Wassermann Reaction

WASSERMANN REACTION. The problem of the serodiagnosis of syphilis has been treated in world literature since 1906, when Wassermann, together with Neisser and Bruck (Neisser, Bruck), proposed the reaction that bears his name. An enormous body of literature has accumulated on this subject, generated by the work of about 1,800 researchers from all over the world, who have performed, in general, no fewer than 4 million experiments. The process caused by the introduction of the pale spirochete into the human or animal organism is general; spirochetes are found in the vessels (both lymphatic and blood) of the most important parenchymatous organs (spleen, liver, heart, bone and nervous systems, as well as the endocrine apparatus); cytologically, lymphocytosis is noted with a profound disturbance of basic enzymatic processes, entailing a complete perversion of protein and, especially, lipid metabolism of the cells. The consequence of this profound influence of the spirochete is the special properties of syphilitic serum that distinguish it from so-called normal serum and lie at the basis of serological reactions for syphilis. The features of syphilitic serum are as follows: I. The chemical properties of its colloids (proteins and lipids) are as follows: a) an increased amount of globulins and lipids; b) a change in the quality of globulins: 1) lesser stability of their colloidal solutions in view of the weakening of the bond with the surrounding crystalloid medium, and consequently, easy precipitatability (under the influence of extract-lipids, cholesterol, alcohol, acetone, ammonium sulfate, lactic acid, formol, concentrated NaCl, colloidal gold, etc.); 2) thermostability (the greater part), i.e., having fallen out of solution, globulins do not dissolve at 37°—in contrast to the globulins of normal serum, which, upon falling out of solution, dissolve again (thermolability) at 37° in 2-18 hours; 3) so-called active acidity (determined by the concentration of free H and OH ions) is lower than in normal serum. II. Physical properties of syphilitic serum: a) dispersion of colloids (i.e., the fragmentation of their particles) is reduced; particles visible only ultramicroscopically are coarser, larger, and distributed in the form of agglomerates (i.e., a pre-existing precipitate is present); b) surface tension and viscosity are increased; c) rotation of the plane of polarization is increased; d) autotropy, i.e., the sum of the hemolyzing and antihemolyzing capacity, is increased; this property is weakened upon starvation (Finkelstein) and heating to 60° (Neufeld); e) all seroreactions proceed faster and more regularly at the "moment of emergence" (in statu nascendi); f) its physicochemical state acquires somewhat greater stability upon heating (3/4 h at 37°—inactivation). III. Electrophysical properties: globulins (their colloidal particles-micelles) are electropositive, in contrast to normal serum globulins and lipid extracts, which are electronegative. Proceeding from the cited properties of syphilitic serum, all seroreactions for syphilis can also be explained. One distinguishes 1) the Wassermann reaction (RW) proper and its modifications, 2) flocculation reactions (Sachs-Georgi, D. Meinicke, Kahn, etc.). The essence of the reactions is the same, but the method of detection is different. Common to the methodology of all reactions for syphilis is the addition to the syphilitic serum of a so-called antigen extract, which is prepared differently in different reactions and therefore possesses greater or lesser activity or sensitivity, as well as physicochemical individuality (Aviditat). In the RW, antigens have low activity, giving with syphilitic serum very insignificant (subvisible) precipitates, distinguishable only ultramicroscopically and detected macroscopically with the help of the so-called hemolytic system, which in this case serves merely as a macroscopic indicator (see diagrams). In purely flocculation reactions (Sachs-Georgi, Kahn, etc.), antigens are very sensitive, giving macroscopically visible precipitates with syphilitic serum (by the naked eye or magnifying glass) and, thus, are detected without the assistance of the hemolytic system. Common to all reactions for syphilis is the appearance of a precipitate, which in the RW adsorbs (absorbs) complement and thus prevents the dissolution of the erythrocytes of the hemolytic system, whereas in other reactions this flocculate is the direct macroscopic expression of a positive reaction. The driving force in all these reactions (RW, flocculation) is the same: the generation of an electric current upon the interaction of positively charged particles of syphilitic serum with negatively charged particles of lipid extracts and, as a consequence of the electric discharge, the precipitation of sediment; with normal serums, charged negatively and mixed with a negatively charged extract, there is no generation of current, and no flocculate, i.e., a negative seroreaction is obtained. This physicochemical theory satisfactorily explains to us all the features of the course of all reactions for syphilis, as well as the essence of so-called nonspecific reactions in tuberculosis, malaria, tumors, leprosy, etc., in which there are physicochemical changes in the serum of patients close to those observed in syphilis, but of lesser intensity. The so-called amboceptor theory of the RW is currently defended by only a few researchers; this concerns both the initial, anti-spirochete theory proper, and the later one, put forward by W. as a corrective—the so-called auto-antilipid theory. The latter theory is based on the excessive accumulation of lipids in the body of a syphilitic under the influence of the decay of lymphocytes as a consequence of the toxic effect of the pale spirochete; in response to this, the organism, reacting to excessive lipids as foreign bodies, produces antilipid amboceptors. The latter theory does not explain all the features of the seroreaction and therefore, together with the anti-spirochete theory, is interesting only as a working scheme, convenient for the first stage of familiarization with the serodiagnosis of syphilis. The attached two diagrams, constructed according to the amboceptor type, explain the course of a positive and negative Wassermann reaction. Positive RW (Diagram 1). Luitic extract (lipid extract, organ extract) + syphilitic serum (syn.: luitic amboceptor, antilipid amboceptor, Wassermann substrate) + complement (fresh guinea pig serum); this mixture is kept for 3/4-1 hour in a thermostat, as a result of which a closed antigen-amboceptor system is formed, since complement is also involved in the specific reaction between the antigen and amboceptor (resp., is adsorbed by the precipitate forming thereby) and, thus, disappears from the solution. Then rabbit hemolytic serum (immunized with sheep erythrocytes) with sheep erythrocytes is added. This whole mixture, consisting of five ingredients, is placed again in the thermostat for 1 hour. As a result of this experiment, sheep erythrocytes remain undissolved due to the absence of free complement, which is designated as a positive RW. Antigen-amboceptor system closed Spiroch. pallida Lues-Extract Antigen Lues-Serum Wassermann Substrate Hemolytic system not closed Complement Hemolytic serum Sheep cells

Globulins Lipoids >Wasserm.aggregate Complement Sediment of sheep corpuscles Lipoids Globulins Complement Scheme 1. Wassermann reaction positive (+). In scheme 1 placed here, the course of the reaction and its result in the test tube are visible, where in the sediment, aside from sheep erythrocytes, there are, according to the physical-chemical theory, both extract lipoids and globulins of syphilitic serum, as well as entrapped (adsorbed) complement (inactive in relation to the hemolytic system). Positive RW has its gradations, fitting between complete absence of hemolysis and gradually increasing hemolysis reaching complete hemolysis (i.e., negative reaction). These gradations are designated as follows: + + + + = positive reaction + + + and + + = weakly positive reaction ± = indeterminate reaction - = negative reaction. These gradations, depending on complete or partial adsorption of complement, have some, albeit relative, practical significance as a criterion of the gradual weakening of the tension of that physical-chemical state of the serum which is characteristic of the syphilitic process. Negative RW (scheme 2). In this scheme, where normal serum is schematically depicted instead of syphilitic serum, the course and result of the reaction are different: complete dissolution of erythrocytes is obtained, since in the first phase of the experiment the complement is not used (is not adsorbed); it remains free, active, and therefore completes the hemolytic system in the second stage of the experiment, as a result of which the indicated hemolysis of erythrocytes is obtained (negative RW). Fundamentals of RW methodology and its unification. From the presented scheme it is seen that the Wassermann reaction is composed of five ingredients: syphilitic serum, antigen (extract), complement, hemolytic serum for sheep erythrocytes, and sheep erythrocytes. To obtain a specific course of the reaction, all these ingredients must be checked for quality, introduced into the reaction in a definite sequence and definite quantitative ratios, for which a whole series of preliminary control experiments is set up. In view of the complexity and meticulousness of this "colloidal reaction," as well as the still incomplete finalization of its methodology, many "modifications" were proposed for its simplification and refinement. Thus, a large technical literature was gradually created (about 600 works), in which a trend simultaneously outlined towards standardization (unification) of the RW methodology both in the sense of its performance itself and the manufacture of the ingredients entering into it, which was necessary to smooth out discrepancies in the obtained results with dissimilar methodology. The unification of the serodiagnosis of syphilis as a whole (i.e., not only RW, but also other seroreactions) as a question of great practical importance was the subject of discussion of a whole series of conferences both in Western Europe (Paris, London, Copenhagen) and in the USSR (serological conferences at congresses of bacteriologists and venereologists in Leningrad, Moscow, Kharkov, Odessa). As a result of these conferences in the USSR, a serological instruction was developed, which was proposed for testing on mass material. This instruction, according to the data of the all-Russian verification questionnaire conducted in 1928 by the Central Serological Commission of the People's Commissariat of Health of the RSFSR and based on 400,000 investigations set up in 70 laboratories, gave, on the whole, satisfactory practical results in the sense of agreement with the clinic. It emphasized the necessity of parallel performance along with RW of flocculation reactions (Sachs-Georgi, Kahn, Meinicke). Basic provisions of the serological instruction.—Performance of RW. 1. The reaction must be performed with three antigens obtained from central laboratories (one specific); it is performed with half doses, in a total volume of 2¹/₂ cub. cm. 2. The hemolytic amboceptor, obtained by immunizing rabbits with sheep erythrocytes, must have a titer of not less than 1 : 1,200, i.e., 0.5 cub. cm of it in a dilution of 1 : 1,200 must dissolve 0.5 cub. cm of an emulsion (5%) of sheep erythrocytes in the presence of 0.5 cub. cm of complement (in a dilution of 1 : 10), for 1 hour at 37° in a thermostat. 3. Complement (fresh serum of guinea pigs) is used as a mixture (not less than 5 parts of alcohol; shaking in a Schüttel apparatus (according to Sachs)—9. Method of preparing glassware (washing, sterilization, glass quality). 10. Taking blood from patients for RW (from vena cubiti) under conditions of complete asepsis, obligatorily on an empty stomach. For the experiment, blood serum is inactivated for half an hour at 56–58°. 11. Basic experiment with blood serum (scheme X). 12. Designation of reaction strength: positive reaction = + + + + and + + +; weakly positive reaction = + + and +; indeterminate reaction = ±; negative reaction = -. Scheme X of the serological instruction adopted by the XI Congress of Bacteriologists of 1928 Serum diluted 1:5 Nos. 1, 2 and 3 antigens, working dose in 0.5 NaCl Complement, titrated with antigen in excess NaCl At 37° Sensitized erythrocytes (mixture of sheep erythrocytes and hemolytic serum) At 37° Syphilitic serum 0.5 cub. cm 0.5 » » 0.5 » » 0.5 » » No. 1–0.5 cub. cm No. 2–0.5 » » No. 3–0.5 » » Without antigen 0.5 cub. cm 0.5 » » 0.5 » » 0.5 » » 0 0 0 0.5 » » 1 cub. cm 1 » » 1 » » 1 » » + + + + + + + + + + Г (hemolysis) Normal serum 0.5 cub. cm 0.5 » » 0.5 » » 0.5 » » No. 1–0.5 cub. cm No. 2–0.5 » » No. 3–0.5 » » Without antigen 0.5 cub. cm 0.5 » » 0.5 » » 0.5 » » 0 0 0 0.5 » » 1 cub. cm 1 » » 1 » » 1 » » Г (hemolysis) Test serum 0.5 cub. cm 0.5 » » 0.5 » » 0.5 » » No. 1–0.5 cub. cm No. 2–0.5 » » No. 3–0.5 » » Without antigen 0.5 cub. cm 0.5 » » 0.5 » » 0.5 » » 0 0 0 0.5 » » 1 cub. cm 1 » » 1 » » 1 » » + + + + + + + + + + Г (hemolysis) from 3 healthy male guinea pigs); the strength of the complement must be not less than 0.05 cub. cm of undiluted or 0.5 of diluted NaCl 1 : 10, i.e., such a dose of complement together with the titrated dose of hemolytic amboceptor must for 1 hour at a temp. of 37° dissolve 0.5 cub. cm of a 5% emulsion of sheep erythrocytes. 4. Sheep erythrocytes (not older than a year, from vena jugularis, prepared in the form of a 5% emulsion) from defibrinated and washed blood (in chemically pure physiological NaCl solution) or a 3% emulsion of sediment. 5. Testing of hemolytic serum—its titer (scheme given). For the basic experiment, the 3rd titer is taken (e.g., if the titer = 1 : 1,500, then for the experiment 1/1,500 is taken)—6. Titration of complement without antigen and in the presence of antigen in the working dose (scheme 1 given); for the basic experiment, a complement dose is taken with an addition to the titrated one of 10 to 25%. 7. Titration of antigen (approximate scheme given). The working dose (i.e., specific working dose) = ¹/₂ of the fully dissolving dose; it is tested on a large number of positive syphilitic sera (of various strengths: 4+, 3+, 2+, 1+) and normal sera. Determination of the hemotoxicity of the antigen (scheme): only weakly toxic antigen is allowed for use [(+) = in double working dose]. 8. Manufacture of antigens: a) from syphilitic liver (1.0 g of dry liver per 5–6 cub. cm of 96° alcohol—according to Finkelstein); its strength is not less than hundredths of a cub. cm; b) cholesterinated extract (1 : 1,000–2,000) from the heart (bull, horse): 1.0 g of fresh organ per Experimental justification. Seroreactions for syphilis have also received their confirmation in experiments on animals; the old experiments of Wassermann and Neisser's school on monkeys are well known, but the newest investigations of German scientists on rabbits (Blumenthal, Weidanz, Blum, et al.) have a much greater scientific significance, as well as those of the Russian school (experiments at the State Venereological Institute by Yu. A. Finkelstein and his coworkers—Aristova, Segal, Yaskolko; in this connection, various seroreactions for syphilis and their course in diverse forms of rabbit syphilis were studied: primary syphilis, secondary, tertiary, latent, ocular, nervous). In view of the increased "autotropicity" of animal serum, it is necessary to use the so-called micromethodology in this case (proportionally smaller quantities of ingredients than in human serodiagnosis).

WASSERMANN REACTION

in connection with raising the issue of the state campaign against syphilis, from a scientific and practical standpoint divides syphilis into two stages: prior to the appearance of the RW (sero-negative stage) and after the appearance of the RW in the blood (sero-positive stage). Such a division, in Wassermann's opinion, is more practical than the old division into lues I, lues II, lues III, because it more correctly indicates the course of the spread of the pale spirochete in the organism, which is of particular importance in the individual direction of therapy. In the sero-negative period (prior to the RW), according to Wassermann, there is only local multiplication of the pale spirochete, and therefore here therapia magna sterilisans by the abortive method is indicated and possible: namely, early energetic therapy with the aim of killing the spirochetes with Ehrlich's preparations. The sero-positive stage, which already corresponds to the penetration of the pale spirochete into all organs ("constitutional syphilis!"), requires periodic combined therapy acting mainly on the altered tissue of the organs and then also on the pale spirochete; however, other researchers (Hoffmann, Uhlenhuth) object to the categorical nature of Wassermann's stated propositions, since sero-negativity does not absolutely exclude tissue syphilis, in view of the existence of facts of a negative RW in lues II manifesta and the obtaining of rabbit lues from the blood of people with a negative RW. In addition, according to Hoffmann, abortion of syphilis is sometimes possible even in the sero-positive stage. In view of this, Hoffmann, for practical reasons, proposes to retain the old division of syphilis. To illustrate the importance of the early start of therapy, Table 4 is given. Table 4. Start of therapy

Statistics by Merz: In the seronegative period: RW = - 80%; In the seropositive period: RW = - 60%. It can be seen from Table 4 that the percentage of negative Wassermann reactions upon therapy in the seronegative period is significantly higher than in the seropositive period. According to other authors, in secondary, tertiary, and congenital syphilis, the Wassermann reaction responds to therapy much more difficultly than in primary syphilis and, in general, not for long. The persistence of a positive Wassermann reaction has a poor prognostic significance. The cited facts consolidated the proposition advanced by Citron that for the correct individualization of therapy, it is necessary to reckon with the course of the Wassermann reaction (control-therapeutic value of the Wassermann reaction); however, at present, the clinician also has to take the latter into account from the prognostic standpoint: when deciding the question of a cure in each specific case, a prolonged negative Wassermann reaction in the blood and cerebrospinal fluid (especially after repeated provocations with Ehrlich's preparations) is, if not an absolute, then in any case a serious adjunct to other methods (chemical and cytological examination of the cerebrospinal fluid) confirming the clinical persistence of the cure; but if a negative Wassermann reaction has no absolute prognostic significance, then a positive Wassermann reaction in the blood and, especially, in the cerebrospinal fluid, even with clinical well-being, in any case excludes the presence of recovery (prognostic value of the Wassermann reaction). After these basic propositions of the serology of syphilis were established (diagnostic, control-therapeutic, and prognostic value of the Wassermann reaction), its development began in all branches of medicine. Internal diseases. The doctrine of visceral syphilis was greatly deepened by serology, which revealed the syphilitic character of many processes in internal organs. Gradually, through the works of a whole pleiad of investigators, the syphilitic pathogenesis of certain diseases of the heart and blood vessels was established: aortitis (70-90%), vascular sclerosis (about 60%), heart valve insufficiency (20-25%), myocarditis (about 60%), cardiac sclerosis, as well as certain liver cirrhoses (from 30 to 40%). Nephritis with a positive Wassermann reaction was described by Bauer, Nevlin (about 29%); Finkelstein at the State Venereological Institute observed kidney syphilis in a syphilis-infected rabbit, cured with bismuth. Serologically, syphilis of the lungs, as well as chronic joint diseases proceeding under the guise of ordinary arthritis deformans and chronic rheumatism, were repeatedly recognized. Extremely important for the topical diagnosis of syphilis is the Wassermann reaction not only with blood, but also with effusion fluids (with ascites in liver cirrhoses, with pleural fluid, and joint fluid). The syphilitic nature of paroxysmal hemoglobinuria and certain cases of Banti's disease has also been established serologically. Nervous diseases and psychiatry. The Wassermann reaction has acquired the greatest importance in the pathology of nervous diseases, in which both blood and cerebrospinal fluid are tested for the Wassermann reaction. The first works in this field belong to Plaut and Nonne's school. Plaut established that in syphilitics without nervous changes, a persistently positive Wassermann reaction is obtained with blood, but it is absent with the cerebrospinal fluid. In progressive paralytics, on the other hand, even in early stages, a positive Wassermann reaction is obtained in 98% with both the cerebrospinal fluid and the blood (Morgenroth, Lesser, Citron, Levaditi, Neisser, Bruck). In tabes, a positive Wassermann reaction is observed in only 50% (Schütze, Citron, Plaut). This constant presence of a positive Wassermann reaction in progressive paralysis and tabes finally established their syphilitic nature. In brain syphilis, a positive Wassermann reaction with the blood is a constant phenomenon (60-70%), while with the cerebrospinal fluid, conversely, it is an exception (10%); therefore, a constant negative Wassermann reaction with the cerebrospinal fluid is an important differential diagnostic sign, making it possible, when the clinical picture is unclear, to exclude progressive paralysis, in which the cerebrospinal fluid always (90-100%) gives a positive Wassermann reaction. In syphilitic diseases of the spinal cord (myelitis, meningitis, gumma), the Wassermann reaction in a large percentage (60-70%) is successful with the patient's blood, much less often with the cerebrospinal fluid. What is important is that the Wassermann reaction is often already positive in the initial stages of the most serious nervous processes; a positive Wassermann reaction with the cerebrospinal fluid gives psychiatrists the opportunity to distinguish the early neurasthenic form of progressive paralysis from simple neurasthenia; this early serodiagnosis of progressive paralysis, even in the absence of noticeable mental changes, in connection with the newest therapy can change the poor prognosis of this disease for the better. The cerebrospinal fluid is analyzed not only by the Wassermann method, but also by other methods (Nonne-Apelt, Pandy, sublimate, Goldsol, Mastix reaction; investigation for pleocytosis, hemolysin, etc.); the most frequently used is the Wassermann reaction performed according to Hauptmann-Hößli (not with a single dose of cerebrospinal fluid, but with a whole series, starting from 0.1, 0.2, 0.5, 1 cubic centimeter). This is important in a differential diagnostic respect, since in some diseases (progressive paralysis) the Wassermann reaction is successful with small doses of cerebrospinal fluid (0.1-0.2), and in others (tabes) only with large doses (0.5-0.7, up to 1 cubic centimeter). A positive Wassermann reaction with the cerebrospinal fluid indicates the presence of the pale spirochete somewhere in the nervous system; but this "somewhere" often turns into a definite diagnosis, since the Wassermann reaction with blood serum, in combination with the Wassermann reaction of the cerebrospinal fluid, in the presence of pleocytosis and altered chemistry of the cerebrospinal fluid, makes it more precisely possible to differentiate various forms of neurolues (progressive paralysis, tabes, cerebrospinal meningitis, brain syphilis, etc.); moreover, such an analysis of the cerebrospinal fluid provides the physician with material not only for diagnosis, but also for the individualization of therapy and prognosis. In the works of Dreyfus and Nonne, based on long-term observations of the same patients (more than 2,000 people) with various forms of both early syphilis without nervous symptoms and various nervous diseases of a syphilitic and non-syphilitic nature, the following propositions were formulated: 1) cerebrospinal fluid with a positive Wassermann reaction indicates active neurolues; 2) cerebrospinal fluid with a negative Wassermann reaction, although it does not speak with absolute certainty for the cure of the nervous system, does so with high probability for the absence of a tendency for the process to progress; 3) in therapy, it is necessary to strive to obtain a negative Wassermann reaction of the cerebrospinal fluid; 4) salvarsan therapy, converting a positive Wassermann reaction of the cerebrospinal fluid into a negative reaction, undoubtedly and most often gives a prolonged improvement of the process; 5) one cannot be guided in the therapy of syphilis only by the Wassermann reaction of the blood, a parallel examination of the cerebrospinal fluid is necessary; 6) not single, but periodic examinations of both blood and cerebrospinal fluid are necessary; 7) serology provides much data for judging the prognosis (curability), but they are not absolute; it acquires significance only together with other indicated reactions, as well as when compared with the clinical condition of the patient. Congenital syphilis. The Wassermann reaction presented the so-called laws of Profeta and Colles in a new light. Immunity (according to Colles' law) against syphilis in apparently healthy mothers who gave birth to sick children turned out, in reality, not to be true insusceptibility to the pale spirochete, but only an asymptomatic infection with a positive Wassermann reaction. Profeta's law, which states that apparently healthy children born to syphilitic parents remain immune against syphilis, was also debunked by the Wassermann reaction discovered in such children; consequently, the latter, according to Kolle's terminology, are "asymptomatic" syphilitics. A number of foreign and Russian authors have discovered a high percentage of positive Wassermann reactions in children with various signs of stigmata not entirely typical of syphilis (97.2%); the Wassermann reaction in them is difficult to treat (in only 41%) and moreover not for long, which is a poor prognostic sign. In children under one year old, the Wassermann reaction is often negative and only later becomes positive in view of the lesser lability of the globulins of their serum; in such cases, repetition of the Wassermann reaction is required. Obstetrics and gynecology. Examination of pregnant women and women in childbirth who have a peculiar metabolism favoring the appearance of non-specific reactions makes it necessary to treat a positive Wassermann reaction in them with particular caution. These non-specific reactions in pregnant women, women in childbirth, and newborns, which are characterized by inconstancy, often depend on improper bowel function and in most cases disappear when blood is taken on an empty stomach and with preliminary bowel cleansing; when performing the Wassermann reaction in pregnant women, women in childbirth, and children, it is necessary to observe certain technical conditions (selection of antigens, individuality of working doses). In the first week after childbirth, the percentage of positive reactions is somewhat lower than the actual one in both women in childbirth and newborns, and therefore the Wassermann reaction is repeated after 2-3 weeks. In pregnant women, according to Finkelstein, lues is detected serodiagnostically in 5.5% (based on 12,000 examinations). Surgery. The Wassermann reaction, according to a number of authors (Karewsky, Coenen, Betzke, etc., among Russians—Vvedensky, Fronshtein, Finkelstein), has great diagnostic significance in surgery (55-60% positive Wassermann reactions).

There are reports of positive serodiagnosis of syphilis in a number of surgical diseases proceeding atypically (processes of joints, bones, testicles, chronic suppurations, tumors of various regions). In the presence of effusions (joints, etc.), their examination for the Wassermann reaction is extremely important, since with a positive Wassermann reaction with such fluid the diagnosis of syphilis is absolute. Ophthalmology. According to the data of many authors, the syphilitic nature of a number of eye diseases (cornea - 83-98%, iris - 33-48%, retina - 26-35%, optic nerve and muscular apparatus - about 50%, etc.) was determined with the help of the Wassermann reaction; therefore, its importance in ophthalmology must be recognized as enormous. The importance of the Wassermann reaction in otolaryngology is no less great than in other fields. Ozaena, which before the Wassermann reaction was considered a manifestation of syphilis, thanks to serology (which has been confirmed at the present time by bacteriological studies) has been excluded from the list of diseases suspicious for syphilis. Deafness and otosclerosis, thanks to the Wassermann reaction, very frequently have to be linked with syphilitic infection (from 50 to 76%). Pathological anatomy and forensic medicine. Of other fields where the Wassermann reaction has rendered great services, one can point to forensic medicine (Bonne, Langer, Weissenbach, and others) and to pathological anatomy (Abrikosov, Lubarsch, Marchand, Wolff, and others). The latter on the autopsy table confirmed the correctness of intravital serological diagnoses; the evaluation of a positive Wassermann reaction with cadaver blood requires great caution. In forensic medical practice, the Wassermann reaction is sometimes the only objective criterion untangling very obscure casuistics of family and social relations (sources of infection of litigating spouses, children, nursing staff in institutions, etc.). Nonspecific Wassermann reactions. At the present time, control material has accumulated on the so-called "nonspecific" Wassermann reactions described in a number of non-syphilitic processes (acute infectious diseases, malaria, leprosy, tumors). Those physiological states during which the appearance of the Wassermann reaction is possible were also noted, such as: the state of digestion, pregnancy, lactation, taking certain drugs (digitalis, alcohol, chloroform); some authors (Finkelstein) experimentally on rabbits managed to establish the significance of starvation, during which nonspecific positive Wassermann reactions turned into negative ones. The question of the practical significance of partial nonspecific reactions can be formulated (Finkelstein) as follows: 1) a partial reaction (+, ++...) is significant only if it is constant; 2) such a reaction clinically has significance as a symptom of syphilis only in subjects with undoubted syphilis in their anamnesis, who have not been ill in the immediate past two weeks with an acutely contagious process and do not have a malignant tumor; 3) from the cited data follows the rule according to which blood should be taken for examination by the Wassermann method: a) at normal temperature, b) on an empty stomach, c) outside of taking, for at least three days, any drugs whatsoever. The prophylactic significance of the Wassermann reaction became especially relevant after the experienced period of wars, which left as a heritage to humanity a lot of latent syphilis (especially in women and children); this is convincingly stated by the statistics of Strumpff and Hubert, who, on the basis of mass examination of case histories of a number of hospitals, established the presence of about 10% of latent syphilis without anamnesic indications on the part of the patients. In view of this, in hospitals in Germany, the same view of the Wassermann reaction has established itself as of urine examination for protein and sugar: every patient is obligatorily examined for the Wassermann reaction. The USSR, according to the data of the Central Serological Commission, at least in large centers, is following the same path, especially regarding persons subject to admission to institutions with a dormitory character (children's homes, nurseries, mother and infant homes, barracks, etc.). To illustrate this provision, see below the summary of materials of the Bacteriological Institute of the Moscow Department of Health (Table 5) on the basis of many thousands of examinations. Table 5. Wassermann reaction in foundlings, in pregnant women, in wet nurses. Strongly positive: foundlings 12.6%, pregnant women 5.5%, wet nurses 11%. This table, summarizing the group of prophylactically examined individuals, shows how great the significance of the Wassermann reaction is in this sense. This stands out especially convexly in relation to foundlings and wet nurses, in whom the anamnesis yields nothing. The serological material of the same institute, presented in Table 6, also shows that serodiagnosis can be used as a criterion of the success of the fight against venereal disease (Finkelstein). Table 6. Number of positive Wassermann reactions in Moscow (in %) 1927: 12.5, 28.5, 18.9, 19.3, 11.8, 16.1, 12.7. This table clearly shows a sharp decrease in active lues (from 38 to 12.5%) depending on the planned organization of the fight against venereal disease and, in particular, on energetic salvarsanization. With such a sanitary approach to the Wassermann reaction, the latter, together with other serodiagnostic methods (Kahn reaction, Sachs-Georgi, and Meinicke reactions), acquires the significance of one of the necessary links in the chain of measures to combat venereal disease.

Yu. Finkelstein.