Streptococcal Toxin Research Articles

A new serum for the treatment of postpartum sepsis

Based on the work of American authors with the isolation of scarlet streptococcus toxin, the authors made an attempt to isolate Puerperal streptococcus toxin and obtain an antitoxic serum from a horse by the American Dochez method (Agarklossmethode), which they used for therapeutic purposes in 200 women with postpartum sepsis, with strict clinical and bacteriological monitoring of each case.

The Newer Knowledge of Diphtheria and Scarlet Fever and its Application in Hospital Practice and in Community Immunisation

1. Scarlatinal streptococci obtained from the throats of cases of scarlet fever can be divided into various groups by means of agglutination and absorption tests. The same type of streptococcus can on occasion originate at least five separate clinically distinguishable diseases, namely, scarlet fever, tonsilitis, erysipelas, puerperal fever, and broncho-pneumonia, and it would appear that, so far as streptococcic infections are concerned, the nature of the disease entity is determined by the toxigenic qualities of the type of streptococcus, by the susceptibility or insusceptibility of the individual as determined by the absence or presence of the specific antibodies in the blood, and by the site of the infection itself (see p. 330).2. Strong corroboration for the view that the S. scarlatinae is the causal organism of scarlet fever is obtained from the following findings, viz.:(a) S. scarlatinae have been isolated from the throat brushings of practically all acutely ill scarlet fever patients (see p. 329).(b) The whole clinical picture of scarlet fever going on to marked desquamation is produced by the subcutaneous injection of the exotoxin derived from the S. scarlatinae, the exotoxin having been haeated to 55° C. for one hour, with a view to destroying any filterable living virus which might be associated with the filtered exotoxin (see p. 342).(c) In the Schultz-Charlton reaction the blanching of the scarlet fever rash is caused by the serum of a horse immunised against S. scarlatinae and its toxins.(d) Dick-positive and Dick-negative reactions as produced by the intradermal injection of the streptococcus toxin have the closet correspondence to the degree of susceptibility or immunity to scarlet fever of the respective reactors (see p. 334).(e) Susceptible nurses once they are actively immunised by injections of scarlatinal streptococcus toxin have been shown to be immune to the toxin of scarlet fever (see p. 337), and susceptible school children similarly inoculated are likewise immune (see p. 338).(f) Return cases of scarlet fever can be prevented by actively immunising susceptible contacts with scarlatinal streptococcus toxin prior to the scarlet fever patient being discharged from hospital (see p. 339).(g) Susceptible contacts can be safeguarded from taking scarlet fever by passively immunising them with a sufficient does of antistreptococcus serum obtained from a horse wich has been immunised by injections of S. scarlatinae and its toxin (see p. 349).3. The limitations of the Schultz-Charlton reaction as an aid in the diagnosis of scarlet fever have been confirmed (see p. 330).4. Evidence has been obtained which firmly establishes the value of the Dick suseptibility test as a measure of susceptibility to scarlet fever (see p. 332).5. Extensive corroboration of the value of the Schick test as a measure of susceptibility to diphtheria has been obtained (see p. 334).6. The efficacy of active immunisation against scarlet fever by means of scarlatinal streptococcus toxin injections has been demonstrated by the fact that, while scarlet fever has been present in epidemic form in Aberdeen, no nurses or maids in Aberdeen City Hospital have contracted scarlet fever since June 1st, 1925, from which date the nursing and domestic staffs of the hospital have been actively immunised before being admitted for duty to the scarlet fever wards; whereas, prior to that date, an average of 8·5 nurses, or 9·5 per cent. of the nursing staff, and 1·4 maids, or 4·2 per cent. of the domestic staff. annually suffered from scarlet fever (see p. 337).7. Coincident with the disappearance of scarlet fever in the immunised nursing staff of the City Hospital, there has been a notable increase in the incidence of streptococcic tonsilitis in these immunised nurses, and the streptococci obtained from these cases of tonsilitis in nurses commonly fall into one or other of the serological groups of scarlatinal streptococci; and accordingly it would appear to be proved that immunised nurses, while protected by immunisation from the toxic effects of the exotoxin of S. scarlatinae, are not protected against tonsilitis due to S. scarlatinae (see p. 338).

Scarlatinal Nephritis Experimentally Induced in the Dog.

Since the publication of the results of our studies upon experimental nephritis in the rabbit with the toxic principle of Streptococcus scarlatinae, we have found that the dog is a more satisfactory animal for the purpose of causing nephritis with this particular injurious agent. This animal has proven to be not only highly susceptible to infection but developed regularly a severe and often fatal form of acute glomerulonephritis following the injection of the specific streptococcal toxin alone. None of the animals showed at any time an exanthem; however, it is significant that the induced kidney lesions completely correspond histopathologically to the glomerular and acute interstitial scarlatinal nophritis of man. This communication is a brief report of the effects upon the kidneys of the dog produced by the viable culture and also the pure toxin of Streptococcus scarlatinae. All dogs employed in the experiment were healthy and under three years of age. The animals were kept under close observation for a period of ten days prior to inoculation, during which time daily analysis of the urine was made and the blood chemistry determined. Only dogs that showed normal kidney function throughout this period were selected for the experiment. The preliminary study of the urine and blood was carried out by our colleague. Professor Denis, of the department of biochemistry. Infectivity of the Dog. Six full-grown, healthy clogs were inoculated with living cultures of Scarlatinal streptococcus. Two animals received the injection intravenously, two subscutaneously and two intraperitoineally. In each instance the dosage was 10 mills of the surface growth from slanted sheep-serum agar which had been washed off and sususpended in 50 mils of sterile normal saline.

CHAPTER V.:The Intracutaneous Scarlatina Streptococcus Toxin Reaction (Dick test) and its Relation to the S. R. Curve.

Acta PaediatricaVolume 7, Issue s1 p. 52-64 CHAPTER V.:The Intracutaneous Scarlatina Streptococcus Toxin Reaction (Dick test) and its Relation to the S. R. Curve. First published: May 1927 https://doi.org/10.1111/j.1651-2227.1927.tb03950.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume7, Issues1May 1927Pages 52-64 RelatedInformation

Further Observations on the Toxins of Hemolytic Streptococci

Abstract It is obviously important that a definite conclusion be reached as to whether, with present methods, it is possible to distinguish a specific group of scarlet fever streptococci. Although agglutination reactions are undoubtedly of value in bringing out certain variations, any differentiation of practical significance must be based ultimately on the action of the toxin. In a report presented last year (1) we recorded the results of studies with a hundred and fifty strains of hemolytic streptococci from different sources, tested on goats. The results of these tests indicate no fundamental qualitative or quantitative differences in the toxins of scarlet and non-scarlet fever streptococci. Similar observations have since been recorded. Dr. Anna Williams (2), Dr. E. C. Rosenow (3) and other investigators find that hemolytic streptococci from infections other than scarlet fever frequently produce toxins similar to those of the scarlet fever streptococci and they also report variable reactions in different individuals.

THE PRACTICAL VALUE OF BIOLOGIC THERAPY IN THE PROPHYLAXIS AND TREATMENT OF SCARLET FEVER

Professor of Pathology and Bacteriology in the Graduate School of Medicine of the University of Pennsylvania <h3>PHILADELPHIA</h3> Since the Schick test has proved so reliable for determining susceptibility to diphtheria, and toxin-antitoxin mixtures have been so successful in vaccination against the disease—to say nothing of the value of diphtheria antitoxin in passive prophylaxis and treatment—it is no wonder that similar attempts have been made in the specific prophylaxis and treatment of scarlet fever. The Dicks discovered three years ago that the disease apparently was caused by a hemolytic streptococcus and its soluble or exogenous toxin. A large amount of investigation has been devoted to the skin test for susceptibility to scarlet fever, to vaccination with streptococcus toxin and to prevention and treatment with antiscarlet fever streptococcus serum. It is my purpose to summarize briefly their practical value and applications at the present time. I fully realize that our information is

Studies of the Toxins of the Hemolytic Streptococci Associated with Scarlet Fever

Abstract Ever since laboratory procedure established the almost constant presence of hemolytic streptococci in the early stages of scarlet fever, researches have been directed toward determining the etiological relationship of these organisms to the disease. It is only recently, however, that a satisfactory evaluation of clinical and laboratory evidence has been made possible through the application of newer methods by Dochez (1, 2, 3, 4, 5,) and the Dicks (6, 7, 8, 9, 10). These studies are so familiar that it is unnecessary to review them here. It is evident, however, that further advances in our conception of the rôle of hemolytic streptococci in scarlet fever and in other infectious processes are largely dependent on a more exact knowledge of streptococcus toxins and their antitoxins. As a basis for such studies, uniform and readily applicable methods for the preparation and standardization of both the toxins and antitoxins must be developed.

"THERAPEUTIC RESULTS WITH CONCENTRATED SCARLET FEVER ANTITOXIN"

ABSTRACT To the Editor: —The discussion by Dr. George F. Dick of the paper by the Dicks on Therapeutic Results with Concentrated Scarlet Fever Antitoxin (The Journal, Nov. 28, 1925) followed a paper which I presented at the same meeting of the Section on Pharmacology and Therapeutics in Atlantic City last May. My paper has not yet been published and my discussion of Dr. Dick's paper was not included.In the article entitled Streptococcus Toxin in Preventive Immunization (The Journal, Feb. 16, 1924), the Dicks reported typical moderate to severe scarlet fever-like symptoms following injections of large doses of the streptococcus toxin, symptoms exactly like those described by Gabritschewsky in the Berliner klinische Wochenschrift, May 6, 1907, after the use of his toxin-vaccine. At that time no other attempt was made by the Dicks to recommend any special dosage, and as I commenced my work with toxin immunization soon after the

Some Experiments with Haemolytic Streptococcus Toxin of Varying Origin in Connection with the "Dick" Test for Scarlet Fever

Some Experiments with Haemolytic Streptococcus Toxin of Varying Origin in Connection with the "Dick" Test for Scarlet Fever

Complexity of the Scarlet Fever Toxin and Antitoxin

Summary and Conclusions The fact that an individual convalescent scarlet fever serum neutralizes the toxin of a certain scarlet fever streptococcus in certain susceptible persons and not in others proves that the toxic filtrate has more than one toxin and that a person may be susceptible to one component and not to another or others. We can conceive that the usual scarlet fever strain makes a toxic filtrate containing the different toxins A, B, C, D. A less common strain A, C, D, E or B, C, D, E. Strains from some septic sore throats C, D, H, I and from some erysipelas cases C, D, K, L. Antitoxins to a greater or less degree would develop in any person or animal injected with any toxic filtrate to neutralize the actual toxins present in the filtrate. The finding that a certain convalescent serum or antitoxic horse serum will fail to neutralize a toxin for certain persons in the same quantity which is successful in others, but in larger amount succeeds, proves that the antitoxic response is different for the different component toxins either because of the different proportions of the toxins in the filtrate or because the child or animal responds differently in degree to the stimulus of the different toxins. We have the analogy of horses receiving the same amount of diphtheria and tetanus toxin. Some produce strong antitoxin for diphtheria but weak for tetanus and others strong antitoxin for tetanus but weak antitoxin for diphtheria. A convalescent scarlet fever serum from a single patient may fail to cause blanching in a true case of scarlet fever because the two cases are due to two strains that differ in at least one toxin and so in one induced antitoxin. It is also probable that there are strains of streptococci that have the power to produce scarlet rash producing toxins which are quite different from the standard Dick strains, so that after convalescing from infection due to one strain a second infection might occur from the other strain. Every year a few cases sent into the hospital with the diagnosis of scarlet fever after recovery develop a second attack. We have been inclined to think that the first attack was not scarlet fever while if we had made a culture, we possibly would have found a strain of streptococci that made different toxins from the usual cases. If this assumption is true a case of scarlet fever at the onset might give a negative Dick test to the Dick strain toxin and its serum would then neutralize the standard toxin and blanch the rash of an ordinary case of scarlet fever. The point is that it is not safe at the present time to limit the diagnosis of scarlet fever to cases due to the usual strains making the standard group of toxins. At most the exceptional strains cause only a small minority of the cases of scarlet fever. Cases that do not respond to the serum should be studied carefully to determine whether their strains are typical ones. It is possible that in these a polyvalent antitoxic serum is indicated or it may simply be that the scarlet fever streptococci or other streptococci or other microorganisms have invaded the deeper tissues and are beyond the help of antitoxins. Further investigation is necessary to determine the value of a bactericidal serum in these cases.

Early and late immunity results with scarlatinal streptococcus toxin.

1. A complete antitoxic immunity to scarlet fever was produced by 4 doses of scarlet fever toxin (250, 1000, 2000 and 3000 skin test doses) in 70 per cent of injected persons, and a partial immunity in 26 per cent. A second series of toxin injections successfully immunized most of the refractory cases.

Studies of the formation of the streptococcus toxin

In a paper read before the American Society of Bacteriologists in December, 1924, Huntoon reported observations on the progressive formation of skin-reacting toxin in the Berkefeld filtrate from a 44 hr. culture of hemolytic streptococcus (scarlet fever). He suggested that this formation of toxin in the absence of organisms was probably due to the action of an enzyme (protease), secreted by the bacteria, in the filtrate. The following experiments were conducted to determine something of the nature of this enzyme action. The organism used was a strain of hemolytic streptococcus isolated from a scarlet fever patient and obtained from the Board of Health. Qualitative tests on filtrates obtained by passing a 36 hr. culture (bacto-veal-horse-plasma broth) through a Berkefeld filter, and on extracts of the bacterial bodies (obtained as described below), failed to show the presence of active protease, using as substrate either fibrin or a solution of proteose (prepared from bacto-peptone). Mass cultures were made by growing the streptococcus on whole blood bacto-veal agar. The growth was carefully removed and dried over concentrated sulphuric acid. Three tenths gm. of dried bacteria was well ground and suspended in a M/15 Na, HP04, KH, PO, mixture having a pH of 7.2. This was shaken at intervals during 12 hours, and filtered through Berkefeld. This filtrate was designated “bacterial extract.” Cutaneous tests were made by intradermal injections, using the Dick teichnique, in the arm of an adult male subject who was skin-sensitive to the Dick toxin. After many repeated injections in this subject, it seemed that some change occurred in the skin which made the readings of the tests difficult to interpret. The later experiments, therefore, were done on infant subjects who gave positive (4 plus) reactions to the Dick test, and negative controls.

Results Obtained with the Dick Test before and after Immunization with the Toxin of the Hemolytic Streptococcus of Scarlet Fever

Results Obtained with the Dick Test before and after Immunization with the Toxin of the Hemolytic Streptococcus of Scarlet Fever

Application of the Ramon Flocculation Principle to the Titration of Scarlet Fever Streptococcus Toxin and Antitoxin

Application of the Ramon Flocculation Principle to the Titration of Scarlet Fever Streptococcus Toxin and Antitoxin

Reactions induced by intracutaneous injections of toxins of streptococci from scarlet fever.

With toxins prepared in this laboratory from a strain of a scarlet fever streptococcus received from Doctor Dochez, no skin reactions were induced in rats, mice, guinea-pigs, kittens, chickens, pigeons, monkeys, sheep or a calf. Questionable reactions were obtained in two young pigs with undiluted toxin and also in four rabbits out of eighteen, the remaining fourteen giving no reactions.Definite skin reactions, however, have been induced in white goats. All fourteen goats tested gave reactions to the toxin, but individual goats appeared to vary in susceptibility. With ten, definite reactions were obtained with 0.2 cc. of a 1:500 dilution of a toxin which gives a reaction in a 1:1000 dilution in a susceptible human being. Four other goats gave reactions to lower dilutions, varying from 1:50 to 1:250. The reactions in goats reached a maximum in 18 to 24 hours and at this stage were usually quite similar to those observed in human beings. In the more susceptible goats according to the potency of the material...

Further studies with the Dick test and active immunization with scarlet fever streptococcus toxin.

5. Retest of a group of children actively immunized with increasing doses of scarlet fever streptococcus toxin. 1. The application of the Dick test to a group of 320 children at the Horace Mann School and at the Riverdale Country School, New York City, has shown a very high percentage of susceptible individuals in this class of children coming from the more well-to-do homes. The test showed that of 320 children varying in age from 5 to 18 years, 266 or 83.0 per cent were susceptible and gave a positive reaction. The Dick test was also given to 80 nurses at St. Vincent's Hospital, and of these 42 or 52.5 per cent showed a positive reaction. The nurses at this hospital had been previously tested with the Schick test and 55 per cent were found susceptible to diphtheria. A group of babies were tested at the Heckscher Foundation with the following interesting results : Of a group of 4570 individuals varying in age from a few weeks to over 20 years we found that 1543 or 34.4 per cent gave a positive Dick reaction. Up to 6 months the percentage of positive reactions was 44.8; from 6 months to 3 years it ranged from 64 to 71 per cent; from 3 to 5 years between 46 to 56 per cent and from 5 to 20 years between 24 to 37 per cent.