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THE CLINICAL PATHOLOGY 
 
 OF 
 
 SYPHILIS AND PARASYPHILIS 
 
PLATE I. 
 
 Fig. I. — Serum from Scraping of a Chancre, (P. Gastou.) 
 
 Numerous Spirochcsta pallida are seen. Above one Spirochcsta 
 refringens with very open spiral is seen. Three epitheUal 
 cells and several red blood-cells (fine circles) are present. 
 
 Frontispiece. 
 
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THE CLINICAL PATHOLOGY 
 
 OF 
 
 SYPHILIS ^ PARASYPHILIS ^ 
 
 AND ITS VALUE FOR 
 
 DIAGNOSIS AND CONTROLLING 
 TREATMENT 
 
 BY 
 
 T.UGH WANSEY BAYLY, M.A., M.R.C.S., L.R.C.P. 
 
 PATHOLOGIS'f TO THE LONDON LOCK HOSPITALS 
 CLINICAL PATHOLOGIST TO THE NATIONAL HOSPITAL FOR THE PARALYZED 
 
 AND EPILEPTIC 
 ASSISTANT IN THE BACTERIOLOGICAL DEPARTMENT OF ST. GEORGE's HOSPITAL 
 
 NEW YORK 
 
 WILLIAM WOOD «& COMPANY 
 
 MDCCCCXII 
 

 f <3 
 
 .f^. 
 
 fi '-:>. 
 
^ 
 
 ^ 
 
 TO 
 
 CHARLES SLATER, M.A., M.B., F.C.S., 
 
 Director of the Clinical Laboratories of, and Bacteriologist {since 1889) 
 
 to, St. George's Hospital ; 
 
 Reader in Bacteriology to the University of London , 
 
 WITH HIS PUPIL'S GRATITUDE AND HOMAGE. 
 
 
 \ 
 
 
AUTHOR'S PREFACE 
 
 This little book is intended for the use of the general 
 practitioner and medical student, and not in any way 
 as a book of reference for the pathologist. I have 
 frequently been asked by students and practitioners if 
 I could tell them of a small book containing the 
 essentials of the clinical pathology of syphilis, and I 
 hope this little book will meet that demand. I have 
 endeavoured to collect and review the essential points 
 in the clinical pathology of syphilis and parasyphilis 
 and to present them in such a manner as to emphasize 
 their practical value for diagnosis and treatment. 
 Theory has been omitted as much as possible, as have 
 also detailed accounts of research and experimental 
 work. The literature on this subject is immense, and 
 I have made no bibliography in this volume. The 
 majority of the references, however, will be found in 
 the books referred to below, or in articles by others 
 and myself that have appeared within the last three 
 years in the Lancet, the Practitiorier, the Bvitish Medical 
 
 vii 
 
viii AUTHOR'S PREFACE 
 
 Journal, and the Quarterly Journal of Medicine. Readers 
 wishing for greater details will find them in the 
 works mentioned on p. 185, from which I have freely 
 borrowed. HUGH WANSEY BAYLY. 
 
 Bacteriological Department, 
 
 St. George's Hospital, S.W. 
 July, 1912. 
 
INTRODUCTION 
 
 Syphilis at the present time furnishes an excellent 
 example of the value of the scientific use of the imagina- 
 tion and of modern methods of research in the elucida- 
 tion of the etiology of a disease, and in the discovery 
 of means for diagnosis and treatment. 
 
 Before 1903 an enormous amount of valuable 
 material had been collected by the clinicians, the 
 various stages and manifestations of the disease were 
 well known, the obscure relations existing between 
 syphilis and certain nervous diseases had been un- 
 ravelled with the greatest ingenuity, and certain lines 
 of treatment had been discovered and adopted with 
 success. This material did not, however, acquire its 
 full value until Roux and Metchnikoff showed that 
 syphilis could be transferred to the lower animals, and 
 could thus be subjected to experimental conditions, 
 and until Schaudinn in 1905 had discovered the cause 
 in the Spirochista pallida, and thus provided an in- 
 fallible means of determining the true nature of a 
 suspicious lesion. 
 
 From a series of bacteriological observations made 
 
 ix 
 
X INTRODUCTION 
 
 in connection with the study of immunity, and remote 
 alike from syphilis and considerations of practical 
 medicine, sprang that most valuable of diagnostic 
 methods, the Wassermann reaction, whose reliability 
 now rests on a solid basis of experience. 
 
 This disease also furnishes an example of the 
 deliberate experimental search for a drug which, 
 while harmless to the patient, should be capable of 
 destroying the causal organism, a search which, as is 
 well known, ended in the discovery of Salvarsan. 
 
 As is to be expected, these new discoveries, which 
 give rise to hopes that we might control if not eliminate 
 a disease so widely spread, so often recurring during 
 many years of a patient's life, and of such social im- 
 portance, are naturally of the greatest interest and 
 importance, and have been the subjects of innumer- 
 able investigations, so that the literature of the subject 
 is enormous. Some guide, therefore, is wanted by the 
 practitioner w^hich shall sift the observations which 
 are of practical importance, and which shall show him 
 how to apply this recent knowledge to the study of 
 his own cases. It is the intention of this book to 
 provide such a guide, and to consider our clinical 
 knowledge of the disease in relation to these new^ 
 diagnostic and therapeutic measures. 
 
 CHARLES SLATER. 
 
CONTENTS 
 
 CHAPTER I PAGE 
 
 Parasitology ...... i 
 
 History of parasitology — Character oi Spirochata pallida — 
 Granule shedding — Agglutination — Spirolysins — Vis- 
 cosity — Examination of fresh and stained preparations 
 — Differential diagnosis of various spirochaetae — Im- 
 portance of early diagnosis — Reliability of micro- 
 scopical diagnosis 
 
 CHAPTER II 
 
 Parasitology — Continued, - - - - - 20 
 
 Culture of Spitochata pallida — Habitat — Inoculation — In- 
 cubation period — Reinfection— Immunity 
 
 CHAPTER III 
 
 Syphilitic Anaemias - - - - - 37 
 
 Red cells, leucocytes, haemoglobin — Types of anaemia in 
 adults — Types of anaemia in infants — Ansemia of 
 different stages of syphilis 
 
 CHAPTER IV 
 Theories for and Nature of Wassermann Reaction 46 
 
 Pfeiffer's phenomenon — Antigen - antibody reactions — 
 Complement fixation — Bordet-Gengou phenomenon 
 — Wassermann reaction 
 
 CHAPTER V 
 
 Preparation and Titration of Reagents required 
 
 FOR Wassermann Reaction - . - - 59 
 
 Syphilitic Pseudo-antigen — Test-serum — Complement 
 Hsemolytic system : {a) sheep's corpuscles, (6) haemo- 
 lytic serum 
 
 xi 
 
xii CONTENTS 
 
 CHAPTER VI PAGE 
 
 Wassermann Reaction, Original Technique - - 70 
 
 Quantitative measurement by variation in amount of com- 
 plement — The Wassermann-Neisser original technique 
 — Quantitative measurement of complement - fixing 
 body — (a) By variation in amount of complement, 
 {b) by variation in amount of test-serum, [c) with a S7nall 
 amount of blood — Reasons for superiority of original 
 technique 
 
 CHAPTER VII 
 
 Wassermann Reaction, Simplified Techniques - 81 
 
 Sources of error 
 
 CHAPTER VIII 
 
 Wassermann Reaction, Specificity of Reaction - 86 
 
 Reaction in conditions other than syphilitic — Wasser- 
 mann reaction at the various stages of infection 
 
 CHAPTER IX 
 
 Cerebro-Spinal Fluid - - - - - 96 
 
 Lumbar puncture — Cytological examination — Wasser- 
 mann reaction — Chemical examination 
 
 CHAPTER X 
 
 Urine - - - - - - - - no 
 
 Acute syphilitic nephritis — Subacute syphilitic nephritis 
 — Chronic syphilitic nephritis — Lardaceous disease of 
 the kidney 
 
 CHAPTER XI 
 Clinical Value of Wassermann Reaction - - 113 
 
 (a) In latent syphilis — (b) For differential diagnosis — (c) 
 For controlling treatment — (d) As regards marriage and 
 offspring 
 
CONTENTS xiii 
 
 CHAPTER XII PACE 
 
 Serum and Cerebro-Spinal Fluid in Nervous Diseases 123 
 
 General paralysis — Tabes dorsalis — Cerebral syphilis — 
 Mental deficiency — Differential diagnosis 
 
 CHAPTER XIII 
 Treatment ...---. 135 
 
 (i) Salvarsan : Method of administration — Dosage — 
 Therapeutic results in different stages — After-effects — 
 Relapses — Contra - indications — Conclusions — (2) 
 Mercury 
 
 CHAPTER XIV 
 
 Effect of Treatment on the Wassermann Reaction 
 
 BY Mercury and Salvarsan - . . - 159 
 
 Mercury : Pills, suppositories, inunction, intramuscular 
 injection — Salvarsan : Intramuscular injection — Intra- 
 venous injection 
 
 CHAPTER XV 
 
 Anaphylaxis and Syphilis ... - 172 
 
 Anaphylaxis — Arthus phenomenon — Theobald Smith 
 phenomenon — Noguchi's luetin reaction 
 
 CHAPTER XVI 
 
 Life Insurance and the Wassermann Reaction - 179 
 
 Registrar-General's report : Deaths from syphilis alone 
 —Deaths from diseases syphilitic in origin— Deaths 
 from diseases partly attributable to syphilis — Deaths 
 in which syphilis may be a contributing cause — In- 
 creased mortality-rate amongst syphilitics 
 
 Index -------- 186 
 
CHAPTER I 
 
 PARASITOLOGY 
 
 History of Parasitology. — Since the occurrence 
 of the historical epidemic of syphilis that spread 
 over Europe in 1495, the contagious character of the 
 disease has been recognized, and this was verified by 
 means of experiments by Hunter in 1778. In 1819 
 Swediaur put forward the suggestion that the syphilitic 
 virus was a ferment spreading by the lymphatics and 
 so infecting the lymphatic glands, and that the action 
 of this ferment was capable of producing ulcerations. 
 Donne, in 1837, made the first bacteriological re- 
 searches of syphilitic ulcerations and demonstrated the 
 presence of spirilla, which he considered were the causal 
 organisms. Klebs, in 1878, described small bodies 
 which he named ' helicomonades,' resembling small 
 grains or short rods, which were easy to cultivate, and 
 which he said produced syphilitic lesions in animals. 
 Lustgarten, in 1884, discovered a bacillus, somewhat 
 like the tubercle bacillus, in chancres, papules, 
 enlarged glands, and gummata. This bacillus was 
 more easily decolourized than the tubercle bacillus, 
 and was about 3 to 4 /a long and 0*3 fx broad. It was 
 stained by means of a solution of gentian violet, 
 heated to 40° C. for two hours, and the preparation 
 
2 SYPHILIS AND PARASYPHILIS 
 
 then decolourized by a mixture of permanganate of 
 potash and sulphuric acid, and dehydrated by alcohol, 
 when the Lustgarten bacillus remained stained. 
 Lustgarten's results were confirmed by Doutrelepont 
 and Giacomi, who used i per cent, solution of gentian 
 violet and decolourized for a few seconds in a dilution 
 of acetic acid and then in 60 per cent, alcohol. In 
 1896 Neisser discovered a polymorphic bacillus in the 
 blood of syphilitics. In 1897 P^^^ cultures of the 
 bacillus of smegma were obtained by Laser and 
 Czaplewsky, who considered that this might be the 
 causal organism of syphilis. 
 
 The above are only a few of the organisms claimed 
 by their discoverers to have been the cause of 
 syphilis, but there was never sufficient evidence of 
 their specificity to satisfy the profession at large. 
 
 In 1905 Schaudinn discovered a thin spiral 
 organism which could be demonstrated in Hunterian 
 chancres in practically every case. He gave this 
 organism the name of Treponema pallidum, on account 
 of its slight refractive and staining qualities, which, 
 combined with its extreme tenuity, rendered it difficult 
 of demonstration by most methods of staining. This 
 organism was so constant in its appearance and char- 
 acteristics that Schaudinn was able to write : 
 
 * It is easy, after a certain amount of diligence, to 
 differentiate the Treponema pallidum from other types of 
 spirochsetes in fresh preparations. The fineness and 
 feeble refractility of this spirochaete, the constant, 
 close, deep, and regular character of its spirals which 
 are numerous (10 to 20), render it impossible to confuse 
 it with other micro-organisms of the same type. Its 
 chief characteristic, however, lies in the fact that it 
 
PARASITOLOGY 3 
 
 retains its spiral arrangement not only during move- 
 ment, but also in the state of rest, while the spirals of 
 most of the other spirochsetes disappear when they are 
 in the condition of repose.' 
 
 This description of Schaudinn's still holds good, 
 and makes it one of the easiest organisms to diagnose 
 in fresh preparations. As its characteristic movements 
 are one of its diagnostic features, it is best examined 
 by the dark-ground illumination method (ultra-micro- 
 scope), which is the only satisfactory means of examin- 
 ing the organism alive. 
 
 Characters of Spirochaeta Pallida. — When 
 examined by dark-ground illumination, its charac- 
 teristic appearance is that of an extremely fine, 
 silvery spiral from 5 to 25 /x in length, with very 
 regular and closely set spirals (about seven to the 
 diameter of a red blood-disc), the distance between the 
 spirals being i /x. The number of the spirals range 
 from 5 to 25, and the extremities of the organism are 
 pointed. It may happen that the light is only reflected 
 from the summit of the spirals, in which case the 
 organism will have the appearance of a chain of equi- 
 distant luminous dots not unlike a chain of streptococci. 
 By careful focussing, however, this chain of dots 
 will be seen to be a spiral (see Figs, i and 2). The 
 living Spirochcdta pallida preserves a helicoidal form, 
 but as its vitality diminishes the spiral tends to dis- 
 appear. 
 
 In serum, but never in water, giant forms up to 45 ju 
 are sometimes seen ; these are probably formed by 
 several spirochsetae becoming attached end to end. 
 This Dr. Comandon describes as * linear agglutination.' 
 
4 SYPHILIS AND PARASYPHILIS 
 
 If a drop of water is added they are seen to break up 
 into several organisms. 
 
 The movements are more active and last longer in 
 the patient's own serum than in distilled water or 
 saline. In serum, also, the movements are more 
 rapid and the spirals closer together than in water. 
 The movements vary with the vitality, and are 
 increased by warming the preparation. 
 
 In water the Spirochata pallida is but feebly motile 
 compared with most of the other spirochaetse met with. 
 If there is no current in the fluid the spirochaete will 
 remain in the field for a long time. Care must be taken 
 to distinguish the movements proper to the organism 
 from those imparted to it by a current of the fluid 
 in which it is being examined. It preserves its spirals 
 during rest, while all other analogous spirochsetes, 
 which present marked undulations, show them only 
 when they are moving vigorously, and when at rest 
 they have long, flattened-out undulations, and, indeed, 
 are very nearly straight. This peculiar appearance of 
 the Spirochata pallida is due to the fact that in it the 
 spiral arrangement is permanent, whilst in other 
 varieties the deep spiral is only produced during rapid 
 movement, and is straightened out at rest. There is 
 only one spirillum, that of the mouth or Spirochata 
 denthmi which has a small fixed spiral arrangement, 
 but this variety can be distinguished by other 
 characteristics from the organism of syphilis. No 
 undulating membrane has yet been demonstrated 
 in SpirochcBta pallida. 
 
 The movements consist of — 
 
 I. Bending, which is the most marked. 
 
PARASITOLOGY 5 
 
 2. Snake-like undulations. 
 
 3. Rotation round its long axis like a screw. 
 
 4. Concertina-like movements, by which the spirals 
 are drawn out or approximated, so that organism 
 becomes lengthened or shortened respectively. 
 
 5. Occasionally a local wave of contraction may be 
 seen which flattens out the spirals. This movement 
 is very rarely seen with any other spirochsete than 
 Spirochceta pallida. 
 
 Schaudinn considered that on section the Spirochceta 
 pallida was probably round, and that the organism was 
 cylindrical and not flattened, as is the case with most 
 of the other spirochaetae. 
 
 The peripheral protoplasm is continued at each end 
 of the organism in the form of a cilium whose length 
 equals about four to six undulations. The largest 
 Spirochceta pallidcB are distinguished by the presence of 
 two cilia at one pole. Schaudinn considered that 
 these double cilia indicated the commencement of 
 longitudinal division, and wrote in December, 1905 : 
 
 ' I have already succeeded in three cases in 
 observing the longitudinal division of the organism. 
 To follow out this process I have chosen individuals 
 which already possessed two fine cilia at one of the 
 poles, and 1 have seen the longitudinal division 
 progressing rapidly after beginning at this pole. At 
 the moment of division the organism abandoned its 
 marked spiral form, and appeared to be very irregularly 
 contorted.' 
 
 The question whether the Spirochceta pallida is to 
 be classed with the bacteria or protozoa has still to be 
 settled, and its cycle of development has still to be 
 demonstrated. Krzyztalowicz and Siedelecki think 
 
6 SYPHILIS AND PARASYPHILIS 
 
 that they have recognized female elements in the form 
 of large spirilla, and male elements in the form of 
 small spirilla, and state that they have seen these two 
 elements unite. 
 
 A. Neisser hazards the opinion that there may exist 
 an unknown stage of development, or rest stage, of 
 the spirochsete, analogous to the spores and granular 
 forms of many bacteria, which may be far more diffi- 
 cult to influence by any medicament than the spiro- 
 chaete itself. 
 
 The possibility of this theory being correct is 
 heightened by the observations of Dr. Reinke, of 
 Wiesbaden, who in 1910 demonstrated granules in the 
 lung of a congenital syphilitic infant in an autopsy 
 performed after treatment with salvarsan. He con- 
 sidered that the granules were derived from spiro- 
 chaetes, and Dr. A. Balfour is of the opinion that 
 granule-shedding in Spirochata pallida occurs before 
 any treatment of the case is begun. It is, therefore, 
 in all probability, a feature in the life-history of the 
 spirochaete. This same phenomenon of granule-shed- 
 ding is true of other spirochaetes associated with that 
 of syphilis, and is especially well seen in the case of 
 the Spivochata refringens. Balfour thinks that the 
 granules are of the nature of resistant spores, that 
 they play an important part in relapse, and that they 
 are influential factors in the occurrence of the later 
 manifestations of syphilitic infection. 
 
 AGGLUTINATION 
 
 The Spivochceta pallidce may be preserved in normal 
 saline solution for several hours without showing any 
 
PARASITOLOGY 7 
 
 traces of agglutination, but if to the saline solution the 
 filtered product of a chancre or syphilitic papule is 
 added, agglutination is at once produced. 
 
 There is only a feeble agglutination if the serum of 
 the same individual is used, showing that the agglutinins 
 are present in smaller quantity in the serum than in 
 the fluids immediately surrounding aggregations of 
 spirochaetae. 
 
 Agglutination has been observed in the blood in 
 very intense general infection. 
 
 Agglutination phenomena are most clearly observed 
 in the serum during the period of the rash. 
 
 Agglutination has never been seen at a higher dilu- 
 tion than I in i,ooo, and usually only occurs in a 
 dilution of i in lo. 
 
 SPIROLYSIS 
 
 Spirolysins — that is to say, substances having the 
 property of dissolving spirochaetae — have also been 
 observed in the serum, and clumps of agglutinated 
 spirochaetes after some time become granular, of 
 irregular form, and finally disappear, whereas control 
 specimens, treated with normal serum or salt solution 
 instead of specific serum, preserve their shape for 
 several days or even weeks. 
 
 VISCOSITY 
 
 In fresh serum the spirochaete pushes past any solid 
 object that it touches, but as it becomes less mobile it 
 develops a tendency to stick to any such object. 
 
8 SYPHILIS AND PARASYPHILIS 
 
 MICROSCOPICAL EXAMINATIONS 
 
 I. Dark-Ground Illumination. —By means of a 
 disc of black enamel painted on the under surface of 
 the condenser (see Fig. 3), all rays of light from the 
 
 Fig. 3. — Under View of Ultra-Microscope, showing Lens 
 IN Centre (White), with Black Enamel Disc fainted 
 ON IT. The two Centring Screws and the Spring are 
 also shown. 
 
 microscope mirror, with the exception of those at the 
 periphery of the condenser, are cut off. Those passing 
 through the clear periphery are deflected by suitably 
 
 Fig. 4. — Upper Surface, showing Concentric Circles 
 scratched on it, by means of which it can be 
 rapidly and accurately centred. 
 
 cut lenses so that they converge obliquely on the 
 object examined, which appears as a bright refractive 
 body on a dark background. In this way very trans- 
 
PARASITOLOGY g 
 
 parent objects, which are invisible by direct illumina- 
 tion, are easily seen, and their shape and movements 
 , studied. 
 
 On the upper surface of the condenser are lightly 
 scratched several concentric circles, by means of which, 
 using a i-inch or |-inch objective and a No. i or 2 
 
 Slide and cover-glass, t^ 
 
 Stop. 
 
 Ultra-microscope. 
 
 Fig. 5. — Section of Objective showing 'Stop,' and of 
 Reflecting Conversion Condenser. 
 
 The black line below the condenser represents section of 
 the black enamel disc. 
 
 eyepiece, the apparatus can be readily centred (see 
 
 Fig. 4)- 
 
 An ordinary ^^ oil-immersion objective admits too 
 much light, and a special mount for the lenses, con- 
 taining a stop, is required. A sectional diagram of 
 the condenser and objective with stop is shown in 
 Fig. 5. It will be seen that no rays from the source 
 
PLATE II. 
 
 Fig. 2. — Scraping from Centre of a Syphilitic Chancre. 
 Dark-Ground Illumination. (J. Comandon.) 
 
 In centre is seen a mass of epithelial debris containing numerous 
 Spirochatid pallidcs. Below free Spirochceto pallida are seen. 
 Above and to right some bacilli are seen. 
 
 To] ace p. n. 
 
PARASITOLOGY ii 
 
 now gently scraped until blood just begins to exude. 
 The surface is now again dried with some sterile 
 gauze, and a little blood or serum expressed. A 
 small drop of this is removed with a platinum needle, 
 and mixed with a drop of distilled water on a thin 
 glass slide. If this slide is too thick, the rays of light 
 may come to a focus below the surface, and an un- 
 satisfactory illumination be obtained. A large cover- 
 glass is now pressed down firmly so that only a thin 
 layer of the fluid remains between the slide and cover- 
 glass. This can be conveniently done by spreading 
 a piece of lint over the knee and holding the slide by 
 each end, with the cover-glass downwards, and press- 
 ing it against the knee till the superfluous fluid is 
 squeezed out and absorbed by the lint. After use the 
 lint can be destroyed. A drop of immersion oil is now 
 placed below the slide and also on the upper surface of 
 the cover-glass. The slide is now placed in position 
 on the microscope stage so that the drop of oil on the 
 under surface touches the upper surface of the con- 
 denser. The j~ objective is now lowered into the 
 drop of oil on the upper surface of the cover-glass in 
 the usual way. The condenser must now be racked 
 up or down, and the mirror adjusted until bright 
 illumination with a dark background is obtained. 
 
 Distilled water is the best medium in which to 
 examine the spirochsete, as by osmosis the organism 
 becomes swollen and so is more easily seen than if 
 examined in normal saline or serum. The distilled 
 water, also, by producing haemolysis of the red cells, 
 gives a clearer view of any organism that may be 
 present. After about half an hour, the spirochaete 
 
12 SYPHILIS AND PARASYPHILIS 
 
 becomes more rigid and the movements sluggish, and 
 in two to three hours' time all movement ceases in the 
 majority of cases. 
 
 Phillips and Glynn recommend a slightly modified 
 technique for the collection of material for examination 
 by dark-ground illumination. The primary sore is first 
 cleaned with absorbent wool, rubbed with the wool, 
 and then swabbed two or three times with wool soaked 
 in methylated spirit ; in a minute or two the spirit is 
 wiped off, and soon clear serum begins to exude, which 
 is collected in a capillary tube. The following advan- 
 tages are claimed : 
 
 (i) There is very little or no blood. 
 
 (2) The serum washes the spirochsetes from the 
 deeper parts where they are more constantly present ; 
 other spirochsetes and bacteria are usually absent. 
 
 (3) Plenty of material is obtained, more than by 
 any other way. 
 
 2. Bum's Indian-Ink Method. — The ink (Gun- 
 ther- Wagner's) must be well centrifuged, and after 
 the coarser particles have been deposited the super- 
 natent fluid containing the finer particles should be 
 pipetted off and kept in a stoppered bottle. 
 
 The material from the chancre is obtained in the 
 same way as that for the dark-ground illumination, and 
 a drop of the Indian-ink suspension is used instead of 
 distilled water. The mixture is spread in a thin film 
 and allowed to dry without heat. No fixation is 
 required, neither is a cover-glass necessary unless a 
 permanent specimen is desired. 
 
 When employing Burri's method, Phillips and Glynn 
 use I drop of serum to twice the volume of Indian ink. 
 
PARASITOLOGY 13 
 
 3. Staining of Films. — Giemsa Stain, which con- 
 sists of azur II eosin, 3 grammes; azur II, 8 grammes; 
 chemically pure glycerine, 250 grammes ; and methyl 
 alcohol, 250 grammes. The following are Giemsa's 
 directions : 
 
 (i) Fix films in absolute alcohol from fifteen to 
 twenty minutes ; dry with filter-paper. 
 
 (2) Dilute the stain with distilled water, i drop of 
 stain to i c.c. of water, the mixture being well 
 shaken. 
 
 (3) Stain for fifteen minutes. 
 
 (4) Wash in a brisk stream of distilled water. 
 
 (5) Drain with filter-paper, dry, and mount in Canada 
 balsam. 
 
 The SpirochtBta pallida should appear stained rose- 
 pink. This staining reaction, however, is not invari- 
 able, and MetchnikofF and Roux give instances where 
 Spiyochata pallidce, obtained from the experimental 
 chancre of an ape, were distinctly blue with Giemsa's 
 stain. 
 
 Phillips and Glynn, when staining by Giemsa's 
 method, spread a drop of the serum, obtained as for 
 dark-ground illumination, as thin as possible on a slide, 
 and, after drying and fixing in absolute alcohol, it was 
 stained face downwards with Giemsa's stain diluted, 
 I in 8, for twelve hours. They considered this long 
 method of staining the most reliable. 
 
 Marino's Stain. — The films are first dried without 
 being fixed in any way, then they are treated with a 
 mixture of Marino's blue (o-i gramme) and of methyl 
 alcohol (20 c.c.) ; after three minutes some drops of a 
 watery solution of eosin (o'oo5 per cent.) are added. 
 
14 SYPHILIS AND PARASYPHILIS 
 
 Two minutes after this the films are thoroughly washed 
 and are then ready to be examined. 
 
 Loeffler's Method should be employed to show the 
 terminal cilia. A freshly made mixture is used, con- 
 sisting of 10 c.c. of a 20 per cent, solution of tannin, 
 5 c.c. of a cold saturated solution of sulphate of iron, 
 and I c.c. of saturated alcoholic solution of fuchsin. 
 This mixture is put on the films and heated three 
 minutes until steam comes off. It is then washed in 
 distilled water and stained with Ziehl's solution of 
 carbol-fuchsin, gently heated at the same time. By 
 this method the spirochaete is stained a dark red, while 
 its cilia are shown in a light rose colour. 
 
 Care must be taken in all these methods to dilute 
 the syphilitic products with some drops of distilled 
 water. 
 
 Leishman's Method. — A film dried in the air 
 and not fixed is treated with a mixture of distilled 
 water and Leishman's stain in the proportion of 
 2 parts of water to i of stain. Optimum staining 
 takes place in twenty-five minutes, when the stain 
 must be washed off very gently with distilled water, 
 and, when blotting in order to dry, care must be taken 
 that only slight pressure is used, and that the film is 
 not rubbed. 
 
 4. Levaditi's Silver Method for Staining Sec- 
 tions. — (i) Fix small pieces of tissue in 10 per cent, 
 formalin for forty-eight hours. 
 
 (2) Wash for an hour in water. 
 
 (3) Keep in 96 per cent, alcohol for twenty-four 
 hours. 
 
PARASITOLOGY 15 
 
 (4) Place in a 1-5 solution of nitrate of silver in a 
 dark bottle. 
 
 (5) Incubate at 37° C. for three days. 
 
 (6) Wash in water for twenty minutes. 
 
 (7) Place in a mixture consisting of pyrogallic 
 acid 4 parts, formalin 5 parts, distilled water up to 
 100 parts. Keep the material in this mixture 
 in a dark bottle for forty hours at room tempera- 
 ture. 
 
 (8) Wash in water for a few minutes, take through 
 an increasing strength of alcohol, and embed in 
 paraffin in the usual way. 
 
 The sections ought to be as thin as possible. In 
 satisfactory preparations the spirochaetae appear almost 
 black against the pale yellow background of the 
 tissues. 
 
 Differential Diagnosis of Various Spirochsetes 
 likely to be Confused with the Spirochaeta 
 Pallida. 
 
 The Spirochaeta Refringens, found in ulcerative 
 lesions, is much larger, longer, and thicker than the 
 Spifochceta pallida^ the curves are much more open and 
 shallow, and the organism moves with far greater 
 rapidity (see Fig. 7). 
 
 The Spirochaeta Buccalis, found in the mouth, is 
 also much coarser, and is quite unlike Spiyochceta pallida 
 (see Fig. 8). 
 
 The Spirochaeta Dentium, found in carious teeth, 
 is very like the Spiyochceta pallida, but it is shorter, 
 being only 5 to 10 /x, and the depth of the spirals is 
 
i6 
 
 SYPHILIS AND PARASYPHILIS 
 
 considerably less than in the SpirochcBta pallida. Like 
 the Spirochata pallida^ it retains its spirals during rest 
 (see Fig. 9). 
 The Spirochaeta Pertenuis of Yaws, described 
 
 Fig. 7. — Spiroch.^ta 
 Refringens. 
 
 Fig. 8. — Spiroch^ta 
 buccalis. 
 
 Fig. 9, — Spiroch^ta 
 
 DENTIUM. 
 
 Fig. 10. — SpiROCHiETA 
 Pseudo-Pallida. 
 
 by Castellani, is the organism most like that of syphilis, 
 and it is extremely difficult, if not impossible, to 
 distinguish them morphologically. 
 
 The Spirochaeta Pseudo-Pallida of ulcerated 
 cancerS; described by Loewenthal, does not appear to 
 
PARASITOLOGY 
 
 17 
 
 justify its name, as it is not very like the true pallida, 
 and is not likely to be mistaken for it except, perhaps, 
 in badly stained films (Fig. lo). 
 
 The Spirochaeta Balanitis of Hoffmann is a 
 band-shaped spirochaete with 6 to lo twists, is 0*5 to 
 0*75 /x broad, with an undulating membrane, and moves 
 rapidly backwards and forwards, crossing the whole 
 field at one dash. It moves by snake-like undulations 
 or by screw-like rotation on its long axis (Fig. 11). 
 
 Fig. II. 
 
 Fig. 12. 
 
 Fig. 13. 
 
 Other spirochaetes occasionally seen are pictured in 
 Figs, 12 and 13. 
 
 Diagnosis by Gland Puncture.— Phillips and 
 Glynn have recorded that they obtained the Spivochata 
 pallida in 37 per cent, of cases of puncture of en- 
 larged lymphatic glands corresponding to the primary 
 lesion. 
 
 Preis states that he was successful in nearly 100 
 per cent, of cases in the secondary latent stage, and 
 that he never failed to find the organism during the 
 period between the typical hardening of the glands 
 and the first appearance of a rash. 
 
18 syPHILlS AND PARASYPHILIS 
 
 Phillips and Glynn, however, state that they never 
 failed to find the spirochsete in the primary sore in any 
 of the cases when they found the organism by gland 
 puncture. 
 
 The fact that gland puncture has been successfully 
 performed can be demonstrated by the presence of 
 lymphocytes in the material obtained. 
 
 Importance of Early Diagnosis. 
 
 In the absence of treatment, a sore, the nature of 
 which is clinically doubtful, can in a few moments be 
 demonstrated to be clearly syphilitic, and so much 
 valuable time may be saved, and the annoyance and 
 discomfort of secondary manifestations prevented. 
 
 Neisser has observed that the earlier in the course 
 of the disease that treatment is commenced, the more 
 probability there is that a negative serum reaction 
 will be obtained after a course of treatment. Thus, 
 cases showing no symptoms of syphilis (early latent) 
 that had received treatment as soon as possible after 
 the primary lesion had appeared, give a negative serum 
 reaction in 75 per cent, of cases, whereas in similar 
 cases in which the treatment had not been commenced 
 until six months after the primary lesion occurred, 
 only 33 per cent, of cases were negative. 
 
 By early treatment the period of infectivity is 
 shortened, which is obviously a matter of the greatest 
 possible importance from both the public health and 
 social points of view. An early diagnosis is therefore 
 of paramount importance, both to the patient and to 
 those with whom the patient is brought in contact. 
 
PARASITOLOGY 19 
 
 Reliability of Microscopical Diagnosis. 
 
 Either general or local treatment has a marked 
 effect on the number of Spiwchcstce pallidas found, and 
 the organisms tend to disappear from the site of the 
 primary inoculation after a few weeks, even without 
 treatment. If a local antiseptic has been applied, the 
 patient should be instructed to wash it away with plain 
 warm water, and return in a few days' time for another 
 examination. 
 
 As with most pathological findings, however, a 
 positive result is much more conclusive than a negative 
 one, and syphilis cannot be put out of court till three or 
 four examinations on different days have been made, 
 and the possibility of all antisyphilitic treatment, 
 either general or local, excluded. 
 
 Out of a very large number of recent untreated 
 chancres, very few have failed to show the SpivochcBta 
 pallida when examined by this method. The demonstra- 
 tion of this organism in primary syphilis is therefore, 
 from a diagnostic point of view, of equal importance 
 to, or even, perhaps, of greater importance than, that 
 of Koch's bacillus in pulmonary tuberculosis or the 
 Klebs-Loeffler bacillus in diphtheria. 
 
 The use of this method of diagnosis has shown that 
 sores diagnosed from their clinical appearance to be 
 non-syphilitic were really syphilitic, and vice versa — 
 that sores considered syphilitic were not syphilitic. No 
 patient, therefore, should be condemned as a syphilitic 
 and placed on antisyphilitic treatment on the clinical 
 appearance of the sore alone, but only after demonstra- 
 tion of the Spivochceta pallida. 
 
CHAPTER II 
 PARASITOLOGY— Cow^ww^rf 
 
 CULTURE OF SPIROCH^TA 
 
 NoGucHi claims to have cultivated the Spiyochceta 
 pallida in serum water (sheep's, horse's or rabbit's) to 
 which a piece of sterile rabbit tissue has been added. 
 He considered the rabbit tissues best adapted to this 
 purpose are the kidney and testicle. He uses test- 
 tubes 20 cm. high and ij cm. wide, and fills them 
 with 1 6 c.c. of serum water, i part serum and 
 3 parts distilled water. After completion of the usual 
 precautionary sterilization at ioo° C. for three days, 
 fifteen minutes each day, a small piece of freshly 
 removed sterile tissue is placed in each tube. The 
 tubes are incubated at 37° C. for two days, and then 
 examined for their sterility. To each tube a layer of 
 sterile paraffin oil is now added in order to shield the 
 medium from contact with the air and to prevent 
 evaporation. Strict anaerobic conditions are very 
 important in obtaining the first generation of Spiro- 
 chceta pallida, and Noguchi employs a combination 
 of hydrogen gas, vacuum, and pyrogallic acid in an 
 anaerobic apparatus. 
 
 To obtain the first generation of Spivochceta pallida 
 in virulent focm, it is essential that there should be — 
 
 20 
 
PARASITOLOGY 21 
 
 1. Suitable fresh sterile tissue in serum water. 
 
 2. Strict anaerobic conditions. 
 
 3. A slightly alkaline reaction furnished by the 
 serum and tissue. 
 
 4. Temperature, 35° to 37° C. 
 
 A large number of unsuccessful attempts will be 
 made for one successful. Noguchi states that in the 
 serum - water tissue the spirochaetse commence to 
 multiply after forty-eight hours, and continue to grow 
 slowly for four or five weeks. He states that in the 
 young cultures many short and rather heavy specimens 
 are seen, some with only few curves, while in a culture 
 ten or twelve days old the spirochsetae are of the usual 
 length and have typical curves. As they grow older 
 the spirochaetae may become very long and often form 
 a tangled mass. Noguchi also states that of two 
 strains of pure cultures experimented with, both 
 produced typical lesions in the testicle of the rabbit. 
 
 HABITAT 
 
 In experimental infection the spirochaetes are found , 
 at the point of inoculation. They stay in its immediate 
 neighbourhood for a certain time while they adapt 
 themselves to their new environment before they 
 commence to multiply. . They irritate the tissues by 
 their toxins, and provoke a characteristic reactionary 
 infiltration and development of the connective tissues. 
 The body-cells oppose to the spirochaetes their specific 
 antitoxins, to which the spirochaetes gradually become 
 accustomed. They then develop along the lymphatic 
 vessels and invade the lymphatic glands, which repre- 
 
22 SYPHILIS AND PARASYPHILIS 
 
 sent the first line of defence. They then develop in 
 the glands and provoke a reactionary adenitis. 
 
 The spirochsetes are irregularly distributed in the 
 hard chancre and in the lymphatic glands. In the 
 chancre they are found in the deeper layers around the 
 vessels or in the vessel walls In the glands they are 
 unequally disposed in groups, which explains the rarity 
 of their presence in sections. The largest masses of 
 spirochsetes are found in the walls of the vessels and 
 the trabeculae of the glands. The spirochsetes pene- 
 trate little by little into the blood-stream. 
 
 Agglomerations of spirochsetes produce embolism 
 of the capillaries, and as a consequence the charac- 
 teristic lesions of the skin and mucous membrane. 
 
 During the secondary period the spirochsetes are 
 found in the papules, blood, and organs. 
 
 It is very difficult to find spirochsetes in the blood 
 on account of their small numbers. 
 
 In congenital syphilis spirochsetes are often found in 
 large numbers in the liver, spleen, and lungs. The 
 spirochsetes are usually disposed around the vessels. 
 They are also found in the vesicles of pemphigus. 
 Spirochsetes have been found in the blood, the skin 
 lesions, in the lymphatic glands, in the liver, in the 
 suprarenal capsules, in the ovaries or testicles, in the 
 lungs, in the spleen, in the pancreas, in the nerves, 
 and in the bone cartilages. They are also found in 
 the rachidien fluid and nasal mucus, sputum, ascitic 
 fluid, bile, urine, meconium, and in the gastric juices. 
 
 Levaditi and Roche quote nine instances of inocula- 
 tion of syphilis on men by means of syphilitic blood, 
 including Julien's two cases. 
 
PARASITOLOGY 23 
 
 Hoffmann was the first to demonstrate the infectivity 
 of blood obtained from patients in the florid secondary 
 stage of syphilis by inoculation experiments on apes. 
 He showed that the blood was infective before the 
 rash appeared, and remained so for as long a period 
 as six months after the first appearance of the disease. 
 The blood, however, cannot contain any large numbers 
 of spirochaetes, as only a small percentage of experi- 
 ments give positive results. The infectivity of the 
 spermatic fluid of a secondary syphilitic was demon- 
 strated by Finger and Landsteiner. 
 
 Trinchese has reported his results of the examination 
 of the placenta in a hundred cases in which the foetus 
 was syphilitic. He found the results agreed with 
 those from examinations of the foetal organs, and 
 only failed in one case to find spirochsetes in the 
 placenta when their presence could be demonstrated 
 in the foetal organs. They are, however, much less 
 numerous in the placenta than in the organs. He 
 was able to demonstrate the passage of the spirochaeta 
 through the walls of the villus, and he considers that 
 the spirochaetae circulate in the foetal blood and pene- 
 trate through the vessel and villus, setting up a 
 nodular thickening of the syncytium. The macro- 
 scopic appearance of the placenta in these cases did 
 not differ from that of the normal placenta. In the 
 foetal organs the spirochaetes were found in the largest 
 number in the adrenal bodies ; the liver and lungs 
 were the next most infected organs, and here the 
 organism occurred most frequently in the neighbour- 
 hood of the vessels. The ovary, testicle, and epi- 
 didymus almost constantly contained organisms. 
 
24 SYPHILIS AND PARASYPHILIS 
 
 Experimental inoculations in animals have proved 
 that blood in secondary syphilis, semen in secondary 
 syphilis, saliva in secondary syphilis, and gummata in 
 tertiary syphilis, all contain the syphilitic virus. 
 
 The occurrence of spirochaetae in the semen is a 
 tardy proof of conceptional syphilis, which was long 
 suspected, and appears to have been clinically proved 
 by the case recorded by Buschke and Fischer, in 
 which a mother, previously healthy, gave birth to a 
 syphilitic child, and subsequently developed the disease. 
 
 INOCULATION 
 
 The first successful inoculation on animals was per- 
 formed by MetchnikofF and Roux on a female chim- 
 panzee two years old. The sites selected were the 
 clitoris and eyebrow, and the material used was serum 
 from a human primary sore. After about twenty-six 
 days a chancre developed on the clitoris, and a papular 
 rash occurred a month after the appearance of the 
 chancre. 
 
 MetchnikofF and Roux have since reported the 
 development of a secondary rash in 60 per cent, of 
 animals whose inoculation was followed by a primary 
 sore, and that this rash usually commences thirty-three 
 days after the first appearance of the chancre. In the 
 chimpanzee the rashes can be seen on the skin of the 
 head, back, and abdomen, and are usually either papular 
 or macular. Mucous plaques also are found on the 
 mucous membranes. 
 
 The lower monkeys can also be successfully inocu- 
 lated, and a chancre produced, but there is not such 
 
PARASITOLOGY 25 
 
 a large percentage of successful inoculations, and 
 secondary symptoms seldom, if ever, occur. 
 
 Bertarelli was the first experimenter to obtain satis- 
 factory results with rabbits. He inoculated the cornea, 
 and a well-marked keratitis was produced, which com- 
 menced four weeks after inoculation. The lesion first 
 appeared as a greyish opacity, accompanied by some 
 injection of the ciHary vessels. The opacity increases 
 in size until half the cornea may be affected, and later 
 the bloodvessels grow in from the sclerotic. The 
 lesion tends to heal spontaneously, and in a couple of 
 months or so recovery usually takes place. 
 
 Parodi later was successful in inoculating rabbits in 
 the testicle. He introduced the virus into the sub- 
 tance of the testicle, but Truffi soon afterwards was 
 able to show that it was sufficient to introduce the 
 virus under the skin covering the testicle. When 
 transmitting the infection, some observers use the 
 serum obtained in a similar way to that required for 
 examination by dark-ground illumination, which has 
 already been described ; others use the fluid obtained 
 from the inside of an infected testicle, and others 
 transplant small pieces of the lesion containing spiro- 
 chastes. 
 
 One of two techniques is usually employed for the 
 inoculation. In the first the epithelial layers of the 
 skin are scarified with a scalpel, and the virus then 
 rubbed in, the procedure being similar to that of 
 ordinary vaccination with calf-lymph. Finger and 
 Landsteiner introduced the second, or subepidermal 
 technique. Here the epithelium is deeply scarified, 
 and the virus rubbed and pushed into the deeper 
 layers of the skin. 
 
26 SYPHILIS AND PARASYPHILIS 
 
 With a primary inoculation, in from five to eight 
 weeks a small nodule occurs in the skin, which 
 gradually increases in dimensions up to about the size 
 of a pea, which may or may not ulcerate. Occasionally, 
 infiltration of the skin takes the place of a definite 
 nodule. 
 
 If the testicular substance is involved, the testicle 
 will become enlarged, hard, and nodular. 
 
 Repeated passages apparently increase the virulence 
 for the species, as the incubation period is shortened, 
 even to as little as a fortnight, and a far higher per- 
 centage of successful inoculations are recorded, even 
 up to 80 or 90 per cent. 
 
 The infection in rabbits is nearly always a local one. 
 Repeated rabbit passages do not apparently increase 
 the virulence of the spirochaete for apes. 
 
 Roux, MetchnikofF, Levaditi, and Roche, of the 
 Pasteur Institute, have elicited many interesting facts 
 bearing on the pathology of syphilis, by means of 
 inoculation experiments on the higher apes. They 
 found that a small effusion of blood or serum facilitates 
 the penetration of the virus, that a larger haemorrhage 
 prevents successful inoculation, and that the most 
 constant results were obtained with superficial scarifica- 
 tion of the epidermis. The spirochaetes were found 
 to be easily destroyed by phagocytes, and were seen 
 inside the macrophages and polymorphonuclears in 
 the lungs, liver, and spleen of new-born congenital 
 syphilitics. Neisser, in fifty-one cases of subcutaneous 
 injection, did not obtain one positive result. Thirty- 
 three of these cases showed themselves later sensitive 
 to inoculation by the epidermis, and certain of these 
 
PARASITOLOGY 27 
 
 which resisted the first scarification reacted to the 
 second. Thirteen were immune to all methods of 
 inoculation, probably due to natural immunity, and 
 not to the fact that the subcutaneous inoculation had 
 ' taken.' Probably the subcutaneous inoculations excite 
 a greater leucocytosis than inoculation of the super- 
 ficial layers of the skin, with the result that the spiro- 
 chaetes are destroyed. Intravenous or intraperitoneal 
 inoculation gave no positive results ; inoculation into 
 a lymphatic gland was also negative. Inoculation 
 into testicles was followed in one case by a general 
 immunity without local lesion, and in a second the 
 spirochsete was found in the bone-marrow of an animal 
 killed fifty-six days after the inoculation. The general 
 opinion of experimenters seems to be that the spiro- 
 chaeta is incapable of effecting an entrance through 
 sound skin or mucous membrane, and if their results 
 are correct the great importance and danger of little 
 superficial erosions and abrasions are emphasized. 
 
 J. Hutchinson, junior, expresses the firm belief in 
 the frequent passage of the syphilitic virus through 
 unabraded or normal skin and mucous membrane. 
 
 Positive inoculations were obtained in orang-outangs 
 (not in other apes) with material from bone-marrow 
 and spleen, and much less frequently with material 
 from the testicle and lymphatic glands, thus showing a 
 marked preference for blood-forming tissues. Negative 
 results were obtained with inoculation with material 
 from broken-down gummata, but with unbroken gum- 
 mata that were opened and scraped, and the evacuated 
 material ground up and inoculated, chancres developed 
 in 60 per cent, of cases. 
 
28 SYPHILIS AND PARASYPHILIS 
 
 In man seven positive results were obtained out of 
 eighteen cases inoculated with blood taken from cases 
 with marked secondary syphilis. 
 
 Spermatozoa may occasionally contain the virus ; 
 inoculations with milk have so far all proved negative, 
 and cerebro-spinal fluid has only very rarely given a 
 positive result. 
 
 Filtering destroys the power of the virus as estimated 
 by inoculation. The virus may be sterilized by desic- 
 cation, by keeping for three hours at a temperature of 
 io° C, or half an hour at 48° C, or subjecting it to 
 the rays of the uveal lamp or the X rays. After 
 twenty-two passages through apes the virus becomes 
 attenuated, and the period of incubation lessened from 
 nineteen to seven days. 
 
 Levaditi and Roche, in their book, ' La Syphilis,' 
 mention the case of a man, aged seventy-nine, who 
 was inoculated with a virus attenuated by passage 
 through several apes, and who developed small papules 
 at the point of the inoculation ; but no ulceration of the 
 papules occurred, nor any secondary symptoms. 
 
 INCUBATION PERIOD 
 
 It has been observed that the more resistant the 
 animal is to infection, the shorter is the incubation 
 period. Neisser considers that the duration of in- 
 cubation depends, not on the virulence of the organism, 
 nor on the resistance of the individual, but only on 
 the quantity of virus introduced. Levaditi, on the 
 other hand, considers that resistance and virulence 
 both play an important part. Of six animals in which 
 
PARASITOLOGY 29 
 
 the scarified spots were excised ten minutes, twenty 
 minutes, two hours^ four hours, ten hours, and twelve 
 hours after, no subsequent lesion appeared. In another 
 experiment, when the points of inoculation were 
 excised eight and fourteen hours after scarification, 
 chancres appeared. The duration of the period of 
 incubation is due to the slowness of multiplication 
 of spirochaetae transplanted into new surroundings. 
 Already, long before the appearance of the chancre, 
 the virus has reached the circulation. The organism 
 spreads by the blood, and, perhaps by preference, by 
 the lymphatics. 
 
 REINFECTION 
 
 There appears to be conclusive evidence that no 
 individual is immune to syphilis, or that a syphilitic 
 infection confers immunity. Numerous well-authen- 
 ticated cases are now reported of reinfection with 
 syphilis, and if an individual is immune to syphilis, we 
 may conclude that he is still infected with it. 
 
 Cases of tabes and general paralysis have been 
 inoculated without success. 
 
 J. Hutchinson, junior, has shown that the interval 
 between two attacks of syphilis may be so short a 
 time as eighteen months, and that the second attack 
 may be either slighter or more severe than the first. 
 Nothing positive can be laid down on this point. 
 
 J. Hutchinson, senior, has recorded one definite 
 example of a patient having three attacks of syphilis. 
 
 Only a small number of undoubted cases have been 
 recorded of the development of acquired syphilis in 
 
30 SYPHILIS AND PARASYPHILIS 
 
 congenital syphilitics, and J. Hutchinson, junior, 
 doubts whether he has seen more than three or four 
 in twenty years' very extensive experience. 
 
 Since the introduction of salvarsan several cases of 
 reinfection within a few months are recorded, and 
 successful reinfection has been performed on a chim- 
 panzee with only three months' interval between the 
 two inoculations, salvarsan having been administered 
 after the appearance of a chancre had demonstrated 
 that the first inoculation was successful. 
 
 The immunity to superinfection produced by the 
 presence of syphilitic infection is not developed at 
 once, and is not absolute. 
 
 Metchnikoff and Roux obtained positive reinocula- 
 tions in monkeys ten days after the primary chancre 
 had appeared. 
 
 Finger and Landsteiner could not obtain inocula 
 tions after the chancre had been present for more 
 than five days. 
 
 Neisser obtained seventeen positive results in fifty 
 reinoculations on apes ; of these, eight were made on 
 the appearance of the primary sore, and nine later. 
 
 Positive results have been obtained when the second 
 inoculation was made as late as fifty days after the 
 appearance of the primary sore. 
 
 In the secondary stage of syphilis there is usually, 
 but not invariably, complete immunity to super- 
 infection, and this is also true of tertiary syphilis. 
 This pseudo-immunity disappears with cure. 
 
 Frage and Landsteiner have succeeded in obtaining 
 reinfection in the primary period and in the secondary 
 and tertiary periods. According to their observations. 
 
PARASITOLOGY 31 
 
 reinfection was expressed by a sclerosis in the primary 
 period, by papules in the secondary period, and by 
 gummas in the tertiary period. 
 
 The sequence of events in syphilis, which has been 
 roughly divided into primary, secondary, and tertiary 
 syphilis and parasyphilis, is capable of two explana- 
 tions : (i) That the Spivochceta pallida undergoes a 
 series of changes when resident in the tissues, and 
 that in each of these successive phases the symptoms 
 to which it can give rise are peculiar to the stage at 
 which it has arrived ; (2) that it is the tissues which 
 change, so that the longer the spirochaete acts on 
 them, the more the lesions which result from any 
 increased activity of this parasite approach first the 
 characters peculiar to the so-called secondary, and 
 then those of the tertiary, stage. 
 
 The first explanation would be difficult to prove, 
 and against it is the fact that infection with spiro- 
 chaetes derived from a secondary or tertiary lesion 
 results in a primary sore. In favour of the second 
 explanation is the well-known fact that in the majority 
 of cases of syphilis, whether untreated or treated with 
 mercury, reinoculation does not result in the produc- 
 tion of a second chancre. As Queyrat showed, this 
 refractory behaviour of the skin and mucous mem- 
 branes to infection from without is gradually developed 
 during the ten days which succeed the appearance of 
 the primary sore ; as the end of the period approaches, 
 the sore resulting from reinoculation becomes more 
 and more evanescent till, finally, no chancre follows. 
 Finger and Landsteiner succeeded in producing skin 
 lesions in such cases by inserting large amounts of 
 
32 SYPHILIS AND PARASYPHILIS 
 
 syphilitic virus in pockets under the epidermis ; these 
 were not chancres, however, but simulated the lesions 
 from which the patient was suffering at the time. 
 Thus in the secondary stage a papule followed the 
 inoculation, while in patients suffering from guramata 
 or ulcerating syphilides identical lesions formed at the 
 sites of inoculation. That these were due to the newly 
 introduced spirochaetes, and not to those already 
 infecting the patients, was shown by the fact that, 
 if the former were previously killed, the result of the 
 inoculation was negative. 
 
 The evidence is, therefore, strongly in favour of the 
 theory that it is the length of time during which the 
 spirochaetes have acted on the tissues which determines 
 the characters of the successive manifestations of 
 syphilis. 
 
 Neisser argues that a really cured syphilis does not 
 leave behind it a state of immunity, but thinks, on 
 the contrary, that only in those cases in which the 
 disease was still present was there a kind of so-called 
 immunity — that is to say, a resistance to a fresh 
 inoculation. He cannot accept the old dogma that 
 during the presence of syphilis an absolute prevention 
 against new inoculation exists, but neither can he 
 agree with the opinion of Finger, Ehrmann, and others, 
 who regard super-infection as quite a usual occurrence. 
 He, Neisser, believes that we must accept the state- 
 ment that, especially during the first few years of the 
 disease, as long as the virus of syphilis still remains 
 in the body, there exists a nearly complete resistance 
 to a second infection. 
 
 Doubtless in the future many more cases of re- 
 
PARASITOLOGY 33 
 
 infection will occur, since modern methods of treat- 
 ment will probably succeed in rapidly effecting a cure 
 of syphilis in many instances. 
 
 The old supposition is thoroughly false which states 
 that a person with syphilis, or one who has had 
 syphilis, can run the risk of acquiring further infection 
 without fear of penalty. 
 
 IMMUNITY 
 
 The susceptibility of individuals with regard to 
 syphilis depends on the degree of their immunity, 
 either natural or acquired. Certain races have up 
 till now been considered but little susceptible to its 
 infection, as, for example, the inhabitants of Iceland, 
 Greenland, and Central Africa. It is now recognized, 
 however, that this immunity is only apparent, as, since 
 intimate relations with Europeans were established, 
 syphilis has appeared. 
 
 The question of immunity in the descendants of 
 families of a syphilitic taint cannot be considered as 
 proved. The only certain proof is the resistance to 
 inoculation, and it is evidently impossible to state 
 whether the absence of infection after coitus with an 
 individual showing infective lesions has been due to 
 the integrity of the mucous membrane or not. 
 
 The rarity of cases of reinfection has long been 
 considered proof of an acquired immunity. There 
 is, however, a possibility of reinfection. Since the 
 Congress in London in 1896, many reliable observers 
 have published cases of reinfection. 
 
 Numerous works on the serum therapy of syphilis 
 
 3 
 
34 SYPHILIS AND PARASYPHILIS 
 
 have shown that the serum is capable of producing 
 some effect, but the problem cannot be solved until 
 we are able to obtain a very active animal serum. 
 
 The possibility of active immunization of animals 
 against syphilitic virus was shown for the first time 
 by Roux and Metchnikoff, who employed a virus 
 attenuated by several passages through macaques. 
 They considered that the slight form of the disease 
 produced by such an inoculation prevents an infection 
 following an inoculation with non-attenuated virus. 
 
 Metchnikoff has satisfied himself by experiments on 
 macaques that attenuation is obtained by passage. 
 Only local lesions occurred in which the spirochaetes 
 were found, and general symptoms did not appear. 
 
 Metchnikoff and Neisser have tried to obtain passive 
 immunity with the help of serum from monkeys who 
 have recovered from infection. Satisfactory results, 
 however, have not been achieved, and the monkeys 
 were not guarded against subsequent infection. They 
 have also vainly tried to obtain an immune serum 
 from the goat, injected with material very rich in 
 spirochsetes. 
 
 In the hope of provoking an active immunity in 
 cases of primary syphilis, and with a view to prevent 
 the occurrence of secondary syphilis, Kraus and Volk 
 inoculated with a carbolized emulsion of syphilitic 
 lesions ; they consider that they have abated the 
 disease in a few instances. 
 
 For the active immunization of monkeys, emulsions 
 have been tried made with the glands corresponding 
 to the chancre, and also with organs of congenital 
 syphilitics containing large numbers of spirochaetes. 
 
PARASITOLOGY 35 
 
 These emulsions were cooled in the ice-chest, and 
 carbolic acid added in a dilution of 0*5 per cent. 
 Repeated inoculations of the same product have not 
 produced immunization of animals. 
 
 If, also, the degree of immunity of the organism is 
 not very high, it will manifest itself by the presence 
 in the blood and in the organs of specific antibodies, 
 the formation of which corresponds usually with the 
 elaboration of immunity. These antibodies are repre- 
 sented by agglutinins, bacteriolysins, precipitins, and a 
 specific body producing the fixation of complement. 
 The agglutinins are formed after appearance of the 
 primary chancre. 
 
 Effect of Treatment on the Spirochaeta.— 
 Salvarsan, especially if given intravenously and in 
 efficient dosage, causes a very rapid disappearance of 
 the spirochaetae, which usually cannot be found after 
 twenty-four hours, and can practically never be 
 demonstrated after three days. 
 
 Mcintosh and Fildes have recorded an experiment 
 to show the relative merits of salvarsan and mercury. 
 They selected two rabbits with severe testicular 
 syphilitic lesions, and injected one intravenously with 
 o'l gramme of salvarsan, and gave the other two doses 
 of biniodide of mercury intravenously, giving in all 
 0-02 gramme of biniodide. No spirochaetes could be 
 found in the salvarsan-treated rabbit after seven hours, 
 while they persisted in the mercury-treated rabbit for 
 four days. 
 
 Metchnikoff and Roux have found that a chimpanzee, 
 inoculated with virus and the part rubbed for ten 
 minutes with calomel ointment three-quarters of an 
 
36 SYPHILIS AND PARASYPHILIS 
 
 hour after inoculation, developed no signs of syphilis, 
 and showed itself sensitive to subsequent inoculations. 
 A medical student, inoculated with the virus and 
 rubbed with calomel ointment for five minutes one 
 hour after inoculation, developed no signs of syphiHs ; 
 but an unrubbed monkey and a monkey rubbed twenty- 
 four hours after inoculation both developed syphilis. 
 
CHAPTER III 
 SYPHILITIC ANiEMIAS 
 
 Anemia has been recognized for a long time as often 
 associated with syphilis, and it can be looked upon as 
 probably the most constant of the constitutional 
 changes of this disease, and is especially noticeable in 
 the secondary stage. 
 
 In 1869 Virchow demonstrated a leucocytosis 
 coincident with the enlargement of the lymphatic 
 glands, with a relative increase in the number of 
 lymphocytes. Zehleneff examined the blood of twenty 
 patients daily for several weeks, and found a lympho- 
 cytosis in seventeen. 
 
 In 1872 Molassi first demonstrated the existence of 
 a pronounced decrease in the number of red cells in 
 three infected wet - nurses, and considered that the 
 anaemia coincided with the general manifestations of 
 the disease. 
 
 In 1874 Wilbowcheivitch demonstrated a reduction 
 in the number of red corpuscles in the primary period 
 coincident with an increase in the leucocytes. Outre 
 noticed the appearance of large nucleated red cells 
 (megaloblasts) during the appearance of the anaemia, 
 and small nucleated red cells (microblasts) at the end 
 
 37 
 
38 SYPHILIS AND PARASYPHILIS 
 
 of this period. Gram considers that there is an increase 
 in the number of microcytes, and that red cells of an 
 irregular shape (poikilocytes) are always present. 
 
 Marie has recorded that the red cells show a 
 diminished resistance to cold, so that they become 
 laked when placed on ice more easily than normal 
 cells. 
 
 The leucocytosis does not usually go above 15,000 
 to 18,000 per c.mm., but it is an early and very 
 constant symptom and lasts for a long time, so that 
 often it is the first and last syphilitic abnormality of 
 the blood which is recorded. It commences indepen- 
 dently of any local inflammatory or erosive condition 
 of the skin or mucous membrame, and usually occurs 
 between the healing of the chancre and appearance of 
 the rash. 
 
 Most authors agree that ansemia reaches its climax 
 during the secondary period, but different authorities 
 vary as to the exact time of its onset, some stating that 
 it precedes the rash, and others that it coincides with 
 or follows it. 
 
 A lymphocytosis is usually first noticed, to be 
 followed later by a diminution of haemoglobin and 
 in the number of the red cells. All these factors have 
 been noticed three weeks before the appearance of 
 the rash. After the appearance of the rash the 
 anaemia grows worse, and tends to run a parallel 
 course with the clinical manifestations, becoming 
 intense with malignant syphilis, or passing off as the 
 symptoms clear up. 
 
 In certain cases, coincident with the amelioration of 
 the anaemia, there is an increase of nucleated reds and 
 
SYPHILITIC AN MM IAS 39 
 
 blood platelets. The oscillations in the condition of 
 the blood can therefore give an index of the resistance 
 of the individual to infection. 
 
 In latent syphilis with no clinical manifestations, an 
 anaemia may be the only symptom besides the Wasser- 
 mann reaction, which shows that the cure is not com- 
 plete and permanent. Sometimes, however, though 
 the blood appears to have become completely normal, 
 the anaemia returns with a reappearance of symptoms. 
 
 The rise and fall in the amount of haemoglobin is 
 coincident with the increase and decrease in the 
 number of lymphocytes, and Mott considers that this 
 may indicate that, with the pouring out of an abundance 
 of lymphocytes from the lymph-stream into the blood- 
 stream, there was associated a pouring out of the 
 virus, causing the irritation and hyperplasia of the 
 lymph-cell elements. He considers that the anaemia 
 may be due to interference with the functions of the 
 blood-forming tissues. In support of this is the fact, 
 established experimentally by Neisser, that the red 
 marrow and spleen are especially rich in the virus. 
 Since mercury rapidly improves the anaemia, Mott 
 thinks it probable that it does so by arresting the 
 development of the spirochaetes in the blood-forming 
 tissues. 
 
 The anaemia seems to have a particular predilection 
 for w^omen and weak and over-worked young people, 
 and seems to be usually of the nature of a chlorosis. 
 This, however, is not invariable, and syphilis may 
 produce alterations of the most different kinds in the 
 blood, and the blood-picture may not be characteristic 
 of any particular clinical form of anaemia. Though the 
 
40 SYPHILIS AND PARASYPHILIS 
 
 early stages almost invariably show the anaemia of a 
 chlorotic type, later on the appearance may be that of 
 pernicious anaemia. 
 
 In late syphilis the blood is usually very nearly 
 normal, but really severe anaemia, when it occurs in 
 syphilis, does so only in the later stages. 
 
 The cause of this occasional appearance of grave 
 anaemia is unknown. 
 
 That the anaemia is not due to the mercury taken as 
 treatment is shown by the fact that it exists prior to 
 mercurial treatment, and that the blood condition 
 improves under treatment. It is only when mercury 
 has been given for a long time that its deleterious 
 effect upon the blood is shown. 
 
 Dominici divides syphilitic anaemias into three 
 classes : 
 
 1. Chlorotic type, without leucocytosis. 
 
 2. ,, ,, with leucocytosis. 
 
 3. Pernicious type. 
 
 Chlorotic Type, without Leucocytosis : 
 
 Twelve days before rash . 
 
 Red cells ... ... ... 5,350,000. 
 
 Haemoglobin ... ... 100 per cent. 
 
 Leucocytes ... ... 5,000. 
 
 Twelve days after rash. 
 
 Red cells ... ... ... 3,950,000. 
 
 Haemoglobin ... ... 80 per cent. 
 
 Leucocytes ... ... 8,000. 
 
 Chlorotic Type, with Leucocytosis : 
 
 Red cells ... ... ... 4,300,000. 
 
 Haemoglobin ... ... 75 per cent. 
 
 Leucocytes ... ... 12,200. 
 
 Colour index ... ... 0*87. 
 
SYPHILITIC ANEMIAS 41 
 
 Pernicious Type : 
 
 Red cells ... ... ... 1,540,000. 
 
 Haemoglobin ... ... 40 per cent. 
 
 Colour index ... ... 1-33. 
 
 Influence of Treatment on Syphilitic Anaemia. 
 
 Justus states that when a large inunction or injection 
 of mercury is given before the rash appears, but not 
 before the time when the general enlargement of the 
 lymphatic glands shows that the toxin is disseminated 
 throughout the body, the treatment is followed by an 
 immediate decrease in the percentage of haemoglobin, 
 from 10 to 20 per cent., to be followed by a rise, even 
 above normal, in a few days. This fall followed 
 by a rise is so constant that it can be used as a 
 reliable test for the presence of syphilitic infection. 
 Justus considers that this drop in the amount of 
 haemoglobin, which is both rapid and considerable, is 
 a specific test for a case of florid syphilis, and may be 
 obtained in any form of syphilis — late primary, 
 secondary, tertiary, or hereditary — provided the disease 
 be at that time florid, and not when or just before the 
 symptoms begin to recede. It may again be obtained 
 in cases of relapse and until the relapse has passed its 
 climax. It is not present during the primary stage so 
 long as the infection is limited to the chancre and its 
 neighbouring glands, but only after the toxin has 
 become widespread, as shown by the enlargement of 
 distant glands. Justus's claim that this test is pathog- 
 nomic cannot be taken as proved, though it is 
 undoubtedly present in a large percentage of cases. 
 Iron has no, or but a slight and transient, influence on 
 syphilitic anaemia. 
 
42 SYPHILIS AND PARASYPHILIS 
 
 Syphilitic Anaemias of Infancy. 
 
 The form of anaemia occurring in congenital syphilitic 
 children may be divided into three classes : 
 
 1. Chloro-anaemia with Leucocytosis, in which 
 the number of red cells may be normal, and the hgemo- 
 globin greatly reduced with a moderate leucocytosis. 
 The following example is from a child of ten months : 
 
 Red cells ... ... ... 4,637,000. 
 
 Haemoglobin ... ... 35 per cent. 
 
 Leucocytes ... .. 17,880. 
 
 Colour index ... ... 0*38. 
 
 2. Pernicious Type, where the red cells are greatly 
 diminished in number, and, although the haemoglobin 
 is reduced also, it is not so to such an extent as the 
 red cells, and therefore the colour index is raised. In 
 this type there is but slight leucocytosis^ if any. 
 Example : 
 
 Red cells ... ... ... 1,236,000. 
 
 Haemoglobin ... ... 30 per cent. 
 
 Leucocytes ... ... 11,700. 
 
 Colour index ... ... i'25. 
 
 In this type there are usually very few nucleated red 
 cells, but large numbers of megalocytes and giganto- 
 cytes. 
 
 3. LeucaemicType. — Here the leucocytes may reach 
 very large numbers and almost present the appearance 
 of a myologenous leucaemia. The combined count 
 of lymphocytes, myelocytes, and polymorphonuclears 
 may number 50,000 or more. This type usually shows 
 a large number of nucleated reds, many of these 
 showing division of the nucleus. 
 
SYPHILITIC ANMMIAS 43 
 
 Drysdale and Thursfield consider the following blood- 
 count typical of ordinary congenital syphilis : 
 
 Red cells ... 
 
 ... 4,224,000. 
 
 Haemoglobin 
 
 ... 76 per cent 
 
 Leucocytes 
 
 ... 13,463. 
 
 Colour index 
 
 ... 0-9. 
 
 Mott considers that there is nothing in most cases 
 of hereditary syphilis which is in any way remarkable 
 or different from w^hat may be seen in any moderate 
 secondary anaemia in infancy. He considers that it is 
 impossible to lay very much stress on the importance 
 of lymphocytosis, as this is an hereditary feature of all 
 infantile anaemias, and he considers it impossible to 
 name any one feature in the blood-count which is 
 distinctive of syphilis. 
 
 Following mercurial treatment there is often a fall 
 in the number of cells coincident sometimes with 
 haemoglobinuria, owing to the destruction of those red 
 cells which have been weakened by the syphilitic 
 toxin. If the treatment is carried too far it may then 
 be the cause of an anaemia. 
 
 It has been suggested that as cases of spasmodic 
 haematuria practically always show a syphilitic history, 
 the blood of syphilitics contains a haemolysin. The 
 author has examined the serum of twenty-five cases of 
 syphilis, and has been unable to find any trace of such 
 haemolysin. 
 
 Primary Syphilis. — No blood change is noticed 
 during this period, the first alteration usually appearing 
 during the healing of the chancre a fortnight or three 
 weeks before the onset of any secondary manifestations. 
 Probably the first change is that of a leucocytosis with 
 
44 SYPHILIS AND PARASYPHILIS 
 
 a relative and absolute increase of lymphocytes. A 
 slight deficiency in haemoglobin then follows, to be 
 followed again a little later by a decrease in the number 
 of red cells. 
 
 Secondary Syphilis. — The red cells drop very 
 rapidly, about 200,000 a day, and in untreated cases 
 may fall to 2,000,000 ; at the same time the quantity 
 of haemoglobin decreases. The red cells are pale and 
 vary in size and shape, showing a diminished resistance 
 to cold. The leucocytes average 12,000 to 16,000, and 
 may reach 25,000. At this stage the increase is both 
 of polymorphonuclears and lymphocytes, and later 
 there may be a slight eosinophilia. 
 
 Leoper thinks that the polymorphonuclear leuco- 
 cytes appear with each exacerbation of the symptoms, 
 and that the lymphocytes appear in the intervals 
 between such exacerbations, when there may be a 
 diminution in the number of polymorphonuclear leuco- 
 cytes. Nucleated red cells appear to increase with 
 the amelioration of the symptoms. 
 
 Mast cells may be numerous or may appear only 
 occasionally. 
 
 Most observers agree that there is an increase in 
 the amount of albumin in the serum in secondary 
 syphilis. This was first observed by Aparis in 1840, 
 who reported that the albumin of the plasma was 
 increased proportionately with the decrease of red 
 blood cells, the fibrin and serum being still of normal 
 proportions. Gram later confirmed the increase in 
 the amount of albumin. 
 
 In 1896 Valerio noticed a decrease in the alkalinity, 
 density, and the amount of chlorides present in the 
 
SYPHILITIC ANMMIAS 45 
 
 serum, and, proportional to the destruction of the red 
 cells, there must be an increase in pigment, potassium 
 salts, and phosphoric acid. 
 
 Tertiary Syphilis. — There is generally little blood- 
 change at this stage, although, as stated above, very 
 severe anaemias, when they occur, usually are found 
 during this stage. As a rule, there is a slight increase 
 in the number of leucocytes from 9,000 to 13,000, but 
 sometimes the leucocytes are less than the normal 
 (leucopeny). The increase may be either in the poly- 
 morphonuclears or lymphocytes. Some observers state 
 that eosinophiles are present in greater numbers in 
 this than in other stages. 
 
 During the tertiary stage with severe anaemia there 
 is usually leucocytosis with a high lymphocytosis, 
 myelocytes also being present. A marked leucocytosis 
 is an aid in excluding pernicious anaemia. In an adult 
 high lymphocytosis and an increase in eosinophiles 
 suggest syphilis, and in a child this blood-picture 
 might suggest rickets also. A low haemoglobin per- 
 centage and a high percentage of small mononuclears 
 have been considered indications that the infection is 
 acute. 
 
 Parasyphilis. — Tabes.— In tabes there is but little 
 change; perhaps there may be a slight excess of 
 polymorphonuclears. 
 
 General Paralysis, — In G.P.I, the blood-changes are 
 not very constant ; sometimes there is an increase 
 in the number either of polymorphs or lymphocytes ; 
 sometimes there is an increase in the eosinophiles, and 
 sometimes the white count is normal. 
 
CHAPTER IV 
 
 THEORIES FOR AND NATURE OF 
 WASSERMANN REACTION. 
 
 Pfeiffer's Phenomenon. — Pfeiffer found that if 
 certain organisms, such as the cholera spirillum, were 
 injected into the peritoneal cavity of a guinea-pig that 
 had been immunized against these organisms, they 
 almost immediately lost their mobility, and gradually 
 became granular and swollen, and subsequently dis- 
 appeared. Later he found that the same phenomenon 
 was present if a small quantity of antiserum was 
 added to an emulsion of the organisms, and the mix- 
 ture injected into the peritoneal cavity of a normal 
 guinea-pig. Later it was shown by Metchnikoff and 
 Bordet that the destruction of the bacteria (bacterio- 
 lysis) occurred outside the body if to the mixture of 
 antiserum and bacteria a little fresh serum was added ; 
 and Pfeiffer found that if the antiserum was heated at 
 from 55° to 70° C. for an hour, and added to the 
 bacteria emulsion, no bacteriolysis would be produced, 
 but that on the addition of some fresh serum bacterio- 
 lysis would occur. 
 
 Ehrlich gave the name of 'complement' to this 
 substance present in fresh normal serum which had 
 the power of enabling specific antigens and antibodies 
 to produce their action. 
 
 46 
 
NATURE OF WASSERMANN REACTION 47 
 
 Antigen-Antibody Reactions and Complement 
 Fixation. — Before commencing the serum diagnosis 
 it may be stated that by ' antigen ' is meant a substance 
 which, when it is introduced into a living body, stimu- 
 lates the cells of that body to produce a substance 
 which destroys or neutralizes it, and to which the 
 name 'antibody' has been given. It is probably by 
 this antigen-antibody action that recovery takes place 
 in most bacterial diseases, and the antigen or virus 
 is ultimately neutralized by its specific antibody. In 
 the case of toxin and antitoxin this reaction can take 
 place directly in the body or in vitro, and the reaction 
 appears to be a purely chemical one. With cells or 
 micro-organisms, or the extract or solution of cells or 
 micro-organisms, however, the action is more complex. 
 The antigen and antibody do, indeed, become linked 
 together, but the presence of a third substance is 
 necessary to activate or stimulate this union of antigen 
 and antibody before the neutralizing or destructive 
 process can be completed. Various names have been 
 given to this third activating body by different workers, 
 but the author will only refer to it by its most familiar 
 name, * complement.' 
 
 The complement in activating the mixture of antigen 
 and antibody becomes used up, and is therefore not 
 available for further use. 
 
 It need hardly be mentioned that ' lysis ' means 
 solution, and that therefore * bacteriolysis ' signifies 
 solution of bacteria, or * haemolysis ' solution of red 
 corpuscles. 
 
 Antigen and antibody are generally specific, so that 
 a diphtheria antigen produces only a diphtheria anti- 
 
48 SYPHILIS AND PARASYPHILIS 
 
 body, and a haemolytic antigen — viz., red blood-cells — 
 produces only an antibody to the same or closely allied 
 variety of blood-cells. The specificity is so delicate 
 that strains of organisms so closely allied as to be 
 morphologically and culturally similar can be differen- 
 tiated by a complement fixation test. In the case of 
 bloods, however, when the species are closely allied, 
 this method cannot be used for differential diagnosis, 
 as an antibody obtained by injection of a rabbit with 
 ox corpuscles will produce haemolysis of sheep's 
 corpuscles. 
 
 Fischer uses the analogy of a lock and key and 
 hand, for antigen, antibody, and complement respec- 
 tively. Thus, as any hand can turn any key in its 
 own lock, the key can only turn its own lock, and the 
 key cannot turn in the lock without the hand, so any 
 complement can complete the action of any combined 
 antigen and antibody, but the specific antibody only 
 unites with its own antigen, and the combined antigen 
 and antibody cannot complete their interaction without 
 the aid of complement. 
 
 The antibody unites readily with the antigen even 
 at room temperature, so that if, after standing for 
 half an hour, the mixture of antibody and antigen be 
 centrifuged and all the serum removed with a pipette, 
 it will be found, on the addition of complement and 
 incubation for a while at 37° C, that the specific 
 action is produced, thus showing that the essential 
 factor in the immune serum has become linked to the 
 antigen during the period when they were in contact. 
 
 Complement, however, which is a normal and con- 
 stant constituent of all fresh blood sera, is not specific 
 
NATURE OF IVASSERMANN REACTION 49 
 
 (although probably several complements exist), and 
 can activate any antigen that has united with its own 
 antibody. It is as yet an unisolated and little under- 
 stood substance, and is really only the name given to 
 a property, present in all fresh sera, which enables an 
 antigen and antibody not only to unite — which, as 
 shown above, they can readily do without comple- 
 ment — but, having united, to produce their specific 
 action. 
 
 In the Wassermann reaction fresh guinea-pig's serum 
 is generally used for complement, for the reason that 
 guinea-pig's serum contains a large amount of com- 
 plement (usually about five to ten times as much as a 
 similar quantity of rabbit's serum). 
 
 Complement has no power of fixing by itself either 
 to the antigen or antibody. 
 
 The optimum temperature of a complementary 
 action is 37° C. ; it is, however, capable of action 
 slowly at room temperature ; but its action entirely 
 ceases at 0° C. 
 
 Antibodies are very stable and preserve their prop- 
 erties for a very long time, and are not destroyed or 
 greatly decreased in potency by a temperature of 55° 
 to 57° C. 
 
 Complement is not a ferment, and a definite amount 
 of complement is necessary to produce the action of 
 a definite amount of antigen and antibody ; so that if 
 twice the amount of antigen is used, twice the amount 
 of complement will be required. 
 
 Everyone with much experience of the Wassermann 
 reaction, however, has noticed that with a large excess 
 of antibody haemolysis of the sheep's corpuscles is 
 
 4 
 
So SYPHILIS And parasyphiUs 
 
 produced with a smaller quantity of complement than 
 would be necessary with a smaller amount of anti- 
 body. And the converse is also true — an excess of 
 complement will produce haemolysis with a smaller 
 quantity of antibody. 
 
 Browning and Mackenzie have aptly described this 
 interaction when they say : ' The amount of antibody 
 required is a minimum when an excess of complement 
 is present, and vice versa.' 
 
 All complement fixation tests are quantitative, 
 and for this reason beginners are very likely to be 
 led into error, for a reading which at one time would 
 be reported as doubtful, at another time would be 
 reported as positive or negative. 
 
 Bordet-Gengou Phenomenon. — The Bordet- 
 Gengou phenomenon, discovered in 1 901, is founded 
 on the elementary axiom that 2 into i won't go; 
 two antigens, two antibodies, and one complement 
 being used — viz., sufficient complement to activate 
 one combined antigen-antibody. If, for example, 
 an emulsion of cholera vibrios and inactivated anti- 
 cholera serum — i.e., serum containing cholera antibody 
 which has been decomplementized by heating to 55° C. 
 — is mixed with some fresh complement and incu- 
 bated for one hour at 37° C, and sheep's corpuscles 
 and a decomplementized serum containing a haemo- 
 lytic antibody are added, and the mixture incubated 
 for another hour, no haemolysis will take place, 
 because the entire quantity of complement will have 
 been used up in activating the cholera antigen which 
 has united with the cholera antibody, so that solution 
 of the bacteria is produced, and therefore no comple- 
 
NATURE OF WASSERMANN REACTION 51 
 
 merit will be left over to activate the haemolytic system 
 and produce a solution of the corpuscles. 
 
 The converse of this experiment is also true ; for if 
 sheep's corpuscles and haemolytic antibody and com- 
 plement be mixed together and incubated, solution of 
 the corpuscles will occur ; but if this mixture is then 
 added to a mixture of an emulsion of cholera vibrios 
 and cholera antibody, no solution of bacteria will now 
 occur. By this reaction antibodies have been found 
 and demonstrated in typhoid, diphtheria, tubercle, 
 gonorrhoea, dysentery, cerebro-spinal meningitis, and 
 leprosy (James Mcintosh). 
 
 Wassermann Reaction. — The Wassermann 
 reaction, as originally described, was merely a modi- 
 fication of the Bordet-Gengou reaction, using for 
 antigen an aqueous or alcoholic extract of the liver 
 of a syphilitic foetus, which experience has shown to 
 contain enormous numbers of SpivochcBta pallida. 
 
 The test was originally supposed to turn upon 
 ascertaining the presence in the tested serum of any 
 syphilitic antibody, the extract of liver being used as 
 antigen. A haemolytic system is used for the second 
 part of the experiment in order to test whether the 
 complement has been used up in the first part of the 
 experiment or not. 
 
 The addition of the haemolytic system is not an 
 essential part of the test, but simply a biological 
 indicator for the presence of complement, in the same 
 way as the addition of litmus is a chemical indicator 
 for the presence of an acid or alkali produced as the 
 result of a chemical reaction. 
 
 The specific antigen and antibody, or any other 
 
52 SYPHILIS AND PARASYPHILIS 
 
 antibody present in a normal serum, can each sepa- 
 rately absorb a small quantity of complement, but a 
 very much greater quantity of complement is used up 
 in activating the combined antigen-antibody, so that 
 the specific antigen destroying reaction can occur. 
 Thus, if one volume of complement is absorbed by 
 two volumes of specific antigen, specific antibody, or 
 normal serum, when acting on each separately, making 
 three volumes in all, five, ten, or more volumes of 
 complement will be absorbed by the combined specific 
 antigen and antibody. 
 
 Absolute alcohol alone will absorb or destroy a 
 certain quantity of complement. 
 
 When testing for the presence of any antibody in 
 the test serum, therefore, we must add an excess of 
 complement over the amount that could be absorbed 
 by specific antigen, or normal serum. 
 
 If the patient's serum contains no antibody, the 
 complement will remain free, and therefore will be 
 able to sensitize the h?emolytic system, with the result 
 that haemolysis occurs. 
 
 Levaditi considers the Wassermann reaction not due 
 to antibody, but to some other substance produced by 
 a pathological metabolism of cells. He demonstrated 
 that antigen was not true antigen, as extracts from 
 normal liver produced the reaction, while Weil and 
 Braun showed that an extract made from a congenital 
 syphilitic liver, from which all lipoids had been ex- 
 tracted, could still be used as antigen. They also 
 demonstrated that jaundiced and lipaemic sera gave 
 negative reactions, thus showing that lipoids were not 
 the cause of the reaction. 
 
NATURE OF WASSERMANN REACTION 53 
 
 Bordet, with his absorption theory, suggested that 
 the active substance in syphilitic serum brings about 
 some change in the antigen, so that the altered antigen 
 acquires a greater absorptive power for complement. 
 Noguchi and others consider the reaction due to 
 interaction between albumin of the antibody and 
 lipoids of the antigen, probably as the result of the 
 precipitation of some of the colloids of the serum. 
 
 Wassermann thinks that the antigen is derived 
 directly from the Spiwchcstd pallida, but this opinion 
 seems to be based on data inconclusive to most other 
 workers. If the Wassermann reaction is purely a 
 specific one, consisting of the union of antigen (derived 
 directly or indirectly from the spirochaeta) and the 
 antibody present in the infected patient's serum, as 
 the result of infection with the spirochseta, we should 
 expect that the reaction would only be produced when 
 extracts from syphilitic tissues were used. This, 
 however, is not the case, and a mixture of syphilitic 
 serum and an extract of non-syphilitic organs fix the 
 complement very nearly, if not quite, as satisfactorily. 
 
 Whatever may be the nature of the reaction, we 
 are faced with the conclusion that clinically the test 
 is, with a few exceptions, pathognomic of syphilis, 
 and that this test holds good if substances are used 
 for antigen which have nothing whatever to do with 
 syphilis. Plant thinks that the most probable ex- 
 planation is that the antigen obtained in syphilitic or 
 normal tissue is identical, but that syphilitic organs 
 usually contain this antigen in larger amount or in 
 a more easily extractable form than non-syphilitic 
 organs. He considers that it is proved that a sub- 
 
54 SYPHILIS AND PARASYPHILIS 
 
 stance is found in syphilitic serum which reacts also 
 towards the products of normal tissues, and that the 
 original conception of the biological specificity of the 
 reaction is therefore no longer to be held as correct in 
 its full sense. 
 
 Many observers consider the antigen to be in the 
 nature of a lipoid, and Levaditi and Yamanouchi 
 further consider that the antibody found in the 
 cerebro-spinal fluid of general paralytics is also a 
 lipoid, and soluble in alcohol. Pure lipoids, however, 
 although they fix complement, show but little differ- 
 ence in the quantity of complement they fix when 
 mixed with syphilitic serum or normal serum. 
 
 Sodium oleate, cholesterin, sodium glycocolate, etc., 
 have all been proved to fix complement, but fix but 
 little more, if any, in the presence of syphilitic sera 
 than they do in the presence of normal sera. 
 
 Browning and Mackenzie have found that a mixture 
 of cholesterin and lecithin not only fixes much more 
 complement than either of the constituents of the 
 mixture by itself, but that much more complement 
 is fixed in the presence of syphilitic sera than in the 
 presence of normal sera. The author has investigated 
 their claim in over a hundred sera, having made 
 parallel tests of the same sera, using extract of 
 syphilitic organs, extract of normal organs, and 
 cholesterin - lecithin mixture as antigen, and has 
 obtained practically identical results with all three. 
 
 As regards the serum, exposure to a temperature 
 of 55° to 57° C. for half an hour certainly seems to 
 diminish the reaction. Prolonged exposure at these 
 temperatures can destroy the reacting power altogether. 
 
NATURE OF WASSERMANN REACTION 55 
 
 Bruck considers that a temperature of 60° C. increases 
 the complement fixing-power of sera by themselves. 
 It has also been shown that normal sera may have a 
 complement fixing-power in the unheated state which 
 disappears if it is heated at 55** C. 
 
 No definite conclusion has yet been arrived at as to 
 what the Wassermann reaction really is. 
 
 Weil and Braun consider that in the course of the 
 disease tissue-products, mixtures of albumin and lipoid 
 probably, are absorbed and give rise to antibodies. 
 
 Citron considers that the syphilitic toxin becomes 
 combined with lipoids, and that this combination of 
 toxin and lipoid acts as an antigen, and leads to the 
 production of an antibody in the sera. 
 
 Bruck and Stern think that the reaction may be 
 brought about by the interaction between mixtures 
 of albumin and lipoid found in the extract and 
 mixtures of albumin and lipoid found in the serum. 
 
 Mott considers that the substance present in the 
 serum or cerebro-spinal fluid necessary to produce the 
 reaction may be the detachable products of nerve- 
 tissues. 
 
 Neither lecithin nor cholesterin, if used as antigen, 
 can produce antibody. 
 
 Plant comes to the conclusion : 
 
 I. That the Wassermann reaction is a biological 
 specific antigen-antibody reaction for syphilis, in which 
 the antibodies on the one side have the peculiarity of 
 reacting, not alone with syphilitic antigen, but also 
 with normal tissue constituents, and that the antigen, 
 on the other hand, is very closely related to the lipoids, 
 and probably is an albumin lipoid compound. 
 
56 SYPHILIS AND PARASYPHILIS 
 
 2. The reacting substances of the syphilitic serum 
 are not antibodies, but substances which owe their 
 origin to syphiUtic infection and possess a chemical 
 affinity for lecithin. 
 
 3. In the Wassermann reaction specific and non- 
 specific fixation processes go hand in hand. 
 
 That the complement-fixing substance (antibody) 
 exercises no spirochaeticidal action has been proved by 
 experiments both in vivo and in vitro. In the one case 
 an ape was injected with large quantities of serum 
 containing a large amount of complement - fixing 
 substance which, however, did not prevent successful 
 inoculation with syphilitic virus, and in the second 
 serum obtained from a chancre, and containing large 
 numbers of spirochaetes, was treated with a mixture of 
 complement and serum containing a large amount of 
 complement-fixing substance. This mixture was then 
 used to inoculate an ape, with positive results. 
 
 According to Citron's theory, mentioned above, the 
 antibody produced is one in which the mixture of 
 toxin and lipoid is the antigen and not the spirochaete. 
 This antibody, therefore, could not be expected to 
 produce immunity to the Spirochceta pallida^ which 
 agrees with experimental findings. 
 
 Weil and Braun found that an extract of syphilitic 
 liver from which all lipoids were removed yet remained 
 an efficient antigen. 
 
 Mcintosh and Fildes point out that Sach's observa- 
 tion that the Wassermann bodies are destroyed by a 
 temperature which does not affect true antibodies, and 
 that Satta and Donetti's demonstration that fixation 
 of complement in the Wassermann reaction can take 
 
NATURE OF WASSERMANN REACTION 57 
 
 place in the ice-chest as well as at 37° C, and Muter- 
 milch and Mcintosh's observations that the Wasser- 
 mann body does not pass through a filter, all tend to 
 show that the reaction is rather physico-chemical than 
 biological. 
 
 The effect of treatment, also, is to destroy the 
 Wassermann body, and not to produce it, the dis- 
 appearance of symptoms coinciding with the dimi- 
 nution or loss of complement - fixing substance. 
 This is paricularly striking after treatment with 
 salvarsan. 
 
 The physico-chemical theory was first suggested by 
 Levaditi and Yamanouchi, who thought that the fixa- 
 tion of complement was due to an interaction between 
 substances in the serum and in the extract used as 
 antigen, so that the resulting mixture had a greater 
 affinity for complement. 
 
 Wolfsohn and Reicher, and later Boas and Petersen, 
 have shown that if blood is obtained towards the end 
 of a period of deep anaesthesia, some specimens will 
 give a positive Wassermann reaction. These experi- 
 ments certainly suggest that the reaction is produced 
 by some form of cell destruction, and could not be the 
 result of an antibody. 
 
 The high percentage of positive Wassermanns 
 obtained with blood taken from the cadaver also 
 supports this view. 
 
 From the above opposing theories, and from the 
 rather contradictory nature of the evidence at present 
 available, it is obvious that the precise nature of the 
 reaction has yet to be discovered. We are, however, 
 able to arrive at two conclusions : 
 
58 SYPHILIS AND PARASYPHILIS 
 
 1. That the reaction in the absence of a few 
 diseases and conditions, which can easily be eliminated, 
 is a reliable clinical test for syphilitic infection. 
 
 2. That the reaction is not strictly specific, that the 
 substance produced is not a true antibody, and that 
 the so-called antigen is not a true antigen. 
 
CHAPTER V 
 
 PREPARATION AND TITRATION OF RE- 
 AGENTS REQUIRED FOR WASSER- 
 MANN REACTION 
 
 The materials required in the original method for the 
 estimation of the Wassermann reaction are five in 
 number. 
 
 1. Syphilitic antigen, or rather pseudo-antigen, 
 prepared either from syphilitic organs, normal organs, 
 or lecithin and cholesterin. 
 
 2. The patient's blood-serum. 
 
 3. Complement from fresh guinea-pig's serum. 
 
 4. Washed sheep's corpuscles (haemolytic antigen). 
 
 5. A serum haemolytic to sheep's corpuscles 
 (haemolytic antibody). 
 
 I. Syphilitic Pseudo- Antigen. 
 
 (i) Extract of Syphilitic Organs as prepared 
 by Noguchi and Mott. — The weighed liver of a 
 syphilitic foetus is ground up with a sufficient quantity 
 of silver-sand and plaster of Paris, so that after a few 
 hours it can be reduced to a powder ; this powder is 
 then washed with acetone, which removes bodies 
 which have anticomplementary and haemolytic 
 
 59 
 
6o SYPHILIS AND PARASYPHILIS 
 
 properties. The acetone is then filtered off, and 
 the remaining solid material is allowed to dry at 
 room temperature. The dry residue is then trans- 
 ferred to a flask and a sufficient quantity of alcohol 
 added ; this flask is kept at room temperature and 
 occasionally shaken. After two days the alcoholic 
 extract is filtered off, and the filtrate made up with 
 alcoholic washings of the powdered organ so that 
 4 c.c. is equivalent to i gramme of liver. The extract 
 keeps well for several months without much deteriora- 
 tion, and should be stored in the dark and in the cold. 
 
 (2) Extract of Normal Organs. — Human heart, 
 ox's heart, guinea-pig's heart, all have their advocates, 
 but personally the author prefers an extract of rabbit's 
 heart, with which excellent results have been obtained. 
 The heart should be fresh, should be washed in saline 
 to remove all blood, as much connective tissue as 
 possible should be removed, and the opened heart 
 roughly dried between filter-paper. The heart is now 
 weighed and afterwards cut up into small pieces with 
 scissors. A little absolute alcohol is added, and the 
 mixture well ground in a pestle and mortar. More 
 alcohol is slowly added, till the final quantity of 10 c.c. 
 of alcohol to I gramme of heart is reached. The mix- 
 ture is kept in a stoppered bottle at room temperature 
 for two days, and occasionally shaken ; it is then centri- 
 fuged, and the supernatant fluid pipetted off and stored 
 in the cold and in the dark. 
 
 (3) Mixture of Lecithin and Cholesterin 
 (Browning, Cruikshank, and Mackenzie). — The lecithin 
 is obtained by making an alcoholic extract of fresh and 
 finely minced ox liver, one part of liver being taken to 
 
PREPARATION OF REAGENTS 6i 
 
 four parts of 95 per cent, alcohol. This is kept at room 
 temperature and occasionally stirred ; after four days 
 the supernatant fluid is pipetted off and evaporated at 
 60° C. till a syrupy mass remains. This is treated in 
 succession with ethyl-acetate, water-free ether, and 
 acetone, and the alcoholic lecithin solution so 
 obtained is kept in a stoppered bottle in the dark. 
 The cholestevin used by the authors of this method 
 was obtained from Kahlbaum or Roulene Fr^res. 
 It is added in excess to a 075 solution of lecithin 
 in alcohol. As saturation occurs only slowly at 
 room temperature, the mixture should be allowed to 
 stand for a week before the clear fluid is drawn off and 
 stored for use.* 
 
 A good antigen, no matter how prepared, is one 
 producing a large deflection of complement in the 
 presence of a syphilitic serum, and which fixes but 
 little complement by itself or in the presence of a 
 normal serum. Absolute alcohol alone and alcoholic 
 extracts in the presence of normal sera have power 
 to fix a certain amount of complement. 
 
 When standardizing the antigen various quantities 
 of antigen are added to test-tubes containing constant 
 quantities of syphilitic serum and complement, and 
 the tube noted in which the smallest amount of 
 antigen is capable of producing complete inhibition 
 of haemolysis, indicating complete fixation of comple- 
 ment. 
 
 * Particulars of the method of preparation will be found in 
 Browning and Mackenzie's book on ' Recent Methods of 
 Diagnosis and Treatment of Syphilis,' p. 38. The mixed 
 alcoholic solution of lecithin and cholesterin can be obtained 
 from Messrs. Thompson, Skinner, and Hamilton, 38, Sauchiehall 
 Street, Glasgow. 
 
62 SYPHILIS AND PARASYPHILIS 
 
 A second row of test-tubes contain complement and 
 antigen alone, and no serum ; and a third row com- 
 plement and antigen, and normal serum in place of 
 the syphilitic serum. The antigen selected for use 
 should fix very little complement by itself alone pr 
 in the presence of normal serum, and at least three 
 times as much antigen should be necessary to fix a 
 given quantity of complement with normal serum 
 than would be required with syphilitic serum. 
 
 2. Patient's Serum. 
 
 Test Serum. — The blood is collected in a sterile 
 tube. After being allowed to stand for a couple 
 of hours, it is centrifuged and the clear serum drawn 
 off with a sterile pipette, sealed in small sterile glass 
 phials, heated in a water-bath at a temperature of 
 5^° C. for fifteen minutes in order to destroy the 
 complement which it contains, and stored in a cool 
 place in the dark. It is preferable to have a con- 
 siderable quantity of serum, so that a quantitative 
 measurement of the complement-fixing substance may 
 be undertaken, and in order that the experiments may 
 be repeated should the controls not work out satis- 
 factorily. For this reason the author prefers obtaining 
 blood by venipuncture rather than by pricking the 
 finger. When collecting numerous samples of blood 
 by venipuncture, the use of a syringe necessitates 
 a considerable waste of time, as the syringe cannot, 
 after use, be plunged into boiling water for re- 
 sterilization without great danger of cracking, neither 
 can it safely be removed from boiling water. If the 
 temperature is gradually raised to boiling-point, and 
 
PREPARATION OF REAGENTS 63 
 
 then lowered, at least ten minutes will be required for 
 each case. Instead of a syringe, therefore, the author 
 uses a hollow metal holder, 2| inches long, having 
 a finger-grip half an inch from the nozzle end. The 
 bulbous distal end is connected to about 4 inches of 
 rubber tubing, leading to a sterile test-tube, into 
 which the blood flows directly (see Fig. 14). The 
 author uses needles i inch long, and with the calibre 
 of a large exploring needle. 
 
 Technique. — After washing the bend of the elbow 
 with ether and absolute alcohol, a firm bandage is 
 applied round the upper arm, and the patient is told 
 
 Fig. 14. — Venipuncture Needle and Holder (Author's 
 
 Pattern). 
 
 * to make a fist.' Either the median basilic or median 
 cephalic vein can then easily be seen. The needle, 
 after being lubricated with sterile oil, is plunged boldly 
 into the vein with a quick stab, keeping the needle and 
 holder in the direction of the long axis of the vein, 
 taking care not to depress the point too much in order 
 to avoid transfixing the vein. The blood will flow 
 directly into the tube, and it will only take a few 
 seconds to half fill it. The glass test-tube and the 
 needle-holder, with the rubber tubing leading into the 
 test-tube, can be held quite easily in the right hand. 
 Before making the puncture, the skin over the vein 
 should be rendered tense and pulled a little down over 
 
64 SYPHILIS AND PARASYPHILIS 
 
 with the thumb of the left hand. The bandage must 
 be loosened and the patient told to unclasp his hand 
 before the needle is removed, otherwise a subcutaneous 
 haematoma may be produced. If a small pad is held 
 over the puncture, and the patient told to hold his 
 arm in the air for a few minutes, there will be no 
 bleeding, and no dressing will be required. The 
 author always places a sterile swab soaked with 
 methylated spirit over the puncture before removing 
 the needle, and in this way not a single drop of blood 
 escapes, except into the test-tube, and the patient 
 sees no blood at all. 
 
 After standing for a few hours to permit the serum 
 to separate from the clot, the serum is withdrawn with 
 a pipette made by drawing out glass tubing (Fig. 15). 
 It is then placed in small sterile phials, which are 
 sealed in the flame, and the sealed phials are immersed 
 in a water-bath at a temperature of ^^° C. for fifteen 
 minutes to destroy the complement contained in the 
 serum. 
 
 After use, the holder and rubber tube should be 
 washed through with a small glass urethral syringe to 
 remove the blood before replacing in the sterilizer. 
 
 If, as very occasionally happens, a patient objects 
 to venipuncture, or a vein of sufficient size cannot be 
 found, or, as with children or infants, the test has to be 
 undertaken with a smaller quantity of serum, then in 
 these cases the blood is obtained by pricking the finger, 
 or, as the author usually finds more suitable with small 
 infants, the great toe or heel. In small, marasmic 
 infants it will be necessary to soak the limb in hot 
 water before pricking. The blood is collected in 
 
PREPARATION OF REAGENTS 65 
 
 large Widal tubes, which are filled by capillary 
 attraction. 
 
 3. Complement, 
 
 This is obtained from fresh guinea-pig's serum, 
 a guinea-pig being selected because its blood is very 
 rich in complement, and its complement content is 
 very nearly constant ; guinea-pig's serum usually 
 contains from five to ten times the amount of 
 complement found in rabbit's, horse's, or human 
 blood. The author thinks that the largest amount 
 of serum is obtained from a guinea-pig in the fol- 
 lowing way : Some cotton-wool is placed in the 
 bottom of a wide-necked glass jar of such a size as to 
 easily admit the guinea-pig's head ; a few drachms of 
 
 Fig. 15. — Pipette for drawing off Blood or Serum. 
 (One-third natural size.) 
 
 ether are poured on the cotton-wool, and the jar is 
 then slipped over the guinea-pig's head. When anaes- 
 thesia is complete, the chest is opened and the blood 
 removed by puncturing the heart with a pipette 
 (Fig. 15). If the heart and lungs are now removed, 
 a little additional blood can be collected from the 
 thoracic cavity. After standing for a quarter of an 
 hour, the blood should be whipped for a few minutes 
 and then centrifuged, when the clear serum is pipetted 
 off. The author thinks it is best to prepare the com- 
 plement on the evening before, and store it in the 
 ice-chest for use the following day. 
 
 5 
 
66 SYPHILIS AND PARASYPHILIS 
 
 The complement-content of fresh guinea-pig's serum 
 does not usually vary very much, but it is wise to put 
 up three tubes containing the amount of complement 
 to be used in the test, and containing respectively the 
 usual quantities of antigen alone, antigen and normal 
 serum, and antigen and syphilitic serum. Complete 
 haemolysis should be produced in all but the tube con- 
 taining the syphilitic serum, in which there should be 
 no haemolysis. 
 
 4 and 5. Haemolytic System. 
 
 (a) Sheep's Corpuscles. — Fresh blood is col- 
 lected at the slaughter-house into a sterilized wide- 
 necked glass bottle containing several pieces of wire. 
 The bottle is half filled with blood, when it is 
 securely stoppered and briskly shaken for ten minutes. 
 The fibrin will be deposited on the wires, and 10 c.c. 
 of the defibrinated blood is centrifuged and the 
 supernatant fluid pipetted off. Normal saline solu- 
 tion is added to the deposit of red cells, which are 
 shaken up, and the mixture of salt solution and 
 corpuscles again centrifuged. The supernatant fluid is 
 again pipetted off and thrown away, and fresh normal 
 saline added to bring the volume up to the original 
 10 c.c. In this way a suspension of sheep's corpuscles 
 free from serum and complement is obtained. 
 
 Eight c.c. of this suspension is added to 92 c.c. of 
 normal saline solution, producing an 8 per cent, solution 
 of washed sheep's corpuscles, which is the strength 
 the author employs. If stored in an ice-chest, the 
 corpuscles will usually keep three or four days without 
 haemolyzing. 
 
PREPARATION OF REAGENTS 67 
 
 Some observers consider that greater accuracy is 
 demanded, and count the corpuscular suspension with 
 the Throma-Zeiz, in this way insuring that the cor- 
 puscular suspension is always constant as regards 
 numbers. It appears to the author, however, that 
 different corpuscular suspensions vary in their sus- 
 ceptibility to haemolysis, and that therefore we cannot 
 insure that any two corpuscular suspensions are 
 constant factors. 
 
 The quantity of immune body required is in direct 
 proportion to the number of red cells, a 20 per cent, 
 suspension requiring just twice as much haemolytic 
 serum to produce complete haemolysis as does a 
 10 per cent, suspension. 
 
 Some authorities consider that the corpuscles keep 
 longer if a little formalin has been added to the normal 
 saline solution (in proportion of o*i per cent.). Per- 
 sonally, the author prefers to use fresh blood, as he 
 thinks that the formalin tends to harden the corpuscles 
 and retard or prevent haemolysis. 
 
 (b) Haemolytic Serum. — This can be obtained by 
 treating a rabbit with washed sheep's corpuscles. 
 The rabbit may be injected either intravenously in 
 the marginal auricular vein or intraperitoneally. In 
 the latter case, which is easier, but perhaps not quite 
 so satisfactory, the rabbit should be held with its head 
 downwards, the abdominal walls being grasped with 
 the fingers and thumb of the left hand so as to make 
 a fold containing no intestines, and this is transfixed 
 with a needle attached to the syringe containing the 
 sheep's corpuscles. When the left hand is taken 
 away, the fold disappears and the needle is withdrawn, 
 
68 SYPHILIS AND PARASYPHILIS 
 
 SO that the point re-enters the abdominal cavity; the con- 
 tents of the syringe are now injected into the peritoneal 
 cavity, and the needle removed. Usually about three 
 injections are required to obtain a potent serum, the 
 injections being given at intervals of four to six days. 
 
 Recently, Burroughs and Wellcome have placed a 
 haemolytic serum, obtained from the horse, on the 
 market, and the author has found it quite satisfactory 
 in use. The horse serum, however, contains hsemo- 
 agglutinins as well as haemolysins, but the agglutinins 
 do not act in dilution above i in 400. It is important, 
 therefore, that the serum should have a high haemolytic 
 titre, such as i in 800 or i in 1,000, as, if agglutination 
 occurs, the red cells clump and fall to the bottom of 
 the test-tube before the hsemolysin has had time to 
 act on them and dissolve them. 
 
 Haemolytic serum, whether obtained from the rabbit 
 or the horse, keeps its haemolytic power for a long 
 time, and the haemolytic titre falls very gradually as 
 a rule. 
 
 The haemolytic serum should be used in excess, 
 about twice the haemolytic dose being recommended 
 by Wassermann. Varying dilutions of haemolytic serum 
 are added to tubes containing constant quantities of 
 complement and suspension of sheep's corpuscles, and 
 the tube noted in which complete haemolysis is just 
 produced in five minutes in a water-bath at a tem- 
 perature of 37° C. 
 
 If a smaller dilution than i in 400 is necessary, the 
 serum cannot be considered satisfactory, as agglutina- 
 tion of the corpuscles may be produced, which may 
 interfere with the action of the haemolysin. 
 
PREPARATION OF REAGENTS 69 
 
 A rapid dilution can be effected in the following 
 way: Into two test-tubes measure 9 c.c. of saline 
 solution ; to the first add i c.c. of the haemolytic serum 
 to be tested, shake and add i c.c, of this to the second ; 
 this will give a solution of i in 100. Now put 5 c.c. 
 of saline into five test-tubes and to the first tube add 
 5 c.c. of the mixture from the test-tube containing the 
 dilution of i in 100, shake and take 5 c.c. of this and 
 add it to the next tube, and so on. In this way dilu- 
 tions of I in 200, 400, 800, 1,600, and 3,200 will be 
 rapidly effected. If complete haemolysis is produced 
 in I c.c. of an 8 per cent, suspension of sheep's 
 corpuscles containing 0-05 c.c. of fresh guinea-pig's 
 serum with i c.c. of haemolytic serum in a dilution 
 of I in 800 to 1,600, the haemolytic serum may be 
 considered a good one. 
 
CHAPTER VI 
 
 WASSERMANN REACTION 
 
 ORIGINAL TECHNIQUE 
 
 Quantitative Measurement by Variation in 
 Amount of Complement. 
 
 The first technique described is a modification of 
 Neisser's and Wassermann's that the author uses, 
 and in which all the essentials of Wassermann's 
 original technique are preserved. 
 
 Two test-tubes are required for each serum ex- 
 amined, whether sera to be tested or controls. The 
 latter consist of a known syphilitic serum, a known 
 normal serum, and a tube without any serum at all. 
 
 The tubes are arranged in two rows, those in the 
 back row containing three times as much complement 
 as the front row, so as to obtain a roughly quantitative 
 estimation of the complement fixing-povver of the 
 serum. The quantities of the various ingredients, 
 which the author has found to be most convenient, 
 are — For the front row, i c.c. of normal salt solution, 
 o"i c.c. of antigen, and o"05 c.c. of fresh guinea-pig's 
 serum per each tube. Considerable time is saved 
 and greater accuracy obtained if these three constant 
 factors (salt solution, antigen, and complement serum) 
 
 70 
 
WASSERMANN REACTION -ji 
 
 are first mixed in bulk (instead of separately in each 
 test-tube) and afterwards i c.c. of the mixture measured 
 into the test-tubes, to which 0*15 c.c. of the serum to 
 be tested is added. Let us suppose that there are 
 seven sera to be examined, making a total of ten with 
 the three controls. Ten c.c. of saline solution are 
 then taken, i c.c. of antigen, 0*5 c.c. of fresh guinea- 
 pig's serum. These are well mixed together, and 
 I c.c. of the mixture put into each of the test-tubes in 
 the front row. For the back row similar quantities 
 of saline and antigen are used, but three times the 
 amount of complement — namely, o'i5 c.c. per each 
 tube, or 1*5 c.c. for the ten. By this mixing of the 
 saline, extract, and complement in bulk, only two 
 pipette measurements are required instead of four, 
 which would be necessary if the saline, antigen, com- 
 plement, and test-serum were added separately to each 
 tube. 
 
 If the antigen alcoholic extract is mixed with the 
 full quantity of normal saline, only a slight opalescence 
 is produced. If, however, the antigen extract is first 
 mixed with its own quantity of saline, a marked 
 turbidity results, and if this is then added to the rest 
 of the saline, the turbidity remains. Browning and 
 Mackenzie and the author, working independently, 
 arrived at the conclusion that the best results were 
 obtained when the turbid emulsion was used, and this 
 is still the author's opinion. Macintosh and Fildes, 
 on the other hand, consider that if a turbid emulsion 
 is used, there is a liability to complement fixation even 
 with normal sera, and they recommend, therefore, that 
 the antigen extract should be rapidly mixed with the 
 
72 SYPHILIS AND PARASYPHILIS 
 
 full quantity of serum, so that there may be as little 
 turbidity as possible. 
 
 The neck of the ampule containing the decomple- 
 mentized test-serum is now broken off and the required 
 quantity (0-15 c.c.) removed with a teat-pipette 
 (Fig. 16) and added to the front row and corre- 
 sponding back-row tubes. 
 
 After adding the 0*15 c.c. of the various sera to be 
 tested to their respective tubes, using the same 
 quantity for both front and back rows, the tubes are 
 inverted, keeping the thumb over the open end, so as 
 to diffuse the serum equally in the test-tubes. The 
 test-tube rack is now placed in a water-bath at 37° C. 
 
 Fig. 16. — Teat-Pipette, marked to measure o"i5 c.c. 
 
 for half an hour (Fig. 17). Having previously 
 ascertained the strength of the haemolytic serum, a 
 dilution of such serum is now prepared of such a 
 strength that each tube will contain twice the dose 
 necessary to produce complete haemolysis in i c.c. of 
 an 8 per cent, suspension of washed sheep's corpuscles. 
 Let us suppose that the haemolytic serum previously 
 tested produced complete haemolysis of an 8 per cent, 
 suspension of sheep's corpuscles in a dilution of i in 
 1,600. We must obtain a dilution of i in 800 in the 
 final test. For our twenty tubes (ten in each row) we 
 required 20 c.c. of the sensitized corpuscles ; we 
 therefore take 10 c.c. of a dilution of i in 200 of 
 haemolytic serum and add to it 10 c.c. of an 8 per cent, 
 suspension of sheep's corpuscles, when we shall have 
 
WASSERMANN REACTION 73 
 
 a dilution of i in 400, making 20 c.c. in all ; this 
 mixture of htemolytic antigen and antibody is called 
 the ' haemolytic system.' One c.c. of this mixture is 
 then added to each of the tubes which have been 
 incubated for half an hour, so that the final dilution 
 of I in Soo is arrived at. The tubes are now inverted 
 
 Fig. 17. — "Water-Bath. 
 
 again and replaced in the water-bath until such time 
 as complete solution of the corpuscles is produced in 
 the two control-tubes containing normal serum and no 
 serum. When complete solution occurs in these two 
 control-tubes, the test-tube rack can be removed from 
 the water-bath and the tubes examined. 
 
74 SYPHILIS AND PARASYPHILIS 
 
 If the test-tube contains serum from a case of 
 syphilitic infection, a substance having the power of 
 uniting with the antigen will be present, and the 
 complement will have been used up by these two 
 combined substances. There will therefore be no 
 complement left over for the second incubation period 
 after the haemolytic antibody and antigen, were added. 
 No haemolysis can take place in these tubes, and the 
 suspension of corpuscles will remain opaque. On 
 standing, the corpuscles will, after a few hours, sink 
 to the bottom of the test-tube, and the supernatant 
 fluid will be clear and colourless if the inhibition of 
 haemolysis has been complete. If, on the other hand, 
 the test-serumx is free from syphilitic infection, the 
 substance having the power to unite with the antigen 
 will be absent ; the complement will, therefore, not be 
 used up, and will be free to activate the haemolytic 
 system, and solution of the corpuscles will occur and 
 a clear red solution be obtained. 
 
 Between the two extremes of complete inhibition of 
 haemolysis and complete haemolysis there may be 
 many degrees of partial haemolysis which must be 
 estimated by the amount of undissolved red cells at 
 the bottom of the test-tubes and the depth of tint of 
 the supernatant fluid. 
 
 The haemolytic system should be prepared and 
 incubated at 37° C. for a short while before being 
 used, so that the corpuscles may be fully sensitized 
 and only require the addition of complement to 
 produce rapid haemolysis. 
 
 It will be found that a strongly positive serum will 
 contain sufficient complement-fixing substance to fix 
 
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WASSERMANN REACTION 75 
 
 the triple dose of complement in the back row, but that 
 in some cases only sufficient will be present to fix the 
 smaller dose of complement in the front row, and 
 complete haemolysis may be produced in the back row 
 (Fig. 18). 
 
 Frequently, as a patient comes under the influence 
 of treatment, the blood will pass through the stages 
 of— 
 
 (i) Complete inhibition of haemolysis in front 
 and back tubes ; 
 
 (2) Complete inhibition of haemolysis in front 
 
 tubes, partial haemolysis in the back 
 tubes ; 
 
 (3) Complete inhibition in the front tubes, com- 
 
 plete haemolysis in the back tubes ; 
 
 (4) Partial haemolysis in the front tubes ; 
 
 until finally a completely negative reaction is reached 
 — namely : 
 
 (5) Complete haemolysis in front as well as back 
 
 tubes. 
 
 The author uses the symbol + to denote complete 
 inhibition of haemolysis, ± to denote partial haemolysis, 
 and - to denote complete haemolysis. 
 
 If the left-hand symbol of each pair denotes the 
 degree of reaction in the front tube, and the right- 
 hand symbol that in the corresponding back-row tube, 
 the five degrees of reaction mentioned above will be 
 recorded respectively — 
 
 + +, +±, +-, ±-, - -. 
 
 It is obvious that a quantitative measurement for 
 the complement-fixation substance in the serum can 
 
76 SYPHILIS AND PARASYPHILIS 
 
 be made either by using varying quantities of com- 
 plement, keeping the other factors constant, as above 
 described ; or by varying the quantity of antigen, 
 keeping the complement and test-serum constant ; or 
 by altering the quantity of test-serum, keeping the 
 antigen and complement constant. The author finds 
 that the greatest range is obtained when the quantity 
 of the serum is altered ; but, if to be of value, at least 
 five dilutions must be made, and this takes a con- 
 siderable time, and therefore the author only employs 
 this method in doubtful cases. If a serum is strongly 
 positive, it will appear so by both methods, and will 
 by the first one fix a large amount of complement, or 
 by the second will fix complement when the serum is 
 present only in very small quantities. 
 
 Quantitative Measurement by Variation in 
 Amount of Test-Serum. 
 
 In the second method the ingredients are used 
 in the same proportion as in the front row of the 
 first method — namely, i c.c. saline, 0*05 c.c. com- 
 plement, and o'l c.c. antigen. Five tubes are 
 required for each serum to be tested, each contain- 
 ing the above quantity of saline, complement, and 
 antigen, and dilutions of the serum are prepared 
 in the following way : f c.c. saline is put into 
 four small test-tubes, ^ c.c. serum added to the first ; 
 this is shaken, and J c.c. put into the next tube, 
 and so on. In this way dilution of i in 2, i in 4, 
 I in 8, and i in 16 are obtained. 0*2 c.c. of the pure 
 serum and 0-2 c.c. of each dilution are added to the 
 tubes of saline, complement, and antigen. These 
 
WASSERMANN REACTION 77 
 
 tubes will thus contain 0*2, o*i, 0-05, 0-025, 0-0125^ of 
 test-sernm respectively. It will be found that the 
 smallest amount in this series is capable of producing 
 complete inhibition of haemolysis with a very strong 
 serum. This potency of the serum, however, is rare, 
 and a serum is definitely syphilitic when it fixes com- 
 plement completely in the 0-2 or o'l c.c. tubes. 
 Sometimes a case will be found gradually to come 
 down in complement-fixing power, from at first being 
 able to fix complement in all the tubes up to the last 
 tube, until the first tube alone is fixed, then only 
 partially fixed, and at last all the tubes show complete 
 haemolysis. The author considers this method of 
 making a quantitative examination the most satis- 
 factory ; but as the results obtained by the two 
 methods always agree, the longer process is unneces- 
 sary in the majority of cases, and need only be used 
 for the more accurate estimation of improvement 
 under treatment. 
 
 Quantitative Measurement when only a Small 
 Amount of Blood is Available. 
 
 Occasionally, as in infants or fat persons, veni- 
 puncture is impossible, and the pathologist has to 
 content himself with a small quantity of blood 
 obtained from the finger or toe in a Widal tube. 
 In these cases we have to modify the technique as 
 regards the quantity of serum used, though not as 
 regards the relative proportion of the ingredients. 
 
 A piece of glass tubing having been heated in a 
 blowpipe and drawn out so as to form a pipette, the 
 capillary portion of which is about 6 inches long, a 
 
7S SYPHILIS AND PARASYPHILIS 
 
 mark is made with a pencil about i inch from the 
 end of the capillary portion to mark one volume. A 
 rubber teat having been adjusted to the broad end of 
 the pipette, the mixture of saline, antigen, and com- 
 plement is sucked up to the chalk mark ; the point of 
 the pipette is then taken out of the fluid and a little 
 air drawn in, and then another volume is drawn in up 
 to the mark, and so on until seven volumes have been 
 sucked up. These are then squeezed out into a clean 
 watch-glass and again sucked up, this time without 
 leaving any intervening air-bubbles, and a chalk mark 
 made on the capillary at the point to which the 
 mixture reaches (Fig. 19). A small air-bubble is now 
 
 Fig. 19. — Teat-Pipette, marking One and Seven Volumes. 
 
 admitted into the capillary, and then one volume of 
 the serum to be tested is sucked up. The contents 
 of the pipette are then ejected into a front-row test- 
 tube of small bore, made by drawing out glass tubing. 
 The pipette is then washed by sucking up and ejecting 
 normal saline one or twice, and the same process 
 repeated— on this occasion, however, sucking up the 
 mixture v/ith the triple quantity of complement to the 
 7-volume mark, and then ejecting it into a test-tube 
 in the back row. The same technique is followed 
 with each serum to be tested, and with the controls. 
 We have, as before, two rows, the front row contain- 
 ing a third of the amount of complement contained in 
 the back row, the only difference being the absolute 
 
WASSERMANN REACTION 79 
 
 quantities used, relative amounts being practically the 
 same. 
 
 After incubating for half an hour, eight volumes of 
 haemolytic system are added, and the tubes replaced in 
 the incubator until complete haemolysis occurs in the 
 control-tubes containing normal serum and no serum. 
 
 Reasons for Superiority of Original Technique. 
 
 It will be seen that the same principle underlies 
 all the above techniques — namely, that all the 
 factors are constant, except the test-serum. Any 
 difference in haemolysis must therefore be due to this, 
 the only variant factor, and the results obtained will 
 be strictly comparable one with another, though not 
 strictly comparable to another series of tests. Thus, 
 if in any given experiment the guinea-pig's serum 
 is rather deficient in complement, or contains com- 
 plement that is easily deviable, perhaps not quite 
 complete haemolysis will be produced in the tubes 
 containing normal sera. The test-tubes showing a 
 similar amount of haemolysis we may then report as 
 normal, although complete haemolysis is not produced. 
 Or, again, if we use an excessively potent complement, 
 there may be a trace of haemolysis even in the tube 
 containing syphilitic serum ; all the test-tubes showing 
 a similar trace of haemolysis, we may then report as 
 positive. It cannot be too strongly insisted upon that 
 this test is a quantitative one, and not an absolute 
 one, and that therefore a result which in one test we 
 should report as doubtful may in another test be 
 reported as either positive or negative, according to 
 the results obtained from the control-tubes. 
 
8o SYPHILIS AND PARASYPHILIS 
 
 Strictly comparable results cannot be claimed for 
 any of the so-called * simplified methods ' given in the 
 next chapter. 
 
 The author has always urged the importance of 
 maintaining the principle of Wassermann's and 
 Neisser's original technique, and nearly all patholo- 
 gists with an extensive experience of the Wassermann 
 reaction (Wassermann, Neisser, Plant, Noguchi, 
 Harrison, Macintosh, Browning, Mackenzie) now 
 advise that only a technique embodying these prin- 
 ciples is to be recommended for purposes of diagnosis. 
 Practically every worker of experience has his own 
 modifications. These, however, are immaterial so 
 long as the original principles are adhered to — namely, 
 the only variant factor shall be the test-serum, and 
 that the results in any one series of tests shall be 
 strictly comparable. 
 
 The technique employed by the workers at the 
 Lister Institute, and by Mott and Candler in the 
 Pathological Laboratory at Claybury Asylum, is the 
 original one. General experience has shown that this 
 method is by far the most reliable, and admits of 
 more accurate standardization than do any of the 
 labour-saving modifications which have been suggested 
 as substitutes for the original method. 
 
CHAPTER VII 
 
 WASSERMANN RR ACTION— Continued 
 
 SIMPLIFIED TECHNIQUES 
 
 I. Stern's Method. — Margaret Stern makes use of 
 normal complement existing in the serum tested instead 
 of using guinea-pig's complement. This considerably 
 simplifies the reaction in that guinea-pigs are not 
 required, and the test-serum is not decomplementized 
 in the water - bath. The quantity of complement 
 contained in human sera is very variable. Comple- 
 ment is also gradually destroyed by keeping. As each 
 serum tested varies, therefore in the quantity of comple- 
 ment, and, unless all are drawn on the same day, the 
 depreciation of complement produced by time is also 
 variable, the results obtained by this method are not 
 quite comparable. In order to minimize the variability 
 in complement, Stern advises using a large excess of 
 haemolytic serum, and only a weak suspension of 
 corpuscles (2-5 per cent.). Although satisfactory 
 results are obtained by this method in the very large 
 majority of cases, still there is undoubted evidence 
 from records published by independent observers in 
 many countries that with this technique positive 
 results are sometimes recorded in diseases other than 
 
 81 6 
 
82 SYPHILIS AMD PARASYPHILIS 
 
 syphilis, and there is practically always a higher 
 percentage of positive results. Stern herself admits 
 that her method is not reliable in wasting diseases, 
 where there may be a deficiency of complement. 
 There is little doubt but that Stern's method is more 
 delicate than Wassermann's original technique, and 
 Harrison makes use of this method when estimating 
 the result of treatment on the reaction, although he is 
 strongly of the opinion that Stern's modification is 
 unsuitable for diagnostic purposes. Neisser considers 
 this technique useful as a control of the original 
 technique. 
 
 2. Hecht's Method. — This observer uses the test- 
 serum not only for complement, as in Stern's method, 
 but also for haemolytic antibody, for he has shown that 
 an antibody to sheep's corpuscles is present in the 
 great majority of human sera. The author compared 
 the results obtained with Hecht's technique and the 
 original technique with one hundred sera, and found 
 that lo per cent, of human sera contained no, or very 
 little, haemolytic antibody to sheep's corpuscles, and 
 that therefore lo per cent, of human sera cannot be 
 examined with this technique, and of the remaining 
 90 per cent, the author found a higher proportion of 
 positives than with the original technique. Hecht 
 emphasizes the importance of using only fresh serum. 
 Flemming has adapted a capillary tube method of 
 measurement to this technique, and his modification 
 has been considerably used in this country : he states 
 that the freshness of the serum is not of importance, 
 and that satisfactory results are obtained even if the 
 serum is a week old. Little can be said for this 
 
WASSERMANN REACTION 83 
 
 technique on theoretical grounds, as both complement 
 and haemolytic antibody are variants, and variations 
 in haemolysis may be due not only to varying 
 quantities in the complement-fixing substance present 
 in syphilitic sera, but to deficiency in either comple- 
 ment, haemolytic antibody, or both. 
 
 3. Noguchi's Method. — Noguchi, according to his 
 latest method, endeavours to simplify the reaction 
 by substituting human corpuscles for the sheep's 
 corpuscles, using the patient's own corpuscles, acetone 
 insoluble antigen, and fresh guinea-pig's complement. 
 The corpuscles, after washing, are used in a strength 
 of I per cent, suspension. The controls consist of 
 syphilitic serum, normal serum, and a tube without 
 antigen. The decomplementized patient's serum, the 
 patient's washed corpuscles, the fresh guinea-pig's 
 serum for complement, and the antigen are incubated 
 together in a water-bath for half an hour. The serum 
 haemolytic to human corpuscles is now added, and the 
 tubes are reincubated. 
 
 SOURCES OF ERROR 
 
 The dose of complement in different samples of 
 different guinea-pig's serum, though more constant 
 than in human serum, still may vary, and Browning 
 and Mackenzie have shown that different samples 
 of guinea-pig's complement may vary considerably 
 also in deviability, and this deviability is particularly 
 influenced by age ; they found that the comple- 
 ment of freshly drawn serum was hypersensitive 
 in deviability, and considered it best that comple- 
 ment should be kept from eighteen to twenty-four 
 
84 SYPHILIS AND PARASYPHILIS 
 
 hours in the ice- chest, or at room temperature, before 
 use. They consider that complement is hyper- 
 sensitive if five times the quantity of complement 
 is required to produce haemolysis with antigen, 
 corpuscles, and haemolytic serum, than with corpuscles 
 and haemolytic serum alone. 
 
 From the above remarks it will be seen that there 
 are numerous pitfalls open to those inexperienced in 
 the technique when using any of the so-called 
 ' simplified techniques.' 
 
 When using either Stern's or Hecht's technique, or 
 Flemming's modification of Hecht's technique, it is 
 obviously impossible to make a quantitative examina- 
 tion, as we are unable to increase the amount of com- 
 plement-fixing substance which is being tested for in 
 the patient's own serum, without, at the same time, 
 increasing the complement, and with Hecht's the 
 haemolytic antibody also. With cerebro-spinal fluid 
 these techniques cannot be used. 
 
 Reliable quantitative estimation can alone be made 
 by using the original method, in which the patient's 
 own serum or cerebro-spinal fluid is simply used for 
 supplying the complement - fixing substance. The 
 quantitative measurement may be arrived at by giving 
 increasing or diminishing doses of either of three factors 
 — namely, either complement, antigen, or test-serum. 
 It will be seen that false results may be obtained : 
 
 1. By the use of fresh guinea-pig's serum contain- 
 ing abnormally little or abnormally much complement ; 
 by using too much complement or complement which 
 is too easily deviable or not sufficiently deviable. 
 
 2. By using antigen which is too potent or not 
 sufficiently potent ; one which fixes too much comple- 
 
WASSERMANN REACTION 85 
 
 ment by itself, or with normal serum ; or one in 
 which the units of complement fixed in conjunction 
 with syphilitic serum are not sufficiently in excess of 
 those fixed in conjunction with normal serum. 
 
 3. Some corpuscles, also, are more easily haemo- 
 lyzed than others ; or, again, if too thick a suspension 
 of corpuscles be employed, there may not be complete 
 haemolysis, even with normal sera, while, if the 
 suspension is too weak, each corpuscle will be pro- 
 vided with an excess of hsemolytic serum, and 
 haemolysis will be produced with a minimum amount 
 of complement that would fail to produce haemolysis in 
 a thicker suspension. 
 
 4. The haemolytic serum, if too potent, will for the 
 same reason produce haemolysis, and if too weak the 
 serum will have to be used in such large quantities 
 that agglutination of the corpuscles may be produced, 
 and the clumps fall to the bottom of the test-tube 
 before they are dissolved. 
 
 5. The patient's serum, if not decomplementized, 
 may, according to Neisser, Noguchi, and others, fix 
 complement, even if non-syphilitic, or if decomple- 
 mentized at too high a temperature, or for too long, 
 the complement -fixing substance may be greatly 
 reduced in quantity, or even destroyed. 
 
 For this reason none of the outfits supplied by 
 instrument makers can be regarded as satisfactory. 
 The accumulated evidence of responsible workers 
 points unmistakably to the superiority of the original 
 technique in which the only variant factor is the 
 tested serum, and any variation in haemolysis in the 
 final tubes must therefore be due to this the only 
 variant factor. 
 
CHAPTER VIII 
 
 WASSERMANN REACTION— Contimied 
 
 SPECIFICITY OF REACTION 
 
 The first question to be settled is whether the reaction 
 is sufficiently specific to render the test a reliable one 
 for the diagnosis of syphilitic infection. Wassermann 
 states that out of 10,000 sera examined, he has not 
 once diagnosed syphilis wrongly, and Hoehne only 
 obtained two positive results out of 1,100 sera taken 
 from healthy persons, or patients sufiering from 
 diseases other than syphilis, and in neither of these 
 two could syphilis be excluded. McDonagh, Muller, 
 and Morawitz, in reporting 5,000 cases examined by 
 them in Finger's clinic, state that they did not obtain 
 a single positive result in any case where syphilis 
 could be definitely excluded ; and Blaschko of BerHn, 
 as the result of the examination of 900 cases, found 
 the result in accordance with the clinical diagnosis in 
 all but 30 cases. 
 
 Blumenthal found in 3,000 cases a positive reaction 
 in 95 per cent, of secondary and tertiary cases. There 
 was no relation to the duration and the gravity of the 
 disease. Congenital syphilis behaved in just the 
 same way as acquired syphilis. Of 400 control cases 
 
 86 
 
WASSERMANN REACTION 87 
 
 5 only gave a positive reaction. In latent syphilis 
 the reaction was positive in 68 per cent, of cases in 
 the first year of the disease, and in 42 per cent, of 
 cases afterwards. 
 
 Fritz Hoehne found that of 317 known non-syphilitic 
 cases only 3 were positive, and in 2 of these syphilis 
 could not be absolutely excluded, and i was a case 
 of scarlet fever. 
 
 Koefting, R., of Christiania, obtained 100 per cent, 
 of positive results out of 317 secondary cases examined ; 
 and of 426 non-syphilitic cases all were negative. 
 
 Markus, K., of Stockholm, records 374 positive 
 reactions in 445 cases of syphilis examined, and 
 9 out of 338 cases diagnosed as non-syphilitic, but 
 out of these 9, in 7 syphilis could not be excluded, 
 and the remaining 2 consisted of typhoid and tuber- 
 cular meningitis. 
 
 Out of 50 sera examined by Beckers, and taken 
 from patients with tuberculosis, typhoid, scarlet fever, 
 arterio- sclerosis, and heart failure, only 2 gave a 
 positive reaction, in neither of which syphilis could 
 be excluded. 
 
 Jenonck and Meirowski examined no certainly 
 non-syphilitic cases, and only found i positive result, 
 which was that of a child dying with tuberculous 
 meningitis, and they and other observers have 
 recorded that a positive result is often obtained with 
 dying persons or cadavers. 
 
 Statistics taken from very many thousands of obser- 
 vations made by skilled workers in England, France, 
 Germany, Austria, Sweden, America, and Australia, 
 show that of all cases of syphilis examined, from 
 
88 SYPHILIS AND PARASYPHILIS 
 
 80 to 90 per cent, give a positive reaction. The 
 percentage differs but slightly with different observers. 
 The author has determined the reaction in over 500 
 untreated, or but slightly treated, cases, and obtained 
 a positive reaction in 85 per cent., and out of over 3,000 
 sera personally examined by him has not recorded a 
 single positive reaction in any case in which syphilis 
 could be excluded, with the exception of a few post- 
 critical pneumonias. 
 
 Different results are obtained with syphilitic lesions 
 of different tissues; thus a very high percentage of 
 positive results is obtained with aneurism of the aorta, 
 and only a low percentage with cerebral syphilis. 
 
 REACTIONS IN CONDITIONS OTHER THAN 
 SYPHILITIC 
 
 Of the diseases certainly not syphilitic in which a 
 positive reaction is obtained — 
 
 Yaws heads the list, and in this disease as high a 
 proportion of positives is obtained as with syphiHs 
 itself. Baermann obtained 90 per cent, of positives 
 in untreated cases. 
 
 Leprosy also produces a high percentage of positive 
 results, Baermann reporting 40 per cent, and Noguchi 
 80 per cent. Meier also reported that the majority of 
 cases gives a strongly positive result. It appears, 
 however, only to be the tuberculous form of the 
 disease that produces a positive reaction. 
 
 Trypanosomiasis has been reported frequently to give 
 a positive reaction, but the author has been unable to 
 obtain any statistics for the reaction in this disease. 
 
 In malaria Baermann obtained 20 per cent, positive 
 
WASSERMANN REACTION 89 
 
 in untreated cases with fever, and 4 per cent, positive 
 in treated cases without fever. 
 
 Scarlet fever was at first beheved to produce a 
 positive reaction, and Much reported 59 positives out 
 of 130 cases examined. Later observers have, how- 
 ever, failed to confirm his figures, and have only 
 obtained positive results very rarely. In any case 
 the positive reaction is said to be very transient, and 
 Blaschko has observed that when the positive result 
 does occur, it is not till about fourteen days after the 
 rash that it appears, and that it disappears within 
 three months (see Table I.). 
 
 Pnetimonia. — Weil and Braun and the author have 
 reported 36 cases of pneumonia in which a positive 
 reaction was obtained in 11. The author found that 
 the positive reaction did not appear till after the crisis, 
 and only lasted a few days. 
 
 Weil and Braun have also reported 3 positive 
 results out of 20 sera taken from typhoid patients 
 (see Table I.). 
 
 Heart Disease. — No case of heart disease in which 
 syphilis can be excluded has been reported as giving 
 a positive reaction. 
 
 Relapsing fever has been reported as giving a positive 
 reaction. 
 
 Cancer or tuberculosis practically never gives a positive 
 reaction in cases in which syphilis can be excluded. 
 The reports of some experienced observers as regards 
 the reaction in various diseases will be found in Table I. 
 
 Reinhart has not obtained a single positive result 
 in malignant disease, phthisis, typhoid, pneumonia, 
 nephritis, leukaemia, pernicious anaemia, diabetes, 
 
90 SYPHILIS AND PARASYPHILIS 
 
 measles, or diphtheria, but he has recorded positive 
 reactions in scarlet fever and malaria. 
 
 Of 39 cases of various non-syphilitic skin diseases 
 examined by Bassett- Smith, all gave a negative 
 reaction. Of 58 examined by Noguchi, all but i were 
 negative, this solitary case giving a doubtful reaction. 
 Of 15 cases examined by the author, 10 gave a nega- 
 tive reaction, and 5 cases — all leucoderma cervices 
 and probably syphilitic — gave a positive reaction. 
 
 Positive reactions have also been recorded with 
 blood taken during deep anaesthesia, or in narcosis pro- 
 duced by various drugs ; also in moribund patients and 
 in the cadaver. 
 
 Of 80 cases of gonorrhoea examined by Bassett-Smith 
 and the author, only i was positive, and here syphilis 
 could not be excluded. 
 
 Acute rheumatism, measles, and acute nephritis 
 have all given negative results. 
 
 Of 76 cases of aortic aneurism examined by Donath, 
 Gastau, Koefting, and the author, all but 4 have given 
 a positive reaction. Koefting also obtained 15 positive 
 reactions out of 17 cases of aortic incompetence, but 
 out of 21 cases of morbis cordis examined by Bassett- 
 Smith and the author, only i gave a positive reaction, 
 and here there was a history of syphilis. 
 
 Wassermann says : 
 
 ' It should cause no surprise that the serum of 
 patients suffering from other protozoal diseases gives 
 a like reaction, considering the close relationship 
 between spirochaetse, trypanosomes, and other pro- 
 tozoa. It follows that one should employ the reaction 
 with people who have been in the tropics and con- 
 tracted malaria there, only when one is convinced by 
 
WASSERMANN REACTION 
 
 91 
 
 their history that they have had no malarial attack 
 during the last quarter of a year. I also advise you 
 that whenever you wish to employ the serum reaction 
 first to determine by the patient's history that he has 
 gone through no acute febrile infectious disease up to 
 at least a month previously. If one holds to the 
 necessary preliminary precautions regarding the tech- 
 nique and the anamnesis, then, in cases of a positive 
 reaction, it can be said with certainty that the investi- 
 gated case is syphilitic. On the other hand, if the 
 reaction be negative, syphilis cannot be excluded 
 absolutely, but only with a probability of about 
 90 per cent.' 
 
 Table I. — Reaction in Various Diseases. 
 
 
 Typhoid. 
 
 Scarlet 
 Fever. 
 
 Tuber- 
 culosis. 
 
 Carcinoma. 
 
 Pneumonia. 
 
 Cases. 
 
 No. 
 Posi- 
 tive. 
 
 Cases. 
 
 No. 
 Posi- 
 tive. 
 
 Cases. 
 
 No. 
 Posi- 
 tive. 
 
 Cases. 
 
 No. 
 Posi- 
 tive. 
 
 Cases. 
 
 No. 
 Posi- 
 tive. 
 
 Bassett-Smith 
 Bayly 
 Boas . . 
 Browning and 
 
 Mackenzie 
 Hecht 
 Hoehne 
 Jochmann .. 
 Meier 
 Much 
 Noguchi 
 Weil and 
 
 Braun 
 
 3 
 6 
 
 14 
 20 
 
 
 
 
 
 3 
 
 7 
 20 
 61 
 
 37 
 105 
 37 
 33 
 52 
 130 
 
 63 
 
 I 
 I 
 I 
 
 
 I 
 
 
 
 59 
 3 
 
 9 
 22 
 
 II 
 
 52 
 
 
 
 
 I 
 
 
 34 
 5 
 
 5^ 
 
 
 
 
 3 
 
 24 
 4 
 
 12 
 
 7 
 
 
 4 
 
 REACTION AT VARIOUS STAGES OF 
 INFECTION 
 
 The percentage of positive reactions obtained varies 
 considerably with the period of the disease, and whether 
 
92 SYPHILIS AND PARASYPHILIS 
 
 the infection is acute or latent. Thus, primary cases 
 in which the lesion has been present for less than a 
 fortnight almost invariably give a negative reaction, 
 while 75 per cent, of positive reactions are obtained if 
 the primary sore has been present for over a month. 
 Secondary syphilis v/ith symptoms gives a positive 
 result in over 90 per cent, of cases, and tertiary 
 syphilis in about 75 per cent. In cases of latent 
 syphilis — viz., syphilis without symptoms — the early 
 cases give a positive reaction in 75 per cent, and the 
 late cases in 76 per cent., in the untreated cases. 
 
 Primary Syphilis (see Table II.). — Levaditi and 
 Yamanouchi found a positive reaction in primary 
 cases in from ten to thirty days after the appearance 
 of the sore. 
 
 Bruck and Boas collected records of 1,081 cases of 
 
 primary syphilis, and of these 709, or 65 per cent., 
 
 gave positive reactions. 
 
 Fischer found a positive result the rule after five or 
 
 six weeks. 
 
 Blumenthal found a positive reaction in the primary 
 
 period in 63 per cent, of cases. It only appeared in 
 
 the fifth or sixth week, and became more and more 
 
 strong as time progressed. In other periods the 
 
 reaction was positive. 
 
 Secondary Syphilis (see Table II.). — Bruck and 
 
 Boas obtained 90 per cent, of positive results in 
 
 2,754 cases. Probably, however, many of these had 
 
 received some treatment. 
 
 Recent observations seem to show that in florid 
 
 secondary syphilis practically every case gives a 
 
 positive reaction. 
 
WASSERMANN REACTION 93 
 
 Tertiary Syphilis (see Table II.). — In 63 un- 
 treated cases recorded by Boas, every case gave a 
 positive reaction, and in 60 cases examined by Mac- 
 intosh and Fildes, only i negative result was 
 obtained. 
 
 Very many cases of aneurism of the aorta give a 
 positive reaction, and in the majority a history of 
 syphilis can also be obtained. Bassett-Smith has in- 
 formed the author that in his report on late secondary 
 and tertiary syphilis giving positive reactions, he 
 included many cases of aneurism, chronic endo- 
 carditis, and cases with cerebral symptoms in which 
 a distinct history of syphilis had been obtained. 
 
 Congenital Syphilis (see Table 11.). — Practically 
 all infants or children showing symptoms of hereditary 
 syphilis give a positive reaction, but not all babies 
 born of syphilic mothers ; while of living children 
 born of syphilitic mothers nearly 50 per cent, give a 
 negative reaction. 
 
 Of 44 cases examined by Boas, 20 gave a positive 
 reaction and 24 a negative ; of the 20 that gave a 
 positive reaction, 16 either showed symptoms at birth 
 or within three months after birth, and the remaining 
 4 showed no symptoms in three months, and the 
 reaction rapidly became negative. Of the 24 cases 
 showing a negative reaction, 17 remained negative 
 and showed no symptoms, 5 developed both symptoms 
 and a positive reaction, and 2 died with a negative 
 reaction and yet proved to be syphilitic. 
 
 Knopfelmacher obtained 90 per cent, of positive 
 reactions in mothers tested within a few months after 
 the birth of a syphilitic child, and he has shown that 
 
94 SYPHILIS AND PARASYPHILIS 
 
 children with hereditary syphilis almost invariably 
 give a positive Wassermann reaction at the time of 
 the rash and often for long after its disappearance. 
 Older children with hereditary syphilis show a positive 
 reaction even more frequently than adults with acquired 
 syphilis in a late stage, and the reaction often remains 
 positive in children suffering from the disease in spite 
 of energetic treatment. That antisyphilitic treatment 
 of the mother during pregnancy can result in the birth 
 of a healthy child is confirmed by the negative reaction. 
 These children are free from syphilis, and they may 
 be quite healthy or show various defects. In two 
 instances a woman, who had previously had several 
 syphilitic children, has borne a child which has re- 
 mained healthy in the first years of life, and yet given 
 a positive Wassermann reaction. Such children are 
 to be regarded as latent syphilitics. On this basis 
 Profeta's law (immunity of the healthy children of 
 syphilitic mothers) finds its explanation on the ground 
 of latent syphilis in the child. 
 
 Out of 1,822 sera Fritz Hoehne obtained positive 
 reactions in : 
 
 38 per cent, in primary syphilis. 
 
 79 
 
 
 , untreated secondary syphili 
 
 48 
 
 
 , treated secondary syphilis. 
 
 63 
 
 
 tertiary syphilis. 
 
 100 
 
 
 , syphilitic aortitis. 
 
 17 
 
 
 cerebro-spinal syphilis. 
 
 31 
 
 
 , latent syphilis. 
 
 88 
 
 
 , congenital syphilis. 
 
 60 
 
 
 tabes. 
 
 Of 427 doubtful cases, loi were positive. 
 
WASSERMANN REACTION 
 
 95 
 
 Table II. — Reaction at Different Stages of 
 Infection in Cases showing Clinical Symptoms. 
 
 
 England. 
 
 America. 
 
 Germany. 
 
 Sweden. 
 
 
 Bassett- 
 Sniith. 
 
 Bayly. 
 
 Noguchi 
 
 and 
 Kaplan. 
 
 Hoe 
 
 tine. 
 
 Markus. 
 
 Boas. 
 
 cS 
 
 U 
 
 it 
 
 u.-a 
 
 -I 
 
 
 
 
 u5 
 
 
 
 
 u.t: 
 
 
 o.t: 
 
 1) 
 (J 
 
 t- 
 
 Congeni- 
 
 
 
 
 
 
 
 
 
 
 
 tal .. 
 
 — 
 
 
 
 20 
 
 QS 
 
 3,7 
 
 QS 
 
 ? 
 
 88 
 
 29 
 
 90 
 
 72 
 
 100 
 
 Primary 
 
 183 
 
 76 
 
 ^B 
 
 7,S 
 
 208 
 
 QO 
 
 ? 
 
 3a 
 
 120 
 
 75 
 
 7fc 
 
 73 
 
 Second- 
 
 
 
 
 
 
 
 
 
 
 
 
 
 ary . . 
 
 407 
 
 Q4 
 
 308 
 
 qo 
 
 478 
 
 QO 
 
 ? 
 
 79 
 
 250 
 
 91 
 
 2,754 
 
 90 
 
 Tertiary 
 
 51 
 
 94 
 
 52 
 
 76 
 
 363 
 
 80 
 
 9 
 
 63 
 
 45 
 
 100 
 
 63 
 
 100 
 
CHAPTER IX 
 CEREBRO-SPINAL FLUID 
 
 The normal cerebro-spinal fluid is limpid and colour- 
 less, and has a specific gravity of 1005 5 i^ contains 
 no cellular element, except, perhaps, a few large 
 endothelial cells and a very occasional lymphocyte, 
 and its reaction is slightly alkaline. True albumin 
 is absent. Only faint traces of proteid are present, 
 which, however, are sufficient to produce a slight 
 cloudiness on heating. The proteid present consists 
 of globulin. No ferments can be demonstrated. Of 
 salts, the principal is sodium chloride, but it also con- 
 tains traces of carbonates and phosphates. Traces of 
 dextrose and urea are also usually found. 
 
 From 120 to 150 c.c. of cerebro-spinal fluid are 
 usually secreted daily, the secretion being produced 
 at the choroid fringes, and being a definite secretion 
 and in no sense an exudation. The amount secreted 
 varies in pathological conditions, and may be enor- 
 mously increased in general paralysis. 
 
 Hoffman states that he has been able to demon- 
 strate the presence of the SpirochcBta pallida in the 
 cerebro-spinal fluid of infected persons by means of 
 successful inoculation, but the organism itself has up 
 till now not been seen in this fluid. 
 
 96 
 
CEREBROSPINAL FLUID 97 
 
 LUMBAR PUNCTURE 
 
 Cerebro-spinal fluid is best obtained by thecal 
 puncture at the interlaminal spaces, either between 
 the third and fourth or fourth and fifth lumbar 
 vertebrae. The upper border of the fourth lumbar 
 spine is on a level with a horizontal line joining the 
 summit of the iliac crests, and the puncture should be 
 made below this line, ^ inch below and to the right 
 of the fourth lumbar spine, directing the needle 
 forwards and inwards. 
 
 Fig. 20. — Lumbar Puncture Needle and Holder (Author's 
 
 Pattern), 
 
 A, holder ; B, needle ; C, stilette ; D, rubber-tubing. 
 
 Before puncture, the skin should be cleaned with 
 ether and alcohol, and sterilized with a saturated 
 solution of iodine in chloroform. The needle is often 
 attached to the nozzle of a syringe. Most authorities 
 agree that suction should not be employed, and there- 
 fore the syringe usually serves only as a handle. 
 
 The author uses the apparatus illustrated in Fig. 20, 
 which consists of a stout steel needle, about 3 inches 
 long and of fairly large calibre, and a hollow needle- 
 holder to which a piece of rubber-tubing can be 
 
 7 
 
98 SYPHILIS A ND PA RA SYPHILIS 
 
 attached so that the cerebro-spinal fluid is conducted 
 directly into the sterile test-tube without fear of con- 
 tamination. If, after the puncture has been made, 
 the fluid does not flow into the test-tube, the holder 
 is removed and a stilette passed down the needle. 
 Before adjusting the needle to the holder, the needle 
 should be dipped into a test-tube containing auto- 
 claved olive oil. When making the lumbar puncture, 
 the spine should be flexed so as to open out the inter- 
 laminal spaces as much as possible. If the patient is 
 able to sit up, lumbar puncture is most easily and 
 conveniently performed if the patient sits on a stool 
 with his back bent well forward, his knees separated, 
 and hands touching the ground. If, however, he is 
 unable to leave the bed, he should be placed on his 
 side, with his knees and shoulders brought close 
 together. When making the puncture, the needle 
 passes easily in for about ij to 2 inches, when it 
 will meet the interlaminal ligament, through which 
 it must be firmly pushed into the cerebro-spinal canal, 
 when the fluid escapes into the tube. Occasionally 
 the needle becomes blocked in its passage through 
 the tissues, and no cerebro-spinal fluid escapes, 
 although the point is in the cerebro-spinal fluid. The 
 tube should be removed before the needle is with- 
 drawn, as during the withdrawal some blood may 
 escape into the needle and contaminate the fluid. It 
 is obvious that no correct leucocyte count can be 
 made if there is any blood present. It is therefore 
 wisest to allow a few c.c. of cerebro-spinal fluid to 
 escape into the first test-tube, and then, removing this 
 tube, to replace it by a second. Any trace of blood 
 
CEREBROSPINAL FLUID 99 
 
 will be washed away by the passage of the first 
 sample, and the second sample will be uncontamin- 
 ated. The second tube is now removed, and kept for 
 cytological examination. The first tube is used again 
 during the withdrawal of the needle. 
 
 CYTOLOGICAL EXAMINATION 
 
 Lymphocytosis of the cerebro-spinal fluid occurs 
 in tabes and general paralysis, which, according to 
 Mott, is not diminished with antisyphilitic treatment. 
 Plant, however, has recorded a distinct sinking in 
 the cellular contents (424 to 120 cells per c.mm.) in 
 a case of cerebral syphilis, without any change in the 
 Wassermann reaction. 
 
 Lymphocytosis also occurs to a marked degree in 
 sleeping-sickness, and has been found in Landry's 
 paralysis and in the subacute combined degeneration 
 of pernicious anaemia, and, according to Sicard, in 
 herpes zoster. Lymphocytosis, however, cannot be 
 regarded as absolutely diagnostic of meningitis ; but 
 Mott considers it strong presumptive evidence, and, 
 when combined with other facts, he considers the 
 existence of a lymphocytosis of the cerebro-spinal 
 fluid as a valuable sign of syphilitic or para- 
 syphilitic affections of the central nervous system 
 or meninges. 
 
 Normal cerebro-spinal fluid contains no poly- 
 morphonuclears, and very few, if any, lymphocytes. 
 The lymphocytosis of tabes and general paralysis is, 
 according to Purves Stewart, more marked than in any 
 other form of organic disease. In acute inflammatory 
 
loo SYPHILIS AND PARASYPHILIS 
 
 processes there is a polymorphonuclear leucocytosis, 
 and in chronic inflammatory processes a lymphocytosis. 
 In acute tubercular meningitis both polymorpho- 
 nuclears and lymphocytes may be present in large 
 numbers, the majority of cells present being lympho- 
 cytes, though as many as 30 per cent, of polymorpho- 
 nuclears are sometimes present. 
 
 Plant considers that a cytological examination is 
 normal if less than six leucocytes are found per c.mm. 
 If ten or more cells are present, the fluid must be 
 considered pathological. Countings from six to ten he 
 considers doubtful. Out of fifty-six cerebro-spinal 
 fluids obtained from cases that were definitely non- 
 syphilitic, in forty-eight cases the cell-findings were 
 entirely negative, and there were under six cells in 
 each c.mm. In four cases normal findings were 
 increased, but not above the number which was to 
 be regarded as pathological (ten cells to i c.mm.). 
 In the remaining four cases, however, there was found 
 a pathological cell increase, while both the spinal 
 fluid and blood-serum gave completely negative 
 Wassermann reactions. 
 
 Out of ten cases of syphilis with secondary symptoms 
 that were examined, three showed a positive cyto- 
 logical count ; while of nine cases of latent tertiary 
 syphilis showing a positive Wassermann reaction in 
 the blood, two showed a positive cytological count of 
 the cerebro-spinal fluid. 
 
 Ravaut found a marked lymphocytosis of the 
 cerebro-spinal fluid during the secondary stage of 
 syphilitic infection which ran pari passii with the 
 cutaneous eruption. In a case of extensive papula,r 
 
CEREBROSPINAL FLUID loi 
 
 syphilis he found the cerebro-spinal fluid quite turbid 
 with lymphocytes. The lymphocytosis was not seen 
 in tertiary syphilis unless the eye or central nervous 
 system were affected. 
 
 Plant comes to the conclusion that the phenomenon 
 of lymphocytosis does not go parallel with the 
 Wassermann reaction of the spinal fluid, and that 
 the mechanism which produces the lymphocytosis is 
 not identical with that which causes the appearance 
 of a complement-fixing substance in the cerebro- 
 spinal fluid. He also considers that the appearance 
 of the Wassermann reaction in the blood need not be 
 accompanied by an increase of the lymphocytes in the 
 spinal fluid, and that there may be a cellular increase 
 in the cerebro-spinal fluid in the latent tertiary stages 
 without any syphilitic manifestations in the central 
 nervous system. 
 
 There appears to be no parallellism between the 
 results obtained by a cytological examination of the 
 cerebro-spinal fluid and the Wassermann reaction. 
 There may be a distinct lymphocytosis without any 
 power whatever of complement-fixing. 
 
 The cell-count should be made shortly after the 
 withdrawal of the fluid, and the author thinks Fuch's 
 and Rosenthal's counting chamber the most con- 
 venient for the absolute leucocyte count. This 
 chamber has a depth of 0*2 mm., and since its ruled 
 floor occupies an area of 16 mm. square, the entire 
 column which comes under the operation of counting 
 measures 3*2 mm. The fluid is mixed in a mixing 
 pipette whose bulb has a capacity which is ten times 
 greater than that of the capillary portion. The 
 
I02 SYPHILIS AND PARASYPHILIS 
 
 diluent is a stainiog solution of the following com- 
 position : 
 
 Methyl violet ... ... o*io parts. 
 
 Distilled water .., ... 50 ,, 
 
 Glacial acetic acid ... 2 ,, 
 
 With this medium the cerebro-spinal fluid is mixed in 
 the proportion of i of stain to g of cerebro-spinal fluid. 
 To prepare the diluted mixture, obtain a sample of 
 the cerebro-spinal fluid immediately after puncture, 
 and, after repeatedly shaking it up lightly, transfer a 
 small quantity to a dish, aspirate some of the stain 
 with the pipette up to the gauge-mark i, and then 
 draw up a sufficient quantity of the cerebro-spinal 
 fluid until the bulb is filled up to the gauge-mark 11. 
 Close the point of the pipette with the tip of the 
 finger, and shake the fluid in the bulb well for some 
 time. Having insured a good mixture, expel the fluid 
 contained in the capillary stem, and then transfer a 
 drop of the mixture to the counting chamber. The 
 floor of the chamber should be counted right through, 
 since the cerebro-spinal fluid contains a relatively 
 small number of cells. The average number of cells 
 contained in a cubic millimetre of the cerebro-spinal 
 fluid is accordingly : 
 
 10 X ^ lOZ 1 z 
 
 x=^ = -—--, or very nearly -, 
 
 3*2 X 9 28-8 3 
 
 where z is the total number of cells counted over the 
 entire floor of the chamber. 
 
 Should the total number of cells covering the floor 
 of the chamber happen to be excessively small, the 
 latter should be charged once more and a fresh count 
 made. 
 
CEREBROSPINAL FLUID 103 
 
 A differential leucocyte count should also be made, 
 and for this purpose the cerebro-spinal fluid is centri- 
 fugalized in a conical glass tube, and a film made of 
 the deposit at the tapered end of the tube. This film 
 should be stained with Jenner's stain. 
 
 Of 21 normal cases of cerebral syphilis examined 
 by Plaut, only i was cytologically negative ; 3 were 
 on the border-line (5 to 9 cells per i c.mm.), and 17 
 showed a distinct cellular increase, the highest count 
 showing 424 cells. 
 
 Leucocytosis is absent in functional neurosis. 
 
 Ravaut has shown that in acute and chronic 
 meningitis the cellular element and spinal fluid are 
 proportional to the degree and intensity of the inflam- 
 mation. He considers the presence of lymphocytosis 
 as an indication for energetic antisyphilitic treatment. 
 He considers the degree of lymphocytosis greater in 
 early than late cases ; and in old syphilitics, other 
 than parasyphilitics with no manifestations, the 
 cerebro-spinal fluid is normal. 
 
 Babinski and Naglotti have said that lymphocytosis 
 may precede the appearance of the Argyll- Robinson 
 pupil in tabes. 
 
 Funhe considers that lymphocytosis is not charac- 
 teristic of syphilitic nervous diseases, and that it is 
 only present if the meninges are involved. 
 
 From the above it will be seen that most authorities 
 agree that a negative cytological examination — namely, 
 the presence of less than six cells per c.mm. — will 
 exclude general paralysis, syphilitic meningitis, and 
 tabes. In syphilitic or parasyphilitic affections par- 
 ticularly no polymorphonuclear cells are seen ; whereas 
 
I04 SYPHILIS AND PARASYPHILIS 
 
 in chronic tubercular meningitis, although in later 
 stages there may be as many as 10,000 lymphocytes 
 per c.mm., there are usually also a considerable 
 number of polymorphonuclear cells, which will prob- 
 ably|form 25 per cent, of the total leucocyte count. 
 
 With acute meningeal diseases, such as acute 
 syphilitic meningitis, acute cerebro-spinal meningitis 
 (or acute tuberculous meningitis), the cellular increase 
 is chiefly polymorphonuclear. 
 
 WASSERMANN REACTION 
 
 Of 9 cases of active secondary syphilis examined 
 by Plant, the cerebro-spinal fluid was negative in all, 
 as it also was in 4 cases examined in the secondary 
 latent stage. 
 
 Of II cerebro-spinal fluids taken from patients in 
 the latent tertiary stage, all were negative. 
 
 Of 154 cases of general paralysis, 146 were posi- 
 tive, 6 negative, and 2 doubtful ; while of 20 cases 
 of cerebral syphilis, 17 were negative, and only 
 3 positive. 
 
 General paralysis is the only syphilitic or para- 
 syphilic afl"ection in which a negative result is of any 
 very great value ; but here it is of very great value 
 indeed, and a negative Wassermann reaction in the 
 blood or cerebro-spinal fluid will practically exclude 
 this condition. 
 
 A positive Wassermann reaction of the cerebro- 
 spinal fluid indicates that the patient either has general 
 paralysis, tabes, or cerebral syphilis. 
 
 Plant has obtained a positive Wassermann reaction 
 in the blood-serum in every case in which a positive 
 
CEREBROSPINAL FLUID 105 
 
 reaction was recorded in the cerebro-spinal fluid ; but 
 other observers, including the author, have very occa- 
 sionally met a cerebro-spinal fluid that was positive in 
 which the blood-serum was negative. 
 
 In cases in which the question for diagnosis is the 
 presence or absence of general paralysis, Plant recom- 
 mends that the blood should be first examined. If 
 there is a positive result, lumbar puncture is then 
 performed ; but if the blood reaction is negative, 
 lumbar puncture is considered contra-indicated, as 
 the case can be considered almost certainly not one 
 of general paralysis ; whereas a positive reaction in 
 the serum alone indicates absolutely nothing concern- 
 ing general paralysis, and only shows that the patient 
 has syphilis. 
 
 A positive Wassermann reaction in the cerebro- 
 spinal fluid does not appear to be influenced by 
 antisyphilitic treatment. This may possibly be due 
 to the drugs used failing to reach the cerebro-spinal 
 fluid. 
 
 It has been found in certain cases of trypanosomiasis 
 that some arsenical preparations are able to remove 
 the trypanosomes from the blood, but not from the 
 cerebro-spinal fluid ; and it has also been recorded 
 that potassium iodide, though present in the blood, 
 cannot be found in the cerebro-spinal fluid. 
 
 This isolation of the cerebro-spinal fluid may also 
 account for the difficulty in influencing parasyphilitic 
 aff"ections by means of drugs administered either 
 intravenously, intramuscularly, or by the mouth, and 
 possibly there may be a future for treatment directly 
 applied to the cerebro-spinal fluid. Success has already 
 
io6 SYPHILIS AND PARASYPHILIS 
 
 been reported by Macintosh, Martin, Flexner, and 
 Knolle in the treatment of cerebro-spinal fever by 
 means of intraspinal injections of serum containing 
 antibody. 
 
 Schmorl is of the opinion, also, that the cerebro- 
 spinal fluid is cut off from the intraventricular fluid, 
 and finds that in cases of marked jaundice the intra- 
 ventricular fluid contains no trace of bile pigment, 
 although the pigment may be present in the cerebro- 
 spinal fluid. He also reports that in one case of 
 diabetes, though a reducing substance was found in 
 considerable quantity in the spinal fluid, yet none was 
 found in the intraventricular fluid. The cerebro-spinal 
 fluid was examined for the Wassermann reaction in 
 seven cases of general paralysis ; in all cases the 
 Wassermann reaction of the blood and cerebro-spinal 
 fluid was positive, whereas in only one was the re- 
 action of the intraventricular fluid positive. Schmorl 
 therefore considers that the intraventricular cavities 
 are closed off from the subarachnoid space. 
 
 In the cases in which the intraventricular fluid 
 contained bile pigment or gave a positive Wassermann 
 reaction, Schmorl found that the epithelium of the 
 choroid plexus was degenerate ; whereas in those 
 cases in which the fluid was free from pigment, or 
 the Wassermann reaction negative, the epithelium of 
 the choroid plexus was intact. 
 
 Browning and Mackenzie made a similar examina- 
 tion in four cases of general paralysis. The cerebro- 
 spinal fluid was positive in every case, whereas in 
 only two did the intraventricular fluid give a positive 
 reaction. They also found that both the cases which 
 
CEREBROSPINAL FLUID 107 
 
 gave a positive reaction showed a degenerative con- 
 dition of the choroid plexus, whereas in the negative 
 cases these degenerative changes were not observed. 
 
 Mott has also found that, though reactions which at 
 first are negative may later become positive, no patient 
 suffering from general paralysis, whose cerebro-spinal 
 fluid has once given a positive reaction, has ever 
 given a negative reaction at any subsequent examina- 
 tion. He considers that antibodies accumulate in the 
 cerebro-spinal fluid in proportion as the process of 
 decay of the neurones proceeds, and he thinks that 
 there is a parallelism between the amount of decay of 
 the brain and the degree of the positive character of 
 the reaction. 
 
 Marie and Levaditi have also found that there is 
 a parallelism between the rapidity of the progress of 
 general paralysis and the degree and intensity of the 
 Wassermann reaction. 
 
 Mott considers that the Wassermann reaction gives 
 a valuable means of diagnosis, which is especially 
 useful when applied to the cerebro-spinal fluid to 
 determine the presence or absence of general paralysis. 
 He considers that the amount of complement-fixing 
 substance is in proportion to the activity and length 
 of duration of the diseases, and that these substances 
 are lipoids and globulins, which are of tissue origin, 
 and arise from tissue destruction caused by the present 
 or past action of the syphilitic virus. 
 
 Nonne has pointed out that, when making the 
 Wassermann test with cerebro-spinal fluid, consider- 
 ably more of the test-fluid should be used in the case 
 of cerebro-spinal fluid compared with serum. He 
 
io8 SYPHILIS AND PARASYPHILIS 
 
 states that i c.c. can be employed in the original 
 technique without fear of the positive reaction in 
 non-syphilitic cases. 
 
 Candler is also of the opinion that a positive 
 reaction may be missed unless considerable quantities 
 of the cerebro-spinal fluid are used, and instances a 
 case in which complete complement-fixation occurred 
 when 0-8 c.c. of fluid was used, although there was 
 complete haemolysis with 0*5 c.c. 
 
 As the cerebro-spinal fluid contains no complement, 
 it is unnecessary to heat it. 
 
 CHEMICAL EXAMINATION 
 
 The increase in proteid-content can usually be 
 demonstrated in general paralysis and tabes, especi- 
 ally in the former. 
 
 Globulin Reacton : Nonne and Afelt. — The fluid is 
 mixed with an equal quantity of saturated ammonium 
 sulphate. If turbidity appears in three minutes, the 
 reaction is positive. 
 
 Marie also considers that there is a marked 
 parallelism between the Wassermann reaction of the 
 cerebro-spinal fluid and the albumin reaction, for 
 which he uses equal quantities of centrifugalized 
 cerebro-spinal fluid and saturated ammonium sulphate 
 solution. He regards the reaction as positive when 
 boiling produces a turbidity. 
 
 Noguchi's Method. — One or two parts of spinal 
 fluid are mixed with five parts of a 10 per cent, dilution 
 of butyric acid in physiological salt solution, and the 
 mixture is boiled for a few seconds. One part of 
 
CEREBROSPINAL FLUID 109 
 
 normal NaOH solution is added quickly to the heated 
 mixture, and the whole is again boiled for a few 
 seconds. The actual quantities recommended are : 
 
 Cerebro-spinal fluid ... ... o*i c.c. or 0*2 c.c. 
 
 Butyric acid solution ... ... 0*5 c.c. 
 
 Normal sodium hydrate solution o-i c.c. 
 
 The rapidity with which the precipitation falls is 
 proportional to the amount of proteid present, and 
 Noguchi considers that a positive result has been 
 obtained when the precipitate settles within two 
 hours. 
 
 On adding fresh Fehling's solution and boiling, 
 a reducing body (? dextrose) is found in normal 
 cerebro-spinal fluids, which is reduced in amount or 
 may be absent if meningitis is present. 
 
CHAPTER X 
 URINE 
 
 A CONSIDERABLE percentage of syphilitics show 
 evidence of nephritis in their urine. It is, however, 
 difficult to say to what degree this nephritis is primarily 
 syphilitic or only the ordinary forms occurring in 
 syphilitic subjects. 
 
 Speiss has reported that of 220 syphilitic patients 
 examined post-mortem, the kidneys were affected in 
 131, grouped under the following heads : 
 
 Amyloid degeneration ... ... ... 42 
 
 Parenchymatous nephritis ... ... ... 21 
 
 Sclerosis ... ... ... ... ... 18 
 
 Interstitial nephritis ... ... ... 16 
 
 Atrophy ... ... ... ... .., 11 
 
 Sclero-gummatous nephritis ... ... 7 
 
 Various inflammations only partly attributable 
 
 to syphilis ... ... ... ... 16 
 
 Petersen considers that the kidneys are affected in 
 3 per cent, of cases in secondary syphilis. 
 
 The onset of secondary symptoms is frequently 
 accompanied by albuminuria which, however, may be 
 slight and transient, and of the same nature as the 
 albuminuria accompanying any other acute infection 
 which cannot be considered a definite nephritis. 
 
 Acute nephritis arises during the secondary stage 
 
 no 
 
URINE III 
 
 and generally within the first year, or at least two 
 years from infection. 
 
 Many cases of syphilitic nephritis present an extra- 
 ordinarily intense albuminaria with few other signs. 
 The urine becomes solid on boiling, and the conditions 
 may be present for weeks without any other marked 
 signs of illness. Notwithstanding the large quantity 
 of albumin there may be very little sediment and few 
 casts, leucocytes, or red blood-cells. 
 
 In subacute syphilitic nephritis the urine is di- 
 minished in quantity, when at the height of the disease 
 it varies from 200 to 250 c.c, and as the case improves 
 it increases, and, if the patient be encouraged to drink, 
 may reach 5 to 6 litres. Its specific gravity is normal 
 or slightly increased, in some cases up to 1040. The 
 albumin is present in quantities of about 0*4 to o"8 per 
 cent. The specific gravity varies inversely with the 
 quantity. The reaction is faintly acid, but in some 
 cases alkaline, even when fresh, and in all cases 
 quickly becomes alkaline. It is usually cloudy from 
 the large amount of sediment, and foaming easily on 
 shaking, because of the amount of albumin which is 
 present. It seldom reaches i per cent., though for 
 months it may vary from 0*4 to o-8. The urine is 
 somewhat diminished. Red blood-cells are practically 
 always found, and coarsely granular, fatty, and waxy 
 casts. 
 
 Several writers state that they have found the 
 Spivochcdta pallida in the urine of patients suffering with 
 florid secondary syphilis, but the majority of observers 
 have failed to detect the organism in urine. 
 
 In chronic intestitial nephritis the urine is usually 
 
112 SYPHILIS AND PARASYPHILIS 
 
 increased in quantity. The specific gravity is usually 
 lower than normal — 1005 ^'^ loio ; this is especially 
 noticeable in the morning. There is usually only a 
 trace of albumin, which is seldom present in greater 
 quantities than 0*05 per cent. A few hyaline casts, 
 red blood-cells, and epithelial cells are usually found. 
 
 Lardaceous (amyloid) disease of the kidney 
 may be superimposed on any form of nephritis. 
 
 Traube's classical description of urine in lardaceous 
 disease of the kidney is that ' it is increased in amount, 
 pale, clear, faintly acid, of low specific gravity (1002- 
 1005) and that it contains abundant albumin and very 
 few casts.' Albumin, however, may not be found at 
 all, or only in traces, and casts may be numerous when 
 they are usually fatty or hyaline. Epithelial cells and 
 red blood-discs are rarely seen. 
 
CHAPTER XI 
 
 CLINICAL VALUE OF THE WASSER- 
 MANN REACTION 
 
 LATENT SYPHILIS 
 
 In the old days the only method of diagnosing the 
 presence of syphilitic infection was by clinical symp- 
 toms, and it was extremely difficult to give an opinion 
 as to when the patient was cured or for how long 
 treatment should be continued, as frequently, after the 
 patient had been six months under treatment, all 
 symptoms would disappear. At first, a year's treat- 
 ment was considered sufficient. This period was 
 gradually lengthened to two and three years, and 
 recently five years' treatment has been considered 
 necessary by some authorities, with occasional courses 
 prolonged indefinitely afterwards. 
 
 It is generally accepted now that a positive Wasser- 
 mann reaction is sufficient evidence of active infection 
 to justify a continuation of treatment, even when no 
 other symptoms are present. 
 
 In syphilis which has been treated there is always 
 a tendency for the symptoms to disappear spontane- 
 ously, only to recrudesce later. Browning and Mac- 
 kenzie describe this latent period as ' a state of 
 
 113 8 
 
ti4 SYPHILIS AND PARASYPHILIS 
 
 equilibrium between the host and the parasite,' and 
 Ehrlich has given it the name of ' non-sterilizing 
 immunity.' During this latent period about 50 per 
 cent, of cases still give a positive Wassermann reaction, 
 which enables the infection to be diagnosed so that 
 the patient may be placed on appropriate treatment, 
 and the recrudescence of the infection and the conse- 
 quent formation of lesions prevented. 
 
 In some cases in which the blood is examined 
 during the latent period, the Wassermann reaction is 
 found to be negative, but if antisyphilitic treatment is 
 given the reaction becomes positive. Similarly, occa- 
 sionally the symptoms are aggravated for a short time 
 when the patient is put under treatment. This lighting 
 up of the disease, as evidenced by the appearance of a 
 positive Wassermann in a blood which before was 
 negative, or by an increase in the manifestations of 
 the disease, has been given the name of the * Jarisch- 
 Herxheimer reaction.' It is supposed to be caused 
 by the setting free of the endotoxins contained in the 
 bodies of the spirochaetes which have been destroyed 
 as the result of the treatment. Another theory 
 advanced is that the reaction is produced by the 
 stimulation of the spirochaetes by a dose of a drug 
 which has been insufficient to kill them. The author 
 is of the opinion that the former rather than the latter 
 theory is the correct one. 
 
 A positive Wassermann reaction must be regarded 
 as resulting from some alteration or destruction of 
 tissue, caused by a toxin produced by the spirochaetes. 
 It therefore takes a little time for a positive reaction 
 to develop, and the reaction is not due simply to the 
 
CLINICAL VALUE OP REACTION 115 
 
 presence of the spirochaetes themselves. Bruck has 
 shown that the serum of monkeys becomes positive 
 about the same time as the organs become infective, 
 as shown by inoculation experiments, and Levaditi 
 and Yamanouchi consider that the time when the skin 
 becomes immune to further inoculations and the time 
 .when the Wassermann reaction becomes positive, 
 synchronize. 
 
 FOR DIFFERENTIAL DIAGNOSIS 
 
 That the Wassermann reaction is of the greatest 
 possible value for diagnosis has been proved beyond 
 question, and the physician, surgeon, gynaecologist, 
 ophthalmic surgeon, lary ngologist, aurist, dermatologist, 
 and the neurologist^ are all equally aided in diagnosis 
 by this reaction. 
 
 Medicine. — The syphilitic fever, which sometimes 
 accompanies either the primary, secondary, or tertiary 
 lesions, may be accompanied by anaemia, loss of weight, 
 pain or swelling of joints, and may be mistaken for 
 rheumatic fever, phthisis, malaria, or enteric fever. 
 
 Pulmonary syphilis, though extremely rare, when 
 present may be exceedingly difficult to diagnose from 
 phthisis, and, in the absence of the tubercle bacilli 
 from the sputum, the Wassermann reaction is the 
 most important guide to a correct diagnosis. 
 
 In syphilis of the heart, producing symptoms of 
 heart failure or anginal attacks, the syphilitic origin 
 of the disease is often missed, and Osier considers 
 that the presence of heart failure in a young or middle- 
 aged person in whom there is no history of rheumatic 
 
li6 SYPHILIS AND PARASYPHILIS 
 
 fever should always arouse a suspicion of syphilis. 
 It has long been suspected that the majority of cases 
 of aortic aneurism and aortitis were syphilitic in 
 origin. This has been proved to be the case by the 
 Wassermann reaction, practically every case of aortic 
 aneurism giving a positive result. In the absence of 
 antisyphilitic treatment, therefore, a negative Wasser- 
 mann almost excludes aortic aneurism. 
 
 A certain proportion of cases of gastric ulcer are 
 considered by some observers to be syphilitic in origin. 
 
 The liver is frequently attacked in syphilis. Osier 
 and Gibson consider that in about 5 per cent, of cases 
 of tertiary syphilis, exclusive of amyloid diseases, 
 symptoms are referable to diseases of the liver. 
 
 As we have seen in the last chapter, syphilis may 
 frequently be the cause of renal diseases. 
 
 Surgery. — The value of the Wassermann reaction 
 for the differential diagnosis of malignant disease or 
 tubercular disease from syphilis is obvious. 
 
 There is hardly any tumour of the bone or skin, or 
 any form of chronic ulceration, in which operative 
 procedure should be undertaken, without first testing 
 the Wassermann reaction, and, if positive, giving the 
 patient some antisyphilitic remedy with a view to 
 finding out whether the lesion in question is syphilitic 
 or not. 
 
 Syphilitic adenitis, especially that occurring in the 
 tertiary stage, has been erroneously diagnosed as 
 Hodgkin's disease. 
 
 Obstetrics and Gynaecology. — Dr. Franz Weber 
 has shown that some cases of endometritis and of per- 
 sistent menorrhagia may depend on a latent sjj^philitic 
 
CLINICAL VALUE OF REACTION 117 
 
 affection, the recognition of which by the Wassermann 
 reaction may indicate the line of successful treatment. 
 
 Weber determined the Wassermann reaction in 67 
 cases of pregnancy which terminated before the twenty- 
 eighth week, and found that of 35 ending within the 
 first sixteen weeks, not one gave a positive result. 
 On the other hand, of the 32 later cases, 12 without 
 any ascertained history or clinical evidence of syphilis 
 gave a positive reaction, and in the examination of 
 9 dead foetuses from these 12 cases spirochaetes were 
 found in the organs of 6. Among 33 cases of recurrent 
 abortion, 6 only gave a positive reaction. The ex- 
 amination of the macerated foetus show that in 84 per 
 cent, the organs contain spirochaetes, which were found 
 in the largest number in the adrenal capsules. 
 
 Ophthalmology. — Chancre, gummata, and tertiary 
 syphilitic ulcers occasionally occur on the eyelids, and 
 keratitis, iritis, retinitis, choroido retinitis, and optic 
 neuritis may all be syphilitic in origin. 
 
 Nervous Diseases. — The value of the Wasser- 
 mann reaction in nervous diseases is discussed in the 
 next chapter. 
 
 Although, in the absence of a few diseases, a positive 
 reaction can be taken as pathognomic of syphilis, it 
 must always be remembered that a negative reaction 
 does not necessarily put syphilis out of court, especially 
 in cases in which obvious lesions are absent. In the 
 secondary and tertiary stages from 10 to 20 per cent, 
 of cases fail to give a positive reaction, and in latent 
 cases and cases in which there are no symptoms 
 50 per cent, of cases are negative. A succession of 
 negative reactions must be obtained before syphilis 
 
ii8 SYPHILIS AND PARASYPHILIS 
 
 can be excluded, and even then the exclusion would 
 not be absolute, but only probable. 
 
 FOR CONTROLLING TREATMENT 
 
 Neisser is firmly convinced that a positive reaction 
 is a sure symptom of disease and an indication of the 
 continued presence of spirochaetes in the infected body, 
 and that consequently in all cases which give a certain 
 positive reaction a recurrence is possible, and that all 
 such cases should be put under treatment. 
 
 The Wassermann reaction, therefore, furnishes 
 grounds for the treatment of those patients whom 
 we previously did not treat because the affection was 
 not recognized, and of those whom we had ceased to 
 treat because we believed them to be cured. 
 
 Neisser considers that the serum diagnosis is indis- 
 pensable before giving an opinion on any syphilitic 
 cases which presents no manifest symptoms of syphilis, 
 and he considers that the Wassermann reaction alone 
 can help us to decide the difficult question as to how 
 long treatment must be continued. 
 
 In the Cavendish Lecture in 191 1, Neisser said : 
 
 ' I cannot understand how in the present day medical 
 men fail to make use of this excellent aid to the diag- 
 nosis of syphilis. One must urgently demand that 
 every individual, of whom even the slightest suspicion 
 is entertained that any disease may be produced by a 
 known or unknown syphilitic infection, must have his 
 serum examined so as to disclose these hidden or 
 latent cases, and in this way to cure them and to 
 protect them against the much-dreaded parasyphilitic 
 complication.' 
 
CLINICAL VALUE OF REACTION 119 
 
 A single negative reaction obtained with the serum 
 of a patient undergoing treatment by mercury or 
 salvarsan means Httle but that the patient is reacting 
 to such treatment. A series of negative results taken 
 at intervals of three to six months after all treatment 
 has been given up is necessary before the patient can 
 be regarded as cured, and even then, until twenty 
 years have passed, we cannot be absolutely certain 
 that the disease is completely and permanently obliter- 
 ated and that no late manifestations will ever occur. 
 It is most important to remember that about 10 per 
 cent, of untreated cases of syphilis fail to give a 
 positive reaction at the first examination, and that 
 therefore a negative reaction only gives a 90 per cent, 
 probability of freedom from infection. 
 
 If in recently acquired syphilis after several months' 
 treatment the reaction continues to be strongly positive, 
 and large doses of complement are still fixed, this is 
 an indication that the treatment is inefficient, and 
 that more rigorous methods should be adopted. If, 
 however, after each course of treatment a smaller 
 amount of complement is fixed, or the intervals before 
 a positive reaction returns become longer and longer, 
 we may conclude that the treatment is satisfactory, and 
 that there is no necessity to increase the dose. 
 
 MARRIAGE AND OFFSPRING 
 
 Bayet considers that as regards the question of 
 marriage and offspring, the serum diagnosis, con- 
 tagiousness, and the transmission of infection to 
 offspring must be regarded as three distinct matters. 
 
120 SYPHILIS AND PARASYPHILIS 
 
 He thinks that clinical experience must be considered 
 of equal value with the Wassermann reaction, and 
 the question of date of infection, length and nature of 
 treatment, and time since the last appearance of any 
 symptoms, must be thoroughly gone into when the 
 practitioner is asked his advice as to the permissibility 
 of marriage. He does not consider a positive Wasser- 
 mann reaction an absolute contra indication to marriage, 
 providing that all other considerations are satisfactory. 
 If, however, marriage of a man giving a positive re- 
 action is permitted and pregnancy occurs, he advises 
 that the mother should undergo antisyphilitic treat- 
 ment even if she presents no symptoms and gives 
 a negative Wassermann reaction. 
 
 The reaction is of great value in obstetric practice 
 as a means of diagnosing latent syphilis in the mother, 
 for (if positive) then energetic antisyphilitic treatment 
 holds out great hopes of the birth of a full-time and 
 healthy child. Bat and Daunay consider that in a 
 pregnant woman one solitary negative reaction does 
 not authorize the conclusion that the woman is free 
 from infection, but that one positive reaction is diag- 
 nostic of certain maternal and probable fcetal infection, 
 and indicates active treatment. They find, when 
 infection has occurred some time after conception, 
 that there is a higher percentage of positive results 
 with the mother than with the infant. Treatment of 
 the mother during pregnancy produces a negative 
 reaction in the infant, but one negative reaction does 
 not authorize the conclusion that the infant is healthy 
 and can be suckled by a healthy wet-nurse. CoUes's 
 and Prof eta's laws have been proved in part by this 
 
CLINICAL VALUE OF REACTION 121 
 
 reaction. The immunity, however, of the mother in 
 Colles's law and the child in Profeta's law is only- 
 apparent ; they cannot contract the disease because 
 they already have it in a latent form. 
 
 Thomsen and Boas examined the reaction of 44 
 newly born infants, which either themselves showed 
 syphilitic lesions or were born of syphilitic mothers, 
 and obtained 20 positive and 24 negative reactions. 
 Sixteen positive cases either showed clinical evidence 
 of syphilis within three months or died in the interval, 
 the post-mortem examination showing characteristic 
 changes in the organs. In the remaining 4 positive 
 cases the reaction disappeared completely, and did not 
 return in three to nine months, nor did these cases 
 develop any evidence of syphilitic infection. Of the 
 24 negative cases, 17 remained negative, and the 
 infants, during a period of observation extending over 
 several months, showed no signs of disease. Of the 
 mothers of these 17 infants, 10 gave a negative reaction 
 and 7 a positive reaction. 
 
 Of 35 mothers whose children showed signs of 
 syphilis, 26 gave a positive and 9 a negative re- 
 action. 
 
 Browning and Mackenzie conclude that the large 
 majority of cases with a positive reaction of the blood 
 at birth subsequently develop symptoms of disease, 
 and that the large majority of those with a negative 
 reaction at birth remain healthy. They also consider 
 that the examination of the blood from the mothers 
 showed that — 
 
 I. The mother may be positive and the child 
 negative. 
 
122 SYPHILIS AND PARASYPHILIS 
 
 2. The mother may be negative and the child 
 positive. 
 
 3. The mother and child may both be positive. 
 
 4. The mother and the child may both be negative. 
 As regards older children, Thomsen and Boas found 
 
 that 37 children up to two years of age with signs of 
 congenital syphilis all gave positive reactions. They 
 further found that of 27 older children and adults with 
 manifestations of congenital syphilis, each gave a 
 positive reaction. The specific affections in these 
 latter cases included interstitial keratitis, osteitis, 
 choroiditis, and juvenile general paralysis. 
 
 Accordingly, a negative reaction in a case presenting 
 active lesions is strongly against the latter being due 
 to congenital syphilis. 
 
 The presence of the positive reaction can only be 
 held to denote syphilis. A passive absorption of the 
 reaction bodies from the child in utero is excluded 
 by the fact that the reaction is not transient, but 
 permanent. 
 
 Probably a man need have but little fear for the 
 safety of his children so long as his wife has a negative 
 reaction. 
 
CHAPTER XII 
 
 SERUM AND CEREBRO-SPINAL FLUID 
 IN NERVOUS DISEASES 
 
 GENERAL PARALYSIS 
 
 The well-known dogma, ' General paralysis is the 
 product of syphilization and civilization,' was advanced 
 by Krafft-Ebing, and was based on inoculation ex- 
 periments, in which he found that general paralytics 
 invariably gave a negative result when inoculated 
 with syphilitic virus. 
 
 Many authorities consider general paralysis and 
 tabes to be a fourth stage in syphilitic infection, but 
 Mott considers that there is a primary neuronic decay 
 which cannot be accounted for solely by the changes 
 in the supporting, enclosing, and nutrient tissues. 
 He considers that the pathology of parasyphilitic 
 affections is that in certain acquired or congenital 
 syphilitic individuals the durability of the neurones 
 is greatly curtailed, so that they decay and die pre- 
 maturely, thereby giving rise to a series of symptoms 
 which may be associated either with the irritation of 
 definite nerve structures — e.g., lightning pains, visceral 
 crises, mania, and epileptiform convulsions ; or with 
 neural destructions — e.g., ataxy, parassthesia, anaes- 
 
 123 
 
124 SYPHILIS AND PARASYPHILIS 
 
 thesia, paresis, and dementia. The irritative phenomena 
 may be the sign of increased neural irritability due to 
 degeneration of neurones prior to their death and loss 
 of function. He does not, however, affirm that the 
 lymphatic and vascular changes play an unimportant 
 part in the process of decay and death of the 
 neurones. 
 
 He considers that if the Spivochceta pallida is the 
 cause of these neuronic degenerations occurring after 
 a lapse of an average of ten years, this is only to 
 be explained by the existence of an intracellular 
 granular resting form becoming active and causing 
 inflammatory changes in the membranes and vessels 
 and connective tissues, with secondary irritation and 
 destruction of the neural elements. This theory he 
 considers purely hypothetical, and one that cannot be 
 accepted without further proof. 
 
 He points out that, whereas in active syphilis giving 
 a positive Wassermann reaction treatment will cause 
 the reaction to become negative, in general paralysis 
 treatment has no effect on the Wassermann reaction. 
 
 Neisser considers that the late manifestations of 
 syphilis in the form of general paralysis or tabes may 
 be the result of a modification of the action of the 
 specific organism by the widespread use of mercury, 
 and others have put forward the suggestion that there 
 may be a specific spirochsete for these diseases. 
 
 Whereas some strains of spirochaetes seem to affect 
 bone and viscera, others appear to chiefly attack the 
 central nervous system. Both Brosius and Erb quote 
 cases in which several individuals were infected from 
 one source, and in which the majority of those infected 
 
NERVOUS DISEASES 125 
 
 developed later either general paralysis or tabes ; and 
 cases of general paralysis or tabes occurring in both 
 husband and wife appear to be more common than 
 can be accounted for by coincidence. 
 
 Browning and Mackenzie, in reviewing the work 
 of Mott and Spielmeyer, emphasize the resemblance 
 between lesions of the central nervous system pro- 
 duced by dourine, by experimental trypanosome 
 infection in dogs, and by sleeping-sickness, and the 
 lesions produced in parasyphilitic conditions. The 
 lesions of the central nervous system in dourine, in 
 the dogs experimented on, and in sleeping-sickness, 
 were all produced by a trypanosome, and these lesions 
 were very like those found in parasyphilis. They 
 therefore conclude that it seems highly probable not 
 only that parasyphilis is caused by the Spirochceta 
 pallida, but also that the Spivochcdta pallida is a 
 protozoon. 
 
 In countries where syphilis has recently been intro- 
 duced, and the disease often takes a malignant form, 
 general paralysis is almost unknown ; and it has 
 been suggested that general paralysis and tabes may 
 be the result of a partial immunity arising in 
 populations which for several generations have been 
 infected. 
 
 Blood in General Paralysis. — Plant, Mott, 
 Chandler, and many other workers agree that a positive 
 Wassermann reaction is given by the blood of prac- 
 tically all general paralytics. 
 
 Of 156 cases examined by Plant, all were positive; 
 and of 64 cases examined by Mott, Chandler, and 
 Henderson-Smith, 92 per cent, were positive. Boas 
 
126 SYPHILIS AND PARASYPHILIS 
 
 obtained positive results in every case in 139 cases 
 examined. 
 
 Plaut points out that other syphilitic affections, 
 even in the florid stage, exhibit no such complete 
 regularity in reaction, and he considers that general 
 paralysis occupies in respect to the Wassermann 
 reaction a unique position among all the varied 
 clinical forms of syphilis. He considers that we may 
 have to count on the possibility that perhaps the 
 syphilitics who lack the reaction in the florid stage 
 have no tendency to develop paresis later, and that 
 therefore the production of the reacting substance 
 represents a primary condition in the development 
 of a metasyphilitic disease. He considers that the 
 existence of general paralysis can practically be 
 excluded if the serum of the patient gives a negative 
 Wassermann, and that general paralysis is the only 
 one of all the syphilitic afliections in which a negative 
 result is of definite clinical value. He points out that 
 for differential diagnosis the negative result is of more 
 importance than the positive ; for, while a negative 
 finding excludes the diagnosis of general paralysis, a 
 positive reaction proves absolutely nothing concerning 
 general paralysis, but simply shows that the patient 
 has had syphilis. He therefore advises in every case 
 in which general paralysis is suspected that the blood 
 should be first examined, and, if the result is negative, 
 that lumbar puncture should not be proceeded with. 
 If, however, a positive result is obtained in the blood, 
 lumbar puncture should then be performed for the 
 purpose of biological and cytological examination of 
 the cerebro-spinal fluid. 
 
NERVOUS DISEASES 
 
 127 
 
 Cerebro-Spinal Fluid in General Paralysis.— 
 
 Plaut considers that, with few exceptions, there is 
 a positive Wassermann reaction and an increase in 
 the lymphocyte count. 
 
 Of 154 cases examined, all of which gave a positive 
 Wassermann with the blood, 146 cases gave a posi- 
 tive reaction of the cerebro-spinal fluid, 2 a doubtful 
 reaction, and 6 a negative reaction ; 146 gave a 
 lymphocytosis, and 8 showed no cell increase. 
 
 General Paralylis, 154 Cases (Plaut). 
 
 Number of 
 Cases. 
 
 Blood (Wasser- 
 mann Reaction). 
 
 Cerebro-Spinal 
 Fluid (Wasser- 
 mann Reaction). 
 
 Cytology. 
 
 138 
 
 6 
 2 
 
 8 
 
 + 
 
 + 
 + 
 
 + 
 
 + 
 
 + 
 
 + 
 + 
 + 
 
 
 100 per cent. 
 
 95 per cent. 
 
 95 per cent. 
 
 The lymphocytosis in general paralysis, according 
 to most observers, is not influenced by antisyphilitic 
 treatment. 
 
 Chandler reports that in 80 cases diagnosed as 
 general paralysis, in which the cerebro-spinal fluid 
 was withdrawn during life by lumbar puncture and 
 examined by the Wassermann test, the clinical 
 diagnosis has been controlled by post-mortem ex- 
 amination ; 67 cases gave a positive reaction, and 
 the post-mortem examination showed the character- 
 istic changes of general paralysis. Of the 13 cases 
 
128 SYPHILIS AND PARASYPHILIS 
 
 that failed to give a positive Wassermann, 2 were 
 found at the post-mortem examination to be cases of 
 general paralysis : the remaining 1 1 were shown by 
 the post-mortem examination not to be cases of 
 general paralysis, although in six of them this con- 
 dition was diagnosed by the clinical symptoms. 
 
 In another series of six cases which gave a negative 
 reaction with the cerebro-spinal fluid, although general 
 paralysis had been diagnosed, in every case the sub- 
 sequent progress of the cases showed that the diagnosis 
 had been erroneous. Five of these were discharged 
 cured, the remaining case being finally diagnosed as 
 dementia prsecox. 
 
 Chandler concludes that a positive reaction cannot 
 be obtained in the cerebro-spinal fluid except in 
 general paralysis and tabes and in a few rare cases 
 of syphilis of the central nervous system. He con- 
 siders that in all cases an excess of lymphocytes 
 indicates an organic disease, but not necessarily either 
 syphilis or parasyphilis. He thinks that a positive 
 reaction of the cerebro-spinal fluid in conjunction 
 with a lymphocytosis points much more strongly 
 to parasyphilis, especially general paralysis, than to 
 cerebral syphilis or spinal syphilis. 
 
 He considers that if there is a positive reaction with 
 the serum associated with nervous or mental pheno- 
 mena, lumbar puncture should be performed; and if 
 the cerebro-spinal fluid gives a positive reaction, the 
 indication is strongly in favour of general paralysis. 
 
NERVOUS DISEASES 129 
 
 TABES DORSALIS 
 
 The Wassermann reaction is not nearly of as much 
 value in the diagnosis of tabes as in general paralysis, 
 since a positive reaction is only obtained in the blood 
 in about 60 per cent, of cases, and in the cerebro- 
 spinal fluid in only about 50 per cent. Cases some- 
 times occur in which a positive reaction is present in 
 the cerebro-spinal fluid and not in the blood. 
 
 A pathological increase in the lymphocytes is also 
 found in only about 60 per cent, of cases. 
 
 It therefore follows that, though a positive Wasser- 
 mann reaction in the blood and cerebro-spinal fluid 
 accompanied by a cellular increase may be of con- 
 siderable diagnostic value, yet a negative reaction 
 cannot put tabes out of court. 
 
 Of 43 cases examined by Boas, 28 were positive 
 and 15 negative. If these cases v;ere given under the 
 headings of ' treated ' and ' untreated ' cases, it would 
 be found that of the 17 cases that did not receive 
 treatment all were positive, whereas of the 26 cases 
 which had received treatment 11 were positive and 
 15 negative. 
 
 Of 36 cases examined by Browning and Mackenzie, 
 72 per cent, gave a positive reaction with the serum. 
 
 Of 50 cases examined by the author, 30 (60 per 
 cent.) were positive. 
 
 CEREBRAL SYPHILIS 
 
 In this condition a positive reaction is usually given 
 with the serum, but not with the cerebro-spinal fluid. 
 Of 18 cases examined by Plant, 14 were positive 
 
 9 
 
130 SYPHILIS AND PARASYPHILIS 
 
 with the serum and negative with the cerebro-spinal 
 fluid, 3 were positive with both serum and cerebro- 
 s^pinal fluid, and i was negative with both. 
 
 Nonne, however, obtained a positive reaction in the 
 cerebro-spinal fluid in 4 out of 16 cases examined. 
 
 Mott considers that 25 per cent, give a positive 
 reaction with the cerebro-spinal fluid, and that most 
 of the cases show a well-marked lymphocytosis. 
 
 MENTAL DEFICIENCY 
 
 Still found six idiots amongst 142 consecutive cases 
 of congenital syphilis (4-2 per cent.). He considers 
 that the proportion of cases of idiocy due to syphilis 
 would be considerably higher if mental degeneration, 
 as an acquired condition beginning after some years 
 of apparently normal mental power, were included. 
 
 Tredgold found definite clinical evidence of syphilis 
 in 2 "5 per cent, of cases out of 150 inmates of idiot 
 asylums. Doubtless the Wassermann reaction would 
 have greatly raised the percentage of cases demon- 
 strable as syphilitic in this series. 
 
 Of 36 cases examined by Plant, 23 gave a positive 
 Wassermann ; in only 10 cases was the cerebro-spinal 
 fluid examined, and these included 4 cases of general 
 paralysis, which were all positive, and 2 cases of 
 acute cerebral syphilis, which were both positive ; 
 2 cases of secondary syphilis, and 2 cases of meningo- 
 coccus meningitis with manifest hereditary syphilis, 
 were both negative. 
 
 In a very interesting series of 330 cases of congenital 
 mental deficiency examined by Dean, 55 gave a posi- 
 
NERVOUS DISEASES 131 
 
 tive Wassermann reaction — namely, 15-5 per cent. 
 Among the 55 positive cases there were 13 which 
 showed other evidence of syphilitic infection. 
 
 DIFFERENTIAL DIAGNOSIS 
 
 Individuals who have contracted syphilis occasion- 
 ally develop hysteria, hypochondriasis, or syphilo- 
 phobia, and in such cases, as Mott points out, a 
 negative Wassermann reaction may be able to allay 
 their ungrounded fears and their desire for salvarsan 
 treatment. 
 
 Neurotics suffering with arterio-sclerosis may become 
 melancholic and irritable, and develop symptoms sug- 
 gesting general paralysis. Examination of the cerebro- 
 spinal fluid will at once settle the diagnosis. 
 
 Mott considers that parasyphilitic affections may be 
 definitely differentiated from neurasthenic conditions 
 by an examination of the cerebro-spinal fluid, and that 
 a lymphocytosis points definitely to a chronic inflam- 
 matory condition of the central nervous system, of 
 which, however, syphilis may not be the only cause. 
 
 Chronic alcoholism and syphihs are so often associ- 
 ated that cases frequently occur in which there is 
 considerable difficulty of diagnosis from general 
 paralysis. A negative Wassermann in these cases 
 will exclude general paralysis ; but if the reaction is 
 positive, and the symptoms suggest the possibility of 
 general paralysis or syphilitic disease of the central 
 nervous system, recourse should be had to lumbar 
 puncture. 
 
 One must not lose sight of the diagnostic value of 
 
132 SYPHILIS AND PARASYPHILIS 
 
 the influence of treatment on lymphocytosis of the 
 cerebro-spinal fluid. It is difficult to diagnose between 
 syphilitic cerebro-spinal meningitis, tabes, and general 
 paralysis. In all three conditions there may be a high 
 lymphocytosis, and a positive Wassermann may be 
 present, though rarely in the syphilitic cerebro-spinal 
 meningitis, as well as in parasyphilitic conditions. If, 
 however, after a short course of mercurial inunctions 
 or intramuscular injections, a rapid fall in the number 
 of leucocytes in the cerebro-spinal fluid is recorded, 
 parasyphilis can be excluded. 
 
 In toxic peripheral neuritis with ataxia the symptoms 
 may be confused with those of tabes. Examination of 
 the cerebro-spinal fluid, however, will settle the diag- 
 nosis. The reaction will be negative, and there will 
 be no lymphocytosis. 
 
 Mott is of the opinion that a person suffering with 
 an affection of the nervous system, whose blood gives 
 a positive serum reaction, is much more likely to be 
 suffering from a syphilitic affection than one who has 
 had syphilis^ but whose blood does not yield the 
 reaction. An examination of the cerebro-spinal fluid 
 in such a case will afford most valuable evidence, and 
 he considers that srich evidence is of vital importance. 
 
 In the case of acute syphilitic disease, antisyphilitic 
 treatment will cause a disappearance of the Wasser- 
 mann reaction and of the lymphocytosis in the cerebro- 
 spinal fluid. There will be either cure or improvement 
 in the symptoms. 
 
 In the case of general paralysis or tabes, especially 
 general paralysis, however, both the serum and 
 cerebro-spinal fluid will give a positive Wassermann, 
 
NERVOUS DISEASES 
 
 133 
 
 which will be uninfluenced by treatment, and in the 
 majority of cases the lymphocytosis of the cerebro- 
 spinal fluid will not be improved by the treatment. 
 
 Hysteria, hystero-epilepsy, neurasthenia, chronic 
 alcoholism, dementia praecox, disseminated sclerosis, 
 tubercular meningitis, and cerebral abscess, will all 
 give negative Wassermann reactions of the blood 
 except in those cases in which a syphilitic affection 
 may be coincident, but none will give a positive 
 Wassermann of the cerebro-spinal fluid. 
 
 Paraplegia, hemiplegia, cerebral tumour, meningitis, 
 or idiocy, may be syphilitic in origin. An examina- 
 tion of the blood and cerebro-spinal fluid will be 
 of great importance for arriving at appropriate treat- 
 ment. 
 
 The following tables give the relation between 
 the diagnosis of tabes and general paralysis and the 
 Wassermann reaction of the blood and cerebro-spinal 
 fluid as recorded by various observers : 
 
 Table III. 
 
 
 Diagnosed as Tabes. 
 
 Diagnosed as General 
 Paralysis. 
 
 Serum. 
 
 Cerebro- 
 spinal Fluid. 
 
 Serum. 
 
 Cerebro- 
 spinal Fluid. 
 
 
 v.z, 
 
 u.t: 
 
 ,Q in 
 a « 
 
 |u 
 
 U.t! 
 
 ■ t" 
 
 it « 
 
 io 
 12; '0 
 
 a, Oh 
 
 1=1 «S 
 
 ^'0 
 
 O.ti 
 
 Noguchi 
 
 Marie and Levaditi 
 Wassermann 
 Mott, Chandler, and 
 Henderson-Smith 
 
 Bayly 
 
 Plaut 
 
 205 
 50 
 
 60 
 60 
 
 II 
 9 
 
 20 
 
 54 
 66 
 
 53 
 45 
 
 61 
 
 20 
 
 150 
 
 65 
 
 85 
 100 
 
 60 
 
 35 
 
 64 
 
 8 
 
 150 
 
 73 
 94 
 
 92 
 87 
 96 
 
134 
 
 SYPHILIS AND PARASYPHILIS 
 Table IV. 
 
 The Wassermann Reaction of the Blood in 
 Nervous Diseases other than General 
 Paralysis and Tabes (Author's Series). 
 
 Diagnosis. 
 
 Number of 
 Cases. 
 
 Per Cent. 
 Positive. 
 
 Cerebral tumour 
 
 31 
 
 24 
 
 Paraplegia 
 Hemiplegia' 
 Pachymeningitis 
 Disseminated sclerosis 
 
 25 
 16 
 16 
 13 
 
 24 
 25 
 25 
 15 
 
 Epilepsy . . 
 Optic atrophy 
 Mental Deficiency 
 
 10 
 4 
 4 
 
 
 
 75 
 50 
 
CHAPTER XIII 
 
 TREATMENT 
 
 SALVARSAN 
 
 DioxY-DiAMiDO-ARSENo-BENZoL (" 6o6 "), discovered by 
 Ehrlich and Hata in 1909, not by chance, but as the 
 direct outcome of long and patient research, is now 
 universally recognized as one of the most potent anti- 
 syphilitic remedies. Like all new remedies, it has its 
 strong advocates and equally strong detractors. It 
 has now passed through the fire of most searching 
 criticism, and has emerged from the experimental stage 
 to permanently take its place amongst the most 
 valuable antisyphilitic remedies. Its remarkable 
 efficacy in clearing up syphilitic manifestations has 
 been established, and, though at present it is impossible 
 to state that any given number of injections with 
 salvarsan will definitely cure every case of syphilis, 
 still we know that in the vast majority of cases it has 
 great therapeutic value. It would be as foolish to say 
 that salvarsan is useless because it does not perman- 
 ently cure with two or three injections as to say that 
 mercury is useless because two years of pill treatment, 
 or two courses of inunctions or intramuscular injections, 
 do not produce permanent cure in the majority of cases. 
 
 135 
 
136 SYPHILIS AND PARASYPHILIS 
 
 In every case of microbic invasion we have to con- 
 sider a variety of factors — variations in strain of the 
 invading organism, the soil, and the reaction of the 
 individual to the infection. Syphilis is no exception to 
 this general rule, and it is not to be wondered at that 
 no two cases behave in a precisely similar manner 
 either towards the infecting agent or towards the 
 remedy prescribed to combat it. In no given case can 
 the progress of the syphilitic infection be foreseen, and 
 no one who undertakes the treatment of a primary 
 lesion can predict the course that will be taken by the 
 disease. 
 
 Method of Administration. 
 
 Apparatus. — The apparatus used by the author 
 consists of a container surrounded by a hot-water 
 jacket ; a rubber tube about 4 feet long, which connects 
 the container and the needle-holder ; and a stout needle 
 I J inches long and of the calibre of a fine exploring 
 needle. About 3 inches from the needle-holder a piece 
 of glass tubing is let in to act as a window. The con- 
 tainer, tube, and needle-holder are connected up and 
 sterilized before use. The rate of flow is regulated by 
 altering the height of the container, and a clip is 
 applied to the rubber tube about a foot from the needle- 
 holder (Fig. 21). 
 
 Technique. — The patient should be in bed, with 
 the arm selected for the infusion supported on a pillow. 
 Having sterilized in the autoclave a glass measure 
 graduated to 300 c.c. and also a glass stirring rod, 
 100 c.c. of sterilized normal saline is poured into 
 the measure. The end of the phial containing the 
 
Fig, 21. 
 
 Apparatus for Intravenous Injection of Salvarsan 
 (Author's Pattern). 
 
138 SYPHILIS AND PARASYPHILIS 
 
 salvarsan is now broken off, and the contents are 
 slowly shaken into the saline, which is briskly stirred. 
 A clear yellow acid solution results. Sterilized normal 
 sodium hydrate solution is now added slowly drop by 
 drop, till the yellow precipitate which is first produced 
 is just redissolved. More normal saline solution is 
 now added to bring the volume up to 300 c.c. All the 
 solutions employed should be at a temperature of 
 110° F. The water-jacket surrounding the irrigator is 
 also filled with water at a temperature of 1 10° F. The 
 irrigator is now filled with warm saline solution, which 
 is run through till all air-bubbles have been got rid of. 
 The clip is now applied and the needle-holder put into 
 the sterilized tumbler containing some warm sterile 
 saline solution. The skin over the most prominent 
 vein at the bend of the elbow is sterilized by dabbing 
 it with a saturated solution of iodine in chloroform and 
 a bandage applied firmly round the upper arm in order 
 to distend the vein. If the veins are small the arm 
 must be soaked in hot water for a few moments, and 
 the patient told to clasp and unclasp his hand. The 
 needle, having been boiled, is now adjusted to the 
 holder and a little saline solution run through. The 
 irrigator is now lowered and the needle plunged into 
 the vein and the clip removed. If the needle is in the 
 vein the blood will run into the tube and be seen at the 
 * window.' The bandage is now removed and the 
 irrigator raised, and about 50 c.c. of the saline allowed 
 to run in. If no local swelling is produced, the required 
 quantity of the solution of salvarsan can now be poured 
 in. If, however, any local swelling is produced by the 
 saline, the needle must be removed and the procedure 
 
TREATMENT 139 
 
 recommenced in another vein. The solution should 
 only be allowed to run in slowly so as to be well diluted 
 by the blood-stream, and it should take about ten 
 minutes to run in all the solution. o'6 gramme of 
 salvarsan having been diluted up to 300 c.c, 50 c.c. of 
 the diluted fluid contains o'l gramme of salvarsan. 
 0'6 gramme is the author's usual dose for a healthy 
 male adult and o'5 gramme for a woman. About 
 100 c.c. of normal saline solution should be poured into 
 the irrigator when the salvarsan solution has almost 
 run out, so that the needle may be washed free of 
 salvarsan before being withdrawn ; otherwise some 
 salvarsan may escape along the needle track and pro- 
 duce some local inflammation and possibly phlebitis 
 and thrombosis. 
 
 Preparation of the Patient.— The preparation of 
 the patient is of great importance, as, if the infusion is 
 given with a full stomach and high blood-pressure, an 
 alarming condition of feeble rapid pulse and collapse 
 may supervene, which, however, usually passes off 
 when vomiting occurs. Rigors are not uncommon in 
 florid syphilis, and may occur from one to three hours 
 after the infusion. The patient sometimes complains 
 of throbbing in the head and a metallic taste in the 
 mouth and a sense of fulness in the throat. The 
 author prepares the patient by giving a pill the night 
 before and a brisk saline purge on the morning of the 
 infusion. Only a light breakfast is allowed, with but 
 little fluid and no food or drink for four hours before the 
 infusion. Since the author has adopted these precau- 
 tions he has recorded no alarming symptoms. 
 
I40 SYPHILIS AND PARASYPHILIS 
 
 Dosage. 
 
 The question of dosage and mode of administration 
 appear to be of vital importance, and the experiments 
 of Hata carried out upon animals lend great support 
 to this view. In mice inoculated with organisms of 
 relapsing fever, a single injection of g^y gramme 
 (per 20 grammes of weight) of salvarsan gave 100 per 
 cent, of cures, while the administration of half this 
 dose was followed by 82 per cent, of failures. 
 Similarly, suggestive results were obtained in ' syphil- 
 ized ' rabbits with scrotal chancres, 0-0075 P^^ kilo- 
 weight effecting complete cure, while 0*004 gramme 
 proved ineffective. 
 
 The usual dose for adults given by the intravenous 
 route is 0*5 gramme for a woman, and 0*6 gramme for 
 a man. 
 
 In the absence of temperature and nephritis, the 
 author repeats the dose after forty-eight hours. 
 
 Therapeutic Results. 
 
 I. Primary Syphilis.— In the majority of primary 
 cases the effect of salvarsan, whether administered by 
 the intramuscular or the intravenous route, is prompt, 
 and some degree of softening of the hard chancre is 
 frequently observed within twenty-four hours. Accord- 
 ing to Wechselmann, eroded chancres become clean 
 after from twelve to twenty-four hours, and, further, 
 the Spivochceta pallida is no longer found in scrapings 
 taken after one or two days. The rapidity with which 
 absorption takes place depends upon several factors — 
 
TREATMENT 141 
 
 the degree of induration present, the actual size of the 
 lesion, and the dose of the drug exhibited. 
 
 Gibbard, Harrison, and Cane, in order to compare 
 the effect of salvarsan with that of mercury in prevent- 
 ing the onset of secondary symptoms when treatment 
 was commenced in the primary stage, treated 38 cases 
 of primary sore with salvarsan, and another series of a 
 similar 38 cases with mercurial injections. In all 
 cases the Spivochceta pallida had been demonstrated. 
 All the cases were under observation for at least four 
 months. Of the 38 salvarsan-treated cases, only 2 
 (5*2 per cent.) developed secondary symptoms, while 
 of the 38 mercury-treated cases, 36 (94 "8 per cent.) 
 developed secondary symptoms. 
 
 These extremely valuable parallel investigations in 
 strictly comparable cases emphasize clearly and 
 beyond all doubt the very great importance of the 
 early administration of salvarsan. 
 
 2. Secondary Syphilis. — As regards the effect of 
 salvarsan on the manifestations of secondary syphilis, 
 it is almost impossible to write a critical report, as the 
 innumerable contributors to the literature are almost 
 unanimously in favour of the drug. Ernest Lane and 
 C. F. Marshall of this country, working independently, 
 and Engmann, Mark, and Marchildon, working 
 together, consider that equally good effects can be 
 obtained with mercurial treatment. These observers, 
 however, had, when they first advanced these opinions, 
 personal experience of only quite a small number of 
 salvarsan-treated cases, and probably with efficient 
 doses given by the intravenous route their future 
 reports will not be so pessimistic. Ernest Lane, 
 
142 SYPHILIS AND PARASYPHILIS 
 
 indeed, has already modified the opinions he first 
 expressed, which were that intolerance to mercury 
 would be the only justification for looking elsewhere 
 for a remedy. 
 
 As is to be expected, secondary manifestations differ 
 very considerably in their reaction to salvarsan, and 
 sclerosed lesions take much longer to resolve than soft 
 conditions, such as mucous plaques, condylomata, and 
 superficial ulceration of the mucous membrane, which 
 usually disappears in twenty-four to forty-eight hours, 
 Wechselmann stating in respect to mucous plaques 
 of the mouth, ' even if the patient smokes con- 
 tinuously.' 
 
 The pains arising from secondary syphilitic infection 
 of periosteum or joints are frequently relieved in an 
 extraordinarily short time, and, indeed, pain of any 
 kind arising during the course of syphilis, either early 
 or late, is usually most favourably influenced by 
 salvarsan. 
 
 It is particularly in malignant syphilis, reacting little 
 or not at all to mercurial treatment, that the value of 
 salvarsan is most strikingly seen. Numerous cases are 
 recorded of patients apparently doomed to death, owing 
 to the entire failure of mercury to check the morbid 
 processes, who have been saved by the administration 
 of salvarsan. 
 
 Gibbard and Harrison found that of thirty-two cases 
 which were either uninfluenced by or intolerant to 
 mercury, all but one were to all appearance com- 
 pletely cured by salvarsan. Intolerance to mercury 
 on the part of the patient and immunity to mercury 
 on the part of the spirochaete being rare, the cases 
 
TREATMENT 143 
 
 recorded by these officers, which were collected from 
 all the military stations of Great Britain and Ireland, 
 are of extreme interest and value. 
 
 3. Tertiary Syphilis. — In no stage of syphilis is 
 improvement by salvarsan more marked than in the 
 tertiary, and there can be few clinicians with any con- 
 siderable experience of Ehrlich's specific who have not 
 met cases of severe and intractable ulcerations, or bone 
 lesions, in which the new treatment acted ' like a 
 charm.' Within a few hours the symptoms begin to 
 subside, and within one to three weeks not only have 
 the lesions healed, but the patient's general condition 
 has also remarkably improved. Cases of chronic 
 superficial glossitis have been most successfully treated 
 by salvarsan. 
 
 The author's own experience but confirms the 
 results reported by previous contributors to the 
 literature, and only adds to the indisputable evidence 
 as to the value of salvarsan in removing the symptoms 
 of tertiary syphilis. 
 
 4. Congenital Syphilis. — The opinion as to the 
 value of the drug in interstitial keratitis is still divided, 
 and it is only to be expected that the least effect would 
 be produced in non-vascular tissue, such as the cornea. 
 Infants under six months should not, by preference, 
 be treated directly, on account of the enormous number 
 of spirochaetes present and the large quantity of endo- 
 toxin set free by an efficient dose of salvarsan, but 
 indirectly through the milk of the mother who has 
 been treated. If the mother cannot feed her baby, so 
 that treatment via the milk is impossible, intramuscular 
 injection of not more than 0-02 gramme may be given 
 
144 SYPHILIS AND PARASYPHILIS 
 
 to newly born infants in urgent cases, or if the child is 
 several months old, McDonagh does not think 0*004 
 to 0-005 gramme per pound weight of child to be too 
 large a dose. 
 
 Pregnant women, if healthy, may with safety be 
 treated, and Wechselmann has reported a case injected 
 five weeks before delivery, in which an apparently 
 healthy baby with a negative Wassermann reaction 
 was born. 
 
 5. Parasyphilis. — (i) Tabes. — The evidence that 
 has accumulated as to the value of salvarsan in early 
 cases of tabes is considerable. Not every case, how- 
 ever, benefits from the treatment, and, indeed, 
 occasionally an exacerbation of symptoms has been 
 noticed. The rule, however, seems to be that there is 
 diminution in the pain, ataxia, and frequency of crises 
 with improvement in general health, and of the 
 bladder and rectal symptoms. 
 
 Wechselmann and McDonagh have each reported a 
 case in which return of sexual power has followed 
 treatment, and have noticed in a few cases a return 
 of mobility in rigid pupils and of the patella reflex. 
 Wechselmann writes : * In view of extensive subjective 
 improvements I no longer hesitate to administer 
 injections, even in cases where the Wassermann 
 reaction is negative. Undoubtedly an important 
 part in this happy result should be attributed to the 
 stimulating and tonic effect of the remedy. We cannot 
 for some years conclude that the remedy permanently 
 stops the progress of the disease.' 
 
 Out of a large number of cases treated by James 
 Collier, he has recorded no permanent ill-effect referable 
 
TREATMENT 145 
 
 to the medication, and no aggravation of the tabetic 
 symptoms after injection. In the majority of cases 
 marked improvement in general health, nutrition, 
 colour, and feeling of well-being occurred within a 
 couple of weeks of the injection. 
 
 The ataxy improved conspicuously in several cases, 
 and occasionally sphincter trouble seemed benefited ; 
 on the other hand, he did not see any of the character- 
 istic physical signs of the disease disappear entirely. 
 In those cases where pains were present and trouble- 
 some, very striking relief followed the salvarsan 
 injection. Four patients, who suffered from severe 
 gastric crises, improved remarkably. 
 
 The results obtained suggest that salvarsan may be 
 of considerable value in the treatment of tabes, especi- 
 ally in early cases occurring soon after infection. 
 
 Marcus concludes that 'we are certain now that 
 salvarsan is very useful in syphilitic nervous diseases, 
 and that it acts more rapidly and is more convenient 
 than mercury or potassium iodide.' He thinks it 
 justifiable to give salvarsan even in advanced cases of 
 tabes, as it may ameliorate the pains and lengthen 
 life, although there may be no hope of cure. 
 
 (2) General Paralysis. — A few cases of apparent 
 recovery following injection with salvarsan have been 
 reported. Treupel has frequently noticed a transient 
 improvement. Most writers, however, report complete 
 absence of improvement, and the cases that are bene- 
 fited must be few. Still, in the light of occasional 
 successes, early cases should be given the chance of 
 cure or improvement, even if this be an extremely 
 small one. 
 
 10 
 
146 SYPHILIS AND PARASYPHILIS 
 
 Dangers. 
 
 Toxicity. — Professor Ehrlich, after investigating 
 reports of 10,000 cases, stated that only a single fatal 
 case had been recorded in which the patient's life had 
 not been directly in danger from the disease itself. 
 In this connection it is only fair to state that a con- 
 siderable number of the fatalities reported on the 
 Continent have been described as cases of death 
 ' following the administration of salvarsan,' which 
 would have been more justly recorded as cases of 
 death ' occurring in spite of the administration of sal- 
 varsan.' Gibbard and Harrison have not met one case 
 in over 1,000 injections that has given rise to anxiety. 
 
 In the very large number of cases treated at the 
 London Lock Hospitals two deaths have followed 
 treatment. In one, no error of technique or any 
 cause other than the toxicity of the fluid injected could 
 be found. The post-mortem examination showed the 
 changes characteristic of toxaemia. The symptoms 
 did not develop until three days after the second dose. 
 Degenerative changes were found in the liver, and 
 possibly these changes were induced by the salvarsan, 
 and were the cause of the toxic symptoms. The 
 second death was from pulmonary embolism, resulting 
 from the shifting of a clot from a vein inflamed above 
 the point of injection. The emboHsm occurred three 
 days after injection. 
 
 The author, in a considerable personal experience, 
 has met no case giving rise to apprehension, with the 
 exception of two cases of phlebitis, one of slight 
 transient albuminuria, and one of syncope. This last 
 
TREATMENT 147 
 
 case occurred in a patient that had not been properly 
 prepared by starving and purging. 
 
 The author is of the opinion that salvarsan given in 
 the present dosage is practically non-toxic, and that 
 most, if not all, of the few fatal cases recorded are 
 due to some accident, such as decomposition of the 
 drug owing to a flaw in the glass ampule, so that the 
 vacuum is destroyed, or to error in technique. 
 
 Blindness. — Cases of blindness have been recorded 
 in lay journals on the Continent ; but Ehrlich cate- 
 gorically states that no case has been reported to him, 
 and that, despite penetrating research, it has not been 
 possible for him to run one of these rumoured cases 
 to earth. In medical literature the danger has been 
 constantly hinted at, but the author has been unable 
 to find any authenticated case of actual loss of sight 
 following treatment by salvarsan. 
 
 On the other hand, many observers have published 
 cases of optic neuritis which have been definitely 
 improved by the exhibition of salvarsan. 
 
 Phlebitis sometimes occurs in the vein receiving 
 the injection. If this sequel arises, the arm must be 
 kept at rest and the limb fomented with lead and 
 opium lotion. The author knows of one case in 
 which death occurred from pulmonary embolism 
 caused by the shifting of a clot from a vein in which 
 phlebitis had occurred as a result of the injection. 
 
 Nephritis. — Transient albuminuria has been observed 
 in several cases, and a very few cases of severe and 
 acute nephritis have been recorded in the literature. 
 A few cases of suppression and retention of urine have 
 also been reported. 
 
148 SYPHILIS AND PARASYPHILIS 
 
 After-Effects. 
 
 Pain in intravenous injections should, with correct 
 technique, be limited to the momentary discomfort 
 caused by entrance of the needle. Occasionally 
 painful local infiltration has been noted, but should be 
 regarded purely as occasioned by faulty technique, by 
 which some of the salvarsan solution escapes into the 
 tissues around the vein and there sets up an aseptic 
 inflammation. 
 
 Salvarsan Fever and Saline Fever. — As has 
 been pointed out, the intravenous injections of sal- 
 varsan are sometimes followed by a rise in temperature, 
 sometimes reaching 102° F., and occasionally as high 
 as 105° F. This rise in temperature may be accom- 
 panied by rigors, vomiting, headache, and pains in the 
 back. The onset of the symptoms usually occurs 
 from half an hour to two hours after the injection. 
 The symptoms usually subside in a few hours. 
 
 Wechselmann has suggested that these symptoms 
 might be caused by contamination of the saline solution, 
 and not be due to the salvarsan, and Gibbard and 
 Harrison, Macintosh and Fildes, and Holt and Pen- 
 fold, working independently, have all come to the 
 conclusion that in many cases it is the saline solution 
 and not the salvarsan that is the cause of " salvarsan 
 fever.' 
 
 Gross contamination with living organisms is not 
 the only cause, for the fever may be produced if the 
 saline solution is autoclaved just before use, so that 
 all the organisms are killed. 
 
 The question has not been definitely settled as to 
 
TREATMENT 149 
 
 whether the toxic symptoms are produced by the 
 dead bodies of the bacteria acting as a poisonous 
 foreign albumin, or by thermo-stable exotoxins pro- 
 duced in the saline as the result of bacterial action. 
 The results of numerous experiments, however, make 
 it clear that, if the salt solution is only prepared 
 immediately before use, is made with freshly distilled 
 water, and is autoclaved directly it is mixed, these 
 toxic symptoms will only occur in cases of florid 
 syphilis. 
 
 Macintosh and Fildes point out that the rigors and 
 toxic symptoms, which occur in secondary syphilis, 
 must be different in origin from those occurring in 
 other forms of syphilis, because they continue in spite 
 of the use of microbe-free saline solution. These 
 authors also state that the toxic symptoms which 
 occur in secondary syphilis, and are uninfluenced by 
 the careful preparation of the saline, occur later than 
 the saline rigors, the temperature seldom starting to 
 rise for three or four hours. 
 
 Schreiber suggests that fever in secondary syphilis 
 is the result of the liberation of large quantities of endo- 
 toxins from the destroyed spirochaetae, and this view 
 the author shares. 
 
 In order to eliminate the risk of saline fever — 
 
 1. Freshly distilled water should be used. 
 
 2. Pure sodium chloride. 
 
 3. The salt should be added to the distilled water 
 and filtered, and the filtered solution should be auto- 
 claved immediately before use. 
 
 The author, with an experience extending over 
 nearly two years, has not met with rigors in more than 
 
I50 SYPHILIS AND PARASYPHILIS 
 
 5 per cent, of cases, vomiting has been very occasional, 
 and the temperature has rarely been raised above 
 1 00° F. except in a few cases of florid syphilis. 
 
 Vomiting, when it occurs, usually takes place from 
 half an hour to three hours after the injection. 
 
 Rigors are rare, but occasionally occur from half an 
 hour to four hours after injection. 
 
 Headache and pains in the back are met with in 
 a considerable percentage of cases. 
 
 Diarrhoea and constipation are occasional effects 
 of treatment, the former occurring soon after the injec- 
 tion, and the latter after an interval of a few days. 
 Neither condition is, as a rule, of serious import. 
 
 Both jaundice and rectal tenesmus occur as very 
 rare sequels. 
 
 A temporary exacerbation of an existing skin 
 eruption (the Jarisch-Herxheimer reaction) is not 
 infrequently seen. Two hours or so after the injection 
 cutaneous lesions become deeper in colour and more 
 diffuse. This effect reaches its highest point in about 
 twelve hours and then gradually disappears in the 
 course of the next few days. 
 
 A sense of cardiac oppression, sometimes going on 
 to syncope, and throbbing in the head have been 
 described as occurring at the time of intravenous 
 injection, but the author has not observed these symp- 
 toms in properly prepared cases. Purgation and 
 abstinence from food before treatment should be 
 enforced in each case, and this preparation of the 
 patient, combined with slow injection of the drug, can 
 be relied upon to obviate the occurrence of these 
 symptoms. 
 
TREATMENT 151 
 
 The effect on the general health is strikingly benefi- 
 cial in the vast majority of cases. There is at first a 
 slight depression, with loss of appetite, lasting twelve 
 to forty-eight hours, after which rapid improvement is 
 usually seen. In most cases there is a very definite 
 gain of weight, varying from a few pounds up to twenty 
 or more in a month. 
 
 The composition of the blood is modified by salvar- 
 san, but the changes observed are not constant. 
 Normally there is a definite increase in the number of 
 red corpuscles, and also in the amount of haemoglobin. 
 Levy-Bing and Duroeux, however, quote a case in 
 which a fall of red cells, amounting to 1,400,000 is 
 recorded. Leucocytosis is the rule. It may be as 
 high as 30,000, but a more usual count is 17,000. The 
 increase occurs chiefly in neutrophil cells, but eosino- 
 philia has occasionally been observed. Sabrazes has 
 worked out in minute detail the various changes occur- 
 ring in the blood after treatment. Clinically, very 
 striking improvement is seen in cases of syphilitic 
 anaemia, the pallor and sallowness disappearing in the 
 course of a week or two. 
 
 Relapses. 
 
 Several cases of chancre successfully treated, in so 
 far as complete resolution had resulted in a week or so, 
 have subsequently developed typical secondaries. 
 Most of these have cleared up in a few days after a 
 second injection. Many relapses have also occurred in 
 cases treated in the secondary and tertiary stages of 
 the disease, and in these also reinjection has, in the 
 
152 SYPHILIS AND PARASYPHILIS 
 
 majority of instances, caused disappearance of the fresh 
 lesions. 
 
 Various causes have been put forward to explain 
 the incidence of relapse which may be summarized 
 as follows : 
 
 1. That the dose of salvarsan has been insufficient 
 to kill the spirochaetcE. 
 
 In this connection it is interesting to recall the 
 experiments of Hata upon animals, which showed that 
 half a curative dose was ineffective. Moreover, Duhot 
 attributes his success to the large doses (maximum 
 I •! gramme) which he has invariably employed. 
 
 2. That some of the spirochsetae lie embedded in 
 thrombi or protected by dense inflammatory tissue, and 
 only escape after the complete excretion of the drug. 
 
 Reinduration of a chancre might be explained on 
 this hypothesis, and excision of the chancre at the time 
 of the injection, as advocated by many authors, would 
 thus appear to rest on a rational basis. The simul- 
 taneous administration of fibrolysin or reinjection with 
 salvarsan at an early date has also been recommended 
 with the same object in view ; in the latter case on the 
 supposition that the first dose, although unable to reach 
 the ' protected ' spirochsetae, yet promotes sufficiently 
 extensive tissue reaction to enable the second to 
 achieve this purpose. 
 
 3. That in certain cases some or all the spirochaetse 
 are resistant to salvarsan. 
 
 We know that in a few rare instances spirochsetae 
 are resistant to mercury, and it is conceivable that an 
 arsenic-fast strain is occasionally met with, although 
 Ehrlich strongly opposes this view. 
 
TREATMENT 153 
 
 4. That some spirochaetae, which are not originally 
 arsenic-fast, become so after the administration of a 
 dose insufficient to kill them. 
 
 This hypothesis would explain those cases which 
 have relapsed owing to an insuflicient dosage after an 
 apparently successful treatment, and have then failed 
 to react to a second injection. 
 
 Contra- Indications. 
 
 The contra-indications for treatment with salvarsan 
 are few. The remedy is very well tolerated by tuber- 
 culous persons in all stages. Optic atrophy and 
 diabetes were till recently considered contra-indications, 
 but most authorities consider that salvarsan is harmless 
 in these conditions. 
 
 Herxheimer considers lesions of the heart, fcetid 
 bronchitis, and non-syphilitic disturbances of the optic 
 nerves to be contra-indications. Great caution is 
 required with subjects exhibiting haemorrhagic ten- 
 dency. Arsenic exerts a toxic effect upon the walls 
 of arterioles and capillaries, and the drug should not 
 be given in advanced disease of the heart or arteries, 
 but small thoracic aneurisms have been treated by 
 Wechselmann without any injurious effect. McDonagh 
 considers bulbar paralysis a contra-indication. He 
 also recommends that .care should be exercised in 
 cases complicated by jaundice. 
 
 It is generally conceded that cases of nephritis 
 which are not of syphilitic origin should not be sub- 
 jected to the treatment, unless albuminuria is of sHght 
 degree. 
 
154 SYPHILIS AND PARASYPHILIS 
 
 Treatment in cases of intracranial gumma must be 
 regarded as fraught with danger, and advanced de- 
 generation of the central nervous system or cerebral 
 haemorrhage are considered a contra-indication by the 
 majority of observers. 
 
 Conclusions. 
 
 Ehrlich's idea of therapia stevilisans magna — that is to 
 say, complete and lasting cure of the disease by a 
 single dose of the drug — has undoubtedly been realized 
 in relapsing fever. In the case of syphilis the ques- 
 tion must be held to be ' not proven ' at the present 
 date. Many years must necessarily elapse before one 
 can arrive at a definite decision when dealing with a 
 disease which may lie dormant for as long a period as 
 twenty years, and then recrudesce spontaneously. 
 
 Salvarsan has a striking and rapid effect on the 
 clinical manifestations of syphilis ; this is particularly 
 the case in malignant syphilis when ulcerative lesions 
 of skin and mucous membranes are present. 
 
 Pain disappears as if by magic. 
 
 Salvarsan, when it does produce an alteration of the 
 serum reaction, does so more rapidly than mercury. 
 On the other hand, in the present state of our know- 
 ledge, it would appear that the percentage of negative 
 results after one or two injections is lower than that 
 observed after a year's course of efficient mercurial 
 treatment. 
 
 Spirochaetai disappear in two or three days from all 
 superficial lesions, and the period of infectivity is thus 
 reduced to a minimum — a fact of great sociological 
 importance, especially in military stations. 
 
TREATMENT 155 
 
 The danger of death, of bhndness, or other grave 
 lesion, is so sHght in carefully selected cases that there 
 is no justification for withholding salvarsan. 
 
 The best results are obtained with administration 
 by the intravenous route, but this should only be 
 undertaken by workers who are skilled in the 
 technique. 
 
 Neo-Salvarsan, which is the name that has been 
 given to a neutral preparation of the drug, is a recent 
 modification. It is more easily soluble than salvarsan, 
 and does not require neutralizing with sodium hydrate. 
 It is said to be less toxic than salvarsan, but as the 
 toxicity of salvarsan is minimal, the advantages of 
 the new salt consist chiefly in simplicity in prepara- 
 tion. 0-6 gramme can be mixed with 250 c.c. of 
 sterile distilled water, and injected without any further 
 preparation. This simplicity of preparation, however, 
 is of some importance, as it obviates the possibility of 
 adding an excess of alkali, which excess might alone 
 produce toxic symptoms. The question as to the rela- 
 tive therapeutic value of salvarsan and neo-salvarsan 
 has yet to be proved. 
 
 MERCURY 
 
 As will be seen in the next chapter, the administra- 
 tion of mercury by the mouth does not appear to be 
 nearly as effective as when given intramuscularly in 
 the form of insoluble preparations. The administra- 
 tion of mercury by suppositories appears to have little 
 to recommend it, but mercurial inunctions are very 
 potent. There is, however, but little to choose between 
 
156 SYPHILIS AND PARASYPHILIS 
 
 mercurial inunctions and intramuscular injections, any 
 slight superiority in potency in the former being dis- 
 counted by the obvious social inconvenience of this 
 method of treatment in the majority of cases. The 
 only form of mercurial treatment detailed here, there- 
 fore, will be intramuscular injections. 
 
 Site of Injection. — The most convenient sites for 
 the injections are — 
 
 1. An area at the junction of the middle and 
 
 posterior third of a line from the anterior 
 superior iliac spine to the great trochanter. 
 
 2. The upper and external quadrant of the gluteal 
 
 region. 
 The site of puncture should be cleaned with ether and 
 alcohol, and sterilized with a saturated solution of 
 iodine in chloroform. 
 
 Calomel cream is probably one of the most efficacious 
 preparations, and may be used of such a strength that 
 5 minims of the cream contain 0*75 grains of calomel, 
 10 minims being given as a dose for an adult. 
 
 Mercurial cream can be used of such a strength 
 that 5 minims contain i grain of metallic mercury, 
 10 minims being given as a dose. 
 
 A course of mercurial injections usually consists of 
 twelve doses, the first four of which may be calomel 
 cream, and the last eight mercurial cream. 
 
 A detailed account of mercurial treatment of syphilis 
 lies outside the scope of this work, and will be found 
 in any textbook dealing with syphilis. 
 
 As regards parasyphilis, Dr. Risien Russell is fully 
 convinced of the efficacy of mercury administered by 
 inunction or injection in tabes., and considers that no 
 
TREATMENT 157 
 
 patient in the early stages of this disease should be 
 allowed to go untreated. He has obtained no im- 
 provement in general paralysis. 
 
 This appears to be the opinion of the majority of 
 neurologists. 
 
 A convenient syringe and needle for intramuscular 
 injection are shown in Fig. 22. 
 
 Fig. 22. — Syringe and Needle for Administration of Intra- 
 muscular Injections of Mercurial Cream. 
 
 COMBINED SALVARSAN AND MERCURIAL 
 TREATMENT 
 
 Neisser has given it as his opinion that in order to 
 obtain a curative result it must be better to attack the 
 enemy from two sides rather than from one side alone. 
 He states that it is beyond all doubt that a surer, 
 more brilliant, and more lasting curative effect will 
 follow if we combine the two remedies — salvarsan 
 and mercury. 
 
 The author suggests that the combined treatment 
 should be given as a matter of routine in all cases, 
 and in the following way : 
 
 I. The intravenous injection of o'6 gramme of 
 salvarsan to be repeated in forty-eight hours 
 by a second dose, providing that the tempera- 
 
158 SYPHILIS AND PARASYPHILIS 
 
 ture has been normal for twenty-four hours, 
 and that no nephritis has developed. 
 
 2. This is followed by twelve mercurial intra- 
 
 muscular injections, the first four consisting 
 of calomel cream, and the last eight mercurial 
 cream. 
 
 3. Two more intravenous injections of salvarsan 
 
 are now given. If there is any temperature 
 on the second day after the first intravenous 
 injection of salvarsan, the second dose should 
 not be administered, but should be postponed 
 until the temperature has been normal for 
 twenty- four hours. 
 
 4. The Wassermann reaction should be examined 
 
 two months after the last dose of salvarsan, 
 and, if positive, a second course of mercurial 
 injections should be given. If the reaction 
 is negative, immediate further treatment is 
 not indicated. 
 
 5. The Wassermann reaction should be examined 
 
 every three months for two years, and occa- 
 sionally afterwards, and a further course of 
 treatment undertaken should the reaction 
 return to positive. 
 
CHAPTER XIV 
 
 EFFECT OF TREATMENT ON THE 
 WASSERMANN REACTION 
 
 MERCURY 
 
 The effect of mercurial treatment is usually clearly 
 seen, and depends on the time in the history of the infec- 
 tion that treatment began, and the length and nature of 
 the treatment. Neisser has observed that the earlier in 
 the course of the disease that treatment is commenced, 
 the more probability there is that a negative result will 
 be obtained after a course of treatment. Where treat- 
 ment began as soon as possible after the primary 
 lesion had appeared, 75 per cent, of negative reactions 
 were subsequently obtained, whereas, if treatment has 
 been delayed for six months, only 33 per cent, of 
 negatives were obtained after treatment. 
 
 Of late latent cases — that is, cases several years after 
 infection in which there are no symptoms — he found 
 that the early treated cases gave negative results in 
 80 per cent, of cases, and the late treated cases in only 
 58 per cent. Purckhauer reports the result of treat- 
 ment on 165 cases at different stages of the infection, 
 all of which were positive before treatment. Of 
 116 primary and secondary cases, 75 per cent, became 
 
 159 
 
i6o SYPHILIS AND PARASYPHILIS 
 
 negative ; of 15 late latent cases, 4 became negative; 
 and of 18 tertiary cases only 2 became negative. Of 
 4 cerebral cases only i became negative after treat- 
 ment. The longer infection has persisted, the more 
 stable the positive reaction seems to become, and the 
 greater difficulty there is in inducing a negative re- 
 action after treatment. In some late tertiary and para- 
 syphilitic conditions a negative reaction is never 
 produced even by the most rigorous mercurial 
 treatment. 
 
 Occasionally a case is diagnosed as syphilis and 
 gives a negative reaction, and yet after being on 
 mercury for a while positive reaction is obtained. 
 This probably is due to the fact that the mercury 
 destroys numbers of spirochaetae, whose endotoxins 
 are then liberated, and stimulate the production of the 
 complement-fixing substance. If 5 per cent, of com- 
 plement is fixed, the case must be reported as positive, 
 and 15 per cent, of complement is only used in order 
 to obtain a rough idea of progress under treatment. 
 Active syphilis will generally deviate 10 to 15 per cent, 
 of complement, but as the infection becomes less the 
 amount of complement deviated also becomes less. In 
 this way it is possible to make a rough quantitative 
 measurement of the amount of complement fixed and 
 of the progress made under treatment, even though the 
 case must still be returned as ' positive.' 
 
 Using this method, the author has compared the 
 therapeutic value of some of the different methods of 
 administering mercury. 
 
 The tables in this chapter show the results that 
 were obtained with the various treatments as far as 
 
TREATMENT AND WASSERMANN REACTION i6i 
 
 the Wassermann reaction is concerned. Complete 
 inhibition of haemolysis is indicated by the sign + ; 
 partial inhibition, by the sign ± ; and complete haemo- 
 lysis by the sign - . Complete inhibition of haemo- 
 lysis with both amounts of complement the author 
 calls ' strongly positive,' while ' positive ' denotes 
 that, though there is complete inhibition with the 
 smaller amount of complement, there is haemolysis 
 with the larger amount. If the haemolysis with the 
 smaller amount of complement is partial only, the 
 result is recorded as 'doubtful' All the cases re- 
 corded were ' strongly positive ' before the treatment 
 was commenced, and therefore * positive,' ' doubtful,' 
 and ' negative,' all show influence of treatment in a 
 roughly quantitative manner. Very frequently cases 
 are met with that begin at ' strongly positive,' pass 
 through the * positive ' and ' doubtful ' stages, and 
 end at ' negative.' 
 
 Table V. (Harrison). — Effect of Treatment with 
 Intramuscular Injection. 
 
 
 o 
 
 u 
 
 nal 
 lent. 
 
 nt. 
 some 
 of 
 nt. 
 
 + 
 
 + 
 
 
 -a ^ 
 
 ■sE 
 
 rj t! 
 
 ■n't: V 
 
 £?ti S 
 
 "rt 
 
 c 
 <u 
 
 
 S <3 
 
 
 Addi 
 Compl 
 
 Per 
 
 Showir 
 
 Effe 
 
 Treat 
 
 
 
 H 
 
 u 
 
 u 
 Ph 
 
 After I course 
 
 
 
 
 
 
 
 (of 3 months) 
 
 55 
 
 17 
 
 29 
 
 690 
 
 46 
 
 836 
 
 After 2 courses 
 
 49 
 
 24 
 
 14 
 
 51 -o 
 
 38 
 
 77'5 
 
 >> 3 5> 
 
 42 
 
 8 
 
 19 
 
 809 
 
 27 
 
 64 5 
 
 n 4 M 
 
 30 
 
 3 
 
 14 
 
 90*0 
 
 17 
 
 .56-5 
 
 >> 5 M 
 
 34 
 
 4 
 
 13 
 
 88-2 
 
 17 
 
 50-0 
 
 ,, 6 „ 
 
 26 
 
 3 
 
 6 
 
 S8-4 
 
 9 
 
 34-6 
 
 II 
 
l62 
 
 SYPHILIS AND PARASYPHILIS 
 
 Pills and suppositories seem to be of the slowest 
 and least efficient forms of treatment, and inunctions 
 and intramuscular injections of insoluble compounds 
 the quickest and most efficient. Harrison has shown 
 clearly the influence of only short treatment, for, 
 although the percentage of * positives' remains high, 
 some effect of treatment is recorded in 69 per cent, of 
 cases after only one course (see Table V.). 
 
 With pills, on the other hand, 95 per cent, of cases 
 treated for six months or under are positive, and 
 only 5 per cent, show any effect of treatment (see 
 Table VI.). 
 
 Table VI. — Pills (122 Tests). 
 
 Wassermann Reaction with less than Six Months' Treat- 
 ment in 45 Cases. 
 
 Complement, per cent. 
 Wassermann reaction . . 
 
 Number of cases 
 Percentage of cases 
 
 5 15 
 
 4- 4- 
 
 Strongly 
 
 positive. 
 
 41 
 91 
 
 5 15 
 
 4- - 
 
 Positive. 
 2 
 
 4 
 
 5 15 
 ± - 
 
 Doubtful. 
 
 I 
 
 2-5 
 
 5 15 
 
 Negative. 
 
 I 
 
 2-5 
 
 Wassermann Reaction with Six to Twelve Months' Treat- 
 ment in 33 Cases. 
 
 Complement, per cent. 
 
 5 15 
 
 5 
 
 
 15 
 
 5 
 
 15 
 
 5 
 
 15 
 
 Wassermann reaction . . 
 
 4- + 
 
 4- 
 
 
 
 4- 
 
 
 
 
 Number of cases 
 
 20 
 
 
 ^ 
 
 
 3 
 
 
 
 7 
 
 Percentage of cases 
 
 61 
 
 
 9 
 
 
 9 
 
 
 
 21 
 
TREATMENT AND WASSERMANN REACTION 1G3 
 
 Wassermann Reaction ivith Treatment for Eighteen Months 
 or Over in 44 Cases. 
 
 Complement, per cent. 
 Wassermann reaction . . 
 Number of cases 
 Percentage of cases 
 
 5 15 
 
 ^■ + 
 
 8 
 
 18 
 
 5 15 
 
 + - 
 
 5 
 II 
 
 5 15 
 ± 
 
 10 
 22 
 
 5 15 
 
 21 
 
 48 
 
 When the inunction method was employed, after 
 three months' treatment, only i6-6 per cent, remained 
 positive. Daily inunction is obviously an inconvenient 
 method of treatment, and all skins do not tolerate this 
 method, but otherwise inunction would seem by this 
 too short series to be the most satisfactory form of 
 administration of mercury. The author has had but 
 little opportunity of investigating the effect on the 
 reaction of treatment by inunction or suppositories, but 
 the short series examined have been recorded in 
 Tables VII. and VIII. 
 
 Table VII. — Suppositories (33 Cases). 
 Treatment for Six Months and Under, 
 
 Complement, per cent. 
 Wassermann reaction . . 
 Number of cases 
 Percentage of cases 
 
 5 15 
 + + 
 
 20 
 
 61 
 
 5 15 
 
 + - 
 
 6 
 
 18 
 
 5 15 
 + - 
 
 4 
 12 
 
 5 15 
 
 3 
 9 
 
164 
 
 SYPHILIS AND PARASYPHILIS 
 
 Table VIII. — Inunction (26 Cases). 
 Treatment of Two to Three Months. 
 
 Complement, per cent. 
 
 5 
 
 15 
 
 5 15 
 
 5 
 
 15 
 
 5 15 
 
 Wassermann reaction . . 
 
 -H 
 
 + 
 
 + - 
 
 + 
 
 - 
 
 - - 
 
 Number of cases 
 
 
 3 
 
 10 
 
 
 3 
 
 10 
 
 Percentage of cases 
 
 
 Hi 
 
 384 
 
 
 Hi 
 
 38^ 
 
 Table IX. — Calomel Intramuscular Injections 
 (109 Tests). 
 
 Wassermann Reaction after One Course of Twelve Injections 
 
 in 54 Cases. 
 
 Complement, per cent. 
 
 5 15 
 
 5 15 
 
 5 
 
 15 
 
 5 
 
 15 
 
 Wassermann reaction . . 
 
 + + 
 
 + 
 
 + 
 
 — 
 
 - 
 
 - 
 
 Number of cases 
 
 27 
 
 13 
 
 5 
 
 
 
 9 
 
 Percentage of cases 
 
 50 
 
 24 
 
 9 
 
 
 
 16 
 
 Wassermann Reaction after Two Courses in 35 Cases. 
 
 Complement, per cent. 
 Wassermann reaction . . 
 Number of cases 
 Percentage of cases 
 
 5 15 
 
 4- 4- 
 II 
 
 31 
 
 5 15 
 
 4- - 
 
 7 
 20 
 
 5 15 
 ± - 
 
 4 
 II 
 
 5 15 
 
 13 
 
 37 
 
 Wassermann Reaction after Three Courses in 20 Cases. 
 
 Complement, per cent, 
 Wassermann reaction . , 
 Number of cases 
 Percentage of cases 
 
 5 T-5 
 
 4- 4- 
 
 2 
 
 10 
 
 5 15 
 
 4- - 
 
 2 
 
 10 
 
 5 15 
 ± - 
 
 
 
 
 
 5 15 
 
 16 
 80 
 
TREATMENT AND WASSERMANN REACTION 165 
 
 Intramuscular injection, however, appears almost, 
 if not quite, as potent as inunction, and to be undeni- 
 ably superior to pill treatment. That it is not the 
 presence of the mercury itself in the blood that produces 
 a negative reaction, was shown by Bauer, who 
 demonstrated that a strong positive can be obtained 
 when the mercury excretion in the urine is most 
 marked, and that a negative reaction may be present 
 when the mercury excreted in the urine is weak or 
 absent. He showed that a previous negative reaction 
 may become positive in spite of a large quantity of 
 mercury in the blood, and that a reaction which has 
 become negative under treatment can become positive 
 in spite of mercury persisting in the urine. 
 
 Nearly all authorities, both Continental and Ameri- 
 can, agree that in the future treatment, whether by 
 mercury or salvarsan, must be regulated by the 
 Wassermann reaction. A solitary negative reaction 
 obtained with the serum of a patient undergoing 
 mercurial or salvarsan treatment means little but that 
 the patient is reacting to the treatment. A sevies of 
 negative results taken at intervals of three to six 
 months after ail treatment has been given up is neces- 
 sary before the patient can be regarded as cured, and even 
 then until another twenty years have passed we can- 
 not be absolutely certain that the disease is completely 
 and permanently obliterated, and that no late manifesta- 
 tions will ever occur. It is important to remember that 
 about 10 per cent, of untreated cases of syphilis fail to 
 give a positive reaction at the first examination, and 
 that therefore a negative reaction only gives a 90 per 
 cent, probability of freedom from infection. If, in 
 
i66 SYPHILIS AND PARASYPHILIS 
 
 recently acquired syphilis, after several months' treatment, 
 the reaction still remains strongly positive, and large 
 doses of complement are still fixed, it is an indication 
 that the treatment is inefficient, and that more rigor- 
 ous methods should be adopted. If, however, after 
 each course of treatment a smaller amount of comple- 
 ment is fixed, or the intervals before a positive reaction 
 returns become longer and longer, we may conclude 
 that the treatment is satisfactory, and that there is no 
 necessity to increase the dose. 
 
 The author's further experience confirms his original 
 conclusions, that inunction and intramuscular injection 
 are by far the most rapid methods of producing a nega- 
 tive Wassermann reaction by mercurial treatment. 
 
 SALVARSAN 
 
 Salvarsan usually produces a negative reaction 
 more quickly than mercury, but apparently the 
 percentage of negative results after one or two intra- 
 venous injections of the doses employed (0-4 gramme) 
 is lower than that observed after a year's course of 
 efficient mercurial treatment. The following results 
 were obtained in fifty cases where the reaction could 
 be followed for several months : 
 
 Changed from positive to negative . . • • 31 
 
 Reduced quantity of complement fixed . . . . 7 
 
 Reaction unchanged . . . . . . . . 6 
 
 Relapsed from negative to positive . . . . 6 
 
 Of the total 50 cases treated with salvarsan and 
 examined four weeks and over after treatment, 30 
 (60 per cent.) became negative, while, when examined 
 under four weeks, only 9 (18 per cent.) were negative. 
 
TREATMENT AND WASSERMANN REACTION 167 
 
 The results obtained which give 42 per cent, nega- 
 tive after intramuscular injections, 52 per cent, after 
 one intravenous injection, and 74 per cent, after two 
 intravenous injections, seem to indicate that the intra- 
 venous route is the best, and that at least two injections 
 should be given (see Table X.). 
 
 The dose given in the great majority of intravenous 
 cases was 0*4 gramme, and now that we know that 
 usually larger doses can safely be employed, we may 
 hope to obtain a higher percentage of negative results 
 and a lower percentage of relapses. 
 
 Table X. — Injections of Salvarsan (200 Tests). 
 
 Wassevmann Reaction Four Weeks after One Intravenous 
 Injection in 21 Cases. 
 
 Complement, per cent. 
 
 5 
 
 15 
 
 5 15 
 
 5 15 
 
 5 15 
 
 Wassermann reaction . . 
 
 + 
 
 + 
 
 + - 
 
 + - 
 
 
 Number of cases 
 
 
 3 
 
 5 
 
 2 
 
 II 
 
 Percentage of cases 
 
 
 14 
 
 24 
 
 10 
 
 52 
 
 Wassermann Reaction Four to Eight Weeks after Two 
 Intravenous Injections in 50 Cases. 
 
 Complement, per cent. 
 
 5 
 
 15 
 
 5 
 
 
 15 
 
 5 
 
 15 
 
 5 15 
 
 Wassermann reaction . . 
 
 + 
 
 + 
 
 + 
 
 
 
 -H 
 
 
 
 Number of cases 
 
 
 6 
 
 
 ^ 
 
 
 4 
 
 
 37 
 
 Percentage of cases 
 
 
 12 
 
 
 6 
 
 
 8 
 
 
 74 
 
1 68 
 
 SYPHILIS AND PARASYPHILIS 
 
 Wassevmann Reaction Four to Eight Weeks after Intra- 
 muscular Injection of Salvarsan in 12 Cases. 
 
 Complement, per cent. 
 Wassermann reaction . . 
 Number of cases 
 Percentage of cases 
 
 5 15 
 
 + + 
 
 5 
 
 42 
 
 5 15 
 
 + - 
 
 I 
 8 
 
 5 15 
 ± - 
 
 I 
 
 8 
 
 5 15 
 
 5* 
 42 
 
 Relapses. — Wassermann Reaction Six to Twelve Months 
 after Two ov move Intravenous Injections of Salvarsan 
 in 37 Cases that had become Negative as the Result of 
 such Treatment. 
 
 Complement, per cent. 
 Wassermann reaction . , 
 Number of cases 
 Percentage of cases 
 
 5 15 
 
 + + 
 
 2-0 
 5-5 
 
 5 15 
 
 + - 
 
 3 
 
 8 
 
 5 15 
 ± - 
 
 20 
 
 55 
 
 5 15 
 
 30 
 
 81 
 
 It will be seen from Table X. that over 70 per cent, of 
 cases treated with salvarsan became negative in from 
 four to eight weeks after the second intravenous 
 injection, and that 80 per cent, of these negatives 
 remained negative six to twelve months afterwards. 
 Over 50 per cent., therefore, of cases that before treat- 
 ment were strongly positive became negative, and 
 still remained so when examined six to twelve 
 months after treatment. Of course, a negative re- 
 action persisting for six to twelve months does not 
 necessarily mean permanent cure, but it is at least 
 extremely encouraging that there is no pathological evi- 
 dence of relapse in over half the cases. In some cases 
 salvarsan, even in repeated doses (sometimes as many 
 
 * Two of these relapsed to positive or doubtful. 
 
TREATMENT AND WASSERMANN REACTION 169 
 
 as six have been given), has no effect whatever on the 
 reaction. The author is inclined to think that cases 
 that are going to relapse will show evidence of such 
 relapse by the Wassermann reaction in under six 
 months in the great majority of instances. On 
 comparing Tables VI., IX., and X., it will be seen 
 that only 48 per cent, of cases treated with pills 
 become negative after eighteen months' treatment, 
 whereas 80 per cent, become negative after three 
 courses (one year's treatment) of intramuscular in- 
 jections. How many of these, however, would remain 
 negative six months later if all treatment were dis- 
 continued it is impossible to say, as the author had 
 not opportunities for such investigation. At the 
 London Lock Hospitals considerable difficulty is 
 experienced in getting patients to return for blood- 
 examination after they have severed their connection 
 with the hospital. 
 
 Table XI. shows the periods at which reactions 
 became negative in seven cases in which several 
 examinations have been made over the period of 
 twelve months. 
 
 Table XI. 
 
 
 ^ 
 
 
 
 
 
 
 u § 
 
 
 
 
 Month. 
 
 
 E 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 1; rt 
 
 
 
 
 
 
 
 
 
 
 
 
 W JJ 
 
 I. 
 
 2. 3. 
 
 4- 
 
 5- 
 
 6. 7. 
 
 8. 
 
 Q. 
 
 10. 
 
 II. 
 
 12. 
 
 M. 15. 
 
 H 
 h + 
 
 
 
 
 
 
 
 
 
 
 — 
 
 
 _ 
 
 
 1 
 
 
 
 S. C. 
 
 \- + 
 
 
 
 
 
 - - 
 
 + - 
 
 
 
 
 - - 
 
 
 - _ 
 
 C. D. 
 
 + + 
 
 
 - - 
 
 
 
 
 
 - — 
 
 
 
 
 
 - _ 
 
 E. H. 
 
 + + 
 
 
 
 - - 
 
 
 - - 
 
 
 - - 
 
 
 
 
 - - 
 
 - - 
 
 M. L. 
 
 f + 
 
 + - 
 
 f + 
 
 + - 
 
 
 
 
 
 
 
 - - 
 
 
 - _ 
 
 H. S. 
 
 f + 
 
 + - 
 
 f ± 
 
 ± - 
 
 1- — 
 
 
 
 rl- - 
 
 
 
 - - 
 
 
 - - 
 
 A. S. 
 
 \- + 
 
 
 
 ± - 
 
 
 ± - 
 
 
 
 
 ± - 
 
 
 
 ~ ~ 
 
170 
 
 SYPHILIS AND PARASYPHILIS 
 
 Table XII. gives the results obtained in the seven 
 cases in which the quantity of complement - fixing 
 substance was reduced by salvarsan treatment although 
 a negative reaction was not obtained. 
 
 Table XII. — Incomplete Results. 
 
 
 ^ c Month. 
 
 Bef( 
 Treatr 
 
 2. 
 
 3- 
 
 4- 
 
 5- 
 
 6. 
 
 ± - 
 ± - 
 
 + - 
 
 7- 
 
 8. 
 
 9- 
 
 10. 
 
 II. 
 
 12. 
 
 F. H. 
 M. S. 
 J.B. 
 R. C. 
 
 w. e. 
 
 E. H. 
 A. H. 
 
 1 
 + -' 
 + +.+ + 
 
 + +1 
 
 + - + - 
 
 + -| 
 
 + +'+ + 
 
 ± - 
 + + 
 
 + ± 
 ± - 
 
 ± - 
 
 + + 
 
 - - 
 
 
 + - 
 
 
 + - 
 
 
 
 All the six relapses occurred during the first six 
 months following treatment, such cases that were 
 negative six months after treatment still being negative 
 after twelve months (see Table XIII.). 
 
 Table XIII. — Relapses. 
 
 
 
 Month. 
 
 I. 2. 
 
 3- 
 
 4- 5- 
 
 6. 
 
 7. s. 
 
 9- 
 
 10. 
 
 ir. 
 
 12. 
 
 E. D. 
 N. H. 
 B. L. 
 E. R. 
 L. W. 
 L. W. 
 
 + + 
 + + 
 + + 
 + + 
 + + 
 + + 
 
 - -'+ - 
 
 - - + ± 
 
 4_ 
 
 + - 
 + - 
 ± - 
 + - 
 
 + + 
 
 + + 
 
 + + 
 
 
 
 
 
 
 
 ^ 
 
TREATMENT AND WASSERMANN REACTION 171 
 
 If rapidity of change of reaction be taken as a test 
 of efficiency of treatment, the author would place 
 salvarsan first, inunction or intramuscular injection 
 of insoluble mercury compounds second, and mercurial 
 pills and suppositories a bad third. The author con- 
 siders the results obtained suggest the advisability of 
 combined salvarsan and mercurial treatment. 
 
CHAPTER XV 
 
 ANAPHYLAXIS AND SYPHILIS 
 
 By anaphylaxis is meant a condition of increased sen- 
 sitiveness to any antigen as the result of inoculation 
 with such antigen. 
 
 It is therefore the opposite of immunity, which is a 
 state of decreased sensitiveness to the antigen. 
 
 Anaphylactic phenomena, like immunity phenomena, 
 are the result of an antigen-antibody reaction, and are 
 strictly specific in nature. Thus a state of anaphylaxis 
 to any given antigen can only be produced by a second 
 inoculation with the same kind of antigen, and after suffi- 
 cient time has elapsed to permit of the development 
 of the corresponding antibody. 
 
 Although the phenomenon is the result of a specific 
 antigen - antibody reaction, the symptoms of acute 
 anaphylaxis are similar whatever the antigen used 
 may be, whether serum, organism, toxin, or other 
 foreign proteid. 
 
 Two varieties of hypersensitiveness to serum de- 
 serve special mention, as they are typical of ana- 
 phylactic phenomena, however produced : 
 
 I. Arthus' Phenomenon. — Arthus' phenomenon 
 appears when a guinea-pig receives several sub- 
 cutaneous injections, at intervals of a few days, of 
 normal horse serum, a substance which in itself is 
 
 172 
 
ANAPHYLAXIS AND SYPHILIS 173 
 
 scarcely more toxic than normal solution. After a 
 few such inoculations the animal becomes hyper- 
 sensitive, or anaphylactized, and after another injection 
 an oedematous mass, an aseptic abscess, or an area 
 of necrosis, appears at the site of a new inoculation, 
 which need not be in a region in which a previous 
 injection has been made ; the alteration is a general, 
 and not a local one. After several of these injections 
 the animal becomes cachectic, and dies after several 
 weeks. 
 
 2. Theobald Smith's Phenomenon. — Theobald 
 Smith's phenomenon occurs when an animal has been 
 sensitized by a very small injection of horse serum, 
 and kept for a fortnight or more. If, then, a second 
 injection of a larger amount of the same serum be 
 made, the animal develops a series of remarkable 
 symptoms, the most noteworthy being respiratory 
 failure, paralysis, and clonic spasms. Symptoms 
 usually appear within ten minutes, and death occurs 
 within an hour. Death does not always follow. The 
 less sensitive the animal the later the development of 
 symptoms, and the greater the chance of survival. 
 The process evidently affects the nervous system in 
 a very special way. 
 
 Various phenomena that sometimes occur during 
 the course of syphilitic infection may perhaps be the 
 result of a state of anaphylaxis to the toxin produced 
 by the SpirochcBta pallida. Thus — 
 
 The Jarisch Herxheimer Reaction (the tem- 
 porary lighting-up of symptoms very occasionally 
 produced by an injection of salvarsan or by a large 
 mercurial inunction) ; 
 
174 SYPHILIS AND PARASYPHILIS 
 
 Salvarsan Fever, accompanied by rigors, vomit- 
 ing, headache, diarrhoea, etc., that occasionally occurs 
 in florid syphilis ; 
 
 And Justus' Test, in which a fall in the haemo- 
 globin content of the blood follows a large inunction 
 or injection of mercury ; 
 
 may all possibly be caused by a state of anaphylaxis 
 produced by the setting free of a large quantity of 
 specific endotoxin as the result of destruction of the 
 spirochaetae. 
 
 Of the very few deaths following the administration 
 of salvarsan that cannot be explained by errors in 
 technique, several have been preceded by symptoms 
 suggestively similar, in the author's opinion, to those 
 occurring in acute anaphylaxis of the Theobald Smith 
 type. 
 
 Studies in anaphylaxis by numerous observers have 
 shown that the hypersensitiveness to the foreign pro- 
 tein (antigen) takes some time to develop, and does 
 not develop at all if the inoculation process is con- 
 tinuous ; in other words, there must be a cessation of 
 inoculations for a certain period of time, generally 
 about ten to fourteen days, before the anaphylactic 
 phenomenon develops, and the continuance of the 
 inoculations at regular short intervals does not pro- 
 duce anaphylaxis. 
 
 NOGUCHFS LUETIN REACTION 
 
 Noguchi points out that an anaphylactic condition 
 is more likely to develop in those patients who are 
 infected with certain organisms which remain in their 
 
ANAPHYLAXIS AND SYPHILIS 175 
 
 bodies for a long period, during which their activity 
 undergoes fluctuations either spontaneously or as the 
 result of treatment. He considers that the clinical 
 course of syphilis indicates that the infective agent 
 (the Spirochata pallida) fulfils all the requirements that 
 lead to the development of an anaphylactic condition 
 in syphilitic patients. He therefore concludes that an 
 anaphylaxis test should theoretically be as possible in 
 syphilis as in tubercle with Koch's tuberculin test, or 
 with Von Pirquet's cutaneous test, or in glanders with 
 the Malein test. He uses extracts of pure cultures of 
 the Spirochidta pallida as antigen, and to this extract 
 has given the name of ' Luetin.' 
 
 The experiments on rabbits proving successful, he 
 proceeded to test the reaction in man, using the intra- 
 dermic method of inoculation. 
 
 Mantoux and Roux in their original description 
 of the technique of intradermic inoculation, say : 
 ' After having made a fold of skin, the needle is 
 pushed in almost parallel to the surface. Care must 
 be taken that the bevelled side of the needle-point is 
 turned upwards. In subjects with a very thin skin one 
 must boldly push the needle in till it enters the hypo- 
 dermic region, and then elevate the point and enter the 
 dermis from its under-surface. A fine needle and 
 small syringe are required, which must^ of course, be 
 sterilized before use. Only one drop of fluid is injected.' 
 
 Of 250 control non-syphilitic cases examined, all 
 gave negative reactions ; while of 315 cases of syphilis 
 at different stages, 213 gave a positive reaction. 
 
 Noguchi points out that theoretically one would not 
 expect an anaphylactic reaction to appear as long as 
 
176 SYPHILIS AND PARASYPHIUS 
 
 the activity of the Spivochcsta pallida is maintained at 
 its maximum, as would be the case during the early 
 period of infection. This theory was borne out by the 
 results obtained, practically all cases of primary 
 syphilis and secondary syphilis with symptoms giving 
 negative results, as also did congenital syphilitics under 
 one year of age. The majority of cases, however, to 
 which the test was applied after treatment, with a con- 
 sequent absence of symptoms and diminution in the 
 activity of the spirochaete, gave a positive reaction 
 (see Table XIV.). 
 
 Negative Reaction. 
 
 In the majority of normal persons after twenty-four 
 hours, a small erythematous area appears round the 
 point of injection ; there is no pain or itching, and the 
 reaction passes off within forty-eight hours and leaves 
 no induration. Occasionally a small papule may be 
 formed after twenty-four to forty-eight hours, which, 
 however, begins to subside within seventy-two hours, 
 leaving no induration. 
 
 Positive Reaction. 
 
 This Noguchi divides under three headings : 
 I. Papular Form. — A large, raised, reddish, in- 
 durated papule, usually from 5 to 10 millimetres in 
 diameter, makes its appearance in twenty-four to forty- 
 eight hours. The papule may be surrounded by a 
 zone of redness. The dimension and degree of indura- 
 tion slightly increase during the following three or 
 four days, after which the inflammatory processes 
 
ANAPHYLAXIS AND SYPHILIS 
 
 177 
 
 
 
 1- 
 
 c 
 
 
 
 
 •S3SB3 
 
 DUTjiqd^g 
 
 1 
 
 
 
 
 8 
 
 
 + 
 
 
 
 
 
 > 10 
 p) 
 
 •S[EnpiAipui 
 
 ITJIUJO'^ 
 
 1 
 
 
 
 IT) 
 
 
 
 + : : : 
 
 
 
 
 J 
 
 a a 
 
 1 
 
 + 
 
 ^ : : 
 
 
 ~o 1 
 
 „\ 
 
 
 
 
 ^J 
 
 ( " 
 
 ( - 
 
 Cerebro- 
 spinal 
 Syphilis. 
 
 •1U3S3JJ 
 
 buioiduiXg 
 
 1 
 
 I "^ 
 
 lo 
 
 °- 
 
 + 
 
 '. '. "^ 
 
 10 J 
 
 _ -535^3 
 
 1 
 
 
 : " 
 
 
 " ] 
 
 >■ '^ 
 
 0) ^ 
 
 3?HT[ 
 
 + 
 
 
 in ON T*- 
 
 tsOO. 
 
 0^ 
 
 •4B3A 3U0 
 
 1 
 
 
 00 n 
 
 
 
 ^ j.pun 
 
 + 
 
 
 10 H ; 
 
 VO 
 
 / 
 
 •jussqv 
 
 1 
 
 
 : w ro -^ j 
 
 00 
 
 
 suioiauiAg 
 
 + 
 
 
 
 
 Tert 
 Sypl 
 
 ■JU3S3JJ 
 
 1 
 
 
 
 
 
 siuo:idiuAg 
 
 + 
 
 
 (N M 
 
 M ro 
 
 
 
 •}U3sqv 
 siuojduiAg 
 
 . 1 
 
 1 
 
 ro N 
 
 "^ 
 
 ON 
 
 + 
 
 
 ■^ (N VO 
 M rj- in 
 
 •1U3S3J(J 
 
 suiGjduiAg 
 
 1 
 
 
 IT) 
 
 
 + 1 : 
 
 Pi ; H 
 
 ro 
 
 Primary 
 Syphilis. 
 
 •1U3S3J(J 
 
 siuoidtuAg 
 
 1 
 
 M M • • 
 
 "1 
 
 
 + 
 
 : - : : -) 
 
 . 1 
 
 
 c 
 
 tj 
 
 11 
 
 u 
 
 c 
 
 V 
 
 i-S ^ s s g 
 
 -§, iJ Sri -as 
 ^^ P 4-. S 4j <« <^ 
 a a ij >-, a; rt w 
 rt S ^ 6 J2 S .^ - 
 4-1 ti •>-' ^ ■" P '^ 
 
 
 12 
 
178 SYPHILIS AND PARASYPHILIS 
 
 begin to recede. Induration disappears within a week 
 in the majority of cases. 
 
 2. Pustular Form. — In this form at about the 
 fourth day after injection the papule begins to soften at 
 the centre, and within twenty-four hours becomes first 
 vesicular, then pustular. The pustule soon discharges, 
 and a scab is formed, which falls oif after a few days. 
 This form of the reaction occurred in nearly every case 
 of tertiary or late hereditary syphilis. 
 
 3. Torpid Form. — In this, the least common form, 
 the reaction pursues a course practically similar to a 
 negative reaction, but after ten days, or even longer, 
 the reaction lights up again and progresses to the 
 formation of a small pustule. 
 
 Noguchi states that neither in syphilitics nor in para- 
 syphilitics did a marked constitutional change follow 
 the intradermic inoculation of luetin. In most positive 
 cases a slight rise in temperature takes place, lasting 
 for one day. 
 
 The author up to the present has had no opportunity 
 of investigating this test, but if extended trials by inde- 
 pendent observers confirm the results obtained by 
 Noguchi, it would appear that this test will be of con- 
 siderable diagnostic value. 
 
 As, however, this test is not available for early con- 
 genital syphilis, primary syphilis, or early secondary 
 syphilis, it does not appear probable that it will be of 
 very great practical use, except as a confirmatory test 
 in those cases of doubtful latent or tertiary syphilis 
 which fail to give a positive Wassermann reaction. 
 
CHAPTER XVI 
 
 LIFE INSURANCE AND THE WASSER- 
 MANN REACTION 
 
 Syphilis by itself is accountable for a comparatively 
 small number of deaths, with the exception of deaths 
 of children under five years owing to congenital 
 syphilis. 
 
 If, however, the sum of all the deaths produced by 
 diseases either directly or indirectly resulting from 
 previous syphilitic infection be collected together, a 
 considerable number of deaths will be found attribut- 
 able to the SpirochcBta pallida. 
 
 If to this already considerable death-rate we add 
 deaths from intercurrent diseases having nothing to do 
 with syphilis, but in which one may reasonably con- 
 clude that the resisting power of the individual was 
 lowered by syphilitic infection so that a higher death- 
 rate resulted than would have been the case if these 
 diseases had attacked patients free from syphilis, then 
 the death-rate due to diseases in which syphilis is one 
 of the predisposing causes will probably be greatly 
 increased. 
 
 REGISTRAR-GENERAL'S REPORT 
 
 I. Deaths from Syphilis alone.— The Registrar- 
 General's report for 1909 gives the death-rate under 
 
 179 
 
i8o SYPHILIS AND PARASYPHILIS 
 
 the head ' Syphilis ' as 0-047 per thousand persons. 
 This includes 968 deaths amongst males and 717 
 amongst females. Far the greatest number of deaths 
 occurred in children under five years of age, and con- 
 sisted of 677 males and 540 females. Of deaths 
 between the ages of twenty-five and fifty-five, only 
 206 occurred amongst males and 117 amongst females. 
 Syphilis, therefore, as the direct cause of death 
 amongst adults during the period when the majority 
 of people seek insurance, is small. 
 
 2. Deaths from Diseases Syphilitic in Origin. — 
 The deaths from the three diseases — general paralysis, 
 tabes, aneurism of the aorta — however, which are 
 undoubtedly syphilitic in origin, give very different 
 results. 
 
 General paralysis was given as the cause of death 
 of 1,817 males and 546 females, and of this number 
 1,386 deaths occurred amongst males and 338 amongst 
 females between the ages of twenty -five and fifty-five 
 years. The total death-rate per 1,000 from general 
 paralysis was o'o66. 
 
 The death-rate from tabes was about one-third that 
 from general paralysis, and about half the number of 
 deaths out of the total, both of males and females, 
 occurred between twenty-five and fifty-five years of 
 age. ^ > 
 
 The death-rate from aneurism is 0*033; 94^ 
 occurred amongst males and 221 amongst females, 
 and of this number 558 and 82 respectively occurred 
 between the ages of twenty-five and fifty-five. 
 
 The total death-rate from general paralysis, tabes, 
 and aneurism combined, therefore, is o-ii6 per 1,000, 
 
INSURANCE AND THE WASSERMANN REACTION i8i 
 
 and the great majority of these occurred between the 
 ages of twenty-five and fifty-five years. 
 
 It has been shown in the previous chapters that 
 practically all causes of general paralysis and aneurism 
 and 60 per cent, of tabes give a positive Wassermann 
 reaction, and in all probability have given a positive 
 Wassermann reaction for many years before the onset 
 of symptoms. It therefore appears highly desirable, 
 from the point of view of the insurance companies, 
 that the possibihty of the occurrence of these diseases 
 should be excluded if the life is to be returned as a 
 first-class one. 
 
 The death-rate per 1,000 from all causes was 14*5, 
 while the combined death-rate from syphilis, general 
 paralysis, tabes, and aneurism was 0*163 per 1,000. 
 One death in every eighty-eight, therefore, was due to 
 syphilis, parasyphiHs, or aneurism. 
 
 Table XV. 
 
 
 Deaths per 
 
 
 
 
 Cause of Death. 
 
 1,000 
 Persons. 
 
 
 Males. 
 
 Females. 
 
 
 
 All ages 
 
 968 
 
 717 
 
 Syphilis 
 
 0-047 ] 
 
 Under 5 
 
 677 
 
 540 
 
 
 
 25 to 55 
 
 206 
 
 117 
 
 
 f 
 
 All ages 
 
 1,817 
 
 546 
 
 General paralysis . . 
 
 o-o66 < 
 
 Under 5 
 
 I 
 
 
 
 
 [ 
 
 25 to 55 
 
 1,386 
 
 33S 
 
 
 I 
 
 All ages 
 
 496 
 
 123 
 
 Tabes 
 
 o"oi7 \ 
 
 Under 5 
 
 
 
 
 
 
 I 
 
 25 to 55 
 
 250 
 
 59 
 
 
 f 
 
 All ages 
 
 946 
 
 221 
 
 Aneurism 
 
 0-033 -I 
 
 Under 5 
 
 I 
 
 I 
 
 
 
 25 to 55 
 
 558 
 
 82 
 
1 82 
 
 SYPHILIS AND PARASYPHILIS 
 
 Table XVI. 
 
 Deaths per 
 
 
 
 
 Cause of Death. 
 
 i,ooo 
 
 
 Males. 
 
 Females. 1 
 
 Persons. 
 
 
 
 i 
 
 Cerebral haemorrhage 
 
 0-502 - 
 
 All ages 
 
 7,999 
 
 9.939 
 
 and cerebral embo- - 
 
 Under 5 
 
 17 
 
 20 
 
 lism . . 
 
 [ 
 
 25 to 55 
 
 1,289 
 
 1,618 
 
 Chronic Bright's | 
 disease . . . . j 
 
 
 All ages 
 Under 5 
 
 5.627 
 
 4.877 
 
 0294 ■ 
 
 35 
 
 34 
 
 ( 
 
 25 to 55 
 
 1,899 
 
 1,707 
 
 Apoplexy and hemi- \ 
 plegia .. .. !/ 
 
 0*226 - 
 
 All ages 
 Under 5 
 25 to 55 
 
 3.609 
 
 9 
 
 540 
 
 4,485 
 
 7 
 
 688 
 
 
 
 0-149 - 
 
 All ages 
 
 2,902 
 
 2,442 
 
 Meningitis 
 
 
 Under 5 
 
 1,862 
 
 1. 471 
 
 
 
 25 to 55 
 
 325 
 
 287 
 
 
 
 ' 
 
 All ages 
 
 392 
 
 377 
 
 Brain tumour 
 
 
 0"022 - 
 
 Under 5 
 
 22 
 
 12 
 
 
 
 
 25 to 55 
 
 192 
 
 204 
 
 
 
 o'o6o - 
 
 All ages 
 
 1,105 
 
 1,023 
 
 1 Softening of the brain 
 
 Under 5 
 
 2 
 
 
 
 . 
 
 25 to 55 
 
 no 
 
 129 
 
 Paraplegia and dis- \ 
 eases of the cord . . / 
 
 1 
 
 0-059 - 
 
 All ages 
 Under 5 
 
 1. 15'' 
 47 
 
 948 
 48 
 
 25 to 55 
 
 400 
 
 Per Cent. 
 
 311 
 
 
 
 
 
 Per Cent. 
 
 
 
 
 All ages 
 
 15*4 
 
 137 
 
 All causes 
 
 
 14-5 
 
 Under 5 
 
 40-3 
 
 33-2 
 
 1 
 i 
 
 
 25 to 55 
 
 3I-I 
 
 24-8 
 
 Total deaths, all persons, 25 to 55, 111,122. 
 
 ,, ,, Table XV.. ,, 2,996 ( = 1 in 37) deaths. 
 
 ,, ,, Table XVI.. ,, 9,699 ( = 1 in ii) ,, 
 
 3. Deaths from Diseases partly Attributable 
 to Syphilis. — The deaths partly attributable to 
 syphilis will include those from : 
 
 1. Cerebral haemorrhage and cerebral embolism. 
 
 2. i\poplexy and hemiplegia. 
 
 3. Chronic Bright's disease. 
 
INSURANCE AND THE WASSERMANN REACTION 1S3 
 
 4. Meningitis. 
 
 5. Brain tumour. 
 
 6. Softening of the brain. 
 
 7. Paraplegia and diseases of the cord. 
 
 Table XVI. shows the death-rate per 1,000 persons 
 from these diseases, also occurring amongst males 
 and females during the period of twenty-five to fifty- 
 five years. 
 
 4. Deaths in which Syphilis may be a Con- 
 tributory Cause. — It is difficult to estimate the 
 deaths occurring in this class — namely, amongst those 
 debilitated by syphilis, in which death might not have 
 occurred otherwise. It is, however, a matter of 
 common knowledge that tuberculosis is especially 
 apt to develop amongst persons who have recently 
 acquired syphilis, and that tuberculosis occurring in 
 such subjects is particularly to be dreaded. 
 
 INCREASED MORTALITY RATE AMONGST 
 SYPHILITICS 
 
 Brockbank has collected the following statistics of 
 the experience of assurance companies of the mortality 
 of syphilitics, which are of great interest, and appear 
 to point conclusively to the importance of a routine 
 examination of the blood of all proposers for assurance. 
 Practically every series of investigations shows a con- 
 siderably increased mortality amongst syphilitics. 
 
 Runeberg's statistics show that out of 84 cases 
 of acknowledged syphilitic infection, the average age 
 of death was 43-4 years, and out of 734 cases that 
 
1 84 SYPHILIS AND PARASYPHILIS 
 
 had probably had syphilis, 15 per cent, of the deaths 
 were probably directly due to syphilis. 
 
 Tiselius recorded 650 deaths due to syphilis out of 
 5,175 persons (i7"35 per cent.), and he recommended 
 an increased premium of from 20 to 50 per cent, for 
 each proposal with a history of syphilis. 
 
 Salomonson, out of 121 persons w^ho acknowledged 
 syphilis, recorded 17 deaths at an average of 46 years, 
 whereas the mortality expectation was only 9*14. 
 
 Blaschko and Jacobsohn examined the causes of 
 5,724 deaths, and came to the conclusion that 25:5 per 
 cent, were certainly caused by syphilis, and 40 per 
 cent, probably. 
 
 Kleinschmidt states that the average age of death 
 of eighty-eight policy-holders who gave a history of 
 syphilis was 47-5 years. 
 
 Out of the collected experience of several American 
 insurance companies, the mortality amongst those 
 who had a history of syphilis was 3 3 "3 per cent, above 
 the expectation. 
 
 As it is acknowledged to be extremely difficult to 
 get truthful histories in regard to syphilitic infec- 
 tions from candidates wishing to be insured, and as 
 nearly all authorities agree that syphilitics should be 
 accepted with caution, and even the most satisfac- 
 tory cases with an increased premium, the routine 
 examination of the Wassermann reaction appears 
 advisable in the interest of the assurance companies. 
 
CHIEF REFERENCES 
 
 * A System of Syphilis.' Edited by D'Arcy Power 
 
 and J. Keogh Murphy. 
 
 * La Syphilis.' By Levaditi and Roche. 
 'Wassermann Sero-Diagnosis of Syphilis in its 
 
 Application to Psychiatry.' By Felix Plant. 
 
 * L' Ultra Microscope.' By Paul Gastou. 
 ' L'Ultra Microscope.' By J. Comandon. 
 
 * Serum Diagnosis of Syphilis.' By Noguchi. 
 
 ' Syphilis.' By Jas. Macintosh and Paul Fildes. 
 ' Diagnosis and Treatment of Syphilis.' By Carl 
 Browning and Ivy MacKenzie. 
 
 ' Diagnosis of Nervous Diseases.' By Purves 
 Stewart. 
 
 ' Journal of the Royal Army Medical Corps.' 
 Articles by Gibbard and Harrison. 
 
 'Practitioner,' 191 1. Review of 'Treatment by 
 Salvarsan,' by Manuel and Bayly. 
 
 185 
 
INDEX 
 
 PAGES 
 
 Acute nephritis ... ... ... ... ... no 
 
 After-effects of salvarsan ... ... ... ... 148 
 
 Agglutination of Spirochceta pallida ... ... ... 7 
 
 Alcoholism ... ... ... ... ... I3i> I33 
 
 Amyloid disease of kidney ... ... ... ... 112 
 
 Anaemia in syphilis ... ... ... ... ... 37 
 
 cause of ... ... ... ... ... 38 
 
 infantile ... ... ... ... ... 42 
 
 in parasyphilis ... ... ... ... ... 45 
 
 in primary syphilis ... ... ... ... 43 
 
 in secondary syphilis ... ... ... ... 44 
 
 in tertiary syphilis ... ... ... ... 45 
 
 varieties of ... ... ... ... 39, 40 
 
 Anaesthesia, Wassermann reaction under ... ... ... 90 
 
 Anaphylaxis in syphilis ... ... ... ... 172 
 
 Aneurism, death-rate from ... ... ... ... 181 
 
 Anthropoid ape inoculations ... ... ... 24, 26 
 
 Antigen-antibody reactions ... ... ... ... 47 
 
 Antigen for Wassermann reaction ... ... ... 59 
 
 lecithin cholesterin ... ... ... ... 61 
 
 normal organ ... ... ... ... ... 60 
 
 requirements of a good ... ... ... ... 62 
 
 syphilitic organ ... ... ... ... ... 59 
 
 titration of ... ... ... ... ... 61 
 
 Aortic aneurism, Wassermann reaction in ... ... 90 
 
 Apparatus for administration of salvarsan ... ... 136 
 
 for lumbar puncture ... ... ... ... 97 
 
 for venipuncture ... ... ... ... ... 63 
 
 Arthus' phenomenon ... ... ... ... ... 172 
 
 B 
 
 Bacillus of Lustgarten ... ... ... ... i 
 
 Bacillus smeg7natis ... ... ... ... ... 2 
 
 Blindness and salvarsan ... ... ... ... 147 
 
 186 
 
INDEX T87 
 
 PAGES 
 
 Blood and Spirochicta fallida ... ... ... 22, 23 
 
 Bordet-Gengou phenomenon ... ... ... ... 50 
 
 C 
 
 Cadaver, Wassermann reaction in ... ... ... 90 
 
 Cancer and Wassermann reaction ... ... ... 89 
 
 Cardiac symptoms after salvarsan ... ... ... 150 
 
 Cerebral sypliilis ... ... ... ... ... 129 
 
 tm-nour ... ... ... ... ... 133, 134 
 
 Cerebro-spinal fluid ... ... ... ... 96-109 
 
 cytological examination ... ... ... 99 
 
 in general paralysis ... ... ... 104, 107, 127 
 
 in secondary syphilis ... ... ... ... 104 
 
 in tertiary syphilis ... ... ... ... 104 
 
 lymphocytosis of ... ... ... ... 99 
 
 polymorphonuclear leucocytosis of ... ... 100 
 
 quantity of secreted ... ... ... ... 96 
 
 Spirochcxta pallida in ... ... ... ... 96 
 
 Wassermann reaction of ... ... ... 104 
 
 Chemical examination of cerebro-spinal fluid ... ... 108 
 
 Chronic nephritis ... ... ... ... ... 112 
 
 C\\\2i oi Spirochccia pallida ... ... ... ... 5 
 
 C\2L's,?,\^C2it\or\ o^ Spirochceta pallida ... ... ... 5 
 
 Clinical value of Wassermann reaction ... ... ... 113 
 
 CoUes's law ... ... ... ... ... ... 120 
 
 Combined salvarsan and mercury treatment ... ... 157 
 
 Complement ... ... ... 46, 47, 48, 49, 50, 65 
 
 fixation... ... ... ... ... ... 47 
 
 Conceptional syphilis ... ... ... ... ... 24 
 
 Congenital syphihs ... 22, 42, 93, 95, 121, 122, 130, 143 
 
 Contra-indications to salvarsan ... ... ... ... 1 50 
 
 Control of treatment by Wassermann reaction ... 11 8, 119 
 
 Corneal inoculation ... ... ... ... ... 25 
 
 Culture of Spirochata pallida ... ... ... ... 20 
 
 Cytological count, technique of ... ... ... loi 
 
 in cerebral syphilis ... ... ... ... 103 
 
 in general paralysis ... ... ... 99, 103, 127 
 
 in meningitis ... ... ... ... 103 
 
 in secondary syphilis ... ... ... ... 100 
 
 in tabes dorsalis ... ... ..." 99, 103, 129 
 
 in tubercular meningitis ... ... ... 104 
 
 examination of cerebro-spinal fluid ... ... ... 99 
 
 D 
 
 Dark-ground illumination of >S)^/r^r//^?/<z/^//?V/(r7 ... ... 8 
 
 Deaths from diseases syphilitic in origin ... ... ... iSo 
 
SYPHILIS AND PARASYPHILIS 
 
 Deaths from diseases partly attributable to 
 
 syphilis 
 
 ... 182 
 
 from salvarsan 
 
 ... 146 
 
 from syphilis alone 
 
 ... 179 
 
 in which syphilis may be a contributing cause 
 
 ... 183 
 
 Decomplementization of test-serum 
 
 ... 64 
 
 Degeneration of choroid plexus 
 
 ... 106 
 
 Diagnosis by gland puncture 
 
 ... 17 
 
 Diarrhoea after salvarsan 
 
 ... 150 
 
 Differential diagnosis of spirochsetes 
 
 ... 15 
 
 of nervous diseases 
 
 ... 131 
 
 Wassemann reaction for 
 
 ... 115 
 
 Disseminated sclerosis 
 
 133. 134 
 
 Division of Spirochceta pallida ... 
 
 5 
 
 Dosage of mercury 
 
 ... 156 
 
 of salvarsan 
 
 E 
 
 Epilepsy 
 
 ... 140 
 
 ... 134 
 
 Errors in Wassermann reaction ... 
 
 83, 85 
 
 Examination of chancre for Spirochata pallida 
 
 G 
 
 General paralysis ... ... ... 
 
 II, 12 
 
 ... 123 
 
 cerebro-spinal fluid in 
 
 
 127, 133 
 
 death-rate of 
 
 
 ... 181 
 
 Wassermann reaction in 
 
 104, 107, 125, 133 
 
 Giant forms oi Spirochata pallida 
 
 
 3 
 
 Giemsa's stain 
 
 
 ... 13 
 
 Gland puncture 
 
 .. 
 
 ... 17 
 
 Globulin reaction of cerebro-spinal fluid .. 
 
 
 ... 108 
 
 Gonorrhoea, Wassermann reaction in 
 
 . 
 
 ... 90 
 
 Granule shedding of Spirochceta pallida . . 
 
 
 6 
 
 Guinea-pig complement 
 
 
 ... 65 
 
 Gynaecology, Wassermann reaction in 
 
 TT 
 
 . 
 
 ... 116 
 
 H 
 
 Habitat of SpirochcBta pallida ... 
 
 21 
 
 Haemoglobin 
 
 
 38,41 
 
 Haemoglobinuria 
 
 
 ... 43 
 
 Hsemolytic serum 
 
 
 ... 67 
 
 from horse ... 
 
 
 ... 68 
 
 preparation of 
 
 
 ... (>! 
 
 titration of ... 
 
 
 68, 69 
 
 system ... 
 
 
 ... 66 
 
 Headache after salvarsan 
 
 
 ... 150 
 
 Heart disease and Wassermann reaction ... 
 
 
 ... 89 
 
INDEX 
 
 Ilecht's technicjue of Wasserniann rcacLioi) 
 
 Hemiplegia ... 
 
 Human inoculations ... 
 
 Hypochondriasis 
 
 I 
 
 Immunity 
 
 Importance of early diagnosis of syphilis ... 
 Incubation period 
 
 Indian ink method of examination of SpirocJuda pallida 
 Infantile anaemias 
 Inoculation experiments 
 
 Insurance candidates and Wassermann reaction 
 Intramuscular injection of mercury ... 156, 161, 
 
 and Wassermann reaction ... 161, 
 
 of salvarsan ... 
 Intraventricular fluid ... 
 
 Inunction treatment and Wassermann reaction 
 Invasion of Spirochcvta pallida ... 
 Isolation of cerebro-spinal fluid 
 
 189 
 
 i"A{;i':.s 
 ... 81 
 
 ... 28 
 ... 131 
 
 J 
 
 Jarisch-Herxheimer reaction 
 
 33 
 
 18 
 
 28 
 
 12 
 
 42 
 
 24-28 
 
 ... 184 
 
 164, 165 
 
 164, 165 
 
 ... 168 
 
 106 
 
 163, 164 
 
 21 
 
 ... 105 
 
 150, 173 
 
 Lardaceous disease of kidney 
 
 ... 112 
 
 Latent syphilis and Wassermann reaction 
 
 ... 113 
 
 Lecithin cholesterin antigen 
 
 61 
 
 Leishman's stain 
 
 14 
 
 Leprosy and Wassermann reaction 
 
 88 
 
 Leucocytosis of blood ... 
 
 38 
 
 of cerebrospinal fluid 
 
 ... 100 
 
 Levaditi's stain 
 
 15 
 
 Life insurance and syphilis 
 
 ... 179 
 
 and Wassermann reaction 
 
 ... 184 
 
 Loefller's stain 
 
 14 
 
 Luetin reaction 
 
 174-178 
 
 Lumbar puncture 
 
 97 
 
 Lustgarten's bacillus ... 
 
 I 
 
 Lymphocytosis of blood 
 
 38 
 
 of cerebrospinal fluid 
 
 99 
 
 M 
 
 Malaria and Wassermann reaction 
 
 Marino's stain 
 
 Marriage 
 
 13 
 119 
 
1 90 SYPHILIS AND PARASYPHILIS 
 
 PAGES 
 
 Medicine and Wassermann reaction ... ... ... 115 
 
 Mental deficiency ... ... ... ... 130, 134 
 
 Mercury treatment ... ... ... ... •••155 
 
 and Wassermann reaction ... 159, 16I; 164, 165 
 
 Microscopical diagnosis, reliability of ... ... ... 19 
 
 Moribund persons and Wassermann's reaction ... ... '90 
 
 Mortality rate amongst syphilitics ... ... ... 183 
 
 Mothers ofsyphilitic children and Wassermann's reaction 93, 121, 122 
 
 Movements of S/>zroc/zce^a pa/izda " ... ... ... 5 
 
 N 
 
 Narcosis and Wassermann reaction 
 Nature of Wassermann reaction 
 Negative luetin reaction 
 
 Wassermann reaction ... ... 91, 104, 
 
 Neo-salvarsan 
 Nephritis 
 
 and salvarsan 
 Neurasthenia 
 Noguchi's butyric acid test 
 
 luetin test 
 
 technique for Wassermann's reaction 
 Normal organ extract, antigen ... 
 
 O 
 
 Obstetrics and Wassermann reaction 
 Offspring 
 
 Ophthalmology and Wassermann reaction 
 Optic atrophy 
 
 Original technique for Wassermann reaction 
 reasons for superiority of 
 
 Paraplegia ... ... ... ... ... ] 
 
 Peripheral neuritis 
 
 Pfeiffer's phenomenon 
 
 Phlebitis and salvarsan 
 
 Physico-chemical theory for Wassermann reaction ... 
 
 Pill treatment and Wassermann reaction ... 
 
 Placenta and Spirochceta pallida 
 
 Pneumonia and Wassermann reaction 
 
 Polymorphonuclear leucocytosis of cerebro-spinal fluid 
 
 Preparation of patient for salvarsan 
 
 Primary syphilis and Spirochceta pallida ... ... 19 
 
 and ansemia . . . 
 
 and luetin reaction ... ... ... i 
 
 
 90 
 
 5 
 
 ;i-58 
 
 
 117 
 
 119, 
 
 126 
 
 
 155 
 
 no 
 
 »-II2 
 
 
 147 
 
 131, 
 
 133 
 
 
 108 
 
 174 
 
 -178 
 
 
 80 
 
 ... 
 
 68 
 
 117, 
 
 120 
 
 
 119 
 
 
 117 
 
 
 134 
 
 
 70 
 
 ... 
 
 79 
 
 133, 
 
 134 
 
 
 132 
 
 ... 
 
 46 
 
 
 147 
 
 ... 
 
 SI 
 
 
 162 
 
 
 23 
 
 
 89 
 
 ... 
 
 100 
 
 
 139 
 
 ', 21; 
 
 , 22 
 
 ... 
 
 43 
 
 [76, 
 
 177 
 
INDEX 191 
 
 I'AGES 
 
 Primary syphilis and mercury ... ... ... ... 14" 
 
 and microscopical examination ... ... ... 19 
 
 and salvarsan ... ... ... ... 140 
 
 and Wassermann reaction ... ... ... 92 
 
 Profeta's law ... ... " ... ... 94, 121 
 
 Prophylaxis and syphilis ... ... ... ... 3^ 
 
 R 
 
 Reagents required for Wassermann reaction ... ... 59 
 
 Reducing body in cerebro-spinal fluid ... ... ... 109 
 
 Registrar-General's Report ... ... ... ... I79 
 
 Reinfection ... ... ... ... ... ... 29 
 
 Relapses after salvarsan ... ... ... 151, 168, 170 
 
 Relapsing fever and Wassermann reaction ... ... 89 
 
 Reliability of microscopical diagnosis ... ... ... 19 
 
 Resting-stage of Spiroc/ucta pallida ... ... ... 6 
 
 Rigors after salvarsan ... ... ... ... ... 1 50 
 
 Salvarsan ... ... ... ... ... ... 135 
 
 administration of ... ... ... ... 136 
 
 after-effects of ... ... ... ... 14S-151 
 
 and Wassermann reaction ... ... ... 166- 17 1 
 
 contra-indications to ... ... ... •••153 
 
 dangers of ... ... ... ... ... 146 
 
 deaths follovi^ing ... ... ... ... 146, 147, 174 
 
 in congenital ... ... ... ... ... 143 
 
 in parasyphilis ... ... ... ... ... 144 
 
 in primary syphilis ... ... ... ... 140 
 
 in secondary syphilis ... ... ... ... 141 
 
 in tertiary syphilis ... ... ... ... 143 
 
 relapses after ... ... ... ... 151, 168, 170 
 
 toxicity of ... ... ... ... ... 146 
 
 Scarlet fever and Wassermann reaction ... ... ... 89 
 
 Schaudinn's description of Spirochceta pallida ... ... 2 
 
 Secondary syphilis and Wassermann reaction ... 92, 95 
 
 and aneemia ... ... ... ... ... 44 
 
 and cerebro-spinal fluid ... ... 100, 104 
 
 and luetin reaction ... ... ... 176, 177 
 
 and salvarsan ... ... ... ... 141 
 
 '^^z\Aon'&i'^kmx\g'iox Spij'ochceta pallida ... ... ... 15 
 
 Sheep's corpuscles, preparation of ... ... ... 66 
 
 Simplified techniques for Wassermann reaction ... 80-83 
 
 inferiority of ... ... ... 81, 82, 83, 84 
 
 Skin diseases and Wassermann reaction ... ... ... 90 
 
 Smegma bacill us ... ... ... ... ... 2 
 
192 
 
 SYPHILIS AND PARASYPHILIS 
 
 Sources of error in Wassermann reaction 
 Specificity of Wassermann reaction 
 of anaphylactic reactions . . . 
 of antigen-antibody reactions 
 of luetin reaction 
 Spirilla 
 
 Spirochceta balanitis ... 
 buccalis 
 dentiuni 
 pertenuis 
 psetido-pallida 
 refi'ingens 
 Spirochceta pallida in gland puncture 
 culture of 
 habitat of 
 in blood 
 
 in cerebro-spinal fluid... 
 in congenital syphilis 
 in placenta ... 
 in primary syphilis 
 in secondary syphilis . . . 
 in semen 
 invasion of 
 Spirolysis 
 
 Staining of films for Spiroch(2ta pallida 
 Stern's technique 
 Subacute nephritis 
 
 Suppositories and Wassermann reaction 
 Surgery and Wassermann reaction 
 Syphilitic organ extract antigen 
 
 83-85 
 
 86-95 
 
 172 
 
 48 
 
 177 
 
 I 
 
 17 
 
 15 
 
 15 
 
 16 
 
 16 
 
 17 
 
 17 
 
 20 
 
 21 
 
 22, 23 
 
 96 
 
 22 
 
 23 
 22 
 22 
 , 28 
 21 
 7 
 
 13 
 
 80 
 
 III 
 
 163 
 
 116 
 
 59 
 
 21 
 
 24 
 
 Tabes dorsalis 
 
 cell count of cerebrospinal fluid 
 death-rate due to 
 mercury treatment and 
 salvarsan treatment and 
 Wassermann reaction in 
 
 of cerebro-spinal fluid 
 Technique of cell count of cerebro-spinal 
 of luetin reaction 
 of lumbar puncture 
 of salvarsan administration 
 of venipuncture ... 
 original, of Wassermann reaction 
 Techniques, simplified 
 
 m 
 
 m 
 fluid 
 
 129 
 99, 129 
 ... 181 
 ... 156 
 ... 144 
 129, 133 
 104, 129, 133 
 
 lOI 
 
 175 
 
 98 
 
 136 
 
 63 
 
 70 
 
 80-83 
 
INDEX 
 
 Temperature of antigen-antibody action 
 Tertiary syphilis and ancemia 
 and luetin reaction 
 and salvarsan treatment 
 and Spirochicta pallida 
 and Wassermann reaction 
 
 of cerebro-spinal fluid 
 Test-serum, preparation of 
 Testicle inoculation 
 Theobald Smith's phenomenon 
 Therapeutic results of salvarsan 
 Titration of antigen for Wassermann reaction 
 
 of complement for Wassermann reaction 
 
 of haemolytic serum for Wassermann reaction 
 Toxity of salvarsan 
 Treatment and Wassermann reaction 
 
 and Spirochceta pallida 
 
 by mercury 
 
 by salvarsan 
 
 combined 
 
 importance of early 
 
 of pregnant women 
 
 prophylactic 
 T7'eponema pa lliduvi . . . 
 Trypanosomiaris and Wassermann reaction 
 Tubercular meningitis 
 Tuberculosis and Wassermann reaction 
 
 193 
 
 I'AGES 
 ... 48 
 
 ••• 45 
 
 ^n. 178 
 ... 143 
 
 27, 31 
 
 93, 95 
 
 104 
 
 62 
 
 25 
 
 172 
 
 140 
 
 . 61 
 
 . 66 
 68, 69 
 . 146 
 
 • 159 
 
 35 
 
 • 155 
 
 • 135 
 
 • 157 
 . 18 
 
 120 
 
 7>S^ 36 
 
 2 
 
 . 88 
 
 . 104 
 
 • 89 
 
 U 
 
 Urine 
 
 no 
 
 V 
 
 Venipuncture, apparatus for 
 
 technique of 
 Viscosity of Spi7-och(£ta pallida 
 Vomiting after salvarsan 
 
 63 
 
 63 
 
 7 
 
 150 
 
 W 
 
 Wassermann reaction ... 
 and marriage 
 and mercury treatment 
 and salvarsan treatment 
 Flemming's technique 
 for controlling treatment 
 
 159, 
 
 ... 51 
 ... 119 
 161, 164, 165 
 166-171 
 ... 82 
 iiS, 119 
 
194 
 
 SYPHILIS AND PARASYPHILIS 
 
 Wassermann reaction, Hecht's techniques 
 in anaesthesia 
 in aortic aneurism 
 in cerebral syphiHs 
 in congenital syphilis ... 
 in diagnosis ... 
 in general paralysis 
 in gynaecology 
 in medicine ... 
 in moribund patients ... 
 in mothers of syphilitic children 
 in narcosis ... 
 in nonsyphilitic diseases 
 in obstetrics ... 
 in ophthalmology 
 in primary syphilis 
 in secondary syphilis ... 
 in surgery 
 in tabes dorsalis 
 in tertiary syphilis 
 in the cadaver 
 nature of 
 negative 
 
 Noguchi's technique ... 
 of cerebro-spinal fluid ... 
 original technique 
 quantitative 
 reagents for 
 
 simplified techniques ... 
 sources of error in 
 specificity of 
 Stern's technique 
 
 PAGES 
 
 ... 8i 
 ... 90 
 ... 90 
 129 
 93> 95> 121, 122, 130 
 ... 115 
 104, 107 
 ... 116 
 
 115 
 
 ... 90 
 121, 122 
 
 93, 
 
 104, 
 
 91, 104, 
 
 ... 90 
 ... 88 
 117, 120 
 ... 117 
 
 92, 95 
 29, 95 
 
 ... 116 
 
 129, 133 
 
 93, 95 
 ... 90 
 
 51-58 
 
 119, 126 
 
 ... 83 
 
 104 
 
 ••• 75 
 • •• 75 
 ■■■ 59 
 ...80-83 
 
 ... S3 
 ... 86 
 ... 80 
 
 Yaws and Wassermann reaction 
 Spirochcdta pertenuis of 
 
 16 
 
 Bailliere, Tindall ahd Cojc, 8, Henrietta Street, Covent Garden. 
 
COLUMBIA UNIVERSITY UBRARIES 
 
 *0H]2189626* 
 
 HEALTH SCIENCES LIBRAnV