota the state health authori- ties became weary of the clamor against compulsory vaccination and assisted in having the law repealed. They said, in substance, to the people of the state : "Take your choice. Be vaccinated and protect yourself, or run the risk of contracting smallpox; if you get it, it is your own fault." TABLE 1.— DEATHS FROM SMALLPOX IN COUNTRIES WITH COMPULSORY VACCINA- TION AND THOSE WITHOUT COMPULSORY VACCINATION Population Average of 1886 1887 1888 1889 Deaths 1 5 9 2 4 2 14 3 5 24 17 6 12 197 168 112 200 169 275 505 1,026 23 458 182 14 17 3 54 1,213 610 865 1,212 975 16,938 25,884 ? ? 21,411 8,794 9,591 14,138 12,358 11,220 ? 16,249 18,110 13,416 15,925 ? ? 14,378 8,472 11,425 Average per Million of Population Sweden* 4,746,465 Ireland* 4,808,728 Scotland* 4,013,029 Germany* 47,923,735 England* 28,247,151 Switzerland 2,922,430 Belgium 5,940,365 Russia 92,822,470 Austria 23,000,000 Italy 29,717,982 Spain 11,864,000 1 1 3 3.5 16 18.5 164 231 510 536 963 *CompuIsory vaccination. INOCULATION OB VABIOLA INOCULATA The practice of inoculation must be carefully distinguished from that of vaccination. By inoculation we mean the introduction of small- pox matter into the skin of man. The disease thus produced is usually very mild, but is nevertheless true smallpox, and just as contagious as smallpox. This phase of the subject may be made clearer by considering small- pox as existing in three forms: (1) variola vera or true smallpox; (3) variola inoculata or inoculated smallpox; (3) vaccinia, cowpox, or modified smallpox. The differences between these affections are shown in the table on the following page. Emphasis must be placed on the fact that variola inoculata, while usually a mild disease, is just as communicable as true smallpox, and those who contract the disease in this way get true smallpox, often in serious or fatal form. Inoculation, therefore, protects the individual but endangers the community. 24: SPECIFIC PEOPHYLACTIC MEASURES Variola Vera Variola Inoculata Vaccinia or Cowpox True smallpox. Inoculated smallpox. Modifled and attenuated small- pox. Only occurs in man. Occurs in man and monkeys. Man, monkeys, cattle, guinea- pigs, rabbits, rats, camels, and many other mammals. High mortality. Milder: rarely fatal; about 1 in 500. Very mild; never fatal. A general eruption, often confluent or hemorrhagic. A general eruption, fewer pus- tules (rarely over 200) ; seldom confluent or hemorrhagiic. Always local and confined to the site of the vaccination. Highly contagious Equally highly contagious. Not contagious — contracted only by mechanical transfer of vaccine virus. Period of incubation 12-14 days. 8 days. 3-4 days. Inoculation is a very old custom. It was practiced by the Chinese from time immemorial. The method was introduced into western civili- zation through Lady Mary Wortly Montagu, who learned of the method at Constantinople and had her own boy "engrafted" with successful result. In 1717 Lady Montagu wrote her now famous letter to her friend Sarah Chiswell, and the practice soon became popular in England (1721) and spread to America and the Continent. It was introduced into this country by Dr. Zabdiel Boylston at Boston. But the dangers were early realized and inoculation was soon replaced by vaccination. According to Plehn, inoculation is still practiced in central Africa. The method of inoculation is precisely similar to that of vaccina- tion. The matter is obtained from the vesicle or pustule of a case of smallpox. This material is then introduced into the skin by means of a puncture, an incision, or through an abraded surface. The Chinese, it is said, practice inoculation by blowing the dried smallpox crusts into the nostrils. While inoculation has properly fallen into disuse, there are con- ceivable emergencies in which the practice would be justified. For example, on board ship or on an island or isolated place, in the absence of vaccine virus. Under such circumstances it would be essential to inoculate everybody at the same time. The inoculation of smallpox will always remain for the student of preventive medicine one of the most interesting episodes in the develop- SMALLPOX AND VACCINATIOF 25 ment of the sanitary sciences. It' illustrates in the clearest manner some of the fundamental phenomena of infection, susceptibility, and immunity. It was animal experimentation on a huge scale, the like of which we shall never see repeated on man as the subject (Sedgwick). It is now a matter of regret that for the sake of science better advan- tage was not taken of the data. PREVALENCE OF SMALLPOX It is very difficult for us now to realize that smallpox was once much more common than measles and much more fatal. Many of those who recovered were disfigured for life, left blind, or with some other serious consequence of the disease. For centuries smallpox was one of the greatest scourges. It depopulated cities and exterminated nations. In Europe alone, where its ravages were comparatively slight, it killed hundreds of thousands yearly. In the 18th century, of which we have the best records, almost everybody had it before he grew up. Parents sometimes exposed their children to the disease in order to be through with it, just as they now sometimes do with the minor contagious diseases. Smallpox was formerly a disease of children. It was called "kinder- hlattern." Since vaccination protects the child, smallpox has now be- come more prevalent among adults. The distinguished mathematician, Bernouille, estimated that 15,000,- 000 people died of smallpox in 25 years in the 18th century. It has been estimated that 60 million people died of smallpox during that century. Haygarth gives an account of a smallpox epidemic in Chester, England, population 14,713. At the termination .of the epidemic there were but 1,060 persons, or 7 per cent, of the population, who had never had smallpox. Many similar instances are cited in the literature. The French physician de la Condamine (1754) said that "every tenth death was due to smallpox and that one-fourth of mankind was either killed by it or crippled or disfigured for life." Sarcone (1783) esti- mated the number of persons in Italy who suffered from smallpox as 90 per cent, of the population. Smallpox was introduced into the western hemisphere by the Span- iards about 15 years after the discovery of America. In Mexico within a short period three and one-half million persons are said to have died of the disease (Chapman). Catlin (1841) states that of 12,000,000 American Indians 6,000,000 fell victims to smallpox. In Iceland, in 1707, 18,000 perished out of a population of 50,000, that is, smallpox killed 36 per cent, of the total population in one year. A good example is that of Boston in 1752, population at that time 15,684. Of this number 5,998 had previously had smallpox. During the epidemic 5,545 persons contracted the disease in the usual manner. 26 SPECIFIC PEOPHYLACTIC MEASUEBS and 2,124 took it by inoculation. 1,843 persons escaped from the town to avoid the infection. There were, therefore, left in the city but 174 persons who had never had smallpox. ■7777 — "■ — "* mmm "■ ^ ~ ■" ^ "* ■" ^ ^ "" _ '0/6/ %l>k/ _ Aii,' -j.iii I'O j'i,' ' -^ri/ eti,i _ _ _ _ _ — ^ iPi/ - — — — — — — — — — ' — — — -1 ■ d.f&/ £&!/ aJu/ L^i' 'plj/ Jli^/ :/>fj' * ■?p/ * V6/I /ur fU/ ' 'kjl/ ' JJJI ' £UI 4jsi JJi/ ^n/ * ^JJ{ / ' i /-/// i>,jjf ' "ttJi AlSI il.lil 1 ^i,s/ Jii' ■ - - - - - - - - - — 1 ■ ■ ■ m ■ OKMt s s H - - 5 - - - - - ! - ^ ■ oi-ii ■ i'^il 1 Wr _ — _ _ -_ _ _« _ _ _ ~t ^ ■ ^ 1 » - - - - - - - = ~~ - ^ - m ; ; % - - V- - - - - - - - - - - - ' 19SI 1 T^ - - - - - - - - - -1 ■ ■ ■ B -I kJi/ - - - - - - - - - - - 5 5 - 1 IS Jit - z I I - z I - I - -I - - - ■« - - = - — « — - ^ "■ ^ — ;z : ■ 1 ISJSI - - - - - - - - - - - - — . s ^ - - - - - " " " " " ■ ■ : ; itv, ^^ _ _ _ —\ _ _ _ ^ ^ ^ ^ yjTT -^ — — "1 — — — — — — — — — — ■ ■ ■/T/rtl — ~ I - = - ^ - - — - - - - -1 - 1 i 1 ^ ^ i 1 • 1 i ~ J 1 i 1 1 1 ^ « 5 1 "? % J « « w « « ,< ^ b *■ " ^ - .• S5 § a |K o sg O -Oi ft, CM tH w Si O O O O o" PS o M O ■>! O O O t3 ^i CO S '-< o o« ■" c li a|^ ■" O o O (u m ° S 2 « |a T— I -g cc o a « S O > 00 Ph 'S i-i o "3 S > Smallpox is still as serious as it was in former times. Thus, in five years, from 1893-1897, 346,520 persons died of smallpox in sixteen SMALLPOX AND VACCINATION 37 countries. Of this number Eussia alone lost 275^502. These figures are the more terrible when it is realized that these lives might have been saved by the use of a simple prophylactic measure within reach of all. EPIDEMIOLOGY Few of the acute infectious diseases show such a complete inde- pendence of conditions such as race, climate, soil, age, sex, and occu- pation, sanitary surroundings, etc., as does smallpox. It thrives wher- ever the contagion is carried, and wherever it finds susceptible people. Probably no one is naturally immune. The susceptibility of the popu- lation varies, because a smallpox outbrealf leaves so many immune. This is one reason why the disease recurs in waves. The mortality varies greatly in different epidemics. At times it is less than one per cent. ; it frequently reaches thirty per cent, and over. In 1901-1903 the mortality in the United States was as low as 2 per cent., and following that 0.5 per cent. These differences occurred in the prevaccination era as well as now. The epidemiology of smallpox bears no relation to improved sanita- tion, which has diminished the prevalence of tuberculosis, typhoid, cholera, and has practically subdued typhus and relapsing fever. It is evident that general sanitation could not affect contagious diseases lilce smallpox and measles. Smallpox spares neither high nor low, the rich or poor; before the days of vaccination it counted many kings, queens, and princes among its victims. MODES OF INFECTION We are still ignorant of the precise mode by which smallpox is conveyed. The view generally held is that the infection is air-borne and enters the system through the respiratory mucous membrane. It has been surmised that a local lesion may be produced in this favor- able soil, the so-called "propustule," from which general infection through the blood takes place. The blood infection is marked by a sharp onset (the initial symptoms), and the skin eruption is embolic in character. The objection to this view is that a careful search of 54 cases in Boston by Councilman and his colleagues failed to find such a propustule. It is known that the Chinese inoculated the disease by placing a crust from the eruption in the nostrils, but whether the disease so produced was variola vera or variola inoculata is not known. The virus of smallpox is always contained in the skin lesions. Of this we have experimental evidence. It is also supposed to be in the expired air. This, however, has never been experimentally proven. The disease is contagious before the eruption appears. It is even be- lieved to be communicable during the period of incubation. Smallpox 28 SPECIFIC PEOPHYLACTIC MEASURES has always been taken as the type of the contagious diseases; the con- tagion is the most "volatile" of any of the diseases of man. This volatility, however, has been overestimated, and, while probably an air- borne infection, the radius of danger is contracted. English observers have long taken the view that smallpox may be blown for great distances, and they attribute the prevalence of smallpox to the windward of hos- pitals as an indication that the virus may be carried down the wind. My experience with the disease teaches me that the danger from such a source is practically nil. One may safely live next door to a smallpox hospital that is well screened and properly managed. The influence of flies and other insects, or surreptitious visiting, may account for the spread of this disease outside of hospital walls. In addition to more or less direct contact smallpox may be spread indirectly in a great variety of ways. The secretions from the mouth and nose doubtless contain the infection, and, while suspicion has not particularly fallen upon the feces and urine, it is probable that all the secretions and excretions from the body may be infective at some time throughout the disease, or during convalescence. Toys, pencils, books, letters, spoons, cups, towels, handkerchiefs, bedding, and objects of the greatest variety that have in any way come in contact with the patient may carry the infection. Under favorable circumstances the active principle may probably live for a considerable time upon fomites. Smallpox is not usually considered an insect-borne disease, but it is highly probable that a fly lighting upon a smallpox patient and get- ting its proboscis, feet, and other portions of its body smeared with the variolous matter, and then flying to a susceptible person, could thus readily transmit the infection. Other insects may by such mechanical transfer play a similar role. RESISTANCE OF THE VIRUS It is generally, and doubtless correctly, assumed that the active principle of variola has approximately the same resistance to external conditions as vaccine virus. This assumption is confirmed by experi- mental evidence, which shows that the virus of smallpox is even more readily destroyed than the virus of cowpox. Scientific data concerning the viability of variolous matter is meager, owing to the fact that this question can only be settled by prolonged and repeated experiments upon monkeys. Brinckerhoff and Tyzzer ^ found that variolous virus is less resistant to desiccation than vaccine virus; that variolous virus does not pass a Berkefeld filter and is attenuated by long exposure to 60 per cent, glycerin. In general it may be said that variolous virus is killed by exposure to ordinary germicidal substances, both liquid and gaseous, in the litc 'Studies upon Experimental Variola and Vaccinia in Quadrumana " Jour. Med. Research, Vol. XIV, No. 2, Jan., 1906, pp. 223-359. ' SMALLPOX AND VACCINATION" 29 strengths and time commonly employed. It succumbs in fact before the average non-spore-bearing bacteria. There is a probable exception to this statement in the case of car- bolic acid and the coal-tar disinfectants. McClintock and Ferry ^ have shown that such germicides as carbolic acid, cresols, and the like do not destroy the virulence of vaccine virus in 0.5 per cent, solutions in live hours' exposure. In this strength and time almost all non-spore-bearing bacteria would be destroyed. The inference is allowable that this class of disinfectants cannot be relied upon to prevent the spread of smallpox. SMALLPOX IN THE VACCINATED AND UNVACCINATED The experience of over one hundred years offers convincing proof of the pronounced difEerence in the mortality and morbidity from small- pox in the vaccinated and the unvaccinated. The following table from Schamberg shows that, among thousands of cases of smallpox occurring in cities all over the world, the death rate from smallpox has been from five to sixteen times greater among the unvaccinated than among the vaccinated : TABLE 2— DEATH-RATE FROM SMALLPOX AMONG VACCINATED AND UNVAC- CINATED IN VARIOUS COUNTRIES'^ Places and Time of Observation France, 1816-1841 Quebec, 1819-1820 Pliiladelphia, 1825 Canton Vaud, 1825-1829 Verona, 1828-1829 Milan, 1830-18S1 Breslau, 1831-1833 Wurttemberg, 1831-1835 Carniola, 1834-1835 Vienna Hospital, 1834 Carinthia, 1834-1835 Adriatic, 1835 Lower Austria, 1835 Bohemia, 1835-1855 Galicia, 1836 Dalmatia, 1836 London Smallpox Ho.spital, 1836-1856 Vienna Hospital, 1837-1856 Kiel, 1852-1853 Wurttemberg (no date) Malta (no date) Epidemiological Society Returns (no date) Total No. of Cases Observed 16,397 140 ,838 909 ,240 220 ,442 442 360 ,626 ,002 ,287 ,640 ,059 723 ,000 ,213 218 ,258 ,570 624 Death Rate per 100 Cases Among the Unvac- cinated 16.125 27 60 24 46.66 38.33 53.8 27.33 16.25 51.25 14.5 15.2 25.8 29.8 23.6 19.66 35 30 32 38.9 21.07 23 Among the Vac- cinated 1 1.66 2.16 6.66 7.66 2.11 7.1 4.4 12.6 0.6 2.8 11.5 5.16 5.14 8.25 7 5 6 3K 4.2 2.9 ^ Jour, of the Amer. Public Health Assn., June, 1911 (Vol. I, No. 6), p. 418. ^ Extract from papers prepared in 1857 by Sir Jolin Simon, Medical Officer of the General Board of Health of England, and at that time laid before Parlia- ment with reference to the History and Practice of Vaccination. Published in first Report of the Royal Commission on Vaccination, 1889, Appendix 1, p. 74. ^Jour. of the Amer. Public Health Assn., June, 1911 (Vol. 1, No. 6), p. 418. ■za f« sefi- se 4re Sff 7!e fefi/ 6f Pf if fiJ^jP/ J'f ■»* fe 'Z» Tfffi OP Si. U 9igt )\\\\\ ^U\\V'V,IK\V.UV' II K \iu^iiiiii : s i^iEb ELfcu mii -i^ b!!Lii line O'O 0« ev ev i'O O-O 9'ff fO m> sv 09 ly'tf O'O o& «» t'e *'A i'a t'a SI ^i et }fi'0 \e'ff mil HUP "■" "■■■ "■" ■■■" ■■■" ■"■■ "■" I"" Si o o o 02 . 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(j 1 .>ii (Si , : 1 .: ,',}'' Z9 f9PA -l-^"^"^^ § $ §"^ § ^ p. 3 to ■< +^ ^ XI IS ^1 O C) , 'h P^ O O A 0-« o fl ° a K O "O 31 32 SPECIFIC PEOPHYLACTIC MEASUEES TABLE 3— ANNUAL SMALLPOX DEATHS IN SWEDEN BEFORE AND AFTER THE INTRODUCTION OF VACCINATION ' Before Vaccination 17492 4,453 1750 6,180 1751 5,546 1752 10,302 1753 8,000 1754 6,862 1755 4,705 1756 7,858 1757 10,241 1758 7,104 1759 3,910 1760 3,568 1761 5,731 1762 9,389 1763 11,662 1764 4,562 1765 4,697 1766 4,092 1767 4,189 1768 10,650 1769 10,215 1770 5,215 1771 4,362 1772 5,435 1773 12,130 1774 2,065 1775 1,275 1776 1,503 1777 1,943 1778 6,607 1779 15,102 1780 3,374 1781 1,485 1782 2,482 1783 3,915 1784 12,456 1785 5,077 1786 671 1787 1,771 1788 5,462 1789 6,764 1790 5,893 1791 3,101 1792 1,939 1793 2,103 1794 3,964 1795 6,740 1796 4,503 1797 1,733 1798 1,357 1799 3,756 1800 12,032 1801 6,057 Total (S3 years) 125,130 After Vaccination 1802 1,533 1803 1,464 1804 1,460 1805 1,090 1806 1,482 1807 2,129 1808 1,814 1809 2,404 1810' 1811 1812 1813 1814 1815 1816 1817 1818 1819 1820 1821 Compulsory Vaccination in Infancy 824 689 404 547 308 472 690 242 305 161 143 37 Total (20 years) 18,217 1822 11 1823 39 1824 618 1825 1,243 1826 625 1827 600 1828 257 1829 63 1830 104 1831 612 1832 622 1833 1,145 1834 1,049 1835 445 1836 138 1837 361 1838 1,805 1839 1,934 650 237 58 9 6 6 2 13 71 341 1,376 2,488 1,534 279 204 41 1840 1841 1842 1843 1844 1845 1846 1847 1848 1849 1850 1851 1852 1853 1854 1855 1 The population in 1751 was 1,785,727: in 1855 it was 3,639,332. 2 From 1749 to 1773, inclusive, deaths from measles are included. * First successful vaccination in Stockholm. SMALLPOX AND VACCINATION 33 In countries like Germany, Sweden, Ireland, Scotland, and England, where vaccination is more or less compulsory, there is comparatively little smallpox. In countries like Belgium, Russia, Austria, and Spain, which have no compulsory vaccination laws, smallpox yearly claims many victims. See table 1, page 23. THE RESULT OF VACCINATION IN GEEMANY April 8th, 1874, Germany passed a general compulsory vaccination and revaccination law. The law requires the vaccination of all infants before the expiration of the first year of life, and a second vaccination at the age of twelve. Since this law went into effect there have been no epidemics of smallpox in Germany, despite the fact that the disease has been frequently introduced from without. In 1897 there were but 8 deaths from smallpox in the entire German empire — population 54,- 000,000. Since then long periods have passed without a single death from smallpox. From 1901 to 1910 there were only 380 deaths from smallpox in Germany; during the same period there were 4,286 deaths from smallpox in England and Wales, with only about half the popula- tion of Germany; furthermore, many of the deaths in Germany were in foreigners: Thus in 1909, out of 26 deaths from smallpox, 13 were foreigners, 11 of whom were Russians. In the huge German army there have- been only two deaths from smallpox since 1874. One of these was a reservist who had not been successfully vaccinated. Germany has taught the world how to utilize Jenner's great demonstration. ISOLATION AND DISINFECTION Isolation and disinfection are only secondary measures in prevent- ing smallpox. They cannot be regarded as substitutes for vaccination. Isolation should be carried out with strictness for the reason that smallpox is one of the most contagious of the communicable infections. While the patient should be isolated, it is not necessary to isolate the hospital by banishing it to an inconvenient or undesirable location. There is, in fact, no good reason why a smallpox hospital should not be one of the units of the general hospital for communicable diseases. In any event, there is no danger from a smallpox hospital situated upon a high road or near other habitations, provided always proper precau- tions are taken to prevent the spread of the disease. The smallpox hospital should not be a pest house, but should be as inviting and attractive as economic conditions justify. Smallpox should not be treated in the home. From the standpoint of prophylaxis the hospital is the logical and best place to care for this and other com- municable infections. If smallpox is treated in the home, this should 1 %%%%\%^^^ MMM^ I ' ^a ^ 1 eo'o foef 1 >r/^'0 OffSl 1 tit'O ee i go'o ee 1 tio'e ^«- 1 zo'o )9ep/ '"'*- se \»o'e &6 1 eo ve yfa -ie 1 eo ffffff t /i?_ oe i I'i e» \f'ff 9» 1 e-o ca t s'o AMit \s'o ^ff 1 Ve- ■'^ff 1 , 1 *'/■ Eff 1 "Z 'Ttf II se /v»/ --■ II 9g Off ■ 1 9^ « 1 e't M 1 Zi? Jil 1 fiS' Slff ■■■ wv.w--. SI \'."\\'i^v.y-.nL, II si- : ■'■+^& n iHii ■■■■■ ■■■■■ Hir ■■III iiiii iiiiiiiiii mil mr—" " — ■■ ■■"" — ■■ wm C3 s izi o M S3 O gg • gg *S££- o9 €£- *£_ 9£££_ S£_ ?£- 0£_ 6±_ Veil g'st ret 1Z9 . e'9/r »€« (■'n OVA '6J. . e'e/ L9* iff OP 6£ iiiiiiiiiiiiiiiiic::::::: :::::::::::::::::::::::: 02. iiiii iiiii iSIii iiiiiiiiii liiii Siiii iSiii wSr' . ■" OJ o o ■^ rfS 2 t, « M d ^ <13 - 03 36 SPECIFIC PROPHYLACTIC MEASURES only be permitted if skilled nursing and trained attendants can be pro- vided. The room in which the smallpox patient is isolated should be simply furnished to facilitate cleanliness and to permit purification. It must be well screened and frefe from insects and vermin of all kinds. The room should be well ventilated. This may be accomplished by an open fireplace, in which case the contagium, if contained in the outgoing air, is burned in exit. The nurse attending a case of smallpox should also be segregated, and all visiting should be strictly interdicted. A separate kitchen should be provided and care should be taken that the dishes be scalded and remnants of food burned. Bedding, underwear, towels, and other objects should not leave the sick room unless they are first boiled, steamed, or immersed in a suitable germicidal solution, such as bichlorid of mercury, 1-1,000, or formalin, 10 per cent. Carbolic acid should not be trusted. For terminal disinfection either sulphur dioxid or formaldehyde may be used. Objects particularly contaminated or soon to be used by others should be given a separate and special disinfection. Finally, the room should be thoroughly cleansed, aired, and sunned. The patient must be regarded as the source and fountainhead of the infection, and measures should be used at the bedside to prevent the surroundings from becoming contaminated. Cloths, cotton, and other dressings that become soiled with the contents of the vesicles and pustules after they break should be burned. The urine and feces may be disinfected with chlorinated lime. The sputum and discharges from abscesses must be carefully disinfected by an approved method (see Section XII). As a rule, smallpox patients are not dismissed from quarantine until desquamation has ceased. This may be favored by the use of warm baths and a generous use of soap, also by anointing the skin with vaselin or a bland oil. Special attention should be given to the hair, which should be well shampooed, to the interdigital spaces, and the fingernails, as well as to all folds of the skin, before the patient is released. The management of smallpox epidemics is discussed on page 319. RABIES SYNOJi!YMS.— Hydrophobia; Wasserscheu, Wuth, Tollwuth (Ger- man) ; Lyssa (Greek) ; La Rage (French). Rabies is an acute, specific, rapidly fatal infection communicated from a rabid animal to a susceptible animal, usually through a wound RABIES 37 produced by biting. Man always contracts the disease from some lower animal, usually the dog. The infective agent must be inoculated into the tissues; the virus is harmless when ingested. Eabies may be re- garded as a wound infection. The specific principle is contained in the saliva of animals suffering with the disease. The infection, there- fore, may be conveyed by licking provided there are fissures or open wounds in the skin. It is also possible to introduce the virus through autopsy accidents and other unusual ways, but commonly it is intro- duced through wounds produced by the teeth of a rabid animal. Every mammalian animal is susceptible. Even birds may contract the disease. It is most common in dogs, but it also occurs frequently in wolves, Jackals, foxes, and hyenas. Eabies in cats is comparatively rare. Cattle, sheep, and goats are infected relatively in about the same degree. It is less common in horses. Swine contract the disease less frequently than other domestic animals. Skunks have the disease and sometimes transmit it to man. Although all mammals are susceptible to rabies, it is perpetuated in nature almost exclusively by the domestic dog, only to a small extent by wild animals of the dog family, and occasionally by skunks, cats, etc. Outbreaks have been reported under unusual circumstances. Thus Carini ^ reports an epizootic causing the death of about 4,000 cattle and 1,000 horses in Sao Paulo, Brazil. There was no unusual prevalence of rabies in dogs at the time but it was noticed that bats, in broad daylight, attacked and bit the cattle, and Carini suggests that bats may have been the source of the extensive epizootic. The animals affected all died after a few days and the meat and hides were utilized but no mishaps have been known to follow. Eabies exists practically all over the world, except in Australia, and recently in England. It is most common in France, Beliguni, and Eussia. In the United States 111 human deaths were reported in 1908. In the same year there were 535 localities in which rabid animals were reported; in 191] there were 1,381 localities, and 98 deaths in man. In 1890 the United States census reported 143 deaths in 30 states, and in 1900 but 23 deaths. Eabies is remarkable in that the mortality is 100 per cent. After symptoms begin recovery never occurs in man or other animals. Jo- seph Koch (1910), however, describes an abortive rabies. The disease is peculiar in several other particulars, especially the period of incuba- tion, which is more variable and more prolonged than that of any other acute infection. Eabies is commonly supposed to prevail only during the hot months, but it may be just as bad in cold weather. In fact, exposure to cold seems to increase its virulence. More cases occur from April to Sep- ^Ann. de I'Insi. Pasteur, Paris, Nov., XXV, 11, p. 785. 38 SPECIFIC PROPHYLACTIC MEASUEES tember than from October to March in this climate, because dogs run abroad more freely at this season of the year. It is this fact, and not the temperature, that influences the prevalence of the disease. Period of Incubation.— From the standpoint of prevention it is for- tunate that the period of incubation of this disease is prolonged. This period varies from 14 days to a year or more. The average period is as follows: Man, 40 days; dogs, 21-40 days; horses, 28-56 days; cows, 28-56 days; pigs, 14-21 days; goats and sheep, 21-28 days; birds, 14-40 days. The period of incubation depends largely upon the site of the wound, the relation to the nerve, the amount and virulence of the virus. It requires about 15 days to induce an active immunity to the disease by means of the Pasteur preventive treatment. There is, therefore, usu- ally plenty of time, if the case is seen early, to prevent the development of symptoms. It is probable that the prolonged period of incubation is due in part to the fact that the living principle reaches the central nervous system, but remains dormant until favorable conditions permit multiplication and the production of toxic effects (Joseph Koch). Entrance and Exit of the Virus. — The active principle of rabies occurs principally in the saliva and in the central nervous system. It may be in the saliva at least three days (possibly eight) before the ani- mal shows symptoms (Eoux and ISTocard). It is, therefore, sufficient to watch a dog that has bitten a person or another animal for ten days. If no symptoms of rabies appear during this time there is no danger of conveying the disease, and the Pasteur treatment is unnecessary. The virus may also be found in the adrenals, the tear glands, the vitreous humor, the spermatic fluid, the urine, the lymph, the milk, as well as all parts of the central nervous system and the peripheral nerves. It is also found in the spinal and ventricular fluids. It has not been demonstrated in the liver, spleen, blood, or muscles. The virus enters the system through the broken skin and follows the nerve trunks from the seat of injury to the spinal cord, thence to the medulla and brain. The route corresponds to that of tetanus toxin. The mode of invasion of the virus may explain why pain, throbbing, tingling, numbness and other nervous disturbances are the flrst symp- toms to occur in parts of the body that have received the virus. It also partly explains the variable period of incubation, which is shorter in wounds of the face than in wounds of the extremities. It also explains why the disease is more serious when the wounds are in parts of the body where there is an abundant nerve supply. The Relative Danger of Bites.— Wolf bites are most dangerous on account of the savage character of the wound, anc^the virulence of the virus. Cat bites come next, and then dog bites. '^The relative danger RABIES 39 of bites of other animals is as follows : foxes, jackals, horses, asses, cattle, sheep, pigs. There is no authentic instance of the transmission of the disease by the bite of man, though this may be possible. The bites of horses and other herbivora are less dangerous because their blunt teeth usually cause contused wounds without breaking the skin. Bites on exposed surfaces are more dangerous than through the clothing, because the saliva is wiped from the teeth and little or none enters the wound. Long-haired dogs and sheep often escape infection for the same reason. Bites upon the face are most apt to be followed by rabies. Not every person bitten by a mad animal develops rabies. Leblanc's figures are 16.6 per cent. The statistics are difficult to analyze, and it is almost impossible now to collect sufficient data. According to the most reliable data, it would seem that rabies develops in not less than one person in ten bitten by mad dogs, and not receiving the Pasteur treatment. Paltauf places the figures at 6 to 9 per cent. Viability. — The virus of rabies in the spinal cord of rabbits dies in about 14 days when dried at 20°-22° C, if protected from putrefaction and light. Spread in thin layers, it dies in 4 or 5 days, and exposed to the sunlight in 40 hours. It is quite resistant to putrefaction. In a decomposed carcass it may be recovered by placing some of the cen- tral nervous system in glycerin. The glycerin destroys most of the con- taminating bacteria, but preserves the virus. Eabies virus is completely destroyed at 50° C. in one hour, and at 60° C. in 30 minutes. It is not injured by extreme cold. Five per cent, carbolic acid for one hour, 1-1,000 bichlorid of mercury for one hour, or a saturated solution of iodin in water completely destroys its virulence. PROPHYLAXIS The prevention of rabies is considered under three heads: (1) Treatment of the wounds; (2) the Pasteur prophylactic treatment, and (3) tbe control of the disease in dogs by muzzling and quarantine. The cauterization of the wound and the Pasteur prophylactic treat- ment are efficient preventive measures for the individual, but they are not the true and best methods of controlling and preventing rabies. The disease may be avoided, even exterminated, by an intelligent systepi of muzzling and quarantining of dogs. A high tax on dogs and leash- ing are only restrictive measures. In England, when the dogs were muzzled, rabies diminished. The law was repealed, owing to misplaced sympathy for the dog, and rabies promptly increased. The law was again enforced, and in about two years the disease disappeared (see the accompanying chart). Now a strict quarantine of six months is main- tained against dogs Altering England, It is no longer necessary to 40 SPECIFIC PEOPHYLACTIC MEASUEES muzzle dogs in England, but muzzles will again be required should the disease reappear. Consistent muzzling of all dogs for two years will practically exterminate rabies. In Australia there are few carnivorous animals, mostly marsupials; there rabies does not exist, for it has been kept out owing to early and effective quarantine measures. Fig. 9. — Chart Showing Relation of Enfohcement op Mpzzling Law to Preva- lence OF Rabies in Great Britain. The figures in the cross-hatching indicate the number of persons who died of rabies in England and Wales. The ordinates repre- sent cases in dogs. (Frothingham.) Prophylactic measures necessary to control the dog question are: the destruction of ownerless dogs; license fee and tag for all dogs; owners to be legally responsible for damage inflicted by their dogs; education of the dog-owning public concerning the spread of commun- icable diseases, especially rabies; compulsory reporting of all cases or suspected cases of rabies. Further special and temporary measures advocated are: muzzling; restraint with chains, leash, etc.; observation in quarantine, or killing of all animals bitten by dogs; disinfection, etc. THE LOCAL TREATMENT OF THE WOUND Wounds produced by the bite of an animal in which there is any suspicion of rabies should at once be cauterized with fuming nitric acid. The acid is best applied with a glass rod very thoroughly to all the parts of the wound, care being taken that pockets and recesses do not escape. Thorough cauterization at once reduces the danger of wound RABIES 41 complications, and experience Remonstrates that wounds so treated at once, are practically never followed by rabies. Marie obtained conflicting results with local treatment in experimental rabies; Cabot obtained the best results in a series of extensive experiments with nitric acid. Poor ^ was able to save the lives of 45 per cent, of guinea-pigs by cauterization with nitric acid at the end of 24 hours. In the absence of nitric acid the actual cautery may be used. Strong antiseptics, such as carbolic acid and formalin, are less reliable. Nitrate of silver is valueless. In any wound produced by the bite of an animal the rule is to cauterize unless sure that the animal is not mad. It has been shown that the virus may remain alive and virulent in the scar for a long time, and it has become a question whether patients seen after the wound has healed should not have the scar excised; this, however, is not the present practice. THE PASTEUE PEOPHYLACTIC TREATMENT This method of prophylaxis was announced December 6, 1883, by Pasteur, at the International Congress at Copenhagen, and on February 24, 1884, he laid before the French Academy the details of his experi- ments and results. The next year Pasteur, with the help of Roux and Chamberland, worked out the details of the method now used. The principle of the treatment consists in producing an active im- munity by means of an attenuated virus. The virus is attenuated by drying. The fixed virus contained in the spinal cord of rabbits dead of hydrophobia is the material used, for subcutaneous injection. Street Virus and Fixed Virus. — The distinction between fixed and street virus is of fundamental importance in reference to the question of immunity. Street virus refers to the virus obtained from mad dogs naturally infected. When this virus is inoculated into a rabbit, it reproduces the disease after a period of incubation of from 14 to 21 days or more. This street virus may then be conveyed from rabbit to rabbit through a number of transfers. In the passage from rabbit to rabbit the virus becomes more virulent for rabbits, but less so for dogs and other animals. The period of incubation is progressively shortened, until finally the rabbits invariably sicken on the sixth or seventh day and die on the ninth or tenth. When the virus has reached this degree of virulence for rabbits, it is said to be "fixed," for the reason that its potency remains constant. In its passage through rabbits the modifica- tion from street virus to fixed virus is gradual. It is important to note that fixed virus, which has attained a high degree of virulence for rab- ' Collected Studies, Eesearch Lab., Dept. of Health, City of N. Y., VI, 1911, p. 25. 42 SPECIFIC PROPHYLACTIC MEASURES bits, has lost much of its virulence for dogs, and is probably entirely avirulent for man. Proescher^ injected into himself the entire brain and medulla of a rabbit (fixed virus), and another entire brain into a volunteer. No ill effects of any kind were noted in either case. A control rabbit in- jected with a 0.02 dilution of the same emulsion died in seven days with experimental rabies. Marx tested the fresh fixed virus upon monkeys in large doses, with negative results. Ferran in Barcelona in 1887 inoculated 85 persons with the fresh fixed virus as a prophylactic treatment for dog bites with good results, which have been further confirmed by Wysokowiez and Nitsch. The evidence points clearly to the fact that the fixed virus of rabbits does not produce rabies in man when introduced into the sub- cutaneous tissue. Preparation, of the Virus. —Rabbits are injected under the dura mater with a few drops of an emulsion of fresh fixed virus obtained from the pons or medulla of another rabbit dead of hydrophobia. Strict aseptic precautions are necessary in order to keep out other infections. The rabbit should begin to show symptoms on the sixth or seventh day, and die on the ninth or tenth. Usually the rabbit is not allowed to die, but is chloroformed on the last day in order to avoid terminal in- fections and unnecessary suffering. The spinal cord is removed and hung in a bottle containing potassium hydroxid. These bottles are kept in the dark at a temperature of 20°-22° C. Under these conditions the cord gradually desiccates, and at the same time the virulence of the virus diminishes, until the fourteenth day, when it is no longer infective. This is why Pasteur started the treatment with a cord four- teen days old. One half a cubic centimeter of the cord constitutes a dose. This is ground in sterile salt solution so as to produce a uniform emulsion, which is injected into the subcutaneous tissue of the abdominal wall, lu many institutes the small segments cut each day from the drying cord are placed in pure glycerin. The virulence of the cord in glycerin is not altered for at least 30 days, if kept in the dark and at 15° C. This method, introduced by Calmette, is very convenient, especially where comparatively few patients are treated. Glycerin has the added advan- tage of destroying infections due to non-spore-bearing bacteria that may be present. As a further precaution, bacteriological examinations are made of parts of the spinal cord in order to insure the absence of bacteria, and the rabbit is carefully autopsied as a guarantee that no other disease is present. The scheme of treatment advocated by Pasteur and still used at ITnstitut Pasteur in Paris and many other places is as follows : ^N. ¥. Med. Jour., Oct. 9, 1909, also Arch, of Int. Med., Sept., 1911, VIII, 3, p. 353. EABIES 43 PASTEUR PROPHYLACTIC TREATMENT— RECOMMENDED BY PASTEUR Mild Treatment Intensive Treatment Day of Treatment Age of the Dried Cord Amount of Injected Emulsion 1 cm. to 5 c. c. Day of th Treatment \ee of e Dried Cord Amount of Injected Emulsion 1 cm. to S c. 0. 14 Days 3 c. u. 1 / 14 Days 3 c. .;. 1 13 3 113 3 12 3 11 3 10 3 ri2 3 2 9 3 2 111 3 8 3 7 3 1 10 3 3 6 2 3 \ I ^ 3 I 6 2 4 ■ ^ 8 3 3 4 5 2 5 r 6 2 5 5 2 I 6 2 6 5 2 6 4 2 7 5 2 7 3 1 8 4 2 8 4 2 9 3 1 9 3 1 10 5 2 10 5 2 11 5 2 11 5 2 12 4 2 12 4 2 13 4 2 13 4 2 14 3 2 14 3 2 15 3 2 15 3 2 16 5 2 16 5 2 17 4 2 17 4 2 18 3 2 18 3 2 19 5 2 20 4 2 21 3 2 Many Pasteur institutes now use a modified treatment, starting with an 8-day instead of a 14-day-old cord, which is exemplified in the scheme on next page, used at the Hygienic Laboratory, Public Health Service. The Pasteur scheme has been further modified in various ways. Bujwid and Babes use stronger treatment than that advocated by Pas- teur. Puscariu in Jessy uses a method based upon the experiments of Babes, which show that an emulsion of fixed virus when heated to 50°- 58° C. is attenuated in virulence. Tizzoni and Cattani attenuate the virus in gastric juice, and Hoyges simply dilutes the fresh virus. The original dilution is 1-100, and the first dose is one ten-thousandth of this. Ferran in Barcelona, Proescher in Pittsburgh, and others in- ject patients with the unaltered, fresh, fixed virus. The advantages of using the virus as fresh and strong as possible are that an active im- munity is produced more quickly, and this is of considerable importance in wounds of the face; also in wolf and cat bites, which frequently have a short period of incubation. Further, onljf one or two injections 44 SPECIFIC PEOPHYLACTIC MEASURES PASTEUR PROPHYLACTIC TREATMENT— HYGIENIC LABORATORY, WASHINGTON, D. C. Age of the Dried Amount Day Cord Adult 5 to 10 Years 1 to 5 Years Scheme for Mild Treatment 1 8-7-6 2 . 5 c. c. 2.5 0. c. 2.0 0. .;. 2 5-4 2.5 2.5 1.5 3 4-3 2.5 2.5 2.0 4 5 2.5 2.6 2.5 5 4 2.5 2.5 2.5 6 3 2.5 2.5 2.0 7 3 2.5 2.5 2.0 8 2 2.5 1.5 1.0 9 2 2.5 2.0 1.5 10 5 2.5 2.5 2.5 11 5 2.5 2.5 2.5 12 4 2.5 2.5 2.5 13 4 2.5 2.5 2.5 14 3 2.5 2,5 2.0 15 3 2.5 2.5 2.0 16 2 2.5 2.0 1.5 17 2 2.5 2.0 1.5 18 4 2.5 2.5 2.5 19 3 2.5 2.5 2.5 20 2 2.5 2.5 2.0 21 2 2.5 2.5 2.0 Scheme for Intensive Treatment 1 8-7-6 2.5 CO. 2.5 c.c. 2.5 c.c. 2 4-3 2.5 2.5 2.0 3 5-4 2.5 2.5 2.5 4 3 2.5 2.5 2.0 5 3 2.5 2.5 2.0 6 2 2.5 2.0 1.5 7 2 2.5 2.5 2.0 8 1 2.5 1.5 1.0 9 5 2.5 2.5 2.5 10 4 2.5 2.5 2.5 11 4 2.5 2.5 2.5 12 3 2.5 2.5 2.0 13 3 2.5 2.5 2.0 14 2 2.5 2.5 2.0 15 2 2.5 2.5 2.0 16 4 2.5 2.5 2.5 17 3 2.5 2.5 2.5 18 2 2.5 2.5 2.0 19 2 2.5 2.5 2.0 20 3 2.5 2.5 2.5 21 2 2.5 2.5 2.0 of the fresh virus are necessary to produce an immunity, and this shortens and simplifies the treatment very much. EABIES 45 Harris ^ has shown that rabic material may be completely desiccated without destruction of virulence, provided the dehydration takes place at a low temperature. The lower the temperature the greater will be the amount of virulence preserved. Virus so desiccated contains per weight as much infectivity as the fresh virus. The loss of virulence of the dried virus is so slow that it may be standardized, permitting an accuracy of dosage hitherto impossible. The unit is the smallest amount which, when injected intracerebrally into a full-grown rabbit, will pro- duce paresis on the seventh day. The use of this desiccated virus in the prophylactic immunization of animals and persons offers many ad- vantages over other methods. Treatment at a distance from a Pasteur institute is now possible by sending a piece of cord, or the emulsion in glycerin. Care During the Treatment.— During the treatment the patient may go about his usual business. It is not necessary to stay in bed. The patient should, however, avoid fatigue, cold, and alcohol. It has been shown that these are important predisposing factors to the disease. It was found that customs' officers returning to the Siberian borders after prophylactic treatment for wolf bites showed an unusual mortal- ity, which seemed to be due to exposure to cold. The disease has been observed to be brought on after a cold bath, falling into the water, and similar depressing influences. Complications of the Treatment.- — The Pasteur prophylactic treat- ment may be complicated by (1) local reactions or (2) paralysis. Local reactions at the site of the wound are usually trivial. Ab- scesses almost never occur. The local reactions consist of redness and induration. Their occurrence increases with the progress of the treat- ment; they are most frequent in the second week. As the treatment in- volves the introduction of a large quantity of foreign proteins into the body, it is probable that these reactions represent a phase of hyper- susceptibility. (See Anaphylaxis.) Paralysis. — Paralysis occasionally occurs and may be fatal. There is doubt concerning the cause of this paralysis, and a question whether it may be a mild or modified type of rabies, or a form of anaphylaxis. In a case treated at the Hygienic Laboratory the paralysis came on 18 days after treatment, and was transient. The New York Pasteur In- stitute reports a death from "ascending paralysis," which came on four days after the treatment. W. A. Jones - reported two cases with re- covery. In 1905 Eemlinger, head of the Constantinople Institute for Eabies, reported 40 cases of paralysis; Miiller found 16 cases in the liter- ature, and had two of his own ; Panpoukis, three cases ; Jones, 2 ; mak- ing a total of 63, 2 of whom died. ^Jour. of Infect. Dis., May, 1912, X, 3, pp. 369-377. 'Jour. A. M. A., Nov. 13, 1909, p. 1626. 46 SPECIFIC PEOPHYLACTIC MEASURES The Immunity. — Duration. — The imiminity appears two weeks af- ter the treatment and lasts a varying period of time, depending upon the individual — at least for several years. In this respect it does not differ from other instances of acquired immunity. The fact that the immunity appears on about the fifteenth day after the end of the treat- ment was discovered by Pasteur as a result of animal experimentation. The statistics of the Pasteur Institute, giving the mortality from rabies in persons following the prophylactic treatment, exclude instances in which the disease develops within fifteen days after the end of the treatment. Natuee. — The nature of the immunity is not clear. It certainly is not due to an antitoxin. Immune bodies are demonstrable in the blood twenty days after the last injection. This is determined by mixing in vitro the active virus with the blood serum, which neutralizes its activity. This neutralization is generally considered to be microbicidal or lytic in nature. Degree. — The degree of the immunity also varies, as is evidenced by the fact that a certain small percentage of the persons treated die of rabies. The Eesults of the Treatment. — Statistics giving the results of the treatment are somewhat difficult to analyze, as many factors are unob- tainable. Patients should be kept under observation at least a year. Exceptional cases occur one year following the treatment. Cases that occur within fifteen days after the treatment are excluded from the French statistics, for reasons that have already been stated. The fig- ures on this, basis show a mortality which averages about 0.5 per cent. Better results are being obtained from year to year. The table on the following page gives the general results at ITnstitut Pasteur, Paris, since beginning the treatment. When we compare these figures with the fact that from 6 to 10 per cent, and sometimes 16.6 per cent, of all persons bitten by rabid dogs die of rabies, the prophylactic value of the Pasteur treatment is evident. Some series of cases give a much higher mortality. Thus, of 855 cases collected by Tordieu, Thamehayn, and Bouley, 399 ended in death, or 46.6 per cent. In another series of cases given by Bouley, out of 266 persons bitten by mad dogs, 152 died of hydrophobia. But of these 120 were bitten on the face and hands, the greater danger of which has been mentioned. The mortality of bites from wolves is placed at from 60 to 80 per cent. Contraindications. — ^There are no particular contraindications to the treatment. All ages and conditions should be treated if exposed. Ap- parently no harm is done pregnant women. I have injected patients having malaria without trouble following. The treatment nlay be con- BABIES RESULTS OF TREATMENT AT L'INSTITUT PASTEUR, PARIS. 47 Year Persons Deaths Mortality 1886 2,671 25 0,94% 1887 1,770 14 0.79 1888 1,622 9 0.55 1889 1,830 7 0.38 1890 1,540 5 0.32 1891 1,559 4 0.25 1892 1,790 4 0.22 1893 1,648 6 0.36 1894 1,387 7 0.50 1895 1,520 5 0.38 1896 1,308 4 0.30 1897 1,521 6 0.39 1898 1,465 3 0.20 1899 1,614 4 0.25 1900 1,420 4 0.28 1901 1,321 5 0.38 1902 1,005 2 0.18 1903 628 2 0.32 1904 755 3 0.39 1905 727 3 0.41 1906 772 1 0.13 1907 786 3 0.38 1908 524 1 0.19 1909 467 1 0.21 tinued in patients having colds, fevers, and other ailments without no- ticeable harm. When to Give the Pasteur Treatment. —It is sometimes difficult to decide whether the Pasteur prophylactic treatment should or should not be given. The treatment causes sufficient personal inconvenience, not to speak of the danger (however slight) of paralysis, to avoid ad- vising it if unnecessary. In many cases it is impossible to discover whether the dog which inflicted the bite is mad or not. The rule in cases of doubtful exposure is to advise the treatment. Persons not infrequently apply for advice giving the following his- tory: They have not been bitten, but they have been licked on the hands and face by a dog which subsequently developed the disease. Persons are sometimes similarly exposed by washing the mouth of a rabid horse. In these cases the important question is whether there were fissures or abrasions in the skin at the time. There may be little wounds in the skin not evident to the naked eye. In such cases the danger is slight, but in apprehensive subjects the assurance of protection which the treatment affords is an important element in arriving at a decision. In all cases it is important to know whether the dog is mad or not. If the dog can be found and kept under observation for 10 days and no symptoms appear, the Pasteur treatment is not necessary. Animals killed early in the course of rabies may fail to show the miscroscopic 48 SPECIFIC PKOPHYLACTIC MEASURES evidence of the disease, thus causing an indefinite delay in diagnosis awaiting inoculation tests. Should symptoms develop, the question of diagnosis is all-important. Diagnosis of Rabies in Dogs.— The diagnosis of rabies in dogs may be made in three ways: (1) from the symptoms; (2) from the presence of Negri bodies in the central nervous system, and (3) by animal inoculations. 1. The symptoms may be very suggestive, but a diagnosis must always rest upon the pathological lesions and the inoculation tests. The course of the, disease may be divided into three stages: a pre- monitory stage, a stage of excitement, and a paralytic stage. The first two stages may be absent or transient. All rabid animals invariably become paralyzed before they die. In dogs the first symptom consists solely in a change in the disposition of the animal. He is easily ex- cited, but does not show a disposition to bite. Soon the restlessness becomes more marked, and the animal may become furious and even show signs of delirium. The animal does not fear water, as is com- monly supposed, but rushes about attacking every object in his way. Dogs suffering from furious rabies have a tendency to run long dis- tances (25 miles or more) often biting and inoculating large numbers of other animals and persons en route. Very soon paralysis sets in, commencing in the hind legs, and finally becomes general. The course of the disease is always rapid, averaging from 4 to 5 days, rarely exceed- ing 10 days. When the stage of excitement is brief or absent, the disease is known as dumb rabies. This is the prevailing type in Turkey. This explains the relative rarity of rabies in man in Turkey, where dogs abound. 2. There is a difference of opinion concerning the significance of the Kegri bodies {Neuroryctes hydrophobice) , which, however, are very constant in rabies and peculiar to it. If Negri bodies are found in the dog, the Pasteur treatment should be started at once. The absence of Negri bodies, however, does not necessarily mean the absence of rabies. These bodies are sometimes difficult to find, or may not be present in the parts of the central nervous system which are examined. Negri bodies for diagnostic purposes may best be demonstrated by im- pression preparations stained according to Van Gieson, as recommended by L. Frothingham; or smears stained by the Mallory eosin-methylene- blue method recommended by Williams and Lowden. Smears are prepared by crushing a small portion of the brain matter between two slides; portions are selected from Ammon's horn and also from the cerebellum, cerebral cortex, and medulla. These smears are then fijxed and stained as follows: (a) Zenker's solution for 15 minutes. (b) Wash in tap water. THE VENEEEAL DISEASES 49 (c) Ninety-five per cent, alcohol tinted with iodin. (d) Absolute alcohol five minutes. (e) Five to ten per cent, watery solution of eosin (Griibler W. g.) five minutes. (f) Stain in Unna's polychrome methylene blue two to three min- utes. (g) Wash in water. (h) Differentiate in ninety-five per cent, alcohol. (i) Blot ofl:, dry, and examine with oil immersion lens. The lesions of Van Gehuchten and Nelis, described in 1900, are the most characteristic anatomical changes. These lesions are found in the peripheral ganglia of the cerebrospinal and sympathetic systems, espe- cially in the plexiform ganglia of the pneumogastric nerve, and also the Gasserian ganglia. The normal nerve cells of these ganglia lie in a capsule lined with a single layer of endothelial cells. In rabies these endothelial cells proliferate and the nerve cells are pushed aside and even destroyed. The ganglion may finally contain only round cells. 3. The final diagnosis of rabies rests upon animal experimenta- tion. A small quantity of the suspected material is placed under the dura mater of a rabbit or guinea-pig. The diagnosis by this method, however, requires so much time (on account of the long period of in- cubation of the disease) that it is of no practical value in deciding whether or not the Pasteur prophylactic treatment should be given, but in any critical case the positive evidence furnished by animal experi- mentation is incontrovertible. THE VENEREAL DISEASES As a danger to the public health, as a peril to the family, and as a menace to the vitality, health, and physical progress of the race, the venereal diseases are justly regarded as the greatest of modern plagues, and their prophylaxis the most pressing problem of preventive medicine that confronts us at the present day. There are three venereal diseases : syphilis, gonorrhea, and chancroid. In order to have a clear understanding of the problems of venereal prophylaxis it is necessary to have a knowledge of the essential features of these preventable infections. Two of them, syphilis and gonorrhea, are of great importance, because they are very prevalent and because they are very serious infections with grave consequences. 50 SPECIAL PEOPHYLACTIC MEASUEBS SYPHILIS There are many striking things about syphilis, but nothing so strik- ing as its persistence in spite of knowledge complete enough to stamp it out and in view of the popular dread in which the disease is held. It is preventable, even curable- — yet scarcely another disease equals it in the extent and intensity of its ravages. Syphilis is a good illustration of the fact that it is much more diffi- cult to control a disease transmitted directly from man to man than a disease transmitted by an intermediate host, or one in which the infective principle is transferred through our environment. We have a certain amount of control over our surroundings, and we have dominion over the lower animals, but the control of man requires the consent of the governed. Civilization and syphilization have been close companions, but syph- ilis is now less prevalent among civilized than uncivilized peoples — this is promising. Civilization, however, should not be content until it has controlled syphilis as effectively as it has a few other preventable in- fections. The effort to do so, at least, must be persistent and sincere. From the economic side, syphilis is not a serious disease in its pri- mary and secondary stages; that is, persons with syphilis during the early stages are usually not ill enough to cease work. Acutely fatal cases, such as frequently occurred in the sixteenth century, are now rare; in other words, the disease has lost much of its early virulence. It is the late manifestations, the sequelae and the so-called parasyph- ilitic lesions, as well as the inherited consequences of the disease, that cause great economic loss. About one-fifth of all the iasane in our asylums are cases of general paresis; 90 per cent, of these give the Wassermann reaction. Syphilis, alcohol, and heredity fill our insane asylums. The consequences of syphilis are often more severe upon the off- spring than upon the syphilitic parent. The infection itself, or various defects, especially of the nervous system, resulting from the consequences of syphilis, may be transmitted from parent to child, often with fatal results. When death does not ensue the results may be still more tragic. Syphilis is an infection caused by the Treponema pallidum (formerly known as the Spirochceta pallida). It is a communicable disease ac- quired by direct contact with infected persons or things. It runs a chronic course with local and general manifestations, usually divided into three stages, which are not always well defined. The primary stage consists of the chancre which forms at the site of the initial in- fection. The chancre is a hard indurated ulcer in the skin or mucous membrane, and appears about three weeks (not less than ten days) THE VENEEEAL DISEASES 51 after the receipt of the infection. The secondary stage is characterized by a general invasion of the spirochete throughout the system, as in- dicated by a general involvement of the lymph nodes, eruptio.ns upon the skin and mucous membranes, fever, anemia, and other indications of a generalized infection. The third stage is characterized by a localized granulomatous growth known as a gumma. Gummata may appear in almost any tissue or organ of the body. A fourth stage is sometimes added to the picture, consisting of the sequelae or parasyphilitic phe- nomena, such as general paresis, arteriosclerosis, locomotor ataxia, an- eurysm, etc. The health officer should regard syphilis just as he does the acute febrile exanthematous diseases. Because syphilis runs a slow and often chronic course with mild constitutional symptoms during its early stages, it is often placed in a class by itself. This is a mistake. Syph- ilis has its period of incubation, eruption, and decline, just as measles and smallpox have. There is no natural immunity to syphilis ; all are susceptible, but the severity of individual cases varies greatly. This is due either to the virulence of the strain, the amount of the infection, or to variation in individual resistance. The disease is now much less severe than it was following the pandemic which spread over the civilized world after 1494, when the army of Charles VIII, 32,000 strong, started out to conquer the Italian peninsula. One attack of syphilis confers an immunity, in that reinfections do not produce another chancre. That is, the virus cannot be inoculated upon a person who has or has had the disease. The immunity is pe- culiar in that, while the person cannot have a second chancre, this fact has no influence upon the development of the secondary and tertiary lesions resulting from the first infection. For CoUes' and Profeta's laws of syphilitic immunity and the transmission of syphilis see page 447. In a large majority of all cases of syphilis the infection is trans- mitted during sexual approach. It is, therefore, spoken of as a venereal disease ; many cases, however, are contracted out of venery. These ac- cidental infections are more common than is ordinarily supposed. MetchnikoflE reports that a great number of cases of non-venereal syph- ilis occur among children in Kussia, where the peasants live huddled together and in ignorance. Syphilis may be passed from one person to another by kissing, and the danger is greater when there are mucous patches or other open lesions upon the mouth. The disease may also be transmitted in wounds inflicted by the teeth of syphilitics. In sur- gery and midwifery practice physicians are not. infrequently infected through minute abrasions — a pin prick or a scratch from a scalpel is sufficient to introduce the virus. Midwifery chancres are usually upon 52 SPECIAL PEOPHYLACTIC MBASUEBS the fingers. Chancre of the Hp is the most common of the erratic or extragenital forms, and may be acquired in many ways apart from direct infection, such as the use of spoons, glasses, pipes, etc., which have recently been mouthed by a syphilitic. The virus may also be trans- mitted by towels, clothing, razors, handkerchiefs, surgical and dental instruments, human vaccine virus, etc. The list of articles that have conveyed the contagium is comprehensive. The Treponema pallidum is a fragile organism and soon dies upon fomites,' but the infection is suflB- ciently prevalent and the danger sufSciently real to demand care. Chancres of the mouth and on the tonsils result, as a rule, from per- verted practices. Wet nurses are sometimes infected on the nipple, and it occasionally happens that the relatives of a syphilitic child are acci- dentally infected. The hereditary and congenital transmission of syph- ilis is discussed on page 446. Syphilis lowers the standard of health and paves the way for other diseases. Whatever the etiological relationship may be, it is definitely known that syphilitics are prone to die early from affections of the heart and vessels, general paresis, diseases of the central nervous system (loco- motor ataxia), chronic nephritis, arteriosclerosis, aneurysm, etc. The actuaries of all life insurance companies know that the morbidity and mortality rates among syphilitics are very much higher than that of any other class of individuals of the community who enjoy apparent good health at the time of examination. Most insurance companies refuse to accept syphilitics at all. Some companies require extra premiums to compensate for the extra risks; a few companies will accept exceptionally favorable cases who have had a thorough course of treatment, and who have shown no symptoms for 3 to 5 years, but under these circumstances only special policies are contracted for which do not keep the applicant on the companies' books after 55 years of age. Syphilis was regarded as an infection peculiar to man until Nicolle and Hamonic in 1902, and Metchnikoff and Eoux in 1903, transmitted the disease to the higher apes. As a result of these experiments cer- tain important facts in reference to prophylaxis were discovered. Metch- nikoff and Eoux found that bichlorid of mercury, 1-3,000, applied one hour after inoculation, does not prevent the development of the pri- mary lesion in the monkey. This is probably due to the fact that the action of the bichlorid is limited to the surface; it lacks penetration owing to its well-known property of coagulating albumin. Other anti- septics were tested, but in a long series of experiments, carried out on chimpanzees, baboons, and Macacus monkeys, Metchnikoff and Eoux showed that mercurial inunctions are most successful in preventing the development of the chancre. The mercurial inunctions may be made with metallic mercury, calomel, white precipitate (ammoniated mer- THE VENEREAL DISEASES 53 cury), or salicyl-arsenite of mercury. Calomel ointment appears to be the best, and is the one now generally used. It is rubbed up in lanolin in the proportions of 1 to 3 or 1 to 4. The ointment should be rubbed upon the place for 4 to 5 minutes and not later than 20 hours after the receipt of the infection. This will usually prevent the development of the disease. Excision, or destruction of the chancre with the actual cautery or with corrosive antiseptics does not influence the development of the disease. GONORRHEA Gonorrhea is much more prevalent than syphilis, and common opin- ion regards it as a comparatively trivial infection, that is, "no worse than an ordinary cold." As a matter of fact, gonorrhea is one of the serious infectious diseases, and the gonococcus occupies a position of high rank among the virulent pathogenic microorganisms. Erom an economic and public health standpoint, gonorrhea does not fall very far short of syphilis in importance; in fact, some give it first place. The serious consequences of gonorrhea are: complications such as periurethral abscess, gonorrheal prostatitis in the male, and vaginitis, endocervicitis, and inflammation of the glands of Bartholin! in the fe- male. Perhaps the most serious of all the sequela of gonorrhea are those which result from the spread by direct continuity of tissues, such as inflammation of the Fallopian tube, and sometimes of the endomet- rium, the ovary, or even the peritoneum. The gonococcus has been found in pure culture in cases of acute general peritonitis. Other in- flammations caused by the spread of the infection are cystitis, which sometimes extends upward through the ureters to the kidneys. The gonococcus sometimes invades the blood and produces a general septicemia and pyemia; death may occur from acute endocarditis. Gon- orrheal arthritis is, in many respects, the most damaging, disabling, and serious of all the complications of gonorrhea. It may even follow ophthalmia neonatorum. It is more frequent in males than in females, but a gonorrheal arthritis of great intensity may occur in a newly mar- ried woman infected by an old gleet in her husband (Osier). The serious nature of gonorrheal complications in the eye will be considered separately under Ophthalmia Neonatorum. Gynecologists tell us that the greater part of their practice is made up of the consequences of gonorrhea. Sterility is one of the serious consequences of gonorrhea. This may be caused in the male through epididymitis, which is a very com- mon complication, and in the female by salpingitis, which closes or ob- structs the Fallopian tube. Stricture of the urethra in the male is a frequent sequel. 54 SPECIAL PEOPHYLACTIC MEASUEES Gonorrhea is usually transmitted by sexual congress; however, ac- cidental or innocent infections are not infrequent. Paul Bendig ^ reports the following instance: Of 40 girls sent for convalescence to a brine bath, 15 showed signs of gonorrhea after the return. The infection came from an eight-year-old girl, who apparently had been suffering from gonorrhea for several years, and was spread through indiscriminate bathing in one bath tub and the use of the same bath towel. Gonorrheal infections in children require special consideration. The frequency of such infections may be judged from the observations of Pollack, who reports 187 cases treated in the Woman's Venereal De- partment of Johns Hopkins Hospital during the year 1909.^ Pollack estimates that 800 to 1,000 children are infected each year in Balti- more, and that the same proportion probably holds good for other cities. The cause of the freqiient infection among children is in part the su- perstition that a person infected with syphilis or gonorrhea may get rid of it by infecting another — especially a virgin. When gonorrhea enters a children's hospital or an infants' home it is prone to become epidemic and is very difficult to eradicate. The story of the infection in the Babies' Hospital, New York, for eleven years, as told by Holt,^ illustrates the singular obstinacy of the infec- tion. In spite of the greatest care and precaution, there were, in 1903, 65 cases of vaginitis with S of ophthalmia and 13 of arthritis. In 1904 there were 52 cases of vaginitis, only 16 of which would have been recognized without the bacteriological examination. In all, in the eleven years, there were 273 cases of vaginitis; 6 with ophthalmia and 26 with arthritis. Holt urges isolation and prolonged quarantine as the only measures to combat successfully the disease (Osier). It is impossible to control such epidemics without bacteriological diagnosis. Chancroid is not discussed separately because its prevention .is sim- ilar to the measures used against syphilis and gonorrhea. Chancroid sometimes directly results in severe, even fatal, results, but does not, as a rule, leave dangerous sequelae. VENEREAL PROPHYLAXIS AND HYGIENE OF SEX The same principles apply to the prevention of the venereal diseases as apply to the prevention of other communicable diseases. The fight against venereal diseases, however, is especially complicated and difficult because of the close association with prostitution, the problems of sex hygiene, and alcoholism — in fact, the question pervades the woof and " Miinchener med. Wochenschr., 1909, p. 1846. ^ Johns Hopkins Hospital BuUetin, May, 1909, p. 142. ^ New York Med. Jour., March, 1905. VENBEBAL PEOPHYLAXIS AND SEX HYGIENE 55 warp of society. There are three primitive appetites of man — hunger, thirst, and the sexual appetite. The first two persist throughout life; the last comes on at puberty, grows stronger during adolescence, and wanes with age. Any program for the control of the venereal diseases or the hygiene of sex must take into account the fact that we are deal- ing with a primal, impulsive, and natural passion which is the greatest force for social good, when used in accordance with the laws of nature, but may result in dire consequences when these laws are transgressed. The venereal diseases are among the most widespread and universal of all human ills, and enter more largely in the making and marring of domestic happiness than any other disease known to man. The diffi- culties of the situation should not deter the health officer and all those who labor for social uplift, for there is no more pressing problem in preventive medicine. Attitude. — Our attitude toward the venereal diseases is very incon- sistent. There is a natural aversion toward these afflictions. The sani- tarian should make no distinction between the venereal diseases and other epidemic diseases; he should regard the greatpox in the same light that he regards the smallpox. The principles for the control of syphilis and gonorrhea differ in no wise from those used to control smallpox, leprosy, tuberculosis, measles, diphtheria, etc. The health officer must not regard venereal disease as a punishment for sin and crime — the victim or culprit needs help and sympathy. The immediate problem is the prevention of further spread of the infection. A person afflicted with a venereal disease should be treated in the same humane spirit that actuates the physician in other diseases. Furthermore, the interests of the community require that the patient be accorded the best possible care and attention. The usual attitude toward the venereal diseases may well startle us when we consider that in most of our large cities no hospital will take a case of syphilis or gonorrhea during the acute stages, when these diseases are especially communicable. Morrow holds that the notoriously inadequate provision made for the reception and treatment of venereal patients is a disgrace to our civilization. Formerly lepers were segregated in vile lazarettos and cases of smallpox isolated in horrible pest houses; now we have comfortable and congenial isolation wards or special sanatoria for these diseases. From the stand- point of prevention suitable hospital accommodations should be provided for the venereal diseases. Education. — Education in sex hygiene and the venereal peril accom- plishes a certain amount of good. It may be questioned how much a knowledge of the consequences will prevent some persons committing crime. However, the old-style innocence must be regarded as present- day ignorance. Every boy and girl, before reaching the age of pu- berty, should have a knowledge of sex, and every man and woman be- 56 SPECIAL PEOPHYLACTIC MEASURES fore the marriageable age should be informed on the subject of repro- duction and the dangers of venereal diseases. Superficial information is not true education. On the other hand, it is a mistake to dwell un- duly upon the subject, for in many instances the imagination and passion of youth are inflamed by simply calling attention to the sub- ject. One of the objects of education is to avoid the dangers of sex impurities, and all agree that this may often best be accomplished by keeping the mind clean, that is, away from the subject. The education must, therefore, be clear, pointed, brief, and direct. The object of education is not alone to help the individual to help himself, but to influence necessary legislation and concerted public action; also to les- sen the influence of quacks. A simple knowledge of the facts is a suffi- cient deterrent for some; others may be influenced through fear of the consequences. In general, it may be said that the best plan of education in mat- ters sexual is to answer the questions of children upon the subject of maternity frankly and truthfully, but to offer them no information on the subject. The growing child at the age of puberty should be offered a certain amount of information concerning unnatural habits and should study physiology, biology, especially botany, and the facts of fertiliza- tion. At about the age of sixteen or eighteen girls as well as boys should be instructed as to the venereal peril. The pamphlets issued by the Committee on Sex Hygiene of the Massachusetts Association of Boards of Health are admirable. One circular is for young men, an- other for young women, and a third for those having venereal disease. Some of the facts all young men should know are: that the true purpose of the sex function is reproduction and not sensual pleasure; that the testicles have a twofold function, (a) reproduction and (h) to supply force and energy to other organs of the body; that occasional seminal emissions at night are evidences of normal physiological activ- ity; that sexual intercourse is not essential to the preservation of virility; that chastity is compatible with health; and that the sex instinct in man may be controlled. The primary function of the testicles is to build the boy into the man. Castration in early life, as in the case of eunuchs, results in a loss of the internal secretion of the testicles and a failure in develop- ment of the secondary sexual characters which distinguish the male. There are an alteration in physical conformation and in the voice, lack' of beard, development of the mamma, etc. — in other words, an ap- proach to the feminine type. Healthy sexuality stimulates the imagina- tion, sentiment, the esthetic sense, and the higher creative functions. Excesses or any influence which weakens the sexual system impair the will power, influence self-respect, and diminish mental force. Experi- ence shows that arduous physical and mental labor, even after maturity VBNEEEAL PEOPHYLAXIS AND SEX HYGIENE 57 is attained, is best performed when the sex organs are not exercised; while sexual excess distinctly impairs muscular strength and mental efficiency. It is unwise to frighten boys by exaggerating the results of self-abuse, which is rather the effect and not the cause of idiocy, insanity, degeneracy, and other defects of the central nervous organization. Self- abuse is no worse in its effects than natural coitus, except for its influ- ence upon character. Both are alike harmful when indulged in to excess. Registration of Cases.— It is not possible to control any communi- cable disease, especially one that is pandemic, such as syphilis or gonor- rhea, without a knowledge of the cases and deaths. It is perhaps even more important to collect morbidity and mortality statistics of the great- pox than it is of the smallpox. But the public registration of private disease at once defeats its own object. Compulsory methods have here- tofore failed, and little may be expected from voluntary registration. When we consider that in our country we have no means of knowing the amount and distribution of smallpox, except to a limited degree in the registration area (which is less than one-third of our domain), what can we expect from the registration of the closely guarded secrets of- the underworld? The public registration of ophthalmia neonatorum is successful because this form of gonorrhea is so apparent and the con- sequences so immediate and serious. The difficulties, however, need not deter us, and registration should be attempted even though the returns are incomplete. A start should be made, and, though the returns will be only partial at first, a gradual improvement may be ex- pected. Every case known and properly cared for is a focus of infection neutralized. Continence. — One of the important facts to teach boys is that con- tinence is compatible with health. The testicles are like the tear glands and the sweat glands, in that they do not atrophy with disuse. Ben- jamin Franklin taught, as many another man of influence believes to- day, that the exercise of the sexual functions is necessary for health. This is a mistake and has done much harm. The sex principle is universal in nature. It is the force behind the constructive and progressive processes of all life, from the color adaptations of birds and flowers to the highest leadership in men. Re- production is only one of its many functions; and the man who as- sumes that the so-called physical desire that at times thrills him indi- cates a need of sexual intercourse is in danger of depleting and wasting from his life a chief source of physical and mental growth. The single standard for men and women must be insisted upon, and the parent or guardian is justified in demanding a clean bill of health of the young man who proposes marriage. The young man, in turn, is entitled to the same from his prospective father-in-law. One of the 58 SPECIAL PEOPHYLACTIC MEASUEES defects of our artificial civilization which leads to harm is the post- ponement of the marriage age. Carnal lust may be cooled and quelled by hard work of the body, as well as attention to personal hygiene — hence, one of the great ad- vantages of athletic sports for growing young men. Personal Hygiene.— Idleness, stimulating food, overeating, impure thoughts, evil associates, and alcohol excite the passions and are the bed- fellows of the venereal diseases. Purity of mind and cleanliness of body are helpful prophylactics. Physical exercise and an out-of-door life divert the mind and help the body; it is a good safety valve for the excess animalism of youth. The public should be taught the necessity for thorough daily cleans- ing of the external genitals in both sexes, even in children. The large number of secreting glands and the decomposition of their secretions are liable to induce irritation and even minute lesions which open portals to infection of all kinds. Alcohol. — ^The strongest indictment against alcohol is that it excites the passions and at the same time diminishes the will power. The fact that alcohol lowers moral tone does much more harm than all the cirrhotic livers, hardened arteries, shrunken kidneys, inflamed stomachs, and other lesions believed to be caused by its excessive use. ProstitTition. — The regulation of prostitution by means of medical inspection has been tried and largely abandoned. In other words, it is a failure, for the reason that it makes vice easy and is, therefore, morally wrong. It gives a false sense of security and does not reach clandestine prostitution, which is the great source of the venereal diseases. Under certain limited conditions, such as in army encampments, where clan- destine prostitution can be eliminated, regidation has markedly dimin- ished the prevalence of venereal disease. The elimination of prostitution is beyond the dream of even the theoretical reformer. Its control resolves itself into questions of per- sonal hygiene and public hygiene ; it is inextricably mixed up with alco- holism, and, like the abuse of alcohol, the question may best be reached by that slower, surer process of improving the moral and physical fiber of man. Medical Prophylaxis. — In accordance with the researches of Metch- nikoff and Eoux a reasonably efficient prophylaxis against the venereal diseases is now possible. In the United States Navy the following method is employed : The entire penis is scrubbed with liquid soap and water for several minutes, and then washed well with a solution of mercuric bichlorid, 1 to 2,000 in strength. If there are any abrasions present, they are sprayed with hydrogen peroxid from a hand atomizer. The man is then placed in a sitting position, well forward in a chair in front of a convenient receptacle, and given two injections of a 10 VENEEEAL PEOPHYLAXIS AND SEX HYGIENE 59 per cent, solution of argyrol. He is required to retain each injection in the urethra for five minutes. After talcing the injections, the entire penis is thoroughly anointed with a 33 per cent, calomel ointment. He is told not to urinate for at least two hours, and to allow the ointment to remain on the penis for some hours. A temporary dressing is placed on the parts to protect his clothes. The measures which will prevent gonorrhea will not ward off syphilis, and vice versa. The results attending such prophylactic treatment are very good. Thus Ledbetter ^ reports that at Cavite, before medical prophylaxis was instituted, the percentage of venereal diseases of all classes among the men averaged from 25 to 30 per cent, annually, and at times even higher. The percentage of gonorrhea was reduced to 8 per cent, annu- ally, and this percentage included about 30 patients who did not report for treatment. Chancroid was reduced from 5 to 3 per cent., which included 2 patients not reporting for treatment. Syphilis has been re- duced from about 20 cases annually to one case for the entire year 1910, and this patient did not report for prophylactic treatment. The results speak for themselves and show the efficiency of the prophylactic measures if properly and thoroughly carried out. Holcomb and Gather - report the following as a result of treatment used by them in 3,268 persons in the U. S. Navy between May 1, 1910, and August 31, 1911. The experience is considered to be a fair index of the results of medical prophylaxis. The treatment used by them is as follows: (1) Wash the penis, head, shank, and under frenum with 1-5,000 bichlorid of mercury solution with a cotton sponge. (2) Pass water. Take urethral injection of 2 per cent, protargol solution and hold to count 60. (3) Eub 50 per cent, calomel ointment well into foreskin, head, and shank of penis, with particular care about the fre- num. Treatment taken within eight hours after exposure in 1,385 cases shows 19 infections, or but 1.37 per cent. In the interval of from eight to twelve hours after exposure in 741 cases shows 25 infec- tions, or 3.31 per cent. Between twelve and twenty-four hours in 920 cases shows 46 infections, or 5 per cent. Of the 56 cases of gonorrhea occurring in the first twenty-four-hour interval, 26 were recurrent eases ; the remaining 30 were primary infections. The use of salvarsan early in syphilis will prevent the further spread of the infection. Segregation. — Theoretically, every case of syphilis or gonorrhea should be isolated until the danger of infection is passed. Practically, ' Ledbetter, Robert E., ' ' Venereal Prophylaxis in the U. S. Navy, ' ' Jour. A. M. A., April 15, 1911, Vol. LVI, No. 15, p. 1098. "Holeomb, E. C, and Gather, D. C, U. S. N., "Study of 3,268 Venereal Prophylactic Treatments," Jour. A. M. A., Vol. LVIII, No. 5, Feb. 3, 1912, p. 368. 60 SPECIAL PEOPHYLACTIC MBASUKES however, segregation is impracticable except with a limited number of cases. With better and more attractive hospital facilities and free beds a certain amount of segregation may be accomplished voluntarily and humanely. An alert health officer can trace the source of infection in certain cases and induce the women responsible to take the salvarsan treatment in the case of syphilis, or to submit to hospital care in the case of gonorrhea or chancroid. Eoutine circumcision and a medical examination as a necessary pre- liminary to marriage are further hygienic reforms advocated. Finally, in considering venereal prophylaxis, it should be remem- bered that these diseases are of great antiquity and seem likely to con- tinue indefinitely, that they already afEect a large number of the popu- lation, and are spreading; that the existing means for the treatment of them among the poor is insufficient; that the common mode of propagation is irregular and illicit intercourse; that prostitution arose in response to the strongest instincts and passions in the human breast; and that prostitutes themselves need protection and have claims on the humanity of the law. PREVENTABLE BLINDNESS Preventable blindness is considered in this place because the lar- gest single factor causing needless loss of eyesight is gonorrhea. Among the infectious eye troubles the most destructive is ophthalmia neona- torum. There are 64,000 registered blind persons in the United States. Of these about 10 per cent, (between six and seven thousand) are blind as the result of ophthalmia neonatorum. From 25 to 30 per cent, of all the blind children in all the blind schools of this country owe their infliction to gonorrhea. It has been estimated that probably one-half of the blindness in the world is preventable. Emphasis upon the great harm done by ophthalmia neonatorum should not blind us to the fact that there are other causes of blindness and eye deterioration which are preventable; thus we have to consider the later pus infections, syphilis, sympathetic inflammations, indus- trial accidents, accidents at play, progressive nearsightedness caused by violation of ocular hygiene, and a variety of inflammatory condi- tions. Functional disturbances of vision (amaurosis) and atrophy of the optic nerve may be brought about by poisoning with lead, alcohol, tobacco, and other toxic substances. This form of dimness of vision, or even loss of sight, occurs rather frequently, and in many instances is preventable. Trachoma is a menace to the integrity of sight. It is an infection PEEVENTABLB BLINDNESS 61 caused by a filterable virus.^ It flourishes best where sanitary conditions are worst. The disease is slow and insidious in its development. A mass of sago-like granulations gradually fills in the retrotarsal fold, thereby limiting the lid movements and leaving the eye half closed. The infec- tion is rubbed into the eye by roller towels, handkerchiefs, fingers, and other ways. When once established, the disease is chronic, and per- manent cures are doubtful. Trachoma is much more prevalent in the United States than ordinarily supposed. The public eye clinics of Chicago are filled with patients showing the resulting deformities. Wilder located a center in southern Illinois, and it has also been found in the mountains of Kentucky and Tennessee, while in Oklahoma it has become a public menace. It is more or less prevalent in the poorer sections of all the large centers. Trachoma is of such a serious nature that all immigrants arriving at our shores have their eyelids everted and conjunctivae examined for evidence of this infection. An alien with trachoma is deported and the steamship is liable to a fine of one hundred dollars for bringing every case of trachoma where it can be shown that the disease might have been recognized at the port of departure. Wood alcohol is one of the causes of blindness. As small a quan- tity as a teaspoonful has caused loss of vision. Wood alcohol is used as an adulterant, especially in liquors. The excessive use of tobacco also leads to dimness of vision. In New York State about 200 industrial accidents resulting in total blindness occur annually. Besides this, there is a large number of accidents occurring on railroads in construction work, and in the field and forest. Many of the accidents to the eyes occurring in fac- tories are preventable. The majority of such accidents are due to small flying particles. A material proportion of blindness is caused by accidents to chil- dren at play; sometimes the eyeball is torn by a buttonhook or pierced by a knife or awl ; or a scissors blade, used to untie a knot, slips. Some eyes have been injured by the crack of a whip, by a shot from an air-gun or toy pistol. Accidents also occur to the eyes from fireworks, especially on the Fourth of July. OPHTHALMIA NEONATORUM Ophthalmia neonatorum or inflammation of the eyes of the new- born includes all the inflammatory conditions of the conjunctiva that occur shortly after birth — usually before the end of the first month. 'Bertarelli and Cacchetto, Centr. fiir BaU., Orig., I Abt., Bd. XLVIII, 1908, p. 432. 62 SPECIAL PKOPHYLACTIC MEASUEES The conjunctivse of the newborn are peculiarly liable to infections. This delicate membrane rapidly acquires an immunity of a high order. The gonococcus is usually the cause of severe conjunctivitis occurring in a baby a few days old. The gonococcus has been demonstrated in 65 per cent, of all cases, mild and severe. Ophthalmia neonatorum is not alwa3's gonorrheal, but may be pro- duced by other virulent microorganisms or by irritating substances. The microorganisms other than the gonococcus that sometimes cause conjunctivitis during the early days of life are : streptococci, the menin- gococcus, the Koch-Week's bacillus, the pneumococcus, the diphtheria bacillus, and even staphylococci. These are relatively so rare that we may disregard their etiological significance for our present purpose. The diagnosis of gonorrheal ophthalmia may readily be made by simply examining a stained smear of the secretion. The infection commonly occurs during the passage of the child through the genital tract of the mother and usually just before deliv- ery. It is caused by the entrance of the vaginal secretion containing gonococci into the conjunctival sac. It may also be caused after de- livery by infected hands, towels, sponges, or other objects. The disease varies in severity; sometimes it is very mild, with slow onset and spontaneous recovery. Usually, however, it is severe and serious. The inflammation may extend from the conjunctiva to the cornea and invade the deeper structures of the eye. Corneal ulcers and opacity may result, with complete loss of vision. In a typical case both the ocular and palpebral conjunctivse are red and very much swollen; the eyelids and surrounding tissues are infiltrated and there is a thick, creamy, abundant secretion. There are many grades of mild inflammatory condition, which must not be mistaken for gonorrhea. At birth the eyelids are almost always glued together with the normal sticky secretions. It is common, too, for the lids to remain red and sticky for a day or so. The diagnosis may be made in a few minutes by a microscopic examination. Prevalence.— Kerr calls attention to the fact that there are no com- plete statistics showing the prevalence of ophthalmia neonatorum, and only an approximate idea can be had of the number of cases by study- ing the admissions to schools for the blind. A committee of the Brit- ish Medical Association found that more than one-third of those in blind schools of Great Britain owed their affliction to this disease.^ In the United States and Canada, in 1907, out of 224 admissions to 10 schools for the blind, 59, or 24.38 per cent., were blind as a re- sult of ophthalmia neonatorum •,"■ and out of 351 admissions to certain ^British Medical Journal, May 8, 1909. 'Jour. A. M. A., May 23, 1909, p. 1745, PEEVENTABLE BLINDNESS 63 schools in the United States and Canada in 1910, 84, or 23.9 per cent., were blind from this cause.^ As a result of studies made of ophthalmia neonatorum in 10 man- ufacturing cities of Massachusetts, Greene has presented figures which show that the minimum morbidity rate for this disease was 6.4 per 1,000 births. A more complete census made by him for the practice of 173 physicians in 9 cities revealed an average morbidity rate of 10.8 per 1,000 births.^ It is estimated that the total annual loss from gonorrheal ophthalmia in the United States is seven million dollars, and that an amount of more than one million dollars annually is spent in partially caring for its victims. A blind child costs the community an excess of about $4,500 for its schooling. Prevention.— Ceede's Method. — Crede in 1881 introduced an effi- cient method of preventing ophthalmia neonatorum at the Lying-in Hospital at Leipzig, thereby connecting forever his name with the pre- vention of the disease and the subsequent saving of the sight of many infants. Crede's original method consisted simply in placing one or two drops of a 2 per cent, solution of silver nitrate in each conjunc- tival sac, as soon as practicable after the birth of the head. In order to prevent gonococeic as well as other infections of babies' eyes, the following procedure is recommended : During pregnancy women should be instructed to practice daily external cleansing with soap and water and a clean wash-cloth. In case of any irritating dis- charge or even profuse white discharge, a physician should at once be consulted. Immediately after labor the eyelids should be carefully cleaned with sterile absorbent cotton or gauze and a saturated solution of boracic acid. A separate pledget should be used for each eye and the lids washed from the nose outward until quite free of all mucus, blood, or meconium without opening the lids. Next the lids should be separated and one or two drops of a one per cent, silver nitrate solution should be dropped into each eye, between the outer ends of the lids. The lids should be separated and elevated away from the eyeball so that a lake of silver nitrate solution may lie for one-half minute or longer between them, coming in contact with every portion of the conjunctival sac. One application only of the silver nitrate should be made, and ordinarily no further attention need be given to the eyes for several hours. Each time the child is bathed the eyes should first be wiped and cleaned with pledgets of sterile absorbent cotton wet with a saturated solution of boracic acid. ^ Ihid., July 1, 1911, p. 72. 'Monograph Series of the American Association for Conservation of Vision, Vol. I, No. 1. 64 SPECIAL PROPHYLACTIC MEASUEES Crede used a 2 per cent, solution of silver nitrate, but, as this is sometimes irritating, a 1 per cent, solution is now commonly employed, and seems to afford equally efficient prophylaxis. The silver nitrate solution should be instilled into each conjunctival sac but once. Re- peated applications may cause serious inflammations. In fact, a single treatment sometimes causes a conjunctivitis, known as "silver catarrh." Because of the silver catarrh the strength of the silver nitrate solution has not only been reduced from a 2 to a 1 per cent, solution, but this may be neutralized after instillation with salt solution. Other prophy- lactic substances have been proposed. The best substitutes are a few drops of the newer silver compounds, as argyrol (25 per cent.) or protargol (5 per cent.). The following have also been recommended: Bichlorid of mercury, 1-2,000 or 1-5,000, silver acetate, 0.23 per cent., recommended by Zweifel, who used it in 5,222 cases. Schmidt and Eimpler recommend aqua chloriwi. Carbolic acid (1 per cent.) or other antiseptics have also been tried. No substance, however, is known to be as reliable as silver nitrate, which should be used in all cases where there is any reason for believing that the mother is infected with the gonococcus. If a conjunctivitis is present, a bacteriological examination of the discharge should at once be made. If the inflammation is due to the gonococcus a 2 per cent, silver nitrate solution should be used. In cer- tain mild, non-gonorrheal infection 0.5 per cent, is usually sufficient. If the Klebs-Loeffier bacillus is found, diphtheria antitoxin should be given without delay. If the diplocoecus is present, a weak solution (1 grain to the ounce) of zinc sulphate should be instilled frequently. As a general rule, it is advisable to use a prophylactic as a mat- ter of routine in hospital and private practice. To use Crede's method upon every case necessitates the unpleasant suspicion that every woman is a possible source of gonococcus infection. If statements of the father about his previous life can be relied upon, an eye prophylactic can be safely omitted. In his private work Williams uses a boric acid solution except where there is special reason for believing that the mother has gonorrhea. The responsibility for risking the baby's eyes rests upon the medical attendant. There can only be one safe rule in case of doubt. It should be remembered that gonococcic infections of the con- junctiva occur in about one to every two hundred births (Edgar). The good results of Crede's method are sufficiently convincing to justify criminal proceedings upon those who fail to apply this simple prophylactic. Haab reduced the frequency of ophthalmia neonatorum in hospital practice from 9 to 1 per cent., while the statistics of many hospitals show only a very small fraction of 1 per cent. Stephenson's results are typical. In 2,265 births, ophthalmia neonatorum developed in 10 per cent, of the cases preceding the use of Crede's method. In PREVENTABLE BLIJSTDNBSS 65 1,160 births after this method only 0.17 per cent, developed any trouble. A small number of cases may develop despite the use of silver nitrate. The technique of applying the nitrate of silver is very important, for, in the opinion of Edgar, when ophthalmia neonatorum develops after the use of nitrate of silver, it is due either to a secondary infec- tion or to the fact that the solution does not really bathe the mucous membranes, but remains upon the lashes. The lids must be everted and the silver solution placed in the conjunctival sac either from a glass rod or a pipette. Care must be taken not to touch or injure the delicate membrane. Crede's method does not strike at the root of the evil. It would, of course, be much better to eradicate gonorrhea from men and women than to be compelled to drop silver nitrate into babies' eyes. Wrapped up with the question of ophthalmia neonatorum is the question of midwives, for to prevent blindness we must have intelligent and con- scientious obstetrical attendants, especially for the poor and ignorant classes. Midwifery practice needs regulation, supervision, and eleva- tion. Education is one of the bulwarks of prevention in this as well as other preventable infections. Legislation". — Ophthalmia neonatorum is an instance in which "the protection of the citizen from the assaults of ignorance, indifference, or neglect, when they threaten his well-being and even his economic efficiency, is a duty which the state cannot evade and which he has a right to exact." Laws for the prevention of the blindness of newborn infants are making progress slowly. Among the states in which the disease is notifiable are Connecticut, Massachusetts, Minnesota, Nebraska, New York, Oregon, South Carolina, Utah, Vermont, and Wisconsin. In some states the nurse, midwife, or parent is required to report the dis- ease, in other states the attending physician. Maine was the first state to take legal steps in 1891 to control ophthalmia neonatorum. In. 1892 New York followed, with an amend- ment to the law relative to midwives and nurses. Subsequently most of the other states took legislative action.^ The provisions of the several laws are quite varied. In all of them, however, the object is to insure early treatment, and to this end compulsory notification is generally required. The health authorities of Massachusetts, New Jersey, Vermont, Ehode Island, New York, and the District of Columbia furnish prophylactic outfits to physicians. The outfit ordinarily consists of a small vial containing a 1 per cent, solution of nitrate '^Kerr, J. W., "Ophthalmia Neonatorum: An Analysis of the Laws and Eeg- ulations Relating Thereto in Force in the United States," Fublio Health Bull. No. 49, U. S. P. H. & M. H. S., Oct., 1911. 66 SPECIFIC PROPHYLACTIC MEASUEES of silver, a sterilized dropper and bulb, and a circular of instruc- tions. In order to make material progress against ophthalmia neonatorum, as well as against infant mortality, it is essential that laws require prompt report of all births; it is the duty of the health authorities to see to it that such laws are effectively carried out.^ TETANUS Compared with the major plagues of man, lockjaw has always been a rare disease. It is on account of the characteristic and fatal spasms that it early attracted attention. The student will be well repaid by a study of the historical development of the theories that have been advanced since the time of Hippocrates to explain the cause of tetanus. These theories mirror the prevailing thought upon the nature of dis- ease as it developed from that of evil spirits, through the humoral theory, the realm of miasms and noxious effluvia, to the germ theory. Tetanus could not escape the rheumatism theory which has been such an alluring catchall for symptoms and diseases difficult of explanation. "Taking cold" was assigned its usual role here as elsewhere. Wlien no assignable cause seemed at hand, the disease was given the learned title — idiopathic tetanus. Etiology. — In 1889, with the aid of anaerobic technique, Kitasato * for the first time grew the tetanus bacillus in pure culture, and by ^ The Massachusetts law reads as follows : Section 49. . . . Should one or both eyes of an infant become in- flamed, swollen and red, and show an unnatural discharge at any time with- in two weeks after its birth, it shall be the duty of the nurse, relative, or other attendant having charge of such an infant to report in writing within six hours thereafter, to the board of health of a city or town in which the parents of the infant reside, the fact that such inflammation, swelling, and redness of the eyes and unnatural discharge exist. On receipt of such re- port, or of notice of the same symptoms given by a physician as provided by the fohowing section, the board of health shall take such immediate action as it may deem necessary in order that blindness may be prevented. Whoever violates the PROvisioisrs op this section shall be punished by A PINE OP NOT MORE THAN ONE HUNDRED DOLLARS. Section 50. ... If a. physician knows that ... if one or both eyes of an infant whom or whose mother he is called to visit become in- flamed, swollen, and red, and show an unnatural discharge within two weeks after birth of such infant, he shall immediately give notice thereof in writ- ing over his own signature to the selectmen or board of health of the town; AND IP HE EEPUSES OR NEGLECTS TO GIVE SUCH NOTICE, HE SHALL FORFEIT NOT LESS THAN FIFTY NOR MORE THAN TWO HUNDRED DOLLARS FOR EACH OPPENCE. (Revised Laws, Chapter 75.) ' Zeitschr. f. Eyg., Vol. VII, 1889, p. 225. TETANUS 67 successful inoculation experiments proved that this bacillus was the real cause of tetanus. Kitasato further showed that the tetanus bacillus is not found in the heart's blood of mice dead of tetanus, and therefore concluded that we are dealing with an intoxication, and not an infec- tion. We now regard tetanus as a type of the true toxemias. This work of Kitasato's was one of great importance, and led up to the epoch- making discovery of Behring and Kitasato ^ in the following year (1890) upon tetanus and diphtheria toxines and antitoxins, laying the founda- tion of serum therapy. Tetanus may be regarded almost solely as a wound complication. All wounds are not equally liable to this complication, even though tetanus spores are present. Punctured, lacerated, and contused wounds are much more susceptible to tetanus than cleancut or superficial wounds. The size of the wound is of much less consequence than its character. Fatal tetanus may develop from trivial wounds, such as pin scratches, small splinters, insect bites, vaccinations, etc. Symbiosis is an important factor in tetanus. Wounds infected with pyogenic organisms and other bacteria favor anaerobic conditions and permit the tetanus spores to germinate, and seem to encourage the growth of the bacillus and the development of toxine.^ A few tetanus spores free of tetanus toxin in a clean wound may be taken care of by the phagocytic cells. This may readily be demonstrated experimentally by injecting animals with tetanus spores washed free of toxine. The normal habitat of tetanus is in the intestinal tract of herbiv- orous animals. Sanchez, Toledo, and Veillon" found tetanus in the feces of 4 out of 6 horses and in the feces of 1 of 2 cows. Park found tetanus bacilli in the intestines of about 15 per cent, of horses and calves living in the vicinity of New York City. They are present to a somewhat less extent in the intestines of other animals and of man. It is rather a curious paradox that the horse, which is the most susceptible of all animals to tetanus toxin, is one of the principal hosts of the tetanus bacillus. The spores taken in the food are not affected by gastric digestion, and in the small intestines find ideal anaerobic conditions, food supply and temperature for growth and development. Here they very prob- ably multiply and pass in the dejecta to pollute the soil. The soil, therefore, in all regions inhabited by man and domestic animals is more or less contaminated with tetanus. The bacilli, however, do not multiply in the soil. While the soil acts only as a vehicle, it is the immediate source of the large proportion of tetanus spores. > Deutsch. meat. Wochens., Vol. XVI, No. 40, p. 1113. ^ In the laboratory some of the strongest tetanus toxins have been prepared from mixed or contaminated cultures. ' La Semaine Med., 1890, X, p. 45. 68 SPECIFIC PEOPHYLACTIC MEASUEES It is assumed, but not proven, that tetanus bacilli grow in the in- testinal tract of herbivora. It is conceivable that the spores simply pass through the intestines without multiplying at all, but it is known that tetanus is capable of multiplying in symbiotic relation with other bac- teria wherever protein matter undergoes putrefaction under anaerobic conditions. On account of the great resistance of the spores, they are blown about in dust and are spread everywhere by dirt and manure. Tetanus has been found in hay dust, on horses' hair, in the dust of houses, bar- racks, and hospitals, in the mortar of old masonry, in street dust, in gelatin, and in the greatest variety of places. One of the agencies in the distribution of tetanus spores over limited areas is undoubtedly the common house fly. The arrow heads of certain savages in the New Hebrides contain tetanus spores obtained by smearing the arrowheads with dirt from crab holes in the swamps (Le Dantic). Tetanus bacilli are not equally numerous in all localities. The in- fection is much more prevalent in warm than in cold countries. It is especially severe in the tropics, yet Iceland at one time suffered severely from tetanus neonatorum. Some parts of Long Island and New Jer- sey have become noticeable for the number of cases of tetanus caused by small wounds. Tetanus spores are widely disseminated in India. Goodrich states that in Bombay alone there were 1,955 cases of tetanus in five years. These do not include the puerperal cases. Tetanus occurs either sporadically or in epidemic form. Formerly epidemics in hospitals (especially in lying-in hospitals) and in wars were rather common. Before the days of antisepsis the infection was readily spread through instruments, fingers, bandages, etc. Trismus neonatorum, or tetanus of the newborn, was a common and very fatal infection, especially in the tropics. Before the days of asepsis the infection was permitted to enter through the umbilical wound. In certain of the "West Indian islands more than one-half of the mortality among the negro children has been due to this cause. Since the introduction of proper methods of treating the cord the disease is rare. The wounds produced by blank cartridges are especially liable to develop tetanus. The source of the tetanus spore in these cases is not entirely clear. Wells examined 200 cartridges from five firms without finding the tetanus bacillus. It is probable that the spore is upon the skin and is carried along with the paper and powder from the blank cartridge. The peculiar character of the wound favors the develop- ment of tetanus. The great decrease in the number of eases of tetanus following Fourth of July wounds is due to the vigorous campaign carried on TETANUS 69 by the American Medical Association. In 1903 there were 406 deaths from tetanus; in 1904, 91; 1905, 87; 1906, 75; 1907, 73; 1908, 76; and in 1911 only 18 cases and 10 deaths. Eighty per cent, of these followed blank cartridge wounds. The good results are attributed to the more thorough and careful treatment of the wounds and especially the use of tetanus antitoxin as a prophylactic — and more recently to safer and saner methods of celebration. Tetanus spores or toxine may contaminate bacterial vaccines, anti- toxic sera, vaccine virus, and other biologic products used in human therapy. The possible association of tetanus with bacterial vaccines was demonstrated in the unfortunate outbreak at Mulkowal, India, in 1903. '^ One hundred and seven persons were inoculated with Haffltine's plague prophylactic. Of these 19 were affected with symptoms of tetanus and died. In this case the tetanus probably grew as a contamination in the plague culture, for it is now well known that the anaerobic conditions produced in B. diphtherim, B. pestis, B. subtilis, and other organisms in liquid culture media favor the growth of tetanus and the development of its toxin. In St. Louis (1901) diphtheria antitoxin was taken from a horse during the period of incubation of tetanus and used in amounts from 5 to 10 c. c. upon 7 children, all of whom died of tetanus. Bolton, Pisch, and Walden ^ found that the serum was sterile, but contained tetanus toxin in considerable amount. If the serum had first been tested upon animals, its poisonous properties would have been discov- ered. This test is now required by the United States law of July 1, 1902, for all serums and vaccines sold in interstate traffic. As a fur- ther precaution against this complication horses undergoing treatment for the production of immune sera are given prophylactic doses of te- tanus antitoxin from time to time. Tetanus sometimes occurs as a complication of vaccination. It is not clear in these cases whether the tetanus spores are contained in the vaccine virus or subsequently enter the wound. In many hundreds of special examinations made in the Hygienic Laboratory at Washing- ton tetanus spores have not been found in a single vaccine virus. Ex- periments show that in vaccine virus purposely contaminated the te- tanus spores remain alive and active for a long time (see page 19). It is, of course, not the rust on a nail that is dangerous, so far as tetanus is concerned, but the spore-bearing dirt it carries into the deep, contused wound that causes the trouble. Gelatin may contain tetanus spores, and the subcutaneous injection of imperfectly sterilized gelatin as a hemostatic has sometimes resulted in accidents. ^Jour. Trop. Med. and Hyg., 1907, X, p. 33. ^Bolton, Ksch, and Walden in St. Louis Medical Beview, Vol. XLIV, No. 21, Nov. 23, 1910, p. 361. 7 70 SPECIFIC PEOPHYLACTIC MEASUEES Tetanus is harmless when taken by the mouth. Susceptible animals may be given enormous doses of tetanus toxine by the mouth without producing the disease. The bacillus and its spore may be regarded as a saprophyte in the intestinal tract. There is, however, a suspicion that tetanus spores sometimes invade the organism through small wounds in the digestive or respiratory tract. Perhaps some of the cases follow- ing surgical operations may be accounted for in this way rather than by infection of the catgut used for ligatures. Tetanus sometimes occurs in which no wound can be found. This is the so-called "idiopathic or rheumatic tetanus." One explanation of these cases is to be found in the fact that the spores are numerous in street dust and may enter the respiratory tract. They cannot do harm so long as the mucous membrane is healthy, but may enter through inflamed membranes or through small wounds in the nose. Tetanus bacilli have been found in the bronchial mucus of idiopathic cases. Tet- anus spores have recently been found in the lymph glands, liver, and other parts of the body, upsetting our previous view that they are strictly confined to the site of the wound. These spores may remain latent for a long time, awaiting favorable conditions to grow and produce toxin, thus giving another plausible explanation of some cases of idiopathic tetanus. Incubation. — The period of incubation in man is usually from 6 to 14 days. The period is directly proportional to the amount of toxin and the severity of the disease. This can readily be demonstrated upon susceptible animals. In a study of 600 serial tests, Eosenau and Ander- son found this direct relation between the period of incubation and the severity of symptoms by the subcutaneous injection of varying amounts of toxin into guinea-pigs. Thus, guinea-pigs that showed symptoms on the third day usually died, a very small percentage recovering. The smaller the dose the longer the onset of symptoms is delayed, the milder is the disease, and the greater the chances of recovery. With a short period of incubation, 6 days or less, the disease in man is almost invariably fatal. With longer periods the disease is milder and recovery frequently takes place without the use of antitoxin or other measures. Tetanus toxin travels up the axis cylinders of the nerves to the cord and brain. It is also distributed in the blood. The period of incuba- tion, therefore, depends somewhat upon the point of entrance of the poison and its proximity to large motor nerve endings. Resistance. — The tetanus bacillus is readily destroyed by all the or- dinary agencies that kill spore-free bacteria. It is killed almost at once in contact with the free oxygen of the air. On the other hand, few, if any, forms of life have a greater resistance than the tetanus spore. Hours of exposure to 60° or 70° C. do not affect them. They usually survive an exposure of one hour to 80° C, but, as a rule, are killed in TETANUS 71 streaming steam or boiling water in 60 minutes. Tetanus spores, how- ever, vary greatly in the power to resist the boiling temperature. Kita- sato ^ found them to resist 80° C. for one hour, but to be killed in streaming steam in 5 minutes. Vaillard and Vincent ^ found that the spores heated in the presence of moisture in a closed vessel would resist destruction at 80° C. for 6 hours, at 90° C. for 2 hours, and 100° C. 3 to 4 minutes, that they were not always destroyed in 5 minutes, but never resisted more than 8 minute? at 100° C. Levy and Bruns ^ found that destruction begins at 8% minutes at 100° C; after 15 minutes few survive, after 30 minutes none. Falcioni * studied the subject in view of the dangers of the subcutaneous injection of gelatin. He im- pregnated gelatin with spores of tetanus bacilli grown in agar or broth for 10 or 12 days, and used Koch's steam sterilization. He found the spores to resist destruction for 2%, but not for 3, hours in streaming steam. The experimental results are, therefore, sufficiently varied and con- flicting to suggest that races of tetanus bacilli exist, the spores of which vary widely in their resistance to moist heat at 100° C. Theobald Smith ° found that under certain conditions of cultivation some tetanus spores survive a single boiling or streaming steam for 20 minutes reg- ularly, usually for 40 minutes, and occasionally for 60 minutes; in one case 70 minutes' exposure did not destroy the spores. He also showed the possibility of tetanus spores surviving in culture fluids sterilized by discontinuous boiling or steaming in routine laboratory work for fully 20 minutes on three successive days. Tetanus spores resist the action of 5 per cent, carbolic acid for 10 hours, but are killed in 15 hours. A 5 per cent, solution of carbolic acid, however, to which 0.5 per cent, of hydrochloric acid has been added, destroys them in 2 hours. Bichlorid of mercury, 1-1,000, kills the spores in 3 hours, and in 30 minutes when 0.5 per cent, of hydro- chloric acid is added to the solution. According to Park, silver nitrate solution destroys the spores of average resistance in 1 minute in 1 per cent, solution, and in about 5 minutes in a 1 to 1,000 solution. Tetanus spores are destroyed with certainty when exposed to dry heat at or above 160° C. for one hour, or to steam at 120° C. for 20 minutes. En- tire confidence may be placed upon either of these two methods. Direct sunlight does not kill the spores, but seems to diminish their virulence. IThder certain circumstances they may live a very long time; Henrijean reports that, by means of a splinter of wood which once '■Zeitschr. f. Hyg., VII, p. 225. ^ Annales de I'Institut Pasteur, 1891, V, p. 1. 'Grensgeb. d. Med. u. CUr., 1902, X, p. 235. 'Annali d'igiene sperimentale, 1904, N. S., XIV, p. 319. "Jour. A. M. A., March 21, 1908, Vol. L, pp. 929-934. 73 SPECIFIC PEOPHYLACTIC MBASUEES caused tetanus, he was able after ]1 years again to cause the disease by inoculating an animal with the infective material. Prophylaxis. — Local Treatment of Wounds. — Wounds, however in- significant, should be thoroughly cleansed. Punctured or lacerated wounds in which there is special danger of tetanus should be freely opened, and every particle of foreign matter carefully removed. Prompt- ness in cleansing the wound surgically is almost as important as thor- oughness. Wounds containing garden earth, street dust, or other mate- rial liable to contain tetanus spores should receive special consideration. After laying open and thoroughly cleansing such wounds, it may be ad- visable to disinfect them with the actual cautery or strong chemical agents. Por this purpose carbolic acid (from 25 per cent, to pure) or a strong solution of formalin may be used. Silver nitrate destroys the tet- anus spores in laboratory experiments, but lacks penetration in the pres- ence of albuminous matter. It is sometimes good practice to totally excise the wound, and even amputation must be considered in certain cases. The division of the umbilical cord and the treatment of the navel in the newborn must be done under the strictest asepsis. All wounds in which there is any suspicion of tetanus should be kept open and freely drained, and otherwise treated so as to discourage anaerobic conditions. Tetanus spores gain entrance into wounds not only from manure, garden soil, street dust, and similar sources, but also from the hands, instruments, bandages, suture material, or other objects. It is impor- tant to remember that the tetanus spore is exceedingly resistant to heat and chemical agents, and that in surgical and obstetrical practice con- fidence should not be placed simply upon boiling to destroy the spores. Very particular care must be exercised in the disinfection of substances injected into the body, such as gelatin and other organic materials. For the destruction of tetanus spores complete confidence may be placed in the autoclave, in which a temperature of 120° C. for 20 minutes is attained, or exposure to dry heat at 160° C. for 1 hour. It should be remembered that tetanus toxin is manufactured in the wound and is thence transported mainly along the nerve roots to the spinal cord and brain. It is therefore important to destroy or neutral- ize the toxin in the wound. For this purpose dry tetanus antitoxin inay be dusted upon the wound. Formaldehyde, even in comparatively weak solutions, destroys the activity of tetanus toxin. Specific Prcphylaxis. — Tetanus antitoxin is a specific and trustworthy preventive. Its use, however, must be understood to achieve satisfactory results. The antitoxin must be administered before the advent of symptoms, for after the tetanus toxin has combined with the motor nerve cells in the central nervous system it can neither be displaced nor neutralized with antitoxin. In such cases the most that the antitoxin can do is to combine with and neutralize the free toxin and thus pre- TETANUS 73 vent further damage. This in itself is quite worth while in the treat- ment of tetanus. At least 1,500 units of tetanus antitoxin should be given as a prophylactic dose.^ It is important to remember that the tetanus antitoxin is eliminated or otherwise disposed of in the body in the course of 10 days or 2 weeks. Therefore, in cases in which the wound does not heal well, as a result of mixed infection, or for other reasons, it is desirable to repeat the injection. This may be done at intervals as long as the danger persists. Occasionally tetanus bacilli persist in the pus-infected tissues, and, when the injected antitoxin has been exhausted, there may occur a late development of tetanus. Eowan ''■ reports a fatal case of tetanus in spite of the prophylactic use of 3,000 units of antitetanic serum, given 5 hours after the accident. In this case, however, the symptoms appeared 25 days later. The wound in this case was a compound fracture with a free discharge of rather foul-smelling pus. Instances in which 1,500 units of tetanus antitoxin have failed to prevent the development of tetanus in this country are rare. The few failures in Prance and Germany may be attributed to the fact that in those countries it is customary to use a smaller amount or a less potent serum than is used in this country. Wounds produced by blank cartridges and other Fourth of July accidents should always be regarded as suspicious, and should be given careful local treatment, supplemented with a prophylactic injection of antitoxin. The prevention of tetanus complication of vaccine wounds consists in: 1. The use of a reliable vaccine which has been biologically tested in accordance with the federal act. 2. Proper methods of vaccination to avoid unnecessary scabs and anaerobic wound conditions. 3. Surgical asepsis of the operation and after-treatment. Tetanus and other wound infections may be avoided, in those ex- posed to accidents, by cleanliness of body and clothing. A bath before a battle is a reasonable protection said to be adopted in the Japanese Army and Navy. The common experience of mankind teaches him that most wounds heal without tetanus, and that tetanus is, in fact, a relatively rare infection. The physician, however, is in no case jus- tified in taking chances, and it is one of the duties of the medical pro- fession to teach the public that it pays to thoroughly cleanse and care for wounds, however trivial, at once, and in accordance with modern methods. ' As soon as symptoms appear 20,000 units or more of tetanus antitoxin should be introduced directly into the circulation by intravenous injection; some antitoxin may also be injected into the nerves leading from the wound. In tetanus, as in diphtheria, time is the important element. A few units introduced early are worth more than thousands late. ^Jour. A. M. A., XIV, No. 7, Feb. 12, 1910, p. 533. CHAPTER II DISEASES SPREAD LARGELY THROUGH THE ALVINE DIS- CHARGES TYPHOID FEVER Typhoid fever is a sanitary problem of first magnitude, especially in this country, where it is unduly prevalent. In the United States typhoid fever stands fourth on the list of mortality tables: tuberculosis comes first, then pneumonia, cancer, and typhoid fever. The aver- age fatality from typhoid fever being nearly 10 per cent., it would, therefore, take still higher rank on the morbidity tables. In 1910 there were 25,000 deaths from typhoid fever in the United States, representing at least 250,000 cases. Our general attitude toward typhoid fever is inconsistent; familiar- ity has bred a remarkable indifference to the disease. Every case of typhoid fever means a short circuit between the alvine discharges of one person and the mouth of another. The physician has a dual duty in the care of a case of typhoid fever: one is to assist the patient, the other is to protect the community. On the other hand, the people should learn the lesson that a case of typhoid fever should be regarded as seriously as a case of cholera. These two diseases present many features in common. Both are intestinal infections of bacterial na- ture; in both diseases the alvine discharges contain the microorgan- isms which reinfect another person when taken by the mouth. Both diseases prevail especially in hot weather, both diseases are peculiar to man, so that the patient is the fountainhead of each infection. Water, food, fingers, and flies play a similar role in both instances. In the case of cholera the dread of the disease is an important factor in keeping it out of the country or in preventing its spread when once introduced. By strange contrast, there is a remarkable indifference to typhoid fever. A wholesome fear of typhoid fever would materially assist the health authorities in combating what may be considered one of the greatest health problems of the age. From the standpoint of preventive medicine, it is proper to regard an outbreak of typhoid fever as a reproach to the sanitation and civilization of the community 74 TYPHOID FEVEE 7S in which it was contracted. When the matter is better imderstood health authorities will be held responsible for this and other preventable infec- tions, just as some one is now held responsible for preventable accidentp. Much harm has been done by insisting that typhoid fever is in- fectious, but not contagious; it is both — ^that is, communicable.^ Typhoid fever occurs both in endemic and epidemic forms. It may truly be regarded as pandemic. ' Normally, typhoid fever is a warm weather disease. It recurs as an annual crop from July to Octo- ber.- Epidemics caused by infected wafer occur especially in the early spring, late fall, or winter months. Milk outbreaks may occur at any time of the year. Autumnal typhoid in our cities is due partly to infection contracted at health resorts, and has, therefore, been called a vacation disease. Typhoid fever is more prevalent in rural districts than in cities. In the United States there is more typhoid fever in the southern states than in the northern zone. The only explanation to account for this is the influence of temperature, rural conditions, and asso- ciation with the negro. Typhoid fever is no respecter of rich or poor; it attacks those in robust health, all ages, both sexes. Typhoid fever is a disease which ordinarily attacks the individual during the period of greatest economic value to the community. The economic loss, therefore, is appalling, and has been estimated to reach the sum of no less than $100,000,000 annually in the United States. Again, typhoid fever is an infection against which the individual alone cannot protect himself wholly without the aid of the community. Prevalence.- — Typhoid fever prevails more or less in all countries — the amount of the disease, however, varies greatly. It appears to be a disease of defective civilization, for those communities paying least attention to sanitation, as a rule, suffer most. In the United States there are comparatively few communities of 1,000 inhabitants or more which, during any period of twelve consecutive months within the last decade, have been entirely free from typhoid fever. According to the United States census report for 1900, the average typhoid death rate in the United States was 46.5 per 100,000 inhabitants. In 1908 the death toll from typhoid fever was no less than 35,000 in the United States. In other words, one person in about 200 in the United States contracted typhoid fever that year. It is estimated that in 1910-11 the number of deaths was reduced to about 25,000. The seriousness of these figures may be judged by estimating the probable number of cases of typhoid fever among persons handling the milk supply. Take, for instance, a city, as Washington, receiving its milk from a 'For distinction between these terms see page 317. ' In the southern hemisphere the typhoid season is during our winter, 76 DISEASES SPEEAD THROUGH ALVINE DISCHARGES thousand dairy farms. On the average there will be about four per- sons on each farm who in one way or another come in contact with the milk. That makes 4,000 persons among whom about 200 cases of typhoid may be expected to occur annually. No wonder that milk- borne outbreaks of typhoid fever are common occurrences. The rate of prevalence of typhoid fever in the United States in comparison with the rates of many other countries is very high. Thus, the annual death rate from typhoid fever per 100,000 population for the period 1901-1905 was: in Scotland, 6.2; in Germany, 7.6; in England and Wales, 11.2; in Belgium, 16.8; in Austria (1901-1904), 19.9; in Hungary, 28.3 ; in Italy, 35.2 ; while the rate in the United States during the same period was about 46.5. A comparison between the prevalence of typhoid fever in this country and abroad is impressive. The following ten European cities with a total population of about 15,000,000 have an average typhoid rate of 2.4 per 100,000 during the 10 years 1901-10:^ ANNUAL DEATH RATES FROM TYPHOID FEVER PER 100,000 POPULATION IN 10 EUROPEAN CITIES Average for 10 years, 1901-1910 Average lor 5 years, 1901-1905 190G 1907 1908 1909 1910 Stockholm. . Christiania, . Munich . . . . Edinburgh . . Vienna Hamburg. . . Berlin Dresden. . . . Copenhagen, London 1.7 2.4 2.5 2.9 3.7 3.7 3.8 4.2 4.5 4.7 5 1.7 1.9 1.2 2.8 3.3 4.2 4.2 2.7 2.2 1.8 1.6 1.4 .3 3.8 4.1 2.9 2.2 3.6 3.3 The following fifteen European cities with a population of about 9,000,000 had a typhoid death rate of 5.3 per 100,000 in 1909 and only 4.5 in 1910: ' These facts and the following instructive tables are taken from : ' ' The Necessity of a Safe Water Supply in the Control of Typhoid Fever," by Allan J. McLaughlin, V. S. Pui. Health Reports, XXVII, 12, March 22, 1912 TYPHOID FEVER 77 ANNUAL DEATH RATES FROM TYPHOID FEVER PER 100,000 POPULATION IN 15 OTHER EUROPEAN CITIES City 1910 Frankfort , Antwerp Bristol Nuremberg Birmingham Belfast Lyon Leeda Liverpool Sheffield Rotterdam Amsterdam , Paris Bradford , Leipzig Total average rate 1.5 0.9 1.0 2.3 2.8 2.1 2.6 S.O 3.9 6.2 3.9 5.8 4.4 7.2 3.8 8.4 3.9 9.4 3.0 6.4 6.5, 3.8 6.7 8.4 5.6 4.3 9.2 8.3 7.5 5.3 4.5 The following eight European cities with a total population of 7,500,000 had a typhoid death rate of 13.9 in 1909 and 15.6 in 1910. These rates would be considered low in America, but the European officials consider the persistence of such rates to be a reflection: ANNUAL DEATH RATES FROM TYPHOID FEVER PER 100,000 POPULATION IN 8 OTHER EUROPEAN CITIES City 1909 1910 Glasgow . 12.5 9.4 7.4 15.7 13.9 13.8 13.5 25.2 6.4 13.6 Brussels 16.1 Dublin 12.2 10.3 15.0 Warsaw 17.4 St. Petersburg 33.7 Total average 13.9 15.6 To recapitulate, in northern Europe the 33 principal cities, with an aggregate population of 31,500,000, had an average typhoid death rate per 100,000 population of 6.5 in 1909 and 1910. This includes such notorious typhoid centers as St. Petersburg, which had a rate of 33.7 in 1910. The rate in St. Petersburg is considered to be due to the water supply, which is partly filtered and partly raw Neva water. Let us now compare these fates with typhoid fever in America: 78 DISEASES SPEEAD THEOUGH ALVINE DISCHAEGES ANNUAL DEATH RATES FROM TYPHOID FEVER PER 100,000 POPULATION IN 50 CITIES OF THE UNITED STATES HAVING MORE THAN 100,000 INHABITANTS City Birmingham, Ala. . . Los Angelea, Cal. ... Oakland, Cal San Francisco, Cal. . Denver, Colo Bridgeport, Conn. . . , New Haven, Conn. . , Washington, D. C. . Atlanta, Ga Chicago, 111 Indianapolis, Ind. . . Louisville, Ky New Orleans, La . . . Baltimore, Md Boston, Mass Cambridge, Mass.. . Fail River, Mass . . . Lowell, Mass Worcester, Mass.. . . Detroit, Mich Grand Rapids, Mich Minneapolis, Minn , St. Paul, Minn Kansas City, Mo. . . St. Louis, Mo Omaha, Nebr Jersey City, N. J. . . Newark, N. J Paterson, N. J Albany, N. Y Buffalo, N. Y New York, N. Y . . . Rochester, N. Y Syracuse, N. Y Cincinnati, Ohio.. . . Cleveland, Ohio. . . . Columbus, Ohio. . . . Dayton, Ohio Toledo, Ohio Portland, Oreg Philadelphia, Pa. . , . Pittsburgh, Pa Scranton, Pa Providence, R. I.. . . Memphis, Tenn. . . . Nashville, Tenn. . . . Richmond, Va Seattle, Wash Spokane, Wash Milwaukee, Wis. . . . 1909 1910 59.7 49.5 16.1 14.2 11.2 16.5 13.9 15.5 24.1 27.5 9.0 4.9 20.5 17.9 34.3 23.2 50.6 50.1 12.6 13.7 22.3 28.5 45.0 31.7 28.4 31.5 24.9 42.0 13.8 11.3 7.7 9.5 21.3 15.0 10.5 19.7 8.4 15.7 20.5 23.0 17.2 28.3 21.0 58.7 18.9 19.5 29.3 54.4 16.2 14.9 36.8 86.7 8.8 11.5 11.9 13.1 9.7 7.1 19.0 14.0 23.8 20.4 12.1 11.6 9.4 13.7 11.2 28.2 13.3 8.8 13.3 17.9 19.6 18.1 26.9 21.4 41.7 37.2 22.0 22.4 22.3 17.5 24.6 27.8 16.4 18.9 11.4 17.9 48.8 27.4 52.0 48.9 24.1 21.9 23.8 14.2 43.2 45.4 21.4 45.7 These 50 registration cities in the United States have an aggregate population of over 20,000,000. The average typhoid death rate in these cities for 1910 was 35 per 100,000 inhabitants. TYPHOID FEVER 79 Unit of comparison Aggregate population Deaths per 100,000 from typhoid fever, 1910 33 principal European cities in Russia, Sweden, Norway, Austria- Hungary, Germany, Denmark, France, Belgium, Holland, Eng- land, Scotland, and Ireland 50 American cities of 100,000 inhabitants or over 31,500,000 20,250,000 Excess of deaths from typhoid fever in American cities. 6.5 25.0 The excess of 18 deaths per 100,000 in the urban population alone shows that we have had, in the 50 cities mentioned above, at least 3,600 deaths, and probably 36,000 cases of typhoid fever, which were pre- ventable and should never have occurred. For the whole United States the number of cases for each year readily preventable by methods within our grasp would probably reach 175,000, and the deaths so avoided would total about 16,000. In 1909 there were more cases of typhoid fever in the United States than there were cases of plague in India, in spite of the fact that India's population is two and one-half times that of the United States. 180 160 ai4o 2180 £100 111 !{ 80 H 60 40 so a 1 ^= J \ / 1 \ K ^_ N / \ S / \ s. y 1 X. X V y AT ER / ^ V — — 4i ■THA HON H < s 5 s z i (9 3 111 o z Pio. 10. — CuKVB Showing Death Rate from Typhoid Fever in Albany before AND AFTER FILTRATION OF WaTEE. (WHIPPLE.) Residual or "Normal" Typhoid. — When a city such as Albany, Chicago, Lawrence, Lowell, or Pittsburg, which has been using grossly polluted water, is furnished with a water supply of good sanitary quality, there at once results a marked reduction in the amount of typhoid fever. The curve is not only lowered, but changed in char- acter (Fig. 10 — Albany). The remaining typhoid after the water- 80 DISEASES SPREAD THROUGH ALVINE DISCHARGES borne infection has been removed is known as residual typhoid, and the curve in such cases is spoken of as the "normaF' typhoid curve. The normal curve shows a distinct summer prevalence recurring with marked regularity each year, and lacks the great irregularities which characterize the curve of a community drinking badly infected water. Normal typhoid is endemic typhoid; Sedgwick has proposed the name "prosodemic" {proso, through, and demos, the people) as more ex- pressive of this type of the disease. The amount of residual typhoid varies markedly in different localities; thus it is twice as high in the southern as in the northern part of our country; it is much greater here than in most parts of Europe. Channels of Entrance and Exit. — The typhoid bacillus probably al- ways enters by the mouth. Typhoid fever is generally regarded as primarily a gastrointestinal infection, although the disease itself is not produced unless the blood, glands, and other structures of the body are invaded with the specific microorganism. The typhoid bacil- lus grows and multiplies in the intestinal tract, penetrates the mu- cosa, and thus invades the body. The bacillus leaves the body mainly in the feces and urine, occasionally in the sputum and other discharges. Typhoid bacilli appear in the feces early in the disease; sometimes be- fore the fever. Later in the disease they diminish in number and usually disappear during convalescence, although they may continue in- definitely (see "Bacillus Carriers," page 83). The feces may contain only a few typhoid bacilli; usually they are present in consid- erable numbers; occasionally they occur almost in pure culture, prac- tically replacing the colon bacillus. Typhoid bacilli commonly appear in the urine about the second, third, or fourth week. They grow well in this fluid both within and without the body, and may be present in such enormous numbers that the urine resembles a 24-hour-old bouillon culture. From the stand- point of prevention, it is very important not to neglect the virus in the urine. Urotropin (hexamethylenamin) in ten-grain doses or more three times a day diminishes the frequency of typhoid bacilluria, and is also effective in curing this condition when once established. The sputum ordinarily does not contain the bacilli unless there is a pneumonia or severe bronchitis. The bacilli may be eliminated with the discharges from abscesses, such as periostitis, months and even years after the disease. Diagnosis.— An early diagnosis of typhoid fever is important not only for the successful treatment of the patient, but is of vital impor- tance in controlling the spread of the infection. The early diagnosis can only be assured through laboratory methods. Typhoid bacilli may be isolated either from the blood or the feces. Blood Cultures.— Probably the easiest method, as well as the one TYPHOID FEVEE 81 giving the maximum information, is through blood cultures. The tak- ing of a little blood for this purpose is^no more difficult or annoying to the patient than swabbing the throat for diphtheria. A few drops of blood may be obtained by puncturing the lobe of the ear or the finger, with the usual precautions to prevent bacterial contamination. A much better method, however, consists in withdrawing 5 to 10 c. e. of blood by mfeans of a syringe from one of the veins at the bend of the elbow. The technique is very simple, and, if the needle is sharp, the patient scarcely feels the puncture. In fact, if the attention of the patient is distracted a skillful operator can withdraw 10 c. c. of blood in this way before the patient is aware that anything has been done. The blood may be planted in bouillon, or, better, in bile. After 24 hours in the incubator, any growth that occurs is transplanted to other media, a pure culture obtained, and tested for agglutination. Usually a pure culture is obtained in the first medium, so that the diag- nosis may be established in 24 hours — at most, 2 or 3 days. Typhoid bacilli appear in the blood early in the disease, perhaps occasionally during the prodromal symptoms. Kayser obtained posi- tive results from 90 per cent, in the first week, 65 per cent, in the second, 42 per cent, in the third, 35 per cent, in the fourth. Our results in Washington were approximately the same. The typhoid bacilli probably do not grow in the blood during life. Their presence in the blood stream represents an overflow from the spleen and lym- phatic tissues. The presence of typhoid bacilli in the blood may be taken to mean typhoid fever. The same cannot always be said if found in the feces or urine. The Feces. — From the feces or urine typhoid bacilli are best isolated upon Bndo's medium. This consists of a 4 per cent, alkaline agar containing fuchsin, which has been decolorized with sodium sul- phite. Upon the surface of this medium typhoid colonies appear in 24 hours as translucent, dewdrop-like colonies, whereas colon bacilli and other organisms that produce acid and split the fuchsin appear as red colonies. Suspicious colonies are fished and may be tested at once under the microscope for agglutination, or may be planted in bouillon to obtain a growth sufficient for macroscopic agglutination tests. In any critical case pure cultures should be obtained and studied for morphological, cultural, and other biological characters. A modi- fied Endo's medium and a rapid technique for diagnostic purposes, described by Kendall and used with success in my laboratory, are sum- marized as follows : Technique. — Make plain, nutrient, sugar-free agar as follows: Tap water (cold), one thousand cubic centimeters; powdered agar, fifteen grams; peptone (Witte), ten grams; meat extract (Liebig), three grams. Cook in double boiler one hour. Make the reaction just al- 82 DISEASES SPREAD THROUGH ALVINE DISCHARGES kaline to litmus by the cautious addition of KaOH. Cook fifteen minutes to set the reaction, and then filter through absorbent cotton. The tap water should be as cold as possible and the agar should be "dusted" on the surface and allowed to settle into the medium before heat is applied and before the other ingredients are added. After filtration, the medium is stored in flasks containing known amounts, conveniently in one hundred-cubic-centimeter lots, and steril- ized in the autoclave. To use the medium: (a) Prepare a ten per cent, solution of fuch- sin in ninety-six per cent, alcohol, (b) Prepare a ten per cent, solu- tion of sodium sulphite in water. Add one cubic centimeter of (a) to ten cubic centimeters of (b) and heat in the Arnold sterilizer for twenty minutes^(c). Add one per cent, of lactose (which must be chemically pure) to the agar medium described above, and heat in the Arnold sterilizer until the medium is melted and the lactose thoroughly distributed in it. The decolorized fuchsin solution (c) is then added in the pro- portion of one cubic centimeter of the mixture to each one hundred cubic centimeters of medium; then thoroughly mixed. Plates are then poured and allowed to harden (with the covers removed) in the incubator for thirty minutes, after which time they are ready for inoculation. Preparation of Feces for Inoculation. — The feces are collected preferably in the small rectal tubes described by Kendall.^ A small portion of feces (about a loopful) is thoroughly emulsified in ten cubic centimeters of sugar-free broth, and preferably incubated one hour at 37° C. prior to the inoculation of the plates. This preliminary in- cubation does two things: the clumps of bacteria settle down, leaving a more uniform suspension of bacteria in the supernatant fluid for inoculation, and the bacteria undergo a slight development in a medium particularly suited for their growth. The thin suspension of the stool is now rubbed upon the surface of the agar plates by means of a bent, sterile, glass rod, and the plates incubated for 18 hours at 37° C. The suspicious translucent, colorless colonies are removed entire to small test-tubes containing one cubic centimeter of broth and incubated for two hours at 37° C. At the end of this time there will be sufficient growth to make the customary microscopic agglutination tests. Con- firmatory cultural characters may be obtained by inoculating suitable media from the same tubes as those from which the organisms for agglutination were obtained. Physicians should encourage boards of health to furnish diagnostic aids of a laboratory nature. Such work should be in the hands of "^ Boston Med. and Surg. Jour., CLXIV, No. 1, Sept., 1911. TYPHOID FEVER 83 specialists rather than entrusted to those who make occasional anal- yses. Early and accurate diagnosis is just as important to prevent the spread of other communicable diseases as it is with typhoid. These facts emphasized here will not be repeated under each disease. Bacillus Carriers. — In about 4 per cent, of all cases of typhoid fever the patient continues to shed typhoid bacilli in the urine or feces during and after convalescence. Some persons shed typhoid bacilli without a clinical history of having had the disease. We therefore recognize three kinds of carriers : acute, chronic, and temporary. An acute typhoid bacillus carrier continues to discharge the infection not longer than 6 weeks following convalescence. A chronic carrier con- tinues to discharge the bacilli 6 weeks or longer. A temporary carrier is a person who has not had clinical typhoid fever but who discharges typhoid bacilli for a short period. Albert states that 25 per cent, of all chronic typhoid carriers have never had typhoid fever; and further estimates that one in every 1,000 of the general population is a carrier. While it would seem that typhoid bacilluria should be especially dangerous, a study of the cases indicates that most of the outbreaks that have been traced have been due to carriers who discharge the organisms in their feces rather than in the urine. It seems that typhoid carriers are more dangerous in certain seasons. More cases are traced to women ^ than to men. This is probably owing to the fact that the chief danger lies in handling foodstuffs, so that a carrier occupied as a cook or waitress is a special menace. The question of preventing the spread of the disease through bacil- lus carriers is important and difficult. Surgical methods fail to cure carriers, for the typhoid bacillus may continue to grow in other parts of the intestinal tract than the gall bladder. Medical measures, such as urotropin, are efficient for bacilluria, but are of no avail in the fecal carriers. Attempts have been made to relieve the condition by the use of bacterial vaccines. Petruschky ^ and also Meader have reported en- couraging results, especially with the use of autogenous cultures. So far certain cases resist all attempts to relieve the condition. It is unnec- essary to place bacillus carriers incommunicado. It is sufficient to re- strict their activities so that they may neither infect food nor their sur- roundings. With proper care and cleanliness typhoid carriers may pre- sent little danger to their fellow men. The problem, at present, is to detect the carriers, so as to establish a sanitary isolation, if not an actual quarantine.^ Resistance of the Virus.' — The typhoid bacillus has no spore. It is, therefore, comparatively easy to destroy. The only difficulty present- ' Women are more subject to gall-stones. 'Deut. med. Wochschr., July 11, 1912, XXXVIII, 28. ' The facts covering the infeetivity of carriers are summed up by Ledingham, 39th An. Eeport Local Gov. Board, 1909-10, Supplement, p. 249. 84 DISEASES SPEEAD THROUGH ALVINE DISCHARGES ing itself is getting at the bacillus when imbedded in fecal masses. When dry, most typhoid bacilli die in a few hours; occasionally a few survive for months. The -fact that typhoid bacilli are killed by drying renders infection through dust unlikely. When a moist medium, such as water, milk, or urine, is heated to 60° C, practically all the typhoid bacilli such a medium may contain are killed. An exposure at 60° C. for 20 minutes will surely kill all of these microorganisms. They are not destroyed by freezing (see "Relation to Ice," pages 837 et seq. In their resistance to germicides typhoid bacilli behave like the average non-spore-bearing bacilli. Thus bichlorid of mercury, 1- 1,000, phenol, 2% per cent., formaldehyde, 10 per cent., are effective upon the naked germs. In order to kill the typhoid bacilli in feces special precautions or stronger solutions are necessary (see page 1030). The viability of typhoid bacilli in feces is very variable, depending on the composition of the feces and the varieties of other bacteria present. Sometimes the typhoid bacilli in feces perish in a few hours, usually in a day; under exceptional circumstances they may live for much longer periods. In the Plymouth epidemic typhoid bacilli prob- ably remained alive and virulent in the feces, exposed to the winter's cold, for several months. Levy and Kayser found they remained alive in feces for 5 months in the winter. The life of the organism in privies and in water is usually comparatively short. In nature they die, as a rule, in water in about 7 days and often after 48 hours. They probably live longer in clean water than in contaminated water. In the outer world symbiosis plays an important part, also the presence of deleterious chemicals, temperature, light, desiccation, dryness, and other factors known to be injurious to spore-free bacteria. As a rule, the typhoid bacillus does not survive long in the soil under the usual conditions. Typhoid Bacillus in Nature,— The typhoid bacillus should be re- garded as a pathogen, not as a saprophyte. It lives and grows prin- cipally in the human body. It has a tendency to die in water, air, soil, upon fomites, or in nature generally. The grand exception to this statement is in the case of milk, in which the typhoid bacillus grows well. The typhoid bacillus is much more widely distributed in man than the cases indicate. Thus, in the District of Columbia, of 1,000 healthy persons examined during the typhoid season of 1908, typhoid bacillus was found in the feces in 3 instances. At least one and perhaps two of these individuals were regarded as temporary carriers. In each instance the organisms were found only once. The population of the District of Columbia in 1908 was 300,000, and at the ratio of 1 per 1,000 this would represent about 300 healthy persons in that community har- TYPHOID FEVER: 1902 TO 1906 Dbatr Rate per 100,000 op Populatiox ciTy Hictimonb t>orou«h,K.y. 5u«nswri)U8h,5t.i(. Cam6en.St.3. Uncoln^ttiT. Dauton.Ohio MfinTihts Tenn South BcnA.m6. San Antonio. Tocos ■Saiinnnnh fin Ncu)tott,Mas3. rriTtMniine InA NewOrteatis.Ua. Covington .itu. RictimoiiA.Ua. louisuUlt.Ky. Mtanta 6a. Sfattlf.Wasti. EuansvilU.lnA. Springfifli.lU. Gran6Hapi63,«icli. Uilmmaron, D«l. Uncasfcr.Pa. HarriJt'ura.Pa. w]>ett\njt IT) llii Minneapolis.Minit ToUfto.Ohio Cincinnati, Ohio Philaiclphia.Pa. AUegficnu.Pa. Pit^stl^rd,Pa. icncstcr Hocticstfr.ic.y. Suracuse.jf.u. FaUmwr.iHass. Brofkton.floss. Taunton.Jaass. HttwrhUl.ttoss. Portland) ,ine. Sattm.nass. (lUuauKee.ijis. Detroit, Mien. Chicagclll. Buffalo.«.y. CTe.Pa. CiewlanAiOtoo Duliith Winn cht)u Fitcht)urg.Mass. Cambri6ae.«ajs. 5oracruin<,iHass. Worcester. Mass. Briiflcport.Conn. >tQrfTor6,Conn. Molicn.Mass. Boston, Mass. Cndsea Mass. Wtu)13e6for6,iHQS5. lOilttrbiir^ gonn Scranton.Pa. Portlani.Orcg. JohnsloiDn.Pa. ftltoona.Ptt. SaUlnkfCit^i liMh HolyoKc.Wass. Bronx torougft.M.y. Manhattan t?orough,Jr.y. PauitucKot.n.l. NewarK.i\.J. JaseuCity.M.J. JMiimflliLili Si.Pttut.Minn, iTanfon.Oliio RrooKlyn t)orau5h.A'.« Cotumdus.Ofiio iMcKtcspn rt.Vn TH£ NOKIIIS ^ETKRS CO.. U Fio. 11.— Intltjbncb of Public Water Supplies ok the Typhoid Fever Death Rate. (Diagram prepared by Marshall O. Leighton, U. S. Geological Survey, from figures furnished by Dr. Cressy L. Wilbur, Chief Statistician of Vital Statistics, Bureau of the Census — from Kober.) 8 85 8G DISEASES SPREAD THROUGH ALVINE DISCHARGES boring and shedding typhoid bacilli for a brief period of time during the typhoid season. Modes of Spread. — Typhoid fever is spread either by direct or in- direct contact — indirectly through water, milk, and other foods ; through "contacts," and also flies, fingers, and fomites. Each of these modes of spread needs separate consideration. Water. — Water-borne typhoid is a common occurrence. Not long ago it was regarded as the sole or usual mode of spread; now we know that this was a mistake. Most fecal matter ultimately finds its way to water; most water courses draining inhabited regions are contam- inated with human feces. Surface water is, therefore, apt to contain typhoid bacilli. The fact that there may be no clinical case of typhoid fever in the drainage area is no guarantee that the water may not be infected — in view of the prevalence of missed cases and bacillus car- riers. Fortunately, typhoid bacilli do not grow and multiply in water under natural conditions. They usually die in a few days, and rarely persist longer than 7 days. They succumb more quickly in some waters than others, more quickly in summer than winter. Thus Reudiger "■ has shown that typhoid bacilli die less quickly in the Red Lake River in Minnesota when exposed in dialyzing membranes in the river with ice than in the open river. He ^so showed that colon bacilli as well as typhoid bacilli disappear much more rapidly from polluted water during the summer months than during the vpinter months when the river is protected with a covering of ice and snow. Reudiger considers that the destruction of the typhoid bacillus in river water during the summer months is in a large measure due to the growth of micro- scopic plants, and other organisms which give off dialyzable substances which are harmful to B. typhosus. One of the reasons for believing in the existence of such poisons in water is the fact that typhoid cul- tures in a collodion sac placed in water die more quickly than other- wise. Further, the effect of the direct rays of the sun are entirely lost when the river is covered with ice and snow. Water plays a large but diminishing role in the spread of the typhoid bacillus. The great water-borne epidemics have overshad- owed the other media of communication. We know that the larger part of the typhoid now prevalent in this country is not water-borne; Whipple in 1908 estimated it at 35 per cent. ; it is now no doubt much less. Typhoid fever may be excessively prevalent, even epidemic, in a city having a water supply of good sanitary quality. In the vast majority of cases water-borne typhoid is contracted from a surface supply, that is, a river, small stream, pond, or lake. ' Jour. Am. Puh. Health Ass., June, 1911, Vol. I, No. 16, p. 4H, TYPHOID FEVEE 87 Ground water becomes a source of danger only under special condi- tions (see chapter on water). Water-borne epidemics present certain definite characteristics. They almost always occur in the spring, fall, or winter, when the water is cold. Most of the great water-borne epidemics have occurred in northern cities, both in this country and in Europe. They usually have a sharp onset, the curve rises to a peak, and declines rapidly. The pollution is usually nearby; that is, there is a rather direct trans- fer of fresh virulent infection. Granting that the typhoid bacillus does not grow in cold water, there must be a very considerable dilution in most of the epidemics. Pitts BURSe ,P/1. - -Typh 01 Fever. D£/ITH KATE PEK 100.000 /900 TO 1910 1900 /lOI /<)02 /90^ 11 Ot, 1101 l<)Ot} Ho-j 1101 /Id /I/O /ifO \ \ 5. i« /,MI > L i r »»x "K r v r 2^ 1! no V \ Li r 1' 110 V J\ ft 1 r 100 n S § r i 90 5 1 i- 1 *» 5 s '0 ^ ^ fo '\^ 1 c 5 T' S 5 J_ to 1 r ^ ;^ fo 1 *o 1 • \ ,yn \ L ?« V *" /o Pia. 12. — Immediate and Striking Effect of Purifying a Badlt Infected Water Supply upon the Typhoid Situation. The following examples are given of the fact that water-borne out- breaks of typhoid fever occur during the winter, fall, or early spring, when the water is cold. Thus we have the water-borne epidemic in Plymouth, Penn., in 1885, which began with the spring thaw and was doubtless produced from the frozen accumulation of typhoid ex- 88 DISEASES SPEEAD THEOUGH ALVINE DISCHAEGES crement from a single case. Very similar to the Plymouth outbreak was that at New Haven, Conn., in 1901. The outbreak at Ithaca, N". Y., started in epidemic proportions in January. The epidemic in Sherbourne, England, in 1873, likewise started in January. Four acute epidemic exacerbations are recorded in Philadelphia in Decem- ber of the years 1884, 1890, 1899, and 1903. Several similar epi- demics have occurred in the winter time in Chicago — one in January, 1890, another in January, 1896, and one in March, 1891. Another striking instance is the epidemic in Newark, N. J., in February, 1899, and one in December, 1891. Abroad, epidemics are recorded in Ber- lin in February, 1899, in Paris in February, 1894, and in Vienna in November, 1888. All of these are generally believed to have been water-borne and must have taken place when the water was very cold. In fact, as previously pointed out, extensive water-borne epidemics of typhoid fever rarely occur in the summer time. The epidemiology of water-borne typhoid caused by distant, diluted and attenuated infection is not understood. It was formerly thought that a high typhoid rate necessarily meant badly infected water. We know now that this does not necessarily follow, as has been proven by the experiences in Washington, Winnipeg, army camps, and many southern cities. Almost all the water-borne epidemics of typhoid fever rest upon circumstantial evidence. It is difficult to isolate the typhoid bacillus from water, and the damage is usually done before suspicion points to the water.^ It is clear that in cities which have had safe water supplies for a period of years the rate should not be above 5 per 100,000, unless some unusual condition exists, such as poor control of milk or lack of con- trol over patients and carriers, and disregard of modern sanitary knowl- edge. No single measure in reducing typhoid fever on a large scale ap- proaches the effect of substituting a safe for a polluted water supply. As an instance of this wholesale saving of human life, the reduction of typhoid fever in four American cities is shown in Fig. 13, p. 89. Ice. — Ice may, under exceptional circumstances, occasionally be the vehicle by which typhoid bacilli are transferred. Freezing does not kill B. typhosus, but there is a great quantitative reduction not only in the act of freezing, but during storage, hence the danger is greatly lessened. The most suggestive outbreak of typhoid fever attributed to ice was reported by Hutchins and Wheeler in 1903 in the St. Law- rence Hospital, three miles below Ogdensburg. A few other instances in which ice is believed to have conveyed the infection have been re- ^ Examples of water-borne outbreaks of typhoid fever will be found in the chapter on water. TYPHOID FEVER 89 ported, but are based upon flimsy evidence. The fact that natural ice is usually stored many weeks or months before it is used is a sani- tary safeguard. Manufactured ice made from distilled water and handled with cleanly methods is above reproach. For a discussion of ice in relation to typhoid fever and other infections see page 840. aO ^0 6 80 100 120 140 160 ISO SCO 1 1003 H ^^^^^^^ 1 1 1 1904. H 1905 WaUrTown, )Cf. 1906 laga ■ 1893 r 1894 Lavvrencc,>&6&. I89ff l89e 1998 ■ 1899 r lOOO AlbEUiyXr 1901 I90Q 1908 BB^^^i CmcinnaVi. Otiio. Fig. 13. — ^Abrupt Reduction in Death Bates fbom Typhoid Fever Incident to Water Purification in Four American Cities. Milk. — Trask collected 317 typhoid epidemics up to 1908 caused by infected milk. Since then many more instances have -come to light. Doubtless many milk outbreaks have escaped attention or have been attributed to water or other sources. The typhoid bacillus grows well in milk, and- it is now realized that this medium is a frequent and important mode of communication. Most milk outbreaks are reported either in England or America. On account of the almost universal custom of boiling the milk in European and tropical countries, milk outbreaks are rarely reported from these regions. During the four years' study of typhoid fever in Washington, it was found that at least 10 per cent, of the cases were milk-borne. The milk usually becomes contaminated on the farm, from a case or a carrier. It may also become infected in transportation, at the city dairy, or in the home. Milk outbreaks come abruptly, rise to a peak like a water epidemic, and subside rather sharply. There are comparatively few secondary cases. Milk-borne epidemics of typhoid fever have certain characteristics which permit ready recognition. (a) There is a special incidence of the disease on the track of the implicated milk supply. The outbreak is localized to such areas. (b) The better class of houses are invaded, and persons in better cir- cumstances generally suffer most. 90 DISEASES SPEEAD THEOUGH ALVINE DISCHAEGES (c) Those who drink milk are chiefly affected and those suffer most who are large consumers of raw milk. (d) The incidence is high among women and children. (e) The incubation period is shortened perhaps on account of the large amount of infection taken. (f) More than one case occurs simultaneously in a house. This is a very suspicious circumstance to the epidemiologists. The first in- dication of a milk outbreak in a city with a good water supply is usually the fact that two or more persons in a household came down with typhoid fever within a few days of each other. (g) Clinically the disease usually runs a mild course, owing to the fact, no doubt, that the virus becomes attenuated in the process of multi- plication in the milk. In water-borne typhoid the same germs are in- gested that were passed ; in milk-borne typhoid it is the succeeding gen- erations that are ingested. Milk-borne outbreaks are sometimes very extensive. One of the largest epidemics occurred in Boston (Jamaica Plain) in March and April, 1908. Four hundred and ten cases were reported; 348 of them drank the suspected milk. Among the first victims of the disease was the milkman, who was believed to have infected the milk through tasting it. The number of persons involved in a milk-borne epidemic varies greatly, depending upon the amount of milk infected and other factors. It must not be uncommon for a single bottle of milk or a small quantity to become infected, and thus transmit the disease to one or two persons. Such instances are exceedingly difficult to trace. Oft- times the milk becomes infected from a carrier. An instance of this occurred in Washington (Georgetown) in 1908. In this case the milk- maid had typhoid fever 18 years previously. Examinations showed almost pure culture of B. typhosus in her feces. Fifty-five persons who drank the infected milk contracted the disease. Milk Products. — Fresh milk products, such as cream, ice-cream, butter, and buttermilk, and fresh cheese, may contain the typhoid bacillus, and are occasionally media of communication. Cream contains more bacteria than the milk from which it is taken. The use of infected cream in coffee, on cereals, etc., is sufficient to cause the disease. Several instances in the Washington studies were traced to such use of cream. As a rule, coffee in the cup is not hot enough to kill the typhoid bacillus. Freezing kills only a certain percentage of the typhoid bacilli. In Washington several cases of the disease were traced to ice-cream. Brack has shown that the typhoid bacillus will live in butter for 27 days. Buttermilk may be quite as dangerous as the cream from which it is derived. In cheese the time of fermentation, symbiosis, etc., les- TYPHOID FEVER 91 sens the likelihood of survival of the typhoid bacillus. Fresh cream- cheese, such as Cottage cheese, may be responsible for an occasional case. Otstees, Mussels, and Shellfish. — The first outbreak of typhoid fever attributed to this source was investigated by Conn at Wesleyan University, Middletown, October, 1894. Twenty-five cases were at- tributed to eating infected oysters; 4 died. Not all of those who took sick had clinical typhoid fever. Some had gastrointestinal disturbances with illness lasting but a few days. About one-quarter of those at- tending the dinners at which the oysters were served were made ill. A similar instance occurred at the Mayors' banquets at South Hampton and Winchester, in 1903. In the Washington studies it seems that oysters and shellfish play a minor role in the spread of the disease, which occurs mostly in the summer time, while oysters and similar sea food are relished mainly in winter. Comparatively few of the cases studied gave a history of having eaten oysters within 30 days prior to the onset of the disease. Oysters become especially dangerous when consumed soon after tak- ing them from a polluted bed, or when floated or bloated in infected water. (For further discussion of this topic, see page 566.) Fruits and Vegetables. — Vegetables, such as celery, lettuce, and radishes, partaken of raw, and grown on land fertilized with fresh night soil, may be dangerous, and this probably accounts for an occasional case. In large cities it is practically impossible to trace this source of infection. It therefore remains more a suspicion than a conviction. In Hackney, London, two local outbreaks were traced to watercress taken from a polluted stream. In Springfield, Mass., an outbreak which occurred in the summer of 1905 was attributed to infected fruits and vegetables. Creel ^ found typhoid bacillus upon the tips of leaves of plants cultivated in contaminated soil. Under conditions most unfavorable to the B. typhosus the infection lasted at least 31 days — a period suffi- ciently long for some varieties of lettuce and radishes to mature. Flies. — The evidence is now complete that the common house fly {Miisca domestica) may convey the infection of typhoid. It is not inappropriately called the typhoid fly. The typhoid bacilli may be smeared upon the feet or other parts of the insect, or may live in the intestinal tract and pass in the dejecta in almost pure culture. Flies live, feed, and breed in fecal matter and decomposing organic substances of all kinds. It is easy to see how they may convey infections from this source to our food, lips, or fingers. Alice Hamilton isolated typhoid bacilli from 5 out of 18 house flies captured in Chicago in the privy and on a fence near a sick room. It has been shown experimentally that ^Public Health Reports, Feb. 9, 1912, p. 187, XXVII, 6. 92 DISEASES SPEEAD THEOUGH ALVINE DISCHAEGES living typhoid bacilli may remain upon the bodies of flies for as long as 33 days. Special attention to the role played by the fly was given by Bead, Vaughan, and Shakespeare in their studies of the prevalence of typhoid fever in our army camps in 1898. They concluded that flies undoubtedly served as carriers of the infection and attributed about 15 per cent, of the cases to this mode of communication. They found that "flies swarm over infected fecal matter in the pits and then deposit it and feed upon the food prepared for the soldiers at the mess tents. In some instances, where lime had recently been sprinkled over the contents of the pits, flies with their feet whitened with lime were seen walking over the food." The danger from fly transmission varies very much, and depends upon circumstances. In a camp it is con- siderable; in a well sewered city the risk is diminished. In our Wasli- ington studies we could find no relation between fly abundance in the summer of 1908 and typhoid prevalence. It is not possible to express mathematically the percentage of cases caused by flies — the flgures would vary greatly, depending upon circumstances. The danger of typhoid from flies in cities has doubtless been overstated. However, if only one per cent, of the cases were thus transmitted, the suppression of flies would still be quite worth while (page 323). Dust. — Typhoid bacilli soon die when dried, especially when ex- posed to the sun and air. Dust-borne infection in this disease raust be rare. In the South African war there were frequent dust storms in some localities, so that the food was covered with dust and sand. Some of the infection was believed to have been conveyed in this way. EoMiTES. — The infection may be conveyed upon soiled linen, blan- kets, and other objects. It was believed by Eeed, Vaughan, and Shake- speare that the clothing, blankets, and tents in the Spanish-American war became infected and were a prime factor in spreading the dis- ease. After the South African war some of the blankets used by the troops were sent back to England and used on a training ship, on which typhoid fever appeared. The blankets were found to be dirty and soiled with fecal matter, from which Klein is reported to have obtained living typhoid bacilli. The danger of fomites contaminated with fresh infection is real, and emphasizes the importance of dis- infecting bedding, towels, and other fabrics. Soil. — The soil, long regarded as the most important factor in the spread of typhoid fever, and by Pettenkofer and others considered an essential element, is now given scant consideration. Pollution of the soil, however, cannot be disregarded. The typhoid bacillus may live for a long time in sewage-soaked earth. A surcharged soil may en- danger the water, milk, and other foods, or infect through flies and other means (see Soil). Contact Infection. — "Contact" is a convenient term to indicate TYPHOID FEVER 93 the spread of infection directly or indirectly as a result of close asso- ciation between the sick and the sound. Actual contact is not neces- sarily implied. The term is used to indicate the transfer of the in- fection through a short intervening space in a brief period of time (see page 314). Thus the infection may be passed from one to an- other through kissing, soiled hands, remnants of food, infected ther- mometers, or tongue depressors, contaminated towels or other fabrics, cups, spoons, glasses, etc. If the nurse infects a cup of milk or glass of water that carries the infection to another member of the house- hold, such cases are included under "contacts." The infection may also be spread in the household by flies, fingers, and various other means, usually difficult to trace, and which are, therefore, all included under this group. Eegarded in this light, contacts play a major role in the spread of the disease. Extensive municipal outbreaks have been reported as largely or en- tirely due to contact infection. Winslow in 1901 studied such an out- break in Newport. Others have been reported from Knoxville, Winni- peg, Springfield, and from Germany and England. Koch regarded the spread of typhoid in Trier in the light of contact infection. Free- man says that the majority of outbreaks in the smaller towns of Vir- ginia are due to this cause. Extensive outbreaks in institutions are often due to contact with mild cases or carriers. Plies, fingers, and food (Sedgwick), and dirt, diarrhea, and dinner (Chapin), which too often get sadly confused, explain the occurrence of many a case of con- tact infection in typhoid fever and other infections. In army camps with clean water and good milk, contact infection may rise to epidemic proportions. In the Spanish-American war, of 107,000 of our troops in camp, 30,000 contracted typhoid, mostly by "contact." Similar conditions prevail in rapidly growing cities, in crowded apartments, and congested regions with a susceptible population and other favoring conditions. The danger of contact is well shown by the frequency with which nurses, ward attendants, house physi- cians, and others similarly exposed take typhoid fever. Studies of the incidence of the disease in the Massachusetts General Hospital, Bos- ton, in the Presbyterian Hospital, Philadelphia, and the Johns Hop- kins Hospital, Baltimore, ■ show that typhoid fever is at least twice and may be 8 times as prevalent among those who come in close and fre- quent association with the patient as among the population at large. Further, the disease contracted under such conditions seems to run a course of more than ordinary severity, with a greater number of com- plications and with a high mortality. This is doubtless due largely to the fact that the contactors receive fresh virulent virus. In our studies of typhoid fever in Washington we -were impressed with the importance and frequency of contact infection in that en- 94 DISEASES SPREAD - THEOUGH ALVINE DISCHAEGES demic center. In 1907 we attributed 6 per cent, of the cases to con- tacts; in 1908, 15 per cent., and in 1909, 17 per cent. Tliis included only contact with cases during the febrile stage of the disease. In Strassburg, Kayser attributed 16.8 per cent, of the cases occurring during 3 years in that city to contact infection. Little groups of 4, 6, to 12 or more cases following a primary case in a suburban focus, in my experience, frequently fall in the category of contacts. According to Conradi, the infection is transmissible most often during the early stages of the disease, sometimes even during the period of incubation. The Washington studies do not support this view, for we found the disease is communicated during all stages, and especially during convalescence. This may be due to the fact that during this time the patient moves about and scatters the infection over a wider radius. Typhoid fever, in view of all the facts, must now be regarded as a "contagious" disease. We will never have an end of it until it is so regarded and treated accordingly. Preventive Typhoid Inoculations.' — An active immunity to typhoid fever may be artificially induced by introducing dead typhoid bacilli into the subcutaneous tissue. Living cultures or bacillary extracts may also be used. The procedure is harmless, rational, and effective. Our knowledge of inoculations against typhoid fever began with the work of Pfeiffer and Kolle,^ who inoculated two volunteers in 1896. About the same time Almroth Wright "^ inoculated several per- sons, and in 1898 continued the work upon an extensive scale in India upon 4,000 British soldiers. In 1900, during the Boer war, Wright, together with Leishman, prepared a vaccine ^ and supervised the inocu- lation of 100,000 British troops. The results in India were quite en- couraging, but for various reasons the same procedure in South Africa was not as satisfactory as had been anticipated. Prophylactic inocula- tion on the advice of Koch was used by the Germans in the Herero campaign in southern West Africa in 1904. The prophylactic was voluntary and only about half of the command (7,287 men) availed themselves of it. The results, while good, fell short of expectations. In this country Eichardson was the first to advocate and practice inoculations as a means of protection against typhoid fever. The best results have been obtained in the United States Army under the direc- tion of Major Eussell. Leishman* in his Harben lecture (1910) explains the lack of suc- ^ Pf eififer and Kolle : Deutsche med. Wochnschr., 1896, XXII, 735 = Wright: Lancet, London, Sept. 19, 1896, 807; Brit. Med. Jour., Jan. 30, 1897, 16. ' The material injected is called a vaccine and the process spoken of as vacci- nation. The term in this connection is a little confusing. Inoculation is better. * Leishman, W. B.: Jour. Boy. Inst. Pub. Eealth, London, 1910, XVIII, 394. TYPHOID FEVER 95 cess in early years by saying that the vaccine may have been made less efficient by the use of too great heat in killing the bacilli. Further, it" should be noted that smaller doses and fewer injections were given then than now. The typhoid vaccines may be prepared in a number of different ways. Usually dead bacilli are used, although live bacilli have been inoculated. The bacilli may be killed either with the aid of heat or germicidal substances; the dead or live bacilli may be sensitized by the addition of antityphoid serum; the vaccines may be prepared with pul- verized bacilli, from bacillary extracts, or by the use of various chem- ical methods. Usually the vaccine is made from a twenty-four-hour-old culture killed by heating to 60° C. for one hour or less. Overheating prob- ably impairs the immunizing power of the vaccine. Most typhoid bacilli die before the temperature reaches 60° C. Some of the strains have a lower thermal death point. Stone heats only to 53° C. for one hour, depending upon phenol (0.5 per cent.) to sterilize the culture. Cultures killed without heat have perhaps greater protective properties. Certain cultures seem to cause the production of more antibodies than others. In the earlier work it was believed that the more viru- lent strains produce a greater protection. This is doubtful, for it ap- pears that the protection afforded is not in proportion to the local or general reaction, but to the amount and variety of antibodies stim- ulated. The injections are given subcutaneously at intervals of five days. From 50,000,000 to 100,000,000, sometimes 1,000,000,000, dead typhoid bacilli are injected at each inoculation. The number of inoculations varies with different authorities. At least 3, preferably 4, should be given; the greater the number of injections the greater the immunity induced. A reaction at the site of the inoculation occurs in about 10 per cent, of persons. The reactions are usually moderate and never se- rious. They consist of local manifestations, of irritation, and inflam- mation about the site of inoculation, such as pain, redness, swelling, .edema; also general symptoms, such as malaise, pains in the back and limbs, and fever. Children, as a rule, react less than adults. Of 1,101 persons inoculated by Hartsock, 11 per cent, showed no reaction, 83 per cent, mild reaction, 5 per cent, a moderate reaction, and 1 per cent, a severe reaction. All the cases had a slight local tenderness and redness at the point of inoculation. The symptoms of the reac- tion usually pass in 24 hours. The number and character of the re- actions in the experience of the United States Army ^ are shown in the following table: 'Eussell, F. F.: Jour. A. M. A., LVIII, No. 18, May 4, 1912. 96 DISEASES SPREAD THROUGH ALVINE DISCHARGES • Number of doses Reaction, Absent Reaction, Mild Reaction, Moderate Reaction, Severe 45,680 44,321 38,902 68.2% 71.3% 78.0% 28.9% 25.7% 20.3% 2.4% 2.6% 1.5% 0.3% 0.2% 0.1% Third dose The best time to give the treatment is late in the afternoon, for then the severest part of the reaction is over by the morning. The injections are usually given into the subcutaneous tissue of the outer side of the arm or into the abdominal wall; sometimes the interscapular space. There is no laboratory index of the degree or duration of the im- munity produced as a result of the inoculations. The following anti- bodies appear in the blood: agglutinins, precipitins, opsonins, lysins, stimulins. There are factors involved in the immunity not understood, and, therefore, the presence or absence of typhoid fever among in- dividuals protected in this manner is the only index of value. The negative phase advanced by Wright and denied by Leishman and others probably does not occur. At least there appears to be no increased susceptibility to the disease during the so-called negative phase. There is, therefore, no known objection to giving the prophy- lactic to those exposed to the disease or during an epidemic. In fact, the vaccines have been used as a therapeutic agent during the illness. The immunity varies in degree and also in duration; at least one year (Pfeiffer and Kolle's vaccine) ; four years (Wright's vaccine). On the average, the immunity may probably be depended upon for 2 or 3 years when produced by 4 injections of dead bacilli. The immunity may be prolonged or renewed by recourse to reinoculation. One attack of typhoid fever, however mild, produces, as a rule,- a lasting immunity. Second attacks, however, occur. Draschfeld's figures, based on 2,000 persons in the Antwerp Hospital, show that only 0.7 per cent, of that number were affected twice. The results of typhoid inoculations can no longer be questioned. The morbidity is lowered in those who have been properly "vaccinated" ; the figures are too recent to state just how much. The most striking effect is in the lowering of the mortality. The latest summing up of the antityphoid inoculations is by Leishman in the July and Sep- tember, 1910, numbers of the Journal of the Royal Institute of Public Health, xviii, Nos. 7, 8, and 9; also Report of the French Commis- sion, Public Health Reports, P. H. & M. H. S., October 6, 1911, xxvi, 40, 1507. The best results have been obtained in the United States Army, TYPHOID FBVBE 97 where the vaccinations are done under the supervision of Major Eus- The health record established by the Maneuver Division of the United States Army at San Antonio, Texas, during the summer of 1911, is a triumph in preventive medicine. The division had a mean strength of 12,801 men. All were treated with the typhoid vaccines. The result was that from March 1,0th to July 10th only two cases of typhoid fever developed; no deaths. One patient was a private of the hospital corps who had not completed his immunization, having taken only two doses. His case was very mild and probably would have been overlooked but for the rule that blood cultures were made in all cases of fever of over 48 hours' duration. The other case was a teamster who had not been inoculated. Among the 13,801 men there were only 11 deaths from all diseases. Typhoid fever prevailed at the time in the neighborhood. Thus, there were 49 cases of typhoid fever with 19 deaths in the city of San Antonio during this period. This contrasts markedly with the typhoid record of the United States Army during the Spanish-American war, when the typhoid record of a division of volunteer troops camped at Jacksonville, Florida, in 1898, under conditions similar to those at San Antonio, was as fol- lows: The division at Jacksonville had 2,693 cases with 248 deaths, which was about the average typhoid incidence of the camps. Since the year 1904, with an improved vaccine, more than 100,000 British troops have been inoculated without any untoward result. The protection afforded may be seen from the most recent figures from India, re- ported by Col. E. H. Firth.^ "In that period there were, in all India, 112 cases of typhoid, with six deaths, among the protected men, and forty-five cases with four deaths among the non-protected. The protected population was 63,634 persons, and the non-protected 8,481. From these data we find the case incidence per thousand among the protected to be 1.7 and among the non-protected to be 5.3. If we take the mortality and express it as per million, then the ratio for the protected is 94, and for the non- protected 471. That is to say, the incidence for typhoid for the first half year was roughly five times as great among the non-protected as among the protected." Spooner reports that in the Massachusetts General Hospital, among the nurses and others exposed to typhoid fever, 80 per cent, of whom have been inoculated during the past three years, not a case has been contracted, and for the first year in the history of the institution there were no cases among the nurses or attendants. The case morbidity in training schools for nurses in Massachusetts during three years was nearly nine times greater in the uninoculated than among the inoculated. '^Loc. cit., p. 95. ' Firth, E. H. : Jour. Boy. Army Med. Corps, London, 1911, XVII, 495. 98 DISEASES SPEEAD THROUGH ALVINE DISCHARGES MelchnikofE and Besredka ^ failed to protect chimpanzees against typhoid infection by means of killed bacilli, but obtained immunity ap- parently as definite as that produced by an attack of the disease by the use of living cultures.^ Summary. — Preventive typhoid inoculations involve no risk what- ever, and are especially applicable to those unduly exposed to the in- fection, such as nurses, hospital attendants, physicians, travelers, sol- diers in camps, persons in epidemic localities, and persons in the fam- ily of a bacillus carrier. The method has been proposed for general use among the public in endemic foci, but it is a question whether this artificial method of acquiring immunity would serve as good a purpose in the end as fighting the disease along the lines of general sanitation — which has been so successfully done in many European centers. It would certainly be a mistake to immunize the population with this artificial method to the neglect of general sanitary improvements, such as good water, clean milk, fly suppression, cleanliness, and personal hygiene. The question as to whether the vaccinations may or may not increase the number of bacillus carriers should also be determined. Because a person has received the protection afforded by typhoid inocu- lations is no reason for reckless disregard of other prophylactic meas- ures. Management of a Case so as to Prevent Spread. — Success depends upon an early and accurate diagnosis. All cases of typhoid fever and all cases suspected of being typhoid fever should be isolated. This does not mean imprisonment in a lazaretto. The proper place to care for typhoid fever is in a suitable hospital. A private home is a poor makeshift for a hospital, and it is unreasonable to turn a household into a hospital for 4 to 8 weeks or longer. The room in which the patient is treated should be large and well ventilated, and should con- tain no unnecessary furniture, curtains, carpets, etc. It must be kept scrupulously clean, dry sweeping and dusting prohibited; and well screened. The case should be reported to the health authorities without de- lay, and the house should be placarded so as to warn others, and visit- ing discouraged. Under no circumstances should visitors be admitted into the sick room. The disinfection of the stools, urine, sputum, and other excretions is of the first importance, and should be carried out with great care and conscientiousness. For the urine, sufficient bichlorid may be added to make a 1-1,000 solution, or carbolic, 2.5 per cent., formalin, 10 per cent., and allowed to stand one hour before discarding. Stools may be disinfected with bleaching powder, 3 per cent. ; milk of lime (1 to 8) ; ^Annates de I'Inst. Pasteur, Dec, 1911, XXV, 12, 'p. 865. ^^nm. de I'Inst. Pasteur, Mar. 25, 1911, and Dec, 1911. TYPHOID FEVEE 99 eresol, 1 per cent.; carbolic acid, 5 per cent.; or formalin, 10 per cent. The discharges should be received in a glass or earthenware vessel con- taining some of the germicidal solution. Then add more of the solution so that it shall be present in twice the volume of the excreta to be disinfected; let stand at least one hour, protected from flies. Masses are so difficult to penetrate that they should be broken up by stirring. It takes a carbolic acid solution some 12 hours to penetrate the in- terior of a fecal mass. The sputum may be burned or boiled. Strong carbolic acid, tri- cresol, or formalin are also applicable. The patient should have his own dishes, cups, spoons, glasses, etc., which should be scalded after each use. Eemnants of lunch, especially meat, milk, gelatin, broths, and other organic food in which the in- fection may live and even grow should not be eaten by others. Such remnants may be burned or first boiled and then discarded. Those who nurse the sick should keep out of the kitchen on account of the risk of contaminating the food. Towels, sheets, nightgowns, and all fabrics used about the patient should be disinfected either by boiling, or immersion for one hour in bichlorid of mercury, 1-1,000, carbolic acid, 3.5 per cent., or formalin, 10 per cent. The water used to bathe the patient should be disinfected before it is allowed to run into the sewer. This may be done by adding suffi- cient carbolic acid or bleaching powder ; the latter is cheapest and most practical. Milk bottles must be kept out of the sick room. In any case, they should be scalded before returning to the dairy. The thermometer should be kept in formalin or other suitable ger- micidal solution. Eeetal tubes, especially in hospital practice, must be carefully disinfected each time before using. The nurse must protect herself as well as others; a solution of bi- chlorid should be kept constantly at hand. Every time the patient is bathed, his mouth cleaned, or his buttocks washed, the hands must be disinfected and washed in soap and water. The nurse must exercise especial care if she is to go to the kitchen or to the ice-box, etc., as is frequently the case in private houses, where a special diet kitchen can- not be provided. The nurses, physicians, ward attendants, and others particularly exposed may protect themselves with preventive typhoid inoculations. The physician should be quite as careful as the nurse, not only so that he may not carry the infection to himself or other patients, but also that his practice may serve as a stimulating example. At the conclusion of the case a general terminal disinfection of the room and its contents may be practiced. This is best done with formaldehyde gas, followed by a general mechanical cleansing. 100 DISEASES SPREAD THROUGH ALVINE DISCHARGES Convalescents should not be given liberty until the danger of bacil- lus carrying has passed. This may be determined only by bacteriologic examinations of the stools and urine. Four successive negative results at intervals of several days are required before a conclusive report may be vouchsafed in the case of the stools. One examination of the urine is ordinarily sufBcient. The use of urotropin (hexamethylenamin) diminishes the incidence of bacilluria, and is becoming a routine practice. Summary — Personal Prophylaxis. — The prevention of typhoid fever may be summed up in the word cleanliness — physical and biological cleanliness. By this is meant not only clean food, especially water and milk, but also cleanliness of person and environment. Typhoid fever has always prevailed where cleanliness is neglected and has diminished where it has been intelligently observed. It is true that typhoid bacilli do not breed in the rubbish and dirt of back yards and alleys, or in unkempt city lots, but these conditions in a city may be taken as an index of the general cleanliness of its inhabitants. The eradication of typhoid fever is easier in cities than in country districts; clean cities now have less typhoid fever than the surrounding rural region. Cities can well afford extensive and expensive sanitary works which are beyond the financial possibilities of sparsely settled districts. If a clean water from natural sources is not available, then large volumes of a polluted water may be rendered reasonably safe for municipal use by slow sand filtration or by bleaching powder. Fur- ther, cities can afford to inspect their milk supply and to supervise the pasteurization of all that is not safe. These .two measures would prac- tically eliminate typhoid infection coming into cities in its food supply — especially if in addition to this a supervision is maintained over oysters and shellfish, and vegetables partaken in their raw state. Further, cities can well afford to employ skilled and experienced health officials and are financially able to engage the services of experts. On the other hand, each farmhouse represents, in miniature, all the problems with which the city deals by wholesale, and is often not financially able to meet its sanitary requirements. The country is the weakest link in our sanitary chain. Cities will find it a paying proposition to sup- press flies, rats, and other vermin, which may be done much more easily than in rural or suburban conditions. This should be done not only on account of the suppression of typhoid fever, but other diseases thus conveyed. The city beautiful must also be the city clean in its cellars, garrets, back yards, empty lots, alleys, and stables. To sum up, the main factors in the spread of typhoid fever in our large cities are: (1) water; (2) milk; (3) contact; (4) miscellaneous. In a city having a clean water supply the residual typhoid must be attacked along two definite lines, viz., improvement of the milk supply CHOLEEA 101 and its pasteurization, and a warfare against the disease in the light of an infection spread from man to man. The health officer should establish a laboratory for the early diag- nosis of cases and for the discovery of carriers. The health officer should at once send a trained agent to every house from which a case of typhoid fever is reported. The visit should be made as early as practicable and with the object 'of seeing that the stools and urine are properly disinfected, patients isolated, milk bottles scalded, sick rooms screened, house placarded, visiting discouraged, and other necessary measures taken to prevent the spread of the infection. Convalescents should not be released until the absence of typhoid bacilli from the urine and stools has been demonstrated by four successive examina- tions. Carriers need not be indefinitely quarantined, but should be prohibited from engaging in any employment having to do with foods, or in which close personal contact, as in nursing, is required. Carriers should be instructed concerning the danger and educated to thoroughly wash and disinfect their hands, especially after a visit to the toilet. The health officer alone cannot eliminate typhoid fever from a city. He needs the help of the community. Much can be done through education. A stimulating leader may accomplish a world of good through voluntary effort, but in the end it requires comprehensive laws and an energetic enforcement of them, without fear or favor. The personal prevention of typhoid fever resolves itself into boil- ing the water, if suspicious; partaking only of milk or fresh milk products that have first been pasteurized, and otherwise assuring one- self that all food has been thoroughly cooked. In addition to this, direct and indirect contact with persons who have the disease, or who are known to be carriers, must be avoided. Sanitary habits should be encouraged, especially the one simple precaution of washing the hands before eating, and of keeping the fingers and other unnecessary objects away from the mouth and nose. In certain circumstances in which there is unusual exposure protection may be had by increasing immu- nity through typhoid inoculations; CHOLERA The prevention of cholera corresponds to the prevention of typhoid fever. In the case of cholera vigorous measures have been rewarded with signal success. It is quite possible to live in the midst of a raging cholera epidemic without contracting the disease. Within recent years epidemics have been suppressed and the spread of the infection limited. The home of true cholera is the delta of the Ganges, hence it is usually called "Asiatic cholera" to distinguish it from Cholera nostras or Cholera morbus. During the sixteenth, seventeenth, and eighteenth 9 102 DISEASES SPREAD THROUGH ALVINE DISCHARGES centuries cholera was epidemic at various times in India. It is only in the nineteenth century that cholera has spread along the routes of trade and travel to Europe (first in 1830), Africa, and America in 1832. There have been four pandemics; one from 1817-1823, another 1826-1837, a third 1846-1862, and a fourth from 1864-1875. In 1832 it entered the United States by way of New York and Quebec and reached as far west as the military posts of the upper Mississippi. The disease recurred in 1835 and 1836. In 1848 it entered the country through New Orleans and spread widely up the Mississippi and was dragged across the continent by the . searchers for gold all the way to California (1849). It again prevailed widely through this country in 1854, having been introduced by immigrant ships into New York. In 1866 and 1867 there were less extensive epidemics. In 1873 it again appeared in the United States, but did not prevail widely. In 1892 the great epidemic of Hamburg occurred, and the disease threatened to become pandemic in Asia, Africa, and Europe. Cases were brought by transatlantic liners to New York, and a few cases occurred in the city, but its spread was prevented by aggressive measures. Cholera has prevailed for years in the Philippines, but is now under control. Wliile the home of cholera is in the tropics, there is scarcely a country in the world that has not been visited some time or other by the ravages of this fatal disease. The incubation period of cholera is short, frequently 1 or 2 days, rarely over 5. The period of detention in quarantine is 5 days. One attack produces a mild grade of immunity which is not lasting. The disease is peculiar to man. The Cause and Contributing Causes of Cholera. — The Vibrio cholerce or the "comma bacillus" of Koch is the undisputed cause of the dis- ease. The conditions of infection, however, are complex. Not everyone who talces the specific microorganism by the mouth necessarily gets the disease, but without it there can be no cholera. Many cholera vibrios probably die in the acid juices of the stomach. There is, there- fore, perhaps less danger in taking small amounts of infection during active digestion than upon an empty stomach, for it has been shown ex- perimentally that cold drinks do not stay long in an empty stomach, but pass quickly through the pylorus. After the cholera vibrio has passed the pylorus and reaches the alkaline juices of the intestines, it may find ideal conditions for growth or may still have a hard struggle for existence. Here symbiosis must play a dominant role. It is well known in all cholera epidemics that a deranged digestion is an important pre- disposing factor to the disease. In the Hamburg epidemic a marked access of cases on Monday following the Sunday dissipations was noted. Raw fruits, crude fibrous vegetables, and other fermentable food, difficult of digestion, seem to favor the growth and multiplication of the cholera CHOLEEA 103 vibrio in the intestinal tract. In the light of this view rav7 fruits and vegetables may often be the predisposing factor rather than the medium which conveys the infection. Just what the factors are that favor or handicap the growth of the cholera vibrio in the intestinal tract are undetermined. Pettenkofer stoutly maintained that the "comma bacil- lus" was only one of the factors in the etiology of the disease. He placed special importance upon the condition of the host and his en- vironment, and considered at least three fundamental factors in his X, Y, Z theory. X is the germ, Y the host or soil, Z the environment. In this connection disease may aptly be compared to fermentation, in which X represents the yeast, Y the carbohydrate, and Z the tem- perature, moisture, reaction, and other essential conditions for the growth and activity of the yeast. Pettenkofer maintained that X without Y and Z would not produce cholera, that is, while the cholera vibrio was pathogenic in India or Hamburg (1892), where Y and Z were favorable, it would be harmless in Munich, where Y and Z were unfavorable. To prove this theory, he and his assistant, Em- merich, drank pure cultures of cholera after first rendering the stomach contents alkaline. Pettenkofer, then an old man, had a diarrhea; Emmerich, on the other hand, had a sharp attack from which he almost lost his life. Similar convincing experiments have occurred among lab- oratory workers, who have accidentally gotten pure cultures of cholera into their mouths. On the other hand, a number of persons who imi- tated Pettenkofer's experiment were not affected. Pettenkofer did not regard his own case as cholera, and insisted that the negative results lent confirmation to his theory of the importance of contributing factors (Y and Z). Diagnosis. — The diagnosis of cholera depends upon isolation and identification of the cholera vibrio in pure culture. This has become comparatively simple, but great care must be taken not to confuse the true vibrio of cholera with a great host of other microorganisms which closely resemble it. A presumptive diagnosis of cholera may be made by finding large numbers of comma-shaped bacilli in direct microscopic examination of stained preparations, or in hanging drops of the mucous flakes ordinarily found in cholera stools. This test is only presumptive, the final criterion being the biological reactions of the microorganism ob- tained in pure culture. The two reactions which are specific and re- liable are Pfeiffer's phenomenon and agglutination. Dependence should not be placed upon morphological characters, cultural peculiarities, or pathogenicity upon laboratory animals, for these do not furnish the means of certainly defining the cholera vibrio. For the isolation of the cholera vibrio agar is preferable to gelatin, formerly so much used. The suspected material should be planted upon 104 DISEASES SPEEAD THEOUGH ALVINE DISCHAEGES the surface of ordinary alkaline agar or upon Dieudonne's medium, using one of the small rice-like flakes or an equivalent quantity of feces. Dieudonne's medium is prepared as follows: Sol. A. — Equal parts of a normal solution of potassium hydroxid and defibrinated ox-blood are mixed and sterilized in the autoclave. Sol. B. — Ordinary nutrient agar, exactly neutral to litmus. Seven parts of B are mixed vpith 3 parts of A and poured into Petri dishes. The plates should not be used immediately after their preparation. Dieudonne recommends keeping them several hours in the incubator at 37° C, uncovered and face down, or to heat them for 5 minutes at 65° C. Equally good results can be obtained by keeping them 48 hours at room temperature. The surface of the agar should be slightly dry. Once in condition, the plates should be used in a period not exceeding 5 or 6 days. Upon this medium cholera vibrios grow abundantly. On the con- trary, the organisms which most often accompany them on plate cul- tures, especially B. coli, grow either very poorly or not at all. When it is suspected that the cholera vibrios are few in number, they may be enriched by first planting in Dunham's solution. Ap- proximately 1 e. c. of fecal matter should be placed in 50 c. c. of the peptone solution. This is incubated at 37° C, and in from 6 to 8 hours a loopful is taken from the surface and transferred to ordinary agar or Dieudonne's medium. Suspicious colonies are fished and studied further. A quick method of detecting carriers is given on page 108. Kolle and Gotchlich have shown from a large number of observa- tions that with strongly agglutinative serum, the power of which reaches 1-4,000, the agglutinative power for common vibrios, not cholera, does not, as a general rule, exceed 1-50 and rarely reaches 1-200; agglu- tination in dilutions of 1-500 has been only very exceptionally ob- served. On the contrary, the true cholera vibrios agglutinate in dilu- tions varying from 1-1,000 and 1-20,000. Therefore, with a specific agglutinating serum having a titer of 1-4,000, any organism which is agglutinated in 1-1,000 may be considered true cholera. Organisms agglutinating in dilutions of 1-500 and 1-1,000 should be regarded as doubtful. In any critical case Pfeiffer's reaction (see page 389) should be tried. This is specific. Modes of Transmission. — Cholera is spread by man from place to place. It follows the lines of trade and travel. Seaports are in- variably first attacked. The epidemic at Hamburg in 1892 was brought to that port by immigrants on board vessels from Eussia. There are many similar instances. In 1849 many a gold hunter found another Eldorado than the one he was searching for, as cholera was dragged CHOLERA 105 across the continent by the caravans seeking fortunes in California. The same thing takes place in the Indian pilgrimages to Mecca. The cholera vibrio enters the digestive tract through the mouth. It is taken in the food and drink. Infected water is a frequent me- dium of transference, and probably the sole vector of the great epi- demic outbursts. Cholera, however, may be transferred from man to man directly, also indirectly by flies, fingers, food, and all the innu- merable channels from the anus of one man to the mouth of another that have been described in the case of typhoid. In endemic or residual cholera, water-borne infection plays a minor role. This was well proven in the recent sanitary campaign against the disease in the Philippine Islands, in which the water was practically ignored and the disease conquered in the light of an infection com- municated rather directly from man to man. Cholera was spreading rapidly despite active measures. Its progress was stopped by throwing a sanitary corps across a narrow neck of land . some miles in advance of the march of the disease. Here a quarantine was established and persons held 5 days under observation before they were permitted to pass. The usual disinfection and other measures were practiced and the disease effectively stopped. The cholera vibrio leaves the body in enormous numbers in the dejecta, also sometimes in the matter vomited. The cholera vibrio does not invade the blood and tissues generally, and, therefore, is not voided in the urine. Disinfection in this disease must, therefore, be concen- trated upon the discharges from the bowels and mouths, at the bedside. Water. — The cholera vibrio may live and even multiply in water. Koch in his original investigations found the organism in the foul water of a tank in India which was used by the natives for drinking purposes. It has been shown by experiment that the cholera vibrio may multiply to some extent in sterilized river water or well water; and that it preserves its vitality in such water for several weeks or even months. In recent times cholera organisms have been found not in- frequently in the water of wells, water mains, rivers, harbors, canals, and even sea water (the North Sea near the mouth of the Elbe), which have become contaminated with the discharges of cholera patients. It is plain from the nature of the case that infected water must play a very large role in spreading this infection. The Broad Street Case in London. — The earliest and now classic instance in favor of the water-borne theory we owe to the late Dr. John Snow. This is the well known Broad Street pump outbreak in London in 1854, an account of which will be found on page 815. The best example of water-borne cholera is the Hamburg epidemic of 1892, which I was fortunate enough to see in part. In this case no link in the chain of evidence is missing. Cholera was brought to 106 DISEASES SPEEAD THROUGH ALVINE DISCHARGES Hamburg by immigrants either from Russia or France. The water of the Elbe was infected with their discharges. The Vibrio cholerw was readily isolated from the river water which was distributed through- out the city for drinking purposes without purification. The sewers of Hamburg emptied into the river Elbe near the water intake, which produced an increased concentration of the infection. An account of the epidemic will be found on page 819. Other Modes of Teansfekence. — The fact that water-borne in- fection is practically the only cause of the large cholera epidemics must not overshadow the importance of other modes of transmission. In addition to the violent outbreaks, cholera occurs in nests or smoul- ders like endemic typhoid. It is difficult to trace the connection be- tween cases in endemic areas. Thus, a careful study of the cholera situation in Manila disclosed the fact that isolated cases would crop up at widely different points without any evident connection between them. Cholera carriers were suspected but not proved in this instance. At irregular intervals of several years the disease would gather force, and cases multiply, until it assumed epidemic proportions, it is be- lieved entirely independent of the water supply. The way cholera was dragged across our continent by the "forty-niners," and its occurrence among the Mecca pilgrims, are instances of its spread largely inde- pendent of infected water. Contact Infection". — Contact infection in cholera must not be underestimated. Persons frequently become infected by handling the dejecta or through freshly infected fomites, such as soiled linen. Di- rect transmission from person to person is not infrequent among physi- cians and nurses. In congested quarters, where many persons live un- der uncleanly conditions, contact infection plays an important part. The same thing may be seen on board vessels, in which case the dis- ease may be confined to the firemen, stewards, or sonie other limited group who are required to live in close contact with each other. Epi- demic outbreaks due to contact infection have been recorded, such as the 30 eases which occurred in the fall of 1892 in Boizenburg. Cholera is not highly "contagious," for physicians, nurses, and others in close contact with patients need not become infected pro- vided intelligent measures are adopted. On the other hand, there is great danger of the spread of the disease through devious and hidden routes, as is the case with typhoid and dysentery. Washerwomen and those who are brought in very close contact with the linen of cholera patients or with their stools are prone to contract the disease. Koch, in his original investigations, found that the "comma bacillus" may mul- tiply rapidly upon the surface of moist linen. Milk may be contaminated, but is probably not a frequent medium of infection, for the reason that its acid reaction is inimical to the CHOLEEA 107 cholera vibrio. Green vegetables and fruit that have been washed in an infected water may convey the disease. The bacilli live on fresh bread, butter, and meat for from 6 to 8 days. Flies, Etc. — It has been shown that the cholera vibrios may live in the intestines of flies for at least 3 days, and these and other insects may also spread the infection mechanically. The cholera vibrio is a frail organism and dies rapidly when dried or exposed to light and other injurious influences. Infection through the air is, therefore, not to be dreaded. Fomites, such as bed and body linen or other objects, including floors, walls, toys, etc., contaminated with the dejecta, can be regarded as possible sources of infection. There is, however, a special limitation in this case, owing to the fact that this organism is so readily de- stroyed by desiccation and crowded out by saprophytic microorganisms. Thus, as a rule, only fresh dejecta and freshly contaminated objects are liable to convey the infection. Bacillus Carriers.- — The cholera vibrios are passed in the feces during the early part of the disease. They usually disappear after the fourth to the fourteenth day, but may remain a much longer time. The following are the longest cited by PfeifEer : '■ PERSISTENCE OF CHOLERA VIBRIOS IN STOOLS OF CONVALESCENTS, OR BACILLUS CARRIERS Name of Observer. Longest Duration (days). Name of Observer. Longest Duration (days). 10 12 12 18 24 47 Kolle 48 Lazarus and Pulicke Donitz 49 Michailow . . 15 Simonds Pfeiffer 13 Riimpfil Burgers 69 Rnrrimplfifirp, McLoughlin found bacillus carriers numerous in epidemic centers. Thus he found 6 to 7 per cent, of carriers among healthy individuals living in the infected neighborhoods in Manila. On the other hand, carriers were exceedingly rare in neighborhoods having few cases. Persons in good health may harbor the cholera organism in their in- testines. Cholera carriers, therefore, play a similar role to typhoid car- riers in spreading the infection. Less, however, is known concerning cholera carriers than typhoid carriers. Several different methods for the detection of cholera carriers are applicable. All of them are based upon the facility with which the vibrio grows upon Dunham's solution. Particles of feces are plapted in this medium and subsequently examined for comma-shaped mi- croorganisms. If found, the diagnosis is ' jirtesumptive, Piire cul- ' H^gienische Eundschau, Tebruarj^, 1910, Vp]. XX, No. 4, 108 DISEASES SPEEAD THEOUGH ALVINE DISCHAEGES tures should then be made and studied for agglutination. See page 104. The routine bacteriological examination of immigrants from cholera- infected ports, as practised at the Quarantine Station at New York, in 1913, was as follows:^ 1. Inoculation of feces into Dunham's peptone solution (at 37° C). 2. Subinoculation at the end of six hours of one loop of the sur- face growth into a second Dunham's peptone tube. 3. Examination of a smear taken from the surface growth of the second Dunham's peptone tube, after it has been incubated six to nine hours at 37° C. Bendick uses a modified Dunham's solution containing sodium car- bonate, 1 gram; saccharose, 5 grams; and phenolphthalein solution, 5 c. c, in addition to the usual amount of water, peptone and salt. The cholera vibrios ferment the saccharose ; the acid produced unites with the sodium carbonate and the medium becomes neutral, hence the red color of the phenolphthalein disappears. Immunity and Prophylactic Inoculations. — The immunity produced by an attack of the disease is of short duration. Attempts have been made to produce an artificial immunity by the injection of cholera cultures. These were first made by Ferran of Spain in 1884, but the cultures used by him obtained directly from cholera • stools were not pure. Haifkine tested the method on a large scale in India; over 40,000 persons were inoculated with attenuated cultures up to 1895. Haflfkine proceeded in accordance with the well known methods of Pasteur in anthrax, by using two vaccines of difFerent strengths. The first was obtained by growing the culture at a heightened tem- perature, which produced a very attenuated strain. The second con- tained living vibrios weakened by passage through guinea-pigs. The re- actions produced were generally slight in degree and consisted of a brief elevation in temperature, headache, malaise, as well as redness, swell- ing, and pain at the site of injection. The results were not clear cut on account of the difficulty of comparing the disease in the inoculated with suitable controls. However, the general impression is that the method has some prophylactic value. This opinion has been confirmed by the later work in various parts of India, where, up to the year 1899, of 5,778 inoculated persons, only 27 had cholera and 14 died, whereas, of 5,549 non-inoculated, 198 had cholera, of which 124 died. Kolle showed that the blood serum of the inoculated persons contains a specific bacteriolysin similar to that contained in the blood serum of those who have recovered from the disease. Kolle uses 2 mg. of an agar culture suspended in 1 c. c. of physiological salt solution and killed at 68° C. for one hour for the first injection, and twice this 'Bendick: Jour, of Am. Pub. Health Assn., I, No. 12, 906, Dee. 1911. CHOLBEA 109 dose (4 mg.) for the second; 0.5 per cent, of phenol is added as a preservative. The immunity produced by these protective inoculations lasts a long time, but after a year the specific antibodies begin to diminish in the blood serum. There seems to be little doubt in Japan concerning the value of the protection afforded by the inoculation of dead cultures, for in the district of Hiogo, during the epidemic of 1902, 77,907 persons were inoculated. Of these 47, or 0.06 per cent., took cholera, and 20, or 0.03 per cent., died, whereas, among 825,287 persons not inoculated, 1,153, or 0.13 per cent., took the disease, and 863, or 0.1 per cent., died. It is especially noteworthy that all the cases among the inocu- lated group were in those who received an injection of 2 mg. of the dead culture. Later 4 mg. were .used, and in this group no cases oc- curred. Protective inoculations as a prophylactic measure against cholera will never be popular or necessary in communities with sufficient sani- tation. It may, however, be of value in camps, armies on the march, for physicians, nurses, ward tenders, and others especially exposed. ftuarantine.— Cholera is an infection which fully justifies maritime quarantine practice. The disease may be blocked by a careful system of inspection, detention, and disinfection at the seaport. In order for maritime quarantine to be effective for cholera, it must have the assistance of a bacteriological laboratory to diagnose cases and recog- nize carriers. A strict watch must be kept for mild and ambulant eases of the disease. In the summer of 1912 the quarantine authorities at the large sea- ports on our Atlantic littoral examined about 34,000 specimens of bowel discharges from passengers and crew from cholera-infected ports. At the JSTew York quarantine the cholera vibrio was isolated from 28 persons sick with the disease, and 27 healthy persons were found to be discharging vibrios in their feces. These carriers could not have been discovered except by laboratory examination. Seven cases of cholera were detected at other ports by the same methods. There can be no doubt that the adoption of this measure kept cholera out of the country. The Foreign Inspection maintained by the United States Govern- ment during the epidemic of 1892-93 was a convincing demonstration of the value of this service as one of the safeguards against cholera. Officers of the Public Health and Marine Hospital Service stationed at foreign ports supervised the water and food supply of the depart- ing vessels, inspected the crew and passengers as to their health; those coming from infected localities were detained under observation 5 days before they were permitted to embark. On practically none of the vessels complying with these requirements did cholera appear. 110 DISEASES SPEEAD THROUGH ALVINE DISCHARGES whereas it broke out comparatively frequently on vessels which did not comply with the restrictions, but sailed from the same ports under similar conditions. A similar experience demonstrating the value of a sanitary inspection of vessels leaving an infected port was demonstrated in the Philippines, where, since the American occupation, cholera has been kept off the returning transports and its interisland spread has been cheeked by a sanitary supervision of vessels at both the ports of departure and arrival. Personal prophylaxis requires, first of all, scrupulous cleanliness on the part of the person and his surroundings. Those who handle cholera patients, their dejecta, or infected articles must carefully disinfect their hands each time, and should under no circumstances eat or drink any- thing in the sick room. During cholera times all water and food of every description should be boiled or thoroughly cooked just before it is partaken of. Great care must be exercised that the water or food does not become infected after it has been boiled or cooked. The usual measures should be taken to guard against flies and other vermin. With strict attention to these measures, it is possible to avoid the in- fection. In addition, however, attention to general hygiene and espe- cially to the character of the food and regularity of meals should be given. Slight attacks of indigestion and diarrhea should receive prompt medical attention. Summary — Prevention.' — Preventive measures should first of all be focused upon the cholera cases in order to prevent the spread of the infection at the bedside. This includes early and controlled diagnosis. Cholera patients should be cared for in special hospitals where all these necessary measures may be carried out by trained assistants. The infection in cholera stools may be destroyed with formalin (10 per cent.), carbolic acid (5 per cent.), milk of lime (1 to 8), or chlorinated lime (3 per cent.). Persons leaving a cholera region should either be detained in quar- antine for 5 days or be watched this length of time after arrival at the place of destination. This may be accomplished by requiring them to report twice daily to the sanitary authorities. It is unnecessary to disinfect merchandise shipped from a cholera town. For the control of a cholera outbreak it is important to require that all cases, as well as all suspicious cases, be reported. A bacteriolog- ical laboratory is necessary to confirm the diagnosis and arrangements must at once be made to isolate the cases and to disinfect the dejecta, the body and bed linen, and other materials. Convalescents are not released until two successive examinations at 5-day intervals show the absence of the cholera vibrios. On account of the frail character of the vibrio a general disinfec- tion of the house is not necessary in cholera. The room itself may DYSENTERY 111 be treated with formaldehyde or the surfaces washed down with a bi- chlorid solution or one of the alkaline coal-tar creosotes. The water- closets may be disinfected with formalin, carbolic acid, milk of lime, or chlorinated lime. Spoons, cups, saucers, and remnants of food should be treated as in the case of typhoid. Otherwise the preven- tion of cholera is a strict counterpart of that of typhoid. A summary of the preventive measures necessary to control an out- break of cholera are: centralization of authority in one person; estab- lishment of a system of securing and reporting information; organiza- tion of the personnel for the sanitary work; enactment of necessary ordinances; house to house inspection; safe disposal of feces of entire population; provision for a safe water supply; supervisory control of food and drink; a search for, and control of carriers; isolation and care of patients in special hospitals ; separate hospitals or wards for suspects ; a laboratory; detention camps or barracks for those desiring to leave the infected area; disinfection, etc. For further discussion concerning the control of epidemics, see page 319. DYSENTERY Classification. — For the purpose of prevention we may consider all dysenteries under three heads: (1) bacillary dysentery, (2) amebic dysentery, (3) symptomatic dysentery. Bacillaky dtskntery is an acute infectious disease caused by the B. dysenterim, an organism that closely resembles the typhoid bacillus in cultural respects. It differs from typhoid in that it has limited or no motility. More fundamental differences are found in its biological properties, such as specific agglutination and pathogenic power. There are at least two well recognized types of B. dysenterim. One corre- sponds to the original organism discovered by Shiga in 1897 in the Japanese epidemic, and the other to that found by Flexner in Manila. The Shiga bacillus does not ferment mannite, while the Flexner ferments that "sugar" with the production of acid. Further, the two organisms differ in their properties of agglutination toward specific sera. A very strong endotoxin may be extracted from the Shiga type which, when injected intravenously into rabbits, produces a fatal intoxication with a faithful reproduction of the symptoms and lesions of bacillary dysen- tery. Kraus and Dorr and also Todd have found that the Shiga strain produces such a soluble toxin, which is not the case with the Flexner strain. Amebic dysentery results from infection with the Entamceha hys- tolytica. There are marked differences between the amebic and the bacillary types of the disease. The former is a chronic infection which starts insidiously, is characterized by relapses and recurrences, is fre- 113 DISEASES SPEEAD THROUGH ALVINE DISCHARGES quently associated with sequelsB, such as liver abscesses, and occurs sporadically or in endemic foci, mainly in the tropics. Epidemic out- breaks of the amebic form of dysentery are not known. Bacillary dysentery, on the other hand, is an acute febrile disease, usually self- limited, with marked symptoms of toxemia, sudden onset, no sequelse, and occurs in widespread and severe epidemics. The bacillary disease occurs in the temperate regions as well as in the tropics, and is almost always the cause of dysentery outbreaks in ships, camps, jails, etc. The lesions of the two diseases also differ markedly. In amebic dysentery the ulcers are undermined, whereas in the bacillary disease the inflam- mation is diffuse and of varying grades of severity, which may reach coagulation necrosis or gangrene. There are also notable differences in the treatment; for example, ipecac given early or rectal injections are of service in amebic dysentery, but are of questionable use and may even do harm in the bacillary form. So far as prevention is concerned, how- ever, both diseases may be regarded as intestinal infections entering by the mouth, and therefore the prophylaxis is practically the same and corresponds closely to that of typhoid or cholera. Under symptomatic dysentery are grouped all other conditions with dysenteric symptoms resulting from a great variety of causes. Modes of Transmission. —The dysentery bacillus enters the body by the mouth and leaves the body in the alvine discharges. So far as known, the dysentery bacillus does not penetrate deeply into the tis- sues, and is seldom found in the circulating blood. It therefore does not appear in the urine. The infection is transferred from man to man directly or in- directly in precisely the same ways described for typhoid. Undoubt- edly drinking water frequently contains the infection, and well marked water-borne epidemics have been reported in recent years, particularly in Japan. Contacts, food, and flies also play an important role. The epidemiology of bacillary dysentery is about the same as that of typhoid. It is largely a summer disease. In wars it used to cause great ravages; as in the Crimean war, our own civil war, the Franco-Prussian war, and the recent Russian-Japanese war. Overcrowding, lack of cleanliness, and other unhygienic conditions favor the spread of bacil- lary dysentery, so that it is sometimes called famine, asylum, ship, or jail dysentery. The mortality varies greatly, from 6 or 7 to 26 or 30 per cent. Bacillus carrying in dysentery occurs, and probably plays a more important part in spreading the disease than we now suspect. As a rule, the bacilli soon disappear from the stools in the light eases, but Shiga has found them more persistent in some instances, von Drigalski reports an outbreak in Germany caused by a returning soldier. Recent convalescents are particularly apt to spread the infection. The Entamceha hystolytica is also taken in by the mouth and DYSENTEEY 113 passed by the bowels. It probably exists in its free living state in water, upon vegetables and fruits, and other moist surfaces. There is some suspicion that the buds of the entameba may be carried by the air. There are still large lapses in our knowledge concerning the free living stages, and other facts in the life history of the ameba, so that our preventive measures lack finality. Eesistance. — The dysentery bacillus has about the same resistance to germicides and other unfavorable conditions as the general class of spore-free bacteria. It dies in about 8 to 10 days when dried. It may live for months when moist. It is sensitive to acids. Phenol, 0.5 per cent., kills the dysentery bacillus in 6 hours, 1 per cent, in 30 minutes, 3 per cent, in 1 to 3 minutes. Bichlorid of mercury, 1-1,000, kills it at once, and direct sunlight in about one-half an hour. I have found certain strains of the dysentery bacilli somewhat more resistant to heat than the typhoid bacillus. They are killed with cer- tainty at 58° C. for one hour, or at 60° C. for 20 minutes. The dysen- tery bacillus resists cold and may live for months when frozen. The Entamceba hystolytica is probably less resistant to heat and germicides than the B. dysenterice. Our knowledge concerning the effects of drying, sunlight, and other deleterious influences is still un- certain. Immunity. — The susceptibility to dysentery varies greatly. This is doubtless due in part to the bacterial flora of the intestinal tract as well as the conditions of the intestinal mucosa. Symbiosis must play a very important role either in permitting or hindering the dysentery bacillus to grow in the intestinal tract. There is still a question whether a true immunity is acquired by one attack of bacillary dysentery. This seems probable, although it is not unusual for a person to have two or more attacks of dysentery in one season. Kolle looks upon this as an exacerbation of a chronic type brought on by errors of diet, exposure, etc. The experiments on animals indicate that dysentery probably belongs to that group of diseases which leave a certain amount of pro- tection after one attack. A definite and high grade of immunity can be produced experimentally in several of the lower animals. Upon this question, however, we need light. Horses may be immunized to a high degree, and their sera contain a certain amount of antitoxin and other antibodies. This serum has been used in treatment, but has no par- ticular value as a preventive. There is evidently no immunity in amebic dysentery. Personal Prophylaxis. — To avoid dysentery the two essentials are: scrupulous cleanliness and the boiling of all water and cooking of all food that passes the mouth. The usual precautions against flies and vermin, and care as to personal hygiene, especially diet, are indicated. Bacillary dysentery is a common disease in infants, and it would be 114 DISEASES SPEEAD THEOUGH ALVINE DISCHAEGES a wise precaution to consider all cases of infantile diarrhea as infectious and to take precautions accordingly. D3'sentery should be included in the notifiable diseases and laboratory aid furnished by the Board of Health to assist diagnosis. Cases should be isolated in the same sense that cases of typhoid are isolated and dis- infection practiced at the bedside. Outbreaks in institutions should always be investigated and vigorous measures taken to check further spread and to prevent recurrences. In all respects the prevention of dysentery is a close parallel to that of typhoid. HOOKWORM DISEASE (Uncinariasis or Anchylostomiasis) Theoretically the prevention of hookworm disease is comparatively simple, for here we have an infection of which we know the parasite and its life history, its mode of exit and entrance into the body, and we possess a satisfactory cure for the disease within reach of all. Prac- tically, however, we have ignorance, apathy, poverty, and uncleanliness to deal with before satisfactory prevention, much less eradication, can be achieved. It is now plain that hookworm disease presents a sani- tary problem of first magnitude, not alone in our southland, but in practically all tropical and subtropical countries. Further, there is a large economic and industrial aspect to this question in medical biology. Distribution. — Hookworm disease encircles the globe in the tropical and subtropical climes; it diminishes toward the temperate regions. It is not endemic in the colder latitudes, except in mines, especially those of Wales, Germany, Netherlands, Belgium, France, and Spain. The infection belts the earth in a zone about 66° wide, extending from parallel 36 north to parallel 30 south latitude. The amount of infec- tion is great in American Samoa, where it is found in 70 per cent, of the population; in the southern two-thirds of China, in 75 per cent, of the population ; in India from 60 to 80 per cent, of the 300,000,000 population have the disease; in Ceylon, 90 per cent, in many parts; in Natal, 50 per cent, of the coolies on sugar and tea estates ; in Egypt, 50 per cent, of the laboring class; in Dutch Guiana, 90 per cent, in many parts; in British Guiana, 50 per cent, of all; in Co- lombia, 90 per cent, of those living between sea-level and 3,000 feet, which includes most of the population ; in 1904 the Porto Eican Anemia Commission found that 90 per cent, of the rural population of Porto Eico were infected. Stiles estimates that in this country 2,000,000 in- dividuals have the infection from the Potomac to the Mississippi, along the Atlantic littoral and the Gulf states. In some German mines from HOOKWOEM DISEASE 115 ( ) Fig. 14. — H o o k - WORMS, Natural Size. 30 to 80 per cent, of the miners have been found to be infected. Gunn ■ has shown that from 50 to 80 per cent, of those working in the Cali fornia mines are infected. It is probable that all the older mines em ploying foreign laborers sooner or later become endemic foci. In 1879 an outbreak of hookworm disease (miner's anemia) occurred among the laborers in St. Gothard'"s tunnel. This aroused the interest of the whole scien- tific world. The polluted soil of the tunnel was foiind to be impregnated with the eggs and larvae. Interest in the disease m this country was aroused through the work and enthusiasm of Stiles. Varieties of Hookworm. — Almost all mammalian animals have liookworms, but each host species has a different kind of hookworm ; that is, the hookworms of the dog, fox, horse, the seal, etc., differ from each other, and are specific. The hook- worm of tlie dog will not infest man or other mammalian host; the hookworms of man do not develop to maturity in the lower animals, etc. Two species of hookworm are found in man — the old world form {Anchylostoma duodenale), and the new world form (NecaLor americanus). The distinction between these two worms has a zoological rather than a practical bearing, for both produce the same symptoms, require the same treatment, have the same life history, and call for the same preventive measures. The chief differences between these two hookworms consist in the fact that the old world form has one pair of ventral hooks, two conical dorsal teeth, and the posterior ray of the caudal bursa divides two-thirds its way from the base, and each divi- sion has three tips (tripartite). The new world form has ven- tral lips, a dorsal median tooth, and one pair of dorsal and one pair of ventral lancets deep in the buccal cap- sule. The posterior ray of the caudal bursa divides at its base and each division has two tips (bipartite). According to Stiles, the vast majority of cases of hookworm disease in man in the United States are due to the new world form (Necator ameri- canus). Modes of Transmission. — The usual mode of transmission, perhaps in 90 per cent, of the cases, is through the skin. The infection may also be taken by the mouth in drinking water or soiled food, or from contaminated objects, such as dirty fingers. It has been ^Jour. A. M. A., Vol. LVI, No. 4, Jan. 28, 1911, p. 259, Fig. 15. — Hookworm Em BKYO. 116 DISEASES SPEEAD THEOUGH ALVINB DISCHAEGES shown by experiment that animals can be infected by drinking water containing the embryos. While this source of infection plays a minor role, it is not to be disregarded. The infection leaves the body exclusively in the feces, which con- tain the eggs of the parasite. The Parasite. — Eor a correct understanding of the prevention of hookworm disease it is necessary to have a knowledge of the essential features of the life history of the parasite. Hookworms are round worms (nematodes) belonging to the sub- family Uncinariinm. The adult worm is about one-half to three-quar- ters of an inch long, and about the diameter of a wire hairpin. The adult hookworm lives in the intestinal tract, usually in the small intestine. It attaches itself to the intestinal wall, wounds the mucosa, sucks blood, eats the epithelium, and probably produces a toxic substance which injures the host. The female worm lays a prodigious number of eggs in a never- ending stream, which pass from the host in the feces. The embryo does not mature within the egg except in the presence of oxygen. Hook- worm embryos, therefore, do not undergo full development until the eggs are discharged into the outer world. On the other hand, the eggs of Strongyloides stercoraliSj, the parasite of Cochin-China diarrhea, con- tain fully developed embryos in the freshly passed feces. The hook- worm embryos become mature within the egg in 6 to 8 hours in the presence of moisture, warmth, and oxygen. It is, therefore, necessary to examine the fresh stools in order that this difference between the two infections may be of value in differential diagnosis. Under favorable conditions the embryo escapes from the egg and becomes a larva in about 24 hours. This free-living larva exists and moves in moist soil and feeds upon the organic matter found there. In the course of two days or more the larva sheds its skin (eedysis) and thus passes to the first molt. The larva continues as a free-living parasite, and in about a week again sheds its skin, but now continues to live encysted inside this discarded skin. This is the second eedysis and this encysted larva no longer takes food. This stage in the life history of the parasite is of special importance for the reason that it is capable of piercing the skin; that is, it is the infecting stage. In this condition the parasite may live in a dormant condition for five months, perhaps longer. The hookworm larva passes in all through five ecdyses or molts. Two of them occur during its free-living stage and three of them during its residence in the host. With each eedysis the larva approaches more nearly the appearance and structure of the adult worm. The larva has a slow motion and under favorable conditions prob- ably travels a number of yards, increasing the radius of soil pollution. HOOKWORM DISEASE 117 The larva pierces the skin and passes by a circuitous route to the intestinal tract. The parasite may enter the skin at any place, but it usually goes through the soft and thin skin between the toes. In its passage through the skin the larva produces an inflammatory reaction (ground-itch) which results partly from the irritating action of the presence of the foreign body, but mainly from the bacteria carried along with the larva. These primary lesions may consist of a few itching papules or pustules to a severe dermatitis. Of 4,741 patients questioned by Ashford, King, and Gutierrez in Porto Rico, 4,664, or about 98 per cent., gave a history of ground-itch, which is now recog- nized as the first stage of the disease. The fact that the infection with hookworm disease is usually con- tracted through the skin was discovered by Looss in Cairo, Egypt. He also unraveled the course of the parasite from the skin to the intes- tines. This brilliant discovery, which is one of the romances of med- ical biology, is the foundation upon which prevention against the in- fection depends. In 1895 Looss accidentally spilled a drop of water containing many larvae upon his hand, and noted that they disappeared, leaving their delicate sheaths behind them. Seventy-one days subse- quently he developed intestinal uncinariasis. The experiment was then repeated upon a volunteer, and hookworm eggs appeared in his stools in 74 days. Claude Smith found eggs in the feces 6I/2 weeks and 7 weeks after experimental skin infection on two persons with the Amer- ican parasite {Necator americanus) . The wanderings of the parasite from the skin to the intestine were worked out by Looss partly by placing larvae upon an amputated leg and also by studying the question upon puppies. The hookworm larva usually pierces the skin through a hair follicle, enters the subcutaneous tissue, and then finds its way through the lymphatics to the neighbor- ing lymph nodes. The larvae are able to squirm through the lymph nodes, pass to the thoracic duct, and thence to the vena cava and the right heart. From the right heart they are carried in the blood stream to the lungs. The larvae are too large to pass the capillaries of the lungs. They pierce the capillary walls and appear in the alveoli and are now, to all intents and purposes, again in the outer world. They pass up the bronchi and trachea to the throat, whence they are swal- lowed, and finally lodge in the small intestines. During their travel through the body they pass through three ecdyses. The adult worm attaches itself to the mucous membrane by means of the powerful buccal lancet. The epithelium is drawn into the buc- cal cavity as though by a powerful suction. The worms are usually found in the small intestine, especially in the jejunum, less often in the duodenum, and rarely in the ileum and lower reaches of the in- testinal tract; they are occasionally met with in the stomach. 10 118 DISEASES SPREAD THROUGH ALVINE DISCHARGES The parasites imbibe large amounts of blood, some of which passes through the worm unaltered. The wound continues to bleed after the worm releases its hold, owing perhaps to a hemolytic substance in the mouth parts of the parasite. The worm does not remain fastened to one place indefinitely, but releases its hold and attaches itself anew. This produces numerous minute wounds, favoring secondary infections. The hookworm probably produces a poison which is absorbed and which accounts, in part, for the anemia and other symptoms of the disease. The severity of the symptoms bears no definite relation to the number of worms. The number varies greatly in individual cases; from one or two to thousands. Sandwith counted 250 worms and 575 bites in one case; 2,000 are not an uncommon number. The Porto Rico Com- mission counted as many as 4,600 passed by one individual. Immunity. — There is no acquired immunity to this disease. There is, however, a definite racial immunity, as shown by the negroes and the Filipinos, who are often infected but have comparatively slight symp- toms. Stiles found that in this country the negro is the great reser- voir for hookworm disease in that he is frequently infected but slightly affected. Perhaps the negro has had the disease so many generations in Africa that he has become immune. It is conjectured that the in- fection was brought to America through the negro slave trade. Hook- worm disease lowers resistance and greatly increases the chances of other infections, especially tuberculosis. The secondary results are often more disastrous than the primary effects. Eesistance of the Parasite. — The adult worm in the intestinal tract may be benumbed or killed with thymol, betanaphthol, chloroform, gasoline, eucalyptus oil, and other of the usual vermifuges. From the standpoint of prevention, it is more important to know the resistance of the eggs and larvae during their free-living stages. Stiles and Gardner have shown that the soil under and around privies is not entirely free from infection with hookworm even five months after the privy was last used, although the infection is considerably reduced at the end of four months. When the fecal matter has un- dergone decomposition under water most of the hookworm eggs are dead in about ten weeks, though some still survive, but probably all are dead in three months. It would not be safe to use such material as a fertilizer in less than three months. The larvse may live in water at least thirty days. The encysted stage is most resistant, surviving five months; perhaps longer. The larvae are readily killed by dryness and freezing. The infec- tion was once considered to be dust-borne, but the fact that the para- sites are killed by drying renders the danger from dust negligible. The fact that freezing kills the larvae largely explains why the disease is not endemic in this country north of the Potomac, HOOKWORM DISEASE 119 It has been shown that chlorinated lime fails to kill hookworm eggs in 22 to 40 hours. Schiiffler kept the larvse alive almost four months in water with two or three drops of a one per cent, quinin solution to 10 c. c. Oliver found that sea water killed the larvse in 37 minutes. Prevention. — The prevention of hookworm disease consists in pre- venting pollution of the soil and in treating existing cases so as to diminish the amount of infection. The principles of prevention are easy in theory, but their application is difficult in practice on account of the widespread and enormous amount of the disease. The suppres- sion of hookworm disease means the social and economic uplift of na- tions, the education of millions of people, and an entire change in their daily hygienic habits. Education of the masses is an important factor; calling for cooperation between the health authorities, civic forces, the medical profession, schools, and philanthropic agencies; it is something for the preacher and teacher. Soil Pollution. — The prevention of soil pollution is the essential factor; it is the key to the situation. This one line of prevention would blot hookworm disease out of existence. This requires the build- ing of proper privies, and insisting upon their being used in country districts. In warm countries direct pollution of the soil is much more common and also much more dangerous than in cold countries. Add to this the custom of going barefooted and we have all the factors neces- sary for the dissemination of hookworm infection. Stiles estimates that 68 per cent, of the rural homes in the South are without privies. Even some schools do not have these accom- modations, and are, therefore, hotbeds of infection. For the care and disposal of night soil see chapter on sewage. The Eradication" of the Infection in Man. — Hookworms may be expelled from the intestinal tract by the use of thymol, betanaph- thol, or other anthelmintic. The eradication of the infection through the treatment of all infected persons is an essential factor in preventive measures. The usual treatment is as follows: Saturday evening a full dose of magnesium sulphate or other purge is given to permit direct access of the thymol to the worms, which are often imbedded in the mucus or chyme. The object is to treat the parasite and not the host. On Sunday morning, at 8 o'clock, 2 grams (30 grains) of thy- mol, for an adult, finely powdered in capsules, are given by the mouth. Two hours later, at 10 o'clock, 2 more grams are administered; and at 12 o'clock another dose of salts. During the treatment it is impor- tant to avoid alcohol, fats, and oils, as thymol is soluble in these sub- stances and they are, therefore, dangerous, as they thus favor absorption. The treatment is repeated every Sunday until the eggs disappear. One treatment usually suffices. The Porto Eican Commission sometimes 120 DISEASES SPEEAD THROUGH AI/VINE DISCHAE6ES found it necessary to use two, three, four, and up to eleven treatments. The eradication of the infection in man was carried out on a wholesale scale by the Porto Rican Anemia Commission, consisting of Ashford, King, and Gutierrez. Their- methods were highly successful and will doubtless serve an equally useful purpose in other places. They established a clinic for the microscopic diagnosis and free treat- ment of the disease. The good results of treatment spread rapidly, so that the facilities of the clinic were soon taxed to its utmost capac- ity. 'Not the least important function of the clinic was to educate the profession as well as the people. In a little while the clinic was moved to another point, and so on, until it gradually covered the entire island. Education. — Education is one of the most important factors in eradicating hookworm disease, for the reason that its final control de- pends upon improvements in the sanitary habits of the people, espe- cially in the rural districts. To change the daily habits of half a na- tion is an uplift that requires time and patience. It is perhaps best to begin with the school children ; even then it will take a generation for results. Very little can be accomplished by force, and, if the customs and prejudices of the people are ignored, the reformer and benefactor meet with rebuff and failure. It is a good idea to have a public health day or a public health week in the schools, during which time lectures and educational work upon hookworm, tj'phoid, tubercu- losis, and other prevalent infections are considered. The children carry the lesson into the home. Pamphlets, posters, lectures, exhibits, and popular articles in the magazines and newspapers all contribute their share. The medical profession in the infected areas may need in- struction and a little prodding to awaken interest in the problem. In the popular education on health matters the medical profession should lead, especially through the health authorities. This has also become one of the manifest duties of the practitioner. Cleanliness. — After all, the prevention of hookworm disease is a question of decency and cleanliness. Water sometimes carries the in- fection, hence it should be clean or cleansed by filtration or boiling. Soiled hands may carry the infection to the mouth, hence they should be washed before eating. Vegetables fertilized with night soil may be infected. This practice is not clean and should be forbidden, especially in the case of those vegetables usually eaten raw. With cleanly habits there would be no soil pollution, and the disease would be checked. Personal Pkophylaxis.— Personal prophylaxis consists in wearing shoes and otherwise avoiding contact with the infected soil. Brick makers, miners, and others compelled to work in infected soil should wear gloves. Other measures, such as boiling the water, eating only cooked or clean food, washing the hands, and avoiding the infected area. HOOKWOEM DISEASE 121 have either been dwelt upon or are too obvious to need further em- phasis. Immigration. — An important factor in the spread of hookworm disease in the United States is immigration. Every country that brings laborers from infected regions is bringing in a constant stream of infec- tion. California has established quarantine measures against Indian coolies, 90 per cent, of whom are infected. Collateral Benefits. — The best part of a hookworm campaign is the collateral good it does. This applies as well to a sanitary campaign directed against almost any disease. The suppression of hookworm disease will diminish the amount of tuberculosis, typhoid fever, dysen- tery, and other infections. Thus, in Bilibid prison, Manila, the death rate was formerly excessive — 234 per thousand when the Americans took charge. This was reduced to 75 per thousand by sanitary measures, such as boiled water, screens, disinfection, improved food, less crowding, better air, more sunlight, etc., but despite these sani- tary improvements the death rate could not be hammered down below 75 per thousand. Then it was found that many of the prisoners were infected with hookworms. Thymol was administered and the death rate fell to 13.5 per thousand. Another instance of the collateral bene- fits resulting from sanitary work is the plague campaign in San Fran- cisco, which cut typhoid fever in half, although no special attention whatever was paid to the latter disease. The purification of the water supply in Hamburg by filtration cut down the general death rate and diminished the morbidity of diseases not water-borne. One of the most encouraging phases of sanitary work directed against tuberculosis, ty- phoid fever, and hookworm disease is the assurance that a successful campaign will result in fundamental and permanent control or eradi- cation of other communicable diseases. The prevention of tuberculosis deals especially with personal hygiene, and the prevention of typhoid fever and hookworm with the sanitation of the environment. The com- bination of the two, therefore, embraces almost the entire range of pre- ventive medicine. CHAPTEE III DISEASES SPREAD LARGELY THROUGH DISCHARGES FROM THE MOUTH AND NOSE TUBERCULOSIS Tuberculosis is the most frequent and widespread of all the major infections. In this country 9 per cent, of all deaths, and in Germany 12 per cent., are caused by tuberculosis. The toll falls heaviest dur- ing the period of life of greatest usefulness — thus 30 per cent, of all deaths between the years of 15 and 60 are due to pulmonary tuber- culosis alone. ISTaegeli, from a careful examination of a large number of bodies in Zurich, found evidence of tuberculosis in over 90 per cent. The lowest figures based on the evidence of pathologic anatomy are those of Bitzke, who examined 1,100 bodies in Berlin. In children under 15 he found evidence in 27.3 per cent., and in persons over 15 58.2 per cent. The difference between ISTaegeli's figures and Bitzke's is due to a difference in the interpretation of the pulmonary scars and adhesions at the apices, and the small fibrous nodules in the lungs. Bitzke does not consider such lesions as of tuberculous origin, and leaves them out of his figures. If these were included, his percentage would also be very much higher. The frequency with which we become tnberculized is indicated by the fact that practically all persons more than a few years old give the von Pirquet cutaneous reaction. In the United States it is estimated that 160,000 persons die each year of tuberculosis. Of the 90,000,000 people now living in this country, it is estimated that 8,000,000 are doomed to die of tuber- culosis, unless the disease is checked. The loss in life and treasure is appalling. It is, therefore, most encouraging that preventive measures based upon modern conceptions of the disease as a communicable in- fection are giving encouraging results. Tuberculosis began to decline before the nature of the infec- tion was known. The decline is gradual. Modern methods have so far made little apparent impression upon the gross amount of the infection. The social and economic conditions of the 122 TUBEECULOSIS 123 mass of the population must be improved before any great decline in the mortality rate can be expected, as will presently be pointed out. Tuberculosis is fast becoming, in fact already is, a class disease; it is much more prevalent among the poor than the well-to-do. Hence the prevention of tuberculosis has become a sociological problem. Pov- erty with all its attendant hardships, such as poor food, bad housing, overwork, and worry, diminishes resistance to the infection; while pros- perity, which buys good food, rest, change of air and scene, choice of occupation, and diversion, increases our resistance to the infection. An increase of wage or decrease in the cost of living; shortening the hours of work; improving the conditions of industrial hygiene; adding to the number of holidays; playgrounds, parks, and wholesome recrea- tion, all help to increase our resistance against and diminish the prevalence of tuberculosis. Science has shown the way; it remains for society to apply the knowledge. The Difference Between the Human and the Bovine Tubercle Bacilli. — There are at least three kinds of tubercle bacilli : human, bovine, and avian. The human and bovine varieties resemble each other closely; the essential difference lies in the fact that the human type is very pathogenic for man, but has little pathogenicity for cattle, rabbits, guinea-pigs, monkeys, and other animals. On the other hand, the bovine type is very pathogenic for almost all mammalian animals ex- cept man; it is pathogenic for man, but less so than the human bacil- lus. Even when large numbers of the human variety are injected into a calf, a general disease does not usually result; at most only a local lesion is produced. One one-hundredth of a gram of a pure cul- ture of a bovine race injected subcutaneously is sufficient to cause generalized tuberculosis and death in a rabbit in about 6 weeks; while ten or a hundred times this quantity of a human strain produces at most a slight localized tuberculosis. The human bacillus grows more luxuriantly upon culture media, covering the entire surface of the medium with a rich, dry, crinkled, mold-like vegetation. The growth of the bovine bacillus upon artificial culture media is more sparse, thinner, less extensive, and somewhat slower. According to Theobald Smith, who first pointed out the differ- ences between these two types, the human bacillus produces more acid in artificial culture media and a different reaction curve than that pro- duced by the bovine bacillus. Morphologically the bovine bacillus is usually shorter, plumper, and stains more uniformly than the human bacillus, which is ordinarily club-shaped, irregular, and stains with interrupted markings. The morphological and tinctorial characters are not sufficiently distinctive to distinguish one type from the other. 124 DISCHAKGES FEOM MOUTH AND NOSE It is doubtful whether there are any specific differences between the tuberculins of bovine and human origin. The avian tubercle hacillus is found most frequently in chickens and also in pigeons, pheasants, and guinea-fowl. Geese and ducks ap- pear immune. The avian bacillus is quite pleomorphic and stains some- what more readily than either the human or bovine types. The avian bacillus grows luxuriantly upon artificial culture media at 45° C. and even multiplies at temperatures as high as 50° C, which is in marked contrast to the mammalian types, which do not vegetate above 40° C. The avian bacillus grows rapidly, so that upon glycerin-agar or upon blood serum there is an abundant growth in 10 days, which consists of a white, moist, and fatty mass quite different in young cultures from the dried and crinkled appearance of the human type. Guinea-pigs show a decided resistance to the avian cultures, but rabbits are suscep- tible. Chickens and pigeons may be infected with certainty by feeding, and it is probable that in nature avian tuberculosis is generally trans- mitted in this way. Fisli tuberculosis shows a marked difference to the races found in warm-blooded animals. The bacillus grows between 12° and 36° C, the optimum temperature being 25° C. It was first found in a carp and is pathogenic for frogs. Neither the avian nor the fish tubercle bacilli are pathogenic for man. Bovine Tuberculosis in Man. — Concerning bovine tuberculosis in man we now possess definite knowledge which permits of precise state- ments. At one time the danger of bovine tuberculosis to man was greatly exaggerated. Koch went too far on the other side when he announced at London before the International Congress on Tuberculosis in 1901 that there was practically no danger of man contracting tuber- culosis from cattle. In recent years Koch modified this dictum, for it was soon proven that the bovine bacillus has a certain amount of patho- genic power for man and that some of the tuberculosis in man is con- tracted from bovine sources. If only 1 per cent, of the deaths from tuberculosis in the United States were caused by bovine tubercle bacilli, it would mean 1,600 deaths yearly. It is now estimated that perhaps t per cent, of the tuberculosis in man is of bovine origin. Pulmonary tuberculosis in man is practically never associated with the bovine bacillus. Bovine tuberculosis in man is usually a disease of the lymph glands — the lymph nodes of the cervical region and the lymph nodes in the abdomen being especially attacked. This is doubt- less due to the fact that the portal of entry of the bovine bacillus is usually through the tonsils or the small intestines. Bovine tubercu- losis may become a fatal infection in man when it is generalized through the blood in the form of acute miliary tuberculosis or when it localizes in the meninges or other vital parts. About one-quarter to one-half TUBERCULOSIS 125 of all cases of tuberculosis in children under 5 years of age is associated with the bovine type. It is probable that all these cases derive their infection through the tubercle bacilli in cow's milk. There is little danger from meat, as this is usually cooked, and tubercu- losis of the muscles is exceedingly rare. Meat may become con- taminated with tubercle bacilli as a result of unclean butcher^s tools or unsanitary methods of handling, or from tuberculosis of attached glands. The following table shows the relation between bovine and human tuberculosis in 1,040 cases. Six hundred and six of these cases were collected from the literature and include those studied by the English and German Commissions; 434 of the cases were studied in the re- search laboratory of the New York Board of Health by Park and Krumwiede : TABULATION OP CASES EXAMINED AT THE RESEARCH LABORATORY, NEW YORK CITY DEPARTMENT OP HEALTH, BY PARK AND KRUMWIEDE Diagnosis of Cases Examined. Adults 16 Years and Over. Children 5 Years to 16 Years. Cliildren Under 5 Years. H. B. H. B. H. B. Pulmonary tuberculosis 278 8 5 Tuberculous adenitis, inguinal and axil- lary 1 4 Tuberculous adenitis, cervical 9 19 8 6 12 Abdominal tuberculosis 1 1 1 3 Generalized tuberculosis, alimentary origin 1 1 Generalized tuberculosis 2 1 12 4 Generalized tuberculosis including men- inges 18 1 Tubercular meningitis 1 14 1 Tuberculosis ot bones and joints 1 10 6 Genitourinary tuberculosis 3 1 1 Tuberculous abscesses 1 Totals 296 1 45 9 62 22 Total Cases, 426. 126 DISCHAEGBS FROM MOUTH AND NOSE TABULATED SUMMARY OF CASES COLLECTED PROM THE LITERATUKB Diagnosis of Cases Examined. Adults 16 Years and Over. Children 5 Years to 16 Years. Children Under 5 Years. H. B. H. B. H. B. 290 1(?) 3 7 1 2 Xiihprpnloiia adenitis, cervical 13 1 14 12 9 8 14 3 6 6 6 10 Generalized tuberculosis, alimentary origin 6 1 2 3 12 9 26 3 1 16 1 Generalized tuberculosis including men- 1 3 8 Generalized tuberculosis including men- inges 4 7 27 1 1 Tuberculosis of bones and joints 17 1 16 1 15 8 Tuberculosis of skin 1 1 1 Miscellaneous Cases: i 1 1 i Tuberculosis of mouth and cervical Tuberculous sinus Totals 381 8 54 24 99 37 Mixed or Double Infections, 3 cases: Generalized tuberculosis. Alim. Orig. 30 yrs. Human and bovine type in mesenteric node. Human type in bronchial node. Generalized tuberculosis. Alim. Orig. 5J^ yrs. Human type in spleen. Bovine type in mesenteric node. Generalized tuberculosis incl. meninges. Alim. Orig. 4 yrs. Human type in meninges and bronchial nodes. Bovine type in mesenteric nodes. Total Cases, 606. Prom a study of these 1,040 eases we find: 16 years and over 686 cases — 9 with bovine bacilli — 1.3% Between 5 and 16 years 132 " —33 " " " — 25.0% Under 5 years 120 " — 59 " " " —49.1% Of 568 cases of pulmonary tuberculosis, none had the bovine bacil- lus. Cases under 5 years of age, 15 per cent, TUBEECULOSIS 137 It should be remembered that many of the cases included in the above total were selected cases. The 436 cases studied in the Kesearch Laboratory in New York, however, were not selected; of these cases the following were found associated with the bovine bacillus: Diagnosis Adults Five to Sixteen Under Five Pulmonary tuberculosis None 4% 16% 3% "5% None 37% 50% 40% ■3% Tuberculous adenitis, cervical 57% 68% 26% 15% Abdominal tuberculosis Generalized tuberculosis Tubercular meningitis with or without generahzed lesions Tuberculosis of bones and joints Since the above tabulations Park and Krumwiede ^ have collected a total of 1,511 cases which give the following : PERCENTAGE INCIDENCE OP BOVINE INFECTION Diagnosis. Adults 16 Years and Over. Children 5 to 16 Years. Children Under 5 Years. Pulmonary tuberculosis Tuberculous adenitis, cervical Abdominal tuberculosis Generalized tuberculosis, alimentary origin. . . . Generalized tuberculosis Generalized tuberculosis, including meninges aUmentary origin Tubercular meningitis (with or without general ized lesions other than preceding) Tuberculosis of bones and joints Tuberculosis of skin .4% 2.7% 20% 14% 0% 0% 0% 3.3% 23% 0% 38% 63% 57% 16% 0% 0% 6.8% 60% 2.8% 61% 58% 47% 8.6% 66% 4.6% 0% 0% As is evident from the table summarizing the total cases reported, many of those in children had slight or latent infections, found on their death from other causes. The percentages deduced, therefore, only give the incidence of infection, nothing more. Weber, of the Imperial Board of Health of Germany, has made observations to determine just how much danger there is in drinking milk containing bovine tubercle bacilli. The milk coming from all known cases of udder tuberculosis was traced to the consumer and all the persons drinking such milk or using fresh milk products from in- ^Jour. Med. Beseareh, XXVII, 1, Sept., 1912. 128 DISCHAEGES FEOM MOUTH AND NOSE fected sources were examined with reference to tuberculosis. In all 113 separate investigations were made, including 628 persons (284 of whom were children, 335 were adults, and 9 of unstated age), all of whom had undoubted opportunities of consuming milk or fresh milk products from cows having tuberculosis of the udder. The evidence presented is not equally valuable in each investigation. In 44 of the 113 investigations cited, the milk was either heated, used in coSee or tea, or mixed with milk from apparently tuberculosis-free cows before it was consumed. Three hundred and sixty persons (of whom 151 were children, 200 adults, and 9 of unknown age) were known to use milk or milk prod- ucts, such as butter, buttermilk, sour milk, and cheese, which came from cows having undoubted tuberculosis of the udder. Of these 360 persons 2 were shown, by actual animal experimentation, to have in- fections with the bovine tubercle bacillus. Both positive cases were children with tuberculous neck glands. Six other children and 1 adult had glandular swellings in the neck, and in 4 other children and 1 adult there was a strong suspicion on the part of the attending physi- cian that abdominal tuberculosis was present. In another series of 360 persons, 12 children and 1 adult had swell- ings of the lymph glands of the neck. In this group the diagnosis was not confirmed bacteriologically. Weber concludes from these studies that the danger which man un- dergoes through the consumption of uncooked milk and milk products of cows having tuberculosis of the udder is similar to the danger which persons having well-marked pulmonary tuberculosis exhibit for their fellowmen, although very much less. He believes it is fair to assume from the statistics presented above that the danger from drinking un- cooked milk or using milk products of cows with tuberculous udders is surprisingly small. Woodward voices the prevailing opinion when he maintains that the more deeply we go into the subject, the bovine side of the question comes to take a larger and larger place, especially in connection with surgical and abdominal tuberculosis, not only in the child but even in the adult. From the standpoint of our present knowledge we must consider that practically every case of bovine tuberculosis in man is ingestion tuberculosis, contracted from milk or fresh milk products. How the tubercle bacilli get into milk and the frequency .with which it is in- fected are discussed on page 513. Occasionally butchers and also pathologists at autopsies become in- fected with the bovine bacillus through wounds. These accidents fur- nish further experimental proof that the bovine type of the ' tubercle bacillus possesses a certain degree of pathogenicity for man. TUBEECULOSIS 129 MODES OF INFECTION There are two great sources of human tubereulosis : the principal source is man himself; the. secondary source is cattle. From man tubercle bacilli leave the body mainly in the sputum, where they are found in great numbers in all open cases of pulmonary tuberculosis. Tubercle bacilli may also leave the body in the discharges from any open tuberculous lesion wherever situated, especially in dis- charges from the lymphatic glands, bones, intestinal or genitourinary tracts, or the skin. In pulmonary tuberciilosis some of the sputum is swallowed and the bacilli appear in the feces, therefore any or all of the discharges from the body may be infective. But, from the prac- tical standpoint of prevention, the bacilli in the matter brought up from the lungs is the source of the danger in the overwhelming ma- jority of cases. Practically all observers agree with Koch that human sputum is the main source of human tuberculosis. Whether the tubercle bacillus is usually transferred directly or indirectly, in .moist or in dry state, by inhalation or ingestion, are questions still undetermined. The ques- tion at issue is a quantitative one; that is, how often are we infected by the direct aerogenic route, how often through the tonsils and upper respiratory passages, how often through the digestive tube, etc. ? Aerogenic Infection. — The belief that tuberculosis is air-borne, that is, that pulmonary tuberculosis is a primary inhalation tuberculosis, has long been the natural and favorite theory, from the fact that the lungs are most frequently afEected. This opinion was strongly ex- pressed by Koch in 1884, and repeated by him in 1901, at the British Congress on Tuberculosis. For many years it found practically uni- versal acceptance. Cornet taught that the tubercle bacilli entered the lungs in the dust of dried and pulverized sputum. The evidence of pathologic anatomy strengthens the belief in the importance of aerogenic infections as the chief portal of entry. Thus, the recent studies by Ghon,^ at the St. Anne's Children's Hospital in Vienna, indicate very strongly that the actual path of infection is by the aerogenic route. Approximately 95 per cent, of 184 autopsies studied by him represent a primary localization of the bacilli in the lungs. On the other hand, it seems that direct aerogenic infection has been greatly overestimated, and some students of the subject go so far as to state it is of little or no practical importance. It is supposed that very few bacteria suspended in the air actually reach the lungs, being caught on the moist mucous membranes of the upper air passages. Fur- ther, tuberculosis of the lungs is usually at the apex, which is not in the direct line that floating particles in the air would usually be '"Der primare Lungenherd bei der Tuberkulose der Kinder," Berlin, 1912. 130 DISCHAEGES FEOM MOUTH AND NOSE mechanically carried. It is true that dust under certain conditions may contain tubercle bacilli, but it is now known that this organism soon dies when exposed to the sun and air, and that the dust out of doors is not apt to contain the live bacilli, and when it does so the dilution must be enormous. It is different with house dust. Tubercle bacilli may live a long time in dark, moist places, but even here the danger cannot be as great as might be supposed when we study the na- ture of tuberculous sputum. This substance is usually tenacious and gummy, and dries into tough, glue-like masses, which are pulverized with great difficulty. It therefore seems unlikely that dust under ordi- nary circumstances would contain dangerous numbers of live tubercle bacilli. The danger from this source is further diminished when we consider that a large number of tubercle bacilli die in sputum even when protected from sunlight and other injurious influences. It is now known that even under most favorable conditions in artificial cul- ture media the great majority, perhaps 99 per cent., of the bacilli die within three months. Transplants made from cultures over three months old usually do not grow. The danger of house dust containing live tubercle bacilli from a quantitative standpoint is, therefore, reduced. It is quite possible that the first infection does not produce the dis- ease; that is, when a few tubercle bacilli land upon the lungs the tis- sues do not react and the bacilli are carried to the bronchial lymph glands. This first infection, however, sensitizes the parts, so that the second time the bacilli lodge the tissues react vigorously and a local le- sion may result. A dusty atmosphere, even though it contains no tu- bercle bacilli, is, however, exceedingly dangerous, in that it irritates the delicate mucous membranes and thus opens the door for infection. One point of importance in this controversy is the experimental evidence that it requires very few tubercle bacilli by inhalation to pro- duce the disease, whereas it requires hundreds and even thousands to cause intestinal infection. This is given as a reason why infection via the digestive tract is comparatively rare in man, for he fortunately would seldom receive the necessary numbers of human bacilli by the mouth. Cornet and others have actually found live tubercle bacilli in the dust and upon objects of rooms where tuberculous patients are care- less with their sputum. In one of Cornet's experiments 47 out of 48 guinea-pigs exposed to the dust produced by sweeping a carpet with a stiff broom became tuberculous. The carpet had been purposely in- fected with tuberculous sputum shortly before. Dust containing tu- bercle bacilli may also enter the atmosphere from soiled linen, uphol- stery, handkerchiefs, and other fabrics containing the dried tuberculous sputum. Tuberculous dust may also be stirred up by walking over floors and the dragging of the infection by ladies' skirts. TUBEECULOSIS 131 Droplet Infection. — When it was found that the danger from dust theoretically was not as great as was supposed, Fliigge called attention to the fact that in speaking, coughing, sneezing, and in other violent expiratory efforts the fluid contents of the mouth are sprayed into the air in the form of a fine mist. These tiny droplets contain tubercle bacilli or germs of any other infection that may be in the mouth. Or- dinarily these droplets are carried several feet, but under exceptional circumstances may be carried 30 or 40 feet or more; however, at these distances the dilution is enormous and the danger, therefore, much diminished. The tubercle bacilli contained in the droplets sprayed from the mouth are fresh and virulent, and may land directly upon the mucous membranes of the healthy individual or may be conveyed in- directly through food, fingers, and other objects. There is danger from droplet infection, but it cannot be the usual mode of transmission in tuberculosis from the nature of the circumstances. The danger from droplet infection is increased by close association with the patient in stuffy, ill-ventilated rooms, especially if the individual does not take proper care in coughing and sneezing. For a further discussion of droplet infection see page 632. Ingestion Infection. — Little by little the view gained ground that some cases of tuberculosis, particularly in children, might be due to bacilli entering through the mucous membrane of the alimentary canal. Now we recognize that much of the tuberculosis in children comes through the alimentary tract. Many years before the discovery of the tubercle bacillus Chauveau (1868) was inclined to the belief that the alimentary canal may be the portal of entry in tuberculosis. Woodward in 1894 maintained that the infecting bacilli might reach the lungs through some part of the alimentary canal. He drew attention to the fact that in many children, and also in animals fed on tuberculous material, the lungs may be markedly affected. He traced the course of the infection through caseous or old calcareous mesenteric glands up through the diaphragm to the posterior mediastinal glands, and so to the lungs. Still in 1899 analyzed 259 fatal cases of tuberculosis occurring in the Hospital for Sick Children, London, and concluded that the infection had occurred through the alimentary canal in 20.5 per cent, of the cases. Shennan in 1900, dealing with 316 autopsies at the Royal Hos- pital for Sick Children in Edinburgh, found this ratio to be 28.1 ner cent. There is no doubt that the lungs are more or less involved in all cases of generalized infection, especially in children, but these are not eases of pulmonary tuberculosis (phthisis) in the usual meaning of the term. It is phthisis or pulmonary tuberculosis which causes 70 per cent, of all the mortality from tuberculosis and whose mode of origin is now in question. 133 DISCHARGES FROM MOUTH AND NOSE Behring in 1903 maintained that the tubercle bacilli might be taken up from the intestine and pass through the mesenteric glands, so gain- ing access by the blood stream to the lungs without leaving any le- sion in the gut or glands to mark the portal through which they had entered or the route by which they had traveled, and that pulmonary tuberculosis was commonly caused in this way. Behring's theory of the origin of phthisis did not find a ready acceptance. Nevertheless, the belief that phthisis may be caused by bacilli which have been swal- lowed and absorbed from the digestive tube gradually gained ground. Vallee in 1904 concluded from his own investigations that ingestion of dust or food infected with tubercle bacilli was the quickest and surest method of infection. A little later Calmette (1905) of Lihe appeared as a strong supporter of this view. Calmette went so far as to assert that the immense majority of cases of pulmonary tuberculosis in man are caused by ingested bacilli and not by inhalation. Whitla, in 1908, and Symmers repeated some of this work and became con- verted to Calmette's doctrine, and these views have gained a number of adherents. Cobbett (1910) considers that the ingestion theory is based on a slender substructure of experiments from which too sweep- ing conclusions have been found. Thus Calmette and his colleagues claim that even anthracosis is caused not by the carbon particles in- haled, but the particles ingested, which pass through the intestinal mucosa and lodge in the lungs. Cobbett showed the experimental error and demonstrated that India ink intimately mixed with cream is not absorbed in any great amount from the intestine, for the cream reap- pears of a normal color in the lacteals. He found, however, that feed- ing finely divided carbon matter caused traces of pigmentation in the lung and bronchial glands when long continued. Heller and Vulcan- stein showed that the feeding of large amounts of coal dust never pro- duces that grade of anthracosis which is found after the inhalation of much smaller amounts. There is now sufficient proof to state definitely that tubercle bacilli, when taken in food or drink, may pierce the mucous membrane of the digestive tube and produce lesions in distant parts of the body. It is also demonstrated that the tubercle bacillus may thus travel without leav- ing macroscopic evidence of its passage in its wake. Fraenkel ^ and others have shown that the tubercle bacilli may pass through the un- injured skin of guinea-pigs, leaving no trace of their passage at the place where they had rubbed upon the skin, but causing tuberculosis of the internal organs. Ravenel and others have shown that tubercle bacilli may pass through the intestinal wall' without leaving a trail be- hind them. It does not,- therefore, necessarily follow that the seat of ^Kyg. Rundschau, XX, 15, Aug. 1, 1910, p. 817. TUBEECULOSIS 133 tlie primary lesion in tuberculosis is the site of the entrance of the in- fection. It is also claimed that, no matter how the tubercle bacillus reaches us, whether in dust or droplets, by kissing or through fingers, flies, cups, handkerchiefs, or milk, it either passes through the tonsils or mucous membrane of the upper respiratory passages, or is carried into the intestinal tract and absorbed from the intestines. Viewed in this light, the portal of entry even in dust infection may be through inges- tion rather than through direct aerogenie infection of the lungs. Ex- perimentally it is easy to prove that tubercle bacilli given by the mouth may produce a generalized and fatal tuberculosis; thus, of 100 guinea- pigs given one large feeding of a bovine culture by Eosenau and An- derson, 99 died of tuberculosis. That infection by ingestion does not tell the whole story is judged from the fact that primary tu- berculosis of the mesenteric nodes in man is not as common as we might expect. On the other hand, it is claimed that the tubercle bacil- lus may pass these lymph glands, leaving little or no trace behind them. Thus the work of Weichselbaum and his pupils, Bartel, Neuman, and Spieler, strengthens the importance of ingestion as the portal of entry. These investigators found that the tubercle bacillus produces, in addi- tion to the specific tubercles, other lesions of a simple lymphatic hyper- plastic character. These early lesions are called the "lymphoid stage" ("lymphoide stadium"). The recognition of this early stage is of importance in determining the point of invasion. The evidence ob- tained from the macroscopic appearance of the lesions at autopsy must be supplemented by microscopic studies. Bartel and Spieler found that in ingestion experiments the different lymphatic groups were infected with the following frequency, judged by the lymphoid stage: Tonsils and surrounding. .. .11.7 per cent. Cervical glands 58.8 per cent. Bronchial glands 52.9 per cent. Mesenteric glands 100.0 per cent. These investigators assume that the tubercle bacillus is carried from the mesenteric or the neck glands either through the lymphatics di- rectly or through the thoracic duct and the arterial circulation to the lungs and other tissues and organs of the body. The disease usually localizes itself in the lung because this organ presents the least re- sistance. Weichselbaum believes that ingestion tuberculosis occurs much more often in man than is commonly supposed and especially in children. He assumes that the tubercle bacilli may pass through the mouth, nose, or throat. It seems immaterial whether the bacillus is taken with food 11 134 DISCHAEGES FEOM MOUTH AND NOSE or other substances placed in the mouth, or is contained in the inspired air, or enters the mouth and nose through any other medium. The first lesions do not consist in the formation of specific tubercles, but in the so-called lymphatic tuberculosis. This stage lasts a variable time and may end in recovery or may lead to specific tuberculosis either through reinfection, or it may light up itself without a new infection. The specific tubercles may occur either at the portal of entry or in the lungs and bronchial glands or in other organs. Behring (1903) brought forward the theory that alimentary infec- tion occurs in the early months of life. The tender mucous membrane of babies permits the bacillus to pass readily. The bacilli remain latent in the tissues and acquire increased activity later in life. According to this view tuberculosis of adults is the "end of a song, the beginning of which for the unfortunate patient was sung in the cradle." If this view were correct, the majority of cases of tuberculosis in adults would be associated with the bovine bacillus, unless the bovine bacillus has the power of changing to the human type during its long stay in the body. This is not likely. It is clear from the evidence at hand that pulmonary tuberculosis may arise either by inhalation or by ingestion. The problem for us now to solve is a quantitative one; that is, what percentage of cases are air-borne and what percentage come through the mucosa of the digestive tract? Opinions differ widely, but opinions are of little value. We must have the facts before we can give the final answer to this very important and practical question.^ Flies. — Under certain circumstances flies may readily transfer tu- bercle bacilli from exposed sputum to fingers, lips, or food. This may account for an occasional case. Water. — Large quantities of tuberculous sputum that escape dis- infection and an additional large number of tubercle bacilli in the ex- creta finally reach the drinking water. The tubercle bacillus is particu- larly resistant to putrefactive processes, and may live a long time in water. The use of contaminated water can, therefore, not be disre- garded. A study of the vital statistics of Hamburg, Lowell, and Law- rence seems to show a diminution in tuberculosis following a purification of the water supply by filtration (Mills-Eeinke Phenomenon, page 804). Contact Infection. —The majority of cases of tuberculosis contract the disease through "contact." Contact infection is a general and con- venient term; it implies the rather quick transference of fresh infec- tion in which the bacilli pass from one individual to the other in a brief space of time and through a short distance. Contact infection _ • An exhaustive and able summary of this question will be found in Bulloch 's article in Allbutt's "System nf Moiiioino " -f^n™ ™i,;„i, _j^ j.i.- j!_.i_ ;_ this article have been used. TUBEECULOSIS 135 may be either direct or indirect; through dust, through bacilli in the air, or through contaminated food, through soiled fingers or objects; through flies, as well as in numerous other ways. The infections trans- ferred through kissing, pencils, pipes, toys, cups, and other objects all come under the convenient category of "contacts." Even the infection through droplets is included in the present-day conception of contact infection. The term is a practical one, and implies close association, though not necessarily actual contact, between the sick and the well. Viewed in this sense, tuberculosis is a house disease or a faniily disease. With this conception it makes little practical difference whether the infection enters the body through the respiratory tract "or the digestive tube. Either or both would be possible in regarding the disease as con- tagious in the sense of contact infection. Although there is some doubt concerning the exact mode of trans- mission and the portal of entry that the tubercle bacillus usually takes, we have sufficient knowledge to guide our preventive measures with every assurance of success. One thing is certain : tuberculosis is an infection spread mainly- from man to man, usually through direct as- sociation between the sick and the well; and secondarily from cows, through milk. IMMUNITY Man possesses a considerable resistance to tuberculosis. This is shown by the fact that many cases recover spontaneously and that per- . haps all individuals who reach the age of 30 years and who spend most of this time in association with their fellowmen under the usual urban conditions have at one or more times been infected. The resistance to tuberculosis increases after middle life, due perhaps to the immunity which is induced by these prior infections. There is probably no true racial immunity to tuberculosis. Some races show a smaller incidence to the disease, owing probably to modes of life, habits of nutrition, and conditions of exposure. The human organism is capable of taking care of a certain amount of infection. The dose, that is, the number, of tubercle bacilli and their virulence, is, therefore, a very important factor in determining in- fection. This may readily be demonstrated upon susceptible animals and is doubtless true of man. Frequent reinfections occurring at short intervals with small numbers of tubercle bacilli doubtless break down the immunity. In man the balance between immunity and susceptibility to tuberculosis is delicately adjusted: there is a very small factor of safety. The resistance to the infection may be increased by attention to personal hygiene, fresh air, and good food; immunity may readily be broken down by any weakening influence; herein lies the keynote of personal prophylaxis. 136 DISCHAKGES PROM MOUTH AND NOSE The immunity to tuberculosis is not sufficiently strong to overcome a large amount of infection. As in all other infectious processes, the strongest and most robust individuals in the prime of life succumb to the disease in a short time if they receive into their system a large number of virulent tubercle bacilli. Hence the avoidance of the in- fection is one of the most important of our preventive measures. The mechanism of the immunity to tuberculosis is probably exceed- ingly complex. There is no antitoxic immunity. The tuberculins are not true toxins. Phagocytosis and cellular reactions play a very im- portant role. The recent studies upon anaphylaxis throw a certain amount of light upon the mechanism of immunity in tuberculosis. The phenomenon of hypersusceptibility is beautifully illustrated in the action of tuberculin, "which is a comparatively harmless substance to a normal individual, but produces a marked reaction in a sensitized individual. This reaction must be useful in protecting the organism against the invasion of the tubercle bacillus, and also in guarding it against the spread of the disease after it has become localized. Thus, if tuberculin is placed upon a normal conjunctiva no reaction follows.^ This first application, however, sensitizes the tissues of the conjunctiva so that, if the application is repeated after the lapse of a few weeks, there is a violent reaction. The same phenomenon doubtless occurs when a tubercle bacillus lodges in a lymph gland or in the lung or some other part of the body. The first time it meets with little resistance; the next time the tissues react immediately and vigorously. All of nature's protecting agencies, such as the germicidal substances in the blood, the phagocytic cells, and antibodies, are concentrated upon the point where they are most needed. In the same way the body protects itself against the ex- tension of a tuberculous focus. The parts surrounding a tubercle become sensitized and react so as to encapsulate the focus with a cellular and fibrous coat of mail. This reaction is probably stimulated by small amounts of tuberculin produced within the tuberculous focus. When the tuberculin is not produced autogenously in sufficient amounts, as in chronic lesions of the bones, or inactive processes of the glands or skin, the specific reaction may be stimulated to advantage by the injection of small quantities of tuberculin. If, however, the tuberculin is given in too large amounts or too frequently, the power of reaction is readily broken down. When this occurs the mechanism of immunity has been destroyed, there is little resistance left to the extension of the infection, and death soon occurs. Clinical experience has demonstrated the danger of large doses of tuberculin or small amounts too often repeated in tuber- culosis. The same may readily be demonstrated experimentally in the lower animals. These facts are of fundamental importance in the use of tuberculin. ' Eosenau and Anderson, J. A. M. A., Vol. I, March 28, 1908, p. 961. TUBEECULOSIS 137 It is quite proper to deny dogmatically the hereditary transmission of tuberculosis in educational pamphlets for popular use. The infection is not transmitted hereditarily, although it occasionally passes from mother to fetus congenitally. Tubercle bacilli do not occur in the sper- matozoon, and do not appear in the seminal fluid. They are not found in the ovum; in fact, a tubercle bacillus in the ovum would doubtless result in the death of the egg. The bacilli, however, may pass from mother to fetus through the placenta. Warthin shows that placental tuberculosis is more common than is supposed. The lesions in the placenta are not those of typical tubercle formation. While the tubercle bacillus itself is rarely transmitted from parent to offspring, an hereditary tendency or disposition to the disease may be transmitted. We have no definite knowledge as to what this de- creased resistance consists in; it may be a diminished power of reac- tion. For this view there is analogy in the experiments upon anaphy- laxis in guinea-pigs, in which it has been shown that hypersusceptibility to a foreign protein such as tuberculin may be transmitted from mother to young. A mild infection with bovine tuberculosis in early life seems to leave a certain degree of immunity against the human strain. At least children who have glandular tuberculosis of the bovine type in child- hood are said to be less apt to have tuberculosis of the lungs in later life. Likewise, the human strain injected into cattle produces a defi- nite immunity against the bovine type. Cattle are now immunized by the intravenous injection of 2 c. c. of a suspension of a pure cul- ture of the human tubercle bacillus. This produces an immunity which probably lasts for 1 to 3 years. It should be remembered that the hu- man bacillus under these circumstances remains alive for a very long time, and may appear in the milk provided there is a lesion in the udder. This presents a danger which cannot be disregarded. Trudeau long ago showed that the only definite immunity that could be induced in experimental animals was through the use of live tubercle bacilli. Webb and Williams '■ have produced a certain amount of im- munity in ' guinea-pigs and monkeys by the injection of live tubercle bacilli. The first injection consists of the introduction of a few bacilli (from 1-200), which is repeated subcutaneously at varying intervals. Two children have also been successfully "vaccinated" with upward of 600 virulent human tubercle bacilli without infection being produced. RESISTANCE OF THE VIRUS We have no easy method of determining just when the tubercle bacil- lus dies. The criterion of death depends upon animal experimentation. '"Immunity in Tuberculosis," J. A. M. A., Oct. 28, 1911, Vol. LVII, No. 18, p. 1431. 138 DTSCHABGES FROM MOUTH AND NOSE The tubercle bacillus has no spore and may be classed with other non- spore-bearing organisms so far as its viability is concerned. Its virulence fades before it dies. It is doubtful vi^hether the waxy substances protect the bacillus against external harmful influences to any unusual extent. The thermal death point is 60° C. for 20 minutes. This is much less than was once considered.^ Failure to recognize the lesions produced by the dead tubercle bacillus is responsible for some of the false conclusions reached by experimenters upon this subject. From a practical standpoint the resistance of the tubercle bacillus in sputum is of prime importance. Protected from the sunlight it is now known that they may live in dried sputum for months. All the bacilli do not survive under these conditions, but we lack methods to determine the quantitative reduction. The tubercle bacillus withstands cold very well. It has a marked resistance against putrefactive processes. It will live a year in water, which is a fact not to be neglected, as many tubercle bacilli finally find their way into drinking water, and infection through this source is possible. For the destruction of the bacilli in sputum only very strong germicides or exposure to steam or boiling water should be depended upon. Five per cent, carbolic acid is sufficient, provided equal parts of sputum and solution are mixed and the exposure continued for 24 hours. Ten per cent, lysol acts in 12 hours. Bichlorid of mercury is not ap- plicable for sputum disinfection, as it cannot penetrate the albuminous mass. Formalin, 10 per cent., may be used. Sunlight is one of the best germicides and often destroys tubercle bacilli quickly. In direct sunlight the bacilli die in a few hours, in diffuse sunlight in a few days, provided the sputum masses are not too thick. Antiformin is a differential germicide, killing most non-spore-bear- ing bacteria, but acting more slowly upon the tubercle bacillus. Anti- formin is a strongly alkaline solution of sodium hypochlorite. (Page 1020.) PREVENTION Preventive measures are based upon two important facts: that tu- berculosis is an infection mainly spread from man to man through direct association, and secondarily from cattle through infected milk. Preventive measures fall into two categories: (1) avoiding the infec- tion, and (2) increasing resistance through personal hygiene. Both are necessary. The infection may be avoided through segregation; the use of milk from tuberculin-tested cattle, else pasteurized; education; ' The thermal death point of pathogenic microorganisms in milk M J. Eosenau, Hyg. Lab. Bull. U. S. Pub. Health and Mar. Hosp. Serv., No. 42. TUBEKCULOSIS 139 disinfection; proper disposal of tuberculous sputum; the avoidance of contact with open cases, especially with those who do not use proper precautions; early diagnosis, etc. Increased resistance may be gained through fresh air, good food, rest, and compliance with the dictates of personal hygiene. This part of the subject includes sociologic and economic reforms, without which the warfare against tuberculosis can- not succeed. Improvement in housing conditions, lowering of the cost of living, increase in the scale of wages, and all forms of uplift help secondarily to diminish the amount of the disease. Furthermore, it will be necessary to consider secondary agencies, as preventive clinics, indus- trial insurance, notification, open-air schools, day and night camps, etc. It is well to remember that tuberculosis has gradually declined in England and also in Massachusetts since about 1850 — before the tu- bercle bacillus was discovered. Segregation. — Tuberculosis is a "contagious" disease, and it is now perfectly plain that one of the most important single preventive meas- ures in this as in all other communicable diseases consists in isolation. A case isolated is a case neutralized, hence the great value to the com- munity of sanitarium treatment. Isolation in this case refers only to those individuals having tubercle bacilli in their sputum, and especially to the advanced and helpless cases. The isolation in tuberculosis need not go to the extreme practiced in the acute communicable fevers. In fact, we cannot for many years to come object to giving a case of open pulmonary tuberculosis his complete liberty, provided he is careful and cleanly and uses proper precautions in the disposal of his expectora- tion. When the disease becomes less prevalent more stringent and ar- bitrary measures may then be enforced. "Every case of tuberculosis isolated means an average of at least three less new infections." Sanatoria should, therefore, be attractive and as cheap as it is possible to run them. Free hospital care for the incurable cases is necessary, especially for the poor. Tuberculosis has diminished most in those countries where sanatoria are most in use. Personal Prophylaxis. — Personal prophylaxis consists in avoiding the infection and in obeying all the dictates of personal hygiene — that is, living a clean, normal, and temperate life. Close association with persons known to have tubercle bacilli in their sputum is hazardous. This becomes especially dangerous when the contact is prolonged and intimate, such as working in the same room, especially if it is small and ill-ventilated, or sleeping in the same bed. The more intimate the association and the less care the tu- berculous individual takes with the expectoration, the greater is the danger. The infection may further be avoided by refusing to drink from common cups, by taking care in placing objects to the mouth that do not belong there, by avoiding dusty atmospheres, and refusing to 140 DISCHAEGES FEOM MOUTH AKD NOSE drink milk _ that does not come from tuberculin-tested cattle unless it is pasteurized. Mechanical obstructions to breathing should be corrected, by surgical methods if necessary. Functional lack of. proportion in the chest and lungs of young people favor infection, and every effort should be made to help the child to outgrow them. Breathing exercises and outdoor play are especially useful. A generous diet is one of the best prophylactics against tuberculosis. A fat-rich food favors the development of a vrater-poor body, and it is knovm from experimental observation that animals with the largest pro- portion of water in their tissues yield to infection more readily than others. Eesistance to the disease is increased by rest, fresh air, good food, sunshine, the avoidance of all depressing influences, such as worry, overwork, intemperance, and excesses of all kinds. Attention should be given to slight colds and other conditions known to be predisposing causes to the disease. Education. — The prevention of tuberculosis, like all other wide- spread infections, depends for its success upon the education of the people. We are now in possession of sufficient information of a pre- cise nature to place the facts in plain words before the public. This has been done in numerous excellent pamphlets and popular articles in the daily press and magazines, through lectures, exhibits, and meet- ings, so that there is now a widespread and correct understanding of the problem. The modern message in tuberculosis has been one of hope, in that the disease is curable ; and one of fear, in that it is trans- missible. The former has been a great encouragement and has added strength to the movement; the latter is also helpful, although it has run to extremes in some quarters. An unwarranted fear of tubercu- losis (phthisiophobia) has subjected the tuberculous individual to se- vere hardships by branding him as a leper. Even cured cases of the disease now find difficulty in obtaining work. A wholesome regard for the infection is useful and helpful in preventive medicine, but an hys- terical fear of tuberculosis is quite as unwarranted as a total disregard for the infection. Notiication.— Tuberculosis should be included among the list of diseases requiring compulsory notification. Without this important fea- ture preventive measures are handicapped. The objection to compul- sory notification is based largely upon sympathy with the large num- ber of individuals affected and the sensitiveness of the afflicted. Com- pulsory notification may result in unnecessary harm, in that the knowl- edge of the fact may result in loss of occupation and an avoidance by his fellowmen on account of the fear people now have of associating with a tuberculous individual. These effects may, for the present, be TUBEECULOSIS 141 neutralized by considering the records as confidential communications between physician and health ofl&cer. Tuberculosis is required to be reported in Maine, Michigan, Massa- chusetts (since 1907) ; many cities: Alameda, California; Asbury Park, N. J.; Boston, Buffalo, Cincinnati, New York, Salt Lake City, Trenton, Yonkers — also in Washington, D. C, Minneapolis, San Francisco, and Syracuse. The list is growing and the returns are gradually improving. Disposal of the Sputum. — As the tuberculous sputum is the principal source of the infection, it should be disinfected or disposed of so that it will be harmless to others. Perhaps the best way is to receive the expectorated matter into cloths, which may be burned, or the material may be received into one of the various forms of sputum cups and finally burned or disinfected. Persons with pulmonary tuberculosis must be warned against the possible danger to others of coughing with- out holding the handkerchief before the mouth and nose; under no cir- cumstances should they spit upon the floor. Penalty for spitting upon the sidewalk, upon the floor of public buildings, and in street cars serves a useful purpose in diminishing the spread of tuberculosis as well as other diseases. In sanatoria and hospitals the infected material may be burned or disinfected with steam under pressure in a special autoclave, or disin- fected with phenol (5 per cent.), lysol (3 per cent.), tricresol (2 per cent.), or formalin (10 per cent.). Disinfection. — Eooms occupied by tuberculous individuals should be kept clean and disinfected from time to time. A thorough disinfec- tion and cleansing should also be practiced before such rooms are oc- cupied by other persons. This may be accomplished by mopping sur- faces with the usual solutions of bichlorid of mercury or one of the coal-tar preparations, followed by formaldehyde fumigation and a me- chanical cleansing, and then a thorough airing and sunning. Early Diagnosis. — Early diagnosis plays an important role in suc- cessful prevention; not only does it give the individual the best chances of cure, but at the same time it assures the possibility of maximum protection to others. Through the use of tuberculin and through re- finements of clinical methods it is now possible to diagnose tubercu- losis at a stage when it was formerly not suspected. It is a great mis- take, from the standpoint of prevention, to wait until tubercle bacilli appear in the sputum before making a diagnosis of tuberculosis. Prob- ably many cases of "a, slight run-down condition," of transient and irregular febrile attacks, are due to a small focus of tuberculosis hid- den from the ken of the clinician. In such cases a course of rest, fresh air, and better food, with a change of scene, may often prevent irreparable damage. The establishment of preventive clinics to look after such cases and the maintenance of medical clinics to diagnose and 142 DISCHARGES FROM MOUTH AND NOSE care for the early cases are important adjuncts to preventive measures. Housing Conditions. — It has long been realized, even before the rea- sons were understood, that improvement in housing conditions dim- inishes the incidence to tuberculosis. This is a common observation in the stabling of cattle as well as the domicile of man. The reasons why improving the housing conditions diminishes the spread of tuber- culosis are complex. In addition to raising the standard of living, better houses diminish the chances of contact infection, afford better air and more sunshine, and tend generally to the well-being and up- lift of mankind. Municipalities do well to enact and enforce stringent laws regulating the construction of houses, offices, stores, and work- shops. The congested and squalid slums are both a disgrace and a menace. Germs are social climbers, and many a palace is invaded with an infection from a nearby neglected alley. Philanthropists cannot do better than assist in improving the housing conditions of the poor. Bovine Tuberculosis. — The prevention of bovine tuberculosis con- sists simply in using milk, cream, and fresh milk products from tu- berculin-tested cattle. The cattle should be tested frequently; at least twice a year, for the disease may develop in the cow in a few months. When milk is used from non-tested cattle, it should be pasteurized, and the same precaution applies to the milk used for making cream, but- ter, ice-cream, and other fresh milk products. Industrial Insurance. — Industrial insurance patterned after the plan used in Germany is a useful adjunct in the fight against tuberculosis. The German industrial associations under government supervision do more than care for the tuberculous workman. The heavy drains upon the funds of the industrial associations have been checked by the estab- lishment of "preventoria." These are attractive country places where the working man can go when he is "run down." This simple meas- ure is a great boon, and prevents the development of many a case of tuberculosis as well as other diseases. Day camps, night camps, visiting nurses, and similar agencies are all helpful. In addition to the direct benefits, they teach the patient how to prevent the spread of the infection, how to sleep out of doors and its beneiits. The prevention of tuberculosis is no longer a medical problem — rather a sociological problem. The battle against tuberculosis has been waged with enthusiasm and the results are encouraging. Its eradica- tion will, however, take a long time on account of the chronic nature of the disease and its widespread prevalence. We should be satisiied if we diminish the amount of tuberculosis appreciably in a generation. The momentum thus gained will increase rapidly. The time will then come when the comparatively few cases left may be treated by compulsory isolation or other aggressive measures. Persistence along the lines now DIPHTHEKIA 143 understood will in time control the disease, which will be the crowning achievement in preventive medicine. DIPHTHERIA Our knowledge of diphtheria is most "satisfactory in that we know the cause of the disease and its modes of transmission ; we are able to check its spread, and possess a specific preventive and curative agent of great potency. Diphtheria spreads slowly from person to person and from com- munity to community. It is not necessary to consider it endemic in special indigenous foci, because it is seldom completely absent in any large community. Newsholme points out that diphtheria epidemics and pandemics occur cyclically. The intervals between the years of epi- demic prevalence vary greatly. In Boston diphtheria was epidemic in 1863-64, 1875-76, 1880-81, 1889-90, and 1894; in New York in 1876- 78, 1880-82, 1886-88, and 1893-94; in Chicago in 1860-65, 1869-70, 1876-79-81, 1886-87, and 1890. The causes of these epidemic out- bursts are not clear. They may be due to a fortuitous combination of such circumstances as a new crop of susceptible children, a particu- larly virulent strain of the bacillus, the opening of the schools, and similar factors favoring the spread of the infection. On the other hand, external conditions, such as dryness, may be important, for "diph- theria only becomes epidemic in years in which the rainfall is deficient. There is no instance of a succession of wet years in which diphtheria was epidemic." It is more than likely that the great outbreaks are due to a combination of the three factors — man, the bacillus, and the en- vironment. Just as a spark in a forest may cause a brush fire or a con- flagration, depending upon the amount of vegetable growth, its distribu- tion, its condition as to dryness, the direction and force of the wind, the topography and nature of the soil, and a thousand and one other con- ditions, so diphtheria and other infections will smolder or burst into flame, depending upon many factors. Diphtheria is said to prevail more in rural than in urban dis- tricts. Sir George Buchanan first pointed out that it has always dis- played a more marked tendency to prevail in sparsely settled districts than in centers of population, although outbreaks in congested centers, schools, camps, on board ships, and in other crowded places, are common. In the tropics diphtheria is practically absent. Kewsholme pointed out that it is more of a continental than an insular disease. The fatality from diphtheria has been greatly lowered since 1904, owing to the use of antitoxin and owing also to refinements of diagnosis, as a result of which many mild cases are now included that were formerly omitted from the statistical records. Whether or not there has been a 144 DISCHAEGBS FEOM MOUTH AND NOSE natural tendency for the disease to become milder in recent years can- not be stated. Diphtheria reaches its maximum prevalence in the autumn of each year, which corresponds to the seasonal prevalence of scarlet fever. In 1878 Dr. Thrushfield published papers illustrating the way in which diphtheria hung about damp houses. A damp dwelling favors sore throats and colds, and may thus open a way for invasion of the bacilli, just as any de- pressing influence may pre- dispose to the infection. Chil- dren with scarlet fever or measles are especially prone to take diphtheria if the in- fection is around. Formerly imperfect drains and sewer gas were given as the causes of diphtheria ; this is a fetish which dies hard. Modes of Transmission. — The diphtheria bacillus almost always enters by the mouth or nose, and the lesions are usually localized in the mucous membranes of the throat, nose, larynx, or upper respiratory tract. The bacillus leaves the body in the discharges from the mouth and nose. Diphtheria occa- sionally afEects other mucous membranes or abraded sur- faces, such as the conjunctiva or vaginal mucous membrane, or open wounds, in which case the discharges from these lesions contain the infection. The bacillus may be transmitted directly from one person to an- other, as by kissing, or exposure to droplet infection in coughing, speak- ing, and sneezing; or the infection may be conveyed indirectly from one person to another in a great variety of ways ; most common among children, perhaps, are toys, slate pencils, food, fingers, handkerchiefs, Jau Kt wu Apr ^^ June Jul^ Auq SepIO a Nov Dec (•Jooo \ \ uooo / \ \ \ P2000 / 1 MOOO \ ( 1 ■ iODOO \ I / eooo \ \ / / 6000 % S, ^* — 1 1 1 / fOOO -^ \ •v. 1 1 / 6000 k i. 1 ~ 9000 N ^ / *000 Fig. 16. — Chart Computed from the United States Census Report to Show how the Opening of the Schools in Autumn In- creases Diphtheria. The broken line shows the number of cases among school children five to fourteen years old during 1900-04 in the registration area of the United States. The unbroken line shows the number of cases among children, from birth to five years of age, for same period and area. On this chart the augmented increase in diphtheria among school children from five to fourteen years of age, as compared with children under five years, is strikingly shown. (Mass. State Board of Health, if 07i«W2/B«H, Sept., 1910.) DIPHTHBEIA , 145 or other objects that have been mouthed first by the infected child and then by the susceptible child. Experience points clearly to the conclu- sion that diphtheria infection is transmitted usually by direct exchange of the flora of the nose and throat, rather than through inanimate objects. Bacillus carriers play a large role in spreading the infection. Milk and other foods may become infected and transmit the disease. The diphtheria bacillus is frail and soon dies when dried or ex- posed to sunlight, therefore air-borne infection is probable only in the case of close association, that is, within a few feet of the infected per- son and within the radius of the possibility of droplet infection. The following description by Chapin illustrates how diphtheria and all other infections contained in the secretions from the mouth and nose may be transmitted ; it also emphasizes the importance of edu- cation in personal hygiene based upon habits of biological cleanliness: "Not only is the saliva made use of for a great variety of purposes, and numberless articles are for one reason or another placed in the mouth, but, for no reason whatever, and all unconsciously, the fingers are with great frequency raised to the lips or the nose. Who can doubt that if the salivary glands secreted indigo the fingers would not con- tinually be stained a deep blue, and who can doubt that if the nasal and oral secretions contain the germs of disease these germs will not be almost as constantly found upon the fingers? All successful com- merce is reciprocal, and in this universal trade in human saliva the fingers not only bring foreign secretions to the mouth of their owner, but there, exchanging it for his own, distribute the latter to everything that the hand touches. This happens not once, but scores and hun- dreds of times, during the day's round of the individual. The cook spreads his saliva on the muffins and rolls, the waitress infects the glasses and spoons, the moistened fingers of the peddler arrange his fruit, the thumb of the milkman is in his measure, the reader moistens the pages of his book, the conductor his transfer tickets, the lady' the fingers of her glove. Everyone is busily engaged in this distribu- tion of saliva, so that the end of each day finds this secretion freely distributed on the doors, window sills, furniture, and playthings in the home, the straps of trolley cars, the rails and counters and desks of shops and public buildings, and, indeed, upon everything that the hands of man touch. What avails it if the pathogens do die quickly? A fresh supply is furnished each day. Besides the moistening of the fingers with saliva and the use of the common drinking cup, the mouth is put to numberless improper uses which may result in the spread of infection. It is used to hold pins, string, pencils, paper, and money. The lips are used to moisten the pencil, to point the thread for the needle, to wet postage stamps and envelopes. Children ''swap' apples^ 14G DISCHARGES FROM MOUTH AND NOSE cake, and lollipops, while men exchange their pipes and women their hat pins. Sometimes the mother is seen 'cleansing' the face of her child with her saliva-moistened handkerchief, and perhaps the visitor is shortly after invited to kiss the little one. "Children have no instinct of cleanliness, and their faces, hands, toys, clothing, and everything that they touch must of necessity be continually daubed with the secretions of the nose and mouth. It is well known that children between the ages of two and eight years are more susceptible to scarlet fever, diphtheria, measles, and whooping- cough than at other ages, and it may be that one reason for this is the great opportunity that is afforded by their habits at these ages for the transfer of the secretions. Infants do not, of course, mingle freely with one another, and older children do not come in close contact in their play, and they also begin to have a little idea of cleanliness." Milk-borne Diphtheria. — The diphtheria bacillus grows well in milk without appreciably changing its flavor or appearance. Trask col- lected 33 diphtheria epidemics from the literature between 1895 and 1907. Fifteen of these occurred in the United States and 8 in Great Britain. The milk is usually contaminated by cases of the disease occur- ring on the farm or at the dairy or milk shop. In some cases the diseased person milks the cows or the same person nurses the sick and handles the milk. In two instances the outbreak was supposed to be due to disease of the cow. One of these instances studied by Dean and Todd is instructive. In certain families supplied with milk from two cows there occurred two cases of clinically typical diphtheria and three of sore throat, whereas in another family using the milk, only after sterili- zation, no case occurred. One of the cows had mammitis and furnished a scanty, ropy, semi-purulent, and slightly blood-tinged milk. The Klebs-LofBer bacilli were isolated in all cases and also from the milk of the cow with mammitis. Experiments justified the conclusion that the ulcers upon the udder of the cow with mammitis had become secon- darily infected with B. diphtherice, probably accidentally from some ap- parently healthy person. As a rule diphtheria epidemics caused by infected milk are more limited both as to numbers and area than milk-borne outbreaks of ty- phoid or scarlet fever. Bacillus Carriees.— It was in the case of diphtheria that the dan- ger of bacillus carriers was first realized. It is now known that per- sons who come in contact with diphtheria patients are very apt to harbor diphtheria bacilli, though they may remain in good health. It is also now well known that a certain percentage of the population at large harbor the diphtheria bacilli in their nose or throat, even though they have had no known association with the disease. Graham- Smith found that 66 per cent, of the members of the family to which DIPHTHERIA 147 the diseased person belonged were infected; the proportion being higher (100 to 50 per cent.) in families in which no precautions were taken to isolate the sick^ and much lower (10 per cent.) when such precau- tions were taken. Of the more distant relatives examined, 29 per cent, were found to be infected. Bacilli were found in 37 per cent, of per- sons in attendance on the sick. Observations of the inmates of hos- pital wards and institutions showed that 14 per cent, are likely to give positive cultures when diphtheria occurs among them. In in- fected schools 8.7 per cent, of the scholars were found to be bacillus carriers. In New York, Scholley examined 1,000 children from the tenement districts, and found 18 with virulent and 38 with non- viru- lent bacilli. Slack, Arms, Wade, and Blanchard took cultures at the beginning of the school year from about 4,500 pupils in the Brighton district, Boston. Diphtheria was not prevailing at the time. Never- theless, at least 1 per cent, of all these healthy school children were found to carry morphological typical diphtheria bacilli. It is estimated that this is the average ratio in the population at large. Ordinarily the bacilli found in diphtheria carriers under such cir- cumstances have little or no virulence. It is possible, but not very likely, that the virulence of such strains may be raised by passing through a susceptible individual. It is probable, however, that diph- theria is kept alive in a community rather by the virulent organisms in immune persons than by these non-virulent strains. None of the children in the Brighton district above mentioned had any known association with the disease, nor did they afterward develop diphtheria. The danger of such carriers is, therefore, problematic, and, on account of their large number, it is a question whether they should be isolated. The dangerous carrier is he who harbors the virulent strain, and this is usually obtained from the patient, convalescent, or from a third person who has come in contact with the patient. From our present standpoint it seems impractical to stamp out diphtheria from a large city by cul- tural tests of all its inhabitants and isolation of all carriers, especially where dependence is placed upon morphological diagnosis. Some harm- less bacteria have the morphological appearance of the diphtheria bacil- lus. On the other hand, the control of diphtheria outbreaks in institu- tions, camps, on shipboard, schools, and in similar places, where a num- ber of people are crowded together, as well as the control of epidemic outbreaks in cities and towns, depends eventually upon the recognition of carriers and their isolation. Park points out that diphtheria bacilli of like toxic power may difEer in their liability to infect the mucous membrane. Virulence, therefore, has two distinct meanings when used in connection with the diphtheria bacillus. The virulence of the bacilli cannot be accu- rately determined from the severity of an isolated case. The most 148 DISCHAEGES FEOM MOUTH AND NOSE virulent bacillus found by Park was obtained from a mild case simu- lating tonsillitis. In localized epidemics the average severity of the cases probably indicates roughly the virulence of the bacillus causing the infection. However, individual susceptibility and the character of the associated bacteria are important factors in determining the se- verity of the disease. The length of time it requires for diphtheria bacilli to disappear from the throat and nose varies greatly. Beebe and Park found that in 304 of 605 consecutive cases the bacilli disappeared within 3 days after the disappearance of the false membrane. In 176 cases they per- sisted for 7 days, in 64 cases for 13 days, in 36 for 15 days, in 13 cases for 3 weeks, in 4 cases for 4 weeks, and in 3 cases for 9 weeks. In some instances the virulent organisms may remain for months. The disappearance of the bacilli from the throat and nose cannot be hastened by the usual injections of antitoxin, although Price states that diphtheria antitoxin applied locally hastens the disappearance of the bacilli. Diphtheria antitoxin, when injected subcutaneously, pro- tects the individual but does not harm the bacilli. Careful attention to the hygiene and cleanliness of the mucous membranes may hasten their disappearance, and this is favored by copious washing of the throat and nose with large volumes of physiological salt solution. Anti- septics, such as silver nitrate, applied locally seem to be of little service. In recent years other measures have been proposed to rid the mu- cous membranes of diphtheria bacilli. A serum containing agglutinins has been used with some success. This serum in powdered form is blown into the throat. The diphtheria bacilli are thereby agglutinated and may then be more readily washed away by gargling and douching. In case these procedures fail, a substance proposed by Emmerich known as "pyocyanase" may be used. This contains a ferment from bouillon cultures of the Bacillus pyocyaneus. It is applied locally and acts by its power of bacteriolysis. Encouraging results have recently been reported by "over-riding" the throats of diphtheria carriers with suspensions of Staphylococcus pyogenes aureus, which are sprayed into the throat and nose. The method was introduced by Schiotz in 1909, who reported the prompt disappearance of diphtheria bacilli in six carriers. Page, also Catlin, Scott and Day, Lorenz and Eavenel, and others, have reported success- ful results. Hewlett and Nankivell, and also Petruschky, report encouraging re- sults in clearing up diphtheria carriers by the subcutaneous injection of a diphtheria vaccine. We must acknowledge that all these measures often fail. The re- lief of bacillus carriers is one of the rewardful problems in preventive medicine. DIPHTHEEIA 149 Resistance. — The diphtheria bacillus has less resistance to adverse conditions than the majority of the spore-free bacteria. It is more read- ily destroyed by lights heat, and disinfecting substances than the typhoid bacillus. In this regard it corresponds more to the frailer streptococci. Under certain circumstances the diphtheria bacillus resists drying for a long time. When buried in the false membrane or other albuminous ■substances, they may remain virulent for some months. Immunity.' — Immunity to diphtheria is very largely an antitoxic im- munity and persists for some months or years following a natural attack of the disease. Frequently immunity is of short duration, and second and third attacks are not uncommon. The fact that healthy persons may harbor virulent bacilli upon their mucous membrane for a long time vciihout contracting the disease shows that other factors are in- volved. These predisposing causes are inflammations or lesions of any kind of the mucous membrane, depressed vitality due to bad air, over- crowding, poor food, etc. Persons vary markedly in susceptibility. During the first 6 months of life there is but little susceptibility. Children between the ages of 3 and 10 are most susceptible; after that age the susceptibility again decreases. It is known that guinea-pigs born of immunized mothers inherit a certain degree of resistance, which may explain the relative insusceptibility of children under 6 months. This may also be accounted for by the diminished danger of exposure of babies during this age, especially in those that are breast-fed. Moth- er's milk, even colostrum, contains protective antibodies, which are ab- sorbed by the infant, and thus may protect it. Prevention. — Control of Outbreaks in Institutions. — Diphtheria frequently appears in asylums, hospitals, jails, on shipboard, and similar places. Under these conditions of crowding the disease has a highly contagious tendency. It may, however, be controlled with every as- surance of success by the application of well-tried measures. It is cus- tomary first of all to give a prophylactic dose of antitoxin to all the persons within the institution, including both inmates and adminis- trative force. This, however, must be regarded more as a measure of temporary personal protection than as a radical means of stamping out the infection. It is not possible by the use of diphtheria antitoxin alone to wipe out diphtheria. The bacilli remain in the throats of the immunized and the disease continues to crop out after the antitoxic immunity has passed away, which may be a matter of only a few weeks. When diphtheria antitoxin is used as a prophylactic, the dose is 1,000 units, which should be repeated every ten days or two weeks — as long as the danger persists. The most important measure to suppress diphtheria in an institu- tion is to isolate all cases and all carriers. This is possible in an in- stitution, although not very practical among the population at large. 13 150 PISCHAEGES FEOM MOUTH AND NOSE The isolation of both cases and carriers is the most important and radical of our preventive measures. In the case of institutions, jails, ships, and similar places all those who show cultures containing organisms which morphologically resemble the diphtheria bacillus should be iso- lated, whether the strains are virulent or not. The bacilli frequently grow in the mucous membrane of the nose and nasal pharynx without symptoms indicating their localization. Un- less cultures are taken from the nose, many carriers will be overlooked, leaving a large loophole in our preventive measures. Ward and Hen- derson in a public school epidemic in Berkeley in 1907 found that all attempts to isolate infected children had no effect on the epidemic so long as they made throat cultures alone. When they took both nose and throat cultures and quarantined all the children showing positive cultures, the epidemic stopped. Convalescents should not be released from quarantine until at least two cultures taken from both the nose and throat are negative. In addition to the above-mentioned measures, care must be taken that the infection is not spread by the use of cups, spoons, dishes, towels, handkerchiefs, and other articles used in common. The in- fected discharges should be rendered harmless at the bedside, and all objects that come in contact with patients or carriers should be disin- fected. A general disinfection with formaldehyde may be practiced, but in a well-ordered institution the usual cleanliness of floors, walls, and other surfaces will suffice. Control of Epidemics. — The principles which guide us for the con- trol of outbreaks among the population at large are precisely the same as those described for the control of epidemics in institutions. The only difference is that in the population at large it is more difficult, if not impossible, to apply the one real important measure, namely, that of isolating the carriers. What is needed is a convenient and re- liable method of distinguishing the virulent and dangerous bacilli from those that look like diphtheria bacilli but lack pathogenic power and danger to man. In almost all communities diphtheria is now one of the diseases which must be reported to the health authorities. The houses are placarded and the cases isolated. There is no great objection to treat- ing a case of diphtheria in the household provided the patient and the nurse may also be quarantined from the rest of the household. Under these circumstances and with intelligent care and disinfection at the bedside there is little danger to the rest of the family; but the great menace that some of the members of the family will harbor bacilli of a dangerous type and transmit them to others makes it advisable to treat all cases of diphtheria in a special hospital. The prompt and early diagnosis of diphtheria has now become one DIPHTHERIA 151 of the routine measures of board of health laboratories. This example in the case of diphtheria could be extended with advantage to the other communicable diseases for which we have satisfactory laboratory aids. Especially commendable is the general practice of refusing to lift the quarantine until two successive cultures prove negative. Disinfection in diphtheria should be applied especially to the se- cretions from the mouth and nose. These may be received upon a piece of gauze and burned. For the hands and other objects bichlorid of mercury (1-1,000), carbolic (2% per cent.), formalin (10 per cent.), tricresol (1 per cent.), are efficient. As a terminal disinfectant for- maldehyde gas may be used, but the ordinary fumigation, as practiced by Boards of Health, seems to have little influence in checking the spread of the disease. Evidence is accumulating that the infection usually comes from persons rather than from things. Bed linen, towels, and other fabrics should be boiled or steamed. Personal Peophtlaxis. — In individual cases diphtheria may be avoided by the use of diphtheria antitoxin. The antitoxic immunity, however, depends upon the free circulation of the antibodies in the blood, and as the antitoxin is gradually eliminated it cannot be de- pended upon to protect more than 2 or 3 weeks. Diphtheria antitoxin is a specific and sovereign remedy. When given in sufficient amounts during the first 24 hours of the disease it reduces the mortality to practically nil. Ordinarily 500 units are sufficient for prophylactic purposes, but 1,000 units are preferable, as this amount produces an immunity of higher degree and longer duration. When the exposure to the infection continues the antitoxin may be adminis- tered at successive intervals of about 2 or 3 weeks. Upon the first ap- pearance of sore throat, fever, or other suggestive symptoms in persons who are exposed to diphtheria a full dose of 3,000 to 10,000 units should be administered without delay. In order to obtain the full life-saving benefits of diphtheria antitoxin, it should be given early in the disease. Time is the most important factor. When the damage to the cells has been done, it may be too late. It is not always advisable to wait for bacterial confirmation. Personal prophylaxis is further fa- vored by the individual having his own glass, cups, spoons, towels, etc., and exercising personal cleanliness, especially concerning the hands and all objects placed in the mouth. Physicians, nurses, and others who come in close contact with the patient should guard against drop- let infection. PREVENTION OF POST-DIPHTHERITIC PARALYSIS It has been observed that post-diphtheritic paralysis is more fre- quent since the use of antitoxin than before the days of serum therapy. 152 DISCHAEGES FROM MOUTH AND NOSE This is due to the fact that many cases now recover that would for- merly have died. It is also due to the fact that diphtheria antitoxin is sometimes used too late, thus neutralizing only the acute efEects of the toxin, but not neutralizing the after-effects of the toxon, which acts specifically upon the nerves. The prevention of post-diphtheritic paralysis, therefore, consists in giving sufficient amounts of antitoxin early in the disease. The antitoxin does not influence the paralysis after it has once appeared. PBEVENTION OF SERUM SICKNESS This subject may appropriately be considered here, although it is a condition that may follow the injection of any alien serum into the system. Serum sickness is a syndrome which frequently follows the injection of horse serum into man. The symptoms come on after about 8 or 10 days following the injection. They consist of various skin eruptions, usually urticarial or erythematous in character; also fever, edema, glandular enlargements, rheumatic-like pains in the joints, and albuminuria. The eruptions may be either local or general, and sometimes resemble that of scarlet fever or measles. Serum sickness has nothing to do with the antitoxin, but is caused entirely by the foreign proteins contained in the horse serum. It may be produced with normal horse serum as well as with antitoxic horse serum. The studies upon anaphylaxis have thrown much light upon the nature of this complication. The serum of some horses is much more apt to produce the syndrome than that of other horses. A serum that is sev- eral years old is perhaps less apt to produce these reactions than a fresh serum. Manufacturers of antitoxin, therefore, prefer to keep their serum in the ice chest some time before they place it upon the market, although this a doubtful expedient. The occurrence and severity of the symptoms are in direct proportion to the amount of foreign pro- tein injected. Fortunately, this form of anaphylactic reaction soon passes away and is never serious. Under certain circumstances, however, there may be an accelerated or immediate reaction threatening in its consequence or even leading to death. Eosenau and Anderson have col- lected some 19 cases of sudden death following the injection of horse serum, and they know of more instances which have not appeared in the literature. This unusual and serious complication comes on within 5 or 10 minutes of the injection, and is characterized by collapse, uncon- sciousness, cyanosis, labored respiration, and edema. The heart continues to beat after respiration • has ceased. The entire picture is an exact counterpart of the anaphylactic shock so readily reproduced by second injection of horse serum or other foreign protein in the guinea-pig. Con- trary to the experimental work on the lower animals, most of the cases of DIPHTHEEIA 153 sudden death in man follow the first injection of horse serum. The seri- ous symptoms and death in these cases are not due to any inherent poison- ous property in the antitoxic serum, but result entirely from a hyper- susceptibility of the individual. Just how man becomes sensitized in these cases is not known. Most of the cases, however, occur in asthmatics or in persons who gave a history of asthma or discomfort when about horses. This is a practical and important point, and should be inquired into before horse serum of any kind is injected. Horse serum should not be injected into such individuals unless the indica- tions are clear, and then only with a statement as to the possible out- come. In order to prevent this serious complication a small quantity may first be injected, 1 or 2 drops, and after waiting an hour the re- mainder may be given. Vaughan proposed 0.5 c. c. as the trial dose, but this is excessive, as some of the fatal cases have followed the in- jection of about 1 c. c. It is known that in man, as in the experi- mental cases in the guinea-pig, the severity of the symptoms bears a definite ratio to the amount of serum and the mode of injection. Thus, second injections in the guinea-pig are much more fatal when given directly into the circulation than into the subcutaneous tissue. It is sometimes advisable to give antitoxic sera directly into the circula- tion, but in the susceptible persons under discussion this would be hazardous. Friedberger and Mita ^ found it possible to avoid all symptoms of anaphylaxis in experimental work with guinea-pigs by injecting the serum extremely slowly. When thus introduced animals are able to tolerate an amount far beyond the ordinary lethal dose. Historical Note. — A complete summary and bibliography of diph- theria up to 1908 will be found in the system edited by Nuttall and Graham-Smith entitled "The Bacteriology of Diphtheria," containing articles by Loffler, Newsholme, Mallory, Graham-Smith, Dean, Park, and Bolduan; Cambridge University Press, 1908. The original clinical description of the disease is, by common as- sent, attributed to Bretonneau in 1826: Traite de la diphtherite. Des- inflammations speciales du tissu muqueux et en particulier de la diph- therite ou inflammation pelliculaire, connue sous le nom de croup, d'an- gine maligne, d'angine gangreneuse, etc., Paris. The bacillus of diphtheria was first cultivated and adequately de- scribed by Loffler, 1884: TJntersuchungen iiber die Bedeutung der Mikroorganismen fiir die Entstehung der Diphtherie beim Menschen 'Friedberger, E., and Mita, &.: "To Prevent Anaphylaxis in Serotherapy" ("Methode, grossere Mengen artfremden Serums bei iiberempflndliohen Indi- viduen zu injizieren"), Deutsche med. Wochenschr., Berlin, Feb. 1, XXXVIII, No. 5, pp. 201-248. 154 DISCHAEGES FEOM MOUTH AND NOSE bei der Taube und beim Kalbe. Mitth. a. d. K. QesundheiiswmU, ii, 451. The classical article in which Behring and Kitasato announced their discovery of diphtheria antitoxin in 1890 will be found in Deutsche, med. Wochenschr., xvi, 1113. Ueber das Zustandekommen der Diph- therieimmunitat und die Tetanusimmunitat bei Tieren. Ehrlich's important work, in which he laid the foundations of his side-chain theory and established the present satisfactory method of standardizing diphtheria antitoxin, will be found in the following: Die Werthbemessung des Diphtherieheilserums und deren theoretische Grundlagen. Klin. Jahrb., Jena, v, 6 (2), 1897, pp. 299-326. Ueber die Constitution des Diphtheriegiftes. Deut. med. Woch., Leipzig, v, 24 (38), 1898, pp. 597-600. Croonian lecture. On Immunity with Special Eeference to Cell Life. Proc. Eoy. Soc, London, v, 66, pp. 424-448, pis. 6-7. The official method for standardizing diphtheria antitoxin in this country and the principle upon which it is based are described by Eosenau (1905), The Immunity Unit for Standardizing Diphtheria Antitoxin (based on Ehrlich's normal serum). Hygienic Laboratory Bull. No. 21, P. H. and M. H. S., Washington, Govt. Print. Office, 92 pp. MEASLES Measles is usually taken as the type of a contagious disease because it is one of the most readily communicable of all diseases, in this re- gard ranking with smallpox. As a cause of death it ranks high among the acute fevers of children. Measles is an infection peculiar to man, although experimental measles has recently been produced in monkeys. The virus is contained in the blood, as has been shown by Hektoen, who thus transmitted the disease from man to man. More important from the standpoint of prevention, the virus has been demonstrated in the secretions from the nose and mouth by Anderson and Goldberger. The period of incubation is quite constant (from 9 to 11 days), and the rash appears quite uniformly on, the 13th or 14th day after the infection. In Hektoen's two experimental cases the eruption appeared on the 14th day. The cause of measles is not known. Measles is more or less constantly present in all large cities in the temperate zone; it is less common in the tropics. Measles fre- quently becomes epidemic, usually in the cooler months, in this respect resembling smallpox. The epidemics recur cyclically, at irregular in- tervals. Levy and Foster noticed that in Eichmond, Va., epidemic outbreaks recurred at intervals of about 3 years. They were able to predict and warn against an epidemic prevalence of the disease in the MEASLES 155 winter of 1910. During 1909, 40 cases of measles occurred in Eich- mond, but during this year the disease showed no special tendency to spread. In the middle of February, 1910, 8 cases occurred among the pupils of one school and the infection showed a high degree of com- municability. According to the history of the disease, an epidemic year was due and an epidemic was predicted. Over 2,000 cases occurred with 26 deaths. Measles is highly contagious during the preeruptive stage, when the nature of the disease is not recognized and when most of the dam- age is done; it remains contagious for a variable time during conva- lescence. Eecent experimental evidence and clinical experience plainly indicate that the infection of measles soon dies out, and that there is little danger of transmitting the infection after the temperature re- turns to normal. An isolation of two weeks from the onset of the dis- ease is sufficient in public health work; health officers, however, adopt arbitrary times. Thus, in Detroit cases of measles are isolated one week; in Buffalo, Concord, New York, Providence, and Yonkers, two weeks; in Brookline and Fall Eiver, two weeks after the eruption fades; in Boston, two weeks after recovery; and three weeks in Montclair, K J., New Bedford, Mass., Ottumwa, Iowa. Immunity. — One attack of measles usually confers a rather definite protection against subsequent attacks; second attacks, however, are more common than in the other eruptive fevers. Some persons have the disease three or four times. As with smallpox, there appears to be no natural immunity to measles — man is exquisitely susceptible to these two infections. There appears to be a relative immunity sometimes of a high grade during the first few months of life, although measles oc- casionally occurs in infants of a month or six weeks. Adults are susceptible to measles, provided they have not had a previous attack. Susceptibility to the infection does not diminish with increasing age; the disease is apparently one of childhood only on ac- count of the chances of exposure in early life. Before the days of vac- cination smallpox was also a disease mainly of childhood. The following instances demonstrate the susceptibility of adults to measles and also the serious nature of the disease : Measles was intro- duced into the Faroe Islands in 1846 from Copenhagen, and over 6,000 of the 7,782 inhabitants were stricken. In 1775 it was introduced into the Sandwich Islands, and in 4 months 40,000 of the population of 150,000 died. Measles is common in army camps, especially among troops enlisted from country districts, who are thus exposed to the infection for the first time. Measles is often fatal both in adults and children on account of pneumonic complications. It also seems to lower the resistance to tu- 156 DISCHAEGES FEOM MOUTH AND KOSE berculosis; for it is a common history to find tuberculosis develop in children following an attack of measles. Kesistance of the Virus. — In general the virus of measles is known to be much less resistant than that of scarlet fever and many other in- fections. The virus does not Uve long upon fomites. Therei is prac- tically no danger of children contracting the infection from the room in which the patient was treated, even though no disinfection was practiced, provided two weeks have elapsed. Goldberger and Anderson ^ found, as the result of experiments upon monkeys, that the virus in measles' blood is filterable; that is, may pass through a Berkefeld filter. It resists desiccation for 25% hours, loses its infectivity after 15 minutes at 55° C, resists freezing for 35 hours, and possibly retains some infectivity after 34 hours at 15° C. From the standpoint of our present knowledge it is evident that any of the ordinary germicidal agents sufficient to kill spore-free bac- teria will serve as effective disinfectants for measles. Aside from the few scientific observations upon the viability of the virus of measles, epidemiological observations have long pointed out the fact that the virus of measles is frail and soon dies in the convalescent as well as in the environment. Modes of Transmission. — The virus of measles is contained in the nasal and buccal secretions. While it is possible that the virus may leave the body in other secretions, it is highly probable that the dis- charges from the nose and mouth are the means of transmitting the infection in the vast majority of eases. We are less certain concerning the modes of entrance into the body, although it is presumed that the virus also enters by the mouth and nose; however, we lack positive information upon this point. Mayr ^ showed in 1853 by experiments on the human subject that the buccal and nasal secretions were infective. Eecently Anderson and Goldberger^ have demonstrated by experiments upon monkeys that the nasal and buccal secretions of uncomplicated cases of measles may be at times, but are not always, infective. Hektoen * in 1905, as well as Goldberger and Anderson, 1911, demonstrated that the virus of measles is also contained in the circulating blood. The virus appears in the blood at least 24 hours before the eruption appears, and begins to diminish about 25 hours after the first appearance of the eruption.: It has long been assumed that the virus of measles is carried in the fine bran-like desquamating epithelium, which is one of the char- acteristics of the disease. Mayr long ago failed in his attempts to in- V. A. M. A., Vol. LVII, No. 12, Sept. 16, 1911, p. 971. = Mayr, Franz: Zeitschr. d. Tc. Ic. Gesellsch. de Aertze en Wien, 1852, I, 13-14. 'J. A. M. A., Vol. LVII, Nov. 11, 1911, p. 1612. * Experimental Measles : Jour. Infect. Vis., 1905, Vol. II, p. 238. MEASLES 157 oculate children with measles by using the desquamating epithelium. Anderson and Goldberger also obtained absolutely negative results in. three experiments, in which it was shown that the "scales" were not infective for monkeys. These authorities believe that it is highly prob- able, if not altogether certain, that the desquamating epithelium of measles in itself does not carry the virus of the disease. This conclu- sion is warranted by epidemiological evidence. Measles is so readily communicable that clinicians receive the im- pression that the virus is "volatile." It has long been suspected that the virus is contained in the expired breath, but this is very doubtful. In fact, it may now be stated with confidence that measles is not air- borne, in the sense in which this term is usually understood. In any ease, the radius of danger through the air is confined to the immediate surroundings of the patient — that is, within the danger zone of droplet infection. Droplet infection is quite possible, as the virus is contained in the secretions of the mouth and nose; furthermore, it evidently requires an exceedingly minute quantity of the virus to reproduce the disease in man, who is exquisitely susceptible to this infection. Chapin has collected important evidence indicating that the infec- tion of measles is not air-borne. Thus, in the Pasteur Hospital, Paris, each patient is cared for in a separate room opening into a common hall. Trained nurses exercise strict medical asepsis. In 3I/2 years after this hospital was opened in 1900 many cases of smallpox, diphtheria, scarlet fever, and 126 cases of measles were eared for. In no instance did measles spread within the hospital. At the Children's Hospital in Paris (Hopital des Infants Malades), instead of being in separate rooms, the beds are separated only by partitions. Strict asepsis is ob- served. Of 5,017 cases there were only 7 cross-infections, 6 of measles and 1 of diphtheria. Dr. Moizard thinks that this experience proves that even measles is not air-borne, for the few cases of this disease which did arise were not all in cubicles adjoining those occupied by measles patients. Grancher in another Paris hospital had two wards in which there were no partitions, but only wire screens around the beds, simply as a reminder for the nurses. Of 6,541 patients treated from 1890-1900, 115 contracted measles, 7 scarlet fever, and 1 diphtheria. Grancher insists that measles is probably not an air-borne disease. Adjacent patients do not necessarily infect one an- other. At various English hospitals similar methods have beeen tried with success. These various hospital experiences indicate that the danger of aerial infection in measles is much less than is generally supposed. The infection of measles is usually transmitted more or less directly from person to person by means of the excretions from the mouth and nose, and most often during the early stages of the disease. Measles 158 DISCHAEGBS FEOM MOUTH AND NOSE may be transmitted by third persons or by fomites, though such in- stances are rather exceptional. Prevention. — The suppression of measles is one of the most diffi- cult problems we have to face, for the reason that the disease is one of the most highly communicable of all infections, and for the further reason that it is most contagious during the preeruptive stage. To the student of preventive medicine the problem of measles is very similar to that of smallpox, and the final control will probably have to await a specific prophylactic measure. Improved sanitation, better hygiene, and the general advance of civilization, which have made such a marked impression upon typhus fever, relapsing fever, typhoid fever, and other "filth" diseases, have no influence whatever upon such infec- tions as measles or smallpox. Measles is such a common disease that parents are prone to take little pains to avoid the infection; they even sometimes purposely ex- pose their children. This is a mistaken attitude. Special care should be exercised especially during the first five years of life, as over 90 per cent, of the fatal cases occur in this period. While it may be al- most hopeless to lessen the morbidity in measles, it is quite possible to materially decrease the mortality by simply delaying the age inci- dence. Clinical experience plainly indicates that few people die of measles if properly cared for. The mortality may, therefore, be decreased by careful nursing and protection, especially from pneumonia, which is one of the most dangerous complications. Newman sums up the mat- ter of prophylaxis when he states that "the prevention and control of measles, like that of whooping-cough and tuberculosis, is largely in the hands of the public themselves." In the present state of our knowledge the prophylaxis of measles rests almost entirely upon one measure — isolation. Chapin believes that isolation has been a failure in measles. This is because of the unrecognized but infectious preeruptive stage. "No amount of isolation after the disease is recognized can atone for the harm done before the diagnosis is made." Isolation, however, accomplishes one worthy ob- ject, viz., the prevention of further damage. Isolation, as carried out in our large cities, has had no apparent effect upon the prevalence of the disease. In Aberdeen restrictive measures a-pparently protected only 7 to 10 per cent, of the population. Despite its limitations, isolation is quite worth while. Cases should be at once reported to the health officer, the house placarded, and visit- ing prohibited. Quarantine should not be raised nor should the child be permitted to return to school until the manifestations of the disease have disappeared. Measles may be treated in the household, but it is diSicult under ordinary circumstances to prevent the spread of the dis- MEASLES 159 ease to the other children. If the case is treated at home, the children who have not had the disease should be sent away. Mild atypical and unrecognized eases of measles occur, but are far less numerous than such cases in scarlet fever, diphtheria, and typhoid. Clinical evidence points to the fact that "carriers" of measles are not common. The disease is usually spread directly from person to person, occasionally indirectly through a third person, or by fomites. Physi- cians may convey the infection to healthy children. I am convinced that I carried the disease to my own son. When measles is conveyed by a third person or by fomites it is by means of contamination with the fresh buccal, nasal, or bronchial secretions upon the hands, hand- kerchief, or some other object that comes in contact with the mouth or nostrils of a susceptible child. Physicians may readily avoid this dan- ger by wearing a gown and carefully washing the hands, face, and hair, and waiting a reasonable time before visiting healthy children. Terminal disinfection is of comparatively little value in preventing the spread of measles. After the patient is released from isolation a general disinfection with formaldehyde may be practiced, especially if healthy children are soon to occupy the playroom or bedroom. How- ever, if from 3 to 3 weeks have elapsed, there is practically no danger in a well-ventilated, sunny, and clean room. All bedding, towels, hand- kerchiefs, and other fabrics that have been exposed should be boiled or otherwise disinfected. The question of closing the schools in order to prevent the spread of measles requires consideration. If the school is closed at the begin- ning of an outbreak and the disease continues to spread after two weeks, little more will be gained in keeping the school closed, for it must then be evident that other factors are at work in spreading the infection. As the disease is mainly spread in the preeruptive stage, it is sufficient to examine the children each morning before they enter school for symp- toms of a cold, infection of the eyes, running at the nose, cough, sore throat, fever, etc. All such cases should be sent home to await further developments. If these measures are taken the school may be kept open. McVail suggests that when a child develops measles all the children exposed may be allowed to continue at school 8 or 10 days, and then excluded for a week to ten days, when those who do not develop the dis- ease may be allowed to return. This is a rational plan used in certain districts in England. When measles breaks out in an orphan asylum, a public institution, or an encampment, the only chance of checking the spread of the disease is through the early recognition of first symptoms and isolation. 160 DISCHARGES FEOM MOUTH AND NOSE SCARLET FEVER Scarlet fever is an acute febrile infection characterized by a diffuse eruption which apjDears during the first day or two of the fever, and sore throat of variable intensity. The seasonal prevalence of scarlet fever resembles that of diphtheria. The disease increases in the fall of the. year, due, in part, to the gathering of children in the schools. The period of incubation is from 1 to 7 days; usually 2 to 4. In a few instances, in which individuals have been inoculated with the blood of scarlet fever patients, 3 to 4 days elapsed before the onset of symp- toms. Scarlet fever is rare in the tropics; when introduced it soon dies out. There is probably always more or less scarlet fever in any thickly settled district in the temperate zone. The infection is kept alive largely through the mild and unrecognized cases. Scarlet fever varies greatly in intensity in different outbreaks. In some epidemics the death rate .is 30 per cent.; in others it is practically nil. Landsteiner, Levaditi and Prasek ^ apparently succeeded in transfer- ring scarlet fever to chimpanzees and also to monkeys. The aninials were inoculated both by applying throat swabs from scarlet fever patients to the pharynx of the animals, and also by injecting the animals with blood from scarlet fever patients. While the nature of the virus is still unknown, it seems to be present in the tonsils, tongue, blood, lymph nodes, and pericardial fluid. The cause of scarlet fever is not known. Streptococci are almost constantly found in the throat and blood of scarlet fever cases. Klein in 1885 was the first to advocate the Streptococcus scarlatince as the specific cause of scarlet fever. Kurth assigns an etiological factor to the "Streptococcus conglomeratus." It is said to produce a rash in animals and men who are injected with it. The chief reasons for con- sidering streptococci as the cause of scarlet fever are that they are con- stantly found in the throat of scarlet fever patients; that frequently they can be isolated from the blood of scarlet fever patients during life, and almost constantly after death; the cause of the complications and death in the majority of cases of scarlet fever is due to the strepto- coccus. It is probable, however, that the streptococcus plays a secondary role in scarlet fever as it does in sm^allpox; the disease itself may be due to a protozoon-like body described by Mallory, which lowers the resistance of the organism to streptococcal invasion. Modes of Transmission. — It is taken for granted that the virus of scarlet fever is contained in the secretions from the nose, throat, and respiratory tract. The virus probably enters by the mouth and respira- tory passages. Scarlet fever is not contagious during the period of ^ Annales de I'Inst. Pasteur, Oct., 1911, XXV, No. 10, p. 754. SCAELET FEVER 161 incubation; little, if any, during the period of invasion. It is most contagious during the period of eruption. Scarlet fever is readily communicable, but less so than measles or smallpox ; it ranks about with diphtheria. It has long been accepted and taught by the medical profession that the desquamation is the most infectious stage of scarlet fever, and it is now very difficult to unteach the public this erroneous view. It is now known that desquamating patients may, as a rule, be safely released from quarantine in the 6th week of their attack of scarlet fever, provided they have no mucous complications or other sequelse. Convalescents may be a source of danger to others even after desquama- tion has ceased. This fact has been emphasized from a study of the so-called "return cases." Thus convalescents are released from hos- pital and permitted to return home; soon another case appears in one of the members of the household, who in turn comes to the hospital. Neech in a study of 15,000 cases found that the percentage of return cases was 1.86 in those cases who submitted to an average period of isolation of 49 days or under. With an average period of 50 to 56 days the percentage was 1.12 ; where the isolation extended to between 67 and 65 days the percentage of return cases was 1. McCullom states that in the South Department of the City Hospital, Boston, the chil- dren are kept 50 days, and no patient is released who has a discharge from the nose or an abnormal condition of the throat. Of 3,000 pa- tients discharged from the scarlet fever ward, 1.7 per cent, of return cases occurred. McCullom is inclined to regard the infection as com- ing from mild and unrecognized cases of the disease rather than from the discharged case. There is no accurate means of determining just how long a child remains infective after scarlet fever. The period of detention varies very much. Fifty days may be taken as a safe average. In New Ha- ven and Seattle cases are dismissed after desquamation; in North Dakota 5 days after desquamation; in Ohio and South Dakota 10 days after desquamation. In various cities and states the period of isola- tion varies from 3 weeks to 8 weeks unless the physician certifies that desquamation has ceased. In Milwaukee, Paterson, and Pittsburg it is never maintained longer than 30 days, even if desquamation con- tinues. Owing to our lack of knowledge on the subject, the period of isolation must remain more or less guesswork. An unduly long detention is a hardship upon the patient and the family; on the other hand, a scant period is hazardous to the community. Cases with rhinor- rhea, otorrhea, throat trouble, or discharging abscesses must receive spe- cial care, as the secretions from these parts are now known to remain infective for a long time. Many cases of walking scarlet fever present little further evidence 162 DISCHAEGES FROM MOUTH AND NOSE than a passing sore throat. These cases doubtless spread the disease, especially in schools. Third persons may carry the disease perhaps on their clothing and perhaps also as carriers. Toys, cups, spoons, ther- mometers, handkerchiefs, and other objects contaminated by the secre- tions of the mouth play the same role here that they do in diphtheria. Scarlet fever is not air-borne; at least the radius of infection is limited to droplet infection. Milk-borne Scarlet Fever. — Milk is a rather frequent vehicle for scarlet fever infection. The milk is practically always contaminated from human sources. There is, however, some suspicion that strepto- coccal diseases of the cow may in some instances be identical with scarlet fever. This is doubtful. It is known, however, that such diseases of the udders of the cows may cause outbreaks of an infection resembling scarlet fever. Trask collected 51 scarlet fever epidemics reported as spread by milk. Twenty-five of these occurred in the United States and 26 in Great Britain. In 35 of the epidemics a case of scarlet fever was found at the producing farm, the distributing dairy, or milkshop at such a time as to have been the possible source of infection; in 3 of the out- breaks the bottles returned from infected households and refilled without previous sterilization were given as the source of infection; in 3 of the outbreaks scarlet fever persons handled the milk or milk utensils, and in 12 of the outbreaks the cows were milked by persons having scarlet fever; in one epidemic the same person nursed the sick and handled the milk; in 2 of the outbreaks the source of infection was supposed to be due to disease of the cow. A milk-borne outbreak in Washington was traced to a convalescent with a discharging ulcer on the finger. Milk- borne outbreaks of scarlet fever are sometimes very extensive. An unusually extensive milk-borne outbreak of scarlet fever occurred in Boston during April and May, 1910. A total of 842 cases were reported from Boston and the surrounding towns of Chelsea, Winthrop, Cambridge, Somerville, Maiden, and Everett. Investigation showed that most of the cases occurred on the route of a large milk contractor. Of the 409 cases in Boston, 286, or nearly 70 per cent., were on the route of this dealer; while 123, or 30 per cent., used other milk. Of the 155 cases that occurred in Cambridge, 126, or over 80 per cent., were on the route of the same dealer. About the same proportion of the cases in the other cities used the milk of this dealer. The cases appeared suddenly April 25th, and the outbreak ceased May 7th. The epidemic reached its highest mark on April 29th, when 138 cases were reported. The indications were plain that the outbreak was the result of more than a single infection. The milk was pasteurized at 60° C. for 30 minutes on April 27th, and three days following there was a notable and sharp decline in the number of cases. The source of the infection could not be traced, although it probably consisted of a SCARLET FEVER 1G3 "missed" case on one of the 350 dairy farms from which the dealer ob- tained this particular supply of milk. Immunity. — One attack of scarlet fever usually protects against subsequent attacks. In rare instances second attacks may occur after an interval of several years. Children under 10 are most susceptible. Sucklings are rarely attacked, though susceptible. After the 10th year the resistance to the disease increases. Ninety per cent, of the fatal cases occur in children under 10 years old. The reason why infants at the breast are less likely to take the disease may be on account of the diminished chances of the infection entering the mouth. The immunity acquired in later life may in part be due to previous unrecognized mild attacks. Prophylaxis. — Prophylaxis in scarlet fever must necessarily be in excess of the requirements, awaiting more precise knowledge of its cause and modes of transmission. The essential features of prevention consist in isolation and disinfection. It is important to recognize the mild cases in schools through an efficient medical inspection. The answer to the question whether schools should be closed when scarlet fever breaks out varies with the circumstances. In country districts this is advisable, as the children may be kept separate, but in the cities little is gained. There is no objection to treating a case of scarlet fever in the household, provided a suitable room and trained attendant may be had. The infection may be confined to the sick room, but it is preferable to take no chances and send the susceptible individuals out of the house. The nurse should use the precautions described for diphtheria, smallpox, or measles. The physician should wear a gown and thor- oughly disinfect his hands and other exposed parts after the visit. Spe- cial care must be taken with the thermometer and other instruments. The physician may find the necessary precautions and disinfection to be irksome, but they should not be shirked in justice to his other pa- tients and the community. The discharges from the mouth, nose, and respiratory passages, etc., should be collected upon suitable fabrics and burned. Bed and body clothing, dishes, and other exposed objects must be disinfected. Care must be taken concerning remnants of food from the sick room. Scarlet fever is not as highly contagious as measles, but the meas- ures employed should be practically the same until at least we have more definite knowledge concerning the channels of entrance and exit of the virus and its modes of transmission. The virus of scarlet fever is more resistant than that of measles. It clings persistently to cloth- ing and various objects. A terminal disinfection with formaldehyde gas may be practiced, although little seems to be gained thereby. A thorough cleansing of all surfaces, with a good sunning and airing of the room, is always in order. All fabrics and other objects that have been exposed 164 DISCHARGES FROM MOUTH AKD NOSE should be disinfected. The virus is killed with agents that destroy non-spore-bearing bacteria. In Glasgow a sanitary wash-house has been established, where the clothing of scarlet fever cases may be' disin- fected and washed. This is a commendable example that might be fol- lowed with advantage by other cities. Specific Prophylaxis. — Gabritscliewsky first proposed the use of streptococcus vaccines as a prophylaxis against scarlet fever. He used a concentrated bouillon culture of the streptococcus isolated from a person ill with scarlet fever. The culture is killed by heating to 60° C., and 0.5 per cent, carbolic acid added. Gabritschewsky uses 0.5 c. c. of the concen- trated bouillon culture in children 2 to 10 years old. For those younger half this amount, and adults twice this amount, is used. The injec- tions are given subcutaneously in the abdomen, thigh, back, or arm. Another method of dosage is to use 0.1 e. c. for each year of the child's age with 0.25 c. c. as the minimum and 1 c. c. as the maximum. Three doses are given in periods of 7 or 10 days, the dosage increasing at each injection 1% to 2 times the previous dose. The only eases in which the vaccines are withheld are: (1) in those having a high temperature, although even these have received the prophylactic without evident untoward results; (2) in very young in- fants or patients who, from some cause or other, are greatly exhausted; and (3) in those having nephritis. The claim is made that after 3 injections of the vaccine, and usu- ally after 2, a complete immunity is established against scarlet fever. The immunity does not appear until 5 to 7 days after the last dose. The duration and degree of the immunity is problematical, as the vac- cines have been in use so short a time. It appears that the immunity probably remains at least 1% years. The usual reactions, both local and general, follow these injections, but in 10-15 per cent, of the persons injected quite a different reaction occurs. Twenty-four hours after the injection there appears on the chest and abdomen, sometimes extending over the rest of the body, a punctate erythema very much like the eruption of scarlet fever, but not followed by any desquamation. The eruption lasts 1-3 days, and may be accompanied by sore throat, some swelling of the lymph glands, and often a so-called strawberry tongue. Rarely a rather severe reaction with high fever, a little albumin in the urine, and marked prostration occurs, but it rapidly disappears without permanent harm. The reactions following the second injection are usually much less than after the first; often none at all; and after the third injection there are rarely any unpleasant features. The longer the intervals be- tween the injections the more frequently will there be a reaction to the second and third injections. The interval of .a week is considered the SCARLET FEVER 165 most satisfactory. Richard M. Smith ^ has collected over 50,000 in- stances in which the killed streptococcus cultures have been injected with only 1 fatality, which was a child 21/^ years old who had a severe nephritis and died on the third day after the injection. The method has been extensively tried in Russia with favorable re- sults, so far as one may judge from the published reports. Thus Smir- noff used the vaccines in 13 small communities in Russia where the sanitary conditions were very poor and the conditions favorable for the spread of scarlet fever. In one village there were 34 unvaccinated children, of whom 24, or 70.6 per cent., had scarlet fever; 48 vacci- nated children, of whom 4, or 8.3 per cent., had scarlet fever. Of these 4, 3 came down within a week after the first inoculation, the other one 5 days after the second inoculation, too soon for immunity to have been established. The results in the other villages were equally or more satisfactory. Thus, all told, Smirnoff vaccinated 455 cases, only a part of whom allowed second injections. The results are as follows : cases of scarlet fever 1 i] ijectic Dn — 285 cases— 5 ( 2 a —148 " —2 3 a — 22 " —no Of the 7 cases of scarlet fever 3 were within 7 days of first vac- cination, 2 were within 7 days of second vaccination. In the villages without vaccination 20 per cent, contracted scarlet fever and 11.1 per cent. died. In villages with vaccination 3.7 per cent, contracted scarlet fever, none died. Yemelyanoff used the prophylactic in an epidemic in Krakow in which there were 8 or 10 new cases reported every day. Six hundred and ten persons were inoculated; of these not a single one contracted the disease. Often it was possible to keep the schools open in certain districts where inoculations were used, even though the children came from infected houses. Equally good results are reported by a number of other Russian observers. It therefore seems that in the streptococcus vaccines we have a useful means to control epidemics of scarlet fever. Their use, with proper care, is attended with no harmful results, and they de- serve a wider trial in this country. Moser's polyvalent antistreptococcus serum has been used in the treatment of the disease, but has not been advocated as a prophylactic. ^Boston Medical and Surgical Journal, CLXII, 8, p. 242, Feb. 24, 1910. 13 166 DISCHAEGES PROM MOUTH AND NOSE WHOOPING-COUGH Whooping-cough occurs in epidemics, which vary greatly in viru- lence, intensity, and mortality. The disease is more frequent and se- vere in cold climates; otherwise uninfluenced by season and weather. The cause of whooping-cough is a small bacillus, described by Bordet and Gengou.^ This bacillus is found most readily in the beginning of the disease, in that part of the expectoration which comes from the region in which the bacteria are most active; that is, in the products from the depths of the bronchi brought up during the paroxysms. In this exudate, which is white, thick, and rich in leukocytes, the bacilli exist in considerable numbers and sometimes in almost pure culture. Mode of Transmission. — Whooping-cough is usually transmitted di- rectly from person to person in the same ways that diphtheria and other infections contained in the secretions of the mouth and nose are spread; it is less frequently transmitted by indirect contact or by third persons. Handkerchiefs, toys, drinking cups, roller towels, and other objects recently contaminated with the infective secretions may act as directors. It may also be transmitted by droplet infection, although in the ordinary sense whooping-cough is not air-borne. Jahn and others called attention to the fact that domestic animals may be affected by whooping-cough, and that they may be the means of transmitting it to children. It is most frequently observed in dogs, but has also been noted in cats. Whooping-cough may be reproduced in puppies by dropping a pure culture into the nares; once started, it is readily transmitted from puppy to puppy. Klimenco ^ and Fraenkel ' were able to produce what seemed like typical pertussis in monkeys, and Inabo * showed that injection of the bacillus in an ape gave rise to a typical whooping-cough with an incubation period of 13 days. Mallory and Horner ° have shown that the bacilli are found in niasses in the superficial layer of the trachea, thereby mechanically paralyzing the ciliffi. Whooping-cough is apparently not contagious during the period of in- cubation, but is communicable from the appearance of the early symp- toms, and is most contagious during the early stage. It may be trans- mitted in the late stages and after convalescence. While the virus is known to be in the secretions from the respiratory tract, all secretions from the mouth and nose must be regarded as infective. Immunity. — There is no natural immunity to whooping-cough; all are susceptible. The greatest susceptibility is between 6 months to 5 ^Ann. de I'Inst. Pasteur, Vol. XX, 1906, p. 731. = Centralbl. f. BaUeriol, 1908, XL VIII, 64. ' Miinchen. med. Wochschr., 1908, LV, 1683. ^Ztschr. f. Einderh., June 15, 1912. = Jour. Med. Bes., Nov., 1912, XXVII, 2, p. 115. WHOOPING-COUGH 167 years. After 5 years the susceptibility decreases with age. One at- tack confers a definite and prolonged immunity; second attacks are rare. Prevention. — The incubation is probably 1 to 3 weeks, but the time is indefinite, owing to vagueness of the onset of symptoms. If 16 days have passed without symptoms the danger may be considered as having passed. The long-drawn-out nature of the disease, the difficulty of diagnosis in the early stages when it is most contagious, and the fact that patients sometimes continue to spread the infection for 6 weeks after apparent recovery, make the control of whooping-cough an ex- ceedingly difficult problem. Hence, with whooping-cough we have the same difficult problem that confronts us in the prevention of measles. Whooping-cough should be reported, houses placarded, and the pa- tient isolated, but the isolation in this case need not include strict con- finement to a room. This, in fact, may be an unnecessary hardship to the patient, who does better out of doors. If the patient is permitted to take the air, he must avoid contact with his fellowmen and not go to school, theater, church, public assemblies, nor ride in street cars or public vehicles. Children should go out only when accompanied by an intelligent caretaker as a protection to others. It has been suggested that children with whooping-cough who are permitted their liberty should be plainly labeled with a red cross on their arm, or a yellow flag conspicuously displayed on their clothing, to serve as a warning to others. Patients should not be released from quarantine until the spasmodic stage is over. The duration of isolation varies in different cities; thus it is 6 weeks in Montclair, N. J.; on recovery in Providence; as long as the cough lasts in Boston. In Michigan the disease is considered infectious 3 weeks before the whoop and 4 to 6 weeks after apparent recovery. The State Board of Health of that state requires disinfec- tion of the clothing and premises before the patient is released, and forbids public funerals in deaths from whooping-cough. Individual prophylaxis consists in avoiding the infection. The great- est care in this regard should be taken with children before the age of 5 years. Dogs, cats, and other domestic animals should be kept away from the patient, and the possibility of conveying the disease in this way must be guarded against in the susceptible. The control of whooping-cough is a matter which is largely in the hands of the public itself. The dangerous nature of this infection should be emphasized, and people taught that it is contagious both be- fore and after the "whoop." Mild cases which do not have the charac- teristic whoop spread the disease; this is especially common in adults. Mortality. — The dangerous nature of whooping-cough is not gen- erally realized. Thus in Glasgow the annual mortality from whooping- cough for 40 years, 1855-1894, was 13.5 per thousand inhabitants, and 168 DISCHARGES FEOM MOUTH AND NOSE exceeded that from any other acute communicable disease. In Eng- land and Wales in 1891 more deaths occurred from whooping-cough than from measles, diphtheria, scarlet fever, or typhoid fever. In our country the disease ranks high as a cause of death among children. The mortality figures would be still higher if all the deaths directly or indirectly due to it were completely reported, for the fatal termination is usually due to complications and sequelsE which occur in one-third to one-fourth of all cases. As a result of these complications the origi- nal disease is frequently lost sight of entirely in the vital statistics. According to Farr's law — ^that contagious diseases increase as density of population increases — ^the death rate from whooping-cough in our country will undoubtedly increase in our more sparsely settled states with increasing population and rapidly extending lines of railroad and other facilities, and with easy, frequent, and rapid movements of the people. MUMPS Mumps usually occurs between the ages of 5 to 15 years. There is decreased susceptibility both before and after this time. One attack usually confers immunity, but second attacks are by no means rare, and third attacks are sometimes reported. The disease may occur as epidemics in institutions, which usually develop slowly and last a long time. Mumps is contagious before the symptoms appear, and for some time, even 6 weeks, after symptoms have disappeared. The disease is usually spread by direct contact; rarely by indirect contact or by a third person. It is not air-borne. The virus is contained in the secre- tions from the mouth and perhaps the nose. The incubation is variously stated at from 4-25 days; it is usually prolonged. Mumps is required to be reported in Maryland, Grand Eapids, and Raleigh, and placarded in Cleveland. Prevention depends upon the usual practice of isolation and disinfection. LOBAR PNEUMONIA Lobar pneumonia is a communicable disease which should be classi- fied with the infectious fevers. If pneumonia were a new disease it would be regarded as "contagious," and its spread would be guarded against by isolation and the application of antiseptic principles. Many difEerent infections are caused by the pneumococcus, but here we will consider only the specific self-limiting disease associated with massive involvements of one or more lobes of the lung, known as lobar or croup- ous pneumonia. The pneumococcus is found not alone in the local lung lesions, but it also invades the blood. LOBAR PNEUMONIA 169, Pneumonia is one of the most prevalent and fatal of all acute diseases. As a cause of death it rivals and sometimes exceeds tuber- culosis. According to the U. S. Census of 1890, over 9 per cent, of all deaths were due to pneumonia, and in 1900 over 10.5 per cent. Pneumonia is probably on the increase, owing to factors favoring the spread of the infection and to certain devitalizing influences of modern life which heighten susceptibility to the disease; further, more persons are now saved from the acute and fatal infections of childhood and adoles- cence to become victims of pneumonia later in life. Pneumonia occurs everywhere, in all climates, at all times of the year, in both sexes, and at all ages; it is more frequent, however, dur- ing the cold months of the year. The incidence is marked at both ex- tremes of life. It is common in children undet six years; between the sixth or fifteenth year the predisposition is less marked, but for each subsequent decade it increases. Pneumonia occurs in well-marked epidemics. Wells gives an ex- haustive tabulation of the epidemics of pneumonia extending back to 1440.^ Epidemics of pneumonia have occurred in all - parts of the world: in Alaska, at Erlangen, Boston, Ireland, Italy, France, Switzer- land, and on board ships. The disease has also been observed to spread in hospitals and in houses. Epidemics of pneumonia probably only occur when the organism attains an increased virulence and the factors for its dissemination are favorable. It is quite proper to regard pneu- monia as pandemic. Modes of Transmission. — The pneumococcus leaves the mouth main- ly in the discharges from the mouth and nose, and enters the system through the same channels. The infection is spread directly and in- directly through the great variety of waj's discussed under diphtheria and tuberculosis. Indirect transmission through cups, thermometers, handkerchiefs, and other objects contaminated with the fresh discharges occurs; and droplet infection also comes into consideration. Resistance of the Virus. — The pneumococcus is a frail organism; it does not jnultiply in nature outside of the body and indirect trans- mission is not likely except with fresh infectious material. Even upon artificial culture media the life of the pneumococcus is brief; it must be transplanted every 2 or 3 days in order to keep it alive; it is cus- tomary in laboratories to pass it through a susceptible animal, such as a mouse or rabbit, from time to time, in order to maintain its viru- lence. The pneumococcus is readily destroyed by heat; 53° C. for 10 min- utes is sufBcient. On the other hand, it withstands low temperatures very well. The ordinary germicidal agents destroy it quickly and with V. A. M. A., Feb. 23, 1889. Med. News, May 20, 1905. 170 DISCHAEGES FROM MOUTH AND NOSE certainty. It may live for months in dried sputum, in which it also maintains its virulence. Immunity. — One attack of pneumonia does not leave an immunity. In fact, one attack predisposes to subsequent attacks, as is the case with erysipelas and rheumatic fever. Man, however, must possess a certain degree of resistance to the pneumococcus, else the disease would be even more prevalent than it is, and recovery less frequent. The mechanism of the immunity to this infection is not at all un- derstood. Phagocytosis may play a prominent, perhaps a dominant, role. Protective antibodies, rather feeble, have been found in the blood serum of immunized animals, and also in the blood serum of persons who have recovered from pneumonia. The pneumococcic attack, espe- cially the crisis, resembles an anaphylactic reaction, and, while the mechanism of immunity in this infection is probably complex, the best explanation of it at present is in terms of anaphylaxis. Many weakening diseases diminish resistance to the pneumococcus. Pneumonia is frequent in alcoholics, and is commonly brought on by exposure to cold, to trauma, or to local irritation. It is a frequent complication of typhoid fever, influenza, Bright's disease, and other debilitating affections. Old age, as well as other enfeebling conditions, may act as a predisposing cause by lowering immunity. Other factors which predispose to pneumonia are sudden changes in temperature, irri- tation caused by aspiration of foreign substances, or the inhalation of dust or irritating vapors. It should be remembered that pneumonia, like other communicable infections, frequently attacks the strong and robust. Prevention. — The prevention of pneumonia must be based upon gen- eral principles guided by analogy from analogous infections. As long as we are ignorant of the fundamental factors concerned in the etiology and pathogenesis of the disease, our preventive measures must lack precision. The virulent pneumococcus should not be lightly regarded as a nor- mal inhabitant of the mouth, throat, and nose. Because the pneumo- coccus is very widely spread and the disease is ubiquitous, and because the associated factors which determine infection seem complicated and not well understood, are not sufficient excuses for a supine and hope- less attitude. Tlie problem of tuberculosis has been attacked with vigor with scarcely better understanding of the fundamental problems at issue. Each case of pneumonia should be regarded as a focus for the spread of the infection. Ultimate control of the disease will probably have to await the discovery of a specific prophylactic and the recognition of dangerous carriers. Meanwhile we should think of pneumonia very much as we think of whooping-cough and influenza, as an infection which is spread from man to man through the secretions of the mouth LOBAR PNEUMONIA 171 and nose. It is true that the pneumococcus is frequently found in the buccal secretions of healthy persons. Sternberg in 1880 first demon- strated the pneumococcus in his own saliva. Netter found it in 30 per cent, of the persons whom he examined, and the New York Com- mission reported its presence in from 48 to 85 per cent. Pneumococci have been isolated from the throat in 50 out of 80 normal individuals, from 66 out of 74 cases of lobar and lobular pneumonia, from 10 out of 15 "common colds," and from 14 out of 31 cases of miscellaneous diseases; in other words, many persons are pneumococcus carriers. However, there are many different strains of the pneumococcus, which vary greatly in pathogenic power. We therefore do not know how many of these pneumococcus carriers are dangerous to the host and also to his fellowmen. A somewhat analogous situation is noted in the diphtheria-like organisms in the throats of about 1 per cent, of all healthy individuals. It is probable that the virulence of the pneumococcus is higher in pneumonia than in the above-mentioned carriers, although this is a very difficult matter to determine. The findings of the Medi- cal Commission for the Investigation of Acute Eespiratory Diseases seem to make prevention a less hopeless task than at first sight ap- pears possible from the widespread distribution of the pneumococcus. It was shown that, while a number of individuals constantly harbor virulent strains of the pneumococci in their mouths, the majority of people do so only from time to time. Individuals who come in con- tact with pneumonia patients are more apt to harbor the pneumococ- cus than those not so exposed. Patients convalescent from pneumonia may carry virulent organisms in their respiratory passages for weeks or even months. Pneumonia should be added to the list of diseases requiring com- pulsory notification. Cases should be isolated at least in the same sense that tuberculosis is isolated — the discharges from the nose and throat should be burned or disinfected. If the patient is treated at home, the house should be placarded in order to discourage visiting and as an educational measure. There is no specific prophylaxis for pneumonia. Prevention con- sists in avoiding the infection, sustaining the tone of the machine, care and cleanliness of the upper respiratory passages, avoiding chills, exposure, and other predisposing causes, and especially avoiding living in stuffy, ill-ventilated rooms and dusty atmospheres. As carriers doubtless play an important role in disseminating this infection, the education of the public concerning certain sanitary habits should be actively continued. These include the danger of spitting promiscuously and of kissing; the proper care to be exercised in sneez- ing and coughing; the peril in the common drinking cup, the roller towel; and the habit of placing unnecessary things in the mouth. 173 DISCHAEGES FEOM MOUTH AND NOSE It should become common knowledge that anything which tends to reduce vitality predisposes to pneumonia, such as dissipation, loss of sleep, overwork, worry, poor or insufficient food, lack of exercise, al- cohol, colds, or excesses of all kinds; the atonic efEect of living in overheated rooms, and the injurious efEect of excessively dried and warmed air, and sleeping in warmed rooms. Cold baths, regulation of temperature and ventilation, sleeping with open windows or in the open air, are useful prophylactic measures for pneumonia as well as tuber- culosis, "colds," and a large group of diseases. Upon the Isthmus of Panama pneumonia was unduly prevalent owing to the habit of the perspiring workmen sleeping exposed to the trade winds. According to Carter, this was largely controlled by sup- plying the men with blankets. In Chicago, Evans believes that the prevalence of pneumonia was influenced by better ventilation of the street cars. Allaying street dust and house dusb removes one of the predisposing causes of pneumonia and other respiratory infections. Health officers may assist in the cause by disseminating knowledge concerning the disease and by enforcing antispitting regulations, by proper cleansing and oiling of streets, by requiring a stricter compli- ance with building and housing laws, and by the regulation of the ven- tilation and conditions of the air in theaters, schools, street cars, and public buildings. INFLUENZA The cause of influenza is assumed to be a small bacillus which is constantly associated with the disease; it was described by PfeifEer in 1892 and 1893.^ Influenza prevails without relation to climate, wind, weather, or telluric conditions. It occurs sporadically, in epidemics and in great pandemics. In 1889 and 1890 influenza spread to the four quarters of the globe, and, judged by the morbidity and mortality, this was the most extensive and serious pandemic that has occurred in modern times. These worldwide outbreaks usually spread from east to west. Immunity. — ^Immunity to influenza is slight; in fact, one attack seems to predispose to subsequent attacks; second and third attacks are common as a result of new infections or reinfections. Influenza bacil- lus carriers are numerous. Males and the robust individuals in a com- munity seem more susceptible, perhaps on account of greater expo- sure. Modes of Transmission. — Influenza is spread directly from person to person. It is highly contagious in the early stages. The influenza bacillus is found in the secretions from the nose, throat, and respira- ^Veutsch, mecl, Wochenschr., 2, 1892, p. 28. Zeitschr. f. Syg., XIII, 1893, COMMON COLDS 173 tory tract. The bacillus does not multiply outside the body and has a very feeble resistance. It grows with difficulty upon artificial cul- ture media and soon dies out; therefore "contact" infection or the use of handkerchiefs, towels, cups, and other objects contaminated with the fresh secretions are the common modes of transmission. Influenza is kept alive in interepidemic years in carriers. Lord found the bacil- lus influenza in 25 to 59 per cent, of all cases with cough and expectora- tion in an interepidemic period in Boston. Prophylaxis. — Prophylaxis is practically the same as for all other infections transferred by the secretions from the mouth and nose. Iso- lation is not always practicable, but patients for their own good as well as the protection of others should remain in bed during the febrile stage. This one measure would very largely diminish the prevalence of influenza as well as common colds. The infection could be kept out of a country by strict maritime quarantine, provided mild cases and car- riers could be recognized; this, however, is not practicable. The pub- lic has not sufficient regard for influenza to .tolerate aggressive meas- ures. The disease may frequently be avoided by individual prophy- laxis. During epidemics individuals should avoid theaters, mass meet- ings, closed and crowded cars, and close contact with their fellowmen, especially those who have catarrhal symptoms. It is quite worth while to isolate the first case of influenza in a household in order to prevent a house epidemic. This may be done on precisely parallel lines to those described for diphtheria. Influenza is especially dangerous when com- plicating pulmonary tuberculosis, and care should be taken to keep it out of sanitaria. Even during epidemics influenza may successfully be kept out of institutions by an intelligent quarantine. Once within the walls, it is exceedingly difficult to control. Persons who continually carry the influenza bacillus in their nose, throat, or respiratory tract should guard against exposure to wet and cold on account of the dan- ger of reinfection. Influenza is another one of those diseases the con- trol of which rests with the public. Education, therefore, is of prime importance. The danger from the use of the common drinking cup, the roller towel, kissing, droplet infection, handkerchiefs, pipes, toys, soda-water glasses, spoons, and other objects recently mouthed should be emphasized; spitting ordinances enforced, ventilation and overcrowd- ing of street cars corrected, and dust allayed. COMMON COLDS More people probably suffer from common colds than from any other single ailment. Vital statistics give no hint of the prevalence and im- portance of these minor afEections because the mortality is nil and the morbidity records are notoriously imperfect and difficult to collect. Could 174 DISCHAEGES FROM MOUTH AND NOSE the sum total of suffering, inconveniences, sequels, and economic loss resulting from common colds be obtained, it would at once promote these infections from the trivial into the rank of the serious diseases. The common colds here considered are a group of acute infections of the mucous membranes of the nose, pharynx, tonsils, larynx, trachea, or larger bronchi. A common cold is not merely a congestion, it is an infection. Congestion and inflammation of the mucous membrane of the up- per respiratory tract frequently occur as a result of irritants other than bacteria. Thus, chemical and mechanical irritants will produce a congestion or inflammation; an increased acidity causes a flaring up of the mucous membranes, especially of the nose; and many other local and reflex causes lead to acute or chronic catarrhal conditions of these membranes, which may become exquisitely sensitive and sometimes hypersusceptible. In the absence of the proper bacteria, however, these conditions do not develop into infectious colds, and are, therefore, not communicable. The popular fallacy of colds being due to exposure to drafts, sud- den changes of temperature, and chilling of the body clings persistently in both the professional and lay mind. These are predisposing causes and will not produce a cold without the presence of the specific cause. The bacteria usually found associated with these catarrhal infections are: staphylococci, streptococci, pneumococci, influenza bacillus, the Bacillus catarrhalis, and other bacteria. The etiological relationship between these organisms and the disease is not always clear. Many of the above-mentioned bacteria are also found normally upon the mucous membranes of the nose, mouth, throat, and upper respiratory passages; reinfections must, therefore, be common, and predisposing factors which diminish resistance have a special importance. Common colds frequently attack the strong and robust if exposed. Colds are contracted from other persons having colds, just as diph- theria is contracted from diphtheria. Arctic explorers exposed to all the conditions ordinarily supposed to produce colds do not suffer from these ailments until they return to civilization and become reinfected by contact with their fellowmen. A campaign to prevent the spread of the common cold would have much collateral good in aiding the suppression of tuberculosis and causing a diminution of pneumonia and other infections. Common colds occur in epidemics and have all the earmarks of a contagious disease. Colds are apt to go through all the members of a household, and outbreaks in schools, factories, and other places where people are closely associated frequently occur and. result in considerable loss of time and money. While common colds are never fatal, the complications and sequelae, are serious. These are : rheumatic fever, pneumonia, sinusitis, nephritis, COMMON COLDS 175 and a depressed vitality which favors other infections and hastens the progress of organic diseases. Common colds are perhaps most contagious during the early stages. If persons would isolate themselves by remaining in bed during the first three days of a cold, they would not only benefit themselves, but would largely prevent the spread of the infection. The contagiousness and severity of colds vary greatly in different epidemics and in dif- ferent seasons of the year, depending upon the particular microorgan- ism involved and other factors not well understood. Prevention. — The prevention of colds consists, first, in avoiding the infection, and, secondly, in guarding against the predisposing causes. Contact should be avoided with persons who have colds, especially in street ears,, offices, and other poorly ventilated spaces where the risk of persons coughing or sneezing directly in one's face is imminent. Con- tact with the infection may further be guarded against by a careful self-education in sanitary habits and cleanliness based upon the mod- em conception of contact infection. Colds, like other diseases con- veyed in the secretions from the nose and mouth, are often conveyed by direct and indirect contact through lack of hygienic cleanliness and a disregard of sanitary habits. Kissing, the common drinking cup, the roller towel, pipes, toys, pencils, fingers, food, and other objects contaminated with the fresh secretions will transmit the disease. The predisposing causes of colds include a number of conditions that depress vitality and thereby diminish resistance. The mechanism by which immunity is lessened has been discussed on page 351. The principal predisposing factors in catching cold are : vitiated air, dust, drafts, sudden changes of temperature, exposure to cold and wet, over- work, loss of sleep or insufficient rest, improper food, and other con- ditions that lower the general vitality of the body. A special word concerning drafts is necessary. Drafts in them- selves cannot produce an infectious cold. The first symptom of the disease is a chill, which is not the cause, but the effect, of the infec- tion. It is a common belief that the cold is caught when the chill occurs. The rigor frequently consists of only a transient chilliness, and it is during this time that the individual thinks he feels a draft which is producing his cold. Drafts have no appreciable injurious effect upon persons in good physical tone. They are, however, injurious to infants, the aged, and to susceptible individuals. Drafts are particularly apt to harm persons accustomed only to still, warm air. "It is. not the engine drivers and firemen of trains that catch colds, but the passengers in the stuffy carriages." Coddling renders one susceptible to drafts, partly for the reason that the vasomotor impulses which contract the blood vessels of the skin are not sent out by the nervous mechanism, and consequently 176 DISCHAEGES FROM MOUTH AND NOSE undue cooling of the part blown upon, and perhaps of the blood itself, takes place. Normally, when the wind blows upon the skin the vaso- motor contraction reduces the supply of blood and the tendency to cooling is further met by a stimulus which increases heat production. While it is true that a draft can no more cause an infectious cold than it can cause diphtheria, nevertheless, it is true that a draft may be the predisposing cause by which immunity is lowered. It is a mistake to think that the skin alone is involved in the ques- tion of drafts. The hardening of the skin as a prevention of colds is, therefore, a misnomer. The good effects of cold baths, exercise, fresh air, sunlight, and wholesome food do not consist in "hardening" the skin, but in improving the nutrition, stimulating the metabolism, help- ing the control of the nervous system, improving the tone of the vaso- motor system, strengthening the musculature, and enriching the blood. In preventing the ill effects of drafts, therefore, the entire organiza- tion of the body must be considered, and not the skin alone. Other important predisposing factors to colds are mechanical de- fects in breathing, or the filtering power of the upper respiratory pas- sages, also local pathological conditions, such as adenoids, polypus, deviation of the septum, chronic catarrhal conditions, all of which should receive appropriate treatment. One of the most important predisposing factors to colds is breathing vitiated and dusty air. Good ventilation, therefore, with air not too dry nor too warm, and the allaying of dust would prevent many a cold. The bacteria producing colds are frequently found in the mouth, nose, throat and teeth of persons in good health. Cleanliness and care of these parts is, therefore, an important consideration in the prevention of common colds. CEREBROSPINAL FEVER Cerebrospinal fever is an infection with the meningococcus (Diplo- coccus ■ intracellularis meningitidis, Weichselbaum). The essential le- sions of the disease are chiefly focused upon the meninges of the brain and cord. The disease occurs both in localized epidemics and sporadi- cally. The meningococcus is a frail microorganism, closely resembling the gonococcus. Both are biscuit-shaped cocci; both grow feebly on artiiieial media. They are readily killed by drying, sunlight, heat, and other unfavorable conditions. They live a strict parasitic exis- tence and cause diseases peculiar to man, with lesions which resemble each other, both as far as the character of the inflammation and the distribution of the cocci within and without the cells are concerned. As a rule, these two microorganisms are usually distinguished by the CEEEBEOSPINAL FEVER 177 source from which they are obtained. Otherwise the differentiation is difficult and depends upon careful cultural and biological studies. All cases of meningitis are not caused by the meningococcus. Spo- radic cases may be due to the pneumococcus, streptococcus, bacillus of in- fluenza, the colon bacillus, the typhoid bacillus, the bacillus of bubonic plague, and of glanders. The gonococcus may also cause meningitis as a secondary complication. The epidemic form of cerebrospinal menin- gitis is always due to the meningococcus. Only one epidemic so far studied bacteriologically was certainly not due to the meningococcus; in this the microorganism responsible seems to have been the Strepto- coccus mucosus, or a close relative. The first epidemic outbreak of meningitis was reported by Vieus- seux in Geneva in 1805. The next year James Jackson, Thomas Welch, and J. C. Warren investigated an outbreak in Massachusetts. Since then numerous epidemics have occurred. In New York in 1904-05 there were 6,755 cases and 3,455 deaths. The epidemiology of cerebrospinal fever differs from that of infantile paralysis in several respects. The seasonal prevalence of infantile paral- ysis follows the curve of the summer diarrheas (July to September), while cerebrospinal fever prevails especially in the fall and winter months. The seasonal prevalence of cerebrospinal fever is strikingly similar to that of pneumonia and influenza, and corresponds to a num- ber of diseases, such as scarlet fever, measles, diphtheria, and smallpox, in which the principal mode of infection is believed to be through the respiratory tract, and which are supposed to be spread mainly by contact. The epidemics are usually localized. Country districts are more afflicted than cities. Children and young adults are most susceptible. Outbreaks sometimes occur in camp or on shipboard. The immunity produced by one attack is not lasting. Councilman reports five instances in which the same individual is reported to have had the disease twice. It is probable that the meningococcus enters the system through the mucous membrane of the nasopharynx. From this position it may reach the meninges directly through the lymph channels or indirectly through the circulation. The experiments of Flexner in the monkey indicate that when the meningococcus is introduced into the cerebral cavity it escapes by a reversed lymphatic current, so that under these circumstances it may be found in the mucous membrane of the nasopharynx. Fliigge, Weich- selbaum, Scheurer, and others have found the meningococcus present in great numbers in the nose and pharynx in most cases of the dis- ease during the first 12 days of illness. Park states that after the 14th day they cannot usually be found. The admirable monograph of Elser and Huntoon"- includes a careful study of 310 cases of the disease. The most striking conclusion by these authors is the essential impor- ^ Journal of Medical Research, 1909, Vol. XX, pp. 377-536. 178 DISCHAEGES PEOM MOUTH AND NOSE tance of meningococcus carriers in the transmission of epidemic menin- gitis. The number of persons who become such carriers during an epidemic of meningitis is far greater than the number of cases of -ac- tual meningitis. Perhaps 70 per cent, of healthy persons exposed may harbor meningococci in the respiratory passages. Apart from epidemics the meningococcus can be found but rarely in healthy individuals, but apparently there are persons who, once harboring this organism in the nasopharynx, carry it permanently and thus perpetuate the disease. Meyer, Voltmann, Furst, and Grieber ^ studied the question of car- riers in cerebrospinal meningitis. They found 1.73 per cent, of menin- gococcus carriers in over 9,111 healthy soldiers in the Munich garri- son at a time when no cerebrospinal fever was present. One exam- ination was made from each soldier. A special study was made of 1,911 healthy persons who were examined many times, with the result that 2.46 per cent, were found to be meningococcus carriers. Of the total of 11,022 healthy persons, about 2 per cent, examined contained the meningococcus in their throats. Isolation of the carriers had no influence on the incidence of the disease, and epidemiologically they found only exceptional relationship between the carriers and the sick. In one of the years during this study numerous clinical cases occurred; in another year none, although the number of carriers remained the same both years. The authors conclude that extreme painstaking cultural de- tection of meningococcus carriers is unnecessary in combating the spread of cerebrospinal meningitis; that the practical benefits do not justify the care and time necessary for such work. They believe that the chief foci, aside from factors not understood in the spread of this disease, seem to be the sick and especially the mild cases. Great care should, therefore, be taken to isolate the mild case so as to diminish the num- ber of carriers. On the other hand, in the epidemic of cerebrospinal meningitis in Texas in 1912, Thayer examined 421 persons; 59.6 per cent, were healthy carriers, as determined by the examination of stained smears. The results obtained from cultures showed 53.75 per cent, to be positive. It is now believed that cerebrospinal meningitis is transmitted prin- cipally through the medium of healthy carriers. Only a small percentage of the carriers develop the disease. The occurrence of more than one case in families is common. In the recent Texas epidemic there were many instances in which two members developed the disease, and in a smaller number three, four, and five members became infected. The disease is undoubtedly transmitted rather directly from person to person, for the meningococcus is of such low vitality that it suc- cumbs quickly to drying, sunlight, and other injurious influences. On account of its severity, persons suffering from the disease are decidedly ' Miinchener Med. Wochenschr., 1910, No. 30, July 26. CBREBEOSPINAL FEVEE 179 limited in their sphere of influence, and, as only a very small propor- tion of those who receive the microorganism are susceptible to it, the perpetuation and spread of meningitis must depend on the healthy car- riers who pass the meningococcus on from one to another until a sus- ceptible individual is infected and develops meningitis. The virulence of the organism is also a determining factor. Prevention. — From our present knowledge preventive measures are clearly indicated, though very difficult to carry out. Epidemic cerebro- spinal meningitis is a good example of a group of diseases in which a more precise knowledge of the modes of transmission of the disease makes it obvious that prevention is a matter of extreme practical diffi- culty. Fliigge estimates that healthy carriers of this disease are ten times more numerous than recognized cases, and, therefore, are more than ten times as prolific a source of infection. While the isolation of the known cases will prevent a certain number of secondary cases, this measure alone cannot hope to control the disease. It is obviously impractical to undertake to make bacteriological examinations sufficient to discover all the carriers in a community of any considerable size; moreover, the control of so many carriers when discovered would re- quire military rule. We must frankly admit that when cerebrospinal meningitis has once become epidemic it cannot be stamped out by any known means of practical application. This does not mean that we should assume a supine attitude, for, even though the disease cannot be satisfactorily controlled, a certain number of secondary cases can be prevented. Every case and every sus- pected case should at once be reported to the health authorities and the patient isolated. The virus is contained especially in the discharges of the mouth and nose, and these secretions should be disinfected. The house should be placarded, visiting prohibited, and isolation practiced. These measures will help diminish the number of carriers. Personal prophylaxis consists in avoiding the infection so far as possible, and in the use of antiseptic gargles and nasal douches. When the disease is epidemic people should keep away from large public gath- erings, crowded street cars, avoid the use of public drinking cups, and the like. They should be advised to exercise more than the usual care as to personal cleanliness. The closing of the schools may, under cer- tain circumstances, be justified. Urotropin in moderate doses has been suggested as a possible, though quite unproven, prophylactic. While rigid quarantine is not, as a rule, effective in controlling this disease, localized outbreaks in institutions, military camps, or small towns may be kept from spreading by a strict system of isolation, even with a military cordon. Antimeningitis serum is useful in the treatment of the disease; it is not practical as a preventive. It must be introduced into the subdural 180 DISCHAEGES FEOM MOUTH AND NOSE space by lumbar puncture. The serum should be provided free of cost or at a minimum price by health authorities. Further, boards of health should provide laboratory facilities for the bacteriological diagnosis of the disease, and the recognition of carriers. Sophian and Black ^ recommend an active immunization induced by inoculating killed cultures of the meningococcus. The cultures are grown on 2 per cent, glucose agar, and after 18 hours' growth are washed off in distilled water, shaken for 20 minutes, heated at 50° C. for 1 hour, and tested for sterility. One million bacteria are injected at the first dose, 7 days later the same number, and 7 days later 3,000,- 000. The injection of the dead meningococcus confers a considerable immunity, and may prove to be a valuable measure for personal prophy- laxis. Chronic carriers should be inoculated with the killed cultures, and their sphere of activity should be restricted. Furthermore, they should be impressed with the danger to their fellowmen, and given careful in- structions concerning spitting, sneezing, coughing; the care of fomites, such as handkerchiefs, spoons, cups, etc.; and the importance of cleanli- ness of the teeth, mouth, nose, and throat. •J. A. M. A., Aug. 17, 1912, LIX, 7, p. 527. CHAPTER IV INSECT-BORNE DISEASES GENERAL CONSIDERATIONS The fact that disease may be transmitted through the bites of in- sects was suspected for years, but it was not until 1893 that it was demonstrated as a new principle by Theobald Smith in the case of Texas fever of cattle and the tick.^ Since then many diseases have been added to the list, which is constantly growing. We now know that some diseases are always transmitted through insects and others occasionally. A thorough comprehension of the subject is necessary for sanitarians and others in the fight against disease in all climates and in all places. It may be stated as a general law that, if a period of incubation in the insect is necessary, it indicates that the parasite probably be- longs to the animal kingdom and passes part of its life cycle within the insect. This constitutes the so-called extrinsic period of incubation. Malaria and yellow fever are examples of this class, which is spoken of as biological transmission. If, on the other hand, insects convey infection at once without a period of incubation in the insect, the trans- fer is a mechanical one; in this case the insect does not play the part of an intermediate host in the true biological sense, and there is no cycle of development of the parasite within the insect. These cases are almost all bacterial infections. It may be stated as a general rule that the insect hosts are not harmed by the parasites which they harbor and which are pathogenic for man. Thus, the malarial protozoon is pathogenic for man, but a saprophyte for the mosquito. The- same is true of yellow fever and the Stegomyia, Texas fever and the tick, plague and the flea, sleeping sickness and the tsetse fly, typhoid and the house fly, typhus fever and the louse, etc. The intermediate host in the zoological sense is that animal which harbors the asexual phase of the life cycle of the parasite; the definitive 'The other names associated with the early work upon insects and their re- lation to disease are: Manson, Finlay, Boss, Grassi, and the U. S. Army Com- mission — ^Eeed, Carroll, Lazear, and Agramonte. 14 181 182 INSECT-BOENB DISEASES host is the animal which harhors the sexual phase. Thus, in malaria man is the intermediate host, the mosquito the definitive host. In popular parlance, the insects are spoken of as the intermediate hosts in all cases. Insects transfer infections mechanically in a variety of ways. The mouth parts, legs, or outer surfaces of the body may be smeared with the virus, which is thus simply carried to the lips, fingers or food, and thus enter tiie susceptible individual ; or the virus may remain attached to the proboscis of a biting insect, thus transferring the infection very much as a hypodermic syringe would ; or the virus may be contained in the dejecta of the insect and be scratched or rubbed into the wound made by the bite; or the virus may be contained in the digestive tube or the body cavity and be released when the insect is crushed. Insect-borne infections are types of true endemic diseases, as they are necessarily limited in geographical distribution to the habitat of the insect host. As a rule, only one species, or at most a single genus, acts the part of a host for any particular infection, excepting in the mechanical transference of infection by insects. Malaria is confined to Anopheles, yellow fever to Stegomyia, Texas fever to the Margaropus annula- tus, sleeping sickness to the Glossina palpalis, etc. This is a ques- tion of specificity. The specific nature of some of these diseases may be due to the fact that the parasite is not pathogenic for other hosts. Thus, yellow fever and malaria cannot be given to any other animal than man, even though large amounts of the infected blood be inoculated. The disease may be specific, in the sense that it is confined, to one species, because the insect conveying the infection refuses to bite other than its own host. True specificity is found in all the cases of biological transference, whereas mechanical transference of infection may take place through widely separated genera. In some instances the virus is transmitted hereditarily through the insect from one molt to another, and even from one generation to the next. So far as known, however, hereditary transmission takes place only in those "insects" having an incomplete metamorphosis, such as the ticks. Brues suggests that the hereditary transmission of a virus is practically impossible in insects passing through complete metamorphosis, owing to the active phagocytosis during the pupal stage. Protozoa, bacteria, and even parasitic worms may be transferred by insects. The character of the disease cannot be predicated from the nature of the insect host. Thus, ticks convey Pirosoma and also spirochetes; flies convey trypanosomes, bacteria, the eggs of worms, and a variety of other infections; mosquitoes are concerned in the transmis- sion of the Plasmodium, a protozoon, filaria, a round worm, and a filterable virus (yellow fever). GENERAL CONSIDEEATIONS 18£ Insect-borne diseases may occur in great epidemics, as yellow fever, malaria, dengue, plague, relapsing fever, etc. When this occurs it means that the particular insect involved prevails in enormous num- bers in the epidemic area. Ticks and mites belong to the lower class of the Arachnida and are not, strictly speaking, insects (insecta), but are here considered in the same group for practical convenience. All the parasitic animals which live upon man and the higher ani- mals may act as go-betweens in the transportation of the microorgan- isms of disease. Parasites which live upon the sl^in are known as ectoparasites, in contradistinction to en- doparasites, which live within the body. The ectoparasites may be tem- porary parasites, as the mosquito ; or permanent, as the tick, which spends all but its earliest and last days attached to the skin of its host. Between these extremes there are para- sites spending more or less of their life attached to the host; thus, the bedbug and flea are temporary, whereas lice are permanent parasites. Many of the insect-borne diseases were formerly known as "place diseases." Thus, in yellow fever it was realized that the infection was not conveyed directly from man to man, but it was believed that the house or place became infected, and it was thought that the virus lived in the soil, upon the bedding, or on the clothing. This led to the notion that fomites or inanimate objects played an important role in the transference of disease. The early studies in bacteriology gave countenance to this view until our knowledge of the part played by in- sects and the importance of "contacts" has placed fomites in a subordi- nate and oftentimes negligible position. The prevention of the class of infections belonging to the insect- borne diseases depends upon a knowledge and thorough comprehension of three factors: (1) the disease, (2) the parasite, and (3) the insect. The suppression or control of the insect depends upon a thorough knowl- edge of its biology. Entomology, therefore, has become a vitally im- portant subject so far as preventive medicine is concerned. Without an acquaintance with the life history and habits of the insect host there Fig. 17. — ^A South Afkicau Blood-Suckino Fly (Pangonia), Illustrating Long Proboscis to Pierce Heavy Fur of Certain Animals. (Brues.) 184 INSECT-BORNE DISEASES will be economic loss, wasted energy, and disappointing results. The malaria mosquito is active at night and breeds in the swamps; the yellow fever mosquito is active by day and breeds about houses. Other mosquitoes have their own particular breeding and hiding places. The suppression of lice depends largely upon bodily cleanliness, the suppres- sion of the bedbug upon house cleanliness, the dangerous fleas come largely from association with other animals, the flies from manure and decomposing organic filth, the ticks from other animals and from the infested ground and woods. For the control of the insect-borne diseases it is not always neces- sary to exterminate the particular insect host. In fact, the extermina- tion of a particular species, much more a genus, is practically a biologic impossibility. A material reduction in the numbers of the insects in a particular area will often result in an elimination of the disease. The geographical distribution of the disease is always more lim- ited than the geographic distribution of the insect host. Anopheles exist in many places where there is little or no malaria. Stegomyia mosquitoes are numerous in the Philippines, but the infection has not yet been carried there. In the migration of insect-borne diseases it is usually the human host and not the insect that acts as the traveler. Insects, as a rule, do not go great distances of their own volition, and never over seas or from one country to another, unless taken in the conveyances of man or upon some higher animal. When yellow fever or malaria go from one country to another, the infection is translated in man. The infected mosquitoes are rarely transported, except occasionally upon wooden sailing vessels with water barrels that afford breeding places. An apparent exception to this statement is the case of plague. It is. the rat rather 'than man that spreads plague from land to land. In this case, however, the disease is primarily an infection of the rat, which carries the flea along and man is secondarily attacked. Another excep- tion is the house and stable fly, which are known to travel a mile or more upon the wing. An effective campaign against mosquitoes, flies, or other in- sect pests requires the expenditure of time and money. Further, it requires the assistance of the entomologist, the engineer, and the prac- tical administrator. When the campaign involves extensive drainage or filling-in operations, this calls for the services of an engineer who has specialized along these lines. To attack the problem without a complete knowledge obtained from a careful study of the habits and breeding places of the particular, species of insect will probably result in economic waste. Thus, in New Orleans, during the yellow fever campaign of 1905, much time and effort was saved by knowledge of the fact that the Stegomyia mosquitoes did not breed in the street gut- GENEEAL CONSIDEEATIONS 185 ters of New Orleans. The habits and habitat of some species may vary in difEerent localities, and a careful study of the local conditions is important to insure success. In the organization of a mosquito cam- paign the several branches of the work may be allotted to special divi- sions, each consisting of a foreman and crew. These men become skilled in their particular duties, and efficiency is thereby greatly pro- moted. One division should have charge of the oiling, another of the fumigation, another should seek to destroy the natural breeding places, another should attend to the screening, etc. In fly suppression one division should look after the storing and handling of horse manure, another to garbage and organic refuse, and so on. All the work must be centralized under the direction of one person with executive ability and a thorough understanding of the problem. The suppression of insects and household vermin is essentially a question of cleanliness. The most effective measures are those which strike at the breeding places, and these will be considered in detail un- der mosquitoes, flies, ticks, lice, fleas, and bedbugs. Next to the sup- pression of their breeding places, the most important measure in a household is to starve out these pests. Food must be so protected that insects, mice, and rats cannot gain access to it. Floors and other surfaces must he kept clean, so that they do not have the least film of organic dirt upon which insects feed. There should be no cracks or crevices to collect dust and dirt, which offer comfort for insect life. Cleanliness and incessant care must not only be exercised in the house- hold itself, particularly the kitchen, pantry, dining room, cellar, attic, and bathroom, but must also include the back yard and surroundings of the house. Old cans and broken bottles, rubbish, garbage, and general untidiness around the household afford breeding places, hiding places, or food for vermin. All the blood-sucking parasites must be regarded as dangerous. If they do not play the role of an intermediate host in the biological sense, they may occasionally transfer infections in a mechanical way, or the little wounds may allow the entrance of such infections as ery- sipelas, the pus cocci, anthrax, tetanus, and other microorganisms. Fur- ther, all blood-sucking parasites are potentially dangerous, in that new diseases may be established as the old ones must have been established at one time through the triple alliance of host, insect, and parasite. Science has demonstrated the danget from insects. Experience long ago decided that a healthy home must be free of insects and vermin of all kinds — it remains for the future to extend this kind of cleanliness to municipal housekeeping and rural sanitation. The principal insect-borne diseases, their causes, and the insect re- sponsible in each case are stated in the following table : DISEASE CAUSE INSECT MOSQUITOES Malabia (Laveran, 1880, the parasite) (Ronald Ross, 189S-8, relation to the mosquito) Plasmodium malaricB (Laveran) Plasmodium vivaz (Grassi & Feletti) Plasmodium falciparum (Welch) Plasmodium immaculatum (Grassi) Anophelea Yellow Fever (Reed, Carroll, Lazear and Agramonte, 1900-2) A filterable virus Stegomyia calopus FiLABiASis (Demarquay, 1863) (Manson — also James) Filaria hancrofti Culex fatigans, Anopheles niaer- rimus and others Dengue (Graham, 1903) (Ashburn and Craig, 1907) A filterable virus Culex fatigans DiSTOMiAsrs-BiLHARZiosis (Bilharz, 1851) (Katsurada, 1904) Schistosoma hmmatohium, Schistosoma japonicum Anopheles m^culipennis (?) FLIES Nagawa (Bruce, 1894) Trypanosoma hrucei Tsetse fly (a biting fly) — Glossina m,orsitans Sleeping Sickness (Button, 1901, and Todd) Trypanosoma gamhiense Tsetse fly — Glossina palpalis Pappataci Fever — 3-day fever (Adriatic) (Doerr, 1909) Phlebotomus pappatasii — a dip- terous biting gnat "Pink Ete" A little fly or midge belonging to the genus Hippelates PuBULENT Ophthalmia of Egypt, etc. Flies, et al. Poliomyelitis (Rosenau and Brues, 1912) A filterable virus coccal forms (Flexner and Noguchi, 1913) Stomoxys calcifrans — The stable fly Typhoid, 'Cholera, Dysentery, etc. Contagious ophthalmia, ery- sipelas, anthrax, glanders and other skin infections, smallpox and other exanthema, etc. Musca domestica and other flies (Mechanical transmission) TICKS Texas Fever (of cattle) (Th. Smith & Kilborne, 1893) Pyrosoma bigeminum, now Ba- besia bigemina Margaropus annulatus Rocky Mountain Spotted Fever (Ricketts, 1906) Dermacentor occidentalis (now venustus) African Tick Fever (Button, 1905) SpirochcBta duttoni Ornithodoros savignyi Relapsing Fever (Obermeier,1875) (Ph. Ross and Milne, 1904) Spirochceta obermeieri Ornithodoros moubata or Argas persicus PiROPLASMA CaNIS Piroplasma canis La Spirillose des Poules (Mar- choux & Salembeni, 1903) (Ticks are not true Insecta.) Spiroch(Bta gallinarum Argas miniatus BEDBUG Relapsing Fever (Obermeier,1873) SpirochcBta obermeieri Cimex leclularius, Ornithodoros moubata, Argas persicus and perhaps other biting insects, as fleas and lice Kala-azar Trypanosoma leishmanii Cimex lectularius Cimex rotundatus 186 INSECTICIDES 187 DISEASE CAUSE INSECT PlAGDE FLEA Bacillus pestis Loemopsylla cheopis and other fleas LOUSE Tyfsoid Fever (Nicolle, 1909) (Eicketts & Wilder, 1910) (Anderson & Goldberger, 1910) (?) Pediculus vestimenti Also, Pediculus capilis A number of other diseases are suspected; thus, barbiero fever (Conorhinits megistus) ; pellagra {SimuKum) ; hookworm {Musca domestica), etc. INSECTICIDES Practically all the germicidal agents are also insecticides. There are some exceptions to this statement, notably formaldehyde, which is one of our most potent germicides, but has little or no eflEect upon in- sect life in its gaseous state. The action of insecticides may be considered under three classes: (1) those that act as general protoplasmic poisons, such as strong acids or alkalies, hydrocyanic acid, sulphur dioxid, etc.; (2) those that suf- focate the insects, such as oily substances, and (3) those that act upon the nervous structures, such as chloroform, ether, and other general anesthetics. Another classification considers insecticides under four groups: (1) those used by contact in liquid form or in solution; (2) those used by contact in dry or powdered form; (3) those used by contact in vapor form; (4) those used by mixing with food and which are poisonous when ingested. Insects differ markedly in their power of resisting insecticides. Those with well-developed chitinous protection, such as bedbugs and roaches, are more difficult to kill than flies, fleas, and mosquitoes. The most practical of the insecticides for the destruction of the winged insects in an enclosed space are those that may be used in the gaseous state. Of these, sulphur dioxid, hydrocyanic acid gas, carbon bisulphid, or carbon tetrachlorid are most commonly employed and are most reliable. The uses and limitations of these and other insecticidal agents will now be considered in detail. Preparation of the Room for Fumigation. — It is more important to .tightly seal a r.oom in which insects are to be destroyed than where ...only a germicidal 'action of the gas is looked for. Insects may escape through minute openings, and they may hide in nooks and corners 188 INSECT-BOENE DISEASES where the gas permeates slowly and feebly, or may take cover imder the folds of crumpled paper or folded fabrics, and thus escape the in- secticidal action of the gas. Self-preservation tempts mosquitoes and other insects as well as rats and mice to seek the light when in the presence of an irritating gas. It is, therefore, convenient to darken the place to be treated, leaving one source of light. The dead vermin may then be readily collected about this place. Strips of paper should be pasted over doors and windows. Cracks and crevices may be caulked with tow- els, waste, or other suitable substance. Ventilators, f i r e- places, hot-air reg- isters, and all open- ings into the room must be covered, otherwise both the gas and the insects will escape. Closets and small doors should be opened and all the drawers, lockers, and similar places exposed in such a way that the gas may have free access to remote corners. Furniture should be moved away from the walls. Fabrics, paintings, instru- ments, bright metal work, or other ob- jects liable to injury may be removed or covered, especially when sulphur is used. The Relative Efficiency of Insecticides. — McClintock, Hamilton, and Lowe ^ have tested a number of insecticidal substances, the values of which are shown in Table 4, which gives a list of the substances tested and the species of insects used in the experiments, together with the quantity of each substance which, when properly transformed into vapors, was sufficient to kill the species indicated. The coefficient col- ^ Jour. Am. Fub. Health Assn., Vol. II, No. 4, Apr., 1911, p. 227. ♦fflSTmr""""^'^'^^' 1 f: LL FlQ. 18. — Example of Sealing Doors fob Pubpobe of Fumigation. INSECTICIDES 189 umn shows the inverse ratio between this quantity and 8 grams, the weight of sulphur which, when burned, kills the bedbug in the 800,000 c. c. of inclosed space. The efficient dilution of the vapors of any substance may be ob- tained from this coefficient by multiplying by 100,000. For example, if one wishes to use carbon disulphid, by consulting No. 28 in the table it is shown that 24 grams were required to kill bedbugs, while only 8 grams were required of sulphur. It is therefore only one-third as strong and its coefficient is 0.3-j-. Its efficient dilu- tion is 33,000. TABLE 4 INSECTICIDES Time of exposure — ^Varied as conditioos required. Column 1 — Quantity used to kill the specified insect. Column 2 — Coefficient of efficiency compared with the efficiency of sulphur dioxid on bedbugs Substance Bedbug Cockroach Housefly Clothes Moth Mosquito 1 Sulphur Dioxid as Sulphur. . . 2 Pyridin 3 Pyridin Bases (Merck) 4 Quinolin 5 Creosote Oil 6 CarboUc Acid 7 Naphthalene 8 Kerosene 9 Anilin Oil 10 Cedar Oil 11 Citronella OU 12 Cloves Oil 13 Peppermint Oil 14 Pennyroyal Oil 15 Australene 16 Turpentine (Oregon Fir) 17 Oil Pinus Palustris 18 Oil Turpentine IS Turpentine (Mich. Wood).. . . 20 Benzaldehyde 21 Nitrobenzol 22 Ammonia 28% 23 Alcohol, Ethyl 24 Alcohol, Methyl 25 Acetone 26 Chloroform 27 Ether (Ethyl Oxide) 28 Carbon Disulphid 29 Carbon Tetraohlorid 30 Chloretone 31 Camphor 32*Nicotin, 80% Sol 33 Hydrocyanic Acid, as Potas- sium Cyanid 34 Paraform 35tFormaldehyde 40% Sol 36 Stramonium Leaves 37 Sabadilla Seeds 38 Chrysanthemum Flowers .... 8 8 5 8 4 + 8 8 + 16 + 6.3 + 11.5 + 4 + 4 + 4 + 8 + 8 + 36 + 16 + 20 + 16-- 4- 8- 36- 80- 80- 40- 40- 4 4 4 8 4 + 16 + 6.3 + 11.6 4 + 4 + 4 + 8 + 8 + 36 + 16 + 20 + 24 + 4 + 8 36 + 80 + 80 + 40 + 40 + 24 40 4 + 8 + 25 6.3 8 + 54 + 10 8 + 80 + .0.3 0.2 2 1 4 1.3 1 0.1 0.8 0.1 36 40 + 4 + 8 25 6.3 8 + 54 + 10 8 + 80 + 2 2 2 1 2 1 1 0.5 1.3 0.7 2 2 2 1 1 0.2 0.5 0.4 0.3 2 1 0.2 0.1 0.1 0.2 0.2 0.2 0.2 2 1 4 1.3 1 0.1 0.8 0.1 3.2 2 1,6 2 8 2 4 + 6.3 2 4 4 3.2 36 + 4 20 16 2 1.6 20 + 80 + 80 + 40 + 16 + 15 + 4 40 + 4 4 6 2 4 16 + 10 + 16 2.6 2.5 4 5 4 1 4 2 1.3 1 4 4 2 2 2.5 0.2 2 0.4 0.5 4 5 0.4 0.1 0.1 0.2 0.5 0.5 2 0.2 2 2 20 4 2 0.5 0.8 0.5 3 2.6 1.6 1.6 2 1 8 4 4 6.3 2 4 2 4 + 4 8 16 + 4 20 16 2 1.6 36 + 80 + 80 + 40 + 16 + 2 40 + 4 4 25 1 8 16 + 10 + 16 + 4 3 5 5 4 8 1 2 2 1.3 4 2 4 2 2 1 0.5 2 0.4 0.5 4 5 0.2 0.1 0.1 0.2 0.5 3.2 1.6 2.5 5 8 4 1 4 + 4 1 1 1 2 1 2 8 2 10 10 2 8 2 2 8 8 8 4 8 4 1 4 0.8 1 1 20 80 80 + 14 + 16 + 4 0.2 2 2 40 8 1 0.5 0.8 0.5 2 4 40 1 2 1 2 1 8 + 4 4 1 20 0.2 8 4 100 40 8 1 2 2 8 The + sign after a number indicates that this quantity was the largest used and that it was insufficient. * Coefficient of nicotin based on 100% alkaloid. t Quantity of formaldehyde to be an efficient germicide is 13M =■ o. or a coefficient of 0.625. 190 INSECT-BOENE DISEASES The best methods of generating gases for fumigating piarposes are considered below. For further information concerning these substances, with special reference to their germicidal action, see Section XII.. To insure success the gas used to fumigate a room should be liber- ated in a large volume in a short time. If the gas is evolved slowly much of it will be lost before the room can become charged with a sufficient amount to kill the insects. The amount of gas and the time of exposure stated in each case are the minimum. When large, leaky, or irregularly shaped spaces are to be fumigated, the amount of gas should be increased and the time of exposure prolonged. It is also advisable to generate the fumes in as many different places as practicable, as this favors rapid diffu- sion. Sulphur. — Sulphur is one of the most valuable insecticides we pos- sess. It may be used either as a gas — SOj — or in its powdered form — flowers of sulphur. Sulphur dioxid is destructive to all forms of life. It will kill mosquitoes, flies, fleas, roaches, bedbugs, and all kinds of vermin, in- cluding rats and mice. While sulphur dioxid is one of the most de- pendable insecticides it is a rather feeble germicide. It is limited in practice on account of its destructive and corrosive action. This destructive action results from the sulphurous acid and sulphuric acid produced in the presence of moisture. Fortunately the dry gas is quite as poisonous to mosquitoes, flies, rats, mice, etc., as the moist gas. Dry sulphur dioxid, however, has absolutely no germicidal value. Dry sulphur dioxid does not tarnish metals, does not rot fabrics, and does not bleach pigments. Fumigation with SOj may, therefore, be done with little damage to property on dry days. Metal work, fabrics, aud pigments that cannot be removed from the room may be protected from the sulphur fumes by simple mechanical devices. Sulphur dioxid may be produced either by burning sulphur or by liberating liquefied sulphur dioxid. The methods of generating the gas will be found on page 997. One pound of sulphur burned for each thousand cubic feet of air space or two pounds of liquefied sul- phur dioxid and an exposure of two hours is sufficient to kill mos- quitoes, flies, and other insects in a small tight space. Three to four hours are ample for rats and mice. If the space is large or leaky the amount of gas should be increased and the time of exposure prolonged. Sulphur dioxid has surprising power of penetration through clothing and fabrics. In very dilute proportions it will in one hour's time kill mosquitoes even when hidden in eight layers of toweling. It has ab- solutely no power of penetration when used as a germicide. This sub- stance, which has so long been disparaged as a disinfectant because it fails to kill spores and many spore-free bacteria under certain condi- INSECTICIDES 191 tions, must now be considered as holding first rank as an insecticide. For consideration of sulphur dioxid as a germicide see page 997. Flowees of Sulphur. — Sulphur in its dry, powdered state is use- ful against a number of parasites. In this form, however, it has little use as an insecticide in preventive medicine, not being efficacious against bedbugs, ants, roaches, or fleas. It may be applied in several ways, the simplest of which is to sprinkle the dry sulphur about the places where insects are found. Flowers of sulphur may also be combined advantageously with other insecticides, such as kerosene emulsion, resin wash, or soap wash. It should first be mixed into a paste and then added to the spray tank in the proportion of about 1 or 2 pounds to 50 gallons. It is particu- larly efficacious for the destruction of the mites and rust of plants and fruits. Sulphur in the form of an ointment is particularly obnoxious to ticks and other ectoparasites. The itch-mite (Sarcoptes scabiei) is very susceptible to the flowers . of sulphur, which is, therefore, one of the ingredients of almost all ointments used in this skin affection. Sulphur dips are used to destroy the mites on domestic animals. These dips ordinarily contain 1 part of lime to 3 parts of sulphur or tobacco. It is common experience that, while these sulphur dips may be depended upon to destroy the mites, they do not destroy the eggs, hence the treatment should be repeated in about 10 days, which per- mits time for the eggs to hatch and develop into adults. Formaldehyde. — Formaldehyde, while holding the front rank as a germicide, is a feeble insecticide. The gas seems to have no effect whatever upon roaches, bedbugs, and insects of this class even after prolonged exposure to very high percentages. As a differential poison formaldehyde gas is a very remarkable substance. It destroys bacteria almost instantly, but, while it is irritating to the higher forms of ani- mal life, it is not very toxic. I have repeatedly found that roaches and other insects with strong chitinous protection seem unharmed after 12 hours' exposure to formaldehyde gas in very strong atmospheres of the gas, in air-tight disinfecting chambers. Mosquitoes may live in a weak atmosphere of the gas over night. It will kill them, however, if the gas is brought in direct contact with them in the strength and time prescribed for bacterial disinfection. When a weak insecticidal gas is used it is much more difficult to obtain direct contact between the gas and the insects than between the gas and germs, because the sense of self-preservation aids the for- mer in escaping from the effects of the irritating substance. Mos- quitoes and other insects hide in the folds of towels, bed clothing, hangings, fabrics, and out-of-the-way places where the formaldehyde gas does not permeate in sufficient strength to kill them. The gas is 193 INSECT-BOENE DISEASES polymerized and deposited as paraform on the surface of fabrics which prevent its penetration, and large quantities are lost by being absorbed by the organic matter of woolen fabrics. Mosquitoes have a lively in- stinct in finding cracks or chinks where fresh air may enter a room or other places where the gas is so diluted that they escape destruc- tion. Therefore, formaldehyde gas, as well as other culicides, cannot be trusted to kill all the mosquitoes in a room which cannot be tightly sealed. On account of its feeble action, formaldehyde is not recom- mended as reliable. For the best methods of evolving formaldehyde gas, the quantities to be used, and other details of the process, see page 993. Formaldehyde gas in watery solution, known as formalin, is use- ful for the destruction of flies. Small quantities of dilute formalin (4 per cent.) placed in saucers about the room attract flies. They drink the fluid, which soon kills them. Pyrethrum. — Pyrethrum is a popular and much used insecticide be- cause it is comparatively cheap and non-poisonous to man and the higher animals. It is also non-corrosive, but unfortunately it is not very powerful for the destruction of roaches, ants, bedbugs, flies, fleas, mosquitoes, etc. It has no germicidal action. Pyrethrum, also sold under the names of Buhach or Persian insect powder, or simply "insect powder," is the flowers of the Chrysantliemum roseum and the Chrysanthemum carneum, both hardy perennials and resembling camomile in appearance. According to Kalbrunner, 4 grains of the pure powder sprinkled on a fly in a vial should stupefy it in one minute, and kill it in 2 or 3 minutes. It acts on insects exter- nally through their breathing pores. When brought in direct con- tact with them it is fatal to many forms of biting and sucking in- sects, such as roaches, flies, and ants. It may be used either as a dry powder or by its burning fumes. As a dry powder it may be used pure or mixed with flour, in which form it should be puffed about the room, especially into cracks. When pyrethrum powder is ignited it smolders, giving off fumes which stun, but do not always kill, mosquitoes.'- It is not, therefore, a dependable insecticide. This uncertainty and the price of pyrethrum restrict its field of usefulness. Pyrethrum fumes do not corrode metals or act injuriously upon fabrics and pigments. However, a slight brown deposit is occasionally left on exposed surfaces which may stain linen a yellowish color. This deposit or stain is readily washed out, or soon fades. Pyrethrum powder has been used very much in those cases where sulphur is prohibited on account of the danger of damage to paintings, ^ Tobacco smoke and other substances which produce dense fumes, particu- larly those containing pyroligneous products, will kill mosquitoes. INSECTICIDES 193 fabrics, tapestries, metal work, musical instruments, upholstered furni- ture, and the like. It is used in the proportion of 2 pounds per 1,000 cubic feet of air space, the exposure being for not less than 4 hours. As its insecticidal effect is uncertain, it is necessary carefully to sweep up and burn all the mosquitoes that have been stunned and are ap- parently dead after the fumigation. Most of these mosquitoes will be found on the window sill or on the floor close to the window, where they are attracted by the light in their efforts to iind an exit to es- cape the fumes. Advantage should be taken of this tendency of the mosquito to seek the light by darkening all but one window. Sheets of paper containing some sticky preparation may be placed upon the floor and upon the window sill in order to catch the mos- quitoes. A satisfactory adhesive preparation may be made by dissolv- ing, by the aid of heat, 65 parts of colophony resin in 35 parts of castor oil. This simplifies the collection and disposal of the insects. Pyrethrum powder should be distributed in pots or pans and set on fire with a little alcohol, which should first be sprinkled over it. The quantity apportioned to any one pot or pan should not exceed 1% inches in depth, if the exposure is to be for 4 hours. The pots and pans should be set on bricks to prevent scorching the floor. Much of the pyrethrum upon the market is impure, which further weakens what is a feeble insecticide at best. Phenol-camphor (Mim's CuUcide). — Camphophenique or phenol- camphor is prepared by rubbing up equal weights of phenol crystals and camphor. It may be more conveniently prepared by first liquefying the phenol by gentle heat and then pouring it over the camphor.' The cam- phor and phenol combine to form a new chemical compound, which re- mains fluid at ordinary temperatures. This preparation was first used on a considerable scale during the yellow fever epidemic in New Or- leans toward the close of 1905 at the suggestion of Mr. Mim, the city chemist. At this time I took the opportunity of making a number of tests with Dr. Metz concerning the culicidal value of this substance. The effect of the fumes on mosquitoes was later studied by Berry and Francis, '\^^len phenol-camphor is moderately heated it gives off dense fumes, which rise rapidly and diffuse slowly, and after 30 to 60 min- utes, depending upon the amount employed and the temperature of the air, the fumes condense and are deposited as a slight moisture on all exposed surfaces. As a culicide phenol-camphor may be compared to pyrethrum; the fumes stun the mosquitoes, but do not invariably kill them. The fumes are somewhat irritating to the mucous membranes, especially the eyes; they may cause dizziness, headache, cloudy urine, and other mild symptoms of phenol poisoning in susceptible individuals much exposed to their inhalation. The fumes of phenol-camphor do not tarnish metals, rot fabrics, or blea,ch pigments. They, however, 194 INSECT-BOENE DISEASES have the disagreeable property of softening the varnish of surfaces on ■which they condense. On account of its slight power of diffusion, rela- tively high cost, and uncertainty of action, it cannot take the place of sulphur except in the parlor, pilot house, and other compartments where sulphur is prohibited on account of the damage it produces. Compared with pyrethrum, phenol-camphor is less expensive, more certain, and not so objectionable to the housekeeper. Its use involves a little more care and intelligence than that required for the simple burning of py- rethrum. If it is overheated it will take fire, and no culicidal action is produced. Goldberger concludes that, for use on a large scale, as in times of epidemics, in the hands of trained fumigators, phenol-cam- phor is, on the whole, to be preferred to pyrethrum, being more easily transportable on account of the small bulk required, and because the fumes condense quickly and the room may, if desired, be entered in an hour and the apparatus removed, thus making it possible to fumigate a larger number of rooms in a given time with less labor than in the case of either sulphur or pyrethrum. Phenol-camphor is used in the proportion of 4 ounces to every thou- sand cubic feet of air space, and with an exposure of 2 hours. In this proportion and time the film of condensation is slight and is rapidly dis- sipated after the doors and windows are opened. The preparation of the room is the same as that described above. The phenol-camphor ap- portioned to the room to be fumigated should be distributed in agate- ware basins, not more than 8 to 10 ounces to any one basin. Each basin is set over an alcohol lamp at such an elevation and in such a manner aff will permit a rapid evolution of the fumes. Care must be taken not to heat the basin so quickly as to cause the liquid to become overheated and take fire. This point must first be determined experi- mentally for each' type of lamp used. One of the small brass alcohol vapor lamps to be found on the market serves excellently. As a safe- guard against accidents the lamp should stand in a pan containing about one-half inch of water. The basin containing the phenol-camphor may be set upon a section of galvanized iron stove-pipe, at one end of which sectors are cut out so as to form legs of a length equal to the height of the lamp ; just below the upper margin of the pipe a series of holes are punched so as to provide for draft. The stove-pipe should be of such a length as to support the basin containing the phenol-camphor about 10 inches above the flame. This ingenious and simple device, suggested by Berry and Francis, acts as a chimney, protects the flame, is relatively cheap, and has proven satisfactory. Hydrocyanic Acid Gas. — Hydrocyanic acid gas is extremely poison- ous to all forms of life. It kills roaches, bedbugs, mosquitoes, fleas, flies, rats, mice, and other vermin with great certainty and very quickly. It is much less poisonous to the higher forms of vegetable life, al- INSECTICIDES 195 though it has a certain amount of germicidal power. Hydrocyanic acid gas is much used in greenhouses for the destruction of insect pests and for scale and other parasites of fruit trees. The gas has a distinct place in the disinfection of granaries, stables, ships, barns, outhouses, railroad cars, and other uninhabited structures infested with vermin. It is also extensively used in flouring mills against weevils, in rail- road cars against bedbugs, and in tobacco warehouses against insects in general. It should be used in the household only with the greatest precaution, as the least carelessness with it would probably mean the loss of human life. It has the marked advantage that it does not harm metals, fabrics, or pigments, and may be used in the most expensive drawing rooms. Hydrocyanic acid gas is lighter than air and has an agreeable aromatic odor quite familiar in the flavoring essence of bitter almonds. The best method of generating it for the purpose of fumigation is by the action of dilute sulphuric acid upon potassium cyanid, in the fol- lowing proportions: Potassium cyanid 1.0 part Sulphuric acid 1.5 parts Water 2.25 parts The first step is to dilute the acid, which is done by adding the acid to water in a vitrified clay jar or receptacle capable of withstand- ing the heat. The whole amount of cyanid must be put into the acid at once. As the evolution of the gas is very rapid, the operator should be ready to leave the spot immediately. As pointed out by Fulton, it is convenient to tie the cyanid up in a bag made of cheese cloth or tissue paper, which is lowered into the acid by a cord passing outside of the room. The amount of gas used for plant fumigation, expressed in terms of cyanid, is about 1 ounce per 100 cubic feet ; about the same quantity is effective as an insecticide in rooms and confined spaces. Hydrocyanic acid gas is quite as effective as sulphur dioxid, is not destructive, is reasonably cheap, and is certain in its action, but its poisonous nature is such a serious drawback that it has a limited place as an insecticide in the disinfection of houses. Bisulphid of Carbon. — Bisulphid of carbon (CSj) is a very efficient insecticide, but a dangerous one, on account of its infiammable and ex- plosive nature. It quickly kills mosquitoes, roaches, flies, ants, and insects of all kinds, as well as rats, mice, and squirrels. When pure it is a mobile, colorless liquid with an agreeable ethereal odor, but often it has a more or less fetid odor from the presence of other volatile compounds. The liquid must be kept in well-stoppered bottles in a cool place, and away from the light and fire. It evaporates rapidly at ordi- 196 mSECT-BOENE DISEASES nary temperatures, so that in using this substance in a confined space it is sufficient to pour it into open pans. Carbon bisulphid is very in- flammable — more so than ether— and burns with a pale blue flame yielding sulphur dioxid and carbon dioxid or monoxid. In its use every precaution must be taken to see that there is no fire, lighted cigar, etc., in or about the field of operation. On account of its poison- ous nature, if used in a house or other inhabited structure, the rooms must be thoroughly aired after its use. According to Hinds, shallow tin pans or plates make good evaporat- ing dishes for carbon bisulphid. The larger the evaporating area the better. About one square foot of evaporating surface is used to every 25 square feet of floor area, and one-half to one pound of the liquid carbon bisulphid is used for each square foot of evaporating surface. These figures, of course, are only suggestive and approximate. The pans should be placed as high in the room as possible, since the vapor is so heavy that it settles rapidly.. Care should be taken when placing the pans to see that they are nearly level so as to hold the liquid, though ordinarily no particular harm will be done if some of it is spilled. It should not be found necessary to lose time in adjusting such things after the operation has begun. Carbon bisulphid is being extensively used in California in the plague campaign. A piece of waste the size of an orange is saturated with the liquid and the wet ball placed in the mouth of the squirrel hole. Wet clay is then stamped into the warren so that the gas which is generating may have no opportunity to escape. All of the holes of the burrows are treated in this way. In some instances the ball is placed deeply in the hole and then ignited. This is more or less dan- gerous, as an explosion 'Occurs, and, while the gas is thus disseminated to all parts of the warren, its action only covers a limited period of time, and is, therefore, not as certain as simply allowing the carbon bisulphid to evaporate. It not only kills the squirrels, but also the fleas on them. Carbon tetrachlorid may be used in place of carbon bisulphid. It is just as poisonous but neither inflammable nor explosive. Petroleum. — ^Petroleum, kerosene, or coal oil is a very valuable in- secticide, but of limited application, as it must be used in liquid form. As a remedy for mosquitoes it is applied in the proportion of about 1 ounce to 15 square feet of water surface. It should form a uniform film over the surface, and will then destroy the larvae and pupse of the mosquito and the adult females coming to the water to lay their eggs. The oil must be renewed every week or two, depending upon the temperature and other conditions. A light grade of fuel oil is best for this purpose (see page 203). Petroleum is also useful against roaches, bedbugs, fleas, lice, and other insect vermin when used by direct application or by spraying, INSECTICIDES 197 either in the form of the pure oil or as an emulsion. Petroleum is very efficient against fleas. Frequent application to the floor or other places will keep away ants, and by direct application to the breeding, feeding, and traveling places it is a useful remedy against household vermin in general. By direct application to the head or other parts affected, coal oil is the cheapest' and most effective remedy for lice. Emulsion of crude petroleum for application to the skin of animals or to trees, or other plants, or for general insecticidal purposes is made from the formula of T. M. Price: Crude petroleum 2 gallons Water % gallon Hard soap % pound Dissolve the soap in the water with the aid of heat. To this add the crude petroleum; mix with a spray pump or shake vigorously and dilute with the desired amount of water. The emulsion of crude petro- leum made according to this modified formula remains fiuid, and can be easily poured. It will stand indefinitely without any tendency toward separation of the oil and water, and can be diluted in any pro- portion with cold soft water. Arsenic. — The arsenical compounds, according to Marlatt,^ have sup- planted practically all other substances as a food poison for biting in- sects. The two arsenicals in most common use obtainable everywhere are arsenate of lead and Paris green. Scheele's green and arsenite of copper are less known and less easily obtainable, but in some respects are better than Paris green. The use of powdered white arsenic is not recommended on account of its corrosive action, as well as the fact that it is apt to be mistaken for harmless substances. The arsenical poisons may be applied in one of three ways: (1) in suspension, as poisoned waters, mainly in the form of sprays; (2) as a dry powder blown or dusted about the infested areas; or (3) as poisoned bait. It must be remembered that the arsenicals are very poisonous, and should be so labeled, and care taken to prevent accidents. Paeis geeen is a definite chemical compound of arsenic, copper, and acetic acid (acetoarsenite of copper),, and should have a nearly uniform composition. It is rather a coarse powder, or, more properly speaking, crystal, and settles rapidly in water, which is its greatest fault so far as the making of suspensions of this substance is concerned. The cost of Paris green is about 20 cents per pound. Scheele's geeen is similar to Paris green in color and differs from it only in lacking acetic acid; in other words, it is simply arsenite of ^Farmers' Bulletin No. 19, V. S. Dept. of Agriculture. 15 198 INSECT-BOENE DISEASES coiDper. It is a finer powder than Paris green, and, therefore, is more easily kept in suspension, and has the additional advantage of costing only half as m"uch per pound. Aesenite of lead is prepared by combining, approximately, 3 parts of the arsenite of soda with 7 parts of the acetate of lead (white sugar of lead) in water. These substances, when pulverized, unite readily and form a white precipitate, which is more easily kept suspended in water than any of the other arsenical poisons. Bought at wholesale, the acetate of lead costs about 71/2 cents a pound, and the arsenite of soda costs about 7 cents a pound. Its use is advised where excessive strengths are not desirable, and upon delicate plants, where otherwise scalding is likely to result. An average of one pound of either Paris green or Scheele's green, or London purple to 150 gallons of water is a good strength for general purposes in using the wet method. The powder should first be made up into a thin paste in a small quantity of water, and, if the suspen- sion is to be used upon plants, vegetables, or about foliage, an equal amount of quicklime should be added to take up the free arsenic and remove or lessen the danger of scalding. For the distribution of dry poison the arsenieals are diluted with 10 parts of fiour, lime, or dry gypsum. The following mixtures are used in the form of sprays, to destroy insects and fungi upon plants.^ The arsenate of lead mixture has been much used in Massachusetts with success against the gipsy moth and other destructive insects upon trees and plants. These mixtures are equally useful as insecticides wherever sprays or local applications are practicable. ARSENATE OF LEAD Arsenate of soda (5 per cent, strength), 4 ounces. Acetate of lead, 11 ounces. Water, 100 gallons. Put the arsenate of soda in 2 quarts of water in a wooden pail, and the acetate of lead in four quarts of water in another wooden pail. When both are dissolved, mix with the rest of the water. Warm water in the pails will hasten the process. For the elm-leaf beetle use 10 instead of 100 gallons of water. A number of ready-made arsenates of lead are now on the market, and, except when very large amounts are needed, it will probably prove cheaper to buy the prepared material than to make it. With this ready-made material take 3 pounds to 50 gallons of water for codling moth, and 5 pounds to 50 gallons to the elm-leaf beetle and on potatoes. Trom Bulletin No. US, April, 1908, of the Massachusetts Agricultural Experiment Station by Stone and Eerald. INSECTICIDES 199 AESENITE OF LIMB White arsenic, 2 pounds. Sal-soda, 8 pounds. Water, 2 gallons. Boil till the arsenic all dissolves — about 45 minutes. Make up the water lost by boiling and place in an earthen dish. For use take one pint of this stock, 2 pounds freshly slaked lime, and 45 gallons water, and spray. KEROSENE EMULSION Hard soap, shaved fine, I/2 pound.. Water, 1 gallon. Kerosene, 2 gallons. Dissolve the soap in the water, which should be boiling; remove from the fire and pour it into the kerosene while hot. Churn this with a spray pump till it changes to a creamy, then to a soft, butter-like, mass. Keep this as a stock, using one part in nine of water for soft- bodied insects, such as plant lice, or stronger in certain cases. EESIN-LIME MIXTURE Pulverized resin, 5, pounds. Concentrated lye, 1 pound. Fish or other animal oil, 1 pint. Water, 5 gallons. Place the oil, resin and one gallon of hot water in an iron kettle and heat till the resin softens; then add the lye and stir thoroughly; now add 4 gallons of hot water and boil till a little will mix with cold water and give a clear, amber-colored liquid; add water to make up 5 gallons. Keep this as a stock solution. For use take: Stock solution, 1 gallon. Water, 16 gallons. Milk of lime, 3 gallons. Paris green, ^ pound. BORDEAUX MIXTURE Copper sulphate (blue vitriol), 4 pounds. Lime (unslaked), 4 pounds. Water, 25 to 50 gallons. Dissolve the copper in hot or cold water, using a wood or earthen vessel. Slake the lime in a tub, adding the water cautiously and only 200 INSECT-BORNE DISEASES in sufficient amount to insure thorough slalcing. After thoroughly slaking, more water can be added and stirred in until it has the con- sistency of thick cream. When both are cold, dilute each to the re- quired strength and pour both together in a separate receptacle and thoroughly mix. Before using, strain through a fine mesh sieve or a gunny cloth ; the mixture is then ready for use. If the amount of lime in the Bordeaux mixture is insufficient there is danger of burning tender foliage. In order to obviate this, the mix- ture can be tested with a knife blade or with ferrocyanid of potassium (1 oz. to 5 or 6 oz. of water). If the amount of the lime is insufficient, copper will be deposited on the knife blade, while a deep brownish-red color will be imparted to the mixture when ferrocyanid of potassium is added. Lime should be added until neither reaction occurs. A slight excess of lime, however, is desirable, and it is seldom one has to apply these tests. The Bordeaux mixture is a good fungicide, but is less useful as an insecticide. MOSQUITOES Mosquitoes differ markedly in their habits. Some species may be classed as domestic animals because they are commonly or almost ex- clusively found in or close to human habitations. This is notably the ease with Stegomyia calopus, the yellow fever mosquito ; Gulex pungens, the intermediary for Filaria iancroftii (filariasis) ; and Culex fatigans, the carrier of dengue fever. The sylvan or wild mosquitoes, of which the Culex sollicitans, the common salt marsh mosquito of our Atlantic coast, is a well-known example, are seldom met with in human habita- tions. A third or semi-domestic class may be encountered either in or near houses, or in fields or swamps. This class includes the malarial mosquitoes belonging to the genus Anopheles. The adult mosquito may be carried to considerable distances by winds; but of its own volition it does not ordinarily travel outside of a radius of half a mile from its breeding place. Most species do not fly nearly so far. This means that the destruction of all breeding places within a comparatively small radius of a habitation will rid it of all but those mosquitoes which are blown in by the winds from more or less distant marshes, or which are brought in the vessels and vehicles of trade and travel. Life History and Habits. — Mosquitoes pass through four stages: (1) the egg or embryo, (2) the larva, (3) the pupa, and (4) the imago or adult winged insect. The egg, larval, and pupal stages are aquatic. Mosquitoes never breed in damp grass, weeds, or bushes, as is popularly supposed, but the winged insects frequently rest and hide in vegeta- MOSQUITOES 201 tion. The different species of mosquitoes not only differ markedly in their habits, but differ considerably in the character of their breeding places. The domestic species, such as the yellow fever mosquito and Culex pungenSj may be found breeding in any collection of water in or about houses. Thus, they have been found in discarded tin cans, bottles, and broken crockery on the garbage heap; in buckets, tubs, bar- rels, cisterns, and wells; in baptismal fonts; in flower pots and sagging roof gutters; in street and roadside puddles, gutters, and ditches; in cesspools and sewers. The semi-domestic mosquitoes, to which the malarial-bearing insects belong, may occasionally be found breeding in tin cans, barrels, hoof prints, post holes, and hollows in trees or tree stumps, but they usually prefer grass-bordered pools, slowly flowing ditches, the margins of lakes and streams, even such as are stocked with fish, provided the margins are shallow or are more or less choked with reeds and water plants so that the fish cannot reach them. The sylvan or wild mosquitoes select breeding places of much the same character as do the semi-domestic species, with which they are not infrequently found associated, except that such breeding places are more or less remote from human habita- tions, in woods, swamps, and fresh or salt (brackish) coastal marshes. Male mosquitoes are vegetarians. The females of many -spe- cies have developed a taste for blood, and, indeed, blood has become indispensable to nearly all for the full development of their eggs. This is the case with Stegomyia calopus. Eemembering how all-important the generative instinct is, we can now well understand why the yellow fever mosquito, for example, will, when disturbed, return again and again in an endeavor to obtain her fill of this life-giving fluid. The mosquito lays her eggs upon the surface of the water, and these, depending upon the species, either fioat separately on their sides [Stegomyia calopus and Anopheles), or adhere together in irregular, raft-like masses (Culex). In a day or two, under ordinary conditions, the eggs hatch out into larvae or "wiggle-tails." Although the larva is an aquatic animal, it is a true air-breather. The larva of Anopheles ordinarily rests and feeds at the surface, where it lies in an almost horizontal position, its tail and dorsal bristles touching the surface film, while it breathes through a breathing siphon, which is very short and insignificant in appearance. The larvffi of the other species move about more or less, actively searching for food, but at intervals of a minute or two they may be seen to come to the surface for air, where they hang, head down, at- tached by their more or less prominent conical breathing tubes to the surface film. The mosquito remains in the larval stage about a week and is then transformed into a comma-shaped creature known as the pupa. 202 INSECT-BOENE DISEASES The pupa has no mouth and does not feed. It remains quietly at the surface except when "disturbed. It breathes through a pair of trum- pet-shaped tubes, which project from the dorsum of the thorax. The pupal stage usually lasts two or three days, and is terminated by the emergence of the adult winged insect (imago) from its pupal case through a rent in the region of the breathing tubes. The time from the laying of the egg to the winged insect may, there- fore, be as short as nine days. The time depends upon the tempera- ture and the abundance of the food supply. Warmth favors and cold retards; therefore, mosquitoes are most abundant during the summer, late spring, and early fall months in our climate. In the tropics the wild species become more abundant during the wet season. The way in which mosquitoes manage to pass through the rigors of the winter probably varies with the different species. Some, like the malarial Anopheles, hide in sheltered cellars or dark nooks, or hibernate in other out-of-the-way places. Other species survive through the power of the larva or egg to resist cold, for the larvae or eggs of some species will hatch even after they have been frozen. THE DESTRUCTION OF MOSQUITOES The life of a mosquito may be divided into an aquatic and an aerial stage, the former including the egg, larva, and pupa, and the latter the adult winged insect. Accordingly, the measures aimed at the de- struction of the mosquito naturally fall into two classes: (a) those di- rected against the larva and pupa — ^the aquatic stages — and (b) those directed against the winged insect. For the extermination of mosquitoes the most effective measures are those which aim to destroy their breeding places, and thus prevent their multiplication. For the best results both individual and com- miinal effort are necessary, but the importance of individual effort alone cannot be too much emphasized. The individual, by attacking the prob- lem on his own premises, grounds, or estate, can not only do much to rid his own immediate neighborhood of mosquitoes, and thereby in- crease his own comfort and guard against disease, but the example thus set will perhaps stimulate his less enterprising neighbor. To insure success it is important to know the habits and breeding places of the particular species that it is desired to suppress. Natural Breeding Places. — Natural collections of water which may serve as breeding places are best dealt with by filling in or by draining. In this way they are disposed of once for all. For filling, inorganic refuse, such as cinders and ashes, may be employed, or sufficient earth may be dug from a nearby knoll or hill, care being observed that in so doing a depression capable of holding water is not made. Low marshy MOSQUITOES 203 lands adjacent to rivers, lakes, or the sea may be tilled by pumping silt or sand. When filling is not practicable, good and permanent • results may be obtained by drainage. As a rule, the draining of ponds, pools, or marshes is the simpler and cheaper method. By the draining of marshes is meant the draining of the pools of stagnant water, or in the case of coastal marshes the draining of the stagnant Ashless pools that are be- yond the reach of the ordinary tides; it does not necessarily include the draining of the water-soaked soil itself. The underdraining of wide acreages of our arable land in the Middle West has been very effective in suppressing the malarial mosquito. Marshy lands may be drained simply by means of ditches. These must be dug of sufficient depth to completely empty the pools under treatment and have sufficient fall to prevent stagnation in the course of the ditch itself. Where a sufficient fall is not obtainable fishless pools may be connected with those con- taining fish or with a neighboring stream, so that the fish may freely enter. Mosquito breeding places in the pools in coastal marshes may be suppressed by connecting them with tide water, so that they may be freely scoured by the daily tides. Ditches should have straight sides and must be inspected at frequent intervals, and care must be taken to see that they do not become choked. Fish are among the most effective of the natural enemies of the mosquito. The fish may be admitted to ponds and pools in the man- ner just described, or the ponds, pools, ornamental lakes, and fountains may be directly stocked with minnows or gold fish. The margins of pools, rivers, and other bodies of water must be kept free of reeds and water plants, so as to permit the fish to reach the edges — a favorite breeding place for mosquitoes. One of the very best means of clear- ing the land of the numerous small natural collections of water is to place it under cultivation. When radical measures, such as filling in or draining, are not prac- ticable, resort may then be had to coal oil. Coal oil upon the surface of the water acts mainly by suffocating the larvae and pupje. A light quality of oil should be used, and it may be poured upon the surface from an ordinary sprinkling pot, or the surface may be sprayed with a hose. Along the banks of ponds, lakes, and slowly moving streams with shallow margins containing vegetation, which offer favorite breed- ing places for the mosquito, the oil may be applied with a mop. This practice is laborious, but effective. Sufficient oil should be used to cover the entire surface with a thin film. As the oil is volatile, it may disappear within a few days. Furthermore, the film, which should be intact to be effective, may be broken by winds. A strong wind will blow all of the oil to one side, thereby entirely defeating the object desired. It is, therefore, important to repeat the oiling regularly at intervals 204 INSECT-BOENE DISEASES of not more than one week, and as often in addition as necessary. Oiling, though fairly effective when properly carried out, is only a tem- porary expedient, and in the end is rather expensive. (See also page 206.) No body of water is too small for a mosquito nursery. They breed in puddles by the roadside; in water that accumulates in furrows in gardens or fields, especially in claj'ey soil; in street gutters and house gutters; in holes in rocks; in hollows in trees, and anywhere that half a pint of water is allowed to stand. Artificial Breeding Places. — The permanent elimination of artificial breeding places for mosquitoes in a city depends first of all upon provid- ing a good quality and sufficient quantity of portable water by means of a modern closed system. This will permanently do away with the- neces- sity of cisterns, barrels, and tubs for the storage of water about the premises. When domestic storage is a necessity, care must be taken to prevent the mosquito from gaining access to the water. The water bar- rels should be provided with tightly fitting covers. Burlap, sheeting, or several thicknesses of cheese-cloth, or, better, wire screening held in place by a well-fitting hoop, serve this purpose very well. "Wooden covers are unsatisfactory, for they rarely fit accurately enough to keep out the mosquito, and this defect is enhanced by the warping of the wood, which usually makes an old cover worse than useless. More satisfactory than the wooden cover is one made of light galvanized sheet iron, the central portion of which may be made of wire gauze. The rim of the barrel should be trimmed to remove any irregularities that might prevent the cover from fitting evenly all around. Whatever the form of the cover employed, it should not be removed except for cleaning or refilling the barrel. The water should be drawn from a spigot. Where the water is very turbid and must undergo sedimentation before being used, several barrels should be provided for its storage and the water used from each barrel in turn. In such a case the spigot should be placed about a foot from the bottom, so that the sediment need not be disturbed as the water is drawn ofE for use. Wells should be pro- vided with tight covers and the water drawn by pumps. Cisterns and tanks should also be provided witli accurately fittmg covers, and should be inspected frequently for seams and cracks result- ing from warping and shrinking of the wood. To guard against this loophole, wire gauze should be used to screen the joint between the tank and its cover. The gauze should include about one foot of the tank and overlap well upon the cover. The inlet to the tank or cistern should be provided with a cap of copper meshed wire gauze which may be protected by another and coarser meshed cap of stout wire, to pre- vent its choking with leaves, etc. As an additional precaution, the in- let pipe should be long and extend well below the water level. In cases of emergency, as in times of epidemics of yellow fever or dengue, where MOSQUITOES 205 the permanent measures for preventing mosquito breeding have been neglected^ the surface of the vrater in barrels, tanks, and cisterns may be covered with some neutral non-volatile oil which does not impart a taste to the water. Cesspools and privy vaults should be done away with and replaced with dry earth closets or a water carriage cistern. AVhere this has not been done they may be frequently and copiously oiled. Among the artificial breeding places for mosquitoes may be men- tioned chicken-pens in poultry yards; water cups on the frames of grindstones; baptismal fonts; tin cans or broken bottles in back yards; the catch basins of sewers; the water that stands in sagging house gut- ters; flower-pots, and similar places. Screening. — ilosquito screens are the obvious and most effective single measure for personal prophylaxis where disease-carrying mosqui- toes exist. In order to be effective the screening must be intelligently carried out with careful attention to details. The screen itself must be sufficiently close to keep out the mosquitoes. Some of them are able to squeeze through surprisingly narrow chinks. I was able to demon- strate, in the experimental work at Vera Cruz, that the stegomyia mos- quito can pass a metal wire screen containing 16 strands or 15 meshes to the inch, but cannot pass one containing 20 strands or 19 meshes to the inch. When the screen consists of a fabric which is apt to pull out of shape so that some of the meshes are larger than others, it is advisable to use a net woven closer than 20 strands to the inch. Experience in malarial and yellow fever districts has taught this lesson, so that it is customary in those countries to use a. rather closely woven material re- sembling nainsook. Metal screens made of iron wire are cheapest only when first cost is considered. They hardly last a season unless painted, in which ease the size of the mesh is considerably reduced and inter- feres with ventilation, a serious objection in hot weather or a tropical climate. Mesh made of galvanized iron wire has a greater durability. Screens made of brass or bronze are expensive, but cheap in the long run, as they are found to last almost indefinitely. The screening should include the entire house, or at least those parts that are occupied. In the tropics it is better to screen the gal- leries than each individual window. In any case, frequent and repeated inspection should be made to discover breaks in the screen or openings due to warping of the woodwork. In screening care must be exercised not to overlook fireplaces, ventilators, and other openings. The door should be guarded by a screened vestibule' of such a depth as to make it impossible for a person to hold both doors open at the same time. The screen door should open outward and, if possible, should be exposed to the direct sunlight during the day without vines or nearby vegeta- tion of any kind to protect and lodge the mosquitoes. During the night 206 INSECT-BOENE DISEASES the door should not be in an artificial light, which attracts many mos- quitoes. An electric fan directed outward is a very good device to pre- vent mosquitoes flying through the doorway. In addition, a whisk- broom or feather duster should hang in the vestibule to brush off the insects that may rest upon the clothing. A screened house is safe only to careful and intelligent people. In addition to screening the house, mosquito bars over the bed will be found necessary in mosquito-infected places. It is best to suspend the mosquito bar from the ceiling and carefully gather the bottom together so as to keep the insects out during the day time. At night the bar should be carefully tucked in around the bed so as to leave no openings. Mosquitoes have no trouble in biting through the meshes of the bar, provided a restless sleeper comes close enough to it. Persons who are required to go out at night in a malarious district, or who must expose themselves during yellow fever times, may screen themselves effectively with a veil of mosquito netting hanging from a broad-brimmed hat to the shoulders and chest. The hands and wrists may be protected with gloves, and the ankles with leggings or other suitable mechanical device. Miscellaneous Measures. — Spirits of camphor, oil of pennyroyal, and other volatile substances, such as oil of peppermint, lemon Juice, or vinegar, rubbed upon the face and hands, or a few drops on the pillow at night, will keep mosquitoes away only for a time. Oil of citronella is one of the best known substances to be used in this way. Ordinarily a few drops on a bath towel hung over the head of the bed will keep the common house mosquitoes away. When they are very abundant and persist, a few drops rubbed on the face and hands will suffice. All these substances soon lose their efficiency; none of them last until morning. In Panama a larvicide is being used which is made as follows: 150 gallons of carbolic acid is heated in a tank to a temperature of 212° P., then 150 pounds of powdered or finely broken resin is poured in. The mixture is kept at a temperature of 212° P. Thirty pounds of caustic soda is then added, and the solution is kept at the same temperature until a perfectly dark emulsion without sediment is formed. The mix- ture is thoroughly stirred from the time the resin is used until the end. One part of this emulsion to 10,000 parts of water is said to kill Ano- pheles larvas in less than half an hour, while 1 part to 5,000 parts of water will kill them in from 5 to 10 minutes. The Panama larvicide is mixed with 5 parts of water and sprayed upon pools or along the banks of streams. This larvicide added to 5 parts of crude petroleum favors its spread upon the surface of the water. A good method is to place the mixture in a barrel and permit it to drip upon the surface of the stream or pond to be treated. Other larvicides that may be used in water not used for drinking MOSQUITOES 307 purposes are: sulphuric, hydrochloric, and other acids, potassium per- manganate, sulphate of copper, sulphate of iron, bichlorid of mercury, carbolic acid, anilin products, or coal tar. They must be used in rela- tively large amounts to be effective, and frequently renewed according to circumstances. The diseases known to be conveyed by mosquitoes are: malaria (Anopheles spp.), yellow fever {Stegomyia calopus), filariasis (Culex fatigans), dengue {Culex fatigans), and doubtless other infections. MALARIA Malaria is one of the most prevalent of all preventable diseases ; it is the scourge of the tropics. The cause of this infection was one of the first to be discovered (Laveran, 1880), and its mode of transmission was one of the most brilliant discoveries in sanitary science (Eoss, 1895). Despite the fact that we have more exact knowledge of malaria, considering the difficulties of the subject, than perhaps any other dis- ease, despite the fact that we have accurate means of diagnosis and a ready cure, and despite the fact that we have assured measures of pre- vention, malaria counts its victims by the hundreds of thousands annu- ally. In geographic distribution malaria extends from the Arctic circle to the Equator, but becomes more virulent the warmer the climate. At least three separate malarial parasites of man are known, namely : (1) Plasmodium malaria (Laveran), quartan fever; (2) Plasmodium vivax (G-rassi and Filetti), tertian fever; and (3) Plasmodium falci- parum (Welch), estivoautumnal or tropical malaria. These are closely allied hematocytozoa or blood parasites. They produce diseases with well-defined clinical differences, but having the same etiology and mode of transference, so that, as far as prevention is concerned, they may be regarded as one infection. Many species of animals have a malarial-like infection closely re- sembling malaria in man; for example, Texas fever of cattle, piroplas- mosis of dogs and sheep, proteosoma of birds, etc. So far as is known, no other animal than the Anopheles mosquito is subject to the malarial parasites pathogenic for man. Both man and the mosquito are neces- sary to complete the life cycle of the plasmodium. Man is the inter- mediate host harboring the asexual phase, and the mosquito is the defi- nitive host harboring the sexual phase of the life cycle of the Plas- modium. Mosquito Transmission. — It is now definitely known that in nature malaria is transmitted only by the sting of the Anopheles mosquito.^ Experimentally, the infection may be transferred by injecting blood ' The genus Anopheles has recently been divided into several genera. 208 INSECT-BOENE DISEASES (containing the parasites) of one person into the system of another. Nearly 2,000 years ago Varro and Columbella mentioned the possibility that the disease was transmitted by mosquitoes. In Africa some savage tribes call malaria the "mosquito disease." In 1848 Nott, of New Or- leans, considered the matter proven from biological analogies. In 1883 King, of Washington, vigorously advocated the mosquito theory based upon philosophical deductions but no proof. In 1884 Laveran suggested mosquito transmission as probable. In 1894 Manson elaborated the mosquito theory and inspired Eoss, of the Indian Army Medical Service, who in 1895 demonstrated that the crescents of estivoauturanal malaria underwent changes in the mosquito. In 1896 Bignami advocated the theory and compared it to the transmission of Texas fever by the tick. In 1897 Eoss published further convincing observations upon the de- velopment of the estivoautumnal parasite in the mosquito. In 1898 Mc- Collum observed an important missing link in the life cycle by observ- ing the flagellum of the microgametocyte (male) fertilize the macro- gametocyte (female) with the formation of the vermicule. These ob- servations were made upon Halterid.um or malaria of birds; later he saw the same phenomenon in estivoautimmal malaria. The life cycle of the malarial parasite has been confirmed by Daniels, Koch, Grassi, Big- nami, Celli, Manneberg, Schaudinn, and others. Further evidence that malaria is transmitted by the mosquito was furnished by Sambon and Low, of the London School of Tropical Medi- cine, and Dr. Terzi, who lived during the three most malarial months of 1900 in Ostia, a very malarial locality of the Eoman Campagna. These observers escaped infection simply by keeping within their well-screened hut from before sundown until after sunrise. The final proof was fur- nished in 1900 by Dr. P. Thurber Manson and Mr. George Warren, who were bitten by infected mosquitoes forwarded from Italy in cages to London. The Malarial Mosquito.— Of the fifty or more species of the genus Anopheles sixteen are known to transmit malaria. In Europe Anopheles maculipennis, in tropical America A. argyrotarsus or alUpes, in tem- perate America, A. quadrimaculatm, which is probably the same as A. maculipennis, in India A. sinensis, in Africa A. costalis, are the chief culprits. The Anopheles mosquitoes are brownish and rather large. They may be distinguished by the fact that the palpi in both the male and the female are at least as long as the proboscis. Only the female transmits the infection. It sits more or less at right angles upon the wall, the head, thorax, and abdomen being in a straight line. Contrary to the yellow fever mosquito, the malarial mosquito is nocturnal in its habits and breeds chiefly in the open ponds, puddles, and natural collections of water in the woods, fields, and swamps. MOSQUITOES 209 Fig. 19. — Anopheles Punctipenis. The mosquito becomes infected. upon drinking the blood containing the micro- and macrogametocytes. It requires about twelve days before the sporozoites appear in the salivary glands of the insect- It cannot, therefore, transmit the infection to another person until the lapse of this extrinsic period of incubation. The infected mos- quito may live a long time and infect more than one person suc- cessively. The malarial parasite seems to be a harmless sapro- phyte for the mosquito. Immunity. — A person who once has had malaria is more apt to have subsequent attacks. Ordinarily there is an increased susceptibility rather than an im- munity. However, repeated in- fections, especially during early life, leave a very pronounced re- sistance. In malarious regions many children carry the parasites in their circulating blood without any manifestations of the disease. These carriers are important factors in spreading the infection in en- demic areas, and must be taken into account in preventive measures. There is no true racial immunity in this disease. Occasionally a congenital immunity seems to be transmitted ; this must be rare. Prac- tically all persons wlio receive the infection for the first time are sus- ceptible. The freedom from malaria which some persons seem to enjoy may be accounted for partly by the fact that mosquitoes seldom bite such persons. It is well l^nown that on account of the odors, or what not, mosquitoes do not bother certain individuals. No doubt the in- fection of a small number of parasites is often overcome largely through a vigorous phagocytosis. Individual resistance varies in different individuals and in the same individual at different times. The parasite may remain latent in the spleen and other organs for years. Exposure, overeating, fasting, over- work, or worry, or anything that lowers the vitality of such individuals predisposes to an attack of malaria. The disease often breaks out in persons in good health leaving a malarial region for a health resort, whether mountain or seashore. I was enabled 1:o confirm this observa- tion upon the returning transports from Cuba following the Spanish- American war, when many cases of malaria broke out among the troops previously in good health upon reaching the cold winds about Cape 210 INSECT-BOEKE DISEASES Hatteras. Personal prophylaxis, therefore, involves careful attention to personal hygiene. Prevention. — The successful suppression of malaria requires a com- bined attack upon the mosquito and the parasite in the human host. Ultimate success rests upon the suppression of the mosquito. This, however, is a difficult and expensive undertaking in the case of the Anopheles. Immediate relief is most quickly gained by measures directed against the infection in man. Screening and quinin prophylaxis, while practical, are only temporary measures. Measures Directed Against the Mosquito. — If the breeding of the Anopheles mosquito could be stopped malaria would cease. Mosquito suppression is fundamental and radical. The best way to abolish the breeding places of malaria mosquitoes is to fill up low places or to dry the surface of the land with drains. These two measures hold first place as permanent work. The underdraining of large areas of our arable land of the Middle West with tiled drain has been very effective in suppressing malaria. Open ditches properly constructed and cared for are likewise effective. In the tropics the ditches should be lined with cement, on account of the luxuriant vegetation which soon interferes with their efficiency or may actually convert them into breeding places. The open ditches are much the cheapest in first cost, but not when maintenance is reckoned. The draining of swampy lands is an engineer- ing problem in which the economic factor looms large. One of the very best means of destroying the breeding places of the malaria mosquito is to clear the land and to keep it in cultivation. When drainage is not practical, the number of mosquitoes may be kept down by introducing fish into the pools, streams, ditches, and other collections of water. Upon limited water surfaces the larvae may be killed with a film of coal oil. Large open spaces cause the destruction of a number of mosquitoes, as they cannot live long in the hot sun; therefore, clearing the brush and high grass, which furnish shelter to the insects, aids in keeping away wild mosquitoes around dwelling houses. The use of screens and culicides has already been referred to. Personal Prophylaxis. — Persons visiting or residing in a malari- ous region should be particularly careful not to expose themselves at night time. The experience of Sambon and Low on the Roman Cam- pagna is instructive and should be imitated. The location of the resi- dence is important. In a city it should be a reasonably safe distance from the native quarter, because the infection is there most concentrated. The dwelling should, if possible, face the trade winds. A row of tall trees will partly screen the house from the swamp, but the trees must not be too close, else they will furnish shelter for the insects. The house should be on high land if practicable, as it is an old observation MOSQUITOES 311 that the malarial mosquito does not fly high. People living upon the second floor are less apt to contract the infection than those who sleep on the ground floor. If it is necessary to go out in the night tinje, one may protect himself by the use of gloves and mosquito netting hang- ing from the helmet to the shoulders. Care must be taken to guard the ankles against mosquito bites. As all these measures require much time and attention to details, they are usually not sufficient in actual practice. Therefore, quinin prophylaxis is much used. QuiNiN Phophylaxis. — Theoretically the administration of quinin to healthy individuals for the prevention of malaria is not an ideal method of prophylaxis, for it does not prevent infection, hut only de- stroys the parasites in the blood during the period of incubation. It should be remembered that quinin kills only the young and tender forms of the Plasmodium, and has no influence upon the crescents. Quinin prophylaxis is indicated in proportion to the difficulty of pursuing more permanent methods. It is especially valuable vphere screens and bars are not available, as in camping, marching, traveling, or virhere the occupa- tion takes one out at night. When residents of non-malarial countries go into malarial localities, especially in the rural districts, for short periods of time, quinin is a valuable preventive. To be effective as a preventive of malaria, quinin must be taken in sufficient doses during the entire malarial season. The expense of pub- lie prophylaxis vfith quinin on a large scale is enormous; in fact, in some instances prohibitive. The daily ingestion of 2.5 grains would require the annual use of no less than 59.4 tons per million people. The size of the dose and the interval at which the prophylactic is ad- ministered are of the utmost importance. Koch advised one gram of quinin every sixth or seventh day, or every seventh and eighth day, or eighth and ninth, or ninth and tenth day, according to the danger of the infection. This manifestly leaves several intervening days in which there is no quinin in the circulation. In localities, therefore, where estivoautumnal malaria is prevalent, a shorter interval should be pre- ferred on account of the shorter period of incubation of this form of malaria. Ziemann gives a gram of quinin sulphate every four days. The al- kaloid is administered in solution with 5 drops of hydrochloric acid early in the morning or about one and one-half to two hours after a meal. A convenient rule is to give a dose on the first of the month and thereafter on each day of the month divisible by 4. By this method the alkaloid is probably constantly in the circulating blood. Plehn advises one-half a gram of quinin every fifth evening. The administration of small doses of quinin daily is the oldest method of giving quinin as a prophylactic. From II/2 to 6 grains have been given daily. In Italy 0,04 gram (about 3-3 grain) daily is the universally 313 INSECT-BOENE DISEASES adopted dose, and accomplishes good results. The Italian government undertakes the sale of quinin at a low price. This is a beneficent public health measure comparable to the frfee distribution of antitoxin and vac- cine virus. On the Isthmus of Panama good results have been obtained by the use of moderate doses, 3 to 6 grains per day. When the disease in- creases in prevalence or virulence the amount is raised to 8 or 10 grains per day, then dropping ofE to 4 or 5. The particular method of election in giving quinin prophylaxis should be chosen according to the experience of the region. An objection to the use of quinin as a prophylactic has recently been raised by Stitt, -who claims that the malarial parasites gradually become immune to the effects of the alkaloid, and that vi^hen the disease subse- quently breaks out in one who has used quinin as a prophylactic it is not readily amenable to treatment. Ehrlich has shown experimentally that trypanosomes may be immunized in this sense to trypanrot, and that other microparasites belonging to the animal kingdom may similarly be accustomed to unusual amounts of substances ordinarily very toxic. Quinin prophylaxis has advantages that commend it as a prompt and practical measure. It is at best, however, only tentative, and does not take the place of mosquito suppression. YELLOW FEVER The prevention of yellow fever rests entirely upon the fact that it is communicated through the bite of an infected mosquito — the Stego- niyia calopus} The mosquito becomes infected by sucking the blood of yellow fever patients during the first three days of the fever. All the experimental evidence thus far shows that the infection is absent from the blood after the third day, and that mosquitoes do not become in- fective after this period. The importance of this fact in preventing the spread of the disease is evident. The mosquito, after drinking the in- fected blood, is not able to transfer the infection to another person until about twelve days '' have elapsed ; that is, it requires about twelve days for the yellow fever parasite, whatever it may be, to undergo its cycle of development in the mosquito. The mosquito once infected remains so during the rest of its life, which may be many months. Only the female mosquito transmits the infection ; the male Stegomyia calopus is a vegetarian; its proboscis is too soft to penetrate the skin. A single ' This mosquito was first called Culen fdsciatus, which was changed to Stegomyia fasciatus, and then to Stegomyia calopus, and recently expressed as Aedes calopus by Coquillett. ^ This constitutes the extrinsic period of incubation, in contradistinction to the intrinsic period of incubation, that is, the time between the mosquito bite and the onset of symptoms, which is from & to 5 and sometimes 6 days in this MOSQUITOES 213 sting of a single infected mosquito is sufficient to produce the disease. An infected mosquito may infect more than one person at different times. The prevention and control of yellow fever are hased upon a series of epoch-making investigations and discoveries (1900-1902) by a com- mission composed of Walter Eeed, James Carrol, Aristides Agramonte, and Jesse W. Lazear, medical officers of the United States army. These experiments have been fully confirmed, and in some respects amplified, by independent workers, namely, Guiteras .of Cuba (1901) ; Barreto, de Barros, and Eodrigues, of Brazil (1903) ; Eoss (1902); Parker, Beyer, and Pothier (1903); Eosenau, Parker, Francis, and Beyer (1904); Eosenau arid Goldberger (1906), of America; Marchoux, Salimbeni, and Simond (1903); Marchoux and Simond (1906), of France; and Otto and Neumann (1905), of Germany. The cause of yellow fever is unknown. The virus is ultramicroscopic, that is, passes the close-grained pores of the finest porcelain filter. While in nature the disease is transmitted only through the bite of an infected Stegomyia, the disease may be transferred experimentally by taking some of the blood from a patient during the first three days of the fever and injecting it into a susceptible individual. So far as is known, yellow fever is peculiar to man, for all other animals tested have failed to react. At one time it was generally believed that yellow fever infection was conveyed by fomites. This has been disproved, and we now know that there is no danger from soiled clothing or other inanimate things, even though stained with the black vomit and other discharges. The diagnosis of yellow fever rests upon clinical evidence and is fre- quently difficult to make, especially in the early stages. It is, therefore, important to screen all cases of fever in a yellow fever campaign until the nature of the illness is established. Immunity. — There is no natural immunity to yellow fever. All per- sons receiving the infection for the first time seem to be susceptible. Contrary to the usual statement, there is no racial immunity in this dis- ease, for negroes, Chinese, Indians, and other races take the disease. One attack of yellow fever affords protection against a subsequent attack. The acquired immunity in this disease is one of the strongest known and lasts throughout the lifetime of the individual. Two attacks of yellow fever are almost unknown. I reported a supposed instance in a Spaniard in Havana, but the diagnosis of the first attack was not con- clusive. In endemic areas children may have yellow fever, which leaves them immune for life. The disease often runs a mild and unrecognized course in children, and this fact explains the supposed natural immunity of natives in endemic foci. The Yellow Fever Mosquito. — The yellow fever mosquito has a wide 16 21-4 INSECT-BOENE DISEASES distribution ranging from 38 degrees south to 38 degrees north latitude. They are found in the East and West Indies, China, Sumatra, Java, In- dia, Philippine Islands, Japan, Hawaiian Islands, in the southern part of Italy, Africa, Spain, South America, etc. They usually prefer the low- lands. I have found them as far up the mountains as Orizaba in Mexico, 4,- 200 feet above sea level. In the United States they are very prevalent south of the Potomac along the gulf coast, but are absent or rare in the higher elevations of Georgia or Alabama, which are, therefore, non-infectable regions. The yellow fever mos- quito is a domestic in- sect. It breeds by pref- erence in any standing water about the house- hold, such as cisterns, rain barrels, or any col- lection of water in buckets, bottles, old cans, etc. The yellow fever mosquito does not breed in the fields, woods, and swamps, which are the favorite resorts of the malarial mosquito. The Stegomyia mosquitoes do not fly far of their own volition, but show a cat-like tendency to remain about their place of birth or adoption. All these facts have an evident bearing upon preventive measures. A thorough knowledge of the biology of the mosquito is essential to the success of a yellow fever campaign. It is important to remember that the yellow fever mosquito is chiefly active during the day time. It cannot, however, distinguish between artificial light and sunlight. I have watched Stegomyia mosquitoes bite me by electric light at eleven o'clock at night. However, as a rule, they rest at night, which, therefore, diminishes the risk of exposure at that time. The Stegomyia mosquito, however, cannot survive for long in the direct rays of a tropical sun, There is, therefore, little FiQ. 20. — Stegomyia Calopub (female). MOSQUITOES 215 danger in visiting a community where yellow fever is epidemic dur- ing tHe day time, provided the person keeps out of houses. The ex- periences during the last yellow fever epidemic at New Orleans, 1905, showed that the radius of activity of an infected Stegomyia is con- tracted. It may possibly at times fly across the street, but it is evident that it neither flies far nor is it ordinarily transported to any great dis- tance on railroad cars, although it may be carried over seas on ships. The yellow fever mosquito may pass a screen composed of 16 strands or 15 meshes to the inch, but cannot pass one containing 30 meshes or 19 strands to the inch. Effective screens must, therefore, be at least this fine. Stegomyia calopns is a grayish mosquito of average size with beautiful glistening silver-white markings. These markings are lyre-shaped on the back of the thorax; silver- white spots are seen on the side of the thorax. White lines are apparent at each tarsal Fig. 21. — Head op Steqomtia Calopus (male). joint and also on the palpi; the scutellum is white. In the female the palpi are much shorter than the proboscis, which at once distinguishes it from Anopheles. Egg. — The female lays her eggs on the surface of the water or just above the water line. The eggs do not adhere to one another, and hence do not form the compact boat-shaped mass characteristic of the eulex, but float on their sides more or less singly. At the moment of laying the eggs are a cream color, but rapidly become jet black. They are somewhat cigar-shaped, and measure on the average about 0.55 mm. in length and 0.16 mm. in width at the broadest part. The eggs show marked powers of resistance to unfavorable influences. They may be kept dry for sis and one-half months, and still retain their vitality, and hatch out when put back into the water. Freezing does not kill them. The egg probably plays an important role in the hibernation of the yellow fever mosquito. The winged insect may also survive a short winter. Under the most favorable conditions as to temperature (30° C.) Stegomyia eggs hatch out in about 36 hours after they are laid. Under 20° C. they will not hatch at all. Laeva.^ — The egg hatches the larva ("wiggle-tail"), which has a black barrel-shaped respiratory siphon. This distinguishes it from Oulex 216 INSECT-BOENE DISEASES Fig. 22. — Eggs op Stegomtia Calopus. pipiens, its common mess mate, in which the air tube is brown, longer, and more slender. Although the larva lives in the water, it is strictly an air-breather and must come to the surface for air. It thrusts its breathing tube up into the surface film and remains suspended, head down, at an angle of somewhat less than 45 degrees, which distinguishes it from Anopheles larvae, which lie horizontal. A film of oil on the surface of the water is sufficient to obstruct the air tube and thus cause Fig. 23.— Lakva of Stegomtia Calopus. Respiratory Syphon op Culex to the Rigbt. MOSQUITOES 217 the death of the larva by suffocation. The larva is very timid, so that a slight jar or agitation or a sudden shadow will cause it to wriggle rapidly to the bottom, where, indeed, it may very commonly be observed to feed. The duration of the larval stage is never less than 6 to 7 days, and depends upon the food supply and temperature. Under fa- vorable conditions it may be prolonged for weeks. Freezing for short periods does not appear to injure it. Fig. 24. — Pupa op Steqomtia Calopds, Pupa. — The larva changes into the pupa. The pupa is not provided with a mouth and does not feed. It is an air-breather and spends most of its time at the surface of the water. The pupal stage lasts at least 36 hours, during which time metamorphosis occurs into the imago or perfect winged insect. Imago. — Under the most favorable conditions it is at least 9 days from the time the Stegomyia lays its egg to the appearance of the imago. Under natural conditions the length of life of the adult female probably varies greatly. Guiteras succeeded in keeping a presumably infected one alive for 154 days during the fall and winter temperature in Havana. Deprived of water, it does not usually survive longer than 3I/2 to 4 days, and only very exceptionally 5 days. This fact has a bearing on the possibility of transporting the mosquito in band-boxes, trunks, and other containers. "Aerial" Conveyance. — It is notorious that yellow fever is usually conveyed but a short distance "aerially" — perhaps across the street, or, 318 INSECT-BORNE DISEASES more often, to a neighboring house in the rear. This represents a dis- tance of some 75 yards, which is about as far as we may expect it to be thus conveyed, from our knowledge of the habits and flight of the Stegomyia mosquito. The longest distance recorded in recent years of aerial conveyance is one of 335 meters (Melier) and one of 456 feet (Carter). These are entirely exceptional. My experience in the deten- tion of hundreds of susceptible immigrants in quarantine for days in Havana harbor showed that infected Stegomyise do not travel a short distance across the water. This observation is in confirmation of others, that vessels moored within 1,200 feet of the shore are entirely safe so far as yellow fever is concerned, provided, of course, personal intercourse is interdicted or supervised. Prevention. — The prevention or suppression of yellow fever may be attacked in either one of its two hosts, man or insect. If every person developing yellow fever were immediately isolated from the Stegomyia mosquito, the disease would inevitably cease. The elimination of the Stegomyia mosquito would give the same happy result. Usually both methods of attack are employed. It would seem easier to control the human host simply by screening during the first three or four days of the fever. Practically this method has been found insufficient, be- cause the disease is difficult to diagnose in the early stage, and the mild cases escape attention. The essence of yellow fever prevention, therefore, consists in: (1) screening cases of yellow fever and all sus- pected cases of yellow fever; (2) destruction of infected insects; (3) the suppression of stegomyia through the control of their breeding places. It was a combination of these three methods which was first so brilliantly carried out by Gorgas in Havana in 1901, and later in Panama; by White in New Orleans, 1905; by Liceaga for Vera Cruz, and recently by Oswaldo Cruz in Eio de Janeiro, 1909. Yellow fever patients should be isolated only in the sense of separat- ing them from Stegomyia calopus. This may be done by proper screening. It is not necessary to remove the patient to a hospital, al- though this is desirable, for the reason that a special hospital is more carefully guarded than is practicable in a private house, and the trained assistants are an additional safeguard. As soon as the patient is re- moved, the mosquitoes in the house and the surrounding houses should at once be destroyed. Yellow fever patients must be moved with caution, for the reason that undue excitement or exertion seems to increase the severity of the disease. The insecticides best suited for the destruction of mosquitoes are: sulphur dioxid, hydrocyanic acid gas, pyrethrum powder, tobacco smoke, Mim's culicide (camphor and phenol) (see page 187). At first glance it might appear to be a hopeless task to attempt to eradicate the yel- low fever mosquito in a large city, but that this is possible was demon- MOSQUITOES 219 strated in New Orleans in 1905, when, after several months of a vigorous campaign, it was difficult to find a Stegomyia mosquito. The measures consisted mainly in screening the water cisterns and eliminating all standing collections of water in and about the house- hold. Historical Note. — Dr. Charles J. Finlay studied the relation of the mosquito to yellow fever as far back as 1882 and 1883. The first in- sects used by the United States Army Commission to bring about the demonstration of the new doctrine were received from the hands of Dr. Finlay. Finlay believed that the cause of the disease was a micrococcus and considered that the insects were capable of transmitting the dis- ease a few days after they had stung a yellow fever patient. Stern- berg's studies upon yellow fever are published by the Government as a report of the United States Marine Hospital Service on the Etiology and Prevention of Yellow Fever, 1890. Carter's observations at Orville, Mississippi, upon the extrinsic period of incubation were published in the Medical Record, June 15, 1901. The work of the United States Army Commission appeared in the following publications : "The Etiology of Yellow Fever — a Preliminary Note," Proceedings of the 28th Annual Meeting of the Am. Pub. Health Assn., Oct. 22-26, 1900; also Philadelphia Med. Jour., Oct. 27, 1900. "The Etiology of Yellow Fever— An Additional Note," J. A. M. A., Feb. 16, 1901. "Experimental Yellow Fever," Am. Med. Jour., July 6, 1901. "Etiology of Yellow Fever — Supplemental Note," Am. Med. Jour., Feb. 22, 1902. On account of their historical interest and accuracy, the conclusions of the United States Army Commission are here given : 1. The mosquito — C. fasciatus — serves as the intermediate host for the parasite of yellow fever. 2. Yellow fever is transmitted to the non-immune individual by means of the bite of the mosquito that has previously fed on the blood of those sick with this disease. 3. An interval of about 12 days or more after contamination ap- pears to be necessary before the mosquito is capable of conveying the infection. 4. The bite of the mosquito at an earlier period after contamina- tion does not appear to confer any immunity against a subsequent at- tack. 5. Yellow fever can also be experimentally produced by the sub- cutaneous injection of blood taken from the general circulation during the first and second days of the disease. 6. An attack of yellow fever produced by the bite of the mosquito 220 INSECT-BOKNE DISEASES confers immunity against the subsequent injection of the blood of an individual suffering from the non-experimental form of this disease. 7. The period of incubation in thirteen cases of experimental yel- low fever has varied from forty-one hours to five days and seventeen hours. 8. Yellow fever is not conveyed by fomites, and hence disinfection of articles of clothing, bedding, or merchandise, supposedly contami- nated by contact with those sick with this disease, is unnecessary. 9. A house may be said to be infected with yellow fever only when there are present within its walls contaminated mosquitoes capable of conveying the parasite of this disease. 10. The spread of the yellow fever can be most effectually con- trolled by measures directed to the destruction of mosquitoes and the protection of the sick against the bites of these insects. 11. While the mode of propagation of yellow fever has now been definitely determined, the specific cause of this disease remains to be discovered. Prevention of Malaria and Yellow Fever Contrasted. — For the pre- vention of malaria the same principles guide us that have been set forth for the prevention of yellow fever. In practical application, how- ever, our methods of attack differ, owing to differences in the habits of the two mosquitoes, and owing to differences in the two diseases. The malarial problem is much more difficult, because it is harder to get rid of Anopheles than of Stegomyia. The breeding places of the yellow fever mosquito are practically confined to artificial containers in the neighborhood of human habitations, while those of anopheles are found in marshes, pools, or streams, and often in collections of water in the grass or brush. The breeding places of the malarial mosquito cover a much larger area, frequently the whole country, and are rather hard to find and difficult to destroy; also this insect travels much further from its breeding place than the Stegomyia, probably from three to four times as far. Compared to yellow fever, the control of the malarial human host presents special difficulties. In yellow fever man is infec- tive to the Stegomyia only a few days ; in malaria the parasites continue in the circulating blood a very long time. In the case of malaria, then, we have to deal with chronic carriers, which, fortunately for us, does not occur in yellow fever. For malaria we have quinin as a prophylac- tic, whereas no known drug will prevent yellow fever. DENGUE All who visit the tropics or subtropical countries where dengue pre- vails are very apt sooner or later to contract this infection. So far as known, few persons have ever died of dengue. Although the mortality MOSQUITOES 231 is practically nil, the disease is a painful affection and sometimes leaves the body in a weakened condition for long periods of time. In its epidemiology and symptomatology the disease strikingly parallels yellow fever, which adds to its importance. Outbreaks of dengue often precede and may be coincident with those of yellow fever. In the tropics influ- enza and dengue are also frequently confused. Dengue also has some resemblance to the three-day fever or pappataci fever of Herzegovina, which is transmitted by the bite of the Phlehotomus pappatasii, a biting fly. There is no definite immunity produced by an attack of dengue. Persons often give a history of an attack in each outbreak. The cause of the disease is not known. Graham studied dengue in Beirut, Syria, and described a protozoon inhabiting the red blood corpuscles and closely resembling the Plasmo- dium of malaria except for the absence of pigment.^ Graham believed that this organism underwent a developmental stage within the mos- quito {Culex fatigans). He claimed to have observed the spores of this organism "in among the cells of the salivary glands" after 48 hours in mosquitoes which had bitten a dengue patient upon the fourth day of the disease. Graham produced a very severe case of fever resembling dengue by inoculating a man subcutaneously with peptonized normal salt solution containing the salivary glands of a mosquito which had bitten a dengue patient 24 hours before. Graham's observations con- cerning the parasite in the blood and in the mosquito have not been confirmed, although the subject has beeh studied by several experienced microscopists. Carpenter and Sutton,- however, obtained two positive results out of four experimental cases of mosquito inoculation. The period of incubation in one of these, however, was two weeks, and the subjects were not sufficiently controlled to exclude the bites of other mos- quitoes. Agramonte ^ studied an epidemic in Habana which was ac- companied by a plague of Culex fatigans: He attempted to transmit the disease by mosquitoes, trying various species at various intervals after the insects had fed upon dengue patients, but did not succeed in producing the disease in this way. Guiteras and Finlay * endeavored to transmit the disease with Culex pipicns, but with negative results. Guiteras, Finlay, Agramonte, and others who have worked upon this subject state that their faith remains unshaken that the mosquito acts as the vector of dengue, despite the negative results of their experiments. Ashburn and Craig = in 1907 studied the disease in Manila an^ showed that the virus is contained in the blood during the febrile stage. '■Jour. Trap. Med., 1903, Vol. VI, p. 209. '^Jour. A. M. A., 1905, XLIV. "New York Med. Jour., 1906, LXXXIV. *Itev. Med. Trap., 1906, Vol. VII, p. 53. 'PMippine Jour, of Sci., Vol. II, No. 2, Section B, May 1, 1907. 222 INSECT-BORlSrE DISEASES The intravenous inoculation of filtered dengue blood into healthy men is followed by a typical attack of the disease. The cause of the disease is, therefore, probably ultramicroscopic. They transmitted the infec- tion by the mosquito, Gulex fatigans, and concluded that this is probably the most common method of transmission. The period of incubation in the experimental cases averaged 3 days and 14 hours. They con- cluded from their studies that dengue is "not a contagious disease, and is infectious in the same manner as are yellow fever and malaria." All our preventive measures are now based upon the supposition that dengue is a mosquitorborne infection. At times dengue appears to be one of the most contagious of all diseases, for it spreads like wildfire and spares practically no one in the •community. An instance showing the non-contagiousness of dengue is given by Persons, U. S. N. : A squad of marines from the U. S. S. Baltimore were given shore leave at Cavite. Twenty of the 24 marines who had been ashore came down with the disease after returning to the ship, while there was a total ab- sence of infection among those who had remained aboard. Observations made at the Naval Hospital at Canacao demonstrated that in the mos- quito-free wards the disease did not spread, whereas when the hospital was located at Cavite it was noted that practically every case admitted became infected with dengue while under treatment for the original complaint (Stitt). FILABIA8IS The filaria is a long, slender filiform threadworm with a curved or spiral tail. The adult worms live in the connective tissue, lymphatics, and body cavities. The em-bryos or larvae are found in great numbers in the blood. In several species of which the life history is known mos- quitoes act as the intermediate host. The most important filariae of man are : ( 1 ) Filaria hancroftii, the larva of which is known as Filaria nocturna, appearing in the blood at night and occurring especially in Australia and the tropics; (2) Filaria loa, the larva of which is known as Filaria diurna, occurring in the blood by day and prevalent in West Africa and India; (3) the Filaria perstans, the larva of which is known as Filaria perstans, which persists in the blood both day and night, and occurs especially in West Africa and a number of other places. None of these young worms do any appreciable injury in the blood; of the adult worms, only one, namely, Filaria hancrofti, can be viewed as serious, while the second species, Filaria loa, is more or less trouble- some. According to Manson, we are hardly Justified at present in as- suming that all the other species are entirely without effect upon their hosts. These parasites infect man throughout the tropical and sub- tropical belt. In the United States the infection, while not very preva- lent, is endemic as far north as Charleston. FLIES 233 According to Manson, Culex fatigans, and according to James \ihe Anopheles nigerrinus, are the intermediate hosts. When fed on the hlood of a filarial-infested individual, it is found that the filarial larvae soon escape from their shields in the thickened blood within the stomach of the mosquito. They pierce the stomach wall, enter the thoracic muscles of the insect, pass through a metamorphosis which takes from 16 to 20 days (longer or shorter, according to atmospheric temperature) ; they now quit the thorax and a few find their way to the abdomen; the vast majority, however, pass forward through the prothorax and neck, and, entering the head, coil themselves up close to the base of the proboscis and beneath the pharynx and under surface of the cephalic ganglia. This account is taken from Manson, to whose per- sonal interest in this disease we are indebted for the advances in our I - a "o >.-§ s 1 0) o •a 1 11 o i 1 a a & 53 '•s ■a -d t>. t^ TJ J2 ■a a S o m O S 1 00 oj 92 ^ i-^ ffi o --< 1 O p 1 s ai-H l.s" 00 o III Q a il a a o" O^J H H CQ fficc 3 P O Q M a ^; ■3 1 o +3 a esr£ o li el o p s 1 s 3 i i i a 1 1 lil ii II ■Sfl o g e o Si e t-. E^ e^ ti Eh ^ ^ CO *■" ^ a ^soq puB 80U31TUTA 'J3i ]oqdjoin i ir ^uv^euooni I] dnojr) ■■;3 o ■^Boq pa B ooaainiiA a •itSoiOqdJO ca m ^uB^^snoQ I < 236 PLEAS 237 Todd and Wolbaeh ^ suggest a systematic examination of the natives in the endemic area by gland palpation and gland punctiire. The lat- ter consists in withdrawing a drop of fluid from one of the enlarged lymphatic glands by means of a hypodermic syringe. The little drop of bloody fluid thus obtained is examined as a fresh preparation under the microscope for trypanosomes. By this method these investigators found at least 0.8 per cent, of the population of the Gambia to harbor trypanosomes. If all the infected individuals could be collected in vil- lages for observation, treatment, and isolation, it would do much to limit the disease. Trypanosomes are the cause of numerous other diseases in animals, as will be seen by reference to the table on page 236. So far as known, sleeping sickness is the only important disease of man produced by trypanosomes. Kala-azar, however, is produced by a flagellated proto- zoon parasite which probably belongs to the trypanosomes. Practically all animals are susceptible to almost all trypanosomes. The trypanosomes which infect man may readily be transmitted to mon- keys, guinea-pigs, rabbits, etc. PAPPATACI FEVER Doerr and Euss ^ and also Doerr, Franz, and Taussig originally de- scribed a three-day fever which occurs on the shores of the Adriatic, the cause of which is not known, but which is of special interest for the reason that it has been demonstrated to be transmitted through the bite of a dipterous insect commonly called a gnat — Phlebotomus pap- patasii. FLEAS Fleas are flat, wingless insects related to the Diptera. They pass through a complete metamorphosis: embryo, larva, pupa, and imago. The adult female flea deposits her eggs among the hair or fur of the host animal, but, unlike the eggs of many ectoparasites, they are not fastened to the hairs and therefore fall freely to the ground. The eggs are oval, whitish, and smooth and about half a millimeter long. The larvffi escape from the eggs in 2 to 5 days. They are able to break the egg shell by a slender process on the top of the head which disappears after the first molt. The larva is a slender, legless, cylindrical creature, whitish or yellowish in color, with a head and 13 segments. There are a few scattered hairs or bristles on the body, and at the tip is a pair of cor- neus processes. At the front of the head is a pair of biting Jaws or ^Annals of Tropical Medicine and Parasitology, Vol. "V, No. 2, Aug., 1911, p. 245. Jsund Tropen Hyg., 1909, Vol; XIII, No. 22, p. 693. 238 INSECT-BOENE DISEASES mandibles. The larvae feed on almost any kind of refuse. They have been reared on the sweepings from rooms. There is always some or- ganic matter in such dust, and this is doubtless their nourishment. In houses the larvse usually crawl into cracks or in carpets, where they feed \ '^B^ISSKKSKK^BlBafm ■ ) ^ } Fio. 38. — The Indian Rat Flea {Lcemopsylla cheopis Rothac). and grow. Those that infest wild animals probably feed on the refuse in the nests or retreats of these animals. It will be noticed that, con- trary to the mosquito, the larval and pupal stages of the flea are not aquatic. They remain in the larval stage from a week to ten days, sometimes two weeks, molting the skin three times in this interval. Then they spin flat, white, silken cocoons in which they transform to the pupal stage. In from 5 to 8 days the adult flea emerges from the cocoon. The period of their transformation is aflEected by the tempera- ture and moisture. In warm, damp weather a generation may develop in ten days or two weeks, but usually about 18 days to three weeks elapse from the egg to the adult. Although some moisture is neces- sary for their development, an excess is apt to destroy the larvae. The leaping ability of adult fleas is familiar to all. This, however, has been greatly exaggerated. The British Plague Commission de- termined that fleas Jump 3 to 5 inches, never over 6. No part of the leg is particularly enlarged, so that the jump is made by the entire leg, as in the leaf-hopper insect, and not by the femur of the hind leg, as in the grass-hopper. Fleas do not vary much in size. They are mostly about 3 to 3 millimeters long. The adult insect has a hard, strongly chitinized body. The mouth parts resemble somewhat those of the mosquito. Both the male and the female flea are capable of piercing the skin to obtain blood and thus transmit infection. Fleas, as a rule, prefer certain hosts, but are not as particular in this regard as are many parasites. Those species which are best known are found to attack several hosts, including man. This is one reason that makes FLEAS 239 them dangerous parasites, so far as plague and other infections are concerned. Over 300 species are described. Formerly all fleas were classified in the single family Pulicidae, genus Pulex; now they are ar- ranged in many genera and these genera grouped into families.^ Fig. 39. — The Common Rat Flea op Europe and North America (Ceratophyllus fasciatus Bosc.) . Pulex seiraticeps or Ctenoceplialus canis occurs all over the world, infesting cats and dogs, also many other animals. They are fre- quently brought into houses upon domestic animals, and thus become troublesome to man. Pulex irritans is the human flea, sometimes called the "house flea" or "common flea." Fio. 40. — The Human Flea {Pulex irritans Linn.). The fleas concerned in the transmission of plague are Lcemopsylla cheopis, the Indian rat flea, and Ceratophyllus fasciatus, the common rat flea of Europe and North America. Plague may also be transmitted by Ctenocephalus felis, the cat flea; Pulex irritans, the human flea; Ceratophyllus acutus, the squirrel flea, and doubtless other genera and species. 'Banks: "The Eat and Its Eelation to the Public Health," P. H. and M. H. S., p. 69. 240 IKSECT-BOENE DISEASES In addition fleas act as intermediate hosts for certain tapeworms (Dipylidium caninum), and doubtless are the mechanical or biological carriers of other infections. Nicolle incriminates the flea in typhus fever. Pulicides. — Adult fleas succumb to the agents applicable to in- sects in general. Mitzmain ^ has shown that water is of little value in the destruction of mature fleas. Glycerin is also practically inert as a pulieide, but tincture of green soap is very quick and effective. This action cannot be due to the alcohol in the soap, for alcohol in the strength of 70 per cent, and absolute is uncertain in its action and practically inefficient. Kerosene (coal oil) is a very efficient flea de-' stroyer. Formalin, phenol, mercuric bichlorid, and tricresol in the strength used as disinfectants are of little value in killing fleas. Pow- dered sulphur seems to be of no value. Of gases, bisulphid of carbon (CSj), hydrocyanic acid gas (HON), and sulphur dioxid (SOj) are highly efficient in the strengths recom- mended for general insecticidal purposes. Chloroform or ether first anesthetizes fleas, and if continued kills them. This is important for the safe handling of rats, squirrels, and other plague animals. The host may be chloroformed and the fleas and other ectoparasites re- moved with a comb. The anesthetic may be controlled by practice so that the host will recover and the fleas die, or both recover, or both die, as may be desired. In flea-infected houses the larvae, living in the cracks of the floor, etc., may be easily controlled by sprinkling a thin coating of flake naph- thalene on the floor and then leaving the room tightly closed over night. In the morning the naphthalene may be swept up and what remains used again. RELATION OP PLAGUE TO RATS AND FLEAS Plague is primarily a disease of the rat and secondarily of man. This fact is now firmly established not only by the recent experiences, but especially through the admirable studies of the Indian Plague Com- mission,^ which established beyond doubt the fact that plague may be and generally is transmitted from rat to rat and from rat to man through the agency of the flea — Lcemopsylla cheopis — and sometimes by Ceratophyllus fasciatus, et al. During some plague epidemics it has been noted that the rats die in great numbers before and during the out- break. It is now known that this epizootic in the rat is true plague. In nature, rats suffer both with acute and chronic plague. In the laboratory, rats may be infected with plague by ingestion, by ^Public Health Reports, July 29, 1910, Vol. XXV, No. 30, p. 1039. ' Journal of Sygiene, Vol. VI, No. 4 ; Vol. VII, Nos. 3, 6 ; Vol. VIII, No. 2. EELATIOK OP PLAGUE TO EATS AND PLEAS 241 application of the virus to nrncous or cutaneous surfaces, or by sub- cutaneous inoculation. In nature, rats may become infected by any of these means or through flea bites. Eats are great travelers, and have carried the plague to all quarters of the globe. A niore complete discussion of the rat and its relation to plague and other diseases will be found on page 242. \¥ithin the past few years it has been discovered that, while the rat is the great medium for the spread of plague, the disease is probably preserved from extinction in Thibet by another rodent, the marmot (Arctomys hobac). In California the infection has gotten into the ground squirrels {Citelhis beecheyi), in which the disease will doubt- less be kept alive for many years to come. To realize the full impor- tance of these discoveries, it is only necessary to call to mind that, in ■order to eradicate plague forever from the surface of the globe, a war- FiQ. 41. — ^A Squirrel Flea (Hoplopsyllus anomalus Baker.). fare against the rat alone is not sufficient, but must include the ro- dents mentioned and perhaps others. Simond in 1897 advanced the theory that plague was carried by fleas. This theory was developed by J. Ashburton Thompson and others and conclusively proved by the Indian Plague CommissioriT The exact method by which the flea transmits the infection from animal to ani- mal is not definitely understood. The mouth parts appear not to re- main infected. It is possible that the salivary secretions contain the microorganisms. It is known that the plague bacilli may live in the digestive tract and be passed in live and virulent numbers in the de- jecta. It is easy to understand how some of the infected dejecta may be rubbed or scratched into the little wound produced by the flea bite. When it was found that the common rat flea of Europe, the CeratopJiyl- lus fasciatiis, does not readily bite man, considerable doubt was thrown upon the part played by the flea in plague transmission. These nega- tive results, however, are offset by the convincing positive proofs of the British Plague Commission in India, and by McCoy and Mitzmain in 242 INSECT-BORNE DISEASES San Francisco, who showed that under certain conditions the rat flea will bite man, especially if the natural food supply is limited, and that these fleas may feed on a man's hand even in the presence of a rat. Eaybaud ^ calls attention to the fact that the rat flea {Ceratophyllus fasciatus) is able to hibernate for a month or 45 days without nourish- ment, and that virulent plague germs may persist unharmed in its stomach during this length of time and even longer. This fact may be of importance for the transmission of plague to a distance. It should be remembered that, according to the observations of Nut- tall and Yersin, flies and possibly other insects may also occasionally convey the infection. Walker '^ considers, as the result of experiments, that bedbugs and other biting insects play an important role in the transmission of plague. RATS AND OTHER RODENTS Eats, mice, squirrels, and other rodents have become a serious prob- lem in preventive medicine, and their habits and methods of suppression may be considered conveniently at this place. Plague being primarily a disease of rats, the prevention and suppression of this infection re- solve themselves into a war upon these rodents. For the control of plague it is, therefore, necessary to have a knowledge of the life history and methods of attacking the problem in the lower animals. In addition to plague, rats are the great reservoir of trichinosis. They are responsible for the transmission of certain tapeworms and other parasites. They are subject to leprosy, cancer, and numerous other diseases, some of which concern man. Eodents comprise more than one-third of all living species of mam- mals, and exceed any other mammalian order in the number of in- dividuals. They have no canine teeth, but strongly developed incisors. Only the front of the incisors is covered with enamel, which keeps them sharp and chisel-like, owing to the more rapid wearing away of the softer dentine. The incisor teeth continue to grow throughout the life of the animal. The most extensive family of rodents is the Muridm, which includes the true rats and mice, typifled by the genus Mus. Trouessart, in his "Catalogus mammalium," enumerates 250 species of Mus described before 1905. Since that date a number of new forms have been described. The genus Mils is characterized by. narrow, ungrooved incisors; three small-rooted molars; soft fur mixed with hairs, sometimes with spines; a rudimentary pollex (thumb) having a short nail instead of a claw; a long tail bearing rings or overlapping scales and often naked or ^ Fresse Medicale, March 8, 1911, No. 20. * Walker: Indian Med. Gaz., 1910, No. 3, p. 93. RATS AND OTHEE EODENTS 343 nearly so. The ears are rather large, the eyes bright and prominent, and the muzzle somewhat pointed. The distinction between rats and mice is arbitrary and based on size. Of the many species of the genus Mus only three or four have developed the ability to adapt themselves to such a variety of condi- tions as to become cosmopolitan. Four have found lodgment in Amer- ica: The common house mouse, Mus nfmsculus. The English black rat, Mus rattus. The Egyptian or roof rat, Mus alexandrinus. The brown rat, Mv£ norvegicus. The black rat and the roof rat differ from each other mostly in color, and some zoologists regard them as races of the same species. The brown rat is also known as the gray rat, barn rat, wharf rat, sewer rat, and Norway rat. The black rat {Mus rattus) has been known in Europe since the twelfth century, and from there has been carried to America. The brown rat {Mus norvegicus) came later, and, as it is more destructive, larger, and more ferocious, it is rapidly driving the black rat before it. The brown rat differs somewhat in habits from the black rat, especially in that it burrows, which protects it against its enemies and renders its suppression more difficult. The house mouse holds its own everywhere against the brown or Norway rat, as it is able to get into holes too small for the rat to fol- low. Albinism and melinism occur in all species; pied forms are com- mon. The white rat of the laboratory is an albino form of either Mus rattus or Mus norvegicus. Breeding and Prevalence. — The brown rat is more prolific than either the roof rat or the black rat. The brown rat reproduces from three to five times a year, each time bringing forth from six to nine, and sometimes as many as 22 or 23, young. They breed more rapidly in temperate and equable climates than in those of great variability. The number of rats is only limited by the food supply and opportu- nities to nest. Few people have any conception of the enormous num- bers of rats in cities and on farms. Although few are seen in the day time, at night they fairly swarm along river fronts and wharves, as well as in sewers, stables, warehouses, markets, and other places where food may be found. A few instances will illustrate the prolific habits and give an idea of the destructive tendency of rats. In 1901 an estate near Chichester, England, was badly infested with rats;i 31,981 were killed by traps, poisons, and ferrets, while it is esti- "^ne Field, London, Vol. C, p. 545, 1902, 244 INSECT-BORNE DISEASES mated that tenants, at the threshing, destroyed fully 5,000 more. Even then the property was by no means free from rats. During the plague of rats on the island of Jamaica, in 1833, the number killed on a single plantation in a year was 38,000.^ The in- jury to sugar cane on the island caused by the animals was at that time estimated at half a million dollars a year. The report of the Indian Famine Commission in 1881 affords one of the best illustrations of the number of rats that may infest a coun- try. An extraordinary number of the animals at that time inhabited' the Southern Deccan and Mahratta districts of India. ^ The autumn crop of 1878 and the spring crop of 1879 were both below the average, and a large portion of each was destroyed by rats. The resulting scarcity of food led to the payment of rewards for the destruction of the pests, and over 12,000,000 were killed. Migration. — The migrations of rats have often been recorded. The brown rat is known in Europe quite generally as the migratory rat; the Germans call it the Wanderratte. Pallas relates that in the autumn of 1772 they arrived from the East at Astrakhan, southeastern Eussia, in such great numbers and so suddenly that nothing could be done to oppose them. They crossed the Volga in immense troops. The cause of this general migration was attributed to an earthquake, but, since similar movements of the same species often occur without earthquakes, it is probable that only the food supply of the animals was involved in the migration which first brought the brown rat to Europe. Seasonal movements of rats from houses and barns to the open fields take place in the spring, when green and succulent plant food is ready for them. The return movement takes place in the autumn. This seasonal migration is notable even in large cities. In 1903 a multitude of migrating rats spread over several counties of western Illinois. They traveled in great armies and invaded the farms and villages of Rock Island and Mercer counties, and caused heavy losses during the winter and summer of 1904. In one month Mr. Montgom- ery of Mercer county killed 3,435 rats on his farm. He caught most of them in traps. In England a general movement of rats inland from the coast oc- curs every October. This is known to be closely connected with the closing of the herring season. During the fishing the rodents swarm to the coast attracted by the offal left in cleaning the herring, and when this food fails the animals troop back to the farms and villages. An invasion of rats (Mus rattus) in the Bermuda Islands occurred about the year 1615. Within two years they had increased so alarmingly that none of the islands was free from them. The rodents "devoured •■ New England Farmer, Vol. XII, p. 315, 1834. "British Med. Jour., Sept. 16, 1905, p. 623, EATS AND OTHEE EODENTS 245 everything that came in their way — fruits, plants, and even trees" — so that for a year or two the people were nearly destitute of food. A law was passed requiring every man in the island to keep 13 traps. In spite of all efforts the animals continued to increase until they finally disappeared, so suddenly that it is supposed they must have been vic- tims of a pestilence. While stationed upon Angel Island in San Francisco harbor I ob- served several migrations of rats between the army post and the quar- antine station, which were about a mile apart and separated by an in- tervening ridge. Everyone is familiar with the sudden invasion of stores, factories, and other structures with these rodent pests, which causes considerable economic loss. On Vessels. — Eats are found on all vessels; they are great travelers. It is through this seagoing tendency that the rat has become cosmo- politan. Eats get on board vessels readily as they lie at their dock; sometimes they are carried on board in the cargo. It is very important to prevent the introduction of rats on vessels at plague-infected ports; it is also important to prevent the passage of rats from ship to shore, particularly if the vessel is from a plague port. In order to accomplish this, it is necessary to exercise particular care. In extreme cases the ship should not approach the dock, but the cargo should be handled by means of lighters. When the ship lies at its moorings in a stream or in the open bay rats may get on board by swimming, and climbing in through the hawse pipe. Eats rarely swim more than one-quarter to one-third of a mile. If the vessel ties up at the dock, inverted funnels should be placed on the hawsers. The gang- planks should be watched during the day and always taken up at night. Vessels from plague ports should always be treated with sulphur dioxid, preferably when empty, and always before leaving, and also en route, to kill the rats that may be on board. A wise measure in international sanitation would be to require all vessels, whether trading at plague ports or not, to fumigate for rats no less than three or four times a year. Food. — Eats are not strictly herbivorous, as might be inferred from their dentition; they are practically omnivorous. Their bill of fare in- cludes grains and seeds of every kind; flour, meal, and all food products made from them ; garden vegetables, mushrooms, bark of growing trees, bulbs, roots, stems, leaves, and flowers of herbaceous plants ; eggs, chick- ens, ducklings, squabs, and young rabbits; milk, butter, and cheese; fresh meat and carrion; flsh, frogs, mollusks, and crustaceans; they are also cannibals. This great variety of food explains the ease with which rats maintain themselves in almost any environment. Habits. — The roof rat (Mus alexandrinus) and the black rat (Mus rattus) are more expert climbers than the brown rat, which is larger and clumsier. In buildings the brown rat keeps mainly to the cellar 15 24:6 INSBCT-BOENE DISEASES and lower jjarts, where it commonly lives in burrows. From these re- treats it makes nightly excursions in search of food. The roof rat and the black rat live in the walls or in the space between ceilings and roofs. Eats readily climb trees to obtain fruit. In the tropics the roof rat and the black rat habitually nest in trees. In the open rats seem to have defective vision; by daylight they move slowly and uncertainly; on the contrary, at the side of the room and in contact with the wall they run with great celerity. This fact suggests that the vibrissa (whiskers) serve as feelers, and that the sense of touch in them is ex- tremely delicate. The animals always prefer narrow places as highways — another circumstance which may be made use of in placing traps. The ferocity of rats has been grossly exaggerated. The stories of their attacks upon human beings, sleeping infants especially, have but slight foundation. Ordinarily the probability of being bitten by rats is remote, and the bite is not usually poisonous. Miyake ^ has described a "rat-bite disease" called Sodoku in Japan. Plague in Rats. — It is now known that rats are more or less respon- sible for cases of human plague, and in addition are the most frequent medium by which plague is carried from one locality to another. They also convey the plague infection to other rodents, such as ground squir- rels. The clinical manifestations of plague in rats are of little importance. It is generally said that a plague-infected rat staggers about with a drunken gait, loses fear of its natural enemies, and is readily captured. Eats experimentally infected show no marked manifestations of illness until shortly before death, when they become quiet, crouch in the cor- ner of the cage, and try to hide. It is rather surprising that compara- tively few plague rats are found dead in endemic centers. In the San Francisco campaign McCoy estimates that certainly not more than 20 per cent, of the infected rodents were found dead, the remainder being trapped. This is probably due to the fact that plague in rats is of several days' duration, and during this period there are good chances of catching the sick rodent in a trap, while the chance of finding the body after death is handicapped by obvious circumstances. Eats suffer both with acute plague and chronic plague, the lesions of which differ. The diagnosis of plague in rats may be made macroscopically. The Indian Plague Commission, which had the opportunity of examining an enormous number of plague rats in Bombay and elsewhere in India, state that "the results of tests carried out for the purpose of comparison make it manifest that the naked eye is markedly superior to the micro- scopic method as an aid in diagnosis, and as the result of our experi- '^ Mitt. a. d. Grenzgeb. d. Med. u. Chir., 1902; also Proescher, Internat. Clinics, TV, 25th Series, p. 77. EATS AND OTHER RODENTS 247 enee we are prepared to make a diagnosis of plague on the strength of the maeroseopical appearance alone, even though the other results of cutaneous inoculation and culture are negative and the animals show signs of putrefaction." The experience of McCoy and others in the Federal Plague Laboratory in San Francisco leads to the same conclu- sion. It should be remembered, however, that occasionally plague oc- curs in rats without gross lesions. This has been observed by Dunbar and Kister and also by McCoy. In any critical case the bacteriological confirmation is essential. Acute plague in rats is characterized by engorgement of the subcu- taneous blood vessels and a diffuse pink color of the subcutaneous structures and muscles. The diagnosis may often be inferred at the first incision. The lymphatic glands of the neck, axilla, groin, or pel- vis are enlarged and frequently surrounded by a hemorrhagic exudate and edema. The liver is granular with focal necroses, the spleen en- larged and friable, and pleural effusions are common. Chronic plague in rats has been encountered in a considerable num- ber of cases among Mus rattus in the Punjab villages of Kasel and Dhand. It has not been found in California. In the chronic disease the lesions consist of purulent or caseous foci, usually of the visceral type; that is, they occur as splenic nodules and abscesses, or mesenteric abscesses. Sometimes the abscesses are situated in the regions of the peripheral lymph glands. Plague bacilli are either absent or very scanty upon microscopic examination in these abscesses, but they may be recovered by cultural methods or more surely by inoculating the material into susceptible animals. There is no evidence to show that chronic rat plague has anything to do with the recurrence of acute plague among the rats. Eats may be infected by the ingestion of infective material or the application of virulent plague bacilli to a mucous or cutaneous surface, or by subcutaneous injection of the microorganism. The infection may also be transferred from rat to rat through the agency of the fioa. In nature the mode of transference probably takes place through all of these methods, but commonly through the fiea. Contrary to the general impression, the wild rat has a considerable resistance to plague infection. The Indian Plague Commission found that 59 per cent, were immune when inoculated by the subcutaneous method from the spleen of infected rats. A series of experiments con- ducted in the Federal laboratory in San Francisco also showed a high grade of immunity, especially among the large rats. About 15 per cent, of small rats and about 50 per cent, of large rats were found to be immune when inoculated with highly virulent material. The experi- ments demonstrated that this immunity is not acquired through a prior attack of the disease, but must be a natural immunity. 248 I]SrSBCT-BOEi;rE DISEASES The natural subsidence of plague among rats in any community is a point about which much more evidence must be obtained before we can speak with any degree of authority. It may be due to a lack of suscep- tible material, possibly to a loss of virulence of the organism, but it seems more probable that it is due to a change in the number or rela- tions of the ectoparasites of the rat. Rat Leprosy. — Leprosy occurs spontaneously among rats and bears a close resemblance to the disease in man, but it seems that the rat lep- rosy is not communicable to man. For a further discussion of rat lep- rosy see page 293. Trichinosis. — The three most important hosts for the Trichinella spiralis are man, swine, and rats. The infection is spread by one ani- mal eating the flesh of another. It is, therefore, evident that if the disease occurred only in hogs and man it would soon die out. Eats, on account of their habits, may then be viewed as the great reservoir for ■the parasites and for the disease it causes. Hence, a well-directed pub- lic health campaign against trichinosis should consider the eradication of rats, especially around slaughter houses, butcher shops, hog pens, and similar places. Trichinosis is very common among rats; they become infected by eating each other, by eating scraps of pork found on the offal pile of slaughter houses, butcher shops, or in swill. Swine become infected by eating rats and infected offal. Man becomes infected almost exclusively by eating pork or boar meat that has not been thoroughly cooked. Other Parasites. — Eats and mice may harbor eleven species of in- ternal parasites which also occur in man. Seven of these are of academic importance only. Those which concern us principally, in addition to the Trichinella spiralis, are the Hymenolepis diminuta and Laniblia duodenalis. Eats also harbor the Cysticercus cellulosm, and are suscep- tible to experimental infections with Trypanosoma gambiense, the cause of sleeping sickness. Eats have also been accused of dragging typhoid from the sewers to our food. The connection is close and the possibility apparent. A recent outbreak of typhoid fever in an asylum has, in fact, been traced to this source by Dr. Mills.'- Economic Importance, — The destruction of food, merchandise, and property by rats is so great that this alone would justify active measures of suppression, even though they were not responsible for plague, trichi- nosis, and other infections. Eats destroy grain while growing; invade stores, destroy flowers, laces, silks, carpets; eat fruits, vegetables, meat, etc., in the market; destroy by pollution ten times as much as they eat; cause conflagration by dragging matches into their holes; gnaw lead pipes and floors of houses; ruin artificial ponds and embankments by ^Brit. Med. Jour., January 21, 1911. EATS AND OTHER EODBNTS 249 burrowing; destroy eggs and young poultry; damage foundations^, floorSj doors, piers; in short, they have become the worst mammalian pest among us. It is estimated that in the United States alone the losses due to rat depredations vary from $35,000,000 to $50,000,000 annually. Suppression. — The extermination of the rat is hopeless; they are very intelligent and cautious. Extermination seems a biological im- possibility, for killing ofE large numbers gives the survivors an easier living. Millions of rats have been killed in India, Japan, San Fran- cisco, and other places during the recent plague measures without mak- ing an appreciable impress upon the numbers remaining. They may be exterminated and kept out of a limited area, such as a ship, a granary, a stable, a warehouse, a market, or local compound. In the well-built residential sections of a city, with concrete walks, asphalt streets, stone cellars, and few stables, there are very few rats. In 10 years of resi- dence in such a district in Washington I never saw or heard of one in the neighborhood. The measures for the repression and destruction of rats will be considered under: (1) rat-proof buildings, (2) keeping food from rats, (3) natural enemies, (4) traps, (5) poisons, (6) domestic animals, (7) shooting, (8) fumigation, and (9) bacterial viruses. Eat-peoof Buildings. — This is a measure of first importance in the fight against rats. Eats can only gain entrance to a cement struc- ture properly constructed through neglect or ignorance. They come in through drain pipes if left open; through doors, especially from alleys; and through basement windows. Once in, they intrench themselves in out-of-the-way places, nest behind rubbish, and are difficult to dislodge. The lower parts of the outer doors of public structures, such as markets and wharves, should be reinforced with metal to keep the rats from gnawing through. Basement windows should be screened and doors provided with springs to keep them closed. A rat-proof dwelling must have concrete footings and the walls of a wooden house should have one foot of concrete between the sheathing and lathing. All water and drain pipes should be surrounded with ce- ment. Eat holes may be closed with a mixture of cement, sand, and broken glass, or sharp bits of crockery and stone. Aside from dwellings, the chief refuges for rats in cities are sewers, wharves, stables, provision houses, markets, out-buildings, and uninhab- ited structures, Modern sewers are highways and not nesting places for rats. They find a safe retreat from nearly all enemies under wooden sidewalks. In the country it is important to build corn cribs, barns, and granaries rat-proof with the liberal use of cement, iron sheeting, or galvanized iron netting. Keeping Food from Eats. — Well-fed rats mature quickly, breed 250 INSECT-BOEFB DISEASES often, and have large litters. A scarcity of food helps all other sup- pressive measures. Garbage and oilal must be disposed of so that rats cannot get at such stuff. Well-covered garbage cans should be required and' the garbage frequently removed and burned. To deposit it upon the ground anywhere only invites and nourishes rats and other vermin. Slaughter houses are centers of rat propagation. The ofEal is best dis- posed of by burning. Care should also be taken as to the disposal of remnants of lunches in office buildings and the disposal of organic waste generally. Produce in provision stores may be protected with wire cages. Natural Enemies. — The natural enemies of the rat are the larger hawks, owls, skunks, foxes, coyotes, weasels, minks, dogs, cats, and fer- rets. The persistent killing off of the cariiivorous birds and mammals that prey upon rats has been an important factor in the increase of these rodents in the United States. Eats actually destroy more eggs, chickens, and game than all the wild animals combined. Traps. — There are many kinds of traps, such as the guillotine, spring trap, the cage trap, the barrel and pit trap. One of the best is the old- fashioned wire cage trap. The rats get in but cannot get out. In plac- ing the trap it is advisable to leave a rat in as a decoy. The trap should be placed along runways, or the entrance to the trap may be arranged so that the rats first have to go through a pipe, as they like to explore dark passages. It requires ingenuity to successfully trap rats. They are very wary and avoid man-smell. To guard against this the traps may be burned and then smeared with the bait, always handling them with tongs or properly prepared gloves. Cheese, bacon, grain, and bread are the best baits. Poisons. — Poisons are objectionable in dwellings, ov/ing to the odor of the dead rats. They are of service in granaries, stables, wharves, and similar places. Most rat poisons are dangerous to children as well as to chickens and other domestic animals, and, therefore, the greatest care must be exercised in their use. It requires experience in laying out poisons; the old rats are very smart and will refuse the bait imless artfully concealed and judiciously placed. The principal poisons used for rats are barium carbonate, strychnin, arsenic, and phosphorus. In several states the law requires that notice of intention to lay poison must be given to persons living in the neigh- borhood. Poisons for rats should never be placed in open or unsheltered places. Per poisoning rats in buildings and yards occupied by poultry the following procedure is recommended: Two wooden boxes should be used, one considerably larger than the other, and each having two or more holes in the sides large enough to admit rats. The poisoned bait should be placed in the bottom and near the middle of the smaller box, and the larger box should then be inverted over the other. Eats thus' have free access to the bait, but fowls are excluded. RATS AND OTHER RODENTS 251 The cheapest and most effective poison is barium carbonate. This may be made into a dough with four parts of meal or flour to one part of barium carbonate. A good plan is to spread the barium carbonate upon fish, on toasted bread (moistened), or upon ordinary bread and butter. Strychnin is effective and may be used by inserting the dry crystals in a piece of meat, cheese, or sausage, which is placed in the runways. Arsenic is popular; the powdered white arsenic (arsenious acid) may be used as described for strychnin or barium; or a stiff dough may be made by mixing twelve parts by weight of corn meal and one part of arsenic with whites of egg. An old English formula is one pound of oatmeal, one pound of brown sugar, and a spoonful of arsenic. Phosphorus is an effective and attractive bait. The yellow phosphorus in the proportion of one to four per cent, may be mixed with glucose or other suitable material. The use of phosphorus is very dangerous on account of fire. Rats poisoned with phosphorus may die on the prem- ises and decompose, contrary to the statements sometimes made in the advertisements. The following formula is recommended as a poisonous bait for rats, mice, squirrels, etc. : , Strychnin 1 oz. Cyanid of potassium 3 oz. Eggs 1 doz. Honey 1 pint Wheat or barley 30 lbs. Stir eggs well, then mix in honey and again stir. Then put in dry powdered strychnin and cyanid and stir until well mixed. Put wheat in large box or can and pour in the mixture of poison and stir until it is well distributed over the wheat. Stir two or three times during twenty-four hours, then spread out and dry. Before putting it out for squirrels add oil of rhodium, 1 drachm. Domestic Animals. — A well-trained dog may be relied upon to keep the farm premises reasonably free of rats. Small Irish, Scotch, and fox terriers make the best ratters; the ordinary cur and the larger breeds of dogs seldom develop the necessary qualities for ratters. However valuable eats may be as mousers, few of them learn to catch rats. The ordinary house cat is too well fed and too lazy to un- dertake the capture of an animal as formidable as the brown rat. Koch has advised the breeding and distribution of cats capable and willing to attack rats. i Shooting. — ^Many rats may be shot as they come out to forage about sundown. This method is particularly effective in a large building 252 INSECT-BOENB DISEASES which is suddenly overrun with the rodents. The shooting of a number of them upon two or three successive nights discourages the remainder, who leave for some other happier hunting ground. FuMiGATiON.^Rats may be killed with certainty in any inclosed structure by the use of sulphur dioxid, carbon bisulphid, hydrocyanic acid gas, or carbon monoxid. The methods of evolving these substances have been described in Section XII. Sulphur dioxid is particularly useful to destroy rats on board ships, in cellars, stables, sewers, and places where they abound and which are not injured by the corrosive action of the sulphur fumes. Enormous numbers of rats are frequently killed when ships are fumigated with sulphur dioxid. I have seen buck- ets full thrown overboard from comparatively small vessels. Hobdy counted 310 on a lumber-carrying schooner of only 260 tons burden. The S.S. Minnehaha, a new vessel only nine months in commission fumigated in London in May, 1901, yielded a bag of 1,700 rats. For the destruction of rats upon vessels the sulphur dioxid may be produced by the pot method, if the hold is empty, or may be generated in a Kinyoun-Francis or a Clayton furnace, or may be liberated from its compressed liquefied state. No less than three pounds of sulphur should be burned for each 1,000 cubic feet of space, and the exposure should not be less than 5 hours (see page 997). Carbon Monoxid. — Carbon monoxid is an exceedingly poisonous gas. From the fact that it has no odor it is even more hazardous in practice than hydrocyanic acid. Carbon monoxid is fatal to all forms of mam- malian life, but has no germicidal properties whatever. It has been used in Hamburg ^ and other ports for the destruction of rats on ships. Carbon monoxid is a colorless, odorless gas, lighter than air. It forms a stable compound with the hemoglobin of the blood — carbon monoxid-hemoglobin. For the toxic action of this gas and its other properties see page 637. The particular advantages of carbon monoxid for the destruction of rats on»board ship are that it may be generated cheaply, is quickly effective, and does no injury to cargo or vessel. The disadvantages are that it is poisonous and inflammable. The addition of a little sulphur dioxid to the gas makes its presence known and tends to prevent accidents. After exposure the hold must be thoroughly ven- tilated, and it is customary to lower a mouse in a cage for 10 minutes to be sure that it is safe for a man to enter. Divers' helmets should also be kept in readiness so that the hold may be entered in case of need. A gas generator has been made by Pintch which furnishes a mix- ture consisting of CO, 5 per cent., COj, 18 per cent., N, 77 per cent. These gases are generated by the incomplete combustion of coke. The ^Noeht and Giemsa: Arbeiten a. d. Jcaiserlichen Gesundheitsampte, Bd. 20, Ersten Heft, 1904, p. 91. EATS AND OTHEE EODENTS 253 mixture of gases is pumped into the hold of the vessel or other com- partments where it is desired. The hold should be kept tightly closed from 7 to 8 hours. The Bacterial Eat Viruses. — Eats are notoriously resistant to bacterial infection.^ Even plague usually fails markedly to diminish their prevalence. An epizootic of bacterial nature, therefore, cannot be classed with the natural enemies of the rat. We are not surprised, then, to learn that the bacterial rat viruses have signally failed to accomplish their mission. These bacterial viruses belong to the colon-typhoid group of organ- isms. They are either identical with or closely related to the original bacillus of mouse typhoid {B. typhi murium) discovered by Loeffler, or the paratyphoid bacillus, type B, which is frequently the cause of meat poisoning, or the Bacillus enteritidis of Gaertner, which has been asso- ciated with gastrointestinal disorders. The claim that these rat viruses are harmless to man needs revision, in view of the instances of sickness and death reported by various ob- servers. The pathogenicity for man depends upon the virulence 'of the culture, the amount ingested, the nature of the medium in which it grows, and many other factors. Danysz virus (B. typhi murium) is pathogenic for rats under labora- tory conditions, but has feeble powers of propagating itself from rat to rat. It rapidly loses its virulence, especially when exposed to light and air. The result depends largely upon the amount ingested. The other viriises have proven even less satisfactory. Under natural conditions these rat viruses may be likened to a chemical poison, with the great disadvantage that they rapidly lose their virulence and arc comparatively expensive. They also have the further disadvantage that chemical poisons do not possess of rendering animals immune by the ingestion of amounts that arc insufficient to kill or by the ingestion of cultures that have lost their virulence. Squirrels. — In August, 1903, a blacksmith died of plague probably contracted from a squirrel in Contra Costa County, California. In 1904 Currie demonstrated the susceptibility of the ground squirrel to bubonic plague. In 1908 McCoy and Wherry discovered natural plague in ground squirrels. It was then learned that thousands of squirrels had died of some disease during 1904, 190-5, and 1906. This epizootic was doubtless plague. It is now realized that plague has become en- demic in California, in the squirrel. It is also believed that the disease has been kept alive in the endemic foci of Tibet in an- other rodent, the marmot (Arctomys hobac). The eradication of plague "■ ' ' The Inefficiency of Bacterial Viruses in the Extermination of Eats, "M.J. Eosenau. "The Eat and Its Eelation to the Public Health," Bulletin of the P. H. & M. H. S., 1910. 254 INSECT-BORNE DISEASES must, therefore, consider these and perhaps other susceptible wild animals. California is overrun with three species of ground squirrels. The commonest is the Citellus ieecheyi. They live in colonies in burrows or warrens. The booby owl is a frequent companion occupying the same burrow, and they probably spread the infection by carrying fleas. Squir- rels become infected through fleas from each otlier and from' rats. The squirrel flea {Geratophyllus acutus) attacks man just as the rat flea does. The infection may also be conveyed to man through squirrel bites, as in the case of the child in Los Angeles studied by Stimson. Squir- rels make good food for man, but since the danger has been realized the shooting or trapping of them for food purposes is now forbidden in California. Plague in the squirrel may be recognized ^ by the gross anatomical lesions in the lymphatic glands, the liver, and lungs. The pneumonic form of the disease is common in the squirrel. Many cases are subacute or chronic. Smear preparations from squirrels dead of plague are frequently negative for plague-like bacilli. The diagnosis may, there- fore, be made more surely by animal experimentation. Subcutaneous inoculation is surer than the cutaneous method, as the latter often fails on account of the comparatively few plague bacilli present in squir- rel lesions. Squirrels may be destroyed by various means. One of the most successful is to saturate cotton waste the size of an orange with carbon bisulphid and place it in the warren; then close the opening with wet clay. Poisoned bait, such as strychnin, phosphorus, or cyanid of potas- sium, is effective. Traps are not very successful, as the squirrel is wary. Natural enemies, such as the coyote, wolf, badger, skunk, moun- tain lion, the cobra snake, and red-tailed hawk should be encouraged.^ PLAGUE In considering the prevention of plague it is necessary to recog- nize that the different types of the disease are spread in different ways. At least three clinical types are now recognized: (1) bubonic, (2) pneumonic, and (3) septicemic.^ In the bubonic and septicemic types of the disease the plague bacillus is locked up in the glands, blood, and other tissues and organs of the body, and are not eliminated 'McCoy: Jour, of Infect. Bis., Nov. 26, 1909, Vol. V, No. 5. ' In this chapter material has been freely drawn from ' ' The Eat and Its Eelation to the Public Health," Public Health and Marine Hospital Service, 1910, particularly articles by Lantz, McCoy, Brinckerhoflf, Banks, 8tiles, Eucker, Creel, Holdy, Kerr, and Eosenau. This book may be obtained by addressing the Surgeon-General or the Superintendent of Public Documents, Washington, D. C. * Occasionally other varieties occur in which the chief manifestations are in the skin and subcutaneous tissues, or in the intestines, causing diarrhea. In the latter case the infection is excreted in the feces. RATS AND OTHER RODENTS 255 in the usual excretions. These forms of the disease are, therefore, not "contagious," but are spread mainly through the agency of the flea. On the other hand, in the pneumonic type of the disease plague bacilli are contained in enormous numbers in the sputum. The disease is frequently transmitted directly by close association with a patient hav- ing plague pneumonia. The pneumonic type of the disease does not necessarily follow when the infection is taken into the system through the respiratory channel ; on the other hand, it may result from infection through a flea bite. The Bacillus pestis (Yersin, 1894) has more than fulfilled Koch's laws. Several accidents in which pure cultures have been inoculated into man, producing all, the symptoms and lesions of the disease, have added to the proof that this organism is the cause of plague (Vienna, 1898, Ann Arbor, 1902, and also in laboratories in Russia, Berlin, and Japan). The plague bacillus is comparatively easy to isolate and grows readily on artificial culture media, and has characteristics that readily distinguish it from all other species. It is a short rod with rounded ends, not motile, decolorized by Gram's method, and grows better at 30° C. than at blood temperature. Recognition of the plague bacillus rests upon the following charac- teristics: (1) Curious involution forms upon salt agar within 24 hours; (2) stalactite growth in liquid media; (3) characteristic lesions pro- duced by experimental plague in guinea pigs, rabbits, rats, etc. Kolle's method consists in rubbing the material containing the plague bacillus upon a shaved area of the skin of a guinea pig. The plague bacilli pene- trate the skin, leaving other pathogenic organisms behind. The skin of the guinea pig thus acts as a differential filter; (4) the final test of the identity of the plague bacillus is the fact that its pathogenicity may be ueutralized by the use of antiplague serum. The Bacillus pestis does not live a saprophytic existence in nature. It is readily killed by drying, sunlight, heat, and the usual germicides. The organism does not live long in the soil or upon the floors of houses, as was once commonly supposed. There is, therefore, comparatively little danger from these sources. Immunity. — One attack of plague usually protects for life. Occa- sionally second attacks are noted in the same person. In such cases the second attack is usually mild. This is an old observation and led to the employment of persons with a plague history or a plague scar in hospitals and laboratories. Artificial immunity of either an active or passive nature may be acquired by various procedures. The passive immunity produced by the injection of antiplague serum lasts only about three to four weeks. The active immunity produced by vaccination of cultures may be de- pended upon for about six months. 256 mSECT-BOENB DISEASES IlaffJcine's prophylactic consists of a killed culture of the plague bacillus, which is injected subcutaneously. Haffkine used a bouillon culture, six weeks old, grown at 25-30° C. and killed at 65° C, for one hour. One-half of one per cent, of phenol is then added. Prom 3 to 3.5 c. c. (this was later increased to 20 c. c.) of this vaccine are injected subcutaneously. Ten days later a second injection of a still larger amount is given. In twelve districts in India 224,228 persons were inoculated with Haffkine's prophylactic. Of these 3,399 took the disease. Of 639,600 not inoculated in the same districts 49,430 were attacked. C. J. Martin concludes that the chances of subsequent infection are reduced four- fifths, and the chances of recovery are 2.5 times as great as in the cases of the non-vaccinated. The German Plague Commission prepared their prophylactic vac- cine from a fresh virulent agar culture, suspending the bacilli in salt solution or bouillon. The organisms are killed at 65° C. for one to two hours, and 0.5 per cent, phenol added. The amount injected rep- resents one agar culture. Lustig and Galliotti extract the immunizing substance from the bacterial cell (endotoxin) with weak potassium hydroxid. This nucleo- protein is collected and dried, and thus permits of exact dosage. The amount injected is two to three milligrams of the dry extract dis- solved in water. Terni and Bandi recommend the peritoneal exudate of plague- infected guinea pigs, sterilized fractionally at 50° C, and the addition of 0.5 per cent, of phenol, 0.25 per cent, sodium carbonate, and 0.75 per cent, sodium chlorid. Shiga prefers a combined active and passive immunity produced with killed cultures and antipest serum, because this mixed immu- nizing process has the advantage of producing milder reactions. Kolle and Strong started out from the principle that a much higher degree of immunity is produced by living microorganisms than dead ones, and recommend the use of live attenuated cultures. Strong has a strain, an entire agar culture of which may be injected into man without harm. In Manila 42 persons were given a preventive inocula- tion with this culture. The reactions which follow vaccination with a plague culturej whether alive or dead, are sometimes marked. The symptoms consist of a rise in temperature to 39° C, malaise, depression, and headache, and swelling and pain at the site of the inoculation. The symptoms usually pass away in 24 to 48 hours. The production of an active acquired immunity has a distinct prac- tical usefulness in the prevention of the disease, although it cannot take the place of rat and flea eradication. It has been used on a large EATS AND OTHER EODBNTS 257 scale by Haffkine in India, and to a lesser extent by others in many parts of the world during the recent plague pandemic. Those who get plague after Haffkinization usually have a mild form of the dis- ease, which, in the experience in India, rarely results in death. The active immunization of the community in the face of an epidemic is a valuable addition to our preventive measures against plague. It is of first importance in protecting small communities, on ship- board, in camps and barracks, at quarantine stations, in plague labora- tories, among rat brigades, as well as for physicians, nurses, and others who are exposed. Yersin's serum is obtained from a horse that has received repeated injections of plague cultures; at first killed plague cultures, afterward living bacilli, are used. At most this antitoxic serum is weak, and, while it has a certain amount of protective properties, it has slight curative power. Very large quantities must be administered early in the disease to obtain any effect at all. The protection lasts only a few weeks, three to four at most, and is, therefore, of limited practical use. Endemic Foci. — There are four historic endemic foci in which plague has slumbered for ages. One is on the eastern slope of the Himalayas, in the valley of the Yiinnan. The great epidemic in Hongkong in 1894 came from this center. A second endemic focus near, and perhaps con- nected with the first is on the western slope of the Himalayas. From here the infection was carried to Bombay in 1896, where it still prevails. A third plague focus exists from about the center of Arabia to near Meso- potamia. From here the infection was dragged to Samarkand, the Black Sea, and Persia. The fourth endemic area was discovered by Koch in 1898 in the interior of Africa, near the source of the White Nile in Uganda. We must now add to this a fifth endemic focus, for plague has obtained a foothold in California in the ground squirrels, which will take years of well-directed energy to control. The disease has caused dreadful havoc in India since 1892. In 1907 over one million persons died of plague in that country. Plague is kept alive in the endemic foci in the rat, the ground squirrel, the marmot, the brush rat, and other rodents. The campaign of eradicating plague in the ground squirrel in California has been directed to killing as large a number of these animals as possible. For this purpose carbon disulphid, sulphur dioxid, hydrocyanic acid gas, bait poisoned with strychnin, and cyanid of potassium are used. Natu- ral enemies, such as the coyote, wolf, fox, badger, snake, mountain lion, skunk, and red-tailed hawk, are encouraged. Trapping has not proven successful, as the squirrel is a very wary animal. Many squir- rels may be shot, but those killed should not be used for food. Management of a Plague Epidemic. — The handling of a plague epidemic is conducted along two definite lines of activity. One is to 258 INSECT-BOENB DISEASES find and care for the human cases, the other consists in a warfare against rats. The organization and general management of a plague campaign do not differ radically from similar work in other epidemics (see page 319). Cases of the disease must be sought for and early diagnosis confirmed; all deaths from no matter what cause must be investigated, and the body examined by an expert before burial is per- mitted. A bacteriological laboratory is a sine qua non. Cases of the disease should be isolated and the usual disinfection of excreta and surroundings exercised. Particular care must be taken that the isola- tion wards are vermin-free. The place from which the case is removed should then be given a preliminary disinfection with sulphur dioxid or other substance that may be depended upon to kill rats and fleas, and a search made in the neighborhood for secondary cases both in man and rodents. The campaign against the rat is expensive and difficult, but must be vigorously prosecuted to insure success. The rat warfare may be briefly summarized as a simultaneous attack upon the habitation and food supply of the rat; the destruction of rat burrows and nesting places ; the separation of the rat from his food supply by concreting and screening such places as stables, warehouses, markets, restaurants, etc.; the prevention of the entry of the rat into human habitations by the use of concrete, wire netting, or other barriers; and the use of poisons, traps, etc. For further consideration concerning rats and their eradi- cation see page 342. All the rats that are caught in traps or found dead are brought to the bacteriological laboratory, where they are ex- amined and careful records kept concerning the species, the location, the place where the rat was caught, the character of the infection, etc. As it is a hopeless task to exterminate rats from a large city, Heiser has proposed a practical plan which proved effective in Manila. A list of the places in which the plague-infected rats were found was made. Each was regarded as a center of infection. Eadiating lines, usually five in number, were prolonged from this center, evenly placed like the spokes of a wheel. Eats were caught along these lines and examined. Plague rats were seldom found more than a few blocks away. The furthermost points at which the infected rats were found were then connected with a line, as is roughly shown in the diagram. Figs. 38 and 39. The place inclosed by the dotted line was regarded as a section of infection. The entire rat-catching force was then concen- trated along the border of the infected section, that is, along the dotted line. They then commenced to move toward the center, catching the rats as they closed in. Behind them ratproofing was carried out. One section after another was treated in this way, until they had all been wiped out. Once weekly thereafter rats were caught in the previously infected sections and at other places, especially those which had been RATS AND OTHER RODENTS 259 infected in years gone by. Since the above system was adopted plague has disappeared in the city of Manila, and at a cost of only a small fraction of that of a general rat extermination campaign. ftuarantine. — Plague infection is frequently carried over seas in vessels. When this happens it is more apt to be due to the disease in the rat than man. Maritime quarantine, therefore, finds its greatest justification in keeping out plague. To be successful, measures must be directed almost entirely against the rat, although a keen eye must Generai. scheme ^ FOR TCSriM& PLAOUe RAT INFCeriON CiTv OF Manila. ' Sanitary Nap BURCAU or HUITH. FlQ. 42. be kept on the lookout for mild cases known as Pestis minor, or walk- ing plague. Rats may be kept down on board a vessel by the frequent use of sulphur dioxid. All vessels trading with a plague-infected port should have each cargo compartment fumigated with this gas, at least when it is empty, at the port of departure. The vessel must be again fumigated with sulphur dioxid on arrival. Both at the infected port and at the port of arrival care must be taken to prevent the ingress and egress of rats. The period of detention of the personnel for a plague ship is seven days. For further details concerning quarantine see page 331. 260 INSECT-BOENB DISEASES Prevention — Summary. — The principles and many of the details for the prevention of plague have been stated in the foregoing pages, and need not be repeated. Personal prophylaxis consists in avoiding the infected regions and guarding against flea bites. Physicians and nurses should remember that the pneumonic form of the disease is highly "contagious" in the ordinary sense of the term. Attendants and persons who come in con- tact with such cases may protect themselves with Haifkine's prophylac- tic or Yersin's serum. Individual measures to guard against droplet Fig. 43. — Isolated Plague-infested Centek, Manila, P. I. infection, such as the wearing of masks or veils of cheesecloth, may be resorted to. The bubonic and septicemic forms of the disease are not, as a rule, directly communicable, and, therefore, the preventive measures recommended for typhoid fever are effective. The ordinary germicidal solutions, such as bichlorid of mercury, 1-1,000, carbolic acid, 214 per cent., formalin, 10 per cent., are effec- tive against the Bacillus pestis. Of the gaseous disinfectants sulphur dioxid is preferred, because it not only kills the frail plague bacillus, but also destroys rats, fleas, etc. Cases of plague should be isolated in a well-screened room other- wise free of insects. Fabrics and other objects which become contam- TICKS 261 inated with the discharges should be thoroughly disinfected by proper methods. It is important to have prompt reports of all cases of suspected plague, and the diagnosis must be confirmed by bacteriological meth- ods. In all plague centers there should be a special hospital and also a laboratory where diagnostic work may be carried on; this is an es- sential part of the equipment for a successful campaign. A traveling laboratory organized like a flying squadron for quick service should be provided to furnish this service wherever it may be demanded. The prevention of plague, after all, is reduced to warfare against rats and fleas. This has been fully discussed. All seaport towns hav- ing communication with plague countries would do well to examine for plague rats caught from time to time about the wharves. This, in fact, should be one of the routine duties of the port sanitary authori- ties. Plague may slumber in the rats for years before human cases occur. Other preventive measures are obvious from the nature of the infection and its mode of transmission, or have already been stated in the preceding pages. , TICKS Ticks belong to the family Ixodids, and the diseases which they transmit are known as ixodiasis. Quite a number of different species are known to attack man. Ticks, or wood lice, are not true insecta, but belong to the acarines which include the mites, and are closely allied to spiders and itchmites (scabies). Ticks have an unsegmented body with eight legs in the adult stage and six legs in the larval stage. In some of their habits they resemble bedbugs. So far as is known, they take no vegetable food, but live on blood. Ticks are ectoparasites of man and many animals. They frequently hang tenaciously to the skin, in which they partly bury themselves. If covered with oil or vaselin, thus clos- ing their breathing pores situated behind the fourth pair of legs, they may be induced to release their hold. If pulled off roughly the head (capitulum) is likely to break off and remain in the skin. Sulphur in some form is useful to destroy ticks in the adult stage. Sulphur ointment is particularly obnoxious to this group of parasites. Ar- senic and crude oil also act as poisons to the tick, and may be used by local application. The life cycle of the tick consists of four distinct stages, viz.: egg' (embryo), larva, nymph, and adult. The eggs are invariably deposited on the ground in large masses. The larvas which emerge from the eggs are minute six-legged creatures. The larvae attach themselves to a suitable host, upon which they feed, then usually drop to the ground 19 263 INSECT-BOENE DISEASES and molt, becoming nymphs. The nymphs have eight legs. The nymph waits until it can attach itself to a host, engorges blood, usually drops, molts its skin, and becomes adult. The life history of the tick differs from the mosquito in that the larval and pupal stages are not aquatic. It was first shown by Smith and Kilborne that in the case of Texas fever the microorganism within the adult tick passes into the egg and is, therefore, transmitted '^hereditarily" to the next generation. The infection of Rocky Mountain spotted fever, of canine piroplasmosis, and probably also that of African tick fever, is also transmitted by the female to the next generation. Tick-borne diseases are not always transmitted in nature in this way. The virus may be transferred directly by the larva, the nymph, or the adult. Thus some ticks leave their host re- peatedly, and the parasites they draw from one animal may be injected into another animal either during the same or at a subsequent stage in the development of the tick. Ticks upon domestic stock may be controlled by dipping, spraying, or by hand methods. The arsenical dip has practically displaced all others for the destruction of ticks in the various parts of the world. Crude oils have been used to a considerable extent in some cases. They are more expensive than the arsenical dip, and dangerous to cattle under some conditions. Serious losses have followed the use of heavy oils in dry regions, or where it has been necessary to drive the cattle any considerable distance after dipping. The formula for the arsenical dip is as follows: Sodium carbonate (sal. soda) 34 lbs. Arsenic trioxid (white arsenic) 8 lbs. Pine tar 3 gals. Water sufficient to make 500 gals. Sometimes dipping is not practical. Instead of driving cattle con- siderable distances to dipping vats it will be found sufficient to treat them thoroughly by hand methods. The procedure consists simply in applying the arsenical mixture liberally by means of rags, mops, or brushes, or by means of spray pumps. Crude oil may be used by hand instead of the arsenical solution. For most tick-borne diseases cattle must be dipped or treated weekly. The following diseases transmitted by ticks will be given brief con- 'sideration: Texas fever (Margaropus annulatus), South African tick fever {Ornithodoros savignyi), Eocky Mountain spotted fever {Bermw- centor venustus), and relapsing fever (Ornithodoros mouhata). Al- though it is probable that the latter disease is also transmitted by the Argas persicus, and perhaps other biting insects. TICKS 263 TEXAS FEVEB Texas fever or splenetic fever is also known as bovine malaria, tick fever, and hemoglobinuria. The disease does not affect man. It is confined to cattle, and is of very great economic importance. Texas fever is an infection which should be understood by all sanitarians, on account of its scientific and historic importance. The cause of this in- fection and its mode of transmission were ascertained in 1893 by Smith and Kilborne. The discovery that the tick is the intermediate host of Texas fever opened an entirely new principle in the sanitary sciences. Texas fever is caused by a protozoon parasite. This parasite was first named Pyrosoma bigeminum on account of the twin-like, pear- shaped forms commonly seen in the red corpuscles. This genus was changed by Patton in 1895 to Piroplasma. These terms having been preoccupied, the present name of the parasite is Babesia bigemina} Fig. 44. — ^The Texas Fevbb Tick (Margaropus anncUatus). The contagium is carried by the cattle tick, Boophiliis bovis, now M. annulatus. The tick lives upon the skin and feeds upon the infected blood, becomes sexually mature at the last molt; the female drops to the ground and lays about 2,000 eggs; the newly hatched larvse attach themselves to the skin of a fresh host, which they infect. This explains the long extrinsic period of incubation in this disease, 40-60 days; 30 days of which are required for the development of the larvse and the remainder for the development of the parasite within the host. BOCKY MOUNTAIN SPOTTED FEVER This disease, also called tick fever and spotted fever, is an interest- ing infection which occurs chiefly in the Bitter Eoot Valley of Montana, centering around Missoula. Cases also occur in the neighboring states ' These various names are given for the reason that they are all found in the literature. 264 INSECT-BOENB DISEASES of Idaho and "Wyoming. The symptoms closely resemble those of ty- phus fever, including a petechial eruption. Anderson and Goldberger have shown that typhus fever of Mexico, called tabardillo, is not trans- f*arff«en5«*** Fig. 45.— Rocky Mountain Spotted Fever Tick. {Dermacentor venustus). 1, Adult female, unengorged, dorsal -view; 2, Adult male, dorsal view; 3, Adult female, imengorged, ventral view; 4, Adult male, ventral view; 5, Adult female in act of de- positing eggs. missible to guinea pigs, while Eicketts and also King independently demonstrated that some of the infected blood of a case of Eocky Moun- tain fever injected into a guinea pig will reproduce the chief features of this disease. The two diseases are, therefore, distinct. TICKS 265 Wilson and Chowning first suggested that the tick acta as the car- rier of Eocky Mountain spotted fever. This was proven by Eicketts in 1906, who showed that the particular tick is Dermacentor occiden- talis (now venustus). The infection may be transmitted by the larva, the nymph, and both the adult male and female ticks. The infection is also transmitted hereditarily through the ticks to their larvae. The disease has been transmitted through the tick from man to monkey and the guinea pig, and also from monkey to monkey and from guinea pig to guinea pig. A few infected ticks have actually been found by Eicketts in nature. Mayer ^ has proved by experiment that different species of ticks col- lected from various regions [Dermacentor marginatus (Utah), Ambly- omma americarms linncBus (Missouri), and Dermacentor variabilis (Mass.)] are able to transmit the virus of Eocky Mountain spotted fever. The inference is that the disease may find favorable conditions for its existence in localities other than those to which it is now limited. One attack of the disease establishes a rather high degree of immu- nity to subsequent attacks. The blood serum of recovered eases con- tains protective properties of a rather high degree for guinea pigs. The virus is not filterable through a Berkefeld filter. The nature of the virus is not known. The prevention of Eocky Mountain spotted fever is directed en- tirely against the tick. Ticks are to be avoided in the infected region. If it is necessary to work in the fields and woods and about animals where these ticks abound, the bites should at once be cauterized with strong carbolic acid. A vigorous campaign should be carried on by the health authorities to destroy all the ticks in and about each case of the disease. The ultimate control of Eocky Mountain spotted fever depends upon the suppression of the Dermacentor venustus. This, perhaps, is not so hopeless a task as may at first seem likely.^ Henshaw and Birdseye ^ found twenty species of five hundred mammals examined in and around Bitter Eoot Valley to carry ticks either in the immature or adult stage. The mammalian hosts of fever ticks fall naturally into two groups: those that harbor chiefly adult ticks and those that harbor the younger stages. In the former class belong mountain goats, bears, coyotes, badg- ers, woodchucks, and possibly elk, deer, mountain sheep, rabbits, and domestic stock, such as horses, cattle, and sheep. Those of the second class harboring the nymphs and larvae are mainly rodents and comprise ground squirrels, woodchucks, chipmunks, pine squirrels, mice, and "^Jour. Infect. Vis., April 12, 1911. " Fortunately the Dermacentor venustus is the only tick in the endemic region which attacks man. ' U. S. Dept. of Agr., Bureau of Biol. Survey, Cir. 8S. 266 INSECT-BOENE DISEASES wood rats. These smaller animals are too agile to permit the adult ticks to remain upon them. Unquestionably the great bulk of fever ticks (Dermacentor venus- tus) which become engorged in the Bitter Eoot Valley do so on do- mestic stock — horses, cattle, sheep, and sometimes dogs. They ob- tain the ticks from the pastures and other uncultivated land infested by wild animals. It is obvious, therefore, that, if the domestic ani- mals in the valley are rendered tick-free by dipping, spraying, or by some other equally effective method, the chances of the infection of human beings will be vastly lessened. Dipping carried on upon an exten- sive scale throughout the endemic area by McClintic has given surpris- ingly successful results, there having been fewer cases of the disease this season in the Bitter Eoot Valley than for any year of record. Supplementary measures for the control of Eocky Mountain spot- ted fever consist in the reduction of the number of rodents and the clearing of the brush land along the edges of the valley.^ McClintic infected Ehesus monkeys and guinea pigs with spotted fever and treated them with the following drugs : salvarsan, sodium cacodylate, and urotropin. The results obtained, however, do not in- dicate that any of these drugs possess any value whatever either as a prophylactic or in the treatment of spotted fever, but, on the contrary, their administration seems on the whole rather to intensify the severity of the disease in the animals compared with the course of the disease in the controls.^ RELAPSING FEVER Eelapsing fever, also called famine fever and seven-day fever, is found upon all the five continents of the globe. Epidemics of this disease have been reported, especially from Ireland and Eussia. The infection prevails in India, where Vandyke Carter of Bombay made his classic investigations. Eelapsing fever was epidemic in New York and Philadelphia in 1869. It has not reappeared. The disease has receded from civilization where cleanliness is observed. Obermeier in 1868 discovered the spirillum in the blood — Spirillum ohermeieri. Carter and Koch in 1878 showed that the infection may be transferred to apes by the inoculation of the blood of a patient. Miinch and Moczutkowski transferred the disease by the inoculation of relapsing fever blood to healthy individuals. Koch succeeded in dem- onstrating that the spirochetes of African relapsing fever multiplied in the tick {Ornithodoros moubata), and that the bite of this tick may convey the disease to healthy men. The African relapsing fever 1 Hunter, W. D., and Bishopp, F. C. : "The Rocky Mountain Spotted Fever Tick," Bureau of Entomology Bull. No. 105, U. S. Dept. of Agr. " V. S. Pui. Health Reports, Vol. XXVn, No. 20, May 17, 1912. TICKS 367 which Koch studied in East Africa shows some slight differences from the European disease. Although Koch and also Button and Todd demonstrated that the African relapsing fever may be transmitted through the bite of a tick, it is very probable that in Europe and other countries where re- lapsing fever occurs the disease may also be transmitted by the Argas persicus. In fact, other insects, as bedbugs, fleas, biting flies, and lice, may convey the infection. Leishman ^ has demonstrated that the Spirochmta duttoni may be transmitted hereditarily in the tick. He has obtained positive results in the second generation, the bites of which were infective for mice and monkeys. Attempts to carry the infection to the third generation in the tick have so far failed. Leishman considers the hereditary trans- mission of the infection as biological evidence that the spirochetes be- long to the protozoa rather than the bacteria. Schuberg and Manteufe '^ found that a temperature of 23° C. is not favorable for the spirochete in the Ornithodoros moubata. This was shown by experiments upon rats in which the infection through the bite of the tick disappeared more quickly at 22° C. than at higher temperatures. One attack protects against subsequent attacks. Second attacks among negroes in Africa in after years are very light. The only sus- ceptible animals are man, the apes, mice, and rats. The prevention of relapsing' fever is based upon personal and domes- tic cleanliness and the avoidance of tick and other bug bites. Personal prophylaxis depends upon keeping aloof from vermin-infested places, especially where the disease prevails. Manson suggests that a mosquito net, a bed well off the ground, and a night light are indispensable in Africa, where the nocturnal habits of the Ornithodoros moubata ren- der the hours of sleep especially dangerous. SOUTH AFRICAN TICK FEVER This is a febrile disease common in parts of Africa. The incubation is from five to ten days and the attack lasts from two days to a week or more, with abdominal pains, chills, vomiting, diarrhea. Eelapses do not occur as in relapsing fever. The disease is caused by a spirillum very similar to the Spirillum obermeieri, but shown by Novy and others to have slight differences. The spirillum was demonstrated in 1905 by Button, who also showed that the infection can be transferred to monkeys by the bites of young ticks at their first feeding after hatching from infected parents. Here again is an instance of the hereditary ^Lancet, Jan. 1, 1910, Vol. 1, p. 11. 'Zeitschr. f. Immwiitdtsforschung, Orig. Bd. 4, 1910, p. 512. 268 INSBCT-BOENE DISEASES transmission of the parasite in the insect host. Button accidentally inoculated himself through a wound on the hand at an autopsy and developed the disease which caused his death. The particular tick in this case is the Ornithodoros savignyi. The prevention of the disease depends entirely upon a knowledge of the biology of the tick and efforts to guard against its bite, to prevent in- fection of the ticks, and to destroy them, as far as possible, in the in- fected regions. LICE The insects known as pediculi or lice are parasitic during their entire life on warm-blooded animals, including man. They are de- graded, flat, rather elongate, wingless insects with a small head and stout legs which end in a strong claw, opposable to a projection at the tip of the penultimate joint. The mouth parts are of a very pe- culiar nature. There is a short beak or proboscis in front. Through this beak extends a slender stylet which has three parts. The stylet is used to pierce the skin of the host and the blood is thus sucked up through the proboscis. Lice usually walk sideways, but do not travel much and keep fairly close to one host. The eggs are slightly elongated and fastened to the hair of the host or clothing. They hatch in about ten to fifteen days, the young coming out of the top of the egg. These young do not differ much in structure from the adults, but are paler in color. They molt their skin a few times, probably four, before they reach the matured condition. The males are less numerous than the females, and ordinarily smaller. There are several generations each year, dependent, doubtless, on the temperature, but the life history is not thoroughly known for any species. It is the blood-sucking habits of lice which render them dangerous parasites and capable of transmitting disease from one host to another. Fortunately, they do not readily change hosts, so that they cannot be considered quite as dangerous as some more active parasites. There are about 50 or 60 known species which are arranged in 15 genera and 4 families. It is Pediculus vestimenti, the clothes or body louse, which is mainly responsible for the transmission of typhus fever. Three species of lice are found upon man: (1) Pediculus capitis (now humanus), the ova of which are attached to the hairs and can readily be seen as white specks, known as nits. (2) Pediculus vesti- menti (or corporis), the clothes or body louse, lives on the cloth- ing, and in sucking the blood causes minute hemorrhagic specks, com- monly about the neck, back, and abdomen. (3) Pediculus (or Phthirius) pubis or crab louse is found in the parts of the body cov- ered with short hairs, as the pubes; more rarely the axilla and eye- brows. LICE 269 The prevention of lousiness is almost entirely a matter of personal cleanliness. However, the most scrupulous individuals may become infested. Lice may be passed directly from one person to another, or occasionally may be carried by flies, or other means. Beds in hotels and sleeping cars are sources of infection. Human lice may be destroyed with kerosene, turpentine, carbolic acid (1-50), bichlorid of mercury solutions, tincture of coeculus in- dicus, and other well-known insecticides. It is comparatively easy to destroy the adult insect, but the eggs are resistant. On badly infected heads, therefore, the hair should be cut short. To free the hair of lice a good practice is to use equal parts of kerosene and olive oil. Eub the mixture well into the scalp, then cover the hair with a piece of muslin and fasten it about the head. Care must be exercised to avoid a lighted gas jet or flame. In the morning wash the scalp well with soap and hot water, then use a fine-toothed comb wet in vinegar to remove the nits. Eepeat the treatment two or three nights. In the case of the body louse the clothing should be boiled, baked, or steamed. Articles injured by heat may be subjected to sulphur fumes or dipped in carbolic acid solution. Carbon bisulphid and hydro- cyanic acid are also effective. For pubic lice white precipitate or mercurial ointment should be used and the parts thoroughly washed two or three times a day with soft soap and water. The principal disease known to be transmitted by lice is typhus fever, but it is suspected in relapsing fever and other infections. TYPHUS FEVEB Typhus fever was formerly confused with typhoid fever, but Ger- hard in 1829 was the first to insist upon the non-identity of these two diseases. Previous to that time typhus fever was the prominent and prevailing disease, while typhoid fever was of secondary interest. Now the situation is reversed; typhoid fever has become pandemic, while typhus fever has receded with civilization and improvements in sani- tation. Epidemics of typhus fever are now rare, except in a few places, notably the Grand Plateau of Mexico, where the disease prevails extensively and with a high mortality. It prevails also in certain por- tions of Ireland, in some provinces of France, portions of Eussia, particularly Poland and the east sea provinces, and at times in Tunis, Algiers, and Egypt in Northern Africa; in Spain, Hungary, and cer- tain provinces of the Baltic States. Typhus fever last prevailed in epidemic form in the United States in New York in 1881-82 and again in 1892-93, and in Philadelphia in 1883. Since then, except for a few sporadic cases at our seaports, the 270 INSECT-BOENE DISEASES disease has been thought to be non-existent in the United States. How- ever, Anderson and Goldberger ^ have recently shown that the symp- tom-complex known as "Brill's disease" is in reality typhus fever, and that the typhus fever of Europe and the typhus fever or "tabardillo" of Mexico are the same disease. It is now evident that typhus fever has been existent in New York a great many years, certainly since 1896, when Brill first observed cases of what was known, previous to the work of Anderson and Goldberger, as "Brill's disease." The disease in New York is generally mild, but seems to be on the increase; there- fore, we face a new sanitary problem in this country. Typhus fever, when prevalent in epidemic form, has been said by the older writers to be one of the most highly contagious of febrile diseases, doctors and nurses and others in close contact with the dis- ease being almost invariably stricken. The sad case of Eicketts, who lost his life in endeavoring to unravel this pathological puzzle in Mex- ico, is still fresh in mind. The period of incubation of typhus fever is from five to twenty days, with an average of twelve. One attack apparently confers a very definite immunity, second attacks being very unusual. The cause of the infection is unknown. Methods of prevention have been given a sound foundation through the recent work of Nicolle of France, Eicketts and Wilder of the Uni- versity of Chicago, and of Anderson and Goldberger of the U. S. Pub- lic Health and Marine Hospital Service. It is now clear that the virus exists in the circulating blood during at least all of the febrile stage and possibly in some instances for thirty-six hours after the crisis. The disease may be transmitted by blood inoculations to chimpan- zees and probably to all the lower monkeys. The virus as it exists in the circulating blood is apparently held back by the Berkefeld filter. It is not killed by freezing for eight days, but is deprived of virulence by heating at 55° C. for 15 minutes. Monkeys that recover from the experimental disease show a definite immunity to subsequent infection. Nicolle in 1909 was the first to report the transmission of typhus fever by the bite of the body louse (Pediculus vestimenti) . Since then his work has been confirmed by Eicketts and Wilder and by An- derson and Goldberger. These latter authors have recently shown that the head louse (Pediculus capitis) may also transmit the infection. The role of the body louse in the transmission of typhus fever will receive ready support from students of the epidemiology of typhus fever, for this disease presents all the characteristics of insect-borne ^Anderson, John P., and Goldberger, Joseph: "The relation of so-called Brill's disease to typhus fever; an experimental demonstration of their identity " Public Health Reports, XXVII, February 2, 1912. LICE 271 disease. Since the transmission of the disease by the body louse has been shown, we can understand why typhus fever prevails in epidemic form only in overcrowded, filthy, unhygienic surroundings, and the truth is readily understood of the oft-quoted sentence of Hirsch, that "the history of typhus is the history of human wretchedness." The disease has greatly decreased from civilized centers with dim- inution in lousiness. The prevention of typhus now focuses itself upon the eradication of the body louse. Fortunately, this insect does not of itself travel far, but it may be carried many miles upon the body or in the clothing. The eradication of the body louse is largely a question of personal cleanliness, and, so far as typhus fever is con- cerned, is closely interwoven with squalor, ignorance, and poverty. Now that we know how the disease is spread, measures may be in- telligently applied for its prevention, these measures being primarily directed to the destruction of the Pediculus vestimenti and its eggs. When a case of typhus fever is discovered the patient should be re- moved to a vermin-free room or hospital. The patient's clothes should be removed and either placed in boiling water or a 1-500 solution of bichlorid of mercury for the destruction of lice and their eggs. The patient's hair should be clipped and he should then be given a thor- ough sponging with a 1-2,000 solution of bichlorid of mercury for the destruction of lice eggs. The room or apartment from which the pa- tient was removed should be thoroughly fumigated by the burning of sulphur for the destruction of lice, and the room kept sealed for at least 12 hours. The fact should be kept constantly in mind that the louse is neces- sary for the spread of typhus fever, just as the mosquito is for the spread of malaria, and our efforts toward prophylaxis should be con- ducted with this point continuously in mind. Even with the knowledge of the mode of transmission of typhus fever individual prophylaxis is still somewhat difficult, especially where infected insects abound in thickly populated centers. Those whose duties — such as doctors and nurses — take them into an infected area should avoid outer clothing which is liable to brush against the furniture, bedding, etc. The skirts of nurses should be sufficiently short to avoid touching the floor; trousers should be rolled above the shoe-tops and the sleeves above the elbows, so that occasional vermin which may lodge on the hand may be more readily detected. Eucalyptus oil has been recommended for smearing the neck, wrists, and ankles. Personal prophylaxis may also be assisted through the use of gloves, veils, netting, and similar mechanical devices. The cloth- ing worn by those attending cases of the disease where lice are present should be frequently changed and close attention given to personal cleanliness. 272 INSBCT-BOENE DISEASES BEDBUGS Cimex lectularius has been carried by man to all parts of the in- habited world. It has become a true domesticated animal and has accommodated itself well to the environment of human habitations. The bedbug has no wings and a very flat body, which enables it to hide in the narrowest chinks and cracks of beds and wells. It may subsist for incredibly long periods of time without food. It is nocturnal in its habits. The pronounced odor of this insect is produced by certain glands opening on the back of the abdomen in young bugs and on the under Fig. 46. — The Bedbug. o, Adult female, gorged with blood; 6, Same from below; c, Rudimentary wing pad; d. Mouth parts. (Marlatt.) side of the metastemum in the adults. The odor is common to most members of the group to which this insect belongs. It is useful in plant bugs, protecting them from their enemies. The bedbug undergoes an incomplete metamorphosis, the young be- ing very similar to their parents in appearance, structure, and habits. The eggs are white, oval objects having a little projecting rim around one edge, and are laid in batches of from six to fifty, in cracks and crevices where the bugs go for concealment. The eggs hatch in a week or ten days and the young escape by pushing the lid within the projecting rim from the shell. At first the larvae are yellowish-white, nearly transparent, the brown color of the more mature insect increas- ing with the later molts. During the course of development the skin is shed five times, and with the last molt the minute wing pads, char- acteristic of the adult insect, make their appearance. Marlatt found that under favorable conditions about seven weeks elapse from the egg BEDBUGS 273 to the adult insect, and that the time between each molt averages about eight days. Without food they may remain unchanged for an indefinite time. Ordinarily but one meal is taken between molts, so that each bedbug must puncture its host five times before becoming mature, and at least once afterward before it can develop eggs. The presence of bedbugs in a house is not necessarily an indication of neglect or carelessness. They are very apt to get into trunks and satchels of travelers or may be introduced in the homes upon the cloth- ing of servants, workmen, or visitors. The bedbug is quite capable of migrating from one house to another. Ships are almost sure to be infested with them. They are not specially limited by cold, and are known to occur well north. They thrive particularly in old houses which are full of cracks and crevices, in which they can conceal them- selves beyond easy reach. The biting organ of the bedbug is similar to that of other Hemipterous insects. The skin of the host or victim is pierced with four thread-like hard filaments or setae, which glide over each other with an alternating motion and thus pierce the skin. The blood is drawn up through the beak, which is closely applied to the point of puncture. The bite of the bedbug is decidedly poisonous to some individuals, resulting in a swelling and disagreeable inflamma- tion. The Suppression of Bedbugs. — On account of its habits of conceal- ment the bedbug is usually beyond the reach of the ordinary insect powders, which are practically of no avail against it. If iron or brass bedsteads are used, the eradication of the insect is made easier. Large wooden bedsteads furnish many cracks and crevices into which the bugs can force their flat thin bodies, and extermination becomes a matter of considerable difficulty. The most practical way of eradicating bed- bugs is by a very liberal application of gasolene, benzine, kerosene, or any other of the petroleum oils. These must be introduced into all crevices with small brushes or feathers, or by injecting with small syringes; a saturated solution of corrosive sublimate in water is also of value, and oil of turpentine may be used in the same way. The liberal use of scalding hot water or soap suds wherever it may be em- ployed without damage to furniture is also an effectual method of de- stroying both eggs and active bugs. Fumigation with hydrocyanic acid gas, sulphur dioxid, or carbon bisulphid are alike effective. Crevices in warm parts of the room are favorite nesting places, as under picture mouldings, or over door frames. In sleeping cars and other places where hydrocyanic acid gas may be used without fear of accidents, this is the most efficacious and least destructive method. The bedbug has long been under suspicion as an intermediate host in the transference of many communicable infections. There is more 274 INSECT-BORNE DISEASES than a suspicion that it is concerned in relapsing fever, in kala-azar, and it has been accused of carrying the bacteria of tuberculosis, leprosy, and many other diseases. KALA-AZAR Kala-azar is a tropical infection characterized by anemia and en- largement of the spleen. It is caused by a parasite which occurs in great numbers in the spleen and which, upon culture media, develops into a flagellated organism resembling the trypanosomes. The trypano- somes were discovered by Leishman and Donovan in the spleen and liver and the epithelium of the blood vessels. Manson and Low found similar bodies in the ulcerous mucous membranes of the intestines, and Marchand and Ledingham found the same peculiar bodies in the cells of the bone marrow and lymphatic glands. Rogers cultivated the para- sites from the spleen of patients suffering with kala-azar upon agar streaked with fresh human blood. Elagellate forms developed. This was confirmed by Christophers, who used Novy's method of growing trypanosomes upon the water of condensation of blood agar tubes. The kala-azar parasites grown in artificial culture media have a cilium but no membrane. References. — The literature upon insects and insect-borne diseases is very widely distributed. Many of the entomological facts contained in this chapter have been taken from "The Insect Book" by L. 0. Howard and the many excellent publications of Howard and his col- leagues of the Bureau of Entomology, Department of Agriculture. The Government publications may be had upon application to the Su- perintendent of Documents, Washington, D. C. Many of the facts concerning the prevention and destruction of mosquitoes have been taken from articles in the Public Health Reports of the Public Health and Marine Hospital Service. In the chapter upon insecticides free reference has been made to my own book upon "Disinfection and Dis- infectants," as well as my other writings and unpublished work in different phases of this subject. CHAPTEE V MISCELLANEOUS DISEASES INFANTILE PARALYSIS {Acute Anterior Poliomyelitis) An entirely new literature upon the subject of infantile paralysis is now being constructed. The chief contributors to this recent advance in our knowledge have been Wickman of Sweden, who, in 1905-06, gave us a new symptomatology, and defined clinical types not before recog- nized. Wickman made the first systematic study of the disease from an epidemiological point of view, and found evidence that it was con- tagious, though usually slightly so. He directed especial attention to several factors in its spread, viz. : routes of travel, public gath- erings of children, abortive or ambulant cases, and healthy inter- mediate carriers. In the spring of 1909 Landsteiner and Popper succeeded in transmitting the disease to two monkeys by inoculating them with the spinal cord of a child who had died of infantile paraly- sis. Later in the year Flexner and Lewis obtained the same results, and further transmitted the infection from monkey to monkey through an indefinite number of passages. To Harwitz and Scheele of Nor- way we are indebted for formulating the pathologic anatomy of the affection. Infantile paralysis is now properly regarded as a communicable dis- ease. The virus is filterable, that is, "ultramicroscopic," yet coccse forms have been described by Noguchi and Flexner in artificial cultures. {J. A. M. A., Feb. 1, 1913, LX, 5, 362.) It appears that infantile paralysis is becoming more and more com- mon and more widespread of late years. This increase cannot be ac- counted for by the fact that the disease is now better known and more readily recognized. Bergenholtz, in 1881, described the first out- break with sufficient accuracy to accept infantile paralysis as a new disease. Since that time the number of outbreaks and the number of cases have progressively increased, as shown in the following table: 375 276 MISCELLANEOUS DISEASES Av. No. of Cases Cases Outbreaks per Outbreak 1880-1884 23 2 11.5 1885-1889 93 7 13. 1890-1894 151 4 38. 1895-1899 345 23 15. 1900-1904 349 9 39. 1905-1909 8,054 25 322. Eecent outbreaks have occurred in Norway and Sweden, Austria, Germany, Holland, England, Spain, France, the United States, and Cuba. Of the 8,054 cases reported in 5 years (1905-09), the United States contributed 5,514 cases or about five-sevenths of the total number. Epidemics of poliomyelitis have prevailed in all quarters of the world. The disease has been most prevalent in the northern parts of Europe and of the United States. Epidemics have been more severe, and the case rates have been higher, in small towns and rural dis- tricts than in the more densely populated cities. Even in the cities the disease does not especially strike the crowded districts. Cold coun- tries having marked seasonal variations in temperature have been most affected, but the disease is always most prevalent in the warm, dry months, from May to November in the northern hemisphere and No- vember to May in the southern hemisphere. Sporadic cases may occur at any time throughout the year. The great majority of cases occur in children under five years of age. From the standpoint of prevention it is important to note that social and hygienic conditions apparently have no influence whatever in determining the infection. All classes are affected in about equal proportion. The virus of the disease is present in greatest virulence or concen- tration in the spinal cord of infected persons and animals. One one- hundredth of a cubic centimeter of an emulsion of cord, or less, is suf- ficient to infect a monkey. The virus is also quite constantly present in the brain and other organs and tissues, as, for instance, the mucous membrane of the nose and pharynx, the mesenteric glands, the axillary and inguinal lymph nodes, also in the blood, and in the cerebrospinal fluid. The virus has been demonstrated in the feces. The suspicion that the alvine discharges may, therefore, be virulent is sufficient indica- tion that they should be disinfected in all cases until further knowledge of the subject is at hand. The experimental disease in monkeys may be produced with cer- tainty by injecting the virus directly into the central nervous system, preferably the brain. Monkeys may also- be infected by introducing the virus subcutaneously or into the peritoneal cavity, and even by in- travenous inoculation. They have been infected by placing virulent INFANTILE PAEALYSIS 377 material upon the healthy mucous membrane of the nose and also by inhalation of the infectious material forced into the trachea, and finally by introducing the virus into the stomach, along with an opiate, to re- strain peristalsis. Leiner and Weisner have infected monkeys through the uninjured nasal mucous membrane. This, however, is an uncertain method of inoculation. Monkeys have so far never been known to con- tract the disease spontaneously, even though they are kept in intimate association with infected monkeys. There are many similar paralytic diseases of the lower animals, but, so far as known, infantile paralysis as a natural infection is peculiar to man. Eecently Eosenau and Brues, and also Anderson and Erost, have transmitted the disease from monkey to monkey through the bite of the stable fly. Resistance of the Virus. — The virus of anterior poliomyelitis is killed by a temperature of 45° to 50° C. in half- an hour; also by com- paratively weak disinfectants, such as a 1-500 solution of permanganate of potash, 1 per cent, menthol in oil, a powder containing menthol, 0.5 per cent., salol, 5 per cent., boric acid, 20 per cent. (Landsteiner and Levaditi), and a dilution of perhydrol (Merck) equivalent to 1 per cent, of peroxid of hydrogen. The virus is not destroyed by very low temperatures nor by drying over caustic potash, or in vacuo for a con- siderable period. A virulent cord has been kept for almost 5 months in pure glycerin without l-osing its virulence, resembling in this respect rabies, vaccine, and other filterable viruses, and differing for the most part from non-spore-bearing pathogenic bacteria which are usually killed by pure glycerin in a short while. Immunity. — One attack of infantile paralysis apparently confers a high degree of immunity. Eecurrent cases and second attacks have been reported. Monkeys which have recovered from the infection show a high degree of resistance, in that they are not susceptible to infec- tion by again inoculating them, and their blood serum contains anti- bodies capable of rendering the virus harmless. That is, if the blood serum of an inimune monkey is mixed with an emulsion of virulent spinal cord and the mixture allowed to stand for several hours, the virus is no longer capable of producing the infection in susceptible animals. This property has been used by Anderson and Frost to cor- roborate the clinical diagnosis in abortive cases. The blood of a per- son who has not had the disease does not neutralize the virus; there- fore, if the injection of the virus previously treated with human serum fails to produce the infection- in susceptible monkeys, it may be taken as evidence that the serum contained specific antibodies and came from an individual who has had the disease. Modes of Transmission. — Contact theory (based upon the as- sumption THAT THE VIRUS IS DISCHARGED FROM THE MOUTH AND NOSE AND ENTERS THROUGH THE SAME CHANNEL). — There is evidence to sup- 30 278 MISCELLANEOUS DISEASES port the theory that the disease is directly transmissible from person to person and there is a suspicion that healthy carriers play an important role in spreading the infection. This view was enunciated by Wickman and received support through the experiments of Kling, Pettersson and Wernstedt, and also Flexner. It is known that the mucous membrane of the nose and throat contains the virus, and in one case the salivary glands were shown to be infective. Osgood and Lucas demonstrated that the nasal mucous membrane of two monkeys experimentally inocu- lated with poliomyelitis remained infective for 6 weeks in one case and 5% months in another. This very important observation strengthens the suspicion of the existence of chronic human carriers. If healthy carriers continue to spread the infection months after the attack, it in- creases the difficulty of suppressing the disease, and further renders doubtful the efficiency of strict isolation and prophylactic measures di- rected only to persons in the acute stage of the disease. The fact that the mucous membrane contains the virus is not, however, sufficient proof that the virus is liberated and discharged in sufficient amount in the secretions from the mouth and nose to be a menace. In a series of 18 cases Eosenau, Sheppard and Amoss ^ were unable to demonstrate the virus in the nasal and buccal secretions obtained from persons in various stages of convalescence. Strauss ^ had similar negative results in a series of 10 cases. On the other hand, Kling, Pettersson and Wernstedt ^ re- port successful results; by experiments upon monkeys they demonstrated the infectiousness of buccal and intestinal secretions of living subjects. Flexner has recently also reported one successful attempt in demonstrat- ing the virus in the buccal secretions. The Insect-borne Theory. — Infantile paralysis shows no tendency to prevail in congested centers or to spread in hospitals, schools, institu- tions, and other crowded places; its seasonal prevalence corresponds to the seasonal prevalence of most insects, and does not correspond to the seasonal prevalence of diseases spread through secretions of the mouth and nose, such as diphtheria, scarlet fever, smallpox, etc. Many other factors, brought to light by the studies of the State Board of Health of Massachusetts upon the epidemiology of the disease, under the able direction of Dr. Mark Eichardson, indicate that the disease is not a contagious one. These studies * gradually focused attention upon some ' Rosenau, M. J., Sheppard, P. A. E., Amoss, H. L., Boston Med. and Surg. Jour., May 25, 3911, CLXIV, 21, pp. 743-748. "Strauss, I., J. A. M. A., April 22, 1911, LVI, 16, 1192. ' Kling, C, Pettersson, A., and "Wernstedt, W., Report from the State Medical Institute of Sweden to the XV International Congress on Hygiene and Demog- raphy, Washington, D. C, 1912. Also, Zeitschr. f. Immunitatsforch. u. exper. Therapie, Bd. XII, Jena, 1912. ■"Richardson, M. W., Monthly Bull., State Board of Health of Mass., Sept., 1912, 7, 9, pp. 308-315. Lovett, R. W., Report to the Mass. State Board of Health, 1907. Report to the Mass. State Board of Health, 1908, 1909, 1910, 1911. INFANTILE PAEALYSIS 279 insect, the stable fly (Stomoxys calcitrans) in particular. Eosenau and Brues ^ demonstrated that the virus may be transmitted from monkey to monkey through the bite of the stable fly. These results were soon confirmed by Anderson and Frost.- The insect-borne theory seems to fit the case as the disease is known in Massachusetts. It will, however, require much additional study to determine what role Stomoxys cal- citrans plays in spreading the infection in nature. Othee Theories. — It has been suggested that the virus may be air-borne in the sense that it is carried in the dust. Neustaedter and Thro ^ have infected monkeys from dust collected from sick rooms. In- fected food, or transmission through wounds and other means, have not been ruled out of consideration. Prevention. — No definite or effective system of prevention can be formulated until we are sure of the mode of transmission. Meanwhile health authorities are entirely justified in requiring cases to be reported, isolated, and all known lines of preventive measures applied, such as disinfection, screening, and guarding against insects, allaying unneces- sary dust, etc. A fly campaign directed with especial reference to the stable fly is plainly indicated, and the infection must also be fought as one conveyed from man to man directly. Until the modes of transmis- sion of the disease are established, however, we can have no confidence in our prophylactic measures, which most resemble the old "shotgun" prescription. The following measures are recommended: The patient should be isolated as completely as possible in a clean, bare room, well screened to keep out insects. This is a good practice despite the fact that the disease shows no tendency to spread in children's asylums, hospitals, and other institutions, or even in the home. The same statement, however, was made of typhoid fever not many years ago. Visiting should be interdicted and only the necessary attendant should be al- lowed to come in contact with the patient. All discharges, including sputum, nasal secretions, urine, and feces, should be thoroughly disin- fected, and special care should be taken that cups, spoons, remnants of food, etc., which may have become contaminated by the patient are burned, scalded, or otherwise purified. Towels, bed linen, and other fabrics should be boiled or dipped into a germicidal solution strong enough to destroy the typhoid bacil- lus. The nurse and physician should observe the same precautions re- 'Eosenau, M. J., and Brues, C. T., Monthly Bull, State Board of Health of Mass., Sept., 1912, 7, 9, pp. 314-318. Also Brues and Sheppard, Jour, of Eaonom. Entomology, Aug., 1912, V, 4, 305. "Anderson, J. F., and Frost, W. H., Puh. Health Beports, Oct. 25, 1912, XXVII, 43, pp. 1733-1736. 'Neustaedter, M., and Thro, W. C, N. ¥. Med. Jour., Sept. 23, 1911, XCIV, 13. 380 MISCELLANEOUS DISEASES garding their hands and clothing as are recommended in attending a case of scarlet fever. The period during which the isolation should be maintained can- not even be guessed at. Children are usually not permitted to return to school for at least three weeks, but, if chronic carriers play the im- portant role now suspected, this time would be far too short in many instances. Since the virus can be killed experimentally by a 1 per cent, solu- tion of peroxid of hydrogen, antiseptic gargles, sprays, and nose washes of this solution are recommended to be used by the patient, the nurse, and physician, and other members of the family. In the presence of an epidemic, street and house dust should be kept down by sprinkling, oiling, and the other means employed for this purpose. Dust should be allayed whether there is an epidemic of infantile paralysis or not. During epidemics children should be kept away from public gather- ings, prohibited from using public drinking cups, and special attention given to the diet to prevent gastrointestinal disorders, for many a case of infantile paralysis starts with a digestive upset. CHICKENPOX Chickenpox is one of the minor communicable diseases, in that the mortality is practically nil and that complications and sequels are rare. Chickenpox is very readily communicable and spreads through families or institutions, but does not occur in widespread epidemics. The cause of the disease and its modes of transmission are not known. The virus is not contained in the content of the vesicle. Tyzzer and others made numerous inoculations with both clear and clouded vesicle contents without results. The disease is probably peculiar to man; animal inoculations have so far proven negative. The period of incubation is probably from fourteen to sixteen days, and one attack produces a defi- nite immunity. No age is exempt. The differential diagnosis between chickenpox and smallpox is often an important and difficult public health matter. The distinction may be made by introducing some of the contents of the vesicle into the skin of a well-vaccinated person. If chickenpox, an immediate reaction results; if smallpox, no reaction results. Monkeys are not susceptible to chickenpox but may be given smallpox. The differential diagnosis may also be made from the presence of vaccine bodies in smallpox and their absence in chickenpox. These bodies are best demonstrated by introducing some of the virus upon the cornea of a rabbit, and examining the vesicles which form. Health officers should require cases of chickenpox to be reported, if for -no other reason than that it is often mistaken for smallpox. The GLANDERS 381 differential diagnosis may be made in doubtful cases by a histological examination of the pock, or by inoculating the contents of the vesicle upon the cornea of rabbits. In sections of the skin lesion the vaccine bodies are found in smallpox, not in chickenpox; the vesicle of the former is multilocular, the latter unilocular. The vesicle upon the cornea of rabbits produced by smallpox is distinct and contains the vaccine bodies; the lesion resulting from chickenpox is trifling and does not contain the vaccine bodies. The prevention of chickenpox depends upon isolation and disinfec- tion at the bedside. Children with chickenpox should not be permitted to go to school. GLANDERS Glanders or farcy is a widespread communicable disease of horses, mules, asses, and other animals, and is readily communicated to man. In both man and horses it is remarkable for its fatality. The disease is characterized by the formation of inflammatory nodules either in the mucous membrane of the nose (glanders) or in the skin (farcy). Glanders is caused by the Bacillus mallei^ which corresponds to the spore-free bacteria so far as its resistance is concerned. In gen- eral the bacillus of glanders is killed by the same agents used against the tubercle bacillus, which it resembles in some particulars. The infection may be introduced into the system either through the skin or mucous membrane, and is usually communicated directly from the horse to man by contact with the infected discharges. The disease is sometimes communicated from man to man. Washerwomen have become infected from the clothes of a patient. The bacillus of glanders does not have a spore. It is comparatively frail and readily destroyed by the usual physical and chemical germi- cidal agencies used against spore-free bacteria. The bacillus, however, is frequently protected by albuminous matter or buried in the dirt of stables, water troughs, harnesses, and other objects. While the naked germs of glanders are readily destroyed, they are frequently hard to get at; cleanliness is, therefore, imperative. The prevention of glanders in man depends primarily upon the suppression of the disease in horses. The only difficulty in controlling the disease in horses lies in the early diagnosis and recognition of mild or missed cases, which are very common. Horses affected with occult or latent glanders are important factors in the propagation of the infection. The clinical diagnosis in the frank cases is made with- out difficulty from the characteristic symptoms and the lesions, but laboratory aid is necessary to discover the mild cases. Diagnosis. — The diagnosis of glanders may be made by: (1) the mallein test; (2) the agglutination test; (3) the Strauss reaction; 282 MISCELLANEOUS DISEASES (4) isolation of B. mallei in pure culture; and (5) complement fixa- tion. All these tests serve a definite purpose. However, the mallein test, the agglutination test, and the Strauss reaction are not sufficiently reliable to be entirely satisfactory. The isolation of the glanders bacil- lus in pure culture is definite and final, but time-consuming. The diagnosis of glanders by complement fixation is at present our most reliable, most satisfactory, and quickest method of recognizing the disease. The Mallein Test. — Mallein is a product of the glanders bacillus corresponding to tuberculin. The injection of mallein into normal ani- mals produces no reaction, whereas the injection into glanderous ani- mals causes a rise in temperature and a local reaction about the le- sions. With the mallein test a large proportion of latent and occult cases of glanders can be diagnosed, but the test must be made and in- terpreted by an experienced veterinarian, else the results may be un- reliable. The mallein test fails to give a typical reaction in a consid- erable number of glanderous animals; on the other hand, a reaction may follow the injection of mallein in the absence of glanders. Thus mallein is not an entirely reliable diagnostic agent and has never been considered as specific in the detection of this disease as tuberculin for the diagnosis of tuberculosis. The Agglutination Test. — The agglutination test is of value in all cases of recent infection, the blood serum possessing a very high agglutinating power — 1-1,000 and higher. In chronic glanders the agglutinating power of the blood may be very low — 1-400 or less; in some cases even lower than that of normal blood serum — which may be 1-800 and even higher. It is, therefore, plain that agglutination tests alone do not constitute an entirely satisfactory diagnostic method for glanders. It may be used as an adjunct to other tests. The Steauss Reaction. — The Strauss ^ reaction for the diagnosis of glanders consists in inoculating male guinea pigs into the peritoneal cavity with material containing virulent B. mallei, which causes an enlargement of the testicles. A positive reaction associated with organ- isms resembling those of glanders, and typical cultures obtained from the lesions, are unfailing evidence of the presence of the specific virus. Failure to obtain the reaction is not proof that a suspected specimen may not have come from a horse or animal with glanders. Arms '' recommends that it is better to use more than one guine^ pig in test- ing suspected material, and that, before inoculating, it is well to make a microscopic examination as a guide to the dosage. A cul- ture made from the swab often aids in the early diagnosis. Gui- nea pigs should be kept under observation for a month, and if a ^Compt. Mend. Acad. d. So., 1889, CVIII, p. 530. V. A. M. A., LV, 7, Aug. 13, 1910, p. 591. GLANDEES 283 lesion of any kind is present an autopsy should be made and cultures taken. The Isolation op B. Mallei in Pure Culture. — The bacillus of glanders may be isolated by introducing some of the suspected ma- terial subeutaneously and also intraperitoneally into male guinea pigs. In this way pure cultures may be obtained from the pus or necrotic foci in the spleen, which follow subcutaneous inoculation; or from the characteristic enlargement of the testicle which is observed in animals inoculated intraperitoneally. The organism isolated must be studied for cultural, morphological, and biological characters. The isolation of the bacillus in pure culture gives positive information of unquestioned character in any critical case. The method is not generally applicable to the diagnosis of glanders because it requires too much time and may occasionally fail to discover the bacillus. Complement Fixation. — In 1909 Schiitz and Schubert ^ published the results of their important work on the application of the method of complement fixation for the diagnosis of glanders. The splendid results obtained constitute, without doubt, the most reliable method for the diagnosis of glanders which we have at our command at the present time. The complement fixation test is, in fact, one of the most specific of the biological tests in immunity. It is readily applicable to the case of glanders. The essential elements used in the test are as follows : The hemolytic system consists of the washed red blood corpuscles of a sheep and the blood serum of a rabbit which has been injected with the washed red blood corpuscles of a sheep. Strong, vigorous rabbits are selected and three injections of the sheep's corpuscles are made at intervals of 7 days, using 7 c. c, 10 c. c, and 12 c. c. of the red corpuscles of the sheep suspended in like amounts of isotonic salt solution. The blood serum of a rabbit so treated contains the hemolytic amboceptors. The rabbit's blood serum is heated to 56° C. for half an hour in order to destroy the complement. The titer, or amount of amboceptor contained in the rabbit serum, must be determined. The hemolytic system, then, consists of rabbit serum containing ambocep- tor, plus washed red blood corpuscles of the sheep. Complement. — The complement is contained in the fresh blood serum of a healthy guinea pig. The blood serum of the guinea pig should be titrated in order to determine the amount of complement present. It is always necessary to determine the smallest quantity of complement to be used for the final test. Antigen. — The antigen consists in an extract obtained by shaking 'Schiitz and Schubert: "Die Ermittelung der Eotzkrankheit mit Hilfe der Komplementablenkungsmethode. " Archiv fiir wissenschaftliche und praktische Tierheilkunde. Bd. 35, Heft 1 and 2, pp. 44-83, 1909. 284 MISCELLANEOUS DISEASES glanders bacilli in salt solution. The bacillus is grown in pure cul- ture on 2 per cent, acid glycerin agar. A luxuriant growth upon the surface of the medium is usually obtained in 48 hours. This is sus- pended in salt solution, heated to 60° C. for four hours in order to kill the bacilli. After heating the dead bacilli are shaken in the salt solution in a special apparatus for four days. The bacilli are separated in the centrifuge and the clear supernatant liquid is drawn off and pre- served with carbolic acid. The strength of this extract must be deter- mined by suitable methods of titration. Technique. — The test is carried out by adding together, in proper proportions, the following: (1) The blood serum of the horse to be tested; (2) the antigen (extract of glanders bacilli) ; (3) complement (fresh guinea pig serum) ; and (4) the hemolytic system. If the blood serum of the horse to be tested contains the specific amboceptors these will unite with the bacteria, fix the complement, and thus prevent hemolysis. If the blood serum of the horse to be tested does not con- tain these specific amboceptors, this fixation of the complement cannot take place and hemolysis results. Therefore, the absence of hemolysis means the presence of glanders, and vice versa. The tests must always be carried out with controls and carefully conducted as to the amount of each substance used, the temperature and time.^ Prevention. — When glanders is discovered or suspected among horses in a stable, the blood of all the horses in the infected stable should be drawn and tested in the manner above described. All animals whose serum shows complement fixation should be destroyed without further consideration. After the animals have been killed and properly dis- posed of, the stable should be thoroughly cleansed and disinfected. All other horses which have in any way been associated with the infected animals should be carefully watched and tested again after three weeks, and, should there be no indication of the disease in the second test, the stable may be considered free from the infection; otherwise the infected animals should be destroyed and the tests repeated every three weeks until the disease has been eliminated. The eradication of glanders from a stable often means considerable loss and sometimes a sacrifice of valuable animals, but it is only through vigorous measures that the disease may be controlled. In the disin- fection and cleansing special attention should be paid to the stalls, harnesses, water troughs, bits, food containers, curry combs, sponges, and other objects exposed to the infection, which is eliminated mostly in the secretions from the mouth and nose. The common drinking trough for horses spreads the infection. ' A complete description of the diagnosis of glanders by complement fixation, giving in full all the details, will be found in Bull. 136, Bureau of Animal Industry, Apr. 7, 1911, by Mohler and Eichhorn. : ANTHEAX 385 The personal prophylaxis of glanders in man depends upon the education and care of those who have to handle horses. In working with horses known to be infected rubber gloves, disinfection, and other methods of protection should be employed. Special care should be taken to prevent the spread of the infection through the discharges or by infected fomites from human cases. Fatal accidents have occurred in laboratories in research workers handling pure cultures of B. mallei. ANTHRAX Anthrax belongs to that group of diseases which occurs primarily in the lower animals and secondarily in man. The infection is found in horses, cattle, sheep, and other cloven-hoofed animals, and may be transmitted experimentally to mice, guinea pigs, rats, and rabbits. Cold-blooded animals and birds, as well as dogs and swine, are re- fractory. In man the infection may enter the skin (malignant pustule) or may enter the lungs (wool sorters' disease), or may enter the diges- tive tract and produce intestinal lesions. In anthrax of the skin the infection usually enters through slight abrasions, scratches, or small wounds, especially on the forearm, hand, or face. Most of the cases occur in butchers or persons who have to handle infected carcasses. The spores have been carried to the skin by ilies and may be inoculated by the bite of the stable fly. Wool sorters' disease, or anthrax of the lungs, appears to be due to the inhalation of anthrax spores. It is observed only among per- sons who handle skins or who work with horse hair or other raw materials from animals afflicted with anthrax. The mode of transmission in intestinal anthrax is through meat from an anthrax cadaver which is partaken of without proper cooking. Schuberg and Kuhn ^ have shown that anthrax may be transferred from animal to animal through the bite of the stable fly (Stomoxys calcitrans) . Eesistance. — The anthrax spore is exceedingly resistant to heat and external influences, such as dryness and sunlight, and also to germi- cidal agents. Its resistance may be compared to the tetanus spore page 70. Immunity. — A number of species of animals have a natural immu- nity to anthrax, and an artificially acquired immunity majy be induced in cattle or sheep through the injection of attenuated cultures, in ac- cordance with the classical method of Pasteur. These procedures are not applicable to man. The prevention of the disease in man must first be directed to a suppression of the disease in animals. The sick 'Arbeiten a. d. kaiserl, Ges.-Amt., Bd. XL, Heft 2, 1912, 286 MISCELLANEOUS DISEASES animals should be isolated, or, better, killed, and the carcasses burned or buried at least three feet deep. The carcasses may be "tanked," that is, subjected to a prolonged exposure to steam under pressure. Tanks for this purpose are found in all the larger slaughter houses. It is important in handling the body of an animal dead of anthrax not to open it or shed blood, for the bacillus does not produce its spore except in the presence of oxygen, that is, the bacilli are mainly in the blood and internal organs and will not sporulate as long as access to the air is prevented. Prevention. — The chief preventive measure so far as man is con- cerned is the disinfection of all raw material in those trades in which horse hair, hides, and other substances liable to harbor the anthrax spore are handled. Veterinary surgeons who conduct autopsies upon anthrax animals should exercise unusual precautions, and, if practicable, wear rubber gloves. Ponder ^ recommends the following process to destroy anthrax in- fection in hides : The dry hides are placed for 24 hours in a "soak" which is made to contain 1 to 2 per cent, of formic acid and 0.03 per cent, of bichlorid of mercury, and then salting them with sodium chlorid. The action of the "soak" is to swell up the fibers of the hide by causing them to absorb water, the result being that the hide returns to a condition closely resembling that in which it was taken from the animal's carcass. This permits the bichlorid of mercury to per- meate and exert its germicidal action. FOOT-AND-MOUTH DISEASE Foot-and-mouth disease is also known as aphthous fever, epizootic catarrh, and eczema contagiosa. It is an acute and highly commu- nicable disease, generally confined to cloven-footed animals, and char- acterized by an eruption of vesicles on the mucous membrane of the mouth and on the skin between the toes and above the hoofs. The vesicles rupture, forming erosions and ulcers. There are also saliva- tion, tenderness of the ailected parts, loss of appetite, lameness, emacia- tion, and diminution in the quantity of milk secreted. Foot-and-mouth disease is primarily a disease of cattle and sec- ondarily of man. Hogs, sheep, goats, buffalo, American bison, camel, chamois, llama, giraffe, antelope, and even horses, dogs, and cats may occasionally become infected. The disease prevails in European countries and occasions great economic loss. The mortality is low; the serious losses depend chiefly upon the diminution of the milk secretion and the loss of flesh in the affected animals. ^ Lancet^ London, Nov. 4, CLXXXI, No. 4601, pp. 1247-1314. FOOT-AND-MOUTH DISEASE 287 Foot-and-mouth disease has appeared in the United States only on five different occasions— in 1870, 1880, 1884, 1902-3, and 1908. Every outbreak on American soil has thus far been followed by its complete suppression through the application of well-known preventive meas- ures, such as isolation, destruction and burial of the affected herds, disinfection, and a systematic inspection of all farms in the infected area to detect cases of the disease. Loffler and Froeseh in 1898 showed that the virus will pass the finest porcelain filters. This was the first ultramicroscopic virus dis- covered. The specific principle is contained in the serum of the ves- icles; in the saliva, milk, and various other secretions and excretions; also in the blood during the rise of temperature. No definite immunity is rendered by an attack. The period of in- cubation is variable, usually from two to six days or longer, excep- tional instances being prolonged to fifteen or even eighteen days. The disease in man is a direct counterpart of that in cattle. The infection is transmitted to man through the ingestion of raw milk, buttermilk, butter, cheese, and whey from animals suffering with foot- and-mouth disease. It may also, though more rarely, be transmitted directly from the salivary secretions or other infected material which gains entrance through the mucous membrane of the mouth. It is doubtful whether the disease can be transmitted to man by cutaneous or subcutaneous inoculation, though it is probable that tlie infection may be communicated if the virus enters the blood directly through wounds of any kind. Children are most frequently infected by drink- ing unboiled milk during the time in which the disease is prevalent in the neighborhood, while persons in charge of diseased animals may become infected through contact with the afEected parts or by milking, slaughtering, or caring for the animals. The disease is usually very mild in man; death practically never results, except in weakened chil- dren, and then from secondary complications. The original experiments of Loffler and Froeseh, as well as recent experiments which have been made in Denmark and Germany, indicate that the infection is destroyed comparatively readily by heat or the usual antiseptics. Milk pasteurized at a temperature of 60° C. for 20 minutes is safe, so far as infection from foot-and-mouth disease is concerned. Foot-and-mouth disease has a special interest on account of the fact that it may be associated with vaccinia. The symbiosis between the infections of vaccinia and foot-and-mouth disease is remarkable. Animals vaccinated with the mixed virus, as a rule, show the lesions of only one of these diseases, namely, vaccinia. Nevertheless, the in- fectious principle of the other, foot-and-mouth disease, remains in the vaccinal eruption. Vaccine virus has been known to contain the in- 288 MISCELLANEOUS DISEASES fection of foot-and-mouth disease.^ Glycerin acts as a preservative for the virus of foot-and-mouth disease, so that it may remain viable in glycerinated vaccine virus a very long time. No instance of the transmission of foot-and-mouth disease to man through vaccine virus has been recorded, and it is doubtful, in view of the known facts, whether it is possible to reproduce the disease in man by the cutaneous inoculation commonly used in the process of vaccination. The pre- vention of foot-and-mouth infection in vaccine virus is assured through federal inspection and through special tests (see vaccine virus, page 20. The prevention of foot-and-mouth disease consists (1) in a cattle quarantine, to keep it out of countries where it does not exist; (2) in the elimination of the disease in cattle through isolation of infected herds, destruction and burial of the sick animals, and disinfection; (3) the disease in man may be avoided by care in the selection of the animals from which milk is taken or by pasteurization of the milk when foot-and-mouth disease is prevalent. MALTA FEVER Malta fever is a general infection not unlike other specific bactepi- emia, such as typhoid fever. It is caused by the Micrococcus melitm- sis, discovered by Bruce in 1887 during the earlier days of bacteriologj'. Clinically the disease is characterized by profuse perspiration, constipa- tion, frequent relapses often accompanied by pains of a rheumatic or neuralgic character, and sometimes swelling of the joints or orchitis. Malta fever is further characterized by its low mortality and long- drawn-out and indefinite duration. It prevails especially about the Mediterranean basin. Gentry and Ferenbaugh have recently found a nest of malta fever throughout the older goat-raising sections of Texas. This endemic cen- ter embraces an area approximately 300 miles along the Eio Grande extending 90 miles to the north. All the cases of malta fever found have occurred in territory devoted to goat raising, and all the patients there gave a history of drinking unboiled goats' milk or were associated with the goat-raising industry. The Micrococcus melitensis was isolated from several of the cases. ^ Modes of Transmission. — From experimental evidence it would ap- pear that the infection of malta fever may be taken in through wounds, the mucous membranes, or by food and drink. The usual mode of infection is by drinking raw goats' milk. The Micrococcus melitensis ' ' ' The Origin of the Recent Outbreak of Foot-and-Mouth Disease in the United States," by Mohler and Eosenau, Cir. 147, Bureau of Animal Industry, Dept. of Agriculture, 1909. 'J. A. M. A., Aug. 26, Sept. 9, Sept. 23, Sept. 30, 1911. MALTA FEVER 289 leaves the body in various secretions and excretions. Great numbers of the cocci in pure cultures may appear in the urine. The milk of goats also contains the virus. All the secretions from the body must be regarded as infectious until further knowledge on the subject is at hand. In man the coccus may be isolated from the spleen, lymph glands, bone marrow, and mammary glands. In goats it first disap- pears from the blood, then the spleen, and, last of all, from the mam- mary glands. Goats are susceptible to malta fever and continue to discharge the infection in the milk for a long time. The disease is usually contracted by drinking such infected milk. While this is the common mode of infection, occasional cases doubtless arise through other sources; thus one case which arose in England is supposed to have been conveyed from son to father by using a clinical thermometer in the mouth im- mediately after its use by the patient. Monkeys may readily be in- fected either by the inoculation of pure cultures or by feeding them. At least five accidental infections have occurred, in bacteriological laboratories, one in Washington. MacFayden lost his life from a laboratory infection with the Micrococcus melitensis. This microorgan- ism has, therefore, more than ^complied with all the* -requirements of Koch's laws. There has long been a suspicion that malta fever may be conveyed through the bite of an ectoparasite. In fact. Captain Kennedy was able experimentally to infect a monkey- as a result of bites of mos- quitoes (Culex pipiens) which had- fed on patients suffering with malta fever. This probably was an instance of mechanical transference of the infection, corresponding in all respects to a laboratory inoculation with fresh virulent material from a hypodermic syringe. This cannot be a frequent way by which the infection is transmitted in nature, for the specific organisms are found in small numbers in the peripheral blood of malta fever patients. The British Commission found the Micrococcus melitensis only four times from a total of 896 mosquitoes dissected. From the fact that the micrococcus may be successfully introduced either by ingestion, or by inoculation, or through the mucous mem- branes, it is evident that occasionally cases may receive their infection through a great variety of means, such as insect bites and other wounds, infected food, and the various modes of contact infection. Contact infection, however, probably plays a minor role, for there is evidence that the disease is not, as a rule, directly transmitted from the sick to the well. There is little doubt but that the infection can be acquired from the urine secreted by cases of malta fever, and this is probably one way in which the workers in hospitals become infected. There is also experimental evidence to show that monkeys can be 290 MISCELLANEOUS DISEASES infected by dry dust artificially contaminated with cultures of the Micrococcus melitensis. The path of entrance may be through the nares, throat, respiratory passages, or alimentary canal. Dry dust con- taminated with the urine of cases of malta fever has given rise to in- fection in goats but not in monkeys. The experience gained during the work performed in Malta during 1904 and 1905 has convinced Horrocks that men are more susceptible than monkeys and goats. Shaw's work on ambulatory cases of malta fever among Maltese has also shown that opportunities for the creation of infected dust are plentiful in Malta. Infected dry dust as a mode of transmission can- not, therefore, be discarded, but, as a matter of fact, it probably seldom occurs. Goats' Milk and Malta Fever. — We are indebted to the six reports of the British Commission for the investigation of Mediterranean fever (1905-1907) for the fact that malta fever is chiefly spread through goats' milk. Before the researches of this commission the common mode of infection was not definitely known. The usual source of milk in Malta is the goat. The udders, which are abnormally long, often touch the ground and are very liable to be soiled. It was first shown by Zammit in the report of 1905 that goats could be infected by feeding them with the Micrococcus melitensis. In the same year Major Horrocks discovered the Micrococcus melHen- sis in the milk of an apparently healthy goat. Further studies showed that one or more healthy goats in every herd were excreting the Micro- coccus melitensis in their milk and urine, and that about 50 per cent, of the goats reacted positively when examined by serum agglutination tests. All the available evidence points to their food as the main vehicle of infection in goats. The young goats, of course, are infected through their mother's milk. Horrocks and Kennedy consider that 10 per cent, of the goats supplying milk to various parts of Malta excrete the Micrococcus melitensis in their milk. The excretion of the specific microorganism may continue steadily for three months without any change occurring in the physical character or chemical composition of the milk and without the animal exhibiting any signs of ill health. On the other hand, the excretion of the Micrococcus melitensis in the milk may be intermittent, appearing for a few days and then disappearing for a week or more. Major Horrocks in Report No. 5 of the British Commission shows a direct relation between the number of goats in Gibraltar to the num- ber of cases of malta fever. With the reduction in the number of goats in Gibraltar there was also a decrease in the number of cases, so that finally, when the number of goats had decreased to about 200 in 1905, malta fever had practically disappeared. The story of the steamship Joshua Nicholson is instructive in show- MALTA FEVER 391 ing the relation between goats' milk and malta fever in man. Sixty- one milch goats, all healthy in appearance and good milkers (many being prize animals), and four billygoats were shipped on board the cargo steamer Joshua Nicholson August 19, 1905, at Malta for pas- sage to the United States via Antwerp. Many of the ship's company partook freely of the milk. The officers drank "mixed" milk collected in a large vessel; the members of the crew each obtaining the "whole" milk from one goat in his own separate panikin. Subsequent bacterio- logical examination resulted in the recovery of the Micrococcus meliten- sis from the milk of several of the goats. Of 23 men on board the steamer who drank the goats' milk on one or more occasions, no. evi- dence whatever is available as to 13, while of the remaining 10, 9 suf- fered from febrile attacks, 5 of them yielding conclusive e^ddence of infection with the Micrococcus melitensis. Resistance. — The Micrococcus melitensis is readily destroyed by heat. I have shown that 60° C. for 20 minutes is sufficient to destroy this organism in milk and provides at the same time a liberal margin of safety. It is not destroyed at 55° for a short time, but succumbs in one hour; the majority die at 58° ; at 60° all are killed. Phenol, 1 per cent., destroys the coccus in 15 minutes. While this micrococcus shows a com- paratively feeble resistance against heat and the ordinary germicides, it shows a remarkable resistance to dryness, for it may remain alive in this state for months. The micrococcus grows well, but slowly, upon artificial culture media. Visible colonies do not appear until about the fifth day. It may be kept alive indefinitely by transplanting to subcultures at fre- quent intervals. Exceedingly high agglutinating power develops in persons suffering with malta fever — sometimes as high as 1-100,000. In such cases the proagglutinoid zone may appear, that is, the serum may refuse to agglutinate in low dilutions, such as 1-100, but aggluti- nate actively in higher dilutions, such as 1-1,000. Prevention. — Our knowledge of the cause and modes of transmis- sion of malta fever makes the prevention of this disease a compara- tively simple problem. The infection must first be eliminated in the goats. Until this is done goa'ts' milk should be pasteurized. Patients having the disease should be treated upon the same principles laid down for typhoid fever, in order to prevent the spread of the infection through food fomites and indirect contact. Convalescents should not be released until the micrococcus has disappeared from the urine. Gen- eral sanitary measures, such as. the suppression of flies and mosquitoes, allaying dust, and the promotion of general cleanliness, should not be neglected. 292 MISCELLANEOUS DISEASES LEPROSY Leprosy is a contagious disease in the sense that it is probably always communicated directly from the sick to the well, but prolonged and intimate association with a leper ordinarily seems necessary to con- tract the infection. The degree of the contagiousness varies very much, depending upon conditions not well understood, but it is plain that leprosy shows little tendency to spread in any of the more highly civ- ilized nations practicing personal cleanliness and enjoying the benefits of modern sanitation. Leprosy prevailed in epidemic form in Europe in the middle ages, but the disease has disappeared from central Europe, remaining only upon the fringe of the continent, in Norway, Sweden, Spain, Italy, Greece, Turkey, Eussia, and Finland. It is estimated that there are from 5,000 to 6,000 lepers in the Philippine Islands, and there are many cases in China, Japan, and India. The greatest inci- dence is found among the natives of the Hawaiian Islands, where one in every 30 or 40 have the disease. Leprosy was introduced into the Hawaiian Islands about 1859, and there found conditions particularly favorable for spread. A Government Commission in 1902 ^ took a census of the lepers in the United States and found 278. Of these 145 were born in the United States and 186 probably contracted the disease in the United States. Of the entire number 72 of the cases were isolated and 205 were at large. BrinckerhofE again studied the prevalence of leprosy in the United States in 1909 and found 139 cases. The official figures for 1912 are 146. Although these numbers represent only the cases ofiicially known, it is evident that the disease is not on the increase in our country and that, while it may be contracted here, it is "con- tagious" with great difficulty. There are three foci of leprosy in the United States : one among the Scandinavians in the region of the Great Lakes, another among the Orientals on the Pacific Coast, and the third on the Gulf Coast, particularly in Louisiana and Florida. According to the official health reports from our Territories and Dependencies, there were in 1912 in Hawaii 696 lepers, in Porto Eico 28, in the Philippine Islands 2,754, in the Canal Zone 7. The number in Guam and Alaska have not been enumerated. It is known, however, that many eases escape tabulation in the official returns. The cause of leprosy is the Bacillus leprce discovered by Armauer- Hansen in 1874. The bacillus of leprosy resembles the bacillus of tu- berculosis in many respects. It stains more readily and decolorizes somewhat more readily than the tubercle bacillus. It differs from the tubercle bacillus in that it grows with difficulty on artificial culture 'White, Vaughan, and Eosenau, Document No. S69, 57th Congress, 1st Ses- sion, 1902. LEPEOSY 293 media and is much less, if at all, pathogenic for the lower animals. Further, lepra hacilli are usually found in dense clusters and in much greater numbers within the cells than is the ease with the tubercle bacillus. The bacillus of leprosy grows with difficulty upon artificial culture media. For years it has evaded all attempts until Clegg ^ in 1909 suc- ceeded in cultivating it in symbiosis with amebae and 8. cholerce upon plain agar and weakly nutrient agar. Clegg based his work upon the belief that the leprosy bacillus derives its nutrition from the products of the tissue cells in which it is mainly to be seen in leprosy lesions. These results have been confirmed by Currie, Brinekerhoff, and Holman in Hawaii and by Duval in New Orleans. Immunity. — There is no racial immunity to leprosy. The white races suifered severely during the middle ages. Malays and Mongols now appear most liable to the infection, perhaps on account of their mode of life. The disease is remarkable for its prolonged period of incubation and its chronic course. These facts indicate that .the body must possess a high degree of resistance to this infection. So far as known, man is the only animal subject to leprosy under natural condi- tions. Inoculation experiments into lower animals have recently proved successful in the guinea pig (Clegg) ; the Japanese dancing mouse (Sugai) ; and the monkey (Duval). Rat Leprosy. — There is a disease among rats which is a close coun- terpart of leprosy in man. It occurs naturally in the Mus norvegicus and may be transferred by inoculation to the more tractable laboratory white rat. The disease was first observed by Stenfansky in 1903 in Odessa. In the same year Eabinowitsch found the disease among the rats of Berlin, and Dean in 1903 discovered the disease independently in London, and in a later publication (1905) reported success in trans- ferring the infection by artificial inoculation. Since then rat leprosy has been found by Tidswell in the rats of Sydney, Australia, and the England Plague Commission observed the disease among the rats in India. Wherry and McCoy found a number of cases among the rats caught in San Francisco, California. The proportion of rats infected with leprosy in different localities varies greatly. Thus in Odessa from 4 to 5 per cent., in San Francisco 0.2 per cent., and in Sydney only 0.001 per cent. Currie failed to find leprosy among the rats of Honolulu. The fact that the infection is absent among the rats of Honolulu and present among the rats In Berlin is evidence that it plays no part in the epidemiology of the human disease. Leprous rats in a late stage of the disease are usually recognized ' The Philippine Jour, of Science, Vol. IV, No. 77, Apr., 1909. PubUo Health Bull. No. 47, Sept., 1911. 21 294 MISCELLANEOUS DISEASES by the presence of patchy alopecia associated with cutaneous and sub- cutaneous nodules which may or may not be the site of open ulcers. The diagnosis is readily confirmed by microscopic examination of a smear from an ulcer or a nodule, which will show the specific bacillus of the disease in enormous numbers. Currie ^ has recently shown that rats may infect each other by contact, also that bacilli of rat leprosy may often be demonstrated in the heart's blood of infected rats. Currie had no difficulty in demon- strating the presence of acid-fast bacilli in mites contained on the bodies of rats when the latter's heart's blood contained the microorgan- isms. The fact that these mites so frequently contain the bacilli natu- rally leads to the suspicion that they may be one of the means of transmitting the disease from rat to rat, but up to the present time no positive evidence has been adduced that such is the case. In this leprosy-like disease of rats we have an infection which closely resembles leprosy in man. The fact that the infection may readily be propagated in a laboratory animal permits of its investiga- tion, and it is assumed that the further studies now being made upon rat leprosy will throw much light upon the modes of transmission and control of the human disease. Modes of Transmission. — The leprosy bacillus is found in all the lesions of the disease — the nodules on the skin and mucous membranes, in the spleen, liver, and testicles — in fact, in all the internal organs. In the anesthetic type the bacilli are found in the cells of the spinal cord and brain and also in the peripheral nerves. Leprosy bacilli may also be found in the circulating blood during the acute eruptive stage. Frequently they are in the endothelial or in the white blood cells. The leprosy bacillus leaves the body from any of the lesions that are broken down. From the degenerated nodules of the skin or mucous membranes they are discharged in enormous numbers. If we may de- pend upon microchemical evidence, it appears that most of these bacilli are probably dead. Leprosy bacilli also occasionally appear in the feces and urine. They do not occur in the expectoration from the lungs. There is some doubt as to Just how the leprosy bacillus enters the body, whether through wounds of the skin or through the mucous membrane of the nose and throat or through the digestive tract, or possibly during coitus. It may be definitely stated that leprosy is not due to the eating of any particular food, such as fish. This theory has been stoutly main- tained by Jonathan Hutchinson. There is no satisfactory evidence in support of the fish theory and many facts against it. One thing is plain, and that is, leprosy is not contracted from any of the lower 'XT. S. Pub. Health and Mar. Hosp. Ser., Pub. Health Bull. No. 50. Oct., 1911. LEPROSY 295 animals, but is an infection which in all cases passes rather directly from man to man. The suspicion that parasitic insects may play some role in the transmission of leprosy has existed for some time. The evidence is reviewed by ISTuttal/ who says: "It appears that Linnaeus and Rolan- der considered that Chlorops (miisca) leprw was able to cause leprosy by its bite." Blanchard and Corrodor tell of flies in connection with leprosy. Flies frequently gather in great numbers on the leprous ulcers and then visit and bite other persons. An observation by Boeck of the presence of Sarcoptes scdbei in a case of cutaneous leprosy led Joly to conclude that these parasites might at times serve as carriers of the infection. Pediculi are usually present among the poor classes in Algeria, which furnish the greater number of lepers. Sommer of Buenos Aires expresses the belief that mosquitoes act as active agents in the spread of leprosy in warm countries. Carrasquillo of Bogota found the bacillus of Hansen in the intestinal contents of flies. W. C. Goodhue and his assistant. Father Joseph, working at the leper settle- ment at Moloki, found lepra bacilli in the intestinal contents of a female Oulex pungens. Later they found similar organisms in the common bedbug. The British Leprosy Commission investigated the possible role played by insects with entirely negative results. Wherry studied the occurrence of lepra-like bacilli in certain flies and their larva. He found that the fly Chlorops vomitoria took up enormous numbers of lepra bacilli from the carcass of a leper rat and deposited them with their feces, but the bacilli apparently do not multiply in the flies, as the latter are clear of bacilli in less than 48 hours. Larvse of Chlorops vomitoria hatched out in the carcass of a leper rat become heavily infested with lepra bacilli. If such larvae are removed and fed on uninfected meat they soon rid themselves of most of the lepra bacilli. A fly, Mtisca domestica, caught on the face of a human leper was found to be infested with lepra-like bacilli. Most of the evidence bearing on the possible role of insects in the transmission of leprosy may be classified as purely presumptive evidence based upon analogy, or as evidence based simply upon the finding of acid-fast bacilli in certain insects. It must be plain that the simple taking up of para- sites by an insect does not necessarily imply that the insect plays a role in its transmission from one host to another. Further, all acid- fast bacilli are not leprosy bacilli. It cannot be denied that leprosy may be one of the insect-borne diseases; the final verdict will depend upon further studies. A great majority of lepers at some time in the disease have lepra bacilli in their nasal secretions. The importance of the nose in leprosy was brought into prominence at the First International Leper Confer- ^ Johns HopTcins Hospital Seports, 1900, VIII, p. 1. 296 MISCELLANEOUS DISEASES ence in 1897 by the work of Sticker, who made sweeping statements concerning the nose as the site of the primary lesion and the danger of nasal secretions in transmitting the disease. Jeanselme and Lau- rans (1895), Gerber (1901), Werner (1902), Sheroux (1903), and others have shown the frequency with which the bacilli of leprosy ap- pear in the nasal secretions and the importance of the nose as a site of leprous lesions. Sticker cites a five-year-old child of leprous parents seen by him in India with an ulcer on the right side of the nasal sep- tum which contained lepra bacilli and was the only lesion of the dis- ease present in the case. Plumert (1903) mentions the finding of lepra bacilli in the nasal secretions of persons in intimate family con- tact with advanced cases of leprosy. The individuals in question showed no other evidence of the disease. Palkao observed epistaxis associated with small ulcers on the nasal septum of descendants of lepers, and lepra bacilli were found in the crusts from these ulcers. The results of Sticker, Plumert, and Palkao would indicate that in the early stages of the disease the nose is frequently the site of a lesion discharging lepra bacilli. BrinckerhofE and Moore, however, who made a careful study of this question in Honolulu, point out that most of the studies upon the importance of the nose in leprosy have been made upon rela- tively advanced cases of the disease. They found the nose frequently the seat of infection when the disease is well developed, but practically never as a primary or incipient lesion. If the nose were the usual seat of the primary lesion in leprosy, it would indicate that the infection is carried there upon the finger. Hollmann studied 500 persons in the Hawaiian Islands suffering with a recognizable form of leprosy for periods varying from three months to twenty-five years, and found 410 with lesions of the nasal mucous membrane and only 90 in which such lesions were absent. It is sufficient for practical prevention to know that leprosy is spread mainly by direct contact and perhaps occasionally by indirect contact with persons suffering with the disease. Leprosy is most preva- lent under conditions of personal and domestic uncleanliness and over- crowding, especially where there is close and protracted association be- tween the leprous and the non-leprous. There is no evidence that leprosy is hereditary. The occurrence of several cases in a single fam- ily is doubtless due to "contact." The danger of infection from leprous persons is, of course, greater when there is a discharge from the le- sions of the skin and mucous membranes. . Prevention. — The prevention of leprosy depends almost entirely upon isolation, care of the infected discharges, personal cleanliness, and sanitary surroundings. That the disease is transmitted with dif- ficulty is shown by the fact that doctors, nurses, sisters of charity, ward tenders, and others directly exposed in leprosaria seldom become LBPEOSY 297 infected. Notable exceptions have been Father Damien in Honolulu and Father Bogliolo in New Orleans. Evidently close, prolonged and intimate contact is ordinarily necessary to contract the infection. For many years a case of leprosy was cared for as a patient in a hospital with which I was associated. He had his own dishes, towel, soap, etc., otherwise he mingled freely with the patients and others, without spreading the disease. For the control of leprosy the most important administrative meas- ure is to segregate the lepers in settlements or asylums. Compulsory notification of every case of leprosy should be enforced, if for no other reason than to keep track of the disease and to know whether it is on the increase. Segregation of lepers is the most important single pre- ventive measure. The leprosaria should be inviting and should con- tain all modern improvements for the care and treatment of the disease. Leprosy is by no means invariably fatal. In the United States, where there are only a few hundred lepers, the Government should establish a national leprosarium conducted upon the principles of a modern sanitarium for tuberculosis. To require each state to provide suitable accommodations to segregate its few lepers is econom- ically wasteful. It is claimed that the decrease in leprosy in Europe since the middle ages has been due in large part to the segregation of the lepers in leprosaria, which at one time numbered 20,000. On the other hand, the value of segregation in countries where leprosy is very prevalent is disputed. As a rule, only the advanced cases are detected and isolated. Segregation in the Hawaiian Islands has so far had no effect upon the prevalence of the disease. There are factors in the control of leprosy not yet understood. There can be little objection in a country such as ours, where leprosy shows slight tendency to spread, to give a clean leper his freedom. There is no more danger from a leprosy patient of clean personal habits, who exercises care concerning the discharges from the lesions, than there is from a discharging case of tuberculosis of the glands of the neck. The national quarantine regulations forbid the landing of an alien leper. The law requires that such person be deported on the same ves- sel that brought him. A citizen of the United States having leprosy cannot be debarred. Such individuals are admitted and then come un- der the health laws of the state or port of entry. Specific Prevention. — There is no specific prevention or cure for leprosy. Nastin is a substance proposed by Deycke and consists of a neutral fat obtained from a streptothrix. The reports from its use are not particularly encouraging. Eost, of Eangoon. Burmah, uses a substance which he calls "leprolin," a precipitate from leprous tu- bercles. Tuberculin in somewhat large doses injected subcutaneously 298 MISCELLANEOUS DISEASES into leprous patients produces both a general and local reaction, but the repeated injections do not materially influence the disease, although such treatment seems to cause a local improvement or softening of the leprous tubercles. Heiser in Manila reports favorable results from the application of X-rays. Dyer in Louisiana has obtained good results from good food, fresh air, cleanliness, and the general principles applic- able to the modern treatment and prevention of tuberculosis. MENTAL DISEASES THE PREVENTION OF MENTAL DISEASES By Thomas W. Salmon, M.D. Passed Assistant Surgeon, U. 8. Public Health Service; Director of Spe- cial Studies, National Committee for Mental Hygiene; Formerly Chairman of the New YorJc State Board of Alienists. Although, in the prevention of insanity, we have to deal with prob- lems more complex than those which have been considered in the prevention of the infectious diseases, some mental diseases are known to depend upon causes as definite as the infection of the body with pathogenic bacteria. We know, for instance, that if a patient with one of the alcoholic psychoses had not been addicted to the use of al- cohol he would not have acquired this mental disease, whatever other bodily or mental infirmity he might become afBicted with, for recent methods of studying mental diseases have made it possible to recog- nize certain groups of symptoms which can be produced by alcohol and by that cause alone. There are clinical symptoms and laboratory findings which enable us to learn, with small chance of error, that a patient is suffering from general paresis. We know that such a pa- tient owes his mental disease to syphilis, and that for him the preven- tion of insanity would have consisted in the prevention of syphilis. Fot all types of mental diseases, however, have causes so well un- derstood as these. There are many in which the pathology is unknown and in which the symptoms are so variable that at present we are obliged to place them in provisional groups from which we may be able to rescue them later, perhaps, when present diagnostic difficulties have been overcome or when new light has been thrown upon their nature. It seems desirable, in discussing the preventable causes of insanity, to consider first some of the factors which -we know are ca- pable of producing mental disease, either directly or indirectly, at the same time referring to possible means for their control, and then to consider some other causes which we have excellent reasons for believ- MENTAL DISEASES 299 ing influence the prevalence of insanity, but which operate in a man- ner which cannot be shown so conclusively. It is essential to state at the outset that a number of different diseases are included in what we term "insanity." It would be quite permissible to speak of the various mental diseases as "insanities," so greatly do they vary in their symptoms, course, and etiology. Just as the popular term "heart disease" properly includes congenital malfor- mations, changes associated with acute infectious diseases, reactions to toxic substances, disturbances of the nervous mechanism, and the ef- fects of disease of remote organs, so "insanity" includes diseases de- pendent upon congenital mental deficiency or developmental defects, the exhaustion accompanying acute or chronic disease, the introduction of toxic substances into the body or their elaboration within it, organic changes in the brain, and abnormal psychic reactions. INFECTIOUS DISEASES WHICH CAUSE INSANITY It seems desirable to consider infectious diseases as a cause of mental disease first, not because they are responsible for a larger pro- portion of cases than other preventable causes, but on account of their closer relation to that with which we are familiar in the realm of pre- ventive medicine. Typhoid fever may give rise to permanent or transitory mental impairment. The prevention of insanity in this instance consists, of course, in the prevention of typhoid fever. When the evils resulting from the needless prevalence of that disease are counted up, the cases of mental disease caused by it must be included. Other infectious diseases, notably influenza, scarlet fever, malarial fever, erysipelas, and septicemia (particularly from uterine infection), furnish a considerable number of cases of mental disease, chiefly in the infective-exhaustive group, in which exhaustion, elevated tempera- ture, and poisoning of the nervous centers by bacterial toxins are the immediate causes of mental changes. About three per cent, of all first admissions to hospitals for the insane ^ belong in this group. It is impossible to estimate the proportion of cases in which infectious disease is the only cause in other types of mental disease, for an acute infection may "liberate" an attack in a patient subject to a psychosis in which recurrences are common, and this cause may combine with others, alcohol, for instance, in the production of a psychosis in which the infectious disease plays a secondary part. ' This percentage and others following are based upon recent statistical studies of admissions to the state hospitals of New York and Massachusetts. About one-fourth of all the insane under treatment in the United States are patients in the public institutions of these two states, and statements based upon the statistical studies in question are fairly applicable to the United States as a whole. 300 MISCELLANEOUS DISEASES Preventive measures in such types of insanity must consist chiefly in the general work of limiting the prevalence of the infectious dis- eases, but much can be done by improved methods of treating febrile conditions. The full significance of delirium and its pathology must be appreciated and hydrotherapy employed more generally and more carefully if we are to lessen the number of patients with infective- exhaustive psychoses. The indiscriminate use of sedatives or hypnotic drugs in deliria sometimes results in an aftermath of mental disease. Syphilis deserves separate consideration as a preventable cause of mental disease, for it is the essential cause of general paresis, a disease responsible for about 13 per cent, of all first admissions to hospitals for the insane in this country, and for nearly one-fifth of all male admissions. In admissions from American cities more than 22 per cent, of male patients are suffering from general paresis. More deaths resulted in New York State from general paresis in 1911 than from smallpox in the whole registration area of the United States since 1908. Half as inany deaths are known to occur every year from general pare- sis as from typhoid fever. It is believed that a considerable number of deaths from general paresis, when occurring outside of institutions, are reported as "softening of the brain" or by some other indefinite term, and the prevalence of general paresis is, therefore, far greater than mortality statistics would indicate. This disease runs a uniformly fatal course, the average duration of which is from two to five years. It attacks people who have, to all appearances, recovered from syphilis, and most frequently in the fourth decade of life, when their usefulness to the community and to their families is greatest. It is the grimmest specter which follows youth- ful indiscretions and "sowing wild oats." Of course, the prevention of general paresis depends wholly upon the prevention of syphilis, a well-defined field of effort in preventive medicine, but it seems that impetus would be lent the movement for venereal prophylaxis if the appalling prevalence of this result of syphilis were more widely known. It is a rather surprising fact that many of those actively engaged in the campaign against venereal disease are quite unaware of the preva- lence of general paresis or that it depends upon previous infection with syphilis. It is a fact that general paresis is a much more frequent manifestation of syphilis than locomotor ataxia.^ 'It is very desirable to know what proportion of cases of syphilis result in general paresis, but, until recently, no satisfactory studies had been undertaken to determine this, and, on account of the long interval between infection with syphilis and the development of symptoms of general paresis, it seemed impossi- ble to find a group of population in which such studies could be made. A short time ago, however, Mattanschek and Pilcz made public (Berliner IcUnische Woeh- enschrift, Feb. 19, 1912) the results of a careful examination of the histories of 4,134 officers of the Austrian Army who had contracted syphilis during the period 1880-1890. They ascertained that 4.67 per cent, of these officers developed general paresis. MENTAL DISEASES 301 A small number of cases of other types of mental disease are also .directly the outcome of syphilis. Mental deterioration is associated with gummata of the brain and mental changes accompany local menin- gitis due to syphilis. Syphilis is also responsible for a certain propor- tion of cases of congenital mental defect upon which insanity may become engrafted later, and it is often syphilis which first attacks the integrity of the arterial wall, thus laying the train destined to result, years later, in arteriosclerosis and mental disease dependent upon it. Tuberculosis is a cause of mental disease much less frequently than has been supposed. It is exceedingly doubtful if, as has been asserted, tuberculosis ever results in a special clinical form of mental disease, but the exhaustion of a chronic, wasting illness and the action of the tubercular toxin upon the nervous centers are probably immediate causes of mental changes. Although there are no especial measures of prevention of mental disease dependent upon tuberculosis, the fact that this is one of its possible effects might well be added to the in- formation disseminated regarding tuberculosis, for not the least of the benefits from curing incipient cases or preventing the spread of tuber- culosis is that the prevalence of insanity is thereby even slightly les- sened. Pellagra. — It is hardly justifiable, perhaps, to speak of pellagra as a preventable disease when the ground is just being cleared for a satis- factory search for its cause, which at present is assumed to be spoiled corn (see page 577). With the practical application of means for the control of this disease, a certain number of cases of insanity will be prevented in the localities where pellagra prevails. ACUTE AND CHRONIC POISONINGS WHICH CAUSE INSANITY Alcohol. — It is a strange commentary upon human frailty that all the poisons which assail man through accident and the dangerous trades in which he must engage, and all the poisons which are elabo- rated within his system, as in nephritis, diabetes, thyroidism, and ac- romegaly, are together responsible for but a small fraction of the num- ber of cases of mental disease due to his deliberate ingestion of one poisonous substance — alcohol. It is likely that alcohol, as a predisposing or as an immediate cause, is responsible for more than a third of all admissions to our hospitals for the insane. When, however, we consider alcohol as a cause in diseases in which other etiological factors enter, we are upon ground where statements must be made with caution and with many qualifications. Thus a man with a considerable degree of congenital mental defect is induced by some companions to take a few drinks 302 MISCELLANEOUS DISEASES of whiskey, and he thereupon develops an episode of excitement which lasts several months. Alcohol is not the most prominent feature in such cases, perhaps, and yet if it is withheld such persons might never develop acute mental symptoms. In considering alcohol as a cause of mental disease it seems best to confine ourselves at first to those diseases which, from their symptom-complexes, we have come to rec- ognize as the alcoholic psychoses. In these disorders, acute alcoholic hallucinosis, chronic alcoholic insanity, and Korsakow's disease, to diagnose the disease is to know the cause. About 12 per cent, of all first admissions are for these psychoses. They are met in men about three times as frequently as in women, and, as in the case of general paresis, more frequently in admissions from cities than from the country, although there is by no means as much disparity. These alcoholic psychoses are the direct, unmistak- able results of intemperance, acting in many cases upon psychopathic individuals, but it is believed that in less direct ways alcohol is re- sponsible for nearly as large a share of admissions to hospitals for the insane. In the year ending September 30, 1909, alcohol was as- signed as an etiological factor in 31.4 per cent, of the men admitted to the ISTew York State hospitals, and in 9.6 per cent, of the women. As a habit disorder, but not a definite etiological factor, intemper- ance was reported in 14.3 per cent, of cases among male admissions . and 6.1 per cent, among female admissions. So 45.7 per cent, of all the men admitted and 15.7 per cent, of all the women admitted were addicted to the excessive use of alcohol. This is a prevalence of intem- perance enormously greater than in the general population, but it must be remembered that not a few patients admitted to institutions for the insane had become intemperate as a result of mental disease, and a great number, including those with alcoholic psychoses, as a result of constitutional mental inferiority. The idea is spreading among psychi- atrists that, in a world of drinkers, the alcoholic is an abnormal type. This fact does not in any way lessen the importance of alcohol as a cause of mental disease, but it shows the great necessity of throwing especial safeguards about unstable persons in whom intemperance may lead to such disastrous results. There is hardly a mental disease which is not influenced unfavor- ably by alcoholic habits. They lend a tremendous impetus to the retro- gressive changes in senility, and, as has been said, the acquisition of alcoholism by defectives often results in acute mental symptoms when none need have occurred. Statistics collected independently by several investigators show that the parents of nearly 50 per cent, of defective children were alcoholics. It is held by many psychiatrists that no other single cause of imbecility and idiocy except mental defectiveness in the parent can compare with alcoholism in the parents, intemperance of MENTAL DISEASES 303 mothers during pregnancy being thought to be particularly likely to result in mental defect in the offspring.^ The prevention of mental diseases due to alcohol, like the preven- tion of those due to syphilis, is only part of the general movement against these enemies of the race. Excluding poverty and crime, there is probably no more disastrous result of alcoholism than the continual procession of unfortunates who are entering hospitals for the insane because of intemperance, and it is certain that no other fatal termina- tion of syphilis is so frequent as general paresis. Other Exogenous Poisons. — Morphinism and other drug addictions are responsible for less than one per cent, of first admissions to hos- pitals for the insane in this country. Few^er such patients are ad- mitted in New York and Massachusetts now than were a few years ago. This gratifying fact is due, in part at least, to stricter enforce- ment of the laws regulating the sale of narcotics and particularly to the pure food laws which have rendered it a little more difficult to dispense habit-forming drugs in patent medicines. It is well within our power to eliminate this cause of mental disease by wise legislation and its rigid enforcement. A very small proportion of admissions is caused by occupational poisonings, such as lead and carbon monoxid. This small proportion can be still further reduced by increasing attention to measures safeguard- ing workmen in dangerous trades. Endogenous Poisons. — Those poisons originating within the system which produce mental disease are for the most part the result of other diseases, and these diseases — nephritis, heart diseases, and diabetes — are, unfortunately, beyond the reach of preventive medicine. When the infectious diseases have come under our control, and when means have been devised to reduce accidents to a minimum, the preeminence of these diseases as causes of death will only be accentuated. In the case of psychoses dependent upon diseases of the thyroid gland, early treatment of the primary disease is a hopeful means of prevention. It is curious that vaccines and sera should be 'furnished free by the state while any person can remain mentally defective from cretinism, because prolonged treatment is too expensive. The state has such an enormous number of the insane and mentally defective 'It should be said that recent studies by the Francis Galton Laboratory of Eugenics, London, point to directly opposite conclusions. The weight of evidence, however, is in favor of the relation between alcoholism and mental defect indicated above. Bezzola and Hartmann state that examinations of the birth-dates of idiots and imbeciles in Switzerland show that conception recurred in a large proportion of cases at seasons of the year when the celebration of certain festivals were accompanied by much intoxication. It is said that this is popularly recognized and that such children are known in certain districts as rauscMnder ("jag-children")- On the other hand, the birth-dates of defective children in certain fishing villages in Northern Europe where there is much peri- odic intoxication have been carefully studied and no such relation discovered. 304 MISCELLAI^EOUS DISEASES for whom permanent care must be provided that it would be a matter of sound policy to seek out such cases and then provide the best care and treatment absolutely without cost. HEAD INJURIES AND INSANITY A considerable number of the cases admitted to every large public institution present a history of head injuries, usually with fractures of the skull. There are certain symptom-complexes especially frequent in such cases, and so it can be said that injury of the brain is a specific cause of mental disease. Street accidents, railroad accidents, and unprotected machinery are by far the most frequent causes of head injuries in civil life. It is quite justifiable to consider this cause of insanity as pre- ventable, for one has only to read the recent literature on safeguarding workmen in factories and protecting railway employees to see that this is a field in which much may be done. Street accidents have been practically eliminated in some cities by efficient police regulation of traffic. In a consideration of the prevention of insanity this phase is not sufficiently important to receive much space, and yet it seems de- sirable to mention it. HEREDITY AND INSANITY It is probably safe to say that none of the causes of insanity which have been considered, unless it be alcohol, is as important a factor as heredity, and heredity enters largely into the production of alcoholism, or, at least, into the production of the mental type which succumbs to alcohol. Opinion as to the influence of heredity upon the development of mental disease has undergone much change in recent years, as it has in reference to other diseases, but it can be said that studies which have led to heredity being considered of secondary importance in some con- ditions in which it was thought to be paramount have been ofEset by studies in other directions which have disclosed heredity as a factor of the greatest importance. Studies are actively under way to determine the relation of Mendel's laws to heredity in insanity. In large series of admissions for all forms of mental disease in this country and in Europe it has been found that, in the cases in which a satisfactory history was obtainable, about 50 per cent, of the patients had an insane heredity. There are no statistics available in this country to show the proportion of normal people with an insane heredity, but Kraepelin quotes Jost as giving the percentage as 3 and Nacke as giving it as 7.5. There are some mental diseases in which the percentage of insane heredity is only slightly more than this, while in manic-depressive insan- ity the percentage has been found in a large series of cases to be as high as 70, many of the insane ancestors having other forms of mental disease. MENTAL DISEASES 305 This shows very interestingly the unity of some of the factors which underlie mental diseases of different types. Without discussing the influence of heredity further, some possible means of prevention may be considered. This is the domain of eugenics. The means suggested all have for their object either the permanent sequestration of the insane and mentally defective or the prevention of offspring by control of marriage or by sterilization. It has been proposed by some that it should be required by law that no woman in the child-bearing period who secures admission to a hospital for the insane for a psychosis in which heredity is known to play a prominent part should be discharged, even if recovered, until the menopause has been reached, and it is asserted that the welfare of the race Justifies such a procedure. It cannot be denied that such a course might in time effect some reduction in the prevalence of mental diseases. It would seem that society can find justification for adopting some such measures to protect itself in those cases in which every period of parole or dis- charge from a hospital is followed by a pregnancy, but the ethical con- siderations involved are so complex that it is sufficient here merely to state this proposal. It has been proposed to sterilize by vasectomy or other means all patients when they are about to be discharged from a hospital for the insane, if their mental disease was of a type in which heredity is prominent. Here again there are complex ethical questions to be considered, but, as an alternative, it may be suggested that all such patients should at least he offered the opportunity of providing against such an occurrence. It is believed that, if the matter were tactfully and earnestly presented, the freedom from danger pointed out, or even a small bounty paid by the state in suitable cases, there would be a considerable number of acceptances. , Prohibiting the marriage of those in whom insane heredity within a close degree of relationship exists would depend for its effectiveness upon the provisions for obtaining such information and any such meas- ure would be practically without value unless it were required in a number of states. Education as to the dangers of heredity and appeal to social conscience, by physicians, teachers, and clergymen, would un- doubtedly deter a few from marriage, but it is the experience of physi- cians generally that such advice is rarely heeded. Before the matter can be presented in a "campaign of education" there is need for far better information than we possess at present. Facts should be most carefully sifted and statistical studies of broad scope undertaken under the auspices of the government or some national society before infor- mation regarding heredity and insanity is prepared for wide dissemina- tion. 306 MISCELLANEOUS DISEASES PSYCHICAIi CAUSES During the last few years the psychical causes of insanity have been recognized as of great importance, and types of mental disease -which were thought to be almost wholly dependent upon the constitutional make-up of individuals have been shown by Freud, Jung, Meyer, Hoch, and others to be dependent very largely upon errors of education, un- suitable environment, the acquisition of injurious habits of thought, and the suppression of painful experiences, usually in the sexual field, which later in life form the basis for psychoses. The outlook for the prevention of insanity is very hopeful in some of these cases in the individual. Emphasis must be placed upon the important fact that the founda- tions of aberrations in which sexual trends are prominent are laid at an extremely early age. It is only very recently that it has been shown that experiences in childhood and infancy exercise a controlling influ- ence upon the sexual life of later years. The practical application of this is not that children are to be brought up in seclusion, but that there is no higher duty of parents than to establish such relations with their children that sex difficulties can be discussed and straightened out before they give rise to permanent moods or trends. Hypocrisy and false shame are not natural attributes of the child, and when we create them we raise a barrier behind which much damage may take place without our knowledge. In childhood and in adolescence there must be established the closest bonds of sympathy and understanding between parent and child. Wholesome, frank communication and sen- sible consultations at that time regarding sex quandaries may save a child or young adult from disaster later on. In the aberrations which come with adolescence one can usually recognize the results of early mismanagement in these matters, and the urgent need for sound ad- vice and correct guidance needs no elaboration. In dispensaries for '^border-line" cases some hidden sexual trends or other factors in psychogenesis may be discovered, and preventive measures prove successful. Nothing could aid more in the discovery of such factors than general appreciation by physicians that they may exist and may result in insanity. If there were such general recogni- tion of the part such factors play many persons not insane would be referred to the psychiatrists and more psychiatric clinics would be established. ECONOMIC PACTOES Unemployment, overwork, congestion, of population, child labor, and the hundred economic causes which increase the stress of living MENTAL DISEASES 307 for the poor are factors in the production of insanity which often seem to outweigh all others. Weaknesses in constitutional make-up — de- fects in the armor of personality — are disclosed under the stress of such conditions which would have remained undiscovered under happier cir- cumstances. All that can be said of the prevention of such causes is that everything which makes for the betterment of those upon whom the stress of living falls heaviest will save many from mental disease. For the individual careful training, encouragement, wise counsel, and a little financial assistance in times of especial need are helpful meas- ures. If the operation of these powerful causes cannot be prevented, those who are most likely to be harmed would, perhaps, be shielded a little if the dangers which they face were more generally known. IMMIGRATION No consideration of the preventable causes of insanity in this coun- try would be complete without reference to this important element in our national life. It is a question peculiar to the United States. Since 1820 more than 28,000,000 immigrants have come to this country. This vast migration has no parallel in history. In some states the increment to the population from immigration every year exceeds that from births. Under such conditions movements such as those directed against alcohol, heredity, or the economic causes of insanity are feeble compared with a thorough sifting of applicants for admission while they are still at our threshold. We have the absolutely unquestioned right to require any reasonable tests which can be proposed, and yet the present immigration law results in the mental examination of only one in every thousand of the million immigrants who seek admission each year. There is no provision whatever requiring immigrants to present certificates from responsible authorities at home, testifying to their freedom from mental disease. These crowds of immigrants, 30 per cent, of the adults illiterate and less than 20 per cent, with any trade, are, practically without mental examination or selection, projected into our most congested centers of population, to bear, during their first year in America, as severe stress as any group of population can be called upon to endure. One result is that they flood our hospitals for the insane. Hundreds have to be returned during the first year for mental disease due to causes which existed before their arrival. In the succeeding years the proportion rises and in the next generation and the one succeeding it we shall reap the harvest for which our pres- ent policy is sowing the seed. It can be earnestly asserted, after long study of this question, that no measures for the prevention of in^a];ii\ty which have yet been suggested can prove so efficacious/ as artificial selection of accretions to our population, on the vast scyle which an 308 MISCELLANEOUS DISEASES adequate mental examination of immigrants would permit. This is a measure of practical eugenics which can be applied as successfully now as in a generation. As Professor E. DeC. Ward has said, "it is merely a question whether we or foreign steamship agents shall select the parents of future generations of Americans." The provisions of the federal immigration law which deal with the exclusion of insane immi- grants are in need of thorough and immediate revision, and the enforce- ment of the law should receive the attention which its importance deserves. We have been far too careless of the welfare of recently landed immigrants. There seems to be a general impression that, however unsanitary their surroundings or however heavy may be the burdens placed upon them, immigrants are, in some way, fitted for such hard- ships, either by nature or through previous experiences in their homes. Of course, this assumption is wholly without Justification, and it is time that the social, economic, physical, and moral welfare of these newcomers be given the earnest attention of the federal and state gov- ernments and of societies and individuals. By so doing something may be done to lessen the terrible prevalence of mental disease in this large group of our population. THE AGENCIES AVAILABLE FOB THE APPLICATION OP PEEVBNTIVE MEASUEES It is possible to outline only very briefly the agencies which can be utilized in the application of preventive measures. Hospitals for the Insane. — A very large proportion of the insane persons in any state will be found under treatment in public institu- tions. This is not the case with other diseases, sufferers from which are widely scattered, in their homes, at work, and in hospitals. This fact makes the hospital for the insane seem the logical place from which preventive measures should emanate. Every large hospital for the insane, unless entirely inaccessible, should maintain a dispensary. To that dispensary, if it is skillfully conducted with its broadest aims constantly in mind, will come in- cipient cases, "border-land" cases, those who have had previous attacks of mental disease, and relatives seeking advice. Such dispensaries — and several have already been instituted — afford rich opportunities for the practical application of preventive measures and for the dissemina- tion of information. Members of the hospital staffs should also engage in field work in the districts from which their hospital receives its pa- tients. Talks on the preventable causes of mental disease, the advan- tages of earlier treatment, and the necessity of considering insanity as a disease and not a crime can be given by such medical field workers in MENTAL DISEASES 309 schools and churches and before clubs and societies. Such talks should be supplemented by illustrated descriptions of modern methods of caring for the insane and promoting their happiness and comfort. It is usual for citizens to have a local pride in their hospital as a public institution, and this will often insure interest. Every such lecturer will be quite sure to have the relatives or friends of some of his patients among his hearers. Such field work by physicians should be supple- mented by that of well-trained social service workers permanently at- tached to the institution. The hospital should also be the center for instruction in clinical psychiatry in the community. The great wealth of clinical material in a large hospital for insane should be utilized to the fullest extent if a medical school is near enough, but it is believed that better knowl- edge of mental diseases in this country will be brought about much more effectively by developing the opportunities of the general practi- tioner for receiving instruction than by increasing very greatly the time devoted to psychiatry in medical schools. The medical student is often overburdened, and he has much difficulty in deciding upon the relative value of the matters presented to him. In competition with other branches of medicine psychiatry is very apt to fare badly, for it is likely to be regarded as a specialty of slight value or interest to one who is about to engage in general practice. With the practitioner it is different, for he is a dull man who does not learn early in his career that mental diseases are frequently met with and are very important in many of their relations. It is a fact that there is no opportunity in the United States for a graduate in medicine to obtain post-graduate instruction in psychiatry unless he is a member of the stafE of an in- stitution for the insane or a medical officer of one of the government medical corps. The hospital for the insane has many opportunities for instructing general practitioners. Frequent medical meetings at the hospitals, in which clinical talks should have chief place, correspondence with physi- cians who sign commitment papers regarding interesting features or the course of their cases, invitations to necropsies (which in most small communities will be gladly accepted), and consultations when patients are about to be discharged, at which suggestions for after-care can be made, are all means of interesting physicians in mental diseases and their prevention. All these new tasks, which are certain to be assigned to our hospitals for the insane within a few years, will necessitate ad- ditional medical officers, and they make it more necessary than ever that clinical and laboratory work in these institutions should be upon a high plane. This means increased appropriations, but it is doubtful if a state can utilize its funds for a better purpose than in fostering the work of prevention in mental diseases. Placed upon a purely eco- 23 310 MISCELLANEOUS DISEASES nomic basis, such work is immensely profitable. It has been estimated that prevention of the admission of a single patient each year would yield a return to a state larger than the pay and expenses of two social service field-workers for a year. The hospital has also excellent opportunities for disseminating in- formation among the laity regarding the cause and prevention of in- sanity. Leaflets, personal talks, and general literature regarding these subjects will not fail to interest those who have come to the hospital to visit a near relative. Central Boards of Control. — In most states the administration of hospitals for the insane is in some measure under the control of a cen- tral board. Such bodies can do much in the prevention of insanity. In many states they can require such activities on the part of the hos- pitals as have been outlined, and in others they can exert powerful moral influence in having them undertaken. They can conduct statis- tical studies as to the preventable causes of insanity, and secure wide distribution of the material collected. They can suggest and urge legis- lation for the early treatment of the insane and for the adoption of specific preventive measures. They can, particularly by cooperation with similar authorities in other states, secure some reforms in federal legislation regarding the exclusion of insane and mentally defective immigrants, the urgent need for which has been pointed out. National and local Societies for Mental Hygiene. — There is a very clearly defined field of effort for national and local societies in the work of prevention of mental diseases. As has been indicated, the care of the insane is, far more than that of any other class of the sick, in official hands. There is besides a great deal in the methods of com- mitment and provisions for care, which is regarded wholly as an offi- cial matter. For this reason there is decided need of agencies which can bridge the gap between the home and usual environment of the patient and the public institution which is charged with his care. A certain part of the social service work which has so useful a place in the care of the insane, particularly in the period following discharge from institutions, should be done by workers under the direction of institutional authorities, but there is also a very great deal which can be done better by societies cooperating with institutional authorities but not officially connected with them. In New York State the "Com- mittee on Mental Hygiene" of the State Charities' Aid Association has a local committee in each hospital district. Although after-care and efforts to improve the kind of care afforded the insane in that criti- cal period while commitment is pending constitute the chief work of such committees, there is often opportunity for effective work in pre- vention. In Connecticut, Illinois, and Massachusetts there are state societies of mental hygiene doing most useful work. MENTAL DISEASES 311 There is a Kational Committee for Mental Hygiene, coordinating and, in a measure, directing these local activities. This committee has commenced studies into existing provisions for the care of the insane in all the states, methods of commitment and care, the influence of preventable causes, etc. With a carefully prepared plan of work, ac- curate information is to be obtained upon these matters, and, as fast as the facts in the possession of the committee justify it, active work is to be undertaken for amelioration or prevention. It is believed that a great deal can be done, especially in the direction of standardizing work for the care of the insane and the prevention of insanity, and in co- ordinating the efforts of the hospitals, state boards of control, and some of those organizations which sometimes, perhaps unawares, are attack- ing preventable causes of insanity from different angles. Such an organization as the National Committee for Mental Hygiene can stimu-i late interest on the part of the state and local authorities charged with the care of the insane, and it can sustain interest when it might other- wise flag. Standards established in a state where advanced ideas prevail can be made known in states where there is indifference or lack of prog- ress. A central "clearing house" for the collection and distribution of accurate information regarding the care of the insane and the preven- tion of insanity can be provided. Earlier treatment and the transfer of care pending commitment from the policeman to the doctor — the most urgent needs of the insane — can be secured by this organization, and the lamentable failure to provide instruction in mental diseases in the medical schools can be shown, and the means suggested for remedying the defect. It is a fact that the number of beds in the institutions for the insane in this country is greater than the number of beds in all the general hospitals of the United States. The insane are, therefore, the most numerous class of the sick receiving public care. As such, they demand a large share of the interest of every practitioner. Progress in every branch of preventive medicine depends most upon the efforts of physicians, and in this particular field there is need of much wider in- terest on the part of the medical profession than exists to-day. Education. — Under the direction of state boards of control and en- couraged by national and state societies for mental hygiene, much can be done toward placing the education of defective children upon a bet- ter basis. These children are now chiefly interesting to school authori- ties, for they constitute a special class and should receive separate in- struction, both for their own good and the good of normal children, whose progress is retarded on account of the excessive amount of time teachers must give defective children. They should have a far greater interest for the state than this, for every such child is a possible patient in a hospital for the insane or in a colony for the mentally defective. Every effort to prevent this outcome is justified, and it would seem 312 MISCELLANEOUS DISEASES desirable for the state to provide very liberally for the study of these children and for their education. Of even more importance, perhaps, is the permanent segregation of most of them. It has been estimated that in a state which adopts a high standard of caring for the insane about one-fifth of the annual income of the state will be required. Whether insanity is increasing or not, the num- ber of the insane under treatment has, up to this time, increased much more rapidly than the general population. New demands for charitable and social purposes are constantly being made upon state funds, but it would seem that any measures for the prevention of insanity which offer hopes of success should receive the substantial financial support of the state. The attempt has been made to outline some of the preventable causes of mental disease and to indicate, very broadly, possible pre- ventive measures. It seems essential that, notwithstanding the com- plexity of some of the questions involved, the prevention of mental diseases should be considered in the general advance which is being made against microbic diseases, for it is very closely related to all the other fields of preventive medicine. Eecent advances in the field of psychiatry have, upon the whole, given grounds for encouragement, for if the outlook in some directions is not bright the accuracy with which the part played by certain causes has been defined promises much. The fact that it has been definitely determined that there are certain essen- tial causes of mental disease, and that some of these essential causes are entirely controllable, makes it imperative that preventive measures be undertaken. CHAPTER VI SOME GENERAL CONSIDERATIONS Sources of Infection. — There are two great sources of the commu- nicable diseases of man, viz.: (1) man himself, and (2) the lower animals. Most of the communicable diseases of man, especially those which occur in epidemic form, are peculiar to man. This is the case with typhoid fever, cholera, leprosy, malaria, yellow fever, syphilis, mumps, measles, scarlet fever, typhus fever, infantile paralysis, small- pox, chickenpox, relapsing fever, dengue, and even tuberculosis in large part. It is quite true that some of these infections may be communi- cated to the lower animals under experimental conditions, but they do not, as a rule, occur in them under natural conditions. In other words, most of the communicable diseases from which man suffers are specific; the degree of specificity varying slightly with the different infections. It is, therefore, plain that man is the great source and reservoir of human infections. Man is man's greatest foe in this regard. The fact that most of the communicable diseases must be fought in the light of an infection spread from man to man is one of the most important advances in preventive medicine. This new thought has crystallized out of a mass of work in the sanitary sciences during the past decade, especially from researches upon tuberculosis, typhoid fever, cerebro- spinal meningitis, and other communicable diseases. Formerly sani- tarians regarded the environment as the main source of infection. We now know that water, soil, air, and food may be the vehicles by which the viruses of the communicable diseases are sometimes transferred — - that is, they are media of conveyance rather than sources of infection. Most of the microorganisms causing the communicable diseases of man are frail and soon die in our environment, as in the air, soil, or water. Most of them are obligate pathogens and cannot or do not grow or multiply in our environment. Prom the lower animals, particularly the domesticated animals, man contracts a number of infections. Thus we contract rabies from the dog; plague from the rat; glanders from the horse; trichinosis from hogs; anthrax from cattle; malta fever from goats; foot-and-mouth dis- ease from cattle; tuberculosis, in part, from cattle; tapeworms and other animal parasites from the meat of fish, fowl, and mammals. Vari- ous skin parasites are also contracted from the lower animals, as ring- 313 314 SOME GBNEEAL CONSIDEEATIONS worm from cats, fleas from dogs, etc. The number of these diseases and the extent of their ravages are notably less than those contracted from man himself. The knowledge that most infections are spread rather directly from man to man brings in all the forces of sociology to that of preventive medicine. The task of preventive medicine is thereby rendered much more difficult from the fact that most infections depend upon the con- trol of man himself. We ruthlessly wage war against insects or against infected food or water. In other words, we can arbitrarily control our environment to a very great extent, but the control of man himself requires the consent of the governed. Thus it is easier to stamp out yellow fever than to control typhoid fever. It is easier to suppress malaria than tuberculosis, rabies than influenza, trichinosis than measles. Cattle appear to be mutely thankful when protected by inoculation against blackleg or anthrax, but man rebels against one of the best of all specifics — vaccination against smallpox. The fact that man is the chief source and reservoir of most of his own infections adds greatly to the scope and diffieulties of public health work and often makes the prevention of disease depend upon social changes. In this sense pre- ventive medicine is the true sociology. Modes of Transference. — The viruses of the communicable diseases may take various routes of transference from man to man or from animal to man. These routes are spoken of as the modes of infection, the modes of transference, or sometimes as the vehicles of infection. Formerly they were spoken of as the "channels of infection," but now we restrict that term to the special channels by which the infection enters the body. Thus the channel of infection in tuberculosis may be the respiratory tract, the digestive system, or the skin; whereas the mode of infection is from tuberculous sputum, either by direct contact or through the air, as in droplet infection, or through milk or some other vehicle. The modes of transference may be grouped, for convenience, under three general heads: (1) direct, (2) indirect, and (3) through an in- termediate host. In the great majority of cases the virus is transferred more or less directly by what is now known as contact infection. In many instances the virus is transferred indirectly " through water, food, soil, air, etc. In a large group of diseases the transfer is through an intermediate host which furnishes the growing list of insect-borne dis- eases. Contact Infection. — -"Contact infection" is a convenient term in- tended to include a group of circumstances in which infection is spread more or less directly or indirectly from person to person. Contact in- fection assumes a transfer of quite fresh infective material. Actual contact between the two individuals is not necessary, but the convey- CAREIEES 315 ance is, nevertheless, pretty close in time and space. Contact infection alone maji' be resjjonsible for epidemic outbreaks, even in the case of typhoid fever. The diseases in Avhich contact infection plays a dominant role are those in which the virus leaves the body in the discharges from the mouth and nose, as tuberculosis, diphtheria, scarlet fever, measles, in- fluenza, common colds, cerebrospinal meningitis, whooping-cough, mumps, etc. Contact infection also pays a large role in diseases in which the virus leaves the body in the fecal and urinary discharges, as in typhoid, cholera, dysentery, and other intestinal infections. In contact infection the virus may be transferred from man to man directly by actual contact, as in kissing, or more indirectly upon soiled hands, contaminated towels, or infected cups, spoons, toys, remnants of food, and other objects which have recently been mouthed or handled by the infected person. As a matter of fact, the ways by which the infection may be transferred, and still be considered contact infection, are numerous and varied. In every instance, however, the transfer is brought about in pretty close association with the infected person. Indirect Infection. — A large group of diseases are conveyed in- directly from person to person through the water, food, soil, and occa- sionally through the air. Diseases may be conveyed great distances by means of food or water; they are never conveyed long distances through the air. In the large majority of the diseases contracted by indirect infection the virus is taken into the system through the mouth and discharged from the body in the feces. The best examples of this class are typhoid fever, cholera, and dysentery. The relation of soil, food, water, air, and our environment is discussed separately. The insect-borne diseases form a large and important group, which are fully discussed on pages 181 to 374. Carriers. — By the term "carrier" we understand a person who is harboring a pathogenic microorganism, but who, nevertheless, shows no signs or symptom.s of the disease. Thus a person may have diphtheria bacilli in the nose and throat, but, nevertheless, be in good health. The same is true with the pneumocoecus, the meningococcus, strepto- coccus, and many other microorganisms. Persons may have typhoid bacilli, cholera vibrio, or hookworm in their intestinal tract without showing manifestations of these parasites. Furthermore, persons may have Plasmodia in their blood or spleen without having clinical malaria, and so on through a long list of infections. Persons who harbor pathogenic bacteria without showing symptoms are known as "bacillus carriers," those who harbor protozoa are known as "protozoon carriers," etc. Carriers may be acute, chronic, or "tem- porary" — that is, a person who discharges pathogenic microorganisms a few weeks after convalescence is known as an "acute carrier," one who 316 SOME GENEKAL CONSIDEEATIONS continues to harbor the microorganism for months and years is known as a "chronic carrier." A "temporary carrier" is a person in good health who has never had the infection, but who harbors and discharges a pathogenic microorganism for a brief space of time. The demonstration that many persons are carriers of infection has thrown a new light upon the control of the communicable diseases. With the new facts has come a realization of added difficulties. Carriers can only be detected by painstaking laboratory examinations. When discovered their control is as difficult as it is important. We cannot lightly imprison persons in good health, even though they are a menace to others, especially in the case of bread winners. In some infections there are so many carriers that it would require military rule to carry out such a plan. Fortunately in most cases absolute quarantine is not necessary. Sanitary isolation is sufficient. Thus the danger from a typhoid carrier may be neutralized if the person exercises scrupulous and intelligent cleanliness, and is not allowed to handle food intended for others. Such a person might well be engaged as carpenter, seam- stress, or other occupation without endangering his fellowmen. fhe fact that carriers exist in a large number of diseases makes their suppression one of great practical difficulty. The cure of carriers is one of the pressing problems in preventive medicine. One hopeful feature of the carrier situation is that their number may be diminished by isolating and diminishing the cases of the corresponding disease. Thus, the number of typhoid carriers falls off sharply as a result of any successful measure directed only against the clinical case. The facts con- cerning carriers have been discussed separately under each disease in which they occur. Missed Cases. — By missed cases we understand mild and atypical instances of disease which are not recognized clinically. Almost all diseases vary greatly in severity. Thus we have walking typhoid and ambulant plague. Measles, scarlet fever, yellow fever, influenza, and most other infections may be so mild that they escape notice. Even the patient himself may not know he is sick. These mild cases go to school, ride in street cars, attend theaters, continue at their usual work in crowded factories and other places, handle our food, and thus spread infection. It is now well known that missed cases are a prolific source of spreading the infection of many of the communicable diseases; they form an important factor in preventive medicine. Channels of Infection. — There are numerous channels by which in- fection may enter the body. These are usually grouped under three headings: (1) the respiratory tract, (2) the digestive tract, and (3) through the skin. Perhaps 90 per cent, of all infections are taken into the body through the mouth. They reach the mouth in water, food, fingers, dust, and upon the innumerable objects that are sometimes "CONTAGIOUS" AND " INFECTIOUS " 317 placed in the mouth. The fact that the great majority of infections are taken by way of the mouth gives scientific direction to personal hygiene. Sanitary habits demand that the hands should be washed before eating, and fingers should be kept away from the mouth and nose, and that no unnecessary objects should be mouthed. All food and drink should be clean or thoroughly cooked. These simple pre- cautions alone would prevent many a case of infection. "Contagious" and "Infectious." — These are popular terms which lack scientific precision. The words have been used in very diverse senses. A contagious disease is one that is readily communicable — • in common parlance, "catching." Formerly a contagious disease was considered as one which is caught from another by contact, by the breath, or by effluvia. If contagious diseases are limited to those con- tracted by direct contact or touch, as the etymology of the word signifies, only syphilis and diseases similarly contracted would be contagious. As a matter of fact, smallpox and measles are types of contagious diseases, as the term is now usually understood. An infectious disease is usually considered as one not conveyed directly and obviously, as in the case of contagion, but indirectly through some hidden influence or medium. In the days when specific febrile diseases were regarded as caused by miasmata and noxious effluvia, the terms "infectious" and "miasmatic" diseases were more or less synony- mous. Typhoid fever was often taken as a type of an infectious disease. Malaria was the type of a miasmatic disease. These distinctions are entirely artificial, and serve no useful pur- pose. Most of the communicable diseases may be transmitted from the sick to the sound in several ways. Dividing diseases into those which are contagious and those which are infectious entirely leaves out of consideration the important class of insect-borne diseases. The terms contagious and infectious have always 'lacked scientific precision and have been the source of some confusion. The word "communicable" is a much better term and should be given preference. A communicable disease is one caused by a specific virus transferred from person to person, or from animal to animal, in a great \'ariety of ways. The term "communicable" ignores the mode of transference. There is a great difference in the degree of communicability ; some diseases are readily communicable, others transmitted with difficulty. The evidences of communicability are not so obvious in chronic infec- tions, such as tuberculosis, or in diseases with a long period of incuba- tion, such as typhoid fever. The relationship between one case and the next is often far removed in time and space. If tuberculosis were an acute infection like diphtheria it would be regarded popularly as being just as contagious as that disease. Epidemic, Endemic, Pandemic, and Prosodemic, — A disease is said 318 SOME GENEBAL CONSIDEHATIONS to be epidemic (epi=in, and demos=people) when it is common to or affecting at the same time a large number of persons in a commu- nity. A disease whicli spreads rapidly and attacks many people at the same time is usually said to be epidemic. A disease is said to be endemic (en=in, demos^people) when it is peculiar to a district or particular locality, or limited to a class of persons. An endemic disease is one which is constantly present to a greater or less degree in any place, as distinguished from an epidemic disease, which prevails widely at some one time or periodically. A sporadic (occurring singly) disease is one in which a few scattering cases occur now and then. Endemic diseases are apt to flare up and become epidemic. In- sect-borne diseases are the best examples of endemicity, as their preva- lence is strictly limited by the geographic distribution of the intermedi- ate host. Yellow fever has long been endemic in Havana, cholera in India, typhoid fever in Washington, and plague in Tibet. These terms not only lack precision, but are variously conceived and differently defined. Thus typhoid fever is said to prevail in Bos- ton, but a similar number of cases in Germany would be regarded as an epidemic. For the purposes of maritime quarantine a disease is considered epidemic if there is more than one focus of infection; that is, if several cases occur which have no apparent connection with each other. Strictly, therefore, according to this definition, two cases may constitute an official epidemic and the port would, therefore, be regarded as infected. It is not feasible to state just how many cases of a disease constitute an epidemic. Ordinarily a few cases of a communicable disease in a village or small town is not regarded aa an epidemic; however, five cases of typhoid fever in Podunk (population 1,000) is the equivalent of 5,000 cases in a city of 1,000,000. By the same token, one or two cases in a small village would proportionately constitute an epidemic of unknown magnitude in a metropolis. "Pandemic" (pan=all, demos=people) is a term used to describe a disease which is more or less epidemic everywhere. Pandemics affect a large number of people in a large number of countries at the same time. Thus there have been four great pandemics of plague, when it spread to the four quarters of the globe. In 1889-90 influenza was pandemic. It is not usual, although quite proper, to regard tuberculosis and typhoid fever as pandemic. Sedgwick proposes the term "prosodemic" (proso^through, demos=: people) to take the place of the unsatisfactory word "endemic." Proso- demic suggests the prevalence of a disease which is being communicated from person to person through the community by various means, but especially by contact. EPIDEMIC CAMPAIGN 319 The Management of an Epidemic Campaign. — The first essential for success in the suppression of an epidemic is a knowledge of the epidemiology of the disease. The most important ■ single information from a practical standpoint is a knowledge of the mode of transference of the infection. We do not know the cause of yellow fever; however, yellow fever campaigns have been crowned with success because we know it is transmitted through the bite of a mosquito. We know the cause of cerebrospinal meningitis, but there is still uncertainty concerning its usual mode of transmission, and, therefore, our efEorts against this disease have been unavailing. The fact that we know that hookworm disease is transmitted by the larvas through the skin is of vital importance for the control of this disease. Without this knowl- edge at least 90 per cent, of our efforts to repress hookworm disease would be wasted. When typhoid fever was regarded as chiefly a water- borne infection only partial success was achieved, because contacts, milk, flies, and other modes of transference of the typhoid bacillus were disregarded. In case the disease has an intermediate host or the virus is trans- ferred by an insect or other animal, a knowledge of the biology of the animal in question is of prime importance. For example, the habits and habitat of the yellow fever mosquito are quite different from that of the malarial mosquito. A campaign against the rat and flea without an acquaintance with their breeding and feeding places and the best means available to repress or suppress such vermin would be unsuc- cessful. The same is true in' our campaign against tuberculosis with reference to cattle and man; in rabies with reference to dogs and other mammals; in sleeping sickness with reference to the tsetse fly; in Texas fever with reference to the tick; malta fever with reference to the goat; relapsing fever to the bedbug, and typhus fever with refer- ence to the louse. Authority. — Proper authority is necessary in order to enforce the necessary measures. This authority may come from the municipality, the state, or the federal government. In localized outbreaks, municipal authority is sometimes sufficient. More frequently the wider authority of the state is desirable. In our country it is a recognized principle in law that health laws and regulations belong to the police powers of the individual states. In most instances the general authority of the gov- ernment must be had, especially as interstate problems are almost al- ways involved in all epidemic outbreaks. The federal authority is lim- ited in health matters by the constitution. It therefore cannot act within a state unless invited to do so by the duly constituted authori- ties of the state. To send government health officers into a state against the will of the state corresponds to the sending of the regular army into a state to enforce measures against the will of the governor of 320 SOME GENEEAL CONSIDERATIONS that state. Such extreme measures are, therefore, only taken ia times of emergency. Occasionally a state, refusing to take necessary action and protect the other states, is f[uarantined. Thus, when California refused to officially recognize the existence of plague in 1899, the government quarantined the entire state. On account of our dual form of government it is important that the federal govern- ment, the state, and the local authorities cooperate in a friendly spirit. Epidemic diseases recognize no geographical boundary, and energetic and cooperative action is usually called for to suppress an outbreak. It is the common experience of those who have to deal with epi- demics that there is usually insufficient authority in law to provide for an emergency. It is, therefore, often necessary to take the bit in the teeth and adopt arbitrary measures which usually have the support of the better element in the community. Advantage may be taken of an epidemic to obtain laws to improve the health organization or the powers of the health officer. In this way an epidemic serves a useful purpose in arousing action. In the conduct of an epidemic it is very important that all the authority should center in one person. To conduct ah epidemic with a board of health or a health committee or a commission of any kind in- vites failure. It would be just as foolish to have a board of generals to fight a battle. Those who have been through many epidemics realize that it is no figure of speech to compare an epidemic campaign to a battle. It is a fight carried on at high tension, and, although the foe is invisible, it is a battle in every sense of the word. Ways and Means. — It is impossible to carry on a successful cam- paign against an epidemic without material resources. An epidemic campaign is expensive and success depends upon generous support. In most of the campaigns against yellow fever, plague, and cholera that have been waged in this country the expense has been borne in part by the government, in part by the municipality or state, and in part by subscriptions from citizens. The government has an epidemic fund appropriated by Congress and which is usually kept at about a million dollars. This fund is available only for plague, yellow fever, and cholera. Organization. — Headquarters should be organized at a convenient part of the city or the infected area, and headquarters should have all the modern office equipment and transportation facilities necessary for the quick dispatch of business. The city is then divided into sanitary districts. These may correspond to the political wards or the police districts and a subordinate is placed in charge of the work in each district. These districts are known as divisions, and the officer in charge of each division must establish headquarters for the work of that divi- QUARANTINE 321 sion. The actual work is done from division headquarters, under the direction of the chief in charge of the epidemic. It is also necessary to establish a laboratory in case laboratory diag- nosis is necessary for the recognition of cases or carriers, and emergency hospitals and detention barracks must be provided. Few cities have suf- ficient hospital facilities to meet a sudden emergency. Temporary ar- rangements must therefore be made. A modern school building makes a very good hospital and may be equipped for the reception of patients at short notice. Various squads must now be organized to carry on the particular work at hand. In the case of yellow fever these will be mosquito brigades; in the case of plague, rat brigades and disin- fectors, and in the case of smallpox, vaccinators, etc. It is frequently desirable, in fact often necessary, to make a house to house inspection throughout the infected district in oi^der to collect certain data, to determine whether cases are being reported or hidden, and to carry out special measures. These house to house canvasses are under the immediate direction of the officer in charge of the sanitary district and should be repeated as often as the occasion may demand. It is essential that all cases or suspected cases of the disease be promptly reported, for a case of communicable disease known is a case neutralized. It is the missed cases and the hidden cases that are par- ticularly dangerous. Educatiok. — A campaign of education should be carried on at the same time that the disease is being attacked. The people are keenly alive and hungry for information. Well-worded articles in the news- papers, circulars, pamphlets, lectures, demonstrations, and the other usual methods are available. The education of the community is im- portant in order to obtain cooperation, for it is a handicap to fight an epidemic without the active support of the people. While the first duty of the officer in charge is to allay panic and calm the unrea- sonable fears of the stricken community, the opposite extreme must be avoided. A healthy fear of the disease is one of the best instruments in the armamentarium of the sanitarian. It is almost hopeless to make progress against disease where the people supinely accept the conditions. Thus, if the people of the United States feared typhoid fever as they do yellow fever, it would soon diminish to the vanishing point. QUARANTINE The word "quarantine" is derived from the Italian word "quarante," meaning forty. Its present-day meaning dates from the middle ages when Venice and other Hanseatic cities detained arriving ships with cases of pestilence aboard for a period of forty days. This was the first systematic application of maritime quarantine, although from the earliest times lepers were segregated or quarantined. To-day we have 323 SOME GENEEAL CONSIDEEATIONS many kinds of quarantine: maritime quarantine, interstate quarantine, house quarantine, cattle quarantine, j'ellow fever quarantine, shotgun quarantine, etc. The dominating principle in modern quarantine is that it must be a sieve or filter and not a dam. All quarantines based upon the prin- ciple of the Chinese wall are doomed to fail. The object of quaran- tine is, then, to destroy, detain, or isolate infection with the least pos- sible hindrance to trade and travel. The art consists in regulating the openings in the quarantine sieve so as to hold back certain infections, but permit all else to pass. Maritime quarantine may be regarded as a coast defense against exotic pestilence, a defense which guards against an invisible foe ofttimes more damaging than hostile armies and navies. The cure for quarantine is sanitation. If all cominunities, especially seaports, were to place their cities in the best sanitary condition in accordance with the teachings of modern science, there would be little danger of disease spreading to epidemic proportions and very little need of maritime quarantine. If the ports in our southern littoral would free themselves of the Stegomyia mosquito they could laugh at yellow fever. A city containing few rats could not have an epidemic of plague. A port supplied with a pure, well-pro- tected water supply need not fear a water-borne epidemic of cholera. A thoroughly vaccinated community runs no hazard from smallpox. Typhus fever could not spread in a community with cleanly personal habits, that is, one free from lice and other vermin. Maritime Quarantine. — Maritime quarantine in this country is en- forced only against six diseases, viz., cholera, yellow fever, plague, typhus fever, smallpox, and leprosy. We do not quarantine against typhoid fever, tuberculosis, measles, and other infections which are not greatly feared and which are constantly with us. Infections of a non- quarantinable nature, such as scarlet fever, measles, etc., arriving at a port are permitted to enter, but must then comply with the local laws and regulations. The period of detention is based upon the usual period of incubation for each disease and is as follows: Cholera 5 days. Yellow fever 5, sometimes 6 days. Plague 7 days. Typhus fever 12 days. Smallpox : ... 14 days. Leprosy not admitted. The time of detention is usually counted from the completion of disinfection or at least from the last possible exposure to the infection. This is usually not a very difficult matter for the quarantine officer to decide, but in case of doubt the public is given the benefit. QUARANTINE 323 No comrminieation is permitted with a vessel in quarantine except- ing under supervision of the quarantine officer; that is, no one is al- lowed to board the vessel or leave it, and nothing is allowed to be thrown overboard, taken ashore, or brought on board without the express per- mission of the quarantine officer. These restrictions apply alike to foods and to merchandise of all kinds. The vessel itself may be disinfected and furnished with a fresh crew and released from quarantine while the passengers and crew are detained in suitable barracks. Vessels trading with infected ports should carry immune crews; that is, persons who have either had the disease or have been rendered actively immune through one of the vac- cines or viruses. When a quarantinable disease breaks out on board a vessel it is of practical importance for the quarantine officer to determine whether the infection was contracted on board the vessel or on land. In the first case the vessel must be regarded as infected and the measures used for its purification are much more exacting than in the second case. Thus, if plague breaks out within five days from the time a vessel leaves an infected port, and no other case occurs, it is exceedingly probable that the patient contracted his disease ashore and was in the period of incubation when he came on board. If, however, plague breaks out after five days, and especially if secondary cases occur, it is evident that the ship itself is infected. The same reasoning applies to yellow fever and the other communicable diseases. The measures taken at quarantine to keep out these diseases depend upon an accurate knowledge of their cause and mode of transmission. Briefly summarized, the measures applicable in each case are as follows: Cholera. — Cases are removed from the vessel and isolated and that part of the vessel and the objects exposed are disinfected — formalde- hyde for cabins, sulphur dioxid for the hold, bichlorid solution for sur- faces, steam for fabrics and clothing. A search is made for bacillus carriers and a bacteriological examination is made of all cases of diar- rhea. Special attention is given to the water supply, food, and flies. After the sick are isolated the remainder are segregated in small groups. Those especially exposed are first bathed and their body clothing disin- fected before they are sent to the detention barracks. In case of cholera arrangements should be perfected for the disinfection of the dejecta. Baggage which has been exposed is disinfected by an appropriate method, but as there is little danger in the cargo, especially if it con- sist of new manufactured merchandise, this may be passed without spe- cial treatment. If a vessel has taken water ballast at an infected port it is required to empty the same at sea and replace the presumably infected water with sea water. If this has been neglected the vessel must return to 324 SOME GEFEEAL CONSIDERATIONS sea past the three-mile limit for this purpose. The water and the water tanks may be rendered safe by the use of chlorinated lime. The period of detention in the case of cholera is five days. Smallpox. — Ordinarily those who have had smallpox or who have had a recent successful vaccination are not detained. All others must submit to vaccination. Persons declining vaccination are detained for the full period of 14 days before they are released. As a rule, it is not necessary to detain cabin passengers because there is smallpox in the steerage, or to detain the firemen because there is smallpox among the stewards. Vessels arriving with smallpox on board on which the cases have been properly isolated, personnel vaccinated, and other sufficient precautions taken to prevent the spread of the disease, need not be quar- antined further than the removal of the sick, the disinfection of com- partments, baggage, and objects that have been exposed to the liability of infection. Plague. — Passengers and crew from plague-infected ports are care- fully inspected at quarantine. The temperature of each person should be taken and it is desirable to make special examinations for bubos. A careful search is made for cases of Pestis minor, and the pneumonic form of the disease must also be kept in mind. The period of detention in the case of plague is 7 days. The sick are isolated in the hospital and the remainder segregated in small groups. All persons exposed to the infection are bathed and their body clothing disinfected. Eats and fleas on the vessel must be killed and burned. Usually sulphur dioxid is used; sometimes hydrocyanic acid gas or carbon monoxid. Special precautions must be taken to prevent the escape of rats. Vessels quarantined on account of plague should be anchored at suffi- cient distances from shore to discourage rats swimming to the land. If the vessel ties up to the dock, the hawsers must be guarded with inverted cones or balls of tar in order to stop rats reaching the shore along these lines. Gangplanks must be taken in before dark, and, as rats are nocturnal in their habits, a searchlight will help to deter them from leaving the ship. Nothing should be thrown overboard, not even- deck sweepings; these should be burned, but not in the galley. A plague-infected ship is given a simultaneous disinfection with sulphur and the cargo is removed by a special procedure. After sul- phuring, the cargo is removed piece by piece to lighters, each article being examined as it swings overboard for rat nests. This work goes on during the day, while the empty cargo spaces are fumigated with sulphur during the night in preparation for the next day's unloading. Special precautions must also be taken at foreign plague ports to prevent the ingress of rats and' also to prevent unnecessary human com- munication with infected areas. All vessels trading regularly with QUARANTINE 325 plague ports should carry an approved type of sulphur furnace, such as the Clayton apparatus, to use during the voyage, in order to kill rats that may be on board. Such vessels should have an immune crew; that is, persons who have either had the disease or have been protected with Haffkine's prophylactic. CLOSED DPEN Fig. 47. — A Device fob Preventing Rats Tkaveling^'along Hawsers. Yellow Fever. — Vessels arriving at an infectible port from an in- fected port are fumigated and detained five days as a precautionary measure during the yellow fever season, even though there is no evi-' dence of sickness on board. The yellow fever season usually extends from May 1 until October 1. The infectible ports are those situated upon the Atlantic seacoast south of the Chesapeake and those on the Gulf of Mexico. Five days covers the period of incubation of most cases of yellow S3 326 SOME GENEEAL CONSIDERATIONS fever and is sufficient as a precautionary measure, but in special in- stances, as, for example, if a case of yellow fever has occurred on board the vessel, then the detention is six days following fumigation. The sick are isolated by the use of mosquito screens. Patients with yellow fever should not be moved if this involves exertion or excitement, which may aggravate the disease. The vessel is fumigated with an insecticidal substance, preferably SO,, in order to kill the Stegomyia calopus. A search is made for breeding places, such as water casks, fire buckets, and other collections of fresh water where the Stegomyia larvae and pupae may develop. The disinfection of baggage and fomites is no longer practiced in the case of yellow fever. Experience has shown that wooden vessels are more apt to convey yellow fever than iron vessels. This is because wooden vessels carry water casks, which are the favorite breeding places for the mosquito, while iron vessels store their drinking water in tight compartments deep in the hold, inaccessible to mosquitoes. Vessels plying between infected and infectible ports should carry immune crews. Typhus Fever.- — The period of detention for typhus fever is 12 days. If a case of typhus fever occurs upon a vessel and has been properly isolated, and the vessel is in good sanitary condition, there is practi- cally no danger of its spread, the case may be removed, disinfection practiced (insecticides), and the vessel, passengers, and crew permitted to proceed. But, if the case has not been isolated, or if the disease has spread from one person to another upon the vessel, or if the ship is in- fested with vermin and is otherwise in an unsanitary condition, those exposed, are detained in quarantine until the period of incubation has elapsed.' Quarantine procedures in the case of typhus fever are now focused entirely upon the louse, which is the carrier of the infection. Leprosy. — An alien leper is not allowed to land. The law requires the vessel on which he arrives to take him back again. It is unconstitu- tional to forbid the landing of an American leper, but as soon as he lands he comes under the laws of the city or state in which he finds himself. Alien lepers are detained at the quarantine station and placed aboard again when the vessel is outward bound. Quarantine Procedures. — All vessels arriving at any port in the United States from a foreign port are considered to be in quarantine until they are given free practique. The practique is a certificate signed by the quarantine officer to the eifect that the vessel and all on board are free from quarantinable disease, or the danger of conveying the same. In other words, free practique is a permit issued by the quarantine officer which the master of the vessel must present to the collector of the port in order that his vessel may be admitted to entry. Vessels in quarantine are required to fly a yellow flag (letter "Q" of the International Code) from the foremast. The quarantine officer QUAEANTINB 327 boards the vessel usually upon the starboard side and examines the bill of health, the ship itself, the passengers, the crew, as well as the manifests of cargo, and sometimes the food and water supplies, etc. Vessels arriving after sundown must wait until sunrise for this inspec- tion; the time and details, however, vary greatly and depend upon cir- cumstances. Thus, at the port of Boston, there is no more need to ex- amine vessels bringing residents of London or Paris than there would be to examine a trainload of passengers from Kew York. The detection of infection on board a vessel requires knowledge, tact, and sometimes a detective instinct on the part of the quarantine officer. Where one of the communicable diseases is suspected the tem- perature of every person on board should be taken. Sometimes special examinations, as for bubos in the case of plague, are necessary. As a rule, all hands are mustered at a designated place on board the ship and then passed in review, one by one, before the examining physician; the number of persons are counted and compared with the ship's papers ; each person is critically scrutinized for evidence of disease, and suspects are placed aside for more careful examination later. The clinical records of the ship's surgeon are inspected with special reference to the diagnosis of those who have received medical care during the voyage. The manifest of cargo is examined for second-hand goods, upholstered furniture, bedding, hides, hair, or other objects that may require disin- fection. Finally, the ship itself is inspected, attention being given especially to the forecastle, steerage quarters, the galley, etc. The Bill of Health.— The United States Bill of Health is a docu- ment issued by our consul at the port of departure to the master of the vessel. The Bill of Health contains a complete description of the vessel, the number of officers, crew, and passengers (cabin and steer- age), its sanitary history, and the sources and wholesomeness of water, food supply, etc. Finally, it contains a statement giving the number of cases and deaths from yellow fever, cholera, smallpox, typhus fever, plague, and leprosy at the port of departure during the two weeks pre- ceding the departure of the vessel. The American Bill of Health, which is a formidable document, must be obtained by the master of the ves- sel in duplicate; one copy is destined for the collector of customs at the point of entry and the other for the quarantine officer. The Bill of Health is a consular document (State Department) at the port of departure, but becomes a customs paper (Treasury Depart- ment) at the port of entry. Vessels arriving at any port in the United States or its dependencies from a foreign port without this official Bill of Health in duplicate are subject to a fine of $5,000. Before the days of telegraphy the Bill of Health was an important document and often gave the quarantine officer the first information of pestilential disease abroad. The quarantine officer must now keep himself informed not 338 SOME GENERAL COISTSIDEEATIONS only of the health conditions of the port of departure, but of the places from which the passengers and crew are recruited. There are many kinds of bills of health; each country has a form of its own. Formerly a bill of health was simply a statement that the port of departure was or was not free of pestilential disease; that is, the bill of health was either "clean" or "foul." The American Bill of Health gives much more valuable information in detail. The only bill of health that is of service to the vessel upon arrival is the American Bill of Health, although several bills of health may be issued to the vessel at the port of departure. Thus, a British vessel leaving the port of Eio de Janeiro takes three bills of health, one from the British con- sul, required by the British admiralty laws, another from the Brazilian authorities, which is a clearance paper, and the third from the Amer- ican consul, which is the only one of service upon reaching a port in the United States. The Equipment of a Quarantine Station. — The equipment of a quarantine station consists of boarding vessels, such as tugs, launches, and rowboats; of an inspection place where passengers, crew, and sus- pects may be examined (the facilities on board the ship are usually inadequate for this purpose) ; of disinfecting apparatus for the use of steam, sulphur dioxid, formaldehyde, and insecticides; shower baths; detention barracks for steerage, intermediate, and cabin passengers, as well as the crew of the vessel; isolation wards in which cases of the quarantinable diseases may be eared for, and special wards where sus- pects or non-contagious cases may receive treatment. A well-equipped quarantine station further needs dining-rooms and kitchens for the various groups detained; quarters for the quarantine officers and help; a wharf and boat house, and some provisions for recreation of those in quarantine to dispel the ennui of the isolation. Finally, a crema- tory, a steam laundry, and special arrangements for the disposal of sewage and garbage are essential. A laboratory is an essential feature of a modern quarantine station. It is necessary in order to make diagnoses and to recognize bacillus carriers, etc. In other words, a quarantine station, on account of its importance and isolation, must be a well-equipped and self-supporting community. ftualifications of the Quarantine Officer. — The quarantine officer must be a good diagnostician. He should have a special acquaint- ance with the diseases against which he stands monitor. Further he must be familiar with the modes of spread of the quarantinable dis- eases and must know the value and limitations of the germicidal agents and insecticides he uses. Finally, he must be familiar with matters nautical, and have an extensive knowledge of geography. It is the duty of the quarantine officer to keep posted as to the sanitary conditions QUAEANTINB 339 of all countries, especially the towns and places having commerce with his port. Disinfection, of Ships. — The disinfection of a vessel does not dif- fer materially from the disinfection of houses and rooms. It should not, however, be attempted by one not familiar with the intricacies of marine architecture and matters nautical, for many special condi- tions are met with on board ship that are very different from those found on shore. While the principles of disinfecting as applied to a vessel present nothing unusual, the application of these principles calls for much ingenuity and the keenest vigilance on the part of the dis- infector. It is important to enlist the sympathies of those on board with the necessity of disinfection, for the successful accomplishment of the puriiication of the vessel may be materially helped by the cheerful cooperation of the passengers and crew; otherwise the difficulties of the problem are greatly magnified. Formerly a distinction was made between the methods of disinfect- ing a wooden and an iron vessel. This arose from the fact that almost all wooden vessels have some rotten and spongy wood, especially about the forefoot and bilge. There are also many more cracks and open joints about a wooden ship than a metal one which afford lodgment for organic matter. In addition to this, a wooden hull is always dam- per than an iron hull, for almost all wooden vessels leak more or less. It was formerly believed that the microorganisms of disease were apt to become deeply lodged in the moist dirt and organic matter of the many crevices, but we now know that this is largely theoretical. A vessel is rarely so badly infected that it needs a disinfection throughout. Just what portion of the vessel and its contents requires treatment is often a very difficult problem to solve. There is no more reason to fumigate the hold of a vessel because smallpox appeared in the cabin or steerage than there would be to disinfect the basement and subbasement of a tenement house because a case appeared in one of the upper stories of the building. When a communicable disease oc- curs on board a vessel the infection may be confined to one or two compartments or to a limited area quite as successfully as this may be done in buildings on shore. "In case of doubt, disinfect," is not a bad rule for the quarantine officer to follow in his practical deal- ings with ships. For, after all, the measures which must be taken are greatly in excess of the absolute requirements. Much may be learned by a thorough inspection of the vessel. To be sure, we cannot see the germs with our unaided vision, but we can see the dirt and moisture and other conditions which favor their life and virulence and can discover the feeding and breeding places for vermin. It is, therefore, the duty of the quarantine officer to require a very 330 SOME GENEEAL CONSIDERATIONS thorough mechanical cleansing of all parts of the ship which, in his judgment, require it. This matter is dwelt upon because filth and ver- min are conditions too frequently met with on the sea and one of great importance to communities and nations. While the general methods of treating vessels are the same for most of the bacterial infections, special methods are called for with each dis- ease. For example, in cholera particular attention must be paid to the water and food supply; for plague the destruction of rats and fleas is of prime importance; for yellow fever attention must be directed against the mosquito; for smallpox vaccination and the usual disinfec- tion of the living apartments, clothing, bedding, and the like are re- quired, while for typhus fever the warfare must be waged against lice. The disinfection of a large vessel cannot effectively be done with- out all the modern contrivances of a well-equipped quarantine station. A rowboat and launch or a small sailing craft may be disinfected with a tub of bichlorid solution, but good work cannot be accomplished on a large vessel by the use of makeshifts. Before the disinfection of a vessel is commenced it should be brought alongside the pier or barge containing the necessary apparatus. All the passengers are then to be taken off and all the crew, only excepting the few who are necessary for the safety of the vessel and those who are to help in the disinfection. The quartermaster, the boatswain, and the carpenter are very useful hands to aid in the process on account of their practical knowledge of the individual peculiarities of the construc- tion of the vessel and their intelligence in carrying out directions with faithfulness. When the personnel have left the vessel all their effects are removed and disinfected, if necessary, in accordance with the methods outlined for objects of that class. Baggage, bedding, and other objects, no mat- ter what their character, after disinfection should not be returned on board until the treatment of the vessel itself is finished. This injunc- tion applies, of course, equally well to persons. In fact, no one should be allowed on the vessel except those actually engaged in the work, who, as far as practicable, should be immune and should wear suitable garments. All the bedding, bed clothing, hangings, floor runners, and other fabrics that have been exposed to infection must now be re- moved to the steam chamber. Especial care must be taken to obtain all the used and soiled linen, which is usually kept in special compart- ments called the "dirty linen lockers," which are usually under the care of one of the stewards. For some reason there is a dislike to disclose the presence of this soiled wash to the quarantine officer. After all the objects needing disinfection by special process have been removed, attention is then directed to the vessel itself. The vari- ous compartments of the vessel may be disinfected by any one of the QUAEANTINE 331 methods described under Boom Disinfection, formaldehyde being the choice of the gases and bichlorid of mercury (1-1,000) being the most suitable solution for the treatment of walls, floors, etc. The bichlorid solution, which is sometimes used for flushing the forecastle, the steerage compartments, and quarters for petty officers, etc., may be applied with a force-pump or by means of mops and buck- v:ts. In applying the disinfection solution with a hose begin at one end of the deck ceiling and systematically flood every inch of surface, com- ing down the '\\-alls, and finally the floor. In disinfecting large vessels it is well to start forward with the forecastle and work aft systematically, first on the starboard, then on the port side, taking care to require every door to be unlocked and trusting only to a personal inspection concerning its contents and uses. There are certain places, such as the lamp-room, the paint locker, the sail locker, the chain locker, the carpenter shop, and chart room, the pilot house, the engine and boiler rooms, and the machinery, that are rarely infected, and, as a rule, need no treatment. Special care, how- ever, must be given to the sick bay and any apartment in which a pa- tient was cared for, and all living apartments, including the steerage. The water closets on board ship should be thoroughly cleansed and flushed with water and may be disinfected with chlorinated lime or carbolic acid. They may also be hosed with the bichlorid solution while that is being applied. In sailing vessels of the older type the forepeak needs similar treatment. The hold rarely needs treatment on account of bacterial infection. About the best way to disinfect the holds of vessels is by sulphur fumi- gation or by a solution of corrosive sublimate applied with a hose. The bilge may be flushed with carbolic solution or chlorinated lime and then pumped out. When the hold is fumigated with sulphur, this may be burned- in iron pots set in pans of water. The pot should be placed in an elevated position either on piles of ballast or on the 'tween decks. In leading sulphur fumes into the holds from a sulphur furnace it is considered best to lead the pipes down the hatch-well toward the bottom of the hold, so that the apartment may fill up with the fumes from the bottom, displacing the air above. For this reason openings above for the escape of the air must be provided. This is best managed by leav- ing one or two of the ventilators open, or part of the hatch, and after the gas has begun to escape in some quantity to close up tight. The amount of sulphur to be burned may readily be computed from the tonnage of the vessel. A registered ton is 100 cubic feet. Count half a pound for each ton, which will make the necessary five pounds per 1,000 cubic feet. The gross tonnage of a vessel indicates her ac- tual cubic capacity. The net tonnage gives the capacity of her cargo- carrying space. The difference between the two will give the capacity 332 SOME GENEEAL CONSIDEEATIONS of the spaces devoted to the engines, machinery, living apartments, storerooms, etc. In sailing vessels and in freighters the net tonnage may be taken as the cubic capacity of the hold. In estimating freight 40 cubic feet of merchandise is considered a ton, provided the bulk does not weigh more than 2,000 pounds. This ton, used as a commer- cial unit for freight charges, must not be confused with the registered tonnage based upon the measurement of the vessel. In fumigating vessels for yellow fever, plague, and other insect- or animal-borne diseases, the fumigation should be simultaneous in all parts of the vessel. Following this, special rooms and apartments may be given individual treatment, depending upon circumstances. The empty compartments of an iron steamer may be disinfected by steam, provided it is above the water line. The compartments of such vessels usually have steam pipes for use in case of fire. Clothing and other fabrics may also be disinfected by steam, by exposing them in the compartment. The water tanks and casks of vessels sometimes need special treat- ment. The water may be infected with cholera, typhoid, dysentery, or other water-borne infection. The water may be disinfected in situ by the addition of chlorinated lime, using an amount sufficient to make a one per cent, solution. This should stand at least 24 hours before it is pumped out. Water casks on sailing vessels are very apt to be breeding places for mosquitoes. These should be emptied and cleansed. The water con- taining the larvae may be spilled overboard, as neither the anopheles nor the stegomyia may develop in salt water, otherwise the larvs should first be destroyed. For the destruction and treatment of rats, etc., on vessels see pages 245 and 252. Cargo. — As a rule, the cargo of a vessel infected with pestilential disease needs no disinfection. Individual articles of the cargo, such as rags, household goods, second-hand articles, or food products, from in- fected localities may need treatment. New articles of merchandise or new manufactured goods seldom carry infection. In the case of plague the cargo may need special treatment on ac- count of rats (see page 324). Ballast. — ^Vessels bring two kinds of ballast: (1) water, (S) solid. Solid ballast consists of the greatest variety of substances. The kind which is most objectionable from the standpoint of the health officer is called "sand" by the captain, but an inspection of this sand will dis- cover the fact that it often consists largely of street sweepings and rub- bish from the port from, which the vessel hails. Such ballast should not be unloaded on the city front, especially if it comes from an infected district. Ballast consisting of clean, hard rock or sand from the beach QUAEANTINE 333 is not apt to carry infection of any kind, and usually needs no attention from the quarantine ofScer. Modern vessels all use water ballast. The tanks may be filled from a river, fresh water lake, or other body where cholera, typhoid, or dysen- tery prevails. It is a rule in quarantine practice to require vessels in fresh water ballast from cholera-infected districts to return to the open sea, where the ballast tanks are pumped out and refilled with salt water, provided this has not been done on the high seas. Before the water is pumped out it should be treated with chlorinated lime. Foreign Inspection Service. — To aid the quarantine officer every American consul is required to report regularly certain facts concern- ing the presence and progress of epidemic diseases. Medical officers of the government are also stationed at various countries in order to su- pervise the sanitary condition of vessels, their cargo, and passengers leaving for the United States. This may be called preventive quaran- tine, for it is a distinct help in keeping out infection and facilitates trade and travel. Thus, in Italy, during the cholera times, an officer of the Public Health and Marine Hospital Service stationed at Naples suc- cessfully kept that disease oflE vessels sailing from Naples to the United States, whereas vessels sailing from Naples to other ports and without sanitary supervision carried cholera in several instances. National versus State ftuarantine. — All the maritime quarantines in this country are now controlled by the national government, except- ing the ports of Boston and New York. At Boston the maritime quarantine is in charge of the city health authorities, and at New York it is a state institution. At a few other ports a local quarantine is maintained in addition to the national service. The federal quarantine service is administered by the Public Health Service, a bureau in the Treasury Department. It is evident that maritime quarantine should be administered uni- formly so as not to prejudice or favor the commerce of a port. Not only is uniformity insured by a central service, but there is a decided gain in efficiency for obvious reasons. Maritime quarantine deals mainly with foreign shipping. The Constitution reserves for the federal gov- ernment the right of treating with foreign powers; from this point, therefore, maritime quarantine is mainly a function of the federal gov- ernment. Interstate ftuarantine. — In accordance with our Constitution the federal government has limited power within the state, but has practi- cally unlimited authority to prevent the spread of infection from one state or territory, or the District of Columbia, to another state or terri- tory, or the District of Columbia. Interstate quarantine involves in- terstate travel and commerce ; the pollution of streams flowing through more than one state; railroad and steamboat sanitation, and all similar 334 SOME GENERAL CONSIDERATIONS questions. Congress has passed a comprehensive act, Section III of the Act of February 15, 1893, authorizing the Public Health and Marine Hospital Service to enforce interstate quarantines in the case of con- tagious and infectious diseases. The regulations, however, prepared under this act comprehend only the six quarantinable diseases, and have only occasionally been enforced in the case of yellow fever, cholera, or plague. There are no interstate regulations concerning typhoid fever, tuberculosis, measles, and other non-quarantinable diseases. It is evi- dent that this is one of the important phases in which government activity can accomplish especial good; for, while the government has limited power within the state, it has practically unlimited authority so far as interstate relations are concerned. Widespread diseases will never be adequately controlled by the local authorities without the co- operation of the government. It is evident that, if one state should rid itself of typhoid fever, measles, or tuberculosis, it would soon become reinfected from the neighboring states. Interstate sanitation is one of the burning questions needing vigorous action and cannot be adequately enforced without extending the scope and powers of the present federal health authorities. ISOLATION In theory isolation is the most perfect single method to check the spread of a communicable disease. The results in practice, however, have been somewhat disappointing on account of unusual difficulties. The statement has frequently been made, especially with reference to typhoid fever, that if all the cases could be isolated (which includes the disinfection of the discharges) we would soon see an' end of the infection. We now know that this statement is not true, on account of the bacillus carriers and the mild and unrecognized or "missed" cases. Because the isolation of the reported cases represents only a portion of all the foci of infection and, therefore, at best could not in itself control an epidemic disease, discredit has been thrown upon this procedure, which is one of the essential features of all systems of quar- antine. As a matter of fact, it has been shown that in certain diseases, like measles, which is communicable for three days or more before the nature of the disease is recognized, isolation has practically no influ- ence in diminishing the prevalence of this widespread infection. It is true ordinarily that a case of measles does most harm before it is isolated; nevertheless, this is no reason why it should be permitted to further endanger the community. The value of isolation is also dimin- ished by the prevalence of carriers. In fact, its practical usefulness in a given infection is inversely proportional to the number of carriers. If each case isolated prevents on the average only one other fresh infection, there would still be justification sufficient to continue the ISOLATION 335 practice. As a matter of fact, the practical value of isolation varies with each disease, depending upon the degree of its communicabilit}', the time when it is communicable, the promptness by which it may be recognized, the modes by which it is transferred, the existence of latent infections, missed cases, carriers, and other factors which influence the spread of the infection. The degree of isolation varies markedly with the difEerent infections. A case of yellow fever may be isolated under a mosquito screen, and a case of diphtheria or scarlet fever may be eifectively isolated in a bed in a general ward, provided intelligent and painstaking care is exercised to destroy the infection as it leaves the body. Isolation of the more read- ily communicable diseases, as smallpox and measles, should be much more absolute. Typhoid bacillus carriers need not be imprisoned. It is sufficient to limit their activities, especially to prevent their occupation in kitchens, dairies, or about foodstuffs. There is no good reason to isolate a consumptive or leper without open lesions — that is, cases in which the bacilli are imprisoned in the tissues and not discharged into the environment. A careful consumptive or leper may be allowed a wide latitude. On the other hand, isolation in chronic infections, such as tuberculosis and leprosy, with open lesions is the most helpful and at the same time the most difficult single procedure we have to control their spread. The careless, indigent, ignorant, or helpless consumptive is a public menace that needs energetic and sometimes arbitrary iso- lation. Isolation may most readily and effectively be carried out in hospitals or sanatoria. Proper isolation in the home requires a special room or rooms, intelligent nursing, appliances for disinfection, etc., a com- bination often difficult to arrange. House quarantine varies with the different diseases. To carry it out rigorously in all cases and under all conditions is folly. Different diseases need different procedures. Some- times it is sufficient simply to placard the house as a warning. At other times it may be necessary to station sanitary guards about the premises to enforce the quarantine. The imperfections of strict isolation by the "shutting in of houses" are graphically described in Defoe's "Journal of the Plague Year." Isolation camps or temporary barracks in times of epidemics are effective measures in checking the spread of some infections. This method has proved effective in actual practice in the case of smallpox, yellow fever, plague, cholera, and other diseases. It often becomes a difficult question to determine whether the well members of a household should also be quarantined — especially whether the well children should be permitted to attend school. This perplex- ing question must be decided for each disease separately, and the deci- sion in each disease is sometimes modified by attending factors. Usually 336 SOME GENEEAL CONSIDEEATIONS the other children in the family in the case of scarlet fever are excluded from school for four weeks from the beginning of the last case. In most cities the same rule holds for diphtheria, although here we are able to determine whether the children are bacillus carriers or not. At least two negative cultures from the nose and throat should be re- quired before such children are allowed freely to mingle with other children. The principal factors which determine whether the well children in a family shall be permitted to attend school or not in any particular infection rest upon our knowledge as to whether the disease is conveyed by a third person and the frequency of bacillus carrying and missed cases. Isolation becomes one of our most valuable public health measures when communicable diseases affect persons working about milk, meat, and other foods capable of conveying infection. One of the practical objections to isolation and one reason that it meets with so much opposition from the public is that the compensa- tion of the wage earner ceases through no fault of his own. It is evi- dently unjust to practically imprison and thus seriously punish a mem- ber of the community, not for his own good but for the good of the community, because he or some member of his family has contracted an infection, perhaps through some fault of the community itself. It is, therefore, reasonable and just that wage earners and others should be compensated and their personal interests safeguarded during enforced isolation. Isolation only reduces to a moderate degree the prevalence of dis- ease. The limitations of this valuable procedure are now well under- stood. With improved methods of diagnosis and increased knowledge of the methods of spread of disease, isolation will be made increasingly effective. Every case isolated is a focus of infection neutralized. Al- though not as satisfactory in practice as it is in theory, isolation will ever remain one of the chief administrative procedures for the control of the communicable diseases. SECTION II IMMUNITY, HEREDITY, AND EUGENICS CHAPTER I IMMUNITY Immunity or resistance to disease is the very foundation of pre- ventive medicine. It is the overshadowing factor in hygiene. In this sense we use the term "hygiene" to include the care of the person, in contradistinction to ■'"sanitation," which deals with the environment. There is no sharp line of demarcation — we speak of hygiene of the teeth, of sleep, of bathing, of exercise, or food and drink, and of those conditions which are more or less intimately associated with the body; we speak of the sanitation of the home, of schools, of cities, of farms; sanitary science considers the air, soil, climate, and our surroundings as they affect health. Sanitation, then, is largely impersonal; hygiene is personal, and, as far as the prevention of disease is concerned, one of the most important factors in hygiene is immunity. The word "immunity" is a very old term — we still speak of immu- nity to crime,'- but it is only of late years that we are beginning to un- derstand the mechanism by which the body protects itself against in- fection. The advances have been so rapid that these studies may now be grouped into a separate science known as Immunology. Immunity is a function of all living beings (animals and plants), and in its widest form is one of the fundamental properties of life. Thus, as long as we are alive the colon bacillus in our intestinal tract and the spores of the hay bacillus on our skins do us no harm, but the moment we die, and ofttimes shortly before death,'' these and other bac- teria invade our tissues and disintegrate them. Immunity may be defined as the power which certain living organ- isms possess of resisting infections. Immunity is the contrary condi- tion to susceptibility. Hypersusceptibility is a special state of an exag- ^We may speak of immunity "from" a disease, "to" a disease, and ' ' against ' ' a disease. ' Terminal infections. ■ 337 338 IMMUNITY gerated power of reaction and will be discussed separately under anaphy- laxis or allergic. The word resistance has practically the same sig- nification as immunity. The term "tolerance" is commonly used to describe a limited form of immunity usually acquired by the repeated use of alkaloids, alcohol, and other poisons of comparatively simple chemical structure. While a high degree of tolerance may be acquired to such substances, a true immunity in the sense in which the term is now used is never produced. In the case of tolerance, antibodies are not found in the blood. For the most part true immunity is produced against colloidal substances, while tolerance is largely limited to the crystalloids; this distinction, however, is not absolute. There are all gradations and various kinds of immunity. It varies in degree from the weakest appreciable amount to an almost absolute protection. It also varies greatly in duration — from the briefest period to a life span. Immunity, therefore, is a relative term. It may be natural or acquired, active or passive, local or general, pure or mixed, specific or general, family or racial, brief or lasting, strong or weak, etc. Immunity is a function which is not limited to man and other mem- bers of the animal kingdom. It is common throughout the vegetable kingdom. We are indebted to Welch for the thought that the bacteria themselves also have this fundamental property of life. Thus, man is susceptible to the tubercle bacillus because the tubercle bacillus is im- mune to man; on the other hand, man is immune to the hay bacillus because the hay bacillus is susceptible to man. In this sense a micro- organism is called pathogenic or non-pathogenic, depending upon whether it harms or is favored by its host. This is the relation be- tween seed and soil. A fertile soil is susceptible; a barren soil is im- mune. The seed in the first instance may be pathogenic; in the second non-pathogenic. The host is able to resist the intrusion and growth of the non-pathogenic microorganisms and protect itself against harm through its mechanism of immunity. If the protecting devices are in- sufficient to guard against attack, the germs multiply, produce poisonous substances, or harm the host in other ways. The reason that the same microorganism may be pathogenic for one host and harmless for another depends upon the presence or lack of immunity. The virulence of a microorganism is an expression of the intensity of the relation between the seed and the soil. Virulence may be strengthened or attenuated either by increasing or decreasing the resistance of the host or by in- creasing or decreasing the resistance of the microbe. Mechanism of Immunity — Theories of Immunity. — ^It is now quite evident that the mechanism of immunity varies in different infections and, to a certain extent, even in the same infection under different con- ditions. It must further be admitted that we are still in ignorance of MECHANISM AND THEOEY 339 the mechanism by which the body protects itself against many dis- eased states. Historically considered, immunology as a science dates back scarcely 30 years. Many primitive people attempted to immunize themselves in a crude sort of way, but with methods now recognized as essentially sound. Thus, South African tribes tried to protect themselves against snake bites by using a mixture of snake venom and gum; the Moors immunized cattle to pleural pneumonia by placing some of the virus under the skin of the animal. The inoculation against smallpox used from time immemorial, and vaccination with cowpox introduced by Jenner in 1798, are examples of the first practical use of specific meth- ods in the history of immunity. Pasteur was greatly infiuenced by Jenner's demonstration that a mild form of a disease protects against the severe form. Pasteur ex- panded the fact taught by Jenner into a general principle. Practically all of Pasteur^s work in immunity that bore practical fruit, such as vaccinations against chicken cholera, anthrax, and rabies, is based upon this guiding principle. Pasteur in 1888 expounded his "exhaustion" theory, which was the first attempt at a scientific explanation of immunity. Pasteur was a chemist and his theory was a simple chemical conception, largely based upon his work upon the fermentation of sugar with yeasts. He re- garded the body immune because its food supply was used up and the microorganisms could, therefore, no longer grow — just as yeasts cease to grow when the sugar is used up in a culture medium. It is now easy to disprove the exhaustion theory. Bacteria do not cease to grow on account of the exhaustion of the food supply, but rather on account of the production of products toxic to themselves. Further, bacteria may grow well enough in the dead tissues and fluids of immune animals, and, again, immunity may be induced by the inoculation of dead bac- terial products, substances which can hardly use up food material. Ee- cently Pasteur's exhaustion theory has been revived in a modified form by Ehrlich, who considers that there is sufficient evidence for this form of immunity in certain cases, as in cancer. Ehrlich calls it "atreptic" immunity. Chauveau proposed the "retention" theory, the exact opposite of the exhaustion theory. This theory is also based upon the analogy of the behavior of bacterial growth in vitro compared to their growth within the body. It soon became evident that bacterial growth ceases even though abundant food is present, and that this inhibition is due to the retention of products of metabolism of bacterial activity. Chauveau considers that such substances are retained within the body, which thus protects it against further growth and development of the microorgan- isms and thus accounts for immunity. 340 IMMUNITY The above theories are generalizations which have now little more than historical interest. We now know that no one mechanism of im- munity will explain all cases. In some instances phagocytosis plays an important part; in others antibodies of various sorts; the side-chain theory appears to account- for most of the facts in antitoxic immunity. In some cases the immunity is due to a negative property in that there is an absence of specific affinity between the poison and the cells. In others it is a positive factor and is due to the presence of substances able to neutralize the toxic action. The mechanism of immunity in some instances resides mainly in the blood and fluids; in other eases it is evidently more directly associated with cellular activity. In some instances immunity depends upon the power of immediate reaction in the sense of anaphylaxis. In all cases the mechanism is probably com- plex and multiple. The unsatisfactory state of our knowledge in certain fields of im- munity is well illustrated in the case of anthrax. The mechanism of protection is not at all understood in this infection, which was the first and classic illustration of a germ disease. The mechanism of immu- nity in common colds is also complex and obscure. Our resistance to disease is in many cases due to a simple mechani- cal or chemical protection against the invasion of the pathogenic micro- organisms; that is, the tissues are susceptible enough, but are guarded against the invasion of the germs of disease. Many examples may be cited in this category. Thus, one of the important functions of the skin consists in this mechanical protection of the tissues underneath. The smooth conjunctiva is protected by the constant washing of the tears and the motion of the eyelids. The lungs are safeguarded by the shape of the upper respiratory passages and the moisture of the mucous membranes, which act as a mechanical trap for many bacteria. Some of those that pass deeper are carried back by the mechanical action of the cilia. The sensitive and susceptible mucous membrane of the in- testines is partly protected through the acidity of the gastric Juice, which is sufficient to destroy cholera vibrios and other microorganisms susceptible to acid. Within the body the mechanism of immunity is an adaptation of cell nutrition. The mechanism varies with different infections and in different stages of the same infection. In certain diseases the immu- nity seems to reside mainly in the activity of the cells. In other dis- eases the immunity is due chiefly to substances floating in the blood. The first is the cellular and the second the humoral theory. As we shall have occasion to see, the immune bodies in the blood are probably in all cases derived from the cells, so that the cells play the fundamental part in most cases of immunity. However, the great majority of the studies in immunology have been focused upon the changes in the blood. NATUEAL IMMUNITY 341 This is not due to the fact that the blood alone represents these changes, but that it best represents them, and thus aifords the readiest method of attacking the problem. The blood is the most fluid and most cos- mopolitan of all the tissues of the body, visiting every part, bearing to each part certain substances, and removing from each part certain other substances. It is evident that it is easy to study the blood and its changes, as some of it may readily and repeatedly be withdrawn during life in order to observe its changes without in any way harming the animal. The fundamental processes of immunity within the body must all depend upon some chemical change, but we know very little con- cerning the chemical composition of the substances that play the chief role or the chemical nature of the changes. Great advances have been made in immunology despite this lack of chemical knowledge; for these advances we are indebted to experimental biology, through which we have learned the results of many effects without a knowledge of their nature or the intimate processes concerned. Natural Immunity. — Natural immunity is an inherited character possessed in common by all individuals of a given species. It is in- herent to a greater or less extent in all members of that species. It may be present at birth or develop in later years. There are very many examples of natural immunity. Thus, most of the communicable in- fections of man are peculiar to man; that is, the lower animals have a natural immunity to such diseases as measles, mumps, scarlet fever, typhoid fever, cholera, gonorrhea, syphilis, yellow fever, malaria, leprosy, and so on through a long repertoire.^ Even tuberculosis, which is the most common and widespread of infections, has its own particu- lar bacillus to which man is especially susceptible and to which the lower animals show a • marked degree of natural immunity. On the other hand, man shows a high grade of natural immunity to a large number of infections to which the lower animals are subject, as rinder- pest, black leg (symptomatic anthrax), Texas fever, etc. The monopoly which man possesses of being susceptible to infec- tions which the lower animals successfully resist is not confined to the bacteria alone, but includes many protozoa and higher animal parasites. Thus, the hookworm of man is different from the hookworm of the horse, the dog, the seal. Bach host has its own species of hookworm which, though closely allied, are not interchangeable. That is, the horse has a natural immunity to the hookworm that is parasitic for man, and vice versa. There is a group of infections, including the pyogenic cocci, an- thrax, tetanus, malignant edema, glanders, actinomycosis, rabies, plague, ^It is true that some of these infections may be conveyed to monkeys or other animals by artificially introducing large amounts of the virus, but these animals do not contract these diseases naturally and therefore show a high degree of natural immunity. 24 342 IMMUNITY foot-aBd-mouth disease, malta fever, tuberculosis, liiilk sickness, infec- tions with the paratyphoid bacillus, ringworm, and many higher forms of animal parasites, which are coinirion to many species in widely dif- ferent genera. • ' There are certain remarkable facts connected with natural immu- nity. For example, white mice are susceptible to infections with the pneumococcus, whereas the field inouse possesses a high degree of natu- ral resistance. When we consider how slight must be the differences in the structure, the function, the chemistry, ' and the metabolism in the white mouse when compared with its gray cousin, we begin to ap- preciate the subtle dijfferetices and perhaps complex factors upon which immunity depends. If we could find out, for example, why the goat' is resistant to tuberculosis while domestic cattle are particularly suscep- tible, we would have the foundation for a specific preventive and cure for that disease. Practically all the individuals of a certain species have about an equal susceptibility or an equal immunity to a given infection. These factors are more constant than commonly supposed. Laboratory ani- mals react with certainty and with ■ striking uniformity to an infection of known virulence, provided the virus is brought into association with certain tissues. Thus, strikingly uniform results are obtained from a given culture of plague introduced subcutaneously into the guinea pig, or of tuberculosis into the peritoneal cavity of the monkey, or of strep- tococci into the circulation of the rabbit, ■ or of rabies under the dura of the dog, or of anthrax into the mouse. Man is no exception to this general statement, as far as may be judged from the data at hand. Practically all persons are alike susceptible to smallpox, yellow fever, tetanus, and many other infections. In epidemics some individuals escape. In other epidemics the disease varies greatly in severity. These apparent exceptions may not be due so much to varying degrees of immunity, but rather to variations in the dose and virulence of the virus, the channel of infection, symbiosis, and other factors. In some cases the immunity is so weak that the balance between health and disease is quite unstable. This appears to be the case with tuberculosis in man. We possess sufficient natural immunity to tuber- culosis successfully to resist small amounits of infection, but this re- sistance may readily be broken down by any influences which undermine our general vitality. Natural immunity may be broken down by various means that weaken the animal, such as fasting, the production of an experimental diabetes with phloridzin, fatigue, i excessive cooling of the body, as the clipping of the Hair of thick-furred animals, etc. Thus, chickens are ordinarily naturally immune to anthrax, but may be infected if their ACQUIRED IMMUNITY 343 feet are kept in cold water. . White rats are resistant to anthrax, but become susceptible if -the hair is clipped. Acquired Immunity. — By acquired immunity is meant a specific re- sistance to an infection that is not naturally inherent in all the in- dividuals of a species, but, as the term indicates, the immunity is ac- quired during the lifetime of the individual. Immunity may be ac- quired either through some "natural" event, such as an attack of a dis- ease, or may be "artificially" induced by the introduction of some substance, such as a serum, toxine, vaccine, or a virus. Acquired immunity may be either active or passive. Active immu- nity is induced by an' attack of a disease or by the introduction of a virus or suitable toxin into the system. Immunity thus acquired is active in the sense that it depends upon an aggressive stimulation of the protecting mechanism as a result of a series of reactions vsrithin the body. Passive immunity, or transferred immunity, is an antitoxic im- munity. It is passive for the reason that the antibodies (antitoxin) are introduced into the body, which, therefore, takes no part in their formation. The injection of diphtheria toxine into the horse causes an active immunity in that animal; the injection of some of the antitoxin contained in the horse's serum into a child causes a passive immunity in the child. Both are acquired because horse aod man have no inherent or natural immunity to diphtheria. The protection against smallpox produced by vaccination is an example of active immunity; so also is the immunity produced by bacterial vaccines. Mixed Immunity. — Mixed immunity is a combination of the active and passive. This is used practically in plague prophylaxis and has been proposed for other ijifections. It consists in injecting a mixture of antitoxin serum and the appropriate bacterial virus. The advantage of this procedure consists in the fact that the active or antitoxin im- munity diminishes the severe reactions which sometimes follow the in- troduction of a bacterial virus. It also affords an immediate protection and thereby neutralizes the negative phase which is supposed to follow an active immunization. How Immunity May be Acquired.— Immunity may be acquired by: (a) An attack of a disease. (b) By the introduction of a virus. (c) By the introduction of a vaccine. (d) By the introduction of a chemical product (toxine). (a) An Attach of the Disease. — Certain diseases, whether acquired naturally or induced artificially, leave an immunity which varies greatly in degree and duration. : The following diseases leave a definite immu- nity of high, though variable, grade: smallpox, yellow fever, measles, whooping-cough, scarlet fever, cerebrospinal meningitis, infantile paraly- 344 IMMUNITY sis, typhoid fever, typhus fever, ehiekenpox, mumps. Second attacks of smallpox, measles, typhoid fever, and other infections in this list are not uncommon, showing that the immunity is rarely if ever ab- solute. Some diseases, such as pneumonia, erysipelas, and malaria, seem to predispose to subsequent attacks, that is, diminish resistance. Even in this class of infections there must be a certain amount of immunity, however short, else the patient would not recover. The practice of intentionally inoculating smallpox was the first ex- ample in preventive medicine in which use was made of the fact that one attack of a disease confers immunity to a subsequent attack of the same disease. The present-day vaccination of cowpox (a modified small- pox) may be considered as belonging to this category. The principle is used to a much greater extent in veterinary practice either by using a small amount of the infection or by introducing it in an unusual way or by inoculating the animals at a time when they are found to be least susceptible. In this way a benign form of the disease is produced which protects against the severe and fatal forms. These methods are used in Texas fever, rinderpest, pleuropneumonia, anthrax, etc. (b) By the Introduction of a Virus Into the System. — A distinc- tion is made between a virus and a vaccine. If the material used con- tains the living active principle it should be called a virus. If the virus is dead it should be called a vaccine.^ The highest and most lasting degrees of immunity may be produced by the introduction of the living active principle into the system, thus imitating nature. The virus may be diminished in virulence as in an- thrax, vaccinia, or rabies. A high grade of immunity to plague and cholera may be induced in man by the injection of living cultures. In the case of plague the cultures must be greatly diminished in virulence. In the case of cholera virulent strains may be used, as this disease is neither a bacteremia nor septicemia, and there is very much less danger in introducing the cholera vibrios into the subcutaneous tissue than •in taking them by the mouth. This principle of introducing the virus into a resistant tissue can be taken advantage of in various infections, provided the virulence of the disease depends largely upon the channel of infection. The virulence of the virus may also be diminished by certain definite processes, such as growing the culture at an unusually high temperature, as in the case of anthrax; or by prolonged artificial cultivation, as in the classic instance of chicken cholera; or by drying, as in rabies; or by passage through animals, as in smallpox (cowpox) ; or by growing on unfavorable media ; by the use of very small amounts of the virus, as in tuberculosis and many other infections; or by the ^ Vaccine {vacca, a cow) is not a good term, but is now too deeply rooted to change. ACQUIEED IMMUNITY 345 use of closely related strains, such as the human tubercle bacillus for bovine immunization. Eepeated injections of a virus induce a very high and more lasting immunity than single inoculations. (c) By the Introduction of a Bacterial Vaccine. — The immunity produced by the introduction of a vaccine into the body corresponds precisely to the immunity acquired by the introduction of a virus, the only difference being that the living virus produces a more lasting and higher degree of protection than that produced by the dead vaccine. The advantages of using a vaccine instead of a virus are obvious. Dead bacteria, when injected into the tissues, usually produce a local reaction at the site of inoculation and also a general reaction. The local reaction consists of swelling, pain, redness, and other indications of irritation and inflammation. The general reaction consists of fever, headache, pains in the muscles, especially in the back and legs, malaise, and sometimes nausea. The reactions usually come on within a few hours after the vaccine has been introduced and rarely last longer than 24 to 48 hours. It is customary to give the vaccines in the evening, for then most of the symptoms have passed by the next morning. The vaccine is usually prepared from a fresh twenty-four-hour growth of a pure culture of the microorganism upon the surface of agar. In this way secondary metabolic products in the medium are avoided by simply removing the surface growth. When liquid cultures are used the foreign substances contained in the medium complicate the reactions. The cultures f.re usually killed by exposure to heat at from 53° to 60° C. for one hour. High heat, while certain to kill the virus, is undesirable, for the reason that it coagulates the albuminous substances in the germ cell and otherwise alters the chemical structure of the microorganism. The closer the vaccine approaches the virus the better the results, so far as immunity is concerned. Therefore, many investigators prefer to kill the poisons with carbolic acid, chloroform, or some other suitable germicide. The injections are always given subcutaneously. Usually three or four injections are given at intervals of about five to ten days. Several injections produce an immunity of much higher grade and longer dura- tion. In most instances the acquired immunity lasts from two to five years, and may be renewed. Preventive inoculations with bacterial vaccines are now much prac- ticed in the case of typhoid fever, plague, and cholera, and are destined to be extended to other infections. The dose and details have been discussed under each disease. A negative phase is said to follow the introduction of a vaccine or a virus ; that is, a diminished resistance appears to be produced before the curve rises. The negative phase varies in degree, depending upon the amount and virulence of the vaccine and the power of the body to react. 346 IMMUNITY It varies in time from a few hours to several days. The negative phase is an assumption based upon a primary diminution in the amount of specific opsonins in the blood, but it is doubtful whether the opsonic index is a true index of the presence of absence of immunity, which is dependent upon other factors. From a practical standpoint, the negative phase can, as a rule, be disregarded; that is, bacterial vaccines are not contraindicated during the period of incubation. Specificity. — Most of the reactions in immunology are specific — not absolutely so, but relatively; that is, antibodies, such as agglutinins, lysins, precipitins, or opsonins, usually act upon the corresponding an- tigen with much greater vigor than upon any other. An immunity to one disease, no matter how produced, whether natural or acquired, af- fords no protection against other diseases. There is, however, no abso- lute specificity, just -as there is no absolute immunity. Certain microorganisms and their toxic products show a remarkable predilection for certain cells or tissues. In this sense a microparasite or a toxin may be as specific in its action as a qualitative chemical re- action. Thus, there is a specific relation between tetanus toxin and nervous matter, while the poison has little or no affinity for other tis- sues. The poison of infantile paralysis picks out certain cells in the central nervous system upon which it acts specifically. Also in rabies the brunt of the lesions fall upon the cells of the central nervous sys- tem. The toxic products of the Bacillus hotulismus is also a specific nerve poison, and at least one of the poisons in diphtheria toxine (toxone) acts specifically upon the nerves. The toxic substances may also react upon less important or indifferent tissues, but such action is often masked. The specific action of toxins explains in part the local immu- nity enjoyed by some tissues and further explains why certain viruses are comparatively harmless when introduced into the body through unaccustomed channels. We have already seen an example of this in a case of cholera when introduced into the subcutaneous tissue. In this case the subcutaneous tissue is resistant to the invasion of the cholera vibrio, and these microorganisms cannot find their way to the intestinal tract. The case of smallpox is instructive, for this is an in- fection for which the epithelial structures have a specific susceptibility. It is practically impossible to infect a susceptible animal with cowpox when the virus is introduced subcutaneously or directly into the cir- culation. The same is probably true of smallpox. When smallpox virus is introduced by inoculation upon the skin the disease is much milder than when the virus is introduced by way of the respiratory tract. Evidently the skin offers greater resistance to the smallpox virus than is offered by the mucous membranes. On the other hand, foot-and-mouth disease cannot be given to man or the cow when rubbed upon the skin, although these animals are very susceptible when this LOCAL AND ■ GENERAL IMMUNITY 347 vims is introduced into th& general circulation or rubbed upon the mu- cous membrane of the mouth. Every worker in a bacteriological labora- tory is familiar with the difference in susceptibility of different tis- sues and knows the importance in experimental work of bringing the virus in association with appropriate structures. Certain microorganisms, such as tuberculosis, pus cocci, the pneumo- coccus, etc., have the power of affecting almost every tissue and organ of the body. No part of the body is immune to the tubercle bacillus, but even in this infection some tissues are more susceptible than others. Thus, tuberculosis of the muscle is extremely rare; the lungs and lymph nodes are especially vulnerable. The stomach is comparatively rarely attacked by infective processes, although constantly exposed. The vaginal mucous membrane in the adult and the bladder are resistant to gonorrheal inflammations. There are many similar instances of specific immunity, of tissues. The specific action of toxins gives us a ready reason why certain species of animals are immune to certain infections. In this case the immunity is not the result of any special or specific reaction, nor is it the result of any positive character possessed or acquired by the body, but is a negative trait entirely, due to the absence of specific chemical affinity between the cells and the toxin. The turtle is im- mune to tetanus because there is no combining affinity between the nerve cells of the turtle and tetanus toxin. The immunity, therefore, depends upon the absence of the appropriate cell receptors. Eats are highly immune to diphtheria toxin and hogs to snake venom. In these cases antitoxin cannot be demonstrated in the blood of the rat or the hog, and, so far as can be determined, when the toxin is injected into these animals it is not neutralized in the body. The simplest conception of the mechanism of immunity in these cases is to regard it as depending upon a negative factor resulting upon the absence of suitable receptors in the sense of Ehrlich's side-chain theory. local and General Immunity. — Local and general immunity de- pends upon this variation in susceptibility of the different tissues to different infections. It is doubtful if there is a true general immu- nity in any case, for a general immunity is in almost all instances based upon a local resistance. Even antitoxic immunity in diphtheria, due to the • antibodies in the general circulating blood, is the result of a localized neutralization in which many of the organs and tis- sues of the body take no part. There are many examples of local immunity. Trichina spiralis affects especially the muscles and never the bones. Diphtheria seldom extends down the esophagus. The most marked example, perhaps, is the almost perfect local immunity of the scalp to ringworm in adults, which contrasts, so markedly with the ab- solute susceptibility of children, whereas the susceptibility of the skin 348 IMMUNITY of the body to the same parasite is, if anything, greater in adults than in children (Emery). Many remarkable instances of local immunity are shown by the tis- sues and must be familiar to all. Thus, erysipelas does not, as a rule, extend into the subcutaneous tissues, although the streptococcus may be there; rarely does it extend back into the area of the skin recently affected. The immunity of a part is increased or diminished by the presence or absence of an adequate blood supply. As a rule, very vascular struc- tures enjoy a comparative immunity to infections which frequently attack otlier tissues relatively poor in blood supply. It may be stated as a general rule that the more copious the supply of healthy circulat- ing blood the greater the resistance to infection, and vice versa. This largely accounts for the local immunity enjoyed by the mucous mem- brane of the mouth and lips, which are constantly exposed to wound infections. Herein we also have an explanation of the utility of fo- mentations and other hot applications in the initial stages of an in- fective lesion. The same explanation is applied to Bier's method of passive congestion, in which an excess of blood (though partly stag- nant) is made to flush the tissues. The local immunity of the part may be diminished by a local anemia from any cause, by the presence of dead or injured tissue, by the action of irritants, trauma, etc. Metchnikoff has pointed out that in many infections general pro- tection is in inverse ratio to the local reaction at the site of introduc- tion of the virus. A severe and prompt local inflammatory reaction indicates an active power of protection. The increased volume of blood, the cells, the fluids of the blood and tissues are concentrated about the invading bacteria to wall them off and destroy them, that is the im- munity of the body against a general infection frequently depends upon the promptness and the activity of the local power of reaction. Some infections, notably streptococci, plague, or organisms belong- ing to the hemorrhagic-septicemic group, may invade the body with little or no local inflammatory reaction; that is, little or no barrier is set up against these microorganisms, they invade the blood and tissues without resistance and thus cause fatal septicemias. Bacillus Carriers or Immunitas Non Sterilans.— Upon recovery from an infective process the body usually rids itself completely of the infecting agent. In other words, the immunity which follows an attack of an infectious disease is usually associated with a power the body has of disinfecting itself. In most cases the patient is convales- cent or completely restored to health before the cause of the disease has disappeared from the tissues. This bespeaks a vigorous protecting mechanism, but when this resistance is lowered for any reason a relapse may ensue. BACILLUS CAEEIERS 349 In many instances recovery takes place, but tbe living virulent microorganisms continue to live in the body. This constitutes immu- nity without sterilization, a term introduced by Ehrlich, though a more precise expression would be "immunity without disinfection." Such persons are now known as "bacillus carriers." The immunity protects the carrier but endangers his fellowmen. Bacillus carrying is common in diphtheria, typhoid fever, cholera, pneumonia, epidemic cerebrospinal meningitis, influenza, and many other bacterial infec- tions. Protozoon carriers are also a common phenomenon. The best examples are found in malaria, trypanosomiasis, Texas fever in cattle, etc. Analogous instances are also found in the higher parasitic worms in which the individual who carries the parasite is not affected. Thus, the negro and the Filipino show a relatively high degree of immunity to the hookworm and thus endanger their more susceptible white com- panion. An acute bacillus carrier is one who sheds the specific agent of the disease for a few weeks — four to six following convalescence. A chronic bacillus carrier is one who harbors and discharges the specific agent a longer period than six weeks. A temporary carrier is one who harbors the specific infective agent, although he himself has never had symp- toms of the disease. Temporary carriers may be acute or chronic, de- pending upon the length of time they harbor .the particular parasite. Bacillus carriers play an important role in spreading infections. They explain many mysterious facts in the epidemiology of diphtheria, typhoid fever, cholera, cerebrospinal meningitis, malaria, etc. The bacillus carrier is sometimes a danger to himself. This is seen in diph- theria, pneumonia, influenza, and sometimes in typhoid and cholera. Thus, a person may carry the pneumococcus in his throat for years awaiting certain favorable conditions for infection before he contracts the disease. The same is more or less true of other carriers. While it is undoubtedly true that bacillus carriers play a very im- portant role in spreading infection from man to man, the relative im- portance compared with other modes of transmission cannot be stated in percentage. The subject is still too young for definite quantitative figures. There is no doubt that bacillus carriers are more important in some diseases than others and play a variable role under different circumstances in the same disease. In our studies of typhoid fever in Washington one carrier was discovered in the examination of 986 healthy individuals. This would mean approximately 300 typhoid bacillus carriers in the District of Columbia. If this proportion is cor- rect, it would account for the endemicity of typhoid fever in Washing- ton. Perhaps the residual typhoid fever in many places is largely kept alive through bacillus carrying, and there is little doubt that the grad- ual decline of typhoid fever after great sanitary reforms, such as the 350 IMMUNITY change from polluted to pure water, is due to the decrease in the number of carriers. It now seems evident that polluted water and infected milk will not always cause the disease directly in the persons drinking these fluids, but may produce numerous carriers who either contract the disease themselves subsequently or give it to others by passing the virus on in a more concentrated and virulent form, or to more susceptible individuals. It is evident from the nature of the case that the cure and control of bacillus carriers is one of the vital problems in preventive medicine. It is not only largely through them that infection is spread, but the infections themselves are kept alive in these carriers, who bridge over the interval between outbreaks. It is quite conceivable that with our modern methods of isolation and disinfection certain diseases would soon cease to exist were it not for immunitas non sterilans. Immunity is, therefore, a double-edged sword, in that it protects the carrier but endangers his neighbor. The control of bacillus carriers is a difficult problem. Such unfortunate persons cannot always be im- prisoned, nor is strict isolation always necessary. It is sufficient in the case of typhoid fever to restrict the activity of the carrier. Thus, a typhoid carrier should not cook, prepare, or handle food, or have any- thing to do with the production or distribution of milk. We have no satisfactory cure for carriers; this is a problem for the future; but their number may be lessened — this is a problem for the present. It should always be remembered that the number of carriers will diminish proportionately with the number of cases of any infection, and that every improvement in the water supply, the milk supply, the food supply, and our sanitary conditions generally will have a tendency to sharply diminish the number of carriers in any given infection. Therefore, while isolation, disinfection, and other methods used to control the spread of infection will never be completely successful as long as the carrier is omitted, nevertheless, these methods are entirely justified even though only partially useful. It is the duty of public health officers to check the spread of infection wherever it may be found. In time ready methods of recognizing bacillus carriers and means of neutralizing their potential danger will be more effective than is now possible. Latency is closely allied to bacillus carrying. The malarial para- site may remain latent in the spleen and other internal organs for years, during which time the person remains in good health. But when the resistance is reduced by exposure, fatigue, starvation, or other depressing influences the disease again breaks out. The gonococcus may also remain latent for years. I am familiar with one instance in which the tubercle bacillus remained latent in the axillary glands for 10 years and then became active owing to a condition of depressed vitality. Typhoid ostitis may develop years after an attack of typhoid LOWERED EESISTANCE 351 fever, and we can only assume that the bacilli have remained latent in the tissues all that time. The phenomenon of latency also occurs in rabies, tetanus, and other infections. Lowered Resistance. — The factors which lower our general resist- ance to disease are many and varied. The condition known as depressed vitality, lowered tone, general debility, weakened constitution, and terms of similar import imply a condition in which immunity is low- ered in a general and not in a specific sense. The principal causes which diminish resistance to infection are: wet and cold, fatigue, in- sufficient or unsuitable food, vitiated atmosphere, insufficient sleep and rest, worry, and excesses of all kinds. The mechanism by which these varying conditions lower our immunity must receive our attention, for they are of the greatest importance in preventive medicine. It is a matter of common observation that exposure to wet and cold or sudden changes of temperature, overwork, worry, stale air, poor food, etc., make us more liable to contract certain diseases. The tuberculosis propa- ganda that has been spread broadcast with such energy and good effect has taught the value of fresh air and sunshine, good food, and rest in increasing our resistance to this infection. There is, however, a wrong impression abroad that, because a low- ering of the general vitality favors certain diseases, such as tuber- culosis, common colds, pneumonia, septic and other infections, it plays a similar role in all the communicable diseases. Many infections, such as smallpox, measles, yellow fever, tetanus, whooping-cough, ty- phoid fever, cholera, plague, scarlet fever, and other diseases, have no particular relation whatever to bodily vigor. These diseases often strike down the young and vigorous in the prime of life. The most robust will succumb quickly to tuberculosis if he receives a sufficient dose of the virulent microorganisms. A good physical condition does not al- ways temper the virulence of the disease; on the contrary, many in- fections run a particularly severe course in strong and healthy subjects, and, contrariwise, may be mild and benign in the feeble. Physical weakness, therefore, is not necessarily synonymous with increased sus- ceptibility to all infections, although true for some of them. In other words, "general debility" lowers resistance in a specific, rather than in a general, sense. The mechanism by which the various causes that lower vitality and increase susceptibility act is in most cases quite obscure. Here is a field for laboratory research in immunology that offers rich reward of im- measurable practical good. Some of the factors concerned will be briefiy discussed. Exposure to wet and cold, especially in combination, is a frequent source of lowered resistance. The exact way in which such exposure acts is not definitely known, but laboratory researches offer material 352 IMMUNITY for a number of suggestions. Emery ^ sums up our knowledge upon this subject as follows: "Immunity is to a very large extent a function of the leukocytes, which are specialized cells to which the defense of the body is entrusted. Now, the functions (movement and phagocytosis) which can be easily investigated are found to be dependent in a very high degree on tem- perature, acting best at the temperature of the body, or slightly above; and it is highly probable that the more subtle functions of the leuko- cytes may be similarly depressed by a low temperature. The exposure of the skin to cold, especially if the animal heat be abstracted more quickly by evaporation of moisture on the surface, will lead to a cool- ing of the blood which circulates through it, and hence to a slight, though appreciable, cooling of the whole blood. This, it is true, is soon compensated for, and no great amount of cooling of the whole body occurs; but, even so, it is quite possible that the periodical chilling of the leukocytes during their repeated passages through the cold skin may be sufficient to diminish greatly their functional activity, and to lower the resistance to a point at which infection may occur, and when once pathogenic bacteria have gained a foothold the resistance will for a time tend to decrease. There is also some evidence going to show that exposure to cold may lessen the production of the defensive sub- stances which occur in the blood (alexin, antibodies, etc.), though this is not fully proved. It is worthy of note that the loss of immunity due to the action of cold and wet on one part of the body (such as the feet) is a general one, and may result in a nasal catarrh, an attack of pneumonia, acute rheumatism, etc., according to the nature of the in- fection at hand. It is not necessarily a local infection of the chilled region. This is very well shown experimentally. Fowls are immune to anthrax, but are rendered susceptible if they are kept for some time standing in cold water; and this acquired susceptibility is then a gen- eral one, and not merely of the feet. "Cold and wet, as is well known, have less action when accompanied by energetic muscular exercise, so long as this does not reach the ex- tent of undue fatigue. This is not because less heat is lost during exercise. The reverse is the case. The suggested explanation is that the muscular metabolism leads to an increased production of heat, and at the same time the cutaneous capillaries are dilated and the heart accelerated, or that the circulation of blood through the skin occurs quickly; further, the internal temperature of the body may actually be raised several degrees. The result is that the temperature of any given leukocyte never falls much below normal, if at all, since it comes from the internal regions where the temperature is raised, passes rapidly through the skin, and returns again to the interior of the body. ^"Immunity and Specific Therapy," 1909, p. 9. LOWBEED EESISTANCB 353 "The effect of fatigue, either alone or in conjunction with cold and wet, is also well known, and is one reason for the excessive mortality from disease of armies in the field. It is less explicable, but may prob- ably be connected in some way with the presence in the blood of kata- bolic products of muscular activity, which have an injurious action on the cells of the tissues in general and on the leukocytes in particular. Further, the metabolic products formed during the action of the muscles are acid in reaction, and it is found that some at least of the protective substances which occur in the blood (alexins and opsonins) act best in alkaline medium. This diminution of immunity after muscular fatigue is manifested in animals as well as in man. White rats which have been made to work in a revolving cage are more susceptible to anthrax than normal white rats, the preexisting immunity being broken down." De Sandro ^ "injected dogs, rabbits, guinea pigs with typhoid toxins after severe muscular strain. Under the influence of the chemical changes induced by the physical strain, the nervous exhaustion, fatigue of the heart, and disturbances in the blood production, the defensive powers were evidently much weakened; phagocytosis was reduced and also the chemotactic power of the cells, the bacteriolysins, antitoxins, agglutinins, and opsonins showed a marked falling off." Insufficient and unsuitable food is a prime factor in undermining vitality and lowering resistance. The influence upon health of food poor in quality or lacking in quantity is a matter of common experi- ence, but the scientific explanation of the way in which this result is brought about is not at all clear. First of all, it must be remembered that starvation or improper food does not depress immunity to all infections, but lowers resistance only to certain infections. It was for- merly supposed that famine was the direct cause of pestilence. In fact, in India it has commonly been stated that "plague follows famine with some regularity," but we know now that plague in man is second- ary to the disease in rats and is transmitted through the flea. Ee- lapsing fever was formerly called famine fever, and outbreaks of ty- phus fever were frequently connected with famine, but we know now that the former is transmitted by the tick and the latter by the louse. It is evident that famine may be indirectly a cause of epidemic out- bursts without necessarily depressing immunity. Famine is usually accompanied by misery and squalor and an increase of vermin and other factors that favor the transmission of disease. Tuberculosis, of all diseases, is favored by insufficient and unsuit- able food. This is an infection in which poor nourishment lowers, and good nourishment raises, our immunity. Poor and insufficient food, however, is usually associated with poverty, insufficient clothing, un- ^Biforma Medica, Naples, Aug. 1 & 8, Nos. 31 & 32. 354 IMMUNITY cleanly habits, vitiated atmosphere, overwork, insufficient rest, and other depressing influences, so that it is difficult to assign relative im- portance to any one of these factors. For this reason we may perhaps be led to exaggerate its importance; and, while it is, of course, true that semistarvation, in common with other weakening influences, does pave the way for infective processes, we do not find that a supply of food restricted enough to cause a marked reduction of the bodily strength and some degree of anemia is necessarily associated with any infective disease, though the patient may live under conditions in which infec- tive material is present in abundance. This is well seen in fasting men, in hysterical anorexia, and in patients with impermeable esopha- geal strictures. The blood, it may be pointed out, is not one of the tissues that suffers first in starvation, and its importance to the body in many ways is so great that it is kept in good functional activity while other tissues waste quickly. There is a general belief that exposure to infection is less dangerous after a meal than upon an empty stomach. There is little ground for this belief, unless we take into consideration the notable increase in the number of leukocytes in the peripheral blood during active digestion. It was recognized long ago that wounds inflicted during autopsies are much more dangerous when received while fasting than during the process of digestion, and it is possible that this may be due to some extent to the increased number of leukocytes which occur in the blood during the process. Further, infection reaching an empty stomach has greater chances of passing into the small intestines than if it reaches the stomach after a full meal when acidity, time, and the digestive enzymes have a chance to destroy the microorganisms. This may be of impor- tance in cholera, typhoid, dysentery, and other intestinal infections. Exposure to a vitiated atmosphere, if of long duration, is one of the potent causes of breaking down resistance. Here again, however, immunity is lowered in a specific and not in a general sense. Thus, vitiated air renders the individual more susceptible to tuberculosis, pneumonia, common colds, .and other acute respiratory affections. On the other hand, it can have little influence in determining the infec- tion of most of the communicable diseases, although the lowered tone of the body caused by vitiated air may influence the severity of the attack. The mechanism by which vitiated air increases susceptibility is not understood at all. The subject is discussed in the chapter upon air. Excesses of all kinds, symbolized by Bacchus, Venus, and Vulcan, are mighty factors in lowering vitality and in increasing susceptibility to certain diseases. In this category are also found worry, overwork, loss of sleep, and fatigue. Certain drugs, of which the most important is alcohol, have an im- SIDE-CHAIN THEORY 355 portant action in lowering resistance. Emery states that : "The liabil- ity of alcoholic subjects to pneumonia and some other infective dis- eases is well known, and in them the prognosis is more than usually unfavorable. We have but little knowledge of the action of alcohol in this respect. It may be that it acts as a direct inhibitant of the ac- tivity of the leukocytes, and it is known to destroy certain delicate de- fensive substances (alexins and opsonins) which play some part in the defense of the body against microbic invasion, but it is not known whether these effects are actually manifested in the circulating blood. It is also possible that alcohol tends to inhibit the formation of these defensive substances. "Alcohol tends to lower the temperature of the body by increasing the amount of heat lost. It dilates the superficial vessels and accelerates the heart action in a way somewhat similar to muscular exercise, but does not, like it, raise the temperature of the interior of the body. Hence the effect of alcohol in conjunction with cold and wet is to in- crease their ill effects. More blood is forced through the chilled skin and more heat is lost. The injurious effect of alcohol during exposure to cold is well known. The results, however, are different when al- cohol is taken after exposure, and when the sufferer has reached warmth and shelter. There the increased flow in the cutaneous capillaries leads to a warming of the skin and consequent cessation of the chilling of the blood, although the loss of heat may go on." Ehrlich's Side-chain Theory of Immunity.. — Ehrlich's ^ side-chain theory is a brilliant chemical conception, giving the only satisfactory explanation we have of some of the phenomena concerned in immu- nity. In one sense it has been likened to Weigert's teachings of in- flammation and the process of repair in so far that cognizance is taken of nature's prodigality. For instance, a much larger amount of ma- terial is thrown out than necessary to repair a wound. So, too, in an- titoxic immunity a much larger amount of antitoxin is produced than necessary to neutralize the toxin. In Ehrlich's conception the fundamental processes of immunity re- side in the cells of the body. These cells are attacked by the poison, and if not destroyed are stimulated to an overproduction of "anti- bodies" capable of combining with and neutralizing the poison. Just what cells of the body play the most important role in the production of this form of immunity is not exactly clear. It may be, as Ehrlich supposes, that this power resides in any organ or tissue. According to Ehrlich, the hungry protoplasm of any cell, with its ^Ehrlich: "Die Wertbemessimg des Diphtherieheilserums und deren theo- retische Grundlagen. " Klin. Jahrh., Jena, VI (2), 1897, pp. 299-326. "Ueber die Constitution des Diphtheriegif tes. " Deut. med. Woch., Leip- zig, XXIV (38), 1898, pp. 597-600. Oroonian lecture. "On immunity with special reference to cell life," P'nc. Boy. Soc, London, LXVI, pp. 424-448, pis. 6-7. 35G IMMUNITY complicated molecule, having side chains of various combining affini- ties ready to unite with suitable food molecules brought to it by the blood and body juices, lies at the foundation of his explanation of the chemical production of the antitoxin. It is strange that the same com- bining aflfinity should exist between the protoplasm of the cell and the proteid molecules that furnish it food, as between the cell protoplasm and the toxins of the bacterial poisons. In considering Ehrlich's ^ side-chain theory it is necessary to dis- regard the microscopic structure of the cell and to think of the proto- plasm as consisting of living molecules of extraordinary chemical com- plexity. The molecule of protoplasm has a central "nucleus" with "side chains," "lateral chains," or "bonds" of varying combining ca- pacities. These "side chains" serve to bind the molecule to other mole- cules having proper combining affinities. This arrangement of molecules with side chains is a well-known occurrence in organic compounds. The bezol ring forms one of the best and simplest examples. H (OH) (OH) C C C ^\ /\ /'\ HC CH HC CH HC C (OH) I II I II i II HC CH HC C (CH3) HC C (OH) V V V H H H Benzol CeHe Metaoresol C6H4(CH3) (OH) PyrogaUic acid C6H3(OH)j By replacing one of the H atoms in the bezol ring with the methyl radical (CII3) we have toluol; by replacing one of the H atoms with the hydroxyl group (OH) we have phenol; by substituting two hydroxyl groups we have resorcin; three, pyrogallic acid, etc.; by substituting one hydrogen atom of the ring with the hydroxyl radical and another one with the methyl radical we have the cresols. These simple illustrations from well-known organic compounds il- lustrate the central molecular mass with its side chains and combining affinities, to which the molecule of protoplasm is likened. In applying this analogy to the molecule of protoplasm the name "receptor" is given these side chains, or secondary atomic complexes of the molecular group. Contrary to the simple analogies above given, each molecule of protoplasm has many different kinds of receptors, as shown by the schematic diagram in Pig. 44. These receptors have a specific affinity for the molecules of food, and also combine with the toxic molecules. The toxin molecule, according to Ehrlich, consists of two important ^Ehrlioh; "Die Wertbemessung des Diphtherieheilserums und deren theo- retisehe ruBdlagen," Klin. Jahri., Jena, VI (2), 1897, pp. 299-326. SIDE-CHAIN THEORY 357 Fig. 48. — The Cell WITH Its Vabioub Combining Groups OK Side Chains, Known as Recep- tors. Various toxins are shown having specific af- finity for the proper shaped receptors. Hap-lopliOf« Tonophore «yrouip parts. One is known as the toxophore group, the other as the hapto- phore group. The toxophore group of the toxin is that portion of the molecule which exerts a poisonous effect upon the protoplasm of the cell. This group is less stable than the hapto- phore group. The haptophore group is the seizing or combining portion of the toxin molecule (aTtyw^ to seize or attack). The haptophore group of the toxins have specific combining affinities for the receptors of cer- tain cells, which in part explains the selective action of these poisons. Toxines such as diphtheria toxine gradually dim- inish in toxicity, but retain the same power of chemi- cal combination with the antitoxin. This phenom- enon explains the formation of toxoids. Ehrlich inferred the presence of the toxoid from the following simple experiment: He had a toxine which required 0.003 c. c. to kill a guinea pig. After nine months this poison weakened, so that it required three times as much, that is, 0.009 c. c, to kill a guinea pig. Nevertheless, the combin- ing power of the toxine for antitoxin re- mained the same. Toxoids are altered toxins. They con- sist of the toxic molecule in which the toxophore group has been destroyed, leav- ing only the haptophore or combining group, which, while able to satisfy the combining affinities of the antitoxin, is no longer able to poison the protoplasm of the cell. The diphtheria bacillus, during the process of its growth and multiplication in the body or in an arti- ficial culture medium, produces several poisons, one of which is known as diphtheria toxin. As above stated, the diphtheria toxin consists of a toxophore and haptophore group. In the body the latter unites chemically with the receptors of the cells. When this Fia. 50.— The First J. 1 1 J. , ij. -XT. Stage of Anti- takes place one ot two consequences may result : either (1) the cell is so severely poisoned that it dies, or (2) the living molecule of protoplasm is stimulated so as to excite a defensive action by th^ reproduction of the receptors. Continued stimulation produced by the periodical in- jection of toxine results in an overproduction of receptors, which finally 25 Fig. 49. — The Toxin Molecule; Showing the Haptophore (Combining) Group, and the Toxophore (Poison) Group. OF toxin Formation: A Toxin Mole- cule Anchored to A Receptor. 358 IMMUNITY loosen and float free in the blood serum and body juices. Eeceptors fixed upon the cells are called sessile, and those that leave the cell are spoken of as free receptors. Antitoxin consists of these free receptors float- ing in the blood serum. If we now introduce toxin into the blood, it is immediately neutralized by combining with the free receptors through its liap- tophore group. All the combining affinities of the toxin are thus satisfied or saturated, so that the toxin is no longer able to unite with the receptors Fig. 51. — The Second still attached to the cell, and the poison is thus Stage: Continued ^ndered harmless. Stimulation Causes A Reproduction of It is by no means a necessary corollary of the Receptors. side-chain theory, as is often supposed, that the receptors are found only in those organs upon which the poisonous effects of a toxin are particularly manifested. On the contrary, Bhrlich and Morgenroth ^ believe that receptors capable of combining with the toxin are produced in many different parts of the body, especially in tissues and organs having the power of anchoring the toxin without causing serious poisonous effects; /jC The connective tissue is believed to be speciallv lich in receptors, evidenced by the local reaction ^'^^^-'^^^^^^T^i caused by the subcutaneous inoculation of diph- ginning to LeaVe the theria toxine, ricin, abrin, and similar poisons. In ^^^' fact, one would not be far wrong in assigning a particular significance, in the production of receptors, to just those organs which show unimportant vital response, because in such tissues the injurious effects of the toxophore group are absent or of such diminished importance that the regenerative powers of such tissues are not retarded. The presence or absence of receptors capable of binding the toxine, as well as their number and distribution, are factors which determine the sus- ceptibility of different species of animals against the various toxines. These factors also determine the individual variations in the susceptibility to poisons and further explain some instances of natural immunity to toxines. Fig. 53. — Fourth Stage: the Receptors Have Left the Cell and Float Free in the Blood — Antitoxin. Ehrheh, P., & Morgenroth, J. : Wirkung nnd Entstehung der aktiven btoffe im Serum nach der Seitenkettentheorie. Handbuch der pathogen Mikro- organismen, W. Kolle, -and A. Wassermann, Jena, 1904 SIDE-CHAIN THEOEY 359 Fig. 54. — The Neutral- ization OF A Toxin BY Antitoxin ; the F B E E EecEPTOBS IN THE Blood Have United with THE Toxin = Anti- toxic Immunity. An example is given by Sachs,^ who studied the reaction of guinea-pig blood against arachnolysin, a toxine found in spiders. In this case the com- plete immunity of the red blood cells of the guinea pig against arachnolysin is accounted for by the entire absence of the proper receptors, while the susceptibility of the red blood cells of the rabbit to very small quantities of this poison is accounted for by the strong combining affinity which exists between these cells of the rabbit and the arach- nolysin. In some cases the production of receptors may apparently be traced in the development of cer- tain species. Cannus and Gley ^ have followed the development (?) of the receptors in the red blood cell of the rabbit toward the hemolysin found in eel serum. Young rabbits are much less susceptible to this poison than adult rabbits, which is accounted for by Eluiich as being due to a gradual development of the receptors having proper combining affinities for the hemolysin found in the eel serum. The union between the receptor of the cell and its poison is not always a direct one, as described above^ but sometimes takes place through the intervention of a sec- ond body, known variously as the amboceptor, zwischen- horper, immune body, sensitizer, fixative, preparative, des- mon, etc. This second order of immunity is particularly evident in the poisons that have a lytic or dissolving action upon bacteria or the cells of the body, such as the bacteriolysins, hemolysins, and other cytolysins. The poisonous bodies in this order of immunity are usually spoken of as "complement," but also as the "alexin" (Buch- ner) or "cytase" (MetchnikoflE). One of the remarkable facts connected with the phenomena of the lytic poisons is that the poison itself (the complement) is normally present in the blood. Complement is thermolabile, that is, it has less resistance to heat than the intermediary body, which is thermostabile. According to Ehrlich's theory, immunity can only be obtained against the ^'°- q^^~J''^'^^jp'^°j^^ intermediary body, which is believed to be specific. munity, Showing Fig. 55.— The Second Or- der OF Im- munity, Showing C O MPLB- MENT AND Immune Body. ' Sachs, Hans : ' ' Hofmeisters Beitr., ' ' Bd. 'Quoted by Ehrlich, loc. cit. 2, h. 1-3. AN Immune Body Having Two Af- finities. 360 IMMUNITY Ehrlich compares the intermediary body with diazobenzaldehyde, which by means of its diazo group is capable of combining with a series of bodies, such as aromatic amins, phenols, ketomethyl bodies, etc., while by means of its aldehyde group it may combine with a dif- ferent series, such as the hydrazins, ammonia radicals, and hydrocyanic acid. Phenol and hydrocyanic acid will not directly combine, but, with diazobenzaldehyde acting as an intermediary body, these two substances can be brought into combination. Pushing this comparison further, we may say that the aromatic body, or the phenol, represents a constitu- ent of the blood corpuscle. The diazobenzaldehyde is the intermediary body, while the poisonous hydrocyanic acid constitutes the comple- ment.^ Welch ^ very ingeniously extended Ehrlich's conception of immunity to the bacterial cell. According to Welch's views, the bacterial cell has the same power of defensive action against the poisons produced by the cells of higher animals that they have against the toxic products of the bacteria. In other words, there is a chemical battle. Both the bacterial cell and the body cell excrete poisonous substances against each other, and both in turn are building up a chemical defense against the action of these respective poisons. Antitoxic Immunity. — In order to understand antitoxic immunity it is necessary to consider the nature and action of toxins, the forma- tion and production of antitoxins, and the reaction between toxins and antitoxins and related subjects. TOXINES Bacteria produce many different kinds of poisonous substances, but not all of these are toxines in the specific sense in which that term is now used. A toxine may be defined as a specific poison elaborated by bacterial metabolism; it is soluble in water; poisonous in minute amounts; reproduces the essential symptoms and lesions of the dis- ease; acts only after a period of incubation; and produces antibodies, especially antitoxin. The toxines are thermolabile, unstable, and have a complex chemical structure. Toxines are known only by their effects upon animals; they cannot be recognized in any other way. Presumably they belong to the higher proteins, but nothing definite can be stated concerning their chemical structure. They have never been isolated in pure form; they are not toxalbumins, as was once believed, and they only have a remote analogy ^Vaughan and Novy: "Cellular Toxins," 1902, p. 131. =■ Welch, William H.: "Huxley lecture on recent studies of immunity with special reference for their bearing on pathology." Bull. Johns EovMns Eosv Balto., XIII (141) Dec, 1902, pp. 285-299. *^ TOXINES 361 to the enzymes. Toxines may be globulins, at least they come down in the globulin fraction. They may readily be precipitated with am- monium sulphate, for example, but whether they are mechanically car- ried down in the precipitate is not known. The toxine molecule is at least small enough to readily pass through the pores of the finest porce- lain filter, and large enough not to dialyze through a membrane. There are three well-known toxines: diphtheria, tetanus, and hotu- lismus. A number of bacteria, such as cholera, dysentery, pyocyaneus, and others, produce a certain amount of toxic substances soluble in water, but it is very doubtful whether they are true toxines in accord- ance with the above definition. Bacteria produce many poisonous sub- stances other than the true toxins, such as acids, alkalies, nitrites, ptomains, alcohol, hydrogen sulphid, etc. Some of these substances may play a part in the pathogenesis of disease, but while they are poisonous they are not true toxines. Toxines are sometimes divided into exotoxins and endotoxins. The former are the true or soluble toxines; the latter are insoluble under ordinary circumstances, and differ markedly from the true exotoxins. The endotoxins will be considered separately. The tubercle bacillus, the bacillus of glanders, and other micro- organisms produce soluble toxic substances specific in nature but quite different from the true toxines, in that they are harmless to a normal animal, but poisonous to one suffering with the specific disease. Tuber- culin, mallein, and similar "toxins" are very stable, resist heat and other influences, do not produce the specific lesions and symptoms of the disease, do not stimulate antitoxin formation, and in other ways differ from the genuine toxines. A toxine is produced as a result of bacterial metabolism within the body, but whether it is a secretion, an excretion, or a product of the action of the bacteria, upon the medium (as alcohol and carbon dioxid are produced by yeasts) is not known. It is known, however, that toxines do not result simply from the breaking down of the dead bac- terial cells, as was once stated. It is now evident that different groups of bacteria produce poisons that differ essentially in chemical structure as well as in physiological action, just as different species of higher plants produce various poisons that differ markedly in composition and physiologic action. Very few of the bacterial poisons are injurious when taken by the mouth. Diphtheria and tetanus toxines are practically inert, being de- stroyed largely by the digestive juices and not being absorbed in any harmful amount. Enormous doses of these toxins may be adminis- tered by the mouth to susceptible animals without appreciable harm. The antibodies and the consequent slight immunity probably produced by the absorption of dead bacterial cells and their toxic products (such as 362 IMMUNITY typhoid and tubercle) from the digestive tube is an entirely different phenomenon and does not apply so far as the true toxins are concerned. There is one notable exception in the case of the toxine of the Bacillus hotulismus, for this poison is absorbed by the intestinal mucosa, and it is in this way that it produces its harmful effects in man. There are several poisons produced by higher plants that resemble the true bacterial toxines in all important respects. Among them are : ricin from the castor bean, and abrin from the jequirity bean. These toxines of vegetable origin are known as phytotoxins. They are soluble, act only after a period of incubation, are exceedingly poison- ous in small amounts, are destroyed by heating, and produce specific antibodies. They are probably of protein nature, according to Osborne, Mendel, and Harris, who obtained ricin in very pure form. These poisonous substances of vegetable origin have more than theoretical in- terest, for it was through a study of their action that Ehrlich first obtained a deeper insight into the nature of toxines and antitoxic im- munity. There are poisons in the animal kingdom which closely resemble the toxines, such as the venom of snakes, scorpions, spiders, wasps, etc. True toxines are unstable and are readily affected by heat, sunlight, acids, and various chemicals. They are much more unstable in solu- tion than in dry powdered form. Tetanus toxine is more labile than diphtheria toxin, but when precipitated with ammonium sulphate and preserved as a dry powder in a vacuum tube, and in a cool, dark place it may be kept without deterioration for several years. Diphtheria toxine, in solution, weakens rapidly at first, and then comes to a stage of equilibrium which it maintains indefinitely if preserved in a cold, dark place and protected from the oxygen of the air. The poisonous properties of toxines of diphtheria, tetanus, and hotu- lismus are destroyed at once by boiling, and at 65° C. in a short time. At 60° C. for one hour they lose most or all toxic power. It has been stated that one of the characteristics of the toxines is that they are poisonous in exceedingly small amounts. Thus, .000,000,05 of a gram of a partially purified tetanus toxine will kill a mouse. Diph- theria toxines have been obtained so that .0008 c. c. of the unconcen- trated fluid (crude filtrate) will kill a guinea pig. A true toxine reproduces the essential symptoms and essential le- sions of the disease. In this sense they have a specific action. The symptoms produced in a susceptible animal by the inoculation of tet- anus toxine cannot be distinguished from the disease naturally con- tracted. The symptoms produced by the injection of diphtheria toxine closely resemble diphtheria, including coagulation necrosis at the site of the injection, fever, depression, post-diphtheritic paralysis, etc. The symptoms following the ingestion of the toxine of the Bacillus lotulis- TOXINES 363 mils are an exact counterpart of the disease produced by eating food containing the poison of this microorganism. This specific action is very important, and, if it were more generally known, would save many mistakes in experimental biology and its application to serum therapy. It is comparatively easy to obtain useful antitoxins from true toxines. On the other hand, it seems to be impossible to obtain antitoxines of any therapeutic potency from other bacterial poisons. Thus, tuberculin and mallein and other "toxins" do not stimulate antitoxic production and the so-called antitoxic sera thus produced have no protective or curative value. It must not be forgotten that only a comparatively few infections depend upon toxines and may be pre\'ented or cured by corresponding antitoxins. One of the characteristics of the true toxins is that they act only after a period of incubation. In this respect they resemble the natural disease. Simple chemical poisons may act at once, but the toxines produce no apparent effect until a definite time elapses after they have been introduced into the system — even when overpowering doses are administered. Thus, the ordinary period of incubation when tetanus or diphtheria toxine is injected into a susceptible animal is several days. When enormous amounts are injected this may be reduced to about 8 or 12 hours, but never less. The period of incubation is inversely proportional to the amount of poison injected. The longer the period of incubation the milder the symptoms; when the period of incubation is short the result is almost invariably fatal. The cause of the period of incubation is not well understood. A certain length of time is re- quired for the toxine to reach the susceptible cells. This varies espe- cially in the case of tetanus, which travels up the nerves. After the poison reaches the cells further time is required to combine chemically, and then more time to produce the injury. On account of the period of incubation large amounts of toxine may be present in the circulat- ing blood before the appearance of symptoms. Thus, in horses enough tetanus toxin has been found in the blood two days before the onset of symptoms to kill a guinea pig, when only 0.1 c. c. of the blood serum was injected. The distribution of the toxines in the body is unequal. Most of the poison unites with the cells; some is destroyed and some neutralized if antitoxin is present. Most of it probably unites with the cells, as it soon disappears from the blood. Tetanus toxine may remain a long time in the blood of an insusceptible animal. Thus, Metchnikoff could demonstrate the presence of tetanus toxine in the tortoise four months after the injection. After tetanus toxine is injected it soon disappears from the blood, but if the tissues are injected into a susceptible ani- mal tetanus is produced, for it is now known that this poison has a specific affinity for the motor nerve endings. In the case of fowls it 364 IMMUNITY seems that this power of combining with the tetanus toxine is most marked in the leukocytes. Toxines will not combine with all cells in- differently. They have a specific combining affinity for certain cells. Tetanus toxine has a special affinity for the cells of the central nervous system. Diphtheria toxone also acts specifically upon nervous struc- tures. Diphtheria toxin, on the other hand, is a general protoplasmic poison. These facts are of immense importance in the prevention and cure of certain infections, for a correct understanding of the chemical relation between the poison and the particular cell is of the greatest fundamental and practical value. A realization of this fact has stim- ulated studies which are now in progress upon the relation between the chemical constitution and the physiological action of various sub- stances — studies which have already borne fruitful and useful results. Tetanus toxine may combine with certain cells without apparently injuring them. Diphtheria toxine also combines with indifferent struc- tures, such as the connective tissue. There is evidently a wide dif- ference between the power to combine and the power to injure. The power to injure, however, is not always evident, as it depends upon the importance and extent of the cells affected. Thus, tetanus toxine may combine with the leukocytes in such a way as to prevent phagocytosis. This may be demonstrated by injecting tetanus spores washed free of toxine, in which case the spores are taken up by the leukocytes and their development is prevented. If, however, a slight amount of toxine is injected with the spores, the poison inhibits phagocytosis and permits the growth and multiplication of the tetanus microorganisms and the further production of toxin. From our standpoint the most important property of a true toxine is its power to produce specific antitoxins. This will be given separate consideration. Ehrlich conceives the toxin to be a complex molecule containing both a haptophore and a toxophore group. The haptophore or seizing group is that part of the molecular structure which combines in a chemical sense with the antitoxin or with the receptors of the cell. The toxophore group is the poisonous part of the toxin molecule. This is usually represented diagrammatically (see Fig. 49, p. 357). It may readily be demonstrated by simple experiments that the toxophore group is much more unstable than the haptophore group. The toxin may degenerate so that it has little or no poisonous prop- erties left; however, its combining properties remain unaltered. Such a degenerated toxin is known as a toxoid. A toxoid, then, is an altered toxin which possesses the combining property of the original toxin, but has lost its poisonous power. Some years ago I proposed to draw a distinction between the terms "toxine" and "toxin." The toxine is the crude filtered culture and contains several poisonous substances as well ANTITOXINS 365 as other bodies. The toxin is the specific poison in the toxine. Thus, a filtered broth culture of diphtheria is known as diphtheria toxine. This filtrate contains at least two primary metabolic poisons : toxin and ioxone. The toxin produces the acute symptoms and death; the toxone produces the late paralysis. A filtered broth culture of tetanus is called the tetanus toxine. The filtrate contains at least two primary metabolic poisons: tetanoplasmin and tetanolysin. For a further dis- cussion of the diphtheria and tetanus poisons see page 373. ANTITOXINS An antitoxin is an antibody formed in an animal through the stimu- lation of a specific toxin. The usual method of producing an anti- toxin is by the repeated injections of increasing amounts of toxine into a susceptible animal. The strongest antitoxins are obtained from animals that are very susceptible to the toxine, but all susceptible ani- mals by no means produce antitoxins, although repeatedly injected with the appropriate poison. Thus, a guinea pig which is very susceptible to diphtheria will not form diphtheria antitoxin, even after the repeated administration of diphtheria toxine. Guinea pigs are also exceedingly susceptible to tetanus and react characteristically and violently to te- tanus toxine, but the repeated injections of subminimal lethal doses of tetanus toxine into a guinea pig do not immunize that animal, nor do they induce the formation of antitoxin. In fact, Knorr and also Behring and Kitashima have shown that guinea pigs develop an in- creasing sensitiveness to repeated injections of tetanus toxine instead of an increasing resistance. In other words, the guinea pig, a suscep- tible animal, lacks the mechanism of antitoxin formation which is pos- sessed in such a high degree by horses and other animals. Antitoxin produced by the horse or other animal when injected into the guinea pig will protect it. On the other hand, insusceptible animals, as a rule, do not produce antitoxin, but there are notable exceptions to this rule. Metchnikoff has shown that the cayman, an animal insusceptible to tetanus, will, however, produce tetanus antitoxin if the animal is kept at an ele- vated temperature (32° to 37° C), but not if kept cold (20° C). The mechanism of antitoxin formation is not understood, and the only way of determining whether a certain species of animal is suitable or not is by experimental trial. There is a very great difference in the ability to produce antitoxin even among different individuals of a suit- able species. Thus, some horses have this power developed to such an exquisite degree that they produce a high grade of antitoxin for pro- longed periods — years. Other horses cannot be stimulated to antitoxin 366 IMMUNITY production. This difference among horses is well known to manufac- turers, who have no means of I{:nowing beforehand which horses will be profitable. The only practical method at present known is to discard those animals which refuse to respond to the stimulation of the toxine injections. There are several reasons for selecting the horse for the production of immune sera for human use. On account of its size it furnishes large quantities of blood; the serum of the horse is the blandest blood serum of any known species; finally, the horse furnishes antitoxin in higher potency than any other known animal. Just how and by what cells antitoxins are formed in the body is not known. They are not formed directly from the toxines. In some way the toxine excites the cell to the formation of the antibody. The antibody leaves the cell and becomes "dissolved" in the blood and tis- sue Juices. Perhaps the white blood cells (Metchnikoff), perhaps the connective tissue cells (Ehrlich), are chiefly concerned. Within the body most of the antitoxin is found in the blood, but it also exists in greater or less concentration in practically all the fluids of the body and may also appear in the excretions, as the urine, saliva, milk, and bile. Nothing definite can be stated concerning the chemical nature of antitoxins. Evidence strongly points to the fact that they belong to the higher proteins. In all probability antitoxins are globulins, at least they come down with the globulins from which they have not been separated. Antitoxins are somewhat more stable than the toxines; therefore, the standards by which diphtheria and tetanus antitoxins are meas- ured consist of dried and precipitated antitoxins (and not toxines) preserved under special conditions. Further, the toxines have a more complex constitution than the antitoxins. When the toxines deteriorate they change qualitatively as well as quantitatively. The antitoxins have a simpler constitution and deteriorate simply by a loss of power. Antitoxins are destroyed by heat, acids, and many chemicals. They gradually deteriorate spontaneously when in solution. Thus, Anderson has found that the average yearly loss of the potency of diphtheria antitoxin at room temperature is about 20 per cent.; at 15° C. it loses about 10 per cent.; and at 5° C. about 6 per cent. There is little dif- ference between the keeping qualities of untreated sera and sera con- centrated and refined by the Gibson process. Dried diphtheria anti- toxin kept in the dark at 5° C. retains its potency practically unim- paired for at least 51/^ years. Antitoxic sera should always be kept in a cool, dark place. While antitoxin loses some of its potency with time, and while recently tested sera of known unit value are always desirable, there is absolutely no reason why a serum, however old, should not be employed provided a fresh supply is not at hand. It should be remem- ANTITOXINS 367 bered that antitoxins deteriorate quantitatively only, in other words, an old antitoxin is quite as useful in proportion to its unit strength as a fresh serum; in fact, antitoxic sera are frequently two years old when placed upon the market by manufacturers, for the reason that it is helieved an old serum is less apt to produce rashes (the serum disease). Antitoxins are strictly specific; that is, they neutralize the corre- sponding toxine and have no other apparent action within the body. The occasional ill effects, such as the serum sickness, following the injec- tion of antitoxic sera are due to other substances (the proteins in the serum) and not to the antitoxins themselves. Antitoxins may be injected subcutaneously, intravenously, into the subarachnoid space, into a nerve, into the brain substance, or into any of the body cavities. Antitoxins are practically useless when given by the mouth, as very little is absorbed. Antitoxins when injected into an organism disappear rather quickly. Some of the antitoxin is bound to the corresponding toxine, if any is present, some combines with the cells, but the greater part is eliminated as antitoxin in the urine, bile, saliva, etc. The antitoxin contained within the organism that produces it actively, as the result of an attack of the disease or as a result of the injection of toxin, disappears much more slowly from the body than when the antitoxin is injected into the organism, as in passive immu- nity. Passive or antitoxic immunity is, therefore, transient; it cannot be depended upon for more than ten days or two weeks. When antitoxic serum is injected subcutaneously the antitoxin is absorbed slowly. It requires about 48 hours under these circumstances for the antitoxin to appear in the blood in maximum amount. There- fore, when very prompt action is desired, the antitoxic serum may be introduced directly into the circulation by intravenous injection. There are a number of antibodies that are either true antitoxins or closely resemble these antibodies. Some of these antibodies neutralize the true bacterial toxines, others the poisons of animal origin, others the poisons of plant origin, and others neutralize the activity of fer- ments. The principal antitoxins, according to this classification, are brought together as follows : (1) Bacteria Antitoxins. — The three principal and most potent bacterial antitoxins are those of diphtheria, tetanus, and botulismus. The following are also considered to have antitoxic properties: pyo- cyaneus, symptomatic anthrax, antileukocidin and antilysin against bac- terial hemolysins. (2) Animal Antitoxins. — These antitoxins are produced by animal poisons belonging to the venoms. True antibodies are obtained against snake venom and similar poisons in spiders, eels, wasps, scorpions, fish, salamanders, and toads. 368 IMMUNITY (3) Plant Antitoxins. — These are antirisin, antiabrin, antirobin, anticrotin, and poUantin, the pollen antitoxin against hay fever. (4) Ferment Antitoxins. — Antibodies may be obtained against fer- ments, such as pepsin, urease, rosinase, steapsin, trypsin, fibrin ferment, lactase, cyranase; and antibodies may also be obtained against the fer- ments found in bacterial cultures. There are comparatively few antitoxic sera of practical use in human therapy, just as there are relatively few true bacterial toxines. The best known antitoxins are those of diphtheria, tetanus, and botulismus. Numerous other antitoxic sera are found upon the market or have been described, but they are of doubtful or no practical value; any power such so-called antitoxic serum may have is due to antibodies other than antitoxins. Antitoxins are valuable both as curative and immunizing agents. Their preventive action depends upon the fact that they meet the tox- in, unite with and neutralize it, thus rendering it harmless. As already stated, the antitoxins remain in the body a brief time and their immunizing power, while of a high grade, is transitory. They disappear in about ten days or two weeks; the immunity must, therefore, be renewed in special cases by repeated injections of the antitoxin until the danger is passed. This phase of the subject is considered in more detail under the prevention of diphtheria and tetanus. The usual im- munizing dose for diphtheria is 1,000 units, for tetanus 1,500 units. As a curative agent antitoxin must be administered early and in sufficient amount to insure success. It is most important to give the antitoxin early — before the damage is done. Too great emphasis can- not be laid upon this point. After the toxin has united with the cells it cannot be dislodged by the antitoxin. The importance of giving antitoxin early is well illustrated in the case of diphtheria. When moderate amounts (3,000 to 10,000 units) are injected on the first day of the disease the mortality is practically nil. The mortality increases with each hour's delay. The importance of giving this sovereign remedy early is also illus- trated in the experiments of Eosenau and Anderson ^ upon the influ- ence of antitoxin upon post-diphtheritic paralysis. It was foimd that one unit of antitoxin, given not less than 24 hours after a fatal dose of diphtheria toxine in a guinea pig, greatly modified the post-diph- theritic paralysis and saved the life of the animal, whereas 4,000 units given 48 hours after the infection did not modify the paralysis or save the life of the animal. Four thousand units of antitoxin is an enor- mous amount for a guinea pig weighing about one-half a pound. Weight for weight, it corresponds to 400,000 units for a 50-pound child. The fact that one unit of antitoxin saves life when administered timely, ^Eyg. Lab. Bull., No. 38, 1907. ANTITOXINS 369 whereas enormous doses fail totally when delayed, should be sufficient to place physicians on their guard; increased dosage cannot atone for delay. When cases are seen late in the progress of the disease it is good practice to give large doses of antitoxin, for the reason that the poison is being elaborated continuously and some of it is free in the circulating blood. The antitoxin unites with and neutralizes the uncombined poison and thus protects the cells against further damage. This refers to tetanus as well as diphtheria. Tetanus anti- toxin is a very valuable immunizing agent, but is of less value after symptoms have appeared, for then most of the damage has been done. Preparation of Antitoxin. — The antitoxin used in human therapy is practically always contained in the blood serum or blood plasma of the horse. The blood is drawn from the jugular vein into sterile bottles. The bleeding should never be done until a week or more has elapsed since the last injection of toxine, so as to allow time for the disappearance of the poison from the circulation. The horses are given no food for about 24 hours preceding the bleeding, so that the blood may not contain the fresh products of digestion and metabolism. After, the blood is drawn it may be allowed to clot spontaneously. In the case of horse blood this takes place more quickly at room temperature than in the ice chest. The clot is allowed to contract for a few days and the serum containing the antitoxin is then drawn off with a pipette or simply decanted. In this way a clear transparent serum is obtained which, if protected against contamination by the usual bacteriological precautions, is sterile and may be preserved indefinitely. It is almost a universal prac- tice, however, to add a preservative; either chloroform (0.3 per cent.), phenol (0.5 per cent.), or tricresol (0.4 per cent.). These preserva- tives in the amounts named are harmless when injected and have prac- tically no effect upon the antitoxin itself. They gradually precipitate the albuminous matter from the serum, which settles as a white amor- phous deposit and which may be disregarded, as it is harmless. Chloro- form produces a better-looking serum, but the less volatile preservatives are usually preferred on account of their stability and, hence, greater reliability. By the method of allowing the blood to coagulate, as above described, only about one-third of its volume is recovered as antitoxic serum. A much greater yield may be obtained by citrating the blood: sodium citrate prevents the clotting of blood. A solution of this salt is placed in the bottle which is to receive the blood directly from the horse, in sufficient amount to be present in 1 per cent, of the whole blood. The corpuscles soon settle to the bottom, leaving the clear supernatant plasma, which is then decanted or drawn off with a pipette. In this way the yield of antitoxic fluid is about 90 per cent, of the volume of 370 IMMUNITY the blood, and is, therefore, preferred to the less economical method of allowing the blood to clot. The citrated plasma may further be "purified" or concentrated by- various methods, that generally used being a modification of Gibson's ^ method, based upon the earlier experiments of Atchinson. Ordinary antitoxic serum contains serum globulins (antitoxic), serum globulins (non-antitoxic), serum albumins (non-antitoxic), serum nucleoproteids (non-antitoxic), cholesterin, lecithin, traces of bile col- oring matter, traces of bile salts and acids, traces of inorganic blood salts, and other non-proteid compounds. Eefined serum contains serum globulins (antitoxic), traces of serum globulins (non-antitoxic) dissolved in dilute saline solution. Gibson's Method of Concentrating Diphtheria Antitoxin. — Gibson ^ prepared a refined and concentrated diphtheria antitoxin by first pre- cipitating the antitoxic serum with a half saturation of ammonium sul- phate. This throws down the globulins. The precipitate is collected and dissolved in a saturated solution of sodium chlorid. Only a por- tion of the globulins, but all of the antitoxin, passes into the solution. Through the precipitation by ammonium sulphate and solution in so- dium chlorid the nucleoproteins and the insoluble globulins are elim- inated. The soluble globulins with the antitoxin are now precipitated by the addition of acetic acid. The precipitate is collected upon a fil- ter, partially dried, and finally placed in a sac of parchment membrane and dialyzed in running water. The resulting fluid is then an anti- toxic solution of soluble globulins which is rendered neutral, and suffi- cient sodium chlorid is added to make it isotonic. In carrying out the process there is a loss of about 30 per cent, of antitoxin units because of retention on filters, loss in dialysis, etc., but the resulting solution of antitoxic globulins has a greater concentration than the original serum from which it was obtained. Thus, a serum containing only 200 units of antitoxin per c. c. may, after concentration with Gib- son's method, contain as much as 500 units of antitoxin per c. c. ; and one having an original potency of 300 may contain 700 units per c. c. in the final product. The advantages of the antitoxic globulins are that a smaller bulk is required to give a corresponding number of units of antitoxin. Less foreign proteins are injected, and there is a resulting decrease in the number and severity of those showing the serum sickness. By the method of concentration and refining, antitoxic sera too weak for prac- tical purposes are thus saved. Dried Antitoxin. -^The antitoxic serum or the antitoxic plasma may be dried by any of the methods in common use, care being taken to 'Jour, of Biolog. Chem., Vol. I, 1906.. ^Ibid., Vol. I, Nos. 2 & 3, Jan., 1906, p. 161. ANTITOXINS 371 prevent bacterial contamination and also to prevent overheating. The antitoxic fluid is usually dried in shallow layers on pans in a vacuum apparatus, to the form of golden yellow amorphous flakes. These are ground to a powder. About 100 c. c. of serum or plasma yields ap- proximately 10 grams of dried residue. It is, therefore, necessary to re- dissolve the dried antitoxin in at least 10 parts of normal saline solu- tion. The advantages of antitoxin in the dried form are that when pre- served in a cool, dark place it retains its potency practically indefinitely. The only disadvantage is that it goes into solution with some difficulty, and the making of this solution requires not only time, but is rather inconvenient. Mode of Action. — The mode of action of antitoxins is now fairly well understood. One thing is certain, and that is that the antitoxin unites directly with the toxin. This may be readily demonstrated by adding a little antitoxin to some toxin in a test tube and then injecting the mixture into a susceptible animal; no symptoms result. Diphtheria antitoxin combines with diphtheria toxin more quickly than tetanus an- titoxin combines with its poison. Thus, in the case of diphtheria the union between the poison and its antibody is complete in less than twenty minutes at room temperature, while in the case of tetanus it requires one hour. These facts are of practical importance in the work of standardization, in which case the toxines and antitoxins are mixed in the test tube and the combining action must be complete before the mixtures are injected into the test animals in order to insure accurate results. Ehrlich believes and strongly -defends his assumption that an anti- toxin unites with a toxin just as an acid unites with an alkali, that is, the one has a strong chemical affinity for the other, and the union is simple and direct. On the other hand, Arrhenius and Madsen insist that, instead of considering the toxine as a complex mixture of various substances, such as a toxin, toxone, etc., it would be simpler to consider it as a single (at least homogeneous) substance which has a very weak affinity for the antitoxin and that in mixtures containing toxine and antitoxin there are always both free toxin and free antitoxin. Arrhenius draws his analogy from known facts in physical chemistry, particularly from studies upon the relation between solutions of boracic acid and ammonia. These two substances have a comparatively weak affinity for each other, and in mixtures all the boracic acid does not combine with all the ammonia, but there are always present both free ammonia and free boracic acid. When ammonia and boracic acid are brought together in watery solution some of the ammonia at once unites with some of the boracic acid to form ammonium borate. This reaction starts with a certain velocity, but as the mass of ammonium borate increases the velocity of 372 IMMUNITY the reaction gradually diminishes. After a time a condition is reached when the ammonium borate has a maximum value and does not further increase, no matter how long the reaction is allowed to proceed under the given conditions. When this condition of equilibrium is reached the mass contains a certain quantity of water, ammonia, boracie acid, and ammonium borate; but these substances are not at rest. The ammonia and boracie acid will always react when in the presence of each other, whether or not ammonium borate is present. But, as the appropriate amount of am- monium borate remains constant, it is understood while this continuous association between the ammonia and the boracie acid is going on there is at some time a reversible action — that is, a dissociation of the ammonium borate to reform ammonia and boracie acid. These two reactions take place simultaneously. Arrhenius believes that the diphtheria poison changes slowly ac- cording to the laws of monomolecular reactions, that the toxin combines feebly with the antitoxin, the equilibrium constant being equal for both. The claim, however, that the toxine is a simple substance having a weak affinity for the antitoxin and that the combination of toxin and antitoxin follows the Guldberg-Waage law, and that the reaction is, therefore, reversible, seems untenable in the light of the evidence brought forward by Ehrlich, Nernst, Michaelis, and others. ENDOTOXINS In contradistinction to the soluble or exotoxins, there is a group of poisons known as endotoxins. The existence of endotoxins was taken for granted before they were actually demonstrated. As soon as it was found that only some bacteria produce soluble specific toxines it was at once assumed that the other bacteria must contain similar pois- ons, but closely bound within the cell and insoluble in ordinary culture fluids. It was further assumed that these endotoxins were in some way set loose in the body and thereby produced the lesions and symptoms of the disease. The endotoxins are conceived to be poisons very closely bound up with the protein contents of the bacterial cell, and are liberated in the body when the bacterial cell dies and disintegrates. However, it by no means follows that these endotoxins are poisons similar in action and composition to the soluble true toxins; in fact, there is evidence to indicate the contrary. It is true that some bacteria, such as the dysen- tery bacillus, cholera vibrio, and a few other microorganisms that pro- duce little or no soluble toxine, may be ground up so that the bacterial cells are mechanically ruptured, thus liberating the endotoxin. In most cases of so-called endotoxic action the reaction of anaphylaxis ap- pears to be the best explanation. TETANUS TOXINB 373 TETANUS TOXINE On account of its virulence, its solubility, and the characteristic contractions which it induces, the poison of tetanus has been a con- venient and favorite subject of investigation. It was the first of the bacterial toxines to give fruitful results in serum therapy. The toxine is readily soluble in the medium in which tetanus grows, whether fluid or solid; it diffuses throughout gelatin or agar. The culture filtered free of all bacterial cells is called the tetanus toxine. This is really a complex substance containing various poisons and other bodies. Two of these poisons in particular have been studied: tetanospasmin and tetanolysin. It is the former which produces the convulsions charac- teristic of the disease and concerns us especially. This poison is a type of a true toxine. It is exceedingly poisonous in very small quan- tities; is readily rendered inert by heat (60° C.) ; contains both a tox- ophore and haptophore group ; produces antibodies when introduced into susceptible animals, and produces symptoms only after a definite period of incubation. In all these characteristics tetanus toxine resembles diphtheria toxine. Tetanus toxine is one of the most poisonous substances known. Amounts as small as .000,006 gram of the standard precipitated toxine prepared by me in the Hygienic Laboratory at Washington- invariably kills a guinea pig weighing 350 grams in about four days. As this pre- cipitate consists mostly of albumins, peptone, amino acids, volatile sub- stances, ammonium sulphate, and other salts, it will be seen that but a small proportion of the weight consists of pure poison. Brieger and Cohn found that their strongest tetanus toxine killed mice weighing 15 grams when given subcutaneously in doses of .000,000,05 gram, and they calculate that .000,23 gram would be a fatal dose for a man weigh- ing 70 kilograms. Tetanus toxine is not equally toxic for all species of animals; on the other hand, there is an extraordinary constancy in its toxicity upon individuals of the same species; that is, the same quantity of toxine per gram weight of a particular animal always produces similar results. Tetanus toxine is harmless when given by the mouth. It is not ab- sorbed from the intact intestinal tract, but is affected by the digestive Juices. I have fed guinea pigs with as much as 24,000 and mice 18,000 times the minimal lethal dose of tetanus toxine without producing any apparent ill effects. All attempts to isolate the specific toxine as a definite chemical compound have proved unavailing. We are totally ignorant of its chemical nature. The only way by which it may be recognized is through its effects upon animals. By this means we are enabled to de- 36 374 IMMUNITY termine not only the presence of the poison, but also to estimate its concentration in a solution and to watch its deterioration. Brieger in 1886 isolated from a contaminated growth a basic sub- stance or ptomain which he called "tetanin" (CigHgNjO^). Shortly afterward he obtained another ptomain which he named "tetanotoxin" (CjHuN). These substances caused muscular contractions when in- jected into mice, and Brieger believed them to be the true poison of tetanus. They are now only of historical interest, for the studies of Kitasato and Weyl in 1890 with pure cultures of tetanus found that Briegers purified extracts did not produce the characteristic symptoms of tetanus in experimental animals. Brieger and Fraenkel in 1890 obtained an alcoholic precipitate from filtered broth cultures which they termed "toxalbumin" and which had undoubted toxic properties. Hayahsi concludes from his work upon the subject that the toxin isolated according to the Brieger-Boers method, as well as by his own modification, shows a definite albumin reaction. However, this does not prove that the toxin itself is a protein. The powerful action of the tetanus poison in such minute amounts, its thermolability, and the period of incubation lend countenance to the view that the toxin may be a ferment. There is, therefore, nothing but analogy to class tetanus toxin with the ferments. Ehrlich, in a. parallel work to his researches upon the constitution of diphtheria toxine, showed that tetanus toxine contains both a toxo- phore and a haptophore group and that the antitoxic immunity is explained by the presence of free receptors in the blood. The receptors combine directly in a chemical sense with the haptophore group, thus neutralizing the poison. Ehrlich,^ 1898, definitely proved that tetanus toxin contains at least two poisons: (1) tetanolysin, and (2) tetanospasmin. He showed that these two poisons do not always appear in the same relative propor- tion in different preparations. Some of the toxins that have strong tetanic properties have weak hemolytic action, and vice versa. The hemolytic afiinity of the toxin weakens much quicker than the tetano- spasmin. This occurs spontaneously as well as when it is heated to 50° C. for 20 minutes. The two poisons have different combining af- finities. If tetanus toxine is brought into contact with red blood cor- puscles, the greatest part of the tetanolysin is bound by the red cor- puscles, while the tetanospasmin remains in the solution. Each one of these two poisons has its own antitoxin. If several different tetanus sera are examined, it will be found that they have no parallel neutrali- zation for tetanolysin and tetanospasmin. In one particular case Ehr- lich found a serum that was strongly antispastic and had practically no antilytic power. ^Ehrlich, P.: BerJ. IcUn. Wocli., 1898, No. 12. TETANUS TOXINE 375 Bolton and Fisch ^ have Shown that thetoxine makes its appearance in the blood of the horse several days before any symptoms of tetanus are observed, and that it gradually increases until about two days be- fore symptoms become noticeable, and then it suddenly diminishes and even disappears in some cases. The amount of toxine varies consider- ably in different horses. In one instance the serum of a horse, about two days before symptoms of tetanus appeared, was sufficient to kill a guinea pig in the dose of 0.1 c. c. The fact that tetanus toxine may appear in such large quantities in the blood without symptoms of tetanus is of very great practical importance in the production of both diphtheria and tetanus antitoxins and other therapeutic sera. Tetanus toxine is readily destroyed by heat, sunlight, acids, and other agencies. Anderson, in 1907, found that when tetanus toxine is exposed to 5 per cent, formalin for six hours a guinea pig is able to withstand 100 minimal lethal doses of this formalinized poison. Three per cent, formalin after twenty-four hours' exposure destroys the toxine ; it destroys a part of the toxine in one hour, its action increasing with the length of exposure. This indicates that formalin should prove a useful antiseptic and antitoxic substance for local application to wounds. Tetanus toxine is prepared from bouillon cultures grown anaerobi- cally at 37° C. for 6 to 15 days. The culture fluid is then filtered through porcelain or diatomaceous earth; the germ-free filtrate con- tains the poison. This is used to inject into horses for the purpose of producing tetanus antitoxin. Tetanus toxin in solution is so unstable that it cannot be depended upon for the purpose of accurate tests. From a practical standpoint it is all-important to obtain a stable poison. Herein lies the crux of the problem, so far as the standardization of tetanus toxin is concerned. If soluble poisons are used to measure the value of antitoxic serums, as is the case with the German method, it is found necessary to redetermine through a series of mice the strength of the toxine each time a serum is tested. The fact that tetanus toxine does not exhibit the same constancy as diphtheria toxine in solution has thrown much confusion and no little difficulty into the work of standardizing its antitoxin. Eosenau and Anderson succeeded in obtaining a dry poison by pre- cipitating it from solution with ammonium sulphate. The excess of salt is removed in the dialyzer. The toxine may be further purified by again bringing it into solution and reprecipitating it several times. This, however, is not necessary in ordinary work. The precipitate is collected and dried in a vacuum over sulphuric acid and preserved in vacuum tubes, under the infiuence of pentaphosphoric (P2O5) acid in a cool, dark place. Under these conditions the poison does not dim- inish in toxicity during a period of over two years. It loses its toxicity ' Trans. Assoc, of Am. Fhys., XVII, 1902, pp. 462-467. 376 IMMUNITY rather slowly when exposed to light, heat, and other influences. One of the sealed tubes sent from Washington to Manila arrived there with- out appreciable loss of strength. It is this dried poison which is dis- tributed to manufacturers and other laboratories engaged in the work of standardizing tetanus antitoxin. Mode of Action. — It has been known for a very long time that te- tanus toxin affects chiefly the central nervous system, but it is only comparatively recently that it has been demonstrated experimentally in what way the poison reaches the nerve centers. For this information we are indebted especially to the work of Marie and Morax,^ 1902, and Meyer and Eansom,- 1903. It is now definitely known that the motor nerves have a specific affinity for tetanus toxin. When the toxin is placed subcutaneously the adjacent motor nerve endings at once begin to take it up and it is then transported in the axis cylinder to the cord. This action may be compared to the absorption of nourishing liquids by the roots of a plant. The lymphatics also absorb much of the toxin and in a short while it appears in the blood stream, which carries it to all parts of the body, where again it is absorbed by the motor nerve endings which are bathed in the toxin-laden fluid. The toxin does not reach the nerve cells directly through the blood, for even after introduc- ing the poison into the subarachnoid space there is a general poisoning and not a cerebral tetanus. The injection of tetanus toxin into the posterior root of the spinal nerves leads to a tetanus dolorosus which is characterized by strictly localized sensitiveness to pain. According to Meyer and Eansom, the reason why the sensory nerves do not play any role in the conduction of the poison lies in the presence of the spinal ganglion, which places a bar to the advance of the poison. Milchner in 1898 showed that tetanus toxin combines chemically with the central nervous system. A direct combination takes place when tetanus toxin and brain substance are mixed in the test tube. This action has been studied by Metchnikoff, Wassermann, and Takaki, Eoux and Borrel, Denys, and others. It seems that the phenomenon of the fixation of the tetanus toxin by nervous tissue, in spite of some analogies, cannot be likened to the action of antitoxin on toxin. The toxin at first fixed by the nervous substance again becomes free in vitro and in vivo. The union between the tetanus toxin and the nervous tissue appears to be a feeble chemical absorption which may be readily dissociated and which does little harm to the toxin. On the other hand, the union between toxin and antitoxin is much more stable and definite. ^ Marie and Morax: Annales de I'lnstitut Pasteur, XVIII, 1902, p. 818. ^ Meyer and Eansom: Archives fur experimentelle Pathologie und Pharma- eologie, Vol. 49, 1903. TETANUS ANTITOXIN 377 TETANUS ANTITOXIN Tetanus antitoxin is contained in the blood serum of horses highly immunized by repeated injections of tetanus toxine. It is necessary to begin with exceedingly small doses, for the reason that horses are very- susceptible to tetanus. Time may be gained and accidents avoided by guarding the first few injections with tetanus antitoxin. The injections are given at intervals of about a week and may be rapidly increased so that in a few months a horse will be able to stand several hundrfed cubic centimeters of an exceedingly strong poison. The horse should never be bled for the purpose of procuring the antitoxic serum until at least two weeks have elapsed since the last injection of the toxine, in order to be sure that all the poison has disappeared from the circu- lating blood. Tetanus antitoxin is an antibody which corresponds in all essential respects to diphtheria antitoxin. It neutralizes the poison probably by direct chemical combination whether in the body and in the test tube. In human therapy it is used either by subcutaneous or intravenous in- jection, by injecting it directly into the large nerve trunk leading from the wound, by placing it in the subarachnoid space, or by injecting it directly into the brain substance. It is also used in dried form as a dusting powder upon the wound. When tetanus antitoxin is adminis- tered subcutaneously it is absorbed rather slowly. Knorr found the maximum quantity in the blood only after 24-40 hours, and from this time on the amount steadily decreases, so that by the sixth day only one-third of the actual quantity is present; by the twelfth day only one-fiftieth, and at the end of three weeks no antitoxin whatever could be demonstrated. Hence, it is imnortant to give the first dose in a case of tetanus intravenously. The specific action of tetanus antitoxin makes it a valuable prophy- lactic; it has less use as a curative agent, for the reason that after symptoms have appeared most of the damage to the nerve cells has been done. While antitoxin has a limited value as a remedial meas- ure, it is by no means to be neglected, for the reason that it neutral- izes the free poison in the circulating blood and elsewhere in the body and thus prevents further damage of the nerve cells. In the use of tetanus antitoxin as a preventive it should be remembered that it is quickly eliminated from the body, so that in wounds which continue to suppurate with foul-smelling pus, especially when the pus contains end-spore-bearing rods, and in all wounds in which there is a suspicion of special danger about 1,500 units of the tetanus antitoxin should be administered at intervals of about ten days. 378 IMMUJSriTY STANDARDIZATION OP ANTITOXIC SERA The method of measuring the strength of diphtheria and tetanus antitoxins is exceedingly accurate and satisfactory. The tests are physi- ological, that is, depend upon animal experimentation. Guinea pigs are used because they are particularly susceptible to both tetanus and diphtheria toxines and react to these poisons so uniformly that they serve the purpose of an accurate analytical balance. In order to ob- tain precise results it is essential that all the conditions of the test be uniform. It is, therefore, advisable to follow the official methods, which have been prescribed in great detail. All antitoxic sera upon the American market are standardized in accordance with the ofScial unit dispensed by the federal government. This work is done in the Hygienic Laboratory of the Public Health Service. The Standardization of Diphtheria Antitoxin. — The immunity unit for measuring the strength of diphtheria antitoxin may be defined as the neutralizing power possessed by an arbitrary quantity of diphtheria antitoxic serum kept under special conditions to prevent deterioration in an authorized laboratory. Prom a theoretical viewpoint the unit may be defined as that quan- tity of diphtheria antitoxic serum which will just neutralize 200 mini- mal lethal doses of a pure poison. By a "pure" poison is understood one containing only toxin and no toxoid, toxone, or other substance capable of uniting with the antibodies. The first definition may be compared to the platinoiridium bars kept under special conditions in Paris or Washington as the standard yard or meter. If all the meter bars or yardsticks were lost it would be difficult, if not impossible, to reproduce others having the exact lengths of the originals. These standard measures are, therefore, guarded against deterioration just as the standard antitoxic sera are pre- served under strict conditions of light, heat, moisture, etc., in the Hygienic Laboratory of the Public Health Service at Washington. From time to time duplicates of this serum are made to guard against de- terioration or accident to the original. The second definition may be compared to the original conception of the meter, which was intended to be one ten-millionth of the quad- rant of a great circle of the earth. Theoretically, therefore, if all the meter bars were lost this unit of measurement could be reproduced with approximate fidelity. In the same way it is theoretically possible to reproduce the diphtheria antitoxic unit in consideration of the fact that it has just 200 combining units. The test by which the strength of antitoxin is measured is a physio- logical one, and depends upon the neutralization of the toxin by the STANDAEDIZATION OF ANTITOXIC SBEA 379 antitoxin. This neutralization can only be determined by injecting the toxine-antitoxin mixtures into guinea pigs and noting the results. The unit for measuring the strength of diphtheria antitoxin is a meas- ure of physiologic strength, not of quantity. In all the early work on this subject the toxine was used as a basis for measuring the strength of the antitoxin, but as the toxine is a much more complex substance than the antitoxin, and as it is less stable, ac- curate results were not possible. Ehrlich showed that the antitoxin under certain conditions was permanent both in power of chemically combining with and physiologically neutralizing the toxine. One anti- toxin, however, cannot be compared with another antitoxin directly. This can only be done through the toxine. From a practical standpoint, the following illustration of a test will give a clear conception as to how the unit of strength of a serum is determined. Example of a Test. — It is first necessary to obtain our official yardstick. This may be done by applying to the Hygienic Laboratory in Washington, where the standard serum is kept in a dry powdered form in vacuum tubes under the influence of pentaphosphoric acid in a cold place and carefully preserved from the light. This powder is dissolved, carefully tested, and sent to the applicant in a glycerinated solution. Each cubic centimeter of a certain dilution of this standard serum contains just 1 unit. Before, however, we can measure the potency of an antitoxic serum of unknown strength it is first necessary to standardize a toxine. This is done by mixing one unit of the stand- ard antitoxic serum with varying quantities of the toxine, as follows : Mixtures of Antitoxic Serum and Toxine Injected Subcutaneously Result, into Guinea Pigs. 1 immunity unit + 0.14 c. e. toxine = No reaction. " " + 0.15 " " = No reaction. " " -I- 0.16 " " = Slight congestion at site of injection. [This is the Lo dose.] « « _|- 0.17 " " = Apparent reaction at site of injection. " " 4- 0.18 " " = Injection and edema at site. " _[- 0.19 " " = Injection and edema at site ; late paralysis. " " + 0.20 " " = Sometimes death in 5 or 6 days, some- times late paralysis. " " _|_ 0.21 " " =^ Always causes acute death about the fourth day. [This is the L+ dose.] " " + 0.22 " " = Acute death usually on second or third day. " " + 0.23 " " = Acute death on second day. From this series we learn that one unit contains just sufficient anti- toxin to neutralize 0.16 c. c. of the toxine. This is known as the L, 380 IMMUNITY dose.^ By the L„ dose, then, is meant that quantity of poison which just neutralizes or saturates one immunity unit as shown at the necropsy done 48 hours after the subcutaneous injection of the mixture into the guinea pig. The reaction at the site of inoculation at this examination must be hardly noticeable. In the above illustration the L^ dose of this toxine is just 0.21 c. c. By the L^ dose is meant the smallest quantity of poison that will neu- tralize one immunity unit plus a quantity necessary to kill the animal on the fourth day. The L^ dose is the test dose which is used to de- termine the strength of our unknown antitoxic serum, as follows: The L + (or Test Dose of Toxin) + Varying Amounts of Antitoxin Injected into Results. Guinea Pigs. 21 c. c. toxine + 1/150 e. c. antitoxic serum — No effect. u " +1/175 ' = No effect. It " +1/200 ' ^Late paralysis it " +1/225 ' = Late paralysis it " +1/250 ' =^Dies 4th day. 11 " +1/275 ' ^Dies 3d day. u « +1/300 ' = Dies 2d day. From this series it is evident that 1/250 c. c. of the serum contains that amount of antitoxin which will neutralize the toxine in the test dose, leaving sufficient free poison to kill the animal on the fourth day. The serum, therefore, contains one antitoxic unit in 1/250 c. c. of serum. One c. c. of the serum would, therefore, contain 250 units.^ Standardization of Tetanus Antitoxin. — There are four methods of measuring the strength of tetanus antitoxin: (1) the German method described by Behring; (2) the French method described by Eoux; (3) the Italian method after Tizzoni, and (4) the American method established by Eosenau and Anderson. European standards are ad- mitted to be unsatisfactory and for the most part not accurate. Fur- ther, they are complicated and difficult to carry out. The American method, which has been made the official government standard for this and other countries, commends itself for its simplicity, directness, and precision. The tetanus antitoxic unit is based upon the neutralizing value of an arbitrary quantity of antitoxic serum preserved under special conditions to prevent deterioration in the Hygienic Laboratory of the Public Health Service. This arbitrary quantity now contains ten times the amount of tetanus antitoxin necessary to neutralize somewhat less "■ L stands for Limit. L„ stands for the limit of no reaction, and L + the limit of acute death. ^For the details for carrying out these tests the reader is referred to the Hygienic Laboratory Bulletin No. 21 upon ' ' The Immunity Unit for Standard- izing Diphtheria Antitoxin," by M. J. Eosenau, which contains the official description and details of the process and its theoretical considerations. STANDAEDIZATIOjST op antitoxic SEEA 381 than 100 minimal lethal doses of a standard toxine for a 350-gram guinea pig. That is, 0.1 of a unit mixed with 100 minimal lethal doses of the standard toxine contains just enough free poison in the mixture to kill the guinea pig in four days after subcutaneous injection. The official definition of a tetanus antitoxic unit is the following: The immunity unit for measuring the strength of tetanus antitoxin shall be ten times the least quantity of antitetanic serum necessary to save the life of a 350-gram guinea pig for 96 hours against the official dose of a standard toxine furnished by the Hygienic Laboratory of the Public Health and Marine Hospital Service. The standardization of tetanus antitoxin does not diiler radically from the standardization of diphtheria antitoxin. The toxins and an- titoxins are mixed and the mixture injected into guinea pigs. While, however, the unit is based upon the neutralizing value of an arbitrary quantity of antitoxic serum, the antitoxin is not issued for a basis of comparison, as in the case of diphtheria. A stable precipitated toxine, the test dose of which has been carefully determined, is issued to other laboratories for the purpose of testing. The value of an unknown serum is measured directly from this standard precipitated toxine, the L i , or test dose, of which is stated. The L^., or test dose, of the particular toxin now dispensed by the gov- ernment contains just 100 minimal lethal doses for a 350-gram guinea pig. This particular toxine is very stable and has not changed ap- preciably in two years. As soon as it alters or is exhausted the next toxine that will be issued may contain more or less than 100 minimal lethal doses, but the test dose will contain precisely the same neutral- izing power. The tetanus antitoxic unit may be better understood from an ex- ample of a test. An Example of a Test. — Carefully tare a weighing bottle, then add approximately 20 to 50 mg. of the dried poison. Again carefully weigh. Dissolve the toxine in the weighing bottle with salt solution (0.85) in the proportion of 0.1 gram of the dried poison to 166.66 c. c. of the salt solution. This proportion is used for the reason that each cubic centimeter of this solution will represent 0.000,6 gm. of the orig- inal dried poison (=100 MLD's). This proportion is taken because it is very convenient in measuring out the test dose, which represents 1 c. c. of the solution. Thus : 44.5692 gm., bottle + toxine. 44.5300 gm., bottle. .0392 gm., toxine. 0.1 gm. : 166.66 e. c. : : 0.0392 : x. X = 65.33 e. c. 382 IMMUNITY In other words, if the quantity of toxine placed in the weighing bottle should weigh, as in this instance, just 0.0392 gm., carefully deliver from an accurately graduated burette just 65.33 c. c. salt solu- tion into the weighing bottle; and, as before stated, each cubic centi- meter of this solution will be the L , or test dose. ISTow dissolve the serum of unknown value in accordance with the table of dilutions, and mix aliquot parts of the serum with the test dose of toxine, as follows: No. of Weight of guinea pig (grams) Subcutaneous injection of a mixture of — Time of death Toxine (test dosej Antitoxin 1 350 350 350 350 350 Gram. 0.0006 .0006 .0006 .0006 .0006 C. C. 0.001 .0015 .002 .0025 .003 2 days, 4 hours. 4 days, 1 hour. Symptoms. Slight symptoms. No symptoms. 2 3 4 5 According to this series the guinea pig which received the mixture containing 0.0015 c. c. of the serum died in four days and one hour. Therefore, 0.0015 c. c. of the serum contains one-tenth of an immunity unit, as the unit has been defined as ten times the least amount of anti- tetanic serum necessary to save the life of a 350-gram guinea pig 96 hours against the official. test dose. This serum would, therefore, contain just 66 units per c. c. Methods. — In order to obtain reliable and comparable results, it is necessary to take into account all the factors concerned — the composition of the poisons, their concentration, the diluting fluid, length of time the mixtures are allowed to stand, the site of inoculation, etc. ESTABLISHMENTS LICENSED FOR THE PROPAGATION AND SALE OE VIRUSES, SERUMS^ TOXINS, AND ANALOGOUS PRODUCTS. The following table contains a list of the establishments holding on July 1, 1911, licenses issued by the Treasury Department in accordance with the act of Congress approved July 1, 1902, entitled "An act to regu- late the sale of viruses, serums, toxins, and analogous products in the Dis- trict of Columbia, to regulate interstate traflftc in said articles, and for other purposes." The number of the license of each firm is also given, together with the names of the several products for which licenses have been granted. STANDAEDIZATION OP ANTITOXIC SERA 383 No. of license Establishments Products 5 8 9 11 12 14 15 16 17 18 19 21 22 23 Parke Davis & Co., Detroit, Mich. H. K. Mulford Co., Phila- delphia, Pa. Dr. H. M. Alexander & Co., Marietta, Pa. Fluid Vaccine Co., Milwaukee, Wis. The Cutter Laboratory, Berkeley, Cal. Frederick Stearns & Co., De- troit, Mich. Pasteur Institute of Paris, Paris, France. Chemische Fabrik auf Actien, Berlin, Germany. Health Department of the City of New York . Dr. W. R. Hubbert Serum La- boratory, Detroit, Mich. National Vaccine and Anti- toxin Institute, Washington, D. C. Lederle Antitoxin Labora- tories, New York City. Burroughs, Wellcome & Co., London, England. Memorial Institute for Infec- tious Diseases, Chicago, 111. Swiss Serum and Vaccine In- stitute, Berne, Switzerland. Institut Bacteriologique Lyon, Lyons, France. Bacterio-Therapeutic Labora- tory, Asheville, N. C. Diphtheria antitoxin, antigonococcic serum, antistreptococcic serum, antite- tanic serum, antitubercle serum, bac- terial vaccines, erysipelas and prodigio- sus toxines (Coley), tubercuUns, and vaccine virus. Diphtheria antitoxin, antidysenteric serum, antigonococcic serum, antimeningococcic serum, antipneumonie serum, antistrep- tococcic serum, antitetanic serum, tuber- culins, vaccine virus, bacterial vaccines, normal horse serum, and rabies virus. Diphtheria antitoxin, antirabic virus, tu- berculins,, vaccine virus, and normal horse serum. Vaccine virus. Diphtheria antitoxin, antistreptococcic serum, tuberculins, bacterial vaccines, and vaccine virus. Diphtheria antitoxin, streptolytic serum, and pneumolytic serum. Diphtheria antitoxin, antidysenteric serum, antimeningococcic serum, antiplague serum, antistreptococcic serum, serum antivenimeux, antitetanic serum, and antiplague vaccine. Diphtheria antitoxin and antistreptococcic serum. Diphtheria antitoxin, antitetanic serum, antirabic virus, vaccine virus, tubercu- lin, and antimeningococcic serum. Diphtheria antitoxin. Diphtheria antitoxin, antigonococcic vac- cine, vaccine virus, normal horse serum, antistaphylococcic vaccine and antistrep- tococcic vaccine. Diphtheria antitoxin, antistreptococcic serum, antitetanic serum, suspension of lactic acid bacilli, vaccine virus, and anti- typhoid vaccine. Diphtheria antitoxin, antigonococcic se- rum, antidysenteric serum, anticolon ba- cillus serum, antistaphylococcic serum, antistreptococcic serum, antityphoid ' serum, tuberculins, and bacterial vac- cines. Diphtheria antitoxin. Diphtheria antitoxin, antidysenteric serum, antimeningococcic serum, antipneumonie serum, antiplague serum, antistrepto- coccic serum, tuberculins, anticholera vaccine, antiplague vaccine, antityphoid vaccine, and antitetanic serum. Antidiphtheric serum and normal goat serum. TubercuUns. 384 IMMUNITY No. of license Establishments. Products 24 Parbwerke, vormals Meister Diphtheria antitoxin, antidysenteric se- Lucius und Brtining, rum, antimeningococcic serum, antipneu- Hoechst-on-Main, Germany. monic serum, antistreptococcic serum, antitetanic serum, and tuberculins. 25 TuberouUn Society of St. Pe- tersburg, St. Petersburg, Russia. TubercuUnum purum. 27 Institut Pasteur de Lille, Lille, France. Serum antivenimeux. 28 Bacteriologisches Institut Lingner, Dresden, Germany. Pyocyanase. 29 The Behringwerk, Marburg, Germany. Antitetanic serum and tuberculin. 30 Dr. G. H. Sherman, Detroit, Mich. Bacterial vaccines. 31 E. Merck, Darmstadt, Ger- Antidiphtheric serum, antimeningococcie many. serum, antipnevmaonic serum, antistrep- tococcic serum, normal horse serum (dried), and normal horse serum. 32 Kalle & Co., Biebrich, Germany. American Biologic Co., Kansas City, Mo. The Beraneok Laboratory, Tuberculin (Rosenbach). 33 Antirabic virus. 34 Tuberculin (Beraneck). Neuchatel, Switzerland. 35 Dr. Carl Spengler, Da-vos- Platz, Switzerland. I. K. immune blood. PHAGOCYTOSIS Metchnikoff gave us the first physical explanation of immunity, through his brilliant studies upon phagocytosis. Metchnikoff is a biol- ogist, and as a result of his stimulating observations upon the phago- cytes in all the orders of the animal kingdom he has contributed much to our knowledge, not alone of immunity, but to our fundamental knowl- edge of nutrition and inflammation. The ingenuity and fertility of his views caused a flood of work from others upon these basic subjects in medical biology. Phagocytosis is a process common to all cells having amebic mo- tion. A phagocyte is any cell capable of absorbing particulate matter into its substance. The process is best seen with an ameba under the microscope. For a clear understanding of phagocytosis it is necessary to con- sider three phases of the process: (1) the approach, (2) the engulf- ment, and (3) the digestion. The approach or chemotaxis is a phenomenon which is displayed by almost all motile and unicellular organisms, whether animal or vegetable, as well as by the leukocytes. It manifests itself by a move- ment of the unicellular organism or the phagocytic cell toward the PHAGOCYTOSIS 385 particle and seems to be a response to a chemical stimulus. Chemo- taxis is said to be positive when the leukocytes are quickly and ener- getically attracted to a substance, and negative when this attraction is lacking. There is considerable doubt whether there is true negative chemotaxis in the sense of repulsion. The degree of chemotaxis pos- sessed by any substance may readily be determined by placing it in a capillary tube closed at one end and then inserting the open end of the tube into the tissue of an animal or into a fluid containing active phagocytes. If the substance has positive chemotactic power- the phago- cytes soon approach the free end of the capillary tube, which they en- ter; if the substance has negative chemotactic power the phagocytes are not attracted and do not enter the capillary tube. As Emery points out, the leukocytes are in many cases attracted into an infected area to their own undoing, and it must not be forgotten that "even in in- flammatory processes which are mild in nature and favorable in result the number of leukocytes which may be killed in the conflict is enor- mous. The leukocytes are not independent protozoa inhabiting the blood and tissues, but an integral part of the organism. It is to the advantage of the latter that the former should be attracted at once to the seat of invasion, and hence the processes of evolution have led to the development of this function in the nomadic cells of the body. These are extraordinarily susceptible to chemotactic influences. They seem to be attracted by any deviation from the normal situation of the tissues and fluids^ — a slight injury, a hemorrhage, the presence of a poison, or a foreign body of any sort, or any dead or useless tissue — and the leukocytes are immediately attracted into the area affected. The more we regard the process the more we must regard it as one of the most exquisite examples of means to ends met with in the ani- mal economy." The engulfment of the bacteria may readily be studied in amebse in their free living stage. The protoplasm of the ameba is thrown out in the form of pseudopodia; these encircle the particle, which soon appears within the substance of the ameba. The engulfment of particles by the leukocytes and other cells is precisely the same. The digestion within the cell is entirely comparable to gastric di- gestion in higher animals. It is now known that active proteolytic ferments dissolve the albuminous particles, and that this takes place in an acid medium may be demonstrated by the use of delicate indicators, such as neutral red. The phagocytes may take up and digest either live or dead bacteria; they are not simply scavengers. They engulf particles of all kinds, both organic and inorganic. Thus, in anthracosis the particles of coal are mainly carried and contained in the phagocytic cells. The phago- cytes play a similar role with the malarial pigment, with the granules 386 IMMUNITY of pigment left after a hemorrhage, and with other foreign particles in the body. Phagocytes are also enabled to absorb colloidal substances and fluids as well as particulate matter. They are enabled to dispose of comparatively large masses by removing it piecemeal. Thus, the "core" of boils is gradually removed mainly by the phagocytes. Cat- gut and silk ligatures are similarly removed and the absorption of the tadpole's tail is disposed of through the same process. MetchnikofE divides the phagocytes into free and fixed, macrophages and microphages. The free phagocytes are the leukocytes, lymphocytes, and other blood cells, as the myelocytes from the bone marrow. The fixed phagocytes are the connective tissue cells and endothelial cells. The free phago- cytes, according to Metchnikoff, play the more important role. The microphages or microcytes are the mononuclear leukocytes, the polymorphonuclear leukocytes, and the wandering connective tissue cells. The macrophages or macrocytes are the large lymphocytes, the mononu- clear pulp cells of the spleen and bone marrow, endothelial cells of the large vessels, and Kupfer^s stellate cells of the liver. The micro- phages play an active part in all acute infections. They are the first to come in the field and for the most part are vegetarians, that is, they take up bacteria especially. The macrophages, on the other hand, are carnivorous, engulfing other cells and protozoon parasites, and are es- pecially concerned in chronic inflammations, such as tuberculosis and leprosy, rather than in the acute processes. These distinctions between the free and fixed phagocytes, the microphages and macrophages, are entirely arbitrary. All the leukocytes have the power of phagocytosis, though in varying degree. This is readily seen in an opsonic prepara- tion or in an examination of a smear of gonorrheal pus, when some of the polymorphonuclear leukocytes will be loaded with the cocci while others contain few or none. The small phagocytes (microcytes) are able to engulf protozoa and animal cells as well as bacteria. Metchnikoff has insisted since the beginning of his studies upon phagocytosis that this process plays an important, if not the sole, role in immunity. He conceives that a true battle takes place between the cells and the invading germs. When phagocytosis is active and suc- cessful, immunity is the result. If phagocytosis is absent, or the phago- cytes are unsuccessful, the result is susceptibility instead of immunity. Metchnikoff first studied the protective power of the phagocytes in a fresh water crustacean, the daphnia, which, from its transparency and small size, is a very suitable creature for observation. He found that the daphnia is subject to a disease due to the invasion of its body cavity by the spores of a yeast (Monospora), and that if these spores gain access in large numbers they multiply, form into mature or- ganisms, and finally kill their host. When, however, a few spores gain PHAGOCYTOSIS 387 access he found the leukocytes of the daphnia approach them, form a wall around them, and finally digest and destroy them. It is obvious, therefore, that the immunity of the daphnia to this infection depends upon the activity of its leukocytes. Analogous instances are found in many other animals, including man. In the streptococcus infections particularly MetchnikofE believes their virulence depended upon the absence of phagocytic action. It soon became evident to Metchnikoff himself that the mechanism of immunity was a much more complicated process than could be ac- counted for simply by the number and physical activity of the phago- cytes. The simple act of phagocytosis alone could not explain all the phenomena. It, therefore, became necessary to study the processes of digestion and the products of excretion of the phagocytes. It soon be- came evident that the digestive power of the phagocytes is a very pow- erful one, and substances usually deemed entirely insoluble may be gradually removed by their action. Metchnikoff considers two of these substances to be concerned in immunity : the microcytase and the macro- cytase. The microcytase is a ferment-like substance obtained from the microcytes. It is thermolabile and corresponds in all essential respects to the alexin of Buchner or the complement of Ehrlich. The macrocytase is a thermostable substance obtained from the macrocytes. It is concerned with specific acquired immunity. The macroeyte fastens itself to the bacteria, hence was called by Metchni- koff the fixator. It is similar in all essential respects to the "sub- stance sensibilitrice" of Bordet, or the amboceptor of Ehrlich. Buchner, as well as most other unprejudiced students in immunol- ogy, takes the middle ground between tlie doctrines of the cellular theory represented by Metchnikoff and his school and the doctrines of the humoral theory represented by Ehrlich. It now seems quite evident that both the cells and the body fluids play an important role in the mechanism of immunity. It is also equally evident that the mechanism of immunity differs widely with different infections; in some phagocytosis plays a dominant part; in others it seems that the fluids of the body are chiefly concerned. It must not be forgotten that even where the fluids of the body are the chief actors the antibodies are probably in all cases derived from the cells. Just what cells — whether the fixed tissue cells or the free phagocytes — are chiefly con- cerned in the production of these antibodies is not quite clear. All observers are agreed upon one thought, and that is, fundamen- tally immunity is closely allied to the processes of cell nutrition. The receptors of Ehrlich are the mouths of the cells for food. The phago- cytosis of Metchnikoff is primarily a mechanism by which cells pos- sessing amebic motion obtain their food. Anaphylaxis, which offers 388 IMMUNITY another explanation of immunity to certain infections, deals with the fundamental problems of protein metabolism. It is, therefore, plain that any experimental research that gives a deeper insight into protein metabolism as well as the more direct researches in immunology has a fundamental bearing upon the prevention and cure of disease. OPSONINS The name opsonin (opsone: I eater for, I prepare) is given to sub- stances which occur in the blood and which have the power of prepar- ing bacteria and other cells for ingestion by the leukocytes. The op- sonins combine with the bacteria and in that way prepare them for being taken up more easily by the phagocytic cells. In the absence of opsonins, phagocytosis does not take place, and their great importance is, therefore, at once manifest. There is now no doubt concerning the existence of these substances, and the brilliant work of Wright has stimulated a flood of researches which have thrown much light upon this chapter in immunology. The opsonins are normally present in the blood or may be increased or diminished in amount by the injection of bacteria or appropriate antigen. The opsonins are specific, that is, the blood serum may contain opsonins which prepare staphylococci for the phagocytes, but may contain no suitable substance to prepare streptococci, tubercle bacilli, or some other microorganism. The opsonins are probably sim- ilar to the bacteriotropins ; their chemical nature, however, in common with other antibodies, is not understood. The Opsonic Index. — Sir Almroth Wright has modified Leishmann's method for measifring the opsonic power of the blood serum, but the method is somewhat complicated and gives variable results even in the hands of trained workers. It may be questioned whether any of the tests now in use are a true index of the amount of opsonins in the serum, although they may be taken to indicate roughly the measure of their activity. The opsonic index has been especially used as a guide to vaccine therapy rather than in preventive medicine. If, however, we had a satisfactory and ready method by which the specific opsonins of the blood could be measured so that deficiencies could be readily determined and strengthened, we would theoretically at least have a valuable addition to prophylaxis. LYSINS Lysins are substances that have the power of disintegrating or dis- solving cells or other organized structures. Those that dissolve bac- teria are known as the bacteriolysins, those that dissolve red blood LYSINS 389 cells are called hemolysins, those that dissolve epithelial or other body cells are called cytolysins or cytotoxins. The lysins in themselves are not poisonous, but through their action they liberate or generate toxic substances and thus play an important role not only in the pathogenesis of many infectious diseases and diseased states, but also in their cure and prevention. Normally the blood possesses bactericidal properties, and it is be- lieved that this is almost entirely due to its power of dissolving the bacterial cells. The bacteriolytic property of normal blood serum is not specific, whereas the bacteriolysins induced through special proc- esses by immunization are strictly specific. The fact that the blood has the power of resisting decomposition longer than other animal fluids was known to Hunter before the era of bacteriology. It was also early known that this property of the blood diminishes spontaneously after it was shed and could be destroyed by heat — about 55° C. The bac- teriolytic substances in the blood were first studied by Buchner and Kuttall, who called them alexins. When it was discovered that the blood possesses marked powers of destroying bacteria the conclusion was naturally drawn that herein lies the explanation of immunity. It was soon learned, however, that, though the blood of certain animals may possess marked bactericidal properties, nevertheless they are very susceptible; and, further, that the power to kill bacteria is much more marked in the serum than in the circulating blood in the animal. Thus, according to Lubarsch, 16,000 virulent bacilli will kill a rabbit if in- jected intravenously; that is, the blood within the body has not the power of killing this number, yet 1 c. c. of fresh blood serum will destroy this number or more in a test tube. Eabbits are very susceptible to anthrax, although the blood serum of these animals possesses marked bactericidal properties for the an- thrax bacillus; on the other hand, the dog is very resistant to anthrax, despite the fact that its blood serum is very slightly bactericidal. The bacteriolysins were discovered by Eichard PfeifEer ^ in his at- tempt to actively immunize animals against cholera by the injection of live cultures. He observed that the cholera organisms were disin- tegrated anJ dissolved in the peritoneal cavity of the immunized ani- mals. This gave rise to what is now known as Pfeiffer's phenomenon, which, on account of its importance, must be considered. Pfeiffer's Phenomenon. — Guinea pigs are immunized by the subcu- taneous injection of increasing doses of a cholera culture about once a week until they are able to withstand large amounts of a fresh viru- lent strain. This usually required at least three or four injections. Some of the live microorganisms are now injected into the peritoneal cavity of the immunized animal, and from time to time minute drops ^Zeit. f. Eyg., Vol. XVIII, and Deutsche med. Wochen., 1896, pp. 97, 119. 27 390 IMMUNITY of this injected material with the peritoneal exudate are withdrawn by means of capillary tubes and examined under- the microscope. It will be found that the bacteria previously actively motile soon lose their power of motion and die. They then become somewhat swollen and agglutinate into balls or clumps, which gradually become paler and paler. The disintegrating bacterial cells become granular and finally are completely dissolved in the peritoneal fluid. This process usually takes about twenty minutes, provided the animal has been sufficiently highly immunized. For a control a like quantity of the cholera cul- ture is injected into the peritoneal cavity of a normal guinea pig. In this case the microorganisms are not immobilized, agglutinated, or dissolved. Further, the immunized animal remains unaffected while the control animal dies as a result of the infection. This reaction is specific, that is, a guinea pig immunized against cholera will immobilize, agglutinate, and dissolve only the cholera vibrios; a guinea pig immu- nized with typhoid will act upon typhoid and not upon cholera. It was soon discovered by Bordet that this reaction takes place not only in the peritoneal cavity of the immunized animal, but will occur in the test tube when the peritoneal exudate or the blood serum of the immunized animal is mixed with the cholera organisms. It was through a study of this reaction that Pfeiffer and Kolle and later Gru- ber and then Widal discovered and described the ability of blood serum to clump or agglutinate bacteria. It seems evident that this power of the blood serum or the peritoneal exudate of the immunized guinea pig is an important factor in the mechanism of its immunity. Bacteriolysins are absolutely distinct from antitoxins and agglutinins. Even when these three substances coexist they may be distinguished one from the other through physical, chemical, or biological tests. Nothing is known as to their chemical composition. Any general statement concerning the thermal death point or other characters of the lysins must be misleading, from the fact that we now know that lytic action is always due to a combination of two substances : one stable, the other unstable; one readily destroyed by heat, the other quite resistant to heat. This important observation was made by Bor- det, who was the first to show that two substances are necessary for the phenomenon of bacteriolysis. He considered that one of these sub- stances sensitized the bacteria, and, therefore, called it the "substance sensibilitrice" ; this substance is thermolabile. The other substance, which is thermostable, he continued to call alexin. Bordet found that all the essential features of bacteriolysis could be reproduced exactly if red blood corpuscles were substituted for the bacteria. It was this analogy between bacteriolysis and hemolysis that led Ehrlich to an in- vestigation of the latter phenomenon, and his researches led to much. LYSINS 391 new light upon the subject. Ehrlich introduced new names for the substances which Bordet has shown to be necessary for the phenomenon, and applied his side-chain theory to explain the reaction. Many names have been given to the two substances which take part in lysis. The thermostable substance has been called substance sen- sibilitrice, or simply sensibilitrice, immune body, amboceptor, fixator, intermediary body, interbody, philocytase, immunisin, desmon, copula, and preparatory while the thermolabile substance has been called the alexin, complement, addiment, and cytase. We shall speak of the first as the immune body and the second as the complement. One of the remarkable facts connected with the phenomenon of the lytic poisons is that the poison itself (complement) is normally pres- ent in the blood. This substance is a fragile body, readily destroyed at a moderate temperature— 55° C. It disappears spontaneously from the serum when kept for a few days ; it is destroyed by acids and al- kalies and is not specific in its action. Complement appears to be formed by the breaking down of the leukocytes, which accounts for the fact that blood serum -after clotting is much more potent than the whole blood; further, complement is absent from fluids containing no leuko- cytes, such as the aqueous humor. According to Ehrlich, the immune body has two combining affini- ties, and, therefore, he called it the amboceptor. It unites on the one hand with the complement and on the other with the receptor of the cell. Bordet, however, considers that the cell unites directly but separ- ately with both the complement and the immune body. The immune body is stable and specific ; it is more stable than the agglutinins or even the antitoxins. It is not injured by heating to 60° C, it is weakened at 70° C, and finally destroyed by prolonged exposure at this temperature. It is called the immune body because, according to Ehrlich's views, im- munity can only be obtained through it on account of its specific re- action. In bacteriolytic immunity it is the immune body rather than the complement that is increased. Just what service the lysins are in the mechanism of immunity is not clear. Eecent studies indicate that they may at times be harm- ful as well as useful. Thus, by dissolving the bacterial cell they have the power of releasing "endotoxins." The studies upon anaphylaxis have thrown much collateral light upon the probable action of the bacteriolysins in the pathogenesis, cure, and prevention of disease. When the bacteria are dissolved within the body the protein matter which they contain is set free. This may not be poisonous in itself, that is, may not have any of the properties ordinarily attributed to the endotoxins. This foreign bacterial protein, however, may sensitize the organism so that the second time the pro- 392 IMMUNITY tein is liberated it may cause a reaction which may account for some of the pathogenic effects and symptoms of the disease. Buxton and Coleman explain the pathogenesis of typhoid fever as largely due to a solution of the typhoid bacilli within the body, and it is probable that in pneumonia and other infections a like action takes place. An organism that has once reacted to a particular bacterium remains immune so long as it possesses an altered power of reaction, when brought in association with the microorganism in question. Immunity in this sense is an example of allergic and is discussed more in detail under anaphylaxis. HEMOLYSIS The hemolysins are substances that lake the blood; that is, they dissolve the hemoglobin from the red blood corpuscle and set it free in solution. A certain part of the stroma of the red corpuscle is also destroyed in complete hemolysis. Some of the hemolysins are specific and others are not. Thus, distilled water will dissolve the hemoglobin from the red corpuscles of almost all animals. Other known non- specific hemolytic substances are various alkalies and acids; plant poisons, such as recin and abrin; bacterial poisons, such as tetanolysin and staphylolysin ; and animal poisons, such as snake venom, scorpion venom, etc. The specific hemolysins are obtained by treating (i. e., immunizing) one animal species with the blood corpuscles of another. For example, the blood corpuscles of a guinea pig are injected into a rabbit. After several such injections the blood serum of the rabbit will contain hemolytic substances for the guinea pig's corpuscles. The corpuscles used for immunization are obtained by drawing the blood of the animal into isotonic salt solution (0.85 per cent.) containing about 1 per cent, of sodium citrate, which prevents coagulation. The eitrated blood is then centrifugalized, the supernatant fluid drawn oS and replaced with isotonic salt solution. This process is repeated three or four times and is known as washing the corpuscles. The ob- ject is to remove all trace of serum containing complement and other substances. If this is not done the results will be unnecessarily com- plicated and misleading. The washed corpuscles are injected into the peritoneal cavity about once a week or ten days until the blood contains the desired hemolytic action. When this point is reached can only be determined by withdrawing small quantities of the blood and testing it. Hemolytic tests are made by adding together the complement and the immune bodies. The corpuscles are obtained as above described, washed three or four times, and suspended in isotonic salt solution, so that they are present in the proportion of about 5 to 10 per cent, by volume of the salt solution. One c. c. of this suspension is placed in a CYTOTOXICS 393 small test tube. To this is then added the immune body contained in the serum of the animal that had been injected with the corpuscles. This immune serum is iirst heated to 55° or 56° C. for one hour in order to destroy the complement. This degree of heat does not injure the immune body. Uniform amounts of the complement are obtained by adding a definite quantity (0.2 of a c. c.) of fresh serum to each test tube. Each test tube then contains a uniform quantity of the corpuscles to be tested, a uniform quantity of complement in the fresh serum, and a variable quantity of heated immune serum containing the immune body. In most cases normal saline solution is added to bring the whole up to a definite volume — say 5 c. c. These mixtures are now incubated at 37° C. for two hours, being stirred or shaken once or twice in the meantime. The test tubes are now removed and placed in a vertical position in the ice chest from 12 to 24 hours and then examined. If no hemolysis has taken place the supernatant fluid will be untinged and the corpuscles will have settled in a distinct layer at the bottom. If there is complete hemol- ysis the fluid will be deeply and uniformly colored and there will be no sediment or only a minute deposit of stromata. If the reaction is partial, the fluid will be less deeply colored and there will be more or less of a deposit of undissolved corpuscles. It must be remembered that many bacteria produce hemolysis and that, if the mixtures of cor- puscles and sera be incubated for long periods, fallacies may arise from such contaminations. CYTOTOXINS If instead of red blood cells an animal is treated with the body cells or glandular cells of another species, it develops the power to dissolve the cells in question. This power is contained in the blood serum and is brought about by substances known as cytotoxins, which are entirely similar to the bacteriolysins, the hemolysins, and other lytic substances. Cytotoxins have been obtained with the spleen (leu- kocidin), with the sperm (spermo toxin), liver cells (hepatotoxin), kid- ney cells (nephrotoxin), gastric mucosa (gastrotoxin), placental tis- sue (syncytiolysin or placentolysin), prostatic tissue (prostatolysin), brain (neurotoxin), and other organs and tissues. When the cyto- toxins were discovered they aroused great enthusiasm in the hope that it would now be possible to dissolve and destroy such foreign cells as cancer and other tumors, and pathological processes in which it is de- sirable to get rid of certain cellular elements. The practical results have been exceedingly disappointing, as further investigations have shown that these cytotoxins are exceedingly weak and, further, are not very specific. 394 IMMUNITY THE BORDET-GENGOU PHENOMENON— FIXATION OF COMPLEMENT Bordet and Gengou ^ found that bacteria and also red blood cells could be "sensitized" by placing them in heated immune serum. The immune serum is heated to 55° or 56° C. in order to destroy the com- plement, leaving only the thermostable "substance sensibilitrice" which unites with the bacteria or the red blood cells, and thus prepares or sensitizes them to the action of the complement. If, now, these sen- sitized bacteria or red corpuscles are added to fresh serum, all the com- plement contained in the fresh serum is removed or fixed so that the fluid will no longer dissolve bacteria or cells. These facts are of very great importance, and upon them are based the Wassermann reaction for syphilis and other practical applications in immunology. The Wasserinann reaction for syphilis is a special method of ap- plication of the Bordet-Gengou phenomenon. The antigen is a watery extract of the syphilitic liver of a case of hereditary syphilis which contains the Treponema pallidum in great numbers; usually about 0.1 to 0.2 c. c. of the liver extract is used. Lecithin and other fatty-like bodies may also act as antigen. The complement is obtained from some fresh guinea pig serum; about 0.2 c. c. is used. The antibody is usually the unknown quantity, that is, the blood serum of the patient to be tested. This serum is heated to 55° C. to destroy the complement and then diluted in the proportion of 1 to 20 or 1 to 40 with normal saline solution, and 1 c. c. of the dilution is used. The amount must be determined by preliminary tests with known syphilitic serum. The antigen, the unknown serum, and the complement are then mixed in proper proportions in a test tube and incubated at 37° C. for one hour, at the end of which time all the complement will be removed from the fluid if syphilitic antigen is present in the unknown serum that has been used. The hemolytic system is then added to the mixture. The hemolytic system usually consists of sheep's corpuscles sensitized with the heated blood serum of a rabbit which has been injected with sheep's corpuscles. These corpuscles then only need the addition of complement to pro- duce hemolysis. The corpuscles are washed and suspended in normal salt solution, to which the heated immune serum (serum of rabbit which has been treated with sheep's corpuscles) is added. ^Bordet: Anti. de I'Inst. Pasteur, Vol. XIV, 1900, p. 257: Vol XV 1901 D 289. ■ • ' ' ^' Gengou: Ann. de I'Inst. Pasteur, Vol. XVI, 1902, p. 734. Bordet and Gengou: Compte rendu. Acad., Vol. CXXXVl'l, p. 351. DEVIATION OF COMPLEMENT 395 The whole mixture containing the antigen, the antibody, the com- plemept, and the hemolytic system is incubated at 37° G. for two hours, occasionally shaking and stirring the mixture, and is then placed in the ice chest and the result read after 12 to 24 hours. A positive reaction, showing the presence of syphilitic antibody, is determined by the absence of hemolysis. The presence of ' hemolysis indicates the absence of the specific antibody. Control tests are always necessary, especially to determine that the corpuscles will be completely dissolved by the heated immune serum (antibody) and the guinea pig serum (complement) if the other two ingredients are not added, and there should be no hemolysis if all the substances except the fresh guinea pig serum are used. The reaction of fixation based upon the work of Bordet and Gen- gou has many useful practical applications in addition to the Wasser- mann reaction for the diagnosis of syphilis. If either the antigen or the antibody are unknown, their presence may be determined through the reaction of fixation, because it is strictly specific. The problem is something like the theorem in geometry with the triangle; two sides and an angle of a triangle being known, the other side and angles may be determined. The antigen is any substance which, when injected into a suitable animal, has the power of generating as antibody. Practically all patho- genic bacteria and pathogenic protozoa act as antigens ; many albuminous bodies, such as the venoms, the enzymes, and bland proteins, may also act as antigens. As the reaction is specific, it is possible to determine whether a particular microorganism is the true cause of a disease or not. Thus, Bordet was enabled to satisfy himself that the bacillus which he isolated during the early stages of whooping-cough was the true cause of that disease, as it gave the reaction of fixation with a specific antibody. On the other hand, if the antigen is known, the diagnosis may be made through the reaction of fixation, as in the case of syphilis and the Wassermann reaction. THE NEISSER-WECHSBERG PHENOMENON OR DEVIATION OP THE COMPLEMENT Neisser and Wechsberg in 1901 ^ found that, although the addition of a small amount of immune serum renders normal serum more bac- tericidal or increases its power of protection, a greater addition robs it of most, and sometimes of all, of its bactericidal power. In other words, the solvent effect of the immune body on cells or bacteria in the presence of ' complement diminishes as an excess of the immune ^ Miinch. med. Wochenschr., 1901, No. 1§, 396 IMMUNITY body is added. This particular action is explained by Neisser and Wechsberg as due to a locking up (ablenkung) or deviation of the com- plement which is brought about by an excess of the immune body. The phenomenon is better understood from a study of an example given by Neisser: (1) Bacteria+10 units immune serum (i. e., heated immune serum containing the immune body but not complement) + complement (i. e., fresh serum) =no destruction of the bacteria. (2) Bacteria-|-5 units immune serum -(-complement^complete de- struction. (3) Bacteria-f-1 unit immune seruni-|-complement^no destruction. In (3) the destruction of the bacteria is not complete, because there is not enough immune body to sensitize the bacteria to the action of the complement, or, in the terms of Ehrlich, not enough ambocep- tor to unite the complement to the bacterial cell. In (2) the proper proportions of immune body and complement occur and the lytic action is complete. In (3) there is an excess of immune body which, therefore, com- bines with and deviates the complement and thus renders it power- less to unite with the bacterial cell, and thereby the lytic action is prevented. The action, therefore, while speciiic, is strictly quantitative, depend- ing upon the amount, especially of immune serum, present in the mix- ture; that is, though immune sera protect against specific infection, they do so only in certain doses. It is easy to understand how too small an amount of immune serum will fail to protect, but difficult to understand why a large amount should fail; in other words, why an excessive amount of bacteriolytic serum should cause the bacteria to be protected rather than be destroyed. ISOHEMOLYSINS Isoliemolysins have the property of destroying the red blood cells of the same species. They occur naturally in certain animals, prin- cipally in the horse and in man. They may also be produced experi- mentally in certain animals, as in goats, by the injection of the blood of other goats. There is further the possibility that autohemolysins may be produced which destroy the blood cells of the individual him- self. These have not been produced artificially, but are said to occur in paroxysms of hemoglobinuria. PRECIPITINS Another class of immune bodies known as the precipitins may read- ily be produced in the blood serum of animals by the injection of bac- PRECIPITINS 397 teria or albuminous substances. The precipitating action of immune sera was discovered by E. Kraus in 1897. When the clear antiserum is added to the clear antigen in solution, the mixture of the two fluids becomes opalescent, then opaque from the formation of a precipitate, and after a time this settles to the bottom of the test tube, leaving a clear supernatant fluid. The precipitate consists of an insoluble com- bination of two substances, one of which is present in the antiserum, the other in the antigen. This insoluble precipitate is known as the precipitum. The substance in the antigen is known as the precipitable substance or precipitinogen^ and the substance in the antiserum is called the precipitin. Precipitums are doubtless formed both within and with- out the body when proper conditions of antibody and antigen are pres- ent," without, however, always causing a visible precipitum. The precipitins are quite analogous to the agglutinins, and from the standpoint of physical chemistry are often classified with them. It is now known that proteids do not form true solutions, but molecular or colloidal suspensions. The effect of the addition of a precipitin is to cause the agglutination of these molecules in a manner entirely analogous to the agglutination of bacilli. According to Emery, the laws which govern the action of the precipitins and agglutinins are entirely similar, and theoretically it would probably be more accurate to consider them under one head. The practical applications of the two classes of anti- bodies are, however, very different, and it is more convenient to treat them as separate substances. The bacterial precipitins were those first discovered. Kraus added some typhoid serum to a filtered culture of typhoid bacilli and obtained a precipitate when the two clear solutions were brought together. The same happens with cultures of cholera, plague, and other bacteria. Certain bacteria, however, do not produce a precipitable substance. This is notably the case with diphtheria. Thus, when diphtheria antitoxin is added to diphtheria toxin, no visible reaction takes place. In this case the diphtheria antitoxin should contain the antibody or precipi- tinogen. The filtered broth culture is the antigen and should contain the precipitin; however, one or both of these substances must be -absent, as a precipitum is not formed when they are brought to- gether. Tsistowitch in 1899 found that precipitins may be produced by injecting albuminous substances into suitable animals. Thus, if rabbits are injected with horse serum or with eel's blood, the blood serum of the treated rabbit will precipitate the blood serum of the horse or the eel's blood respectively. This reaction is used in forensic medicine for the recognition of blood stains, which will presently be discussed. The chemical nature of the precipitins is not known. They come down with the globulins. In the terms of the side-chain theory they 398 IMMUNITY contain two groups, one a thermostable haptophore or combining group, the other, a thermolabile functioning group. Precipitins are destroyed by heat, light, moisture, and other external influences about as readily as the agglutinins. Precipitating sera should, therefore, be kept in a dry state, in a cool place, and preserved from light. A proprecipitoid zone entirely analogous to the proagglutinoid zone is observed under certain conditions. Precipitins like agglutinins act more quickly at the body temperature and require the presence of certain salts for their action. According to Friedemann, the amount of precipitum formed depends on the quantity of the salts present. The relation of precipitins to immunity is not entirely clear. There is a strong suspicion that, like all antibodies, they play some part in the mechanism of immunity in certain infections, but just what part is obscure. It is quite evident that the presence of precipitins in the blood must have valuable protective properties against the poisons of certain infections. The immunity in this case would be due to the throwing out of solution of the poison, thus rendering it insoluble and inert. ISTuttal in his "Blood Eelationship" made a very careful study of the question of specificity of the precipitins. He showed that the reaction of the precipitins, like the reaction of other similar antibodies, is relatively specific or quantitatively specific. If the antiserum is powerful enough it will react with all the bloods of animals in the same great division of the animal kingdom. Thus, a strong antihuman serum, that is, a serum obtained by injecting hu- man blood into rabbits, will give a precipitate when this rabbit serum and human serum are brought together; it will also react with apes, monkeys, etc., but not in such high dilutions, and a slight trace of precipitum appears after a long period even when mixed with the serum of more remote mammalia, but no precipitate occurs with the blood of birds, fishes, etc. A quite similar relationship holds with lac- tosera and with the precipitating sera for muscle proteids; the anti- sera for egg proteids are apparently less specific. Precipitins, then, are not specific as regards the animal species from which they are derived, but possess that partial specificity seen in the cytotoxins and in the group reaction of the agglutinins. According to Emery, they are spe- cific as regards the antibodies which bring them into existence, irre- spective of the source from which the antigen is derived. For medico- legal purposes the specificity of the reaction may be considered satis- factory, provided the tests are made quantitatively, in which case the reaction is both specific and delicate. In fact, the delicacy of the re- action is truly astonishing. Thus, Ascoli obtained an antiegg albumin serum which gave a precipitate with 1-1,000,000 dilution of egg al- bumin; and Stern an antihuman serum which reacted with serum at a PEECIPITINS 399 dilution of 1-50,000. While these are extreme figures, it is not unusual to obtain precipitates in dilutions of 1-5,000. Tests for Blood. — In carrying out the precipitin tests for the recog- nition of blood stains, as suggested by Uhlenhuth and Wassermann, it is necessary first to obtain an antiserum. This is usually gained from rab- bits, which are injected intravenously or intraperitoneally at intervals of three or four days with human serum. The human serum may readily be obtained by puncturing a vein at the bend of the elbow, or from the placenta, or from a cadaver; pleuritic or ascitic fiuid may also be used. The amount injected rises from 1 to 3 or 4 c. c. in the case of intravenous injections, or twice as much or even more into the peritoneum. The course of treatment lasts three or four months. A simpler method is to give larger doses up to 10 c. c. or more intraperitoneally at intervals of a week. The intervals should not be longer than this, for danger of complicating anaphylactic reactions. The blood may be drawn from a vein or the heart of the rabbit from time to time as needed, or the ani- mal may be chloroformed and exsanguinated through the carotid artery, or as much blood as possible may be collected from the heart. The blood to be tested is usually in the form of a clot or stains upon linen, pistols, and other surfaces. These stains are macerated with normal saline solution or with 1 per cent, sodium hydrate. In the case of very old stains Zienka recommends the use of a strong solution of potassium cyanid which is subsequently neutralized with tartaric acid. The fiuid is then examined with the microscope and tested speetroscopically to determine the presence of blood corpuscles and pigments, so as to be sure we are really dealing with blood. The solution is then filtered. In order to determine the approximate strength of the solution it is sufficient to bubble air through the fluid. A dilu- tion of blood serum in the proportion of 1-1,000 will produce a stable foam. If a stable foam is not produced it indicates that the protein material has not actually passed into solution or is too dilute to be of service in the test. Three tests are made. In the first tube one- part of the fluid under examination is mixed with two parts of the antiserum, the second contains the fluid alone, and the third antiserum plus normal saline solution. Further controls in which the antiserum is mixed with diluted serum from animals other than man may also be made. The tubes are then incubated at 37° C. and examined from time to time. A positive result is obtained if there is a precipitate in the first tube and not in the others. In case a precipitate is obtained further tests are then made with greater dilutions. With a powerful antiserum a reaction may usually be obtained in dilutions so high that evidence of the presence of.proteids is barely obtainable by ordinary chemical means. The weak point in the method is that it is never possi- ble to say exactly how much of the, protein matter of the clot has been 400 IMMUNITY dissolved, and thus it is not possible to obtain precise quantitative results. With an unknown blood serum, unaltered, and in the fluid state the test can be carried out with almost complete certainty, but this is rarely if ever possible in medicolegal cases. Another test for blood has been introduced by ISTeisser and Sachs and based on the Gengou reaction of fixation of the complement. The test is extraordinarily sensitive. ISTeisser and Sachs found that one- millionth part of a cubic centimeter of human serum is readily demon- strable. The technique is complicated, and, according to Emery, it appears, moreover, that complement may be extracted in an altogether non-specific manner by substances other than the combination of anti- gen and antibody. Another serious objection is that a similar deviation of the complement may be brought about by means of sweat, so that if the reaction were obtained in a stain on body linen it would be of little value. The precipitin reaction further finds practical application in deter- mining the nature of meat, whether fresh, as in the case of beef sus- pected to be horse flesh, or prepared, as in sausages, etc. For these tests the antiserum is prepared by injecting rabbits with meat juices or an unheated watery extract of the meat, and the test is carried out on lines similar to those described above. AGGLUTININS Agglutinins were definitely described in 1896 by Gruber and Dur- ham, and a few days later by Pfeiffer and KoUe. Shortly thereafter Widal announced the fact that the blood serum of a typhoid patient will agglutinate the typhoid bacillus in high dilutions. The phenom- enon of agglutination with special reference to typhoid fever is, there- fore, often called the Widal reaction or the Gruber reaction.^ Agglutination consists in a clumping or grouping of the bacteria into clusters, just as though they were iron filings drawn about a mag- netic point. Usually they are immobilized before they are drawn to- gether into a clump or cluster. Theobald Smith has shown that the first phenomenon, the immobilization of bacteria, may be due to a flagellar agglutinin, and that the second phenomenon, the clumping, may be due to a cellular agglutinin. The agglutination of bacteria apparently does little harm to them other than rendering them motionless, for they are not altered in ap- ^ The phenomenon of agglutination had been previously observed by Charrin and Eoger in 1899 in the case of the Bacillus pyocyaneus. It was also observed by Metchnikoff in the case of the Vibrio metchnikovi in 1891. Similar appear- ance had also been seen by Issaeff in 1893. AGGLUTININS 401 pearance, viability, or virulence. Bacteria that have been agglutinated may again multiply and grow vigorously. Agglutination is an im- portant source of error in counting the number of bacteria in any fluid. A cluster will develop into one colony and thereby give misleading re- sults. The apparent diminution in the number of bacteria in freshly drawn milk, judged by the number of colonies that develop upon agar plates and known as the germicidal property of milk, is largely a phe- nomenon of agglutination. Agglutination may occur quickly or slowly, depending upon the temperature, the dilution of the serum or fluid containing the agglu- tinin, and upon other factors; hence, it is important in reporting posi- tive or negative tests in the diagnosis of typhoid fever, malta fever, and other infections always to state the dilution, the time, the tem- perature, and other conditions under which the test was made. The interpretation of the results may depend upon these factors. Agglutination may readily be seen by the naked eye. A uniform suspension of bacteria in a test tube under the action of an agglutinin first becomes granular; the granules increase in size and flock into masses with intervening clear spaces. Then these flocculi settle to the bottom as a precipitate, leaving the supernatant fluid clear. Under the microscope the bacteria are first seen to lose their motion, then to be drawn together into irregular clumps or clusters, which increase in size. The macroscopic method is much more dependable in testing ag- glutinins than the microscopic method. The latter is subject to several sources of error, and the end point is not as sharply defined as in the macroscopic method. Agglutination, like almost all chemical processes, takes place more quickly when warm than in the cold. The reaction is best at 37° C. The clumping usually takes place more slowly with the non-motile bac- teria. Certain strains of some species of bacteria agglutinate more readily than others. Thus, the typhoid bacillus is usually agglutinated readily with its specific serum, but some strains are agglutinated with considerable difficulty; in general, when first isolated, they resist ag- glutination. This resistance or "immunity" of the microorganism usually wears ofl! after a number of subcultures. A very interesting phenomenon in agglutination which has considerable practical impor- tance is the so-called proagglutinoid zone; that is, bacteria sometimes will not agglutinate in a stronger dilution, whereas they agglutinate readily in a weaker. The proagglutinoid zone is occasionally found with the typhoid bacillus, but especially with the Micrococcus meliten- sis. Thus, this coccus may give no reaction in a dilution between 1-10 and 1-100, whereas it will clump strongly at 1-200. Agglutinins are not very resistant to light, putrefactive processes, and dryness. They are not much harmed at a temperature of 55° to 402 IMMUNITY 56° C, but are . destroyed at 65° to 70° C. They are very sensitive to acids; they are partially held back by a Pasteur-Chamberland filter; they are not dialyzable. They may be preserved for a very long time in dried serum protected from light and moisture. The chemical composition of the agglutinins is not known. Like antitoxin and other antibodies, they come down with the globulins when precipitated with ammonium sulphate. They unite directly with the bacteria or other cells and, according to Ehrlich, contain both a hap- tophore and an "agglutinophore" group. Agglutinins may readily be produced by injecting either live or dead bacterial cells into a suitable animal. The injections may be given either subcutaneously, intravenously, intraperitoneally, or the microorganisms may be rubbed upon the closely shaven skin. Agglu- tinins may even be produced by giving the microorganisms by the mouth. Agglutinins in highest concentration may be obtained by repeated in- jections, every 10 or 12 days, continued over a long period of time. In experimental work in the laboratory rabbits are suitable. Three or four injections into the ear vein of the rabbit, spaced at intervals of 8 or 10 days with cultures of cholera or typhoid, will develop ag- glutinins in the blood serum when diluted as high as 1 to 5,000 or 1 to 10,000. Where large amounts are needed the horse is the most suitable animal. Agglutinins also appear spontaneously in attacks of certain infec- tious diseases and continue in the blood for some time after convales- cence. In typhoid fever they appear about the end of the first week. They are usually weak at first, clumping the typhoid bacilli in a dilu- tion of 1-30 in one hour at the body temperature, arid increase with the progress of the disease, so that the serum may agglutinate in dilu- tions of 1-1,000 or more. In malta fever agglutinins appear about the fifth day of the disease and may develop in large amount. Thus, the blood serum from a case of malta fever may agglutinate the Micrococcus melitensis in dilutions as high as 1-500,000. The reaction of agglu- tination is not only practical as an aid to diagnosis of disease, but is of considerable practical use as an aid of recognition of the bacteria themselves. The reaction of agglutination is not absolutely specific; thus, a ty- phoid agglutinin will occasionally clump proteus or other not very closely related microorganisms. Thus, Frost found a Psedomonas pro- tea in the Potomac Eiver water that showed quite constantly the char- acteristic of being agglutinated by specific typhoid immune serum. However, when animals were injected with the Ps. protea they developed agglutinins for this organism, but not for the B. typhosus. Further, there is the phenomenon of group agglutination or group reaction; that is, a typhoid serum will clump the colon bacillus, the paratyphoid. ANAPHYLAXIS 403 the paracolon bacillus, and closely related organisms in the colon ty- phoid group. However, this occurs only in weak dilutions. The reac- tion is, therefore, specific in a quantitative sense. Thus, a good cholera or typhoid serum will agglutinate these organisms in dilutions of 1- 1,000 and over, whereas the group reactions occur in dilutions of about 1-50 or less. In addition to the bacteria, the red blood cells, or cells of any sort, trypanosomes and other protozoa may be agglutinated. We have no satisfactory explanation of agglutination. Analogous phenomena occur in the study of the physical chemistry of colloidal substances. It seems that in agglutination two separate phenomena are involved: the approach of the particles, one to the other, and their ad- hesion subsequently. The phenomenon may be imitated by coating match sticks with soap, floating them upon the surface of water in a basin, and then adding sulphuric acid. The agglutinins affect the sur- face tension between the bacteria and the fluid in which they are sus- pended in some way, but just how is not quite clear. The agglutinins are probably formed in the lymphoid organs, red marrow, and spleen; at least, Pfeiffer and Marx found them early in these organs after injections of cholera vibrios. Metchnikoff found that the peritoneal exudate may be richer in agglutinins than the blood, and believes in that fluid they come from the leukocytes and endothelial cells. The part played by the agglutinins in immunity is not clear. Al- though the bacteria are immobilized, this does not particularly favor phagocytosis. Large clusters of bacteria or agglutinated clumps of closely packed cells afford a mechanical protection against the dissolv- ing action of the lysins. ANAPHYLAXIS Anaphylaxis (ana, against, and phylax, guard, or phylaxis, protec- tion), also called hypersusceptibility, is a condition of unusual or exag- gerated susceptibility of the organism to foreign proteins. In other words, anaphylaxis is an altered power of reaction on the part of the body to foreign proteins. The word anaphylaxis was introduced by Eichet to describe a condition contrary to prophylaxis. As we now regard the phenomenon, the word is a misnomer, for we look upon the condition of hypersusceptibility as a distinct benefit and advantage to the organism; in fact, immunity against a large class of infectious diseases probably depends upon an altered power of reaction, that is, Upon hypersusceptibility or anaphylaxis. The condition of anaphylaxis may be congenital or acquired, local or general, and is specific in nature. It may be brought about by the intro- duction of any strange protein into the body. Hypersusceptibility to 404 IMMUNITY proteins that are non-poisonous in themselves may readily be induced in certain animals. The animal may be in a condition of hypersuscepti- bility and immunity at the same time. The two conditions are closely interwoven. The latter is often dependent upon the former. Von Pirquet suggests the term "allergie" to indicate conditions of acquired immunity associated with anaphylaxis. Allergie, as the word indicates (alios, change, and ergon, action), is an altered power of the organism to react. When this power of reaction is increased we say the body is hypersusceptihle, or in a state of anaphylaxis. Examples of Anaphylaxis.- — In the case of vaccinia, the reaction to a primary "take" appears after an incubation of four days. In a secondary vaccination the period of incubation is shortened and the clinical reac- tion lessened. In other words, the power of the organism to react is changed. This power of accelerated or immediate reaction protects the individual. Therefore, there is no absolute immunity in the class of dis- eases represented by smallpox; the prophylaxis depending upon the anaphylaxis. The tuberculin and mallein reactions are well-known instances of anaphylaxis. These substances are not poisonous when introduced into a healthy individual, but the tuberculous individual is anaphylactic to tuberculin, and an individual suffering from glanders is in a state of hypersusceptibility to mallein. A clinical instance of anaphylaxis is the hypersusceptibility of some individuals to pollen — hay fever. Experimental anaphylaxis may be brought about in various ways, such as the introduction of an alien serum into the body — serum anaphylaxis. Experimental Serum Anaphylaxis.— The essential features of experi- mental anaphylaxis are : (1) The first injection, consisting of a bland alien protein non- poisonous in itself, which sensitizes the animal; (2) An interval of about 8 to 14 days; (3) The second injection of the same protein which produces a reaction known as acute anaphylactic shock. Horse serum, when injected into normal guinea pigs, causes no symptoms. As much as 20 c. c. may be injected into the peritoneal cavity of a guinea pig without causing any apparent inconvenience to the animal. Small amounts of horse serum may even be injected directly into the brain without causing any untoward symptoms. Very characteristic symptoms, however, are produced by horse serum when injected into a susceptible guinea pig; i. e., one that has received a prior injection of horse serum. In five or ten minutes after injection the pig becomes restless and then manifests indications of respiratory embarrassment by scratching at the mouth, coughing, and sometimes by ANAPHYLAXIS 405 spasmodic, rapid, or irregular breathing; the pig becomes agitated and there is a discharge of urine and feces. This stage of exhilaration is soon followed by one of paresis or complete paralysis, with arrest of breathing. The pig is unable to stand or, if it attempts to move, falls upon its side; when taken up it is limp: spasmodic, jerky, and con- vulsive movements now supervene. This chain of symptoms is very characteristic, although they do not always follow in the order given. Pigs in the stage of complete paralysis may fully recover, but usually convulsions appear, and are almost invariably a forerunner of death. Symptom-3 appear about ten minutes after the injection has been given; occasionally in pigs not very susceptible they are delayed thirty to forty- five minutes. Pigs developing late symptoms are not very susceptible and do not die. Death usually occurs within an hour and frequently in less than thirty minutes. If the second injection be made directly into the brain or circulation, the symptoms are manifested with explosive violence, the animal frequently dying within two or three minutes. A fall in temperature occurs which in fatal cases may be as great as 13° C. (Pfeiffer). The blood during anaphylactic shock shows a leukopenia and a diminution in complement. When the chest is opened the lungs show a striking condition resemblisg emphysema. They do not collapse but remain fully distended, forming a cast of the pleural cavities. The heart continues to beat long after respiration has ceased. Asphyxia, due to inspiratory immobilization of the lungs, is, therefore, probably the immediate cause of death. Judged by the severity of the symptoms of the acute anaphylactic reaction, the guinea pig is apparently the most susceptible of animals (being 400 times more sensitive than the rabbit, according to Doerr), but probably all animals may be sensitized to a greater or less degree, although our methods of observation are still too crude to admit of any accurately graded comparison. White mice were long thought to be non-responsive on account of the absence of anaphylactic shock and death from asphyxia, so striking in the guinea pig; but Schultz and Jordan have shown that white mice do react toward horse serum with restlessness, marked irritability of the skin, passage of urine and feces, and temperature and blood pressure changes. In dogs, according to Eichet, the principal symptoms are gastro- intestinal. There is immediate vomiting, followed by tenesmus and bloody discharges from the intestines. Death is infrequent, but there may develop a condition of hemorrhagic inflammation in both the large and the small intestine which is called by Richet "chronic anaphylaxis," and by Schittenhelm and Weichardt, "enteritis anaphylactica." Another important sign is the rapid fall in blood pressure, sometimes 80-100 mm.; coagulation of the blood is delayed. Dyspnea is not marked, but, 38 406 IMMUNITY as in other animals, there is initial restlessness and skin irritability; there may be paralysis and death. Eabbits are apt to react to a re-inJection. of horse serum by edema and even necrosis at the- site of injection — the "Arthus phenomenon," a local anaphylaxis. Arthus also described, in non-fatal eases in rabbits, respiratory disturbance, general prostration, fall in blood-pressure, and increased peristalsis. In cases of acute lethal anaphylaxis produced in rabbits highly sensitized by repeated minute injections, Auer describes the slow respiration, the sudden falling of the animal on its side with a short clonic convulsion, stoppage of the respiration, weak heart beat, and death within a few minutes. The reaction to a second injection of serum has been observed, though not studied so carefully, in numerous other animals, e. g., in cows, horses, goats, sheep, and cats, in hen^ and pigeons, and in certain cold-blooded animals, with symptoms varying according to the species. It is evident that no one symptom, or group of symptoms, can be taken as an adequate criterion of anaphylaxis in all cases. Different species give a widely differing picture with the same proteid agent, because the same organs are not involved to the same degree. An ex- planation of these differences from the physiological point of view has been given by Schultz. He has shown that serum anaphylaxis is essen- tially a matter of hypersensitization of smooth muscle in general. He concludes, as a result of his experiments, that, during anaphylactic shock, all smooth muscle contracts. This is fatal to the guinea pig, owing to the peculiar though normal anatomical condition of its bron- chial tree : the mucosal layer of the secondary bronchi is relatively thick in comparison with the lumen, and the contraction of the smooth muscle throws it into folds which completely occlude the bronchi (Schultz and Jordan). The guinea pig dies of asphyxia, the cause of which is purely local and not in the central nervous system, as the first investigators be- lieved. The bronchi of mice, dogs, and rabbits, however, are relatively poor in mucous membrane, which accounts for the almost complete ab- sence of death from asphyxia. In the dog the contraction of smooth muscle sets up a vigorous intestinal peristalsis and a forced emptying of the urinary bladder; the characteristic initial rise in blood pressure may be due to constriction of the pulmonary, coronary and systemic arteries, and according to Auer, the subsequent marked fall to direct action on the heart muscle itself,' particularly of the right side, causing a venous accumulation of blood, an effect typified most strikingly in the rabbit. This provides also an adequate pharmacological explanation of the action of atropin and the anesthetics in alleviating the symptoms of acute anaphylaxis. Specificity, — The anaphylactic reaction is specific. Thus, a guinea pig sensitized with horse serum does not react to a subsequent injection ANAPHYLAXIS 407 of egg-white, vegetable proteid, or milk. The specificity extends even further than this. In order to give rise to anaphylactic symptoms, the proteid material given at the first and second injections must be from the same species or from some closely related species. Thus a guinea pig sensitized with cow's milk will not react to a subsequenc injection of woman's milk. Guinea pigs sensitized with the albumen of hen's eggs will not react tp a subsequent injection of the albumen of the eggs of pigeons, but do react mildly to duck egg-white. This specificity ac- cording to species is, therefore, of the same degree as that of certain immune reactions, notably the precipitins; that is, there is a group reaction in the proteids of allied species, but no reaction between the proteids of widely different species or between proteids of widely dif- ferent origin. The maximum effect at second injection is obtained by the use of the identical proteid ud|^ for sensitization. Certain sera which react interchangeably to precipitins, as, for example, human and ape, horse and ass, sheep and goat, rat and mouse, remain indistinguishable also by the anaphylactic reaction. The same specificity holds with respect to bacterial proteids: an animal sensi- tized with typhoid -bacilli will react strongly toward paratyphoid, and somewhat toward colon bacilli, but not at all to unrelated species. One of the remarkable facts in relation to the specificity of anaphy- laxis is that guinea pigs may be in a condition of anaphylaxis to three proteid substances at the same time; for instance, a guinea pig may be sensitized with egg-white, milk, and horse serum, and subsequently react separately to a second injection of each one of these substances. The guinea pig may be sensitized by giving these strange proteids either at the same time or different times, in the same place or in different places, or by injecting them separately or mixed. The guinea pig differentiates each anaphylactogenic proteid in a perfectly distinct and separate man- ner. The animal is susceptible to the second injection of each one of the three substances in the same sense that it is susceptible to three separate infectious diseases. That there may be exceptions to the rule of species-specificity is shown in the case of the crystalline lens. A guinea pig sensitized to the lens- extract of one species of animal will react to the lens-extract of widely different species, or even of its own species, but not to other tissues (Andrejew). Here, too, there is an exact parallel in the precipitin reaction which fails to distinguish the lens of one species from that of another (Uhlenhuth). This is an example of organ-specificity. In the vegetable world Osborne has shown that, whereas preparations of globu- lins from hemp, flax, and squash do not react with each other, gliadin from rye reacts strongly with gliadin from wheat, a result in accord with the fact that by chemical and physical means no differences have 408 IMMUNITY been detected which were sufficient to indicate that these gliadins were different substances. It is probable that only proteids which have a complete or partial chemical identity of structure will react with each other. Differences too small to be detected by analytic means at our disposal may yet pre- vent any tendency toward interaction, and the anaphylactic phenomenon may thus be used to determine the finer relationships of proteids. It is evident from these facts, as Osborne concludes, that structural differences exist between very similar proteids of different origin, and that chemi- cally identical proteids apparently do not occur in animals and plants of different species unless they are biologically very closely related. Sensitization by Feeding. — Guinea pigs may be sensitized by feed- ing them meat or serum. The fact that guinea pigs may be ren- dered susceptible by the feeding of strange protein matter opens an interesting question as to whether sensitive guinea pigs may also be poisoned by feeding with the same protein given after a proper interval of time. If man can be sensitized in a similar way by the eating of certain protein substances, this may throw light on those interesting and obscure cases in which the eating of fish, sea food, or other articles of diet sometimes cause sudden and often serious symptoms resembling those of anaphylaxis in all essential respects. Maternal Transmission. — It has been found that hypersusceptibility to the toxic action of horse serum is transmitted from the mother guinea pig to her young. This function is solely maternal; the male takes no part whatever in the transmission of these acquired properties. Whether this maternal transmission is hereditary or congenital cannot be definitely stated. There are certain analogies between the action of tuberculosis and horse serum. Both produce hypersensitiveness and also a certain de- gree of immunity. Now that it has been proved that hypersensitive- ness or anaphylactic action may be transmitted in guinea pigs, may it not throw light upon the fact that tuberculosis "runs in families"? While there are several recorded instances demonstrating that immunity to certain infectious diseases may be transmitted from a mother to her young, this is, so far as is known, the only recorded instance in which hypersensitiveness or a tendency to a disease has been experimentally shown to be transmitted from a mother to her young. Serum Anaphylaxis in Man, or Serum Sickness.- — Serum anaphylaxis in man is met with most frequently following the use of antitoxic sera, and has been carefully described by v. Pirquet and Schick (1905).^ After an injection of serum (usually in from eight to twelve days) there is apt to be a febrile reaction, now generally known as "serum-sickness," or serum disease. The common symptoms are local redness, itching and 'Serum Krankheit," Wien, 1905. 1 "S ANAPHYLAXIS 409 pain af the point of injection, swelling of the lymph nodes, fever, and a general urticaria lasting from two to six days. In more severe cases there is malaise, albuminuria, pronounced joint pains and even effusions, swelling of the mucous membranes, hoarseness and cough, nausea and vomiting, vertigo, and remarkable skin manifestations varying from hyperemias and erythemas to efflorescences resembling measles or scar- latina, and other vasomotor disturbances. Earely there may be subnormal temperature, a weak and rapid pulse, a catarrhal or hemorrhagic enteritis and extreme weakness approaching collapse. These results are independent of the antitoxic qualities of the serum, for Johannessen obtained the same symptoms by introducing normal horse serum into the bodies of perfectly healthy human beings. Indeed, the very earliest animal experiments were particularly concerned in determining whether the antitoxin played any part in the phenomenon, and it was soon conclusively eliminated as a factor. Both the incidence and the severity of serum sickness are propor- tional to the amount injected up to a certain point, but the acute (sometimes fatal) reaction in man is more dependent upon the hyper- susceptibility of the individual than upon the amount of serum injected. If the serum is "concentrated" (i. e., serum-globulin), the reactions are correspondingly lessened because smaller quantities of the foreign pro- teid are injected, the albumens and certain other proteids having been eliminated by the partial purification. The peculiarity of serum sickness in man is that it may follow the first injection of a foreign serum, though only after a definite incu- bation period corresponding to the time required to sensitize an experi- mental animal. There is no proof that other animals do not develop a reaction to the first dose which never rises to the threshold of clinical observation; in fact, Bhrlich, Francione, and others have observed a temporary diminution of complement in the blood of guinea pigs 10-13 days after the first injection. Besides the typical serum sickness, there has been reported since the introduction of serum therapy a certain small number of unforeseen and fatal catastrophes attending the injection of serum into human beings. The following case published by H. F. Gillette will serve to illustrate them all : "The patient was a man of 53, a subject of asthma. He asked me to administer diphtheria antitoxin to him, hoping it might cure his asthma. I administered 3,000 units under the left scapula with the usual precautions. He had about completed dressing when he said he had a pricking sensation in the neck and chest; soon he sat down and said he could not breathe, nor did he breathe again. . . . His pulse at the wrist remained regular and full for some time after respira- tion ceased. He had a mild degree of cyanosis aiid edema of the face. 410 IMMUNITY He died in tonic spasms ten minutes after iiijection. Autopsy revealed no palpable cause of death." The same author collected 28 cases of collapse or death after serum injection, of which 15 died. There was a common history of previous asthmatic trouble in all but five of the 28, and all, after injection, showed common symptoms of sudden intense dyspnea, a sense of over- whelming anxiety, edema and cyanosis of the face, a sudden massive urticaria, tonic muscular spasms and continued beating of the heart long after the ceasing of respiration. Eosenau and Anderson collected 19 eases and were able to examine the serum used in two of them. It was found to be no more toxic to sensitized guinea pigs than normal horse serum. These cases oi severe systemic shock seem susceptible of no other explanation than that the unfortunate individuals had been in some manner, at a previous time, sensitized to horse proteid. They present a picture which is almost the counterpart of typical anaphylactic shock in guinea pigs, and the most striking thing about them is that practically all give a history of respiratory trouble in the past, especially horse-asthma. Schultz and Jordan suggest that these occasional cases of sudden death in man may perhaps be due to an abnormal develop- ment of the mucous membrane and smooth muscle of the bronchi (as in asthmatics), and that the smooth muscle, being hypersusceptible, pro- duces asphyxia by sudden contraction. Eosenau and Amoss '■ have re- cently indicated a possible explanation of the way in which such persons may become sensitized. They have proved that a proteid material is given off in the expired breath of human beings. There is some reason to suppose that the proteid given off by one animal may be absorbed by individuals of different species by way of the lungs. One thing is clear, that these immediate and sometimes fatal reactions are not de- pendent upon any peculiar property in the serum, but to an altered power of reaction of the individual to the foreign proteid injected. The anaphylactic reactions following the injection of serum in man may be summed up briefly as follows: Reactions following first injection: (a) "Serum sickness," incubation 8-13 days (common). (b) Acute anaphylactic shock, with collapse or death (rare). Reactions following second injection: (a) Interval between injections less than 8 days, no reaction. (b) Interval 12-40 daj's, immediate reaction. (c) Interval 15 days-6 mos., either immediate or accelerated reaction, or both. (d) Interval over 6 mos., accelerated reaction. ' Eosenau, M. J., & Amoss, H. L. : Jour, of Med. Bes., Sept., 1911, XXV, 1, pp. 35-84. ANAPHYLAXIS 411 The above table represents the usual course of events, but exceptions may occur, and the time intervals are only approximate. Sometimes the reactions do not appear until the third, fourth, or some subsequent injection. Two precautions are suggested in serum therapy: (1) Except in urgent eases, avoid injecting horse serum into indi- viduals known to be asthmatic, especially those whose symptoms are brought on by being around horses. (2) If hypersensitiveness is suspected, give at first a very small portion of the dose, following it in an hour or so with the rest, injecting it exceedingly slowly and avoiding direct injection into the circulation. HypersTisceptibility and Immunity Produced by Bacterial Proteins. — The problem of hypersusceptibility has an important bearing on the question of immunity, and hence the opinion has been expressed that "resistance to disease may largely be gained through a process of hyper- susceptibility. Whether this increased susceptibility is an essential ele- ment or only one stage in the process of resistance to disease must now engage our attention." We cannot escape the conviction that this phenomenon of hypersusceptibility has an important bearing on the prevention and cure of certain infectious processes. Hypersusceptibility may easily be induced in guinea pigs with pro- tein extracts obtained from the bacterial cell. The first injection of most of the extract seems comparatively harmless to the animal. A second injection of the same extract shows, however, that profound physiologic changes have taken place. A definite period must elapse between the first and the second injection. The symptoms presented by the guinea pigs as a result of the second injection resemble those caused by horse serum. The phenomenon induced by a second injec- tion is followed (in certain cases) by an immunity to the correspond- ing infection. These results strengthen the belief that the phenomenon of hyper- susceptibility has a practical significance in the prevention and cure of certain infectious processes. It also gives a possible explanation of the period of incubation of some of the communicable diseases. Is it a coincidence that the period of incubation of a number of infectious diseases is about ten to fourteen days, which corresponds significantly with the time required to sensitize animals with a strange protein ? In certain infectious diseases with short periods of incubation, such as pneumonia, the crisis which commonly appears about the tenth day may find a somewhat similar explanation. It is evident that disease processes produced by soluble toxins, such as diphtheria and tetanus, do not belong to the category now under consideration. Relation of Anaphylaxis, to Prptein Metabolism.— The whole prob- lem of protein metabolism seems to bp, an adjustment in the sense of a 412 IMMUNITY defense. The power to assimilate and use foreign proteins is not achieved without a certain amount of violence to the body. The rela- tion between the fundamental facts of protein metabolism and immunity to certain diseases becomes clearer in the light of observations upon anaphylaxis. A deeper insight into these problems will throw light on the fundamental processes concerned in both protein metabolism and immunity. Relation of Anaphylaxis to Endotoxins. — The fact that the great majority of bacteria do not produce soluble poisons, such as diphtheria and tetanus, has led to the belief that in such cases we are dealing with an "endotoxin." The endotoxin has long been regarded as a poisonous substance so intimately associated with the cell that it is not released until the microbic cell is broken up in the body. The inability to dem- onstrate many of these endotoxins has cast a doubt on their existence and increased the mystery of their action. It now seems probable that the studies on anaphylaxis may throw light upon this question. •When bacteria grow in the body they are dissolved by lytic agencies and the foreign protein in the individual germ cells may sensitize the body and afterward poison it. The bacterial proteins may not be pois- onous in themselves in the sense of an "endotoxin." We have, in fact, shown that protein extracts of bacterial cells at the first injection may produce characteristic symptoms, and this reaction may be followed by an immunity to the corresponding infection. The Relation of Anaphylaxis to Tuberculosis. — The tuberculin re- action is one of the best known instances of anaphylaxis. Following a local infection with the tubercle bacillus the tissues generally become hypersusceptible to tuberculin. It has been shown that a local hyper- susceptibility may be produced by the direct application of tuberculin to certain tissues (conjunctiva). The same has been demonstrated for the skin, and is probably true of other tissues. This hypersusceptibility of the tissues immediately surrounding a tuberculous focus helps to en- capsulate and limit the process. Should a tubercle bacillus lodge in or on a tissue in a state of tuberculin anaphylaxis, the result is that all of nature's protecting agencies are quickly concentrated on the point where most needed. We conceive that this active power of reacting quickly is not only an important factor in individual prophylaxis against tuberculosis, but is an important agency by which the spread of the disease after it has obtained a lodgment in the body is prevented. The normal individual does not react to tuberculin. The tubercu- lous individual reacts promptly, except in the final stage of the disease. The diilerence between the normal individual and the individual in the final stage of tuberculosis is that the former has not had his ana- phylactic powers developed, while the latter has had them developed and exhausted. A tuberculous individual in whom the specific power ANAPHYLAXIS 413 of hypersusceptibility to the poisons of the tubercle bacillus is broken down presents little or no resistance against the advance of the in- fection. We may adduce a practical lesson from this. When tuberculin is used in large or too oft-repeated doses there is a tendency to break down or to exhaust the useful and beneficial hypersusceptible state of the tissues. In accordance with this line of reasoning, therefore, tuber- culin would be of benefit in tuberculosis only when used in such a way as to develop and not diminish the power of anaphylaxis of the tissues. This explanation has been borne out in the use of tuberculin. Relation of Anaphylaxis to Vaccination. — When the virus of cowpox is introduced into the skin we implant a colony of microorganisms. They grow day by day, and on the eighth day there is an enormous number of them. The contents of the vesicle will start new colonies on thou- sands of other arms, but now the antibodies appear and the colony is attacked and digested, and toxic bodies are formed. This is diffused in the neighborhood and we get an intense local inflammation called the areola. Some of the toxic bodies enter the circulation and cause fever, but the microorganisms are killed and we can no longer vaccinate with the contents of the now yellow pustule; two or three days more, the struggle is over, but the antibodies remain a long time. Let us now revaccinate, and a different series of events takes place, for in the mean- time the body has become educated and instead of waiting some days before attacking the colony of microorganisms in the skin, starts the attack at once. In other words, there is an immediate reaction — a changed power of reaction or anaphylaxis. In brief, the first vaccina- tion has sensitized the tissues, so that they respond at once upon the second vaccination. The invading microorganisms, attacked at once, are soon digested — they are given no chance to multiply, and little toxin is formed. This attractive explanation of the immunity to smallpox or cowpox, developed by von Pirquet, shows that the prophylaxis depends upon the anaphylaxis. Other Practical Eelations of Anaphylaxis. — In addition to hay fever, already mentioned, there are a number of other conditions which find their best explanation as examples of local anaphylaxis. This in- cludes many of the urticarias and sudden vasomotor disturbances of the mucous membranes; various forms of asthma are also associated with hypersusceptibility to foreign substances. Idiosyncrasies with re- gard to articles of diet belong to the same category. Some persons are sensitized to pork, others to eggs, and sensitization to sea-food is com- mon. Other conditions which have been explained in whole or part on the theory of anaphylaxis are puerperal eclampsia, sympathetic ophthal- mia, the onset of labor, the crisis in pneumonia, the spasmophilic dia- thesis, the symptoms attendant on the rupture of the cysts in echino- 414 IMMUNITY coccus disease, etc. The anaphylactic reaction is also used in diagnosis, and in forensic medicine in the identification of blood stains, and, iinally, may be used as a scientific instrument for the detection of minute amounts of protein. Eeferences. — Many of the statements contained in this chapter have been taken from Emery's splendid book upon "Immunity and Specific Therapy," which is recommended to the reader who desires a more ex- tended review upon the subject. Kolle and Wassermann's "Handbuch der Mikroorganismen" has also been consulted, as well as Kraus and Levaditi's "Handbuch der Technik und Methodik der Immunitats- forschung." These volumes also contain selected bibliographies. The current literature upon immunity will be found in the Zeit- schrift fiir Immunitatsforschungen. For those who desire to dip deeper into the subject the original ref- erence to many of the fundamental studies will be found in "Collected Studies on Immunity" by Ehrlich, translated by Bolduan; "Studies on Immunity" by Bordet, translated by Gay; "Studies in Immunization" by Wright, and "L'Immunite dans les Maladies Infectieuses" by Metch- nikofl, translated by Binnie. CHAPTEE II HEREDITY AND EUGENICS Heredity may be defined as the genetic relation between successive generations. It is a condition of all organic evolution. Castle defines heredity as organic resemblance based on descent. It is now perfectly evident that heredity is one of the fundamental factors in preventive medicine — which, after all, is the true sociology. It is well known to students of biology that education and environ- ment have but a limited power to influence imperfect human proto- plasm. One of the best protections we have against diseases of body and mind is that which is inherited from our forebears. The whole prob- lem of improving the human stock, not only from the medical view, but from the broader sociological standpoint, is based upon the breed- ing of the fit and elimination of the unfit. The science of eugenics (normal genesis), therefore, assumes especial importance in preventive medicine. The physician, as well as the sanitarian, stands impotent before many deplorable conditions both in the individual and in so- ciety at large, which are inherited from our ancestors and are, there- fore, incurable — but largely preventable. We are interested in educat- ing the present generation to the facts of eugenics so that future gen- erations may have that best of all birthrights — good human protoplasm. The discoveries of Mendel have made it quite clear how certain char- acters are inherited, why certain characters skip a generation and re- appear in the grandchildren, and why it , is that certain defects are carried from generation to generation through many centuries.^ The defects transmitted hereditarily are not all of equal practical impor- tance. Thus, it makes comparatively little difference to the individual if he has a supernumerary spleen, an extra finger, or an anatomical anomaly of the liver. The defects which are of especial importance both to the individual and to succeeding generations are the defects ^ Mendel 's work has not only made it possible for us to predict with precision whether good or bad traits will or will not appear in the future offspring, but also to foretell with mathematical precision in what proportion certain characters will appear and reappear. 415 416 HBEEDITY AISTD EUGENICS of organization of the nervous system. These comprise the class known as defectives. A slight defect in the structure of the brain which would be unnoticed in the lung, bone, or musculature may render the individual vicious instead of useful. The principal factors which are believed to start a line of defectives are inbreeding, syphilis, and al- cohol; also nervous or physical diseases, mental or nervous exhaustion, and excesses and poisons of all kinds. ^ The defective individual is very easily recognized when the condi- tion is well marked. The mental abnormality is usually accompanied by prominent physical defects known as the stigmata of degeneration (Lombroso and Weismann). An unfortunate side to this problem is that degenerates and defectives generally are not only irresponsible morally, but are very prolific. They lack self-control and have abnor- mal sexual appetites. Defectives beget defectives, and thus insanity, nervous diseases, moral and physical degeneracy are propagated. The typical degenerate is of poor bodily development; the brain is smaller than normal, with convolutions less abundant, and less fully formed. He has a degraded physiognomy, lacks capacity for sustained attention or for prolonged thought, is cunning rather than intelligent, deficient in moral sense — in all points resembling the stigmata of the lower, less developed races of our species. The whole gives the impression of a reversion to a lower type. Prevention of Propagation of Defectives. — Four methods have been proposed to prevent the propagation of defectives: (1) education; (2) legislation; (3) segregation; (4) surgery. Education. — Education directed toward the defective is a failure, for he is incapable of profiting by the lessons. The education of the better class of the community is indirectly helpful in calling attention to the situation as being largely preventable, and to the necessity and means for controlling it. Eesthictive Legislation'.' — Eestrictive legislation is a praiseworthy effort, but has signally failed as a preventive measure, for the evident reason that it only adds illegitimacy to degeneracy, and thus the chil- dren enter on life's battle doubly handicapped. Minnesota has a law providing that within the bounds of the state no marriage shall be permitted, either party to which is epileptic, imbecile, feeble-minded, or afilicted with insanity, unless the woman be over forty-five. Michigan, Delaware, Connecticut, Indiana, New Jersey, and North Dakota have also passed laws for the purpose of preventing marriage among de- fectives. Segregation. — Segregation would be an ideal and humane method ' The real cause or method of origin of defective characters that are trans- mitted hereditarily is no better understood than the origin of ' ' sports ' ' or muta- tions. PEEVENTION OF PEOPAGATION OF DEFECTIVES 417 of eliminating those who are incapable of having normal offspring. The segregation of all degenerates and defectives would be an enormous and impractical task. Further, the great difBculty is to detect the un- fit individual who starts a strain of defectives and degenerates. It is evidently a hopeless task to know where to draw the line between the fit and the unfit, so that for the present we must be satisfied to enforce restrictive measures upon only those who are evident and well-marked examples. Insane asylums, homes for epileptics, reformatory schools, as well as special hospitals and institutions for advanced cases must not be regarded as preventive measures in the true sense, for such segregation provides care and comfort as a terminal measure; that is, it is usually a last resort. Frequently defectives propagate their kind before and sometimes after they are segregated. Stjegert. — Surgery has been proposed as a means of controlling the propagation of defectives. This is done either by severing the vas deferens or the Fallopian tube. At the Indiana Eeformatory Dr. Sharp carries out the law^ of that state providing for the sterilization of defectives. The operation of vasectomy consists of ligation and re- section of a small portion of the vas deferens. The operation is very simple and easy to perform. It may be done without an anesthetic, either local or general. As performed by Dr. Sharp it requires about three minutes, and the subject returns to his work immediately, suf- fering no inconvenience and in no way hampered in his pursuit of life, liberty, and happiness, but is effectively sterilized. In 456 cases Dr. Sharp has had no unfavorable symptoms. The operation is performed as follows : After cleansing the scrotum with soap and water, fol- lowed by alcohol, the spermatic cord is grasped between the thumb and index finger of the left hand. The vas deferens is detected, firmly held and fixed with a pair of bullet forceps. It is then exposed by a small incision and drawn through the scrotum wound by means of a tenaculum. It is stripped of all membranes and the accompanying ar- tery ligated above and severed, care being taken to cut away any por- ^ The Indiana law reads as follows : Whereas, Heredity plays a most important part in the transmission of crime, idiocy, and imbecility; Therefore, Be it enacted by the General Assembly of the State of Indiana, That on and after the passage of this act it shall be compulsory for each and every institution in the State, entrusted with the care of confirmed criminals, idiots, rapists, and imbeciles, to appoint upon its staff, in addition to the regular institutional physician, two (2) skilled surgeons of recognized ability, whose duty it shall be, in conjunction with the chief physician of the institution, to examine the mental and physical condition of such inmates as are recommended by the institutional physician and board of managers. If, in the judgment of this committee of experts and the board of managers, procreation is inadvisable and there is no probability of improvement of the mental and physical condition of the inmate, it shall be lawful for the surgeons to perform such operation for the prevention of procreation as shall be decided safest and most effective. But this operation shall not be performed except in cases that have been pronounced unim- provable. . . . 418 HEEEDITY AND EUGENICS tion of the yas deferens that may have been damaged in the manipula- tion. This is done in order that the end next to the testicle may not become closed. It is very important that the testicular end shall re- main open, in order that the secretion of the testicle may be emptied around the vessels of the pampiniform plexus and there be absorbed, for it is through this process that the body receives the tonic effect of the internal secretion. Further, if the testicular end of the vas defer- ens is closed, there is likely to be cystic degeneration of the testicle. The retraction of the muscle closes the skin wound and no stitch, col- lodion, or adhesive plaster is needed. There is no diminution of the sexual power or pleasure. The discharge at the orgasm is but slightly decreased. The operation in the female is more difficult, but if carefully done no more hazardous. The Fallopian tubes are reached through a median incision and ligated near the uterus and severed beyond the ligature. Opinions vary greatly concerning the proper use of sterilizing crim- inals, insane, degenerates, and defectives generally. There is no doubt concerning its effectiveness. Sterilization is a measure which contains great potential possibili- ties for abuse and injustice. It probably will never receive general acceptance on account of the difficulty of determining upon whom the operation shall be done. Even in perfectly clear cases, such as the in- sane, the epileptic, or the high grade degenerate, the harm has often been done before the operation is decided upon. Statistics of Defectives. — The large number of defectives and unfit in our country may be gleaned from the following figures. The last census report for the United States gives data relative to the dependents and defectives in institutions; the number not in in- stitutions can only be guessed at. Kellicott gives the following ap- proximate numbers in our country to-day: Insane and feeble-minded, at least 200,000 Blind 100,000 Deaf and dumb 100,000 Paupers in institutions 80,000 Prisoners 100,000 Juvenile delinquents in institutions 23,000 The number of persons cared for in hospitals, dispensaries, "homes" of various kinds in the year 1904 was in excess of two million. We have to support about half a million insane, feeble-minded, epi- leptic, blind, and deaf ; 80,000 prisoners, and 100,000 paupers, at a cost of $100,000,000 per year. A new plague affecting 4 per cent, of the population and costing this vast treasure would instantly attract uni- DEGENERATE FAMILIES 419 versal attention. We have become so used to crime, disease, and de- generacy that we take them as necessary evils. "That many of them were so in the world's ignorance is granted; that they must remain so is denied." Statistical studies seem to indicate a rapid (at least an unneces- sary) increase of the unfit, defective, insane, criminal, and, on the other hand, a slow increase, or even a decrease (?), of the fit, normal, or gifted stocks. It is plain to the student of eugenics how such con- ditions account for the rise and fall of nations. The United States census of 1880 reported 40,942 insane in hos- pitals and 51,017 not in hospitals; a total of 91,959 known insane. In 1903 it was estimated that there was a total of 180,000 in the United States. Thus, the ratio of known insane in the total population was 225 per 100,000 in 1903, as compared with 183 per 100,000 in 1880. These figures must not be taken as an index of the increase of insanity in the population at large — for institutional care has been growing much more popular during the past decade, especially since more hu- mane methods have been adopted. Further, the classification of insan- ity now includes many cases that were formerly little noticed.^ The comparatively large and increasing numbers of defectives and weaklings among the civilized races compared with wild animals may be accounted for by the fact that atavism and reversion are more fre- quently met with in artificially cultivated strains, such as civilized man; and the further fact that our charitable and philanthropic efforts foster and even favor the unfit. Degenerate Families. — A careful study has been made of the records of several families in which the mating of unfit individuals has begotten a swarm of unfit descendants. '■A special census of the insane confined in institutions was taken by the Bureau of the Census in 1910, and it was found that 187,454 patients were con- fined in hospitals for the insane in the continental United States. While the population of the United States increased about 11 per cent, in the interval between 1904 and 1910, the population in insane asylums increased about 25 per cent. The number of insane in asylums per 100,000 population in- creased from 186.2 in 1904 to 203.8 in 1910. The number of persons annually committed to hospitals for the insane per 100,000 population increased from 61.5 in 1904 to 65.9 in 1910. If these ratios are accepted as representing insanity rates, it would appear that the number of persons becoming insane, in a com- munity comprising 100,000 persons, was greater by 4.4 in 1910 than it was in 1904. It must be remembered, however, that these figures include only the insane who are committed to hospitals. As to the number of cases of insanity not resulting in commitments to hospitals the census has no data. It is entirely possible that the increase in the number of commitments per 100,000 population is not due to any considerable degree to an increased prevalence of insanity, but simply to the extension of this method of caring for the insane. It is a change which might result from an increase in the number of institutions of this class and from the increasing disposition on the part of the public to resort to such institutions. In this connection it may be noted that the number of institutions for the insane reported by the census increased from 328 in 1904 to 372 in 1910, an increase of about 13 per cent. The average number of inmates per institution increased from 458 in 1904 to 504 in 1910. 430 HEREDITY AND EUGENICS ©^^ One of the best known families of this type is the so-called Jukes family of New York State investigated byDugdale. This family is traced from the five daughters of a lazy and irresponsible fisherman born in 1720. In five generations the descendants of Jukes numbered about 1,200 persons, including nearly 200 who married into it. The histories of 540 of these are well known, and about 500 more are partly known. Some 300 died in infancy. Of the remaining 900, 310 were professional paupers living in almshouses (a total of 2,300 years) ; 440 were physically wrecked by their own diseased wickedness; more than half of the women were prostitutes; 130 were convicted criminals; 60 were habitual thieves; 7 were murderers. Not one had even a common school education; only 20 learned a trade, and 10 of these learned it in State's prison. The descendants of Jukes in five gen- erations have cost New York State over one million and a quarter dollars, and the cost is still going on. Probably the most complete family history of this kind ever worked out is that of the "Familie Zero," a Swiss family whose pedigree has been studied by Jijrger. In the seventeenth century this family divided into three lines. Two of these have ever since remained valued and highly respected families, while the third has descended to the depths. This third line was established Jo by a man who was himself the result 2 of two generations of intermarriage, the second tainted with insanity. He was of a roving disposition, and in the Valla Fontana found an Italian vagrant wife of vicious character. Their son inherited fully the parental traits and himself married a member of a German vagabond family — Marcus. This marriage sealed the fate of their hundreds of descendants. The pair had seven children, all char- acterized by vagabondage, thievery, drunkenness, mental and physical a S DEGENERATE FAMILIES 421 defects, and immorality (Kellieott). How much of this is due to heredity and how much to environment will be discussed presently. Another interesting example of the same type has been described by Poellmann. This family was established by two daughters of a woman drunkard who in five or six generations produced, all told, 834 descendants. The histories of 709 of these are known. Of the 709 107 were of illegitimate birth, 64 were inmates of almshouses, 1G2 were professional beggars, 164 were prostitutes, and 17 procurers, 76 had served sentences in prison, aggregating 116 years, 7 were condemned for murder. Dr. Henry H. Goddard ^ has investigated and compiled the results of his work on the heredity of a most remarkable family, the Kallikak family. During the Eevolutionary days, the first Martin Kallikak (the name is fictitious), descended from a long line of good English ancestr)', took advantage of a feeble-minded girl. The result of their indulgence was a feeble-minded son. This son married a normal woman. They in turn produced five feeble-minded and two normal children. Practically all of the descendants of these defectives have been traced, as well as those of the two normals. From both normal and defective descendants of this union came a long line of defective stock. There were 480 in all. Of these thirty- six were illegitimate, thirty-three sexually immoral, twenty-four con- firmed alcoholics, and three epileptics. Eighty-two died in infancy, three were criminal, eight kept houses of ill fame, and 143 were dis- tinctly feeble-minded. Only forty-six were found who were apparently normal. The rest are unknown or doubtful. But the scion of the good family who started this long line of delinquent and defective progeny is also responsible for a strain of an entirely different character. After the Eevolutionary War was over, he married a Quaker girl of good ancestry and settled down to live a respectable life after the traditions of his forefathers. From this legal union with a normal woman there have been 496 descendants. All of these except two have been of normal mentality. The exceptions were cases of insanity, presumably inherited through marriage with an outside strain in which there was a consti- tutional psychopathic tendency. In all the 496 there is not an instance of feeble-mindedness. The offspring descended from this side of the house have universally occupied positions in the upper walks of life. They have never been criminals or ne'er-do-wells. On the other hand, there has not been a single instance of exceptional ability among the descendants of the first Martin Kallikak and the feeble-minded girl. Most of these descendants have failed to rise above the dead level of ' ' ' The Kallikak Family, a Study in the Heredity of Feeble-mindedness, ' ' New York, Maemillan Company, 1912. 29 423 HEREDITY AND EUGENICS mediocrity; indeed, most of them have fallen far below even this minimum standard. The fact that the descendants of both the normal and the feeble- minded mother have been traced and studied in every conceivable en- vironment, and that the respective strains have always been true to type, tends to confirm the belief that heredity has been the determining factor in the formation of their respective characters. In the cities the descendants of the legal marriage with the normal woman are physicians, lawyers and prominent business men, while the descendants of the feeble-minded mother are almost invariably found in the slums. In the rural districts the descendants of the normal mother and her con- sort are wealthy and influential farmers, while the others never rise above the rank of farm laborers and shiftless men and women who are unable to subsist without the aid of charity. Many representatives of the defective branch are inmates of almshouses, while there are no paupers at all among the normal descendants. In many ways this study of Goddard's far outweighs in importance the famous comparison by Dr. Winship of the Jukes and Edwards fam- ilies. In that case the simple fact was demonstrated that a good family like that of the illustrious Jonathan Edwards had given rise to innu- merable examples of the highest intellectual and moral worth, whereas the criminal Jukes for seven generations contributed nothing to the common good and cost the state of New York large sums of money. But the Jukes family and the Edwards family had no ancestor in common. Their environment was totally different and they lived in entirely separate communities. Although from sociologic and economic points of view the history of the Jukes family and its comparison with that of the family of Jonathan Edwards has great value, it is of but scant scientific importance as compared with that of the Kallikak family, for here a natural object-lesson in eugenics shows unmistakably the manner in which after-coming generations from a given mating receive the characteristics of the dominant strain, which in the elder (illegiti- mate) Kallikak line was the inferior strain, with only a debased and enfeebled heritage to hand on.^ In contrast to these we have the descendants of the families of Wedgwood, Darwin, and Galton, the Edwards family and the Ward family. These three noted families contained a large number of states- men, jurists, professors, physicians, officers in the army and navy, prom- inent authors and writers, and occasionally men and women of genius. They show a long line of usefulness in every department of social prog- ress, and not one of them ever has been convicted of a crime. How much of this is due to heredity and how much to environment are debatable questions. Students of biology are convinced that heredity V. A. M. A., Oct. 26, 1912, LIX, 17, p. 1545. EUGENICS 433 plays the major role in the lives of the individuals in the above-men- tioned families. In how far such extreme instances as those given above represent the rule or exceptions will require much additional data and long years of study to determine. EUGENICS The science of eugenics has been defined as "the science of being well born." According to Galton, "eugenics is the study of the agen- hfeoGwooo Dapw/n 9t*t9 C ALTON «^t9 9T«' 9=p«- c cf 9=|=«r cf-f=9 'tf 9=p«f ® )t F •* eT tr ® r ® ® ~1 f Q shows a man of scicniific ability ; ^ sbows a man of scientific ability, who is alto a Fellow of the Royal Society ; Q shows five other children, and so on. Fig. 58. — History (Condensed and Incomplete) of Thkeb Mabkedlt Able Families (After Whentham) (Kellicott). eies under social control that may improve or impair the racial quali- ties of future generations either physically or mentally." The aim of eugenics is to increase the number of best specimens in each class; that done, leave them to work out their common civiliza- tion in their own way. It also aims to leave a good heritage to the next generation and to repress the propagation of the vicious and de- fective classes. The success of eugenics depends almost entirely upon our knowl- edge of heredity and sociology. Therefore, the fundamental principles of heredity should be familiar to all students of preventive medicine. The present movement started in 1865 when Francis Galton showed that mental qualities are inherited, just as are physical qualities, and 424 HBEEDITY AND EUGENICS pointed out that this opened a way to an improvement of the race in all respects. The student should read Galton's work on "Hereditary Genius," published in 1869, when he again emphasized definitely the possibility and desirability of improving the natural qualities of the human race. The word "eugenics" was coined in 1883 in his "In- quiries Into the Human Faculty." There is no doubt concerning the desirability of breeding better human stock, but how this may be accomplished practically is a diffi- cult question. The program of the eugenist is perplexing and compli- cated. To follow the theoretical extremists would require a social revo- lution — a change from the present method of haphazard mating. The threshold of the subject has scarcely been passed, and we must bear in mind that some of the striking men of genius from whom the world has greatly profited have been individuals whom the student of genetics would regard as degenerates or defectives. Eugenics does not mean free love, nor does the eugenist recommend Burbanking the human race to produce great physical strength, beauty, endurance, mental or moral power. One point only in the program is perfectly clear, and that is that a check should be placed upon the propagation of the crop of defectives by means already pointed out. The known facts of heredity and the study of eugenics make us examine more critically some of the directions which preventive medi- cine, including philanthropy and social uplift, has taken. We must now ask ourselves the question whether it would not be better for the future generations if we helped the fit rather than the weakling and the unfit. These are problems raised by Gallon, who questions whether some of our charitable efforts are well balanced and well directed. The importance of eugenics in medicine is not new. For a while, however, the medical sciences lost sight of heredity, owing to the ultra- materialistic view of disease which became the vogue as a result of the germ theory. A neglect of the personal element in medicine and a wholly impersonal hygiene were laid down as universally applicable. Davenport states : "It has forgotten the fundamental fact that all men are created bound by their protoplasmic make-up and unequal in their powers and responsibilities." It is evidently now of great importance to collect a large number of pedigrees, in which the data shall be stated with scientific exactness and in minute detail. Such a mass of facts may then be studied in the light of our present knowledge in order to determine in how far the laws of heredity apply to human characters. This is being done by the Eugenics Eecord Office at Cold Springs Harbor, New York, under the patronage of the Carnegie Institution. Specifically, the Eecord Office seeks pedigrees of families in which one or more of the following traits appear : short stature, tallness, cor- PRINCIPLES OF HEREDITY 425 pulency, special talents in music, art, literature, mechanics, invention, and mathematics, rheumatism, multiple sclerosis, hereditary ataxy, Meniere's disease, chorea of all forms, eye defects of all forms, otosclero- sis, peculiarities of hair, skin, and nails (especially red hair), albinism, harelip and cleft palate, peculiarities of the teeth, cancer, Thomsen's disease, hemophilia, exophthalmic goiter, diabetes, alkaptonuria, gout, peculiarities of the hands and feet and of other parts of the skeleton. In brief, then, the aim of eugenics is through heredity to give the individual the greatest of all birthrights, viz., good human protoplasm, and to eliminate, as far as may be possible, bad human protoplasm. PRINCIPLES OP HEREDITY For a clearer understanding of the hereditary transmission of dis- ease, malformations, and defects it is necessary to have an understand- ing of the principal views upon organic evolution and the theories of heredity. The student of preventive medicine should especially have a clear comprehension of Mendel's .work, which has thrown a iiood of light upon the problems before us. Mendel has opened new vistas in biology, which have a practical bearing upon public health work. It is evidently impossible in a short space to do justice to such large sub- jects as evolution and heredity, and the student is, therefore, referred to the authorities given at the end of this chapter, which will repay careful study. Variation. — It has been a matter of common observation that like tends to beget like rather than "like legets like," for there is a ten- dency toward new departures. Two distinct sorts of divergences may appear among the members of a single family. The first is known as variation; the second as mutation. By variation we understand those slight differences which invariably distinguish all the members of every family. They consist of individ- ual variations which affect every part and every character. Such dif- ferences are also known as fluctuating, normal, or continuous variations to distinguish them from abnormal, definite, or discontinuous varia- tions, which are more properly termed mutations. As examples of variation in man we may cite the variations in size or stature, color of skin and eyes, curliness of hair, configuration of face, etc. Darwin lays particular emphasis upon the importance of variation in his views of organic evolution. Darwin's Theory. — The Survival of the Fittest. — Darwin's views ^ of heredity are based upon his theory of organic evolution. Two ^Darwin: "The Origin of Species," "The Descent of Man," etc. 426 HEREDITY AND EUGENICS separate factors are primarily concerned : ( 1 ) the fact of fluctuating variation, that is, that no two members of the same family ever resemble one another exactly; and (2) the occurrence of a struggle for existence between organisms, owing to the geometric rate of increase of living things. From these two facts it follows that, when a change of environ- ment takes place, certain members of an existing species will be some- what better adapted than others to withstand the new conditions, and the former will tend to survive to the exclusion of the latter. Darwin assumes that during a long series of generations this process will cause a steady change in the character of the species in the direction of better adaptation to the new conditions. In other words, Darwin considers that an accumulation of a series of small changes due to the influence of environment are transmitted hereditarily through natural selection. The remarkable effects produced in the case of domestic animals and plants by the action of artificial selection greatly influenced Darwin's views upon the selective influences which exist in nature. Darwin be- lieved in the hereditary transmission of acquired characters and re- garded organic evolution as proceeding by a slow, gradual, or continuous process. There can be no doubt but that natural and sexual selection have a great influence, but whether sufficient to originate new species or even new specific characters is a question. Now that the transmis- sion of acquired characters is denied by students of heredity, and the fact that DeVries has actually observed new species arise suddenly, Darwin's theory of organic evolution and the origin of species is receiv- ing critical examination. Darwin firmly believed that the characters of organisms can be modified by selection, and he made this the foundation stone of his theory of evolution. The brilliancy of the mutation theory of DeVries, coupled with his great service to biology in rediscovering the Mendelian laws, has somewhat dazzled our eyes. Castle believes, after ten years of continuous work in selection, that much may be accomplished by this means quite apart from the process of mutation, and considers that the work of DeVries himself argues strongly in favor of this idea, although his interpretation of it is adverse to selection. From the evi- dence at hand we must conclude that Darwin was right in assigning great importance to selection in evolution, that progress results not merely from sorting out particular combinations by large and striking unit characters, but also from the selection of slight differences in the potentiality of gametes representing the same unit character combina- tions. Mutation. — Mutations comprise definite differences, usually of con- siderable magnitude — differences that indicate specific characters or the beginning of new species. Such differences are also known as ab- PRINCIPLES OF HEREDITY 427 normal,' definite, or discontinuous variations, but more properly they are termed mutations, sometimes "sports." Mutations may be either useful or harmful. They arise spontaneously and may be transmitted hereditarily in accordance with Mendel's law. As examples of muta- tions in man we may cite albinism, polydactylism, brachydactylism, etc. DeVries, Bateson, and the "mutationists" are convinced that muta- tion is a much more important factor in the origin of species than variation, as understood by Darwin. In the light of Mendel's work mutations appear to be unit characters which arise "spontaneously'" — in some instances they represent recessive characters that have remained dormant for many generations. DeVries — ^Discontinuous Evolution. — The observations of DeVries upon the evening primrose (QSnoihera lamarclciana) convinced him that species may arise suddenly, that evolution is discontinuous and goes by leaps and bounds rather than by the slow or continuous process of or- ganic evolution described by Darwin. Mutation is the term applied by DeVries to express the process of origination of a new species or a new specific character, when this takes place by the discontinuous method at a single step. DeVries believes that this is the most important, if not the sole, method by which new species or specific characters arise. To those who are convinced that acquired characters are not inherited the explanations of Lamarck and Darwin have always been incomplete. Darwin insisted that nature does not make jumps and that new species arise slowly through the action of natural selection on minute variations — a gradual or continuous evo- lution.^ From his experiments DeVries concludes that when selection is really efficient the full possible effects of this process are exhausted in quite a small number of generations, and that then the only further effect of selection is to keep up the standard already arrived at. De- Vries actually obtained quite a number of new types of plants which arose suddenly and naturally. When they made their appearance the majority of the new types came true to seed. With regard to the causes of mutation little is known, unless we assume that they represent unit characters which have long remained recessive. Weismann's Views. — Weismann's '' views are based largely upon his assumption that the germ plasm is distinct from the body and that ac- quired characters are not inherited. The parent is composed biologi- cally of somatic or body cells which are mortal, and reproduction cells or germ plasm which is distinct, continuous, immortal. The germ cells undergo the least modification from their original condition. In- deed, Weismann believes that there is no reason for supposing that they 'Darwin, however, recognized the facts of mutations or "sports" as he called them and dwelt upon their importance. ^Weismann. A.: "Essays upon Heredity," 1889, and "The EvolutlO^ Theory," 1906, 428 HEREDITY AND EUGENICS have undergone any modification at all. From this point of view we may consider the nature of a given series of animals as being determined only by the particular series of cells which constitute the direct an- cestry of the germ cells in each individual. The cells which make up the bodily structure may be regarded as the result of so many offshoots which come to an end at the death of the organism and have no progeny _ of their own. The minute study of the germ cells taken in connection with modern experimental work on the methods by which inheritance takes place shows a strong tendency to confirm Weismann's view, so far as the inheritance of distinct and definite char- acters is concerned. Wilson ^ has expressed Weismann's theory as follows : It is a reversal of the true point of view to regard inheritance as taking place from the body of the parent to that of the child. The child inherits from the parent germ cell, not from the parent body, and the germ cell owes its characters not to the body which bears it, but to its descent from a preexisting germ cell of the same kind. Thus, the body is, as it were, an offshoot from the germ cell. As far as inheritance is concerned, the body is merely the carrier of the germ cells which are held in trust for coming generations. Fig. 59 illustrates Wilson's theory of inheritance as modi- fied by Lock. Mendel's Law. — We are indebted to Mendel ^ Fig. 59. — ^Wilson's The- for One of the most important observations of biol- ORT OF Inheritance ,i , • j. j. ■ j? j. ■j.i. c Modified by Lock ogJ— the most important, m fact. With reference (G, germ cells; S, to heredity. The essential factors of Mendel's dis- somatio cells). ,^, ■. i j. /ii\ n covery are: (1) unit characters, (2) dominance, (3) segregation. By a unit character is understood any characteristic of an individual that is transmitted from parent to offspring through 1 Wilson: "The Cell in Development and Inheritance," p. 13. " Gregor Johann Mendel was born July 22, 1822, at Heizendorf in Austrian Silesia. In 1843 he entered the Augustine Convent at Altbrunn as a novice, and was ordained priest in 1847. Mendel was a teacher of natural science in the Brunu Eealschule from 1853 to 1868, when he was appointed abbot of his monastery. Mendel published only the results of his work upon hybridization with peas and a few of his experiments with Hieracium. The original paper on ' ' Hybridi- zation ' ' was published in the Verh. Naturf. Ver. in Brunn, Abthandlungen IV, 1865, which appeared in 1866; the paper on "Hieracium" appeared in the same journal, VIII, 1869. The student is advised to read "Mendel's Principles of Heredity" by W. Bateson, 1909, in which he will find a translation of these two important papers. A clear exposition is also given by R. C. Punnett in his book entitled "Meudelism" (1911), ■^ I 1 1 & c •4 ' If: : s \ PEIlSrCIPLES OF HEREDITY 439 successive generations and which conforms to the following: they are usually complementary. When parents with complementary unit characters unite, it is found that one character predominates over the other. This is known as dominance. It has further been found that the unit characters contributed by the respective parents do not, as a rule, blend, but remain separate or distinct. This is known as segrega- tion. The principles of segregation and dominance have been found to apply to the inheritance of many characters in animals and plants. It should be carefully borne in mind that the unit characters themselves are not transmitted as such in the germ cells. Just what is transmitted is not definitely known. It is quite sure that the only thing that is inherited in the germ cells is something which determines the develop- ment of the unit character. This something is called a determiner. The essence of this great discovery was published by Mendel in a short paper in 1866. By some extraordinary chance Mendel's ob- servations were entirely lost sight of until the same facts were inde- pendently rediscovered in 1899 by DeVries, working in Holland, by Correns in Germany, and by Tschermak in Austria. A Schematic Representation of Mendel's Law D R . . . . P' — great-grandparental generation. D R....P'' — grandparental generation. D R....P' — parental generation. D(R) I F' — first filial (hybrid) generation. 2DD Pure dominants 2D(R) Impure dominants IRR F^ — second filial Pure reoessives (inbred) genera- tion. DD IDD 2D(R) IRR RR DD DD IDD 2D(R) IRR RR RR F^ — third genera- tion. F* — fourth gener- ation. D and R represent complementary unit characters, D the dominant character, and R the recessive character. D(R) represents a dominant with the recessive character unexpressed but potentially present. DD means pure dominants, and RR pure recessives. Mendel's law may best be understood from a concrete illustration. One of the simplest cases is that of the heredity of color in the Andalu- sian fowl, which has been so clearly described by Bateson. iSO HEEEDITY AND EUGENICS There are two established color varieties of this fowl: one with a great deal of black and one that is white with some black markings or splashes. For convenience we may refer to these as the black and white varieties respectively. Each of these breeds true by itself. Black mated with black produce none but black offspring. White mated with white produce none but white offspring. Crossing black and white, however, results in the production of fowls with a sort of grayish color called "blue'' by the fancier, though in reality it is a fine mixture of black and white. If we continue to breed succeeding generations from these blue hybrid fowls we get three different colored forms. Some will be blue, like the parents, some black, like one grandparent, some white, like the other grandparent. Further, these different colors appear in certain definite proportions among the three classes of descendants. Of the total number of the immediate offspring of the hybrid blues, ap- proximately one-half will be blue, like the parents, approximately one- fourth black, and one-fourth white, like each of the grandparents. Thus, black bred together produce only blacks; the white similarly produce only whites; the blues, on the other hand, when bred together produce a progeny sorting into three classes, and in the same propor- tion as that produced by the blues of the original hybrid generation. The fact that the black grandchildren and the white grandchildren re- spectively breed true is a very important fact. In this illustration no race of the hybrid blue character can be established, for the blues al- ways produce blacks and whites as well as blues (see diagram). Fig. 60. — Diagram Showing the Course of Color Heredity in the Anbalusian Fowl, in Which One Color Does Not Completely Dominate Another. P, paren- tal generation. The offspring of this cross constitute Fi, the first filial or hybrid gen- eration. Fi, the second filial generation. Bottom row, third filial generation. (Kel- licott.) Another instance which illustrates the phenomenon of dominant and recessive characters as well as segregation is here given. If black and white varieties of guinea pigs are crossed the offspring are all black, PRINCIPLES OF HEEBDITY 431 like one parent; that is, when black and white characters are brought together in the guinea pig, these do not appear to blend into gray or "blue," as in the ease of the Andalusian fowl, but one character alone appears. The black seems to cover up or wipe out the white. The black color is, therefore, said to be dominant and the white recessive. The white character, however, has not disappeared, for when the black offspring are crossed together the progeny falls into two groups : some black and some white. Three-fourths of the progeny are black; that is, they resemble the hybrid form and at the same time one of the grand- parents, while the remaining fourth resemble the other white grand- parent. Some of these blacks will breed true and are, therefore, known as homozygotes. Some of the blacks contain a mixture of the black and white characters and are, therefore, known as heterozygotes. The hereditary transmission of the color character in these two illustrations through the germ cell is shown in the accompanying diagram. <• CD F, FiQ. 61. — Diagram Showing the Course op Color Heredity in the Guinea-pig, in Which One Color (Black) Completely Dominates Another (White) . Refer- ence letters as in Fig. 60. (Kellicott.) Unit characters may either be positive or negative; that is, they may be due to the presence or absence of "something" in the germ cell or sperm cell. This something, known as a determiner, is a force, a molecular structure or an enzyme ( ?) in the nuclear matter of the germ-plasm. Thus, the determiner in the ease of pigment is not the pig- ment itself, but something that activates pigment production. These determiners are transmitted in the germ plasm and are the only things that are truly transmitted. The determiner may be either in the ovum or the spermi. An hereditable character may be due to the presence or absence of a determiner in the germ plasm of both parents. When a character is due to the presence of a determiner it is called positive, when due to the absence of a determiner, negative. Thus, a brown eye depends on a determiner that produces the brown-colored pigment, while the blue eye depends upon the absence of such a determiner. It is not always 432 HEKBDITY AND EUGENICS easy to anticipate whether a given character is positive or negative. For instance, long hair in Angora cats, sheep, or guinea pigs is ap- parently not due to a factor added to short hair, but rather to an absence of a determiner that stops growth in short-haired animals. One of the most important conclusions from Mendel's observations is that the different inherited traits act independently; that is, they do not blend. In other words, the definitely hereditable characters act as independent units that are without any apparent relation to other peculiarities of the individual concerned. Furthermore, these units do not interfere with each other. It follows that all the unit char- acters of an individual are to be regarded as mutually independent as- semblages. This is the doctrine of unit characters. According to this doctrine, each individual is of dual origin, paternal and maternal, and each individual is made up of a mosaic of inherited characters, some of which may be dominant, others recessive. The idea of unit char- acters capable of being inherited independently of one another is one of the most important conceptions which has been added to our knowledge of heredity. We now know from the phenomenon of segre- gation what constitutes purity in a strain of animals or plants; that is, purity does not depend upon the length of time during which a race has exhibited a constant character, for a strain of absolute purity may arise from the second generation of a cross. Mendel's law has not only explained many facts in heredity, but also has important practical bearing in the improvement of the breeds of cultivated plants and do- mestic animals. Atavism and Eeversion. — Atavism (from atavus, a grandfather) is the inheritance of properties not manifest in either parent, but pres- ent in the grandfather or some relatively recent ancestor. Mendel's observations upon recessive characters now make plain some of the phenomena known as atavism. According to Castle, atavism or rever- sion to an ancestral condition can be completely explained by the Men- delian principles. It is nothing more or less than the reassertion of recessive unit characters that have long been overshadowed by dominant characters. It seems that recessive characters may not be lost, no mat- ter how long they remain latent or dormant. The term "atavism" is sometimes employed to mean any reversion- ary condition, whether favorable or unfavorable, while the term "re- version" means a return in the offspring to a lower type, usually of some remote ancestor. The degenerations which run in families may be instances either of atavism or reversion, or mutation. Darwin's classical experiment illustrating reversion consisted in crossing a barbed fan-tail female pigeon with a barbed spot male and producing offspring hardly distinguishable from the wild Shetland species of blue-rock pigeon {Colomba livia). This is a ease of reversion, PEINCIPLES OF HEREDITY 433 in which an artificially bred and highly specialized race quickly re- covered characters which had been lost during many generations. A foal is sometimes born with a few stripes on its forelegs, as if remind- ing us of striped wild horses. Highly cultivated and specialized flowers and vegetables have a tendency to revert, and sometimes produce forms hardly distinguishable from their wild progenitors. Eeversion is due to the reassertion of latent ancestral characters. It is an impelling hereditary force which must be taken into account. True reversion may arise in pure bred races, but is much more frequent as the result of hybridization. The facts of reversion and atavism are of peculiar interest to man, for the reason that the human species has, through unconscious selec- tion and conscious effort, improved the race to its present point of superiority. Whether civilized man to-day is superior to ancient races may be doubted, but the fact is plain that civilization is breeding an artificial and highly civilized strain that shows artificial departures from primitive stock. It is well known that the high bred and "fancy" races of the do- mesticated animals show a marked tendency to reversion or deteriora- tion of type. Likewise, the human race shows the same tendency to revert to tj'pes resembling its forebears. The present level attained by the more highly civilized races can only be maintained by a continua- tion of that struggle for improvement, progress, and desire for per- fection which is an inborn characteristic and an essential element of progress. Owing to the artificial position to which the human race has brought itself, it becomes necessary to continue the struggle — to stand still means rapid deterioration. Some of the stigmata of degen- eration and hereditary defects may be accounted for by this natural tendency on the part of an artificially nurtured standard to slip back- ward. G-alton's Law of Filial Regression. — Filial regression has nothing to do with reversion. The law of filial regression concretely stated is that offspring are not likely to differ from mediocrity in a given direction so widely as their parents do in the same direction. There is a contin- ual tendency to sustain a specific average or a stock average. Let us take a simple instance from Professor Karl Pearson's "Gram- mar of Science." Suppose a group of fathers with a stature of 72 in. : the mean height of their sons is 70.8 in. — a regression toward the mean height of the general population. On the other hand, fathers with a mean height of 66 in. give a group of sons of mean height 68.3 in. — again nearer the mean height of the general population. The "regression" works both ways — ^there is a leveling up as well as a level- ing down. "The father with a great excess of the character contributes sons with an excess, but a less excess of it; the father with a great 434 HEEEDITY AND EUGENICS defect of the character contributes sons with a defect, but less of it" (Thompson). THE CELL IN HEREDITY Each parent (male and female) is composed biologically of somatic or body cells, which are mortal, and germ plasm which is distinct, con- tinuous, immortal. The development and embryology of the germ and sperm cells are of particular interest to the student of heredity. The view has gained ground and general acceptance that the nucleus is the chief or exclusive bearer of the hereditable characters; that is, the female nuclear material transmits the characters of the mother and her forebears and the male nucleus those of the father and his fore- bears to the offspring. Cells divide and multiply in two ways: (1) by direct division or amitosis, and (2) by indirect division or mitosis. Direct division oc- curs more frequently than is usually suspected. The process appears to be a very simple one; the nucleus divides without any preliminary arrangement of its structure, the cytoplasm is constricted, and presently we have two cells in place of one. Indirect division or mitosis appears to be the natural mode of cell development. The chromatin, which is the deeply staining matter in the nucleus, rearranges itself from its "resting" stage. After a complicated process the nuclear matter forms itself into a long cylindrical thread known as the linene thread. This then divides into links or chromosomes.^ The chromosomes are of spe- cial interest, for they are believed to carry the hereditable traits. In amitotic division each chromosome is divided in half longitu- dinally, as a stick might be split up the middle, and after a very com- plex process the halves of each split chromosome migrate to opposite poles. Then each centrosome attracts a group of chromosomes con- sisting of just one-half of the original chromatin material. Each group then, in orderly fashion, rounds itself into a new nucleus, and the body of the cell (the cytoplasm) constricts across the equatorial plane, and two cells are formed. Every species of plant or animal has a fixed and characteristic number of chromosomes which regularly recurs in the division of all of its cells and in all forms arising by sexual reproduction the number is even. Thus, in some of the sharks the number of chromosomes is 36, in certain gastrapodes it is 32 ; in the mouse and salamander, the trout, the lily, 24; in the worm Saggita, 18; in the ox and guinea pig, 16; in man the number was formerly stated as 16, now 24. In ^ For a full understanding of cell division the student is referred to one of the standard text-books upon Cytolo^, or Minot 's ' ' Embryology ' ' ; also, to B. B. Wilson 's ' ' The Cell in Development and Inheritance, ' ' 2d Ed., 1900. THE CELL IN HEEEDITY 435 crustaceans the number of chromosomes may be as high as 168. In a few insects the females have in their body cells one chromosome in addition to the number possessed by the males. This has been inter- preted as bearing upon the determination of sex. Van Beneden in 1885 discovered the important fact that the nu- cleus of the ovum and the nucleus of the spermatozoon which unite in fertilization contain each one-half of the number of chromosomes characteristic of the body cells. As both the germ and sperm cells contain only half the number of chromosomes, a reduction must take place in the history of these cells; in fact, alike in the history of the germ cell and in the history of the sperm cell, there is a parallel reduction in the number of chromosomes to one-half. This reduction appears to be a preparation of the repro- duction cells for their subsequent union, and a means by which the number of chromosomes is held constant in the species. In sexual reproduction each centrosome attracts a group of chromo- somes, half of which are of paternal origin and half of maternal origin. This is interpreted as meaning that the paternal and materual chromo- somes that unite to form the new zygote probably carry the heredi- table characters. The gist and meaning of the whole process to the student of hered- ity is the precisely equal partition of the maternal and paternal con- tributions, so that each of the daughter cells has a nucleus half from the mother and half from the father. Although the ovum is much larger than the spermatozoon, each contributes equally so. far as the amount of nuclear matter is concerned; the new individual is dual in its origin, and the offspring is a double creature and retains its duality to its dying day, and transmits it to succeeding generations. Professor E. B. Wilson states the generally accepted opinion some- what as follows: As the ovum is much larger it is believed to furnish the initial capital — including, it may be, a legacy of food yolk — for the early development of the embryo. From both parents alike comes the inherited organization which has its seat (according to most biolo- gists) in the readily stainable chromatin rods of the nuclei. From the father comes a little body, the centrosome, which organizes the ma- chinery of division by which the egg splits up and distributes the dual inheritance equally between the daughter cells. The ovum may be stimulated to maturation without the sperm cell (parthenogenesis). When this happens individuals are produced similar to, but not as vigorous as, the normal types. The sperm cell similarly is able to develop without the nuclear matter of the egg. In other words, the ovum and the sperm each contain potential factors for the new individual, As we have already seen, in accordance with 436 HBEEDITY AND EUGENICS "Weismann's theory, that the germ plasm is independent of the body and is continuous; therefore, acquired characters not affecting the germ plasm are not inherited in accordance with this conception. Foreign bodies carried along by either the germ or sperm cells are not instances of true heredity; therefore, in the present-day con- ception of heredity it is not possible for a microbic disease to be trans- mitted hereditarily, even though the microorganism is contained in either the germ or the sperm. Thus, hens may be caused to lay col- ored eggs by feeding the hen with anilin dyes. Anaphylaxis is an example of a transmitted property, but the substance, whatever it is, seems to be carried along with the maternal germ cell as a foreign body. In the case of syphilis, the Treponema pallidum may be carried along by the germ or sperm, and the disease is said to be transmitted hereditarily, but, strictly, the microorganism is carried as a foreign body and not as a unit character or constituent part of the nuclear mattfer. BIOMETRY Statistical methods applied to biology have been termed biometry by Professor Karl Pearson. Francis Galton's book on "Natural In- heritance" is a pioneer in the subject, and embodies a lucid introduction to the statistical study of variation and inheritance. The health offi- cer must be familiar with statistical methods not only in their applica- tion to biology, but as they relate to vital statistics. The health officer who lacks the quantitative view or who fails to grasp the statistical values of the facts and factors in preventive medicine works under a decided handicap. The sanitarian who is ignorant of statistical methods must necessarily grope in the dark. Efficiency and economy in public health work depend not alone upon a knowledge of the biological sciences, but also upon a correct sense of proportion. The statistical method is a strong lever which makes for sane administration, economy in expenditure, efficiency of effort; in short, successful results. Statistics deal with groups rather than with individuals. It must be understood that the average of a group may represent something quite different from any individual which the group contains. Also a group may contain individuals of very diverse natures. In collecting statistical material the data must be gathered without any preconceived ideas and without , neglecting any members. In this respect statistical methods differ from biological methods, which require careful discrimi- nation of data. The quantitative determination of a character may be made by various methods, as by counting or by measurement. The statistical method may be illustrated by a simple model, such as that suggested by Galton. This is a modification of the familiar BIOMETEY 437 bagatelle board covered with glass and arranged as shown in Fig. 62. A funnel-shaped container at the top of the board is filled with peas or similar objects. Below this is a regular series of obstacles symmetri- cally arranged, and at the bottom of the board is a row of vertical com- partments also arranged symmetrically with reference to the chief axis of the whole system. If we allow the peas to run through the funnel and fall among the obstacles into the compartments below, we find that their distribution will follow certain laws capable of precise mathe- matical description. The distribution of the peas may be predicted A B \ Fig. 62. — Model to Illusthate the Law of Probability or "Chance." A, Peas held in container at top of board. B, Peas after having fallen through the obstruc- tions into the vertical compartments below. The curve connecting the tops of the columns of peas is the normal probability curve. with fair accuracy. The middle compartment will receive the most; the compartments next the middle somewhat fewer; those further from the middle still fewer ; and the end compartment fewest. If we connect the top of each column of peas by a curved line we get a curve known as the "normal frequency curve." A curve of the same essential char- acter would result from plotting the dimensions of a thousand cobble- stones, the deviation from the bull's eye in a target shooting contest, or by plotting the variability of a biologic character, such as the stature or strength of men, the spread of sparrows' wings, the number of rays on scallop shells, or of ray flowers of daisies. While from the above law of probability we know quite definitely 30 438 HEEEDITY AND EUGEmCS what the general distribution of the peas will be, we do not know at all the future position of any single pea. Of this we can speak only in terms of probability. The chances are very high that it will fall in one of the three middle compartments, very low that it will be one of the extreme compartments. The chances are equal that any individual pea will fall above or below the average or middle position. We there- fore see that in any group there are many more individuals near the average than there are in the classes removed from the average, and the farther the removal of a class from the average the smaller the number of individuals in that class; hence, we have the important fact in statistical methods that an individual may belong to a group with- out representing it fairly. In order to get a correct idea of the whole group we must know first to what extent deviation in each direction Q M Q' Fig. 63. — Normal Curve. (Lock.) occurs above and below the group average; and, second, the average amount by which each individual of the group deviates from this group average; that is, we must know the amount of variability as well as the extent of the greatest divergence from the average. Hence, we have the following definitions and corollaries : The mode of a normal curve is the longest perpendicular which can be drawn from the base line to meet the curve itself, M, Fig. 63. The normal curve is symmetrically on either side of the mode; that is to say, two perpendiculars drawn from the base to the curve on either side of the mode and at the same distance from it will be equal in length. The median is a perpendicular line which divides the area of the curve into two equal halves. In dealing with a symmetrical curve the position of the mode is identical with that of the median. The mean or average of all the values from which the curve is con- structed is the foot of the median. In any actual case obtained by BIOMETEY 439 practical methods the position of the mode, the median, and the mean will only be approximately the same because such a curve is never perfectly symmetrical. The quartile is the distance from the median to a perpendicular line extending from the base of the curve at such a distance from the median that it divides the area inclosed by the median, the base, and half the curve into two equal parts. Any given curve will have two quartiles, one on either side of the median. They are shown at Q and Q'. (Fig. 63.) A variaie is one of the separate numerical values from which a curve of variability can be constructed. The accuracy of the statistical method is usually proportionate to the number of variates out of which the curve is built. The biometrician usually deals with some such number as 1,000 variates. The total number of variates is represented by the area inclosed by the curve, and it will be seen that half the total number of variates falls between the two quartiles and half outside of them. A class may be defined as a group of variates all of which show a particular value or a value falling between certain limits. The frequency of a class is the number of variates which it contains. The amount of variation shown by a particular group of variates is measured by the degree of slope of the curve. A flat curve indi- cates greater variability and a steep curve denotes less variability. The standard deviation, of a normal curve is the measure of vari- ability and is more often used than the quartile and is expressed shortly as ff. The value of ff is found by multiplying the square of the devi- ation of each class from the mean (or mode) by the frequency of the class, adding together the series of products so obtained, dividing this number by the total number of variates, extracting the square root of the result, and multiplying by the number of units in the class arranged. The coefficient of variability is a purely abstract number obtained by dividing the standard deviation by the magnitude of the mean in any particular case and multiplying the result by 100. The prolable error arises from the circumstances that half the total number of variates lies outside the limits of the quartile and half within. The probable error of any statistical determination is obtained by find- ing a pair of values lying one above and one below the true value re- quired. For further details regarding properties of normal curves the student is directed to Davenport's "Statistical Methods with Special Eeference to Biological Variation." 440 HEEEDITY AND EUGENICS HEREDITY VERSUS ENVIRONMENT How much of our physical and mental makeup is due to heredity (nature) and how much to environment (nurture) is one of the much- discussed problems. It seems evident to students of biology that by far the overwhelming factor in our organization is set and definitely fixed at our birth. Heredity appears to be the overshadowing influence of first and prime importance. Herbert Spencer well said that "in- herited constitution must ever be the chief factor in determining char- acter." Environment may influence the individual, but apparently has small and slow power of propagating itself for good; great and rapid power for evil. That is, the hereditary transmission of acquired char- acters is denied, but the transmission of defects of organization, such as insanity, deaf mutism, the consequences of syphilis, alcoholism, and other vices, are fully recognized. Atavism, reversion, and muta- tions must not be regarded as instances of the hereditary transmission of acquired characters in the biological sense. The tendency of the artificially bred strains of the civilized human races to revert and de- teriorate has already been emphasized. Despite the teachings of biology we are convinced that life is in- exorably conditioned by its environment. Jordan states that "among the factors everywhere and inevitably connected with the course of descent of any species variation, heredity, selection, and isolation must appear; the first two innate, part of the definition of organic life; the last two extrinsic, arising from the necessities of environment, and not one of these can find leverage without the presence of the others." In the present state of our knowledge, while we are convinced that hered- ity plays the major role, we are by no means prepared to deny the influence of environment. IMMUNITY GAINED THROUGH INHERITANCE Immunity to disease is either natural or acquired. Natural immu- nity is inherited through successive generations of a species or a race. Acquired immunity, like other acquired characters, is probably not inherited as a "unit character" in the sense of Mendel. Thus, there has been little variation in our natural power to resist most in- fections, such as tuberculosis, yellow fever, plague, smallpox, cholera, tetanus, measles, scarlet fever, diphtheria, and so on through a long list, although these diseases have doubtless afflicted the human species through untold ages. The fluctuating virulence of some infections is a matter of common knowledge, and is doubtless due to many factors. In a few well-known instances a certain amount of tolerance or re- IMMUNITY GAINED THEOUGH INHEEITANCE 441 sistance has been gained and perhaps transmitted through succeeding generations by a process of the survival of the fittest. Thus, syphilis is much less virulent now than it was during the great pandemic of the sixteenth century. The resistance which the natives enjoy to ma- laria in badly infected quarters of the globe is largely acquired as a result of early infections, and this increased resistance is perhaps partly transmitted by a weeding out of the very susceptible (see chapter on Immunity). CHAPTER III THE HEREDITARY TRANSMISSION OF DISEASE We are now prepared to discuss more in detail the hereditary transmission of disease. The question whether disease is ever trans- mitted hereditarily or not rests somewhat upon our conception of dis- ease; that is, whether it is an entity, a process, or a "unit character." The process itself, of course, cannot be transmitted, but the potentiality of it may be involved in some peculiarity in the organization of the germ plasm. This may be, and often is, transmitted through succes- sive generations. In the limited sense in which the word "heredity" is used in biology and in the limited sense in which the word "disease" is used in pathology, there may be no inherited diseases, but this ap- pears to be a quibble of words or a matter of definitions. While we are not familiar with the intimate processes concerned, we are certain that many abnormal conditions of mind and body are transmitted. Some of them follow the Mendelian principles. Formerly a large number of diseases were regarded as transmissible, but the list has been revised and restricted as a result of recent studies. The reappearance of a diseased condition in successive generations does not prove that it has been transmitted or even that it is transmissible. This mistake has been made with tuberculosis and other infections. Lack of completeness vitiates most of the statistics bearing on heredity in relation to human diseases. Even in the case of clearly in- herited diseases there are very few pedigrees sufficiently complete for the study of the applicability of Mendelian and other laws of heredity. Sometimes the disease itself is not transmitted, but a tendency to the disease is transmitted. This will be discussed again. 'Some unit characters as well as certain diseases are transmitted hereditarily, but limited to one sex; that is, the disease or condition appears in one sex only, although transmitted by the other. The best example of a sex-limited disease is hemophilia, which affects males al- most exclusively, but is transmitted through the normal female. Color- blindness is also transmitted hereditarily, but is sex-limited, as it af- fects males almost exclusively. This remarkable sort of inheritance, known as sex-limited inheritance, 443 GENEEAL CONSIDERATIONS 443 occurs when the male parent is characterized by the absence of some character of which the determiner is typically lodged in the sex (x) chromosome. A striking feature of this sort of heredity is that the trait appears only in males of the family, but is not transmitted by them ; it is transmitted, however, through normal females of the family. Examples of this sort of heredity occur in hemophilia, color-blindness, also in multiple sclerosis, atrophy of the optic nerve, myopia, ichthyosis, and muscular atrophy. The explanation is the same in all cases of sex-limited heredity. The abnormal condition is due to the absence of a determiner from the male sex chromosome. The diseases, defects, and conditions believed to be transmitted hereditarily are discussed in the following pages. Some of these dis- eases, malformations, and defects of organization follow Mendel's law. It is probable that other diseases, tendencies, and characters are trans- missible, but the subject has only recently been placed upon a scientific basis, and it will require careful and prolonged observation to estab- lish the facts. It is often difficult to determine whether the disease itself or a tendency to the disease has been transmitted in any particu- lar case, and, further, it is often difficult to decide whether an individ- ual has inherited or acquired his affliction. The transmissible defects which are of principal concern to the human species are the defects of organization of the central nervous system. It is important to remember that the defects of the nervous system do not necessarily propagate just the same defects in the suc- ceeding generations. Thus, an epileptic does not necessarily beget epileptics; epilepsy, insanity, degeneracy, color-blindness, and other stig- mata may arise as the result of deficiencies of various kinds in the forebears. Defects such as harelip, cleft palate, cervical fistula, spina bifida, etc., are, not true instances of hereditary transmission of specific char- acters. They rather represent an inherited deficiency in developmental vigor. These defects for the most part represent the failure of parts to unite during embryological development; in other words, the failure of embryological clefts to close normally. Such deformities, as well as clubfoot, web fingers, and other acquired or congenital deformities or disfigurations, are not, as a rule, transmitted. Some practical problems of great importance arise from our knowl- edge of the hereditary transmission of disease and defects. A man or woman who intends marrying is now more than justified in carefully examining the personal and medical histories of the family of his or her intended mate. It is not only possible to foretell the color of the eyes, the nature of the hair, and other Mendelian characters in the future offspring, but it is also possible to foretell, with mathematical precision, the chances of transmitting defects, such as insanity, epi- 444 THE HEREDITAEY TEANSMISSION OP DISEASE lepsy, degeneracy, deaf-mutism, color-blindness, migraine, and other nervous disorders, as well as hemophilia, polydactylism, brachydactylism, albinism, and other stigmata. In any doubtful ease it may be well to consult a student of heredity, for it is possible to foretell with precision in certain cases which characters will and which will not be transmitted. To illustrate the precision with which the characters of offspring may be predicted in the best studied cases, we need only refer to the color of the eyes. Two parents with pure blue eyes will have only blue-eyed offspring, for they both lack the brown pigment which de- termines the color of the iris. Similarly, if the hair of parents be flaxen, this may be taken as evidence of the absence of a hair-pigment- determiner in the germ plasm, and the offspring will have flaxen hair. For the same reason parents with lack of curliness or waviness of hair will have only straight-haired children. In determining whether transmissible characters are apt to reappear in successive generations or not we must know whether these characters are positive or negative, that is, whether they are due to the presence or absence of determiners.^ Inbreeding may be hazardous, for reasons that are well understood. The marriage of cousins will be evidently hazardous if the objection- able hereditary characters are dominant, for in this case the danger is plain; if the characters are recessive the danger is specially unfortunate, because of unexpected outcroppings in the offspring. Inbreeding tends to secure homozygous combinations, and this brings to the surface latent or hidden recessive characters. Crossbreeding brings together differentiated gametes which, reacting on each other, produce offspring of greater vigor. On the other hand, continued crossbreeding only tends to hide inherent defects, not to exterminate them; inbreeding only tends to bring them to the surface, not to create them. It is not, therefore, correct to ascribe to inbreeding by intermarriage the creation of bad racial traits, but only their manifestation. Further, a racial stock which maintains a high standard of excellence under inbreeding is certainly one of great vigor and free from inherent defects (Castle). The variety of the product of consanguineous marriage is well brought out when we compare localities. Thus, consanguinity on Martha's Vineyard results in 11 per cent, deaf mutes and a number of hermaphrodites; in Point Judith, 13 per cent, idiocy and 7 per cent, insanity; in an island off the Maine coast the consequence is "intellec- tual dullness"; in Block Island, loss of fecundity; in some of the "Banks" off the coast of North Carolina suspiciousness and an inability ^ We do not yet know all the unit characters in man, and it is impossible to foretell which of them are due to positive determiners and which to the absence of such. TENDENCY TO A DISEASE 445 to pass beyond the third or fourth grade of school; in a peninsula on the east coast of Chesapeake Bay the defect is dwarf ness of stature; in George ■ Island and Abaco (Bahama Islands) it is idiocy and blind- ness (G. A. Penrose, 1905). There is thus no one trait that results from the marriage of kin; the result is determined by the specific de- fect in the germ plasm of the common ancestor. The Mierobic Diseases. — It seems a confusion of thought to the student of heredity to speak of the inheritance of any mierobic disease. At one time the hereditary transmission of mierobic diseases was gen- erally believed. ISTow we know that, in the true sense of the term, no infectious disease is transmitted hereditarily — for even in the case of syphilis the Treponema pallidum is carried in the germ or sperm as a foreign body. Tuberculosis at one time was considered as transmitted, but we now know that this occurs so seldom that the popular pam- phlets are entirely justified in denying it entirely. Children are some- times born with smallpox, measles, and other infections; these are not true instances of heredity, but eases of congenital transmission. Congenital Transmission. — Prenatal infection is not a true in- stance of inheritance. Mierobic diseases may be acquired by infection through the placenta during the fetal period. The placenta is a bet- ter filter for some infections than for others. Thus, anthrax and tu- berculosis of the mother are rarely transmitted to the fetus, while there is great liability in the case of syphilis. The fetus in utero may take smallpox, measles, and other infections, but these instances are more properly spoken of as congenital than inherited. We must remember that to be inherited on the part of the offspring or transmitted on the part of the parents biology includes only those characters or their physical bases which were contained in the germ plasm of the parental sex cells (Martius) ; or, as Verco says, "what operates on the germ after the fusion of the sex nuclei, modifying the embryo, or even inducing an actual deviation in the development, can- not be spoken of as inherited. It belongs to the category of early ac- quired deviations which are, therefore, frequently congenital." Hereditary Transmission of a Tendency to a Disease.— While the disease itself may not be transmitted, a tendency to a disease, known as a diathesis, may be transmitted through successive generations. A person may inherit a small bony struciture, a poor musculature, "weak" lungs, susceptible mucous membranes, an abnormal amount, distribu- tion, or development of lymphoid structures, etc. In fact, we are not all born equal, and most persons h^e some vulnerable structure or organ which is commonly spoken of as their "weak point." In many cases this locusminoris resist entim is inherited as a defect in structure or function. Davenport has collected the health record? and other characterig- 446 THE HBEBDITAEY TKANSMISSIOISr OF DISEASE tics furnished for over two hundred families by members of the fam- ilies concerned. He finds certain definite facts in the behavior of some of the commoner diseases. As an example of the inheritance of a gen- eral weakness in an organ he cites the case of the mucous membranes. Thus, in one family the principal diseases to which there was liability were located in the mucous membranes of the nose, throat, and bronchi. In another family the center of susceptibility was more specific, being nearly confined to the nose and throat. In another family the weak- ness was in the ear; in another the lungs; in another the skin; in one family the kidneys were the seat of incidence, etc. The examination of the health pedigrees of a number of families impresses one by the fact that the incidence of disease is not always haphazard, for in any large family the various causes of death do not occur in the proportions given in the census table for the population as a whole. Tuberculosis.' — We know that tuberculosis is never transmitted hered- itarily, and is seldom contracted congenitally. The reason that tu- berculosis runs in a family is twofold: (1) an inherited predisposition to the disease, and (2) increased chances of infection. Just what the tendency or predisposition is is not well understood. We do know, however, that the predisposition is not so great but that it may be overcome; the infection may be avoided and the disease prevented. It is now perfectly plain that the principal reason why tuberculosis runs in families is the close association between the infected and well members of the family, which increases the chances of infection and re- infection. All persons inherit more or less powers of resisting tuberculosis. The inborn immunity is not marked in any case; in some individuals it is quite feeble. The border line between immunity and susceptibility to tuberculosis in the human species is delicately balanced and may readily be overturned (see page 135). Syphilis. — Syphilis and the consequences of syphilis are transmitted from parent to offspring — "even unto the third and fourth generation." Strictly speaking, and in accordance with the present-day conception of heredity, it may not be proper to speak of syphilis as a true in- stance of heredity, but whatever the definition of words may be the facts are plain. The reason that the student of biology refuses to re- gard syphilis as well as other microbic diseases as true instances of heredity is that the Treponema pallidum is transmitted in the germ plasm as a foreign body, and not as a unit character. The transmission of syphilis, therefore, does not obey Mendel's law. It must be remem- bered that while syphilis itself is not a true instance of hereditary trans- mission, the consequences of syphilis may descend as inherited defects through many generations, Syphilis may be transmitted in three ways ; SYPHILIS 447 (a) from the father (sperm inheritance) ; (b) from the mother (germ inheritance); (c) placental transmission (congenital). Osier sum- marizes the hereditary transmission of syphilis as follows: (a) Paternal Transmission {Sperm Inheritance). — This is the most common form — in which the father is infected, the mother being healthy. The Treponema pallidum has not yet been found in the sperm cell, but we do not know its life phases, and from what we do know of the life history of syphilis it seems probable that all the sperm cells are not infective. A syphilitic father may beget an apparently healthy child, even when the disease is fresh and full-blown. On the other hand, in very rare instances a man may have had syphilis when young, un- dergo treatment, and for years present no signs of disease, and yet his first born may show very characteristic lesions. The closer the beget- ting to the primary sore the greater the chance of infection. A man with tertiary lesions may beget healthy children. As a general rule, it may be said that with judicious treatment the transmissive power rarely exceeds three or four years. (b) Maternal Transmission {Germ Inheritance) . — While the father may not be affected, in a large number of instances both parents are diseased, the one having infected the other, in which case the chances of fetal infection are greatly increased. Heredity through the mother alone is much more fatal to the offspring than paternal heredity. It is a remarkable and interesting fact that a woman who has borne a syphilitic child is herself immune, and cannot be infected, though she may present no signs of the disease. This is known as Beaumes' oi Colles' law, and was thus stated by the distinguished Dublin surgeon: "That a child born of a mother who is without obvious venereal symp- toms, and which, without being exposed to any infection subsequent to its birth, shows this disease when a few weeks old, this child will in- fect the most healthy nurse, whether she suckle it, or merely handle and dress it ; and yet this child is never known to infect its own mother, even though she suckle it while it has venereal ulcers of the lips and tongue." In a majority of these cases the mother has received a sort of protective inoculation, without having had actual manifestations of the disease. A child showing no taint, but born of a woman suffering with syphilis, may with impunity be suckled by its mother (Prof eta's law). (c) Placental Transmission. — The mother may be infected after conception, in which case the child may be, but is not necessarily, born syphilitic. If the infection is late in pregnancy, after the seventh month, the child usually escapes. Osier and Churchman state that syphilitics may marry with safety after they have undergone three years of thorough treatment and have been without symptoms at least one year after treatment has ceased. 448 THE HEEEDITAEY TEANSMISSION OF DISEASE Cancer. — It will probably be a long time before the final word can be said concerning the influence of heredity in cancer. At present there is no proof that heredity plays a part in the causation of can- cer, but trustworthy conclusions are not possible in the present incomplete state of our knowl- edge upon the subject. Leprosy. — Lepjosy was for- merly regarded as one of the inherited infections. Leprosy is not transmitted. The children of lepers born out of leper dis- tricts, in England or the United States, for example, never in- herit it. The disease is con- tracted after birth, as tuberculo- sis and other microbic diseases are contracted. Deaf -mutism. — Deaf -mutism is due to a great variety of causes, but in different individuals of the same family the chances are large that it is due to the same defect. This defect is frequent- ly recessive, that is, hidden in the normal children. Two such normal children who are cousins but from deaf-mute stock tend to have about one-fourth of their offspring deaf-mutes. The pro- portion of congenital deaf off- spring is thrice as great among cousin marriages as among others. The conclusions of Fay, based on extensive statistics, deserve to be widely known. "Under all circumstances it is exceedingly dangerous for a deaf person to marry a blood rela- tive, no matter whether the rela- tive is deaf or hearing, nor whether the deafness of either or both or neither of the partners is congenital, nor whether either or both or neither have other deaf relatives besides the other partner." Albinism. — Albinism belongs to a class of cases resulting from the COLOE-BLINDNESS 449 absence of a character or quality — in this instance the absence of a pig- ment determiner. Two albino parents have only albino children. Nor- mal offspring of an albino and a pigmented parent may transmit the albinic condition. Albinism is an extreme case of blondeness, all pigment being absent from skin, hair, and eyes. The method of inheritance resembles that of eye color. When both parents lack pigment, all offspring are like- wise devoid of pigment. When one parent only is an albino and the other is unrelated, then the children are all pigmented. Whenever pigmented parents have albino children, the proportion of the albinos approaches the ideal and expected Mendelian proportions — 25 per cent. Davenport points out that albinos may avoid albinism in their offspring by marrying unrelated pigmented persons. Pigmented persons belong- ing to albinic strains must avoid marrying cousins, even pigmented ones, because both parents might, in that case, have albinic germ cells and produce one child in four albinic. Albino communities, of which there are several in the United States, are inbred communities, but not all inbred communities contain albinos. Color-blindness, or Daltonism. — Color-blindness, or daltonism, is a condition probably not localized in the eyes, but due to some defect in the central nervous structure. It is transmitted hereditarily. Color- blindness is much commoner in men than in women. A color-blind man, however, does not transmit color-blindness to his sons, but only to his daughters. The daughters, however, are themselves normal, pro- vided the mother was, yet the daughters transmit color-blindness to half their sons. A color-blind daughter could be produced apparently only by the marriage of a color-blind man with a woman who trans- mits color-blindness, since the daughter, to be color-blind, must have received this unit character from both parents, whereas the color-blind son receives the character only from his mother; that is, the condition is sex-limited. Color-blindness is apparently due to a defect in the germ cell- absence of something normally associated there, with an X-structure which is represented twice in women, once in men. The following interesting family history, studied by Horner, shows the hereditary persistence of color-blindness and its transmission to male offspring through normal females. 450 THE HEREDITARY TRANSMISSION OF DISEASE M F I M M M 1 F 1 1 1 1 il i 1 1 1 F 1 1 F M M F F M ^ T^^ ^ M F i F F M M M M^Male. F=Female. Bold-faced type=Color-blind subjects. The following pedigree of a family containing color-blind members was worked out by Dr. Rivers among the Todas, an Indian tribe: 1 M 1 i ^ 1 M 1 F F 1 F ~4 1 1 F M F F M M M 1 1 AM F M F M F M F F M M M M M M F M M Hemophilia. — Hemophilia is a condition in which the blood does not coagulate properly, and those having this condition may bleed to death from minute wounds. It is transmitted hereditarily and is largely confined to males, although transmitted by normal females. It is one of the best instances of an hereditable character, sex-limited. M F M M I M I M I I I I I I I I I I M F F MMMF M M F MMMF M F MMF MM MF I J I J. j I MF MFMF MF F M F lil F fM¥ U f (Bold-faced type indicates bleeders.) EETINITIS PIGMENTOSA 451 The foregoing case, given by Klebbs, is instructive in showing how the tendency, though transmitted through daughters, finds expression only in the males, and in illustrating first a diffusion and then a wan- ing of the peculiarity (Thompson). Gout. — It is known that gout runs in families, but just what the predisposition is that favors this condition of deranged metabolism is not known. During four centuries one family history showed that out of 535 gouty subjects 309 had a family taint — about 60 per cent. In another family out of 156 cases 140 had a family taints — about 90 per cent. Statistics show that in from 50 to 60 per cent, of all cases the disease existed in the parents or grandparents. It seems clear that some predisposing factor may be transmitted hereditarily, but in any individual case it is not always plain how much is due to heredity and how much to environment. Brachydactylism.- — A typical example of an abnormality is that of brachydactylism, or short-fingeredness, a condition in which each digit comprises only two phalanges — the fingers are all thumbs. This con- dition seems to be due to an inhibition of the normal growth process, that is, normality implies entire absence of the determiner that stops the growth of the fingers in the brachydactyl. Thus, a brachydactyl person married even to a normal person will beget 100 per cent, or 50 per cent, abnormals, according to circumstances; but two parents who, though derived from brachydactyl strains, altogether lacking the determiner which inhibits the growth of the fingers may have only normal children. According to Punnett, brachydactylism is a good example of a simple Mendelian case. It behaves as a simple dominant to the normal ; that is, it depends upon a factor which the normal does not contain. The recessive normals cannot transmit the affected condition whatever their ancestry. Once free, they always remain free, and can marry other normals with full confidence that none of their children will show the deformity. Polydactylism. — Polydactylism is a condition in which there are supernumerary fingers or toes. This is a defect which may be trans- mitted through successive generations. Myopia. — Myopia can hardly be called a disease in the strict sense, being rather a structural defect in the focusing power of the optical apparatus. It seems that the structural peculiarity which leads to short-sightedness is transmitted. Cataract. — Bateson and others have collected pedigrees in which cataracts run in families. Presenile cataract especially appears to be transmitted hereditarily. Retinitis Pigmentosa. — Eetinitis pigmentosa is a degenerative disease of the retina which is transmitted hereditarily. Normals may carry 453 THE HEEEDITARY TEANSMISSION OP DISEASE the disease, so that two normal cousins from retinitis stock may have offspring with retinitis. A large percentage of cases of retinitis come from consanguineous marriages. a o a is o m m o m K s ^ 2 S 1 a a o I Diabetes Mellitus. — Hereditary influences seem to play an impor- tant role in diabetes mellitus, for cases are on record of its occurrence in many members of the same family. Thus, out of 104 cases of dia- EPILEPSY 453 betes mellitus 22 had a family taint — about 20 per cent. Naunyn ob- tained a history of diabetes in 35 out of 201 private cases, but in only 7 of 157 hospital cases. Orthostatic Albuminuria. — Orthostatic albuminuria occurs in boys more commonly than girls. These are often the children of neurotic parents, and have well-marked vasomotor instability. Defects or pe- culiarities in the filtering apparatus in the kidneys may arise as a germinal variation and be handed on from generation to generation. Under conditions which may mean nothing to normal subjects this defect in the kidney may find expression in active disease. In this case, as in gout, it may not be proper to speak of the disease itself being transmitted hereditarily, but the tendency to deviate is so transmitted. Alcoholism. — It is a common observation that among the offspring of drunkards are many cases of unhealthy, insane, and criminal types. The disastrous results may be manifested by nervous disorders, varying from hyperexcitability to dementia; or as debility and lack of developmental vigor expressed, for instance, in infantilism, want of control, imbecility, or as structural abnormalities, especially of the head and brain. The results are so varied, they suggest that what is inherited is general rather than specific. Thus, the offspring of alcoholic parents are not necessarily predisposed in any one particu- lar direction, except that the nervous system is most liable to be af- fected. They may be epileptic, idiotic, insane, etc. On the other hand, it is necessary to recognize that what may be inherited is not the re- sult of alcoholism, but rather the predisposition which led the parent to become alcoholic. This is clearly illustrated in cases where the parent did not acquire the alcoholic habit until after the children were born. Clouston observes that "it is not the craving for alcohol that was inherited, but a general psychopathic constitution in which the alcoholic stimulus is an undue stimulus and the mental control deficient." (See page 301.) Epilepsy. — Brown-Sequard showed conclusively that artificially in- duced epilepsy in the guinea pig is transmissible. The statistics col- lected for man give from 9 to over 40 per cent, of cases in which heredity is an important predisposing cause. Gowers gives 35 per cent, for his cases. In the Elwyn cases 32 of the 126 gave a family history of nervous derangement of some sort, either paralysis, epilepsy, marked hysteria, or insanity. Chronic alcoholism in the parents is also regarded as a potent pre- disposing factor in the production of epilepsy. Echeherria has analyzed 572 cases bearing upon this point, and divided them into 3 classes, of which 257 cases could be traced directly to alcohol as the cause, 126 cases in which there were associated conditions, such as syphilis and traumatism, 189 cases in which alcoholism was probably the result of 31 454 THE HEEEDITARY TRANSMISSION OF DISEASE the epilepsy. Figures equally strong are given by Martin, who, in 150 insane epileptics, found 83 with a marked history of paternal intem- perance. Of the 126 Elwyn cases in which the family history of this 5 fe ^ point was carefully investigated, a definite statement was found in only 4 of the cases (Osier). Huntington's Chorea.^ — Huntington's chorea is frequently inherited. The disease is known as chronic hereditary chorea. It was described by INSANITY 455 Lyon in 1863, who traced the disease through five generations. Hun- tington in 1872 gave the three salient points in connection with the disease, viz.: (1) its hereditary nature; (3) association with psychical troubles; and (3) late onset between the thirtieth and fortieth year. Huntington's chorea is a typical dominant trait. The normal con- dition is recessive; in other words, the disease is due to some positive determiner. Persons with this dire disease should not have children, but the members of normal branches derived from the affected strain are immune from the disease. This disease forms a striking illustra- tion of the principle that many of the rarer diseases of this country can be traced back to a few foci, even to a single focus; certainly in this case many of the older families with Huntington's chorea trace back to the New Haven colony and its dependencies and subsequent ofEshoots (Davenport). Friedreich's Disease — Hereditary Ataxia. — This disease resembles locomotor ataxia, although differing from it in several essential par- ticulars. It begins in childhood and usually occurs in a family having other members of the family affected ''with the same disease. There are curious forms of incoordination and loss of knee-jerk, early talipes equinus, scoliosis, nystagmus, and scanning speech. The affection lasts for many years and is incurable. In 1861 Friedreich reported six cases of this form of ataxia in one family. Since then it has usually been observed to be a family disease, and is, therefore, assumed to be trans- mitted hereditarily. The eugenic teaching in this affection, according to Davenport, is that normally all the affected fraternities should marry only outside the strain. Whether all cases of ataxic offspring of one normal parent are derived from consanguineous marriage is still un- certain and warrants hesitation in advising the marriage of any ataxic person. Imbecility, Defectives, and Delinquents. — Davenport believes that imbecility is due to the absence of some definite simple factor, on account of the simplicity of its method of inheritance. Two imbecile parents, whether related or not, have only imbecile offspring. Daven- port states that there is no case on record where two imbecile parents have produced normal children. Dr. H. H. Goddard, of the Training School for Feeble-Minded, at Vineland, N. J., has studied the ancestry of children in the Vineland institution and has found almost without exception a history of feeble- mindedness for several generations. Dr. Goddard's remarkable study of the Kallikak family has already been referred to. In this instance he traced the ancestry of a 32-y.ear-old girl through about 1,100 individ- uals as far back as the Revolutionary War. Similar studies are being carried out in other institutions and always with similar results. Insanity, — Insanity is a general term comprising many different 456 THE HEEEDITAEY TEANSMISSION OF DISEASE conditions. N"o general statement can, therefore, be made except that certain forms of insanity are undoubtedly transmitted through succes- d o sB •73 -U" ■M ^ ^ t r S •" ft ■« s •- 3 ^ % O M J3 . §^ C3 ^'' . ca CO -fS ^3 o o . p s •as CQ ^ a "2 a S a -a ' S N (Q Bl . H * Ph .. S 8 u " o| da