Homologous Streptococci Research Articles

Protective Studies with Group A Streptococcal M Protein Vaccine. III. Challenge of Volunteers after Systemic or Intranasal Immunization with Type 3 or Type 12 Group A Streptococcus

Alum-precipitated and soluble, purified M protein vaccines were prepared from type 3 and type 12 group A Streptococcus. Adult volunteers were assigned to one of three groups: group I received placebo by both parenteral and intranasal routes; group 2 received vaccine parenterally (either type 3 or type 12) and placebo intranasally; and group 3 received placebo parenterally and vaccine intranasally (either type 3 or type 12). Subjects were inoculated three times at montly intervals. Thirty to 50 days after the last dose, all subjects were challenged with homologous streptococci applied to the oropharynx. Six subjects (30%) vaccinated subcutaneously had definite illness, three (15%) had probable illness, and 11 (55%) had no illness. In the group vaccinated intranasally, four (14%) had definite illness, two (7%) had probable illness, and 22 (79%) had no illness. Fifteen controls (42%) had definite illness, and 21 (58%) had no illness. The rate of colonization was significantly lower in recipients of intranasal vaccine. Average clinical scores and vaccine side effects were also decreased in subjects vaccinated intranasally. Induced serum antibody as measured by passive hemagglutination was not a reliable predictor of resistance to streptococcal pharyngitis. Penicillin was administered to all subjects five days after challenge. No sequelae of streptococcal infection or other complications occurred. Thus, local immunization with M protein apparently may reduce both colonization and clinical illness after challenge with homologous streptococci.

Electron microscopic studies on streptococci. I. M antigen.

The presence of M antigens on group A streptococci is associated with hairlike fimbriae that cover the surface of the streptococcal cell wall and are demonstrable by electron microscopy. These fimbriae also may be associated with R antigen. Like M protein, the surface fimbriae are destroyed by trypsin treatment and reappear when "trypsinized" streptococci are reincubated in fresh, trypsin-free broth. Ferritin-conjugated, type-specific antibodies localize on homologous M+ cells in a pattern suggestive of several M antigenic sites along the length of individual surface fimbria. The M-associated fimbriae remain on the residual cell wall after removal of the bulk of group-specific polysaccharide through nitrous acid extraction. This suggests attachment of the fimbriae to the mucopeptide and minor polysaccharide components remaining in the nitrous acid-extracted wall. The pattern of localization of ferritin-conjugated antibodies on homologous streptococci before and after trypsin exposure and upon reincubation of the trypsinized cells in fresh medium suggests the following hypothesis: M antigen is secreted by the cell, is partially excreted through the otherwise intact cell wall, and is bound by the wall so that M protein occupies a peripheral, exposed position on the surfaces of the streptococcal cell wall.

Factors involved in treatment failures following oral penicillin therapy of streptococcal pharyngitis

Among 331 children with group A streptococcal pharyngitis who were treated with a 10 day oral regimen of either sodium nafcillin or penicillin V potassium, there were 39 treatment failures. There was no correlation between the incidence of relapse and patient's age, sex, interval between onset of illness and onset of therapy, history of respiratory tract allergy, compliance in completing therapy, concomitant presence of penicillinase-producing staphylococci, or incidence of homologous streptococci in household contacts. There was, however, a significantly higher incidence of relapse in patients harboring M-typable strains, as compared with patients harboring nontypable strains; this was particularly evident for patients with types 3 and 12 streptococci. Among the relapse group, there was no difference in the bacteriologic outcome of those patients who received a second course of treatment as compared with the patients who were not re-treated.

Natural Resistance of Germ-Free Mice and Colostrum-Deprived Piglets to Group A Streptococci

Summary A study was made of the resistance of germfree and conventional mice to direct challenge with Group A streptococci of graded virulence. Germ-free and conventional mice were highly, and equally, resistant to nonencapsulated strains of Group A streptococci lacking M protein. Greater susceptibility of germ-free mice could be demonstrated only with Group A strains containing both M protein and capsules. This difference could be abolished by a globulin fraction of normal mouse serum but not by normal mouse γ-globulin or by homologous type-specific antiserum. In vitro studies with bloods of germ-free mice and colostrum-deprived piglets provided additional evidence that phagocytosis of avirulent Group A streptococci required little, if any, specific antibodies. Bloods from these animals phagocytized and destroyed streptococci as readily as did their conventional counterparts. Thermolabile opsonins against avirulent Group A streptococci were readily demonstrable in the blood of colostrum-deprived piglets, whose serum contains only minute amounts of γ-globulin. Absorption of the sera of these animals at low temperatures with large amounts of homologous streptococci resulted in some decrease in opsonization, but considerable residual phagocytosis was apparent. The leukocytes of colostrum-deprived, and of colostrum-fed, animals were equally capable of phagocytizing and destroying Group A streptococci in the presence or absence of specific opsonins.

THE PRESENCE OF A VIRULENCE FACTOR IN M PROTEIN EXTRACTS OF GROUP A STREPTOCOCCI. I. THE ENHANCEMENT OF VIRULENCE OF HOMOLOGOUS STREPTOCOCCI BY THESE EXTRACTS.

The relation of streptococcal cell products to pathogenicity of the group A streptococci has been the subject of many investigations and has led to the realization that no single extracellular or intracellular component can be equated to the virulence of these organisms. However, there is considerable evidence to establish type-specific M antigen as the most important virulence factor of group A streptococci. The literature regarding the preparation and properties of M antigen and its role as a virulence factor has recently been reviewed by Lancefield (1962). That M antigen is a major virulence factor is based largely upon indirect evidence. Strains virulent for mice and resistant to phagocytosis generally contain M antigen. Blocking M antigen with specific antibody or removing it enzymatically results in a decrease in virulence or in resistance to phagocytosis. Furthermore, mice can be protected against virulent group A streptococci with homologous anti-M serum. In the present study we investigated, by a more direct approach, the role of M protein as a virulence factor. Essentially, acid extracts of M protein were

REACTIONS OF RABBITS TO NON-HEMOLYTIC STREPTOCOCCI

Rabbits immunized intravenously with living culture or nucleoproteins of non-hemolytic streptococci react to subsequent intracutaneous inoculations with homologous streptococci with smaller and harder lesions than are shown by normal animals similarly inoculated; and they do not develop the general manifestations of hypersensitiveness such as are shown by animals previously inoculated into the tissues with the same cultures. A rabbit may react to intracutaneous inoculation with non-hemolytic streptococci in one of four ways, depending on whether it is normal, hypersensitive, immune or cachectic. Most normal animals show a secondary reaction about 10 days after inoculation with suitable strains of non-hemolytic streptococci; hypersensitive, allergic, or hyperergic animals show much larger lesions than do normals with the corresponding doses of the same streptococci, and practically never show secondary reactions; immune animals show smaller and harder early lesions and usually do not have secondary reactions if they are fairly well immunized. Cachectic animals show very soft and rapidly fading primary reactions and no secondary reactions.

TRANSMISSION OF RESPIRATORY ANAPHYLAXIS (ASTHMA) FROM MOTHER TO OFFSPRING

Rabbits immunized intravenously with living culture or nucleoproteins of non-hemolytic streptococci react to subsequent intracutaneous inoculations with homologous streptococci with smaller and harder lesions than are shown by normal animals similarly inoculated; and they do not develop the general manifestations of hypersensitiveness such as are shown by animals previously inoculated into the tissues with the same cultures. A rabbit may react to intracutaneous inoculation with non-hemolytic streptococci in one of four ways, depending on whether it is normal, hypersensitive, immune or cachectic. Most normal animals show a secondary reaction about 10 days after inoculation with suitable strains of non-hemolytic streptococci; hypersensitive, allergic, or hyperergic animals show much larger lesions than do normals with the corresponding doses of the same streptococci, and practically never show secondary reactions; immune animals show smaller and harder early lesions and usually do not have secondary reactions if they are fairly well immunized. Cachectic animals show very soft and rapidly fading primary reactions and no secondary reactions.

Transmission of Respiratory Anaphylaxis (Asthma) From Mother to Offspring.

Rabbits immunized intravenously with living culture or nucleoproteins of non-hemolytic streptococci react to subsequent intracutaneous inoculations with homologous streptococci with smaller and harder lesions than are shown by normal animals similarly inoculated; and they do not develop the general manifestations of hypersensitiveness such as are shown by animals previously inoculated into the tissues with the same cultures. A rabbit may react to intracutaneous inoculation with non-hemolytic streptococci in one of four ways, depending on whether it is normal, hypersensitive, immune or cachectic. Most normal animals show a secondary reaction about 10 days after inoculation with suitable strains of non-hemolytic streptococci; hypersensitive, allergic, or hyperergic animals show much larger lesions than do normals with the corresponding doses of the same streptococci, and practically never show secondary reactions; immune animals show smaller and harder early lesions and usually do not have secondary reactions if they are fairly well immunized. Cachectic animals show very soft and rapidly fading primary reactions and no secondary reactions.

Hyperergic Tissue Response to Non-Hemolytic Streptococci.

Two years ago in collaboration with Andrewes1, 2 we described a peculiar response in the skin of rabbits to the inoculation of certain non-hemolytic streptococci. This was termed the secondary reaction because it occurred after the primary reaction to the inoculation had subsided. It was shown3 not to correspond in its various phases with the Arthus phenomenon which is induced in rabbits by immunization and subsequent skin injection with various coagulable proteins. We, therefore, suggested that if this were an allergic phenomenon it was of the type seen in tuberculosis. Our subsequent investigations have been guided by this hypothesis.The object of this report is to describe some of the concomitant phenomena of the secondary reaction and suggest their significance.Eye Reaction: If the locally anesthetized cornea of a rabbit, which has shown a well marked secondary reaction, is lightly scarified and a drop of broth culture sediment of homologous streptococci is instilled into the conjunctival sac, there u...

Specific Antibodies in Scarlet Fever

I. Agglutinins.?Griinbaum1 seems to have been the first to report on the agglutination of streptococci of scarlet fever by the serums of scarlet-fever patients. He simply states that he was able to isolate a coccus from a case of scarlet fever which agglutinated with scarlet-fever serum. Baginsky and Sommerfeld2 examined the serums of scarlet-fever patients in the third to the sixth week of the disease, for specific agglutinins of streptococci, which were cultivated from cases of scarlet fever. Their results were absolutely negative. At about the same time Moser and von Pirquet* found that in 52 per cent of the cases examined the serum caused marked agglutination of scarlatinal streptococci. The serum from cases other than scarlet fever gave the reaction in a much smaller percentage and only on higher dilution. Salge and Hasenknopf4 made a comprehensive study of this question. They found that emulsions of streptococci of scarlet fever were markedly agglutinated by the serum of scarlatina in a dilution as high as 1:500, whereas the reaction failed with streptococci from other sources, even with a lesser dilution of the serum. This specific property of the serum vanishes toward the end of convalescence. Dopters denies the specific relation of scarlet-fever serum toward homologous streptococci. In his hands streptococci of various origin were agglutinated by the serum of scarlet-fever patients and indeed in some cases the serum did not react with streptococci from scarlet-fever cases. Dopter reaches the conclusion that the streptococcus is not the specific agent of the disease. Detot,6 and Detot and Boucart7 arrived at similar results. Since the agglutination is not specific they reject its application as a diagnostic means and deny the r61e of the streptococcus in the etiology of scarlet fever.

Injections of Homologous Streptococci Killed by Galactose in the Treatment of Suppurative Complications of Contagious Diseases

Ever since the treatment of infections by the injection of dead bacteria was first urged by Wright, interest in this method has been great, but the early reports of brilliant results have not met uniform confirmation. There is on record, however, a sufficiently large number of cases in which good results have followed the use of bacterial inoculations to justify further study of this subject, altho the number of cases in which the most careful use of these methods has