scholarly journals Opsonic Antibodies to the Surface M Protein of Group A Streptococci in Pooled Normal Immunoglobulins (IVIG): Potential Impact on the Clinical Efficacy of IVIG Therapy for Severe Invasive Group A Streptococcal Infections

1998 ◽  
Vol 66 (5) ◽  
pp. 2279-2283 ◽  
Author(s):  
Hesham Basma ◽  
Anna Norrby-Teglund ◽  
Allison McGeer ◽  
Donald E. Low ◽  
Omar El-Ahmedy ◽  
...  
Keyword(s):  
Ivig Therapy ◽  
M Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Streptococcal Toxic Shock Syndrome ◽  
Group A Streptococci ◽  
Streptococcal Infections ◽  
Opsonic Activity ◽  
Invasive Group ◽  
Significant Difference ◽  
Group A

ABSTRACT The surface M protein of group A streptococci (GAS) is one of the major virulence factors for this pathogen. Antibodies to the M protein can facilitate opsonophagocytosis by phagocytic cells present in human blood. We investigated whether pooled normal immunoglobulin G (IVIG) contains antibodies that can opsonize and enhance the phagocytosis of type M1 strains of GAS and whether the levels of these antibodies vary for different IVIG preparations. We focused on the presence of anti-M1 antibodies because the M1T1 serotype accounts for the majority of recent invasive GAS clinical isolates in our surveillance studies. The level of anti-M1 antibodies in three commercial IVIG preparations was determined by enzyme-linked immunosorbent assay (ELISA), and the opsonic activity of these antibodies was determined by neutrophil-mediated opsonophagocytosis of a representative M1T1 isolate. High levels of opsonic anti-M1 antibodies were found in all IVIG preparations tested, and there was a good correlation between ELISA titers and opsonophagocytic activity. However, there was no significant difference in the levels of opsonic anti-M1 antibodies among the various IVIG preparations or lots tested. Adsorption of IVIG with M1T1 bacteria removed the anti-M1 opsonic activity, while the level of anti-M3 opsonophagocytosis was unchanged. Plasma was obtained from seven patients with streptococcal toxic shock syndrome who received IVIG therapy, and the level of anti-M1 antibodies was assessed before and after IVIG administration. A significant increase in the level of type M1-specific antibodies was found in the plasma of all patients who received IVIG therapy (P < 0.006). The results reveal another potential mechanism by which IVIG can ameliorate severe invasive group A streptococcal infections.

scholarly journals Serum Opacity Factor (SOF) of Streptococcus pyogenes Evokes Antibodies That Opsonize Homologous and Heterologous SOF-Positive Serotypes of Group A Streptococci

2003 ◽  
Vol 71 (9) ◽  
pp. 5097-5103 ◽  
Author(s):  
Harry S. Courtney ◽  
David L. Hasty ◽  
James B. Dale
Keyword(s):  
Streptococcus Pyogenes ◽  
Rabbit Antiserum ◽  
M Protein ◽  
Group A Streptococci ◽  
Streptococcal Infections ◽  
Vaccine Candidates ◽  
Human Antibodies ◽  
Serum Opacity Factor ◽  
Group A

ABSTRACT Serum opacity factor (SOF) is a protein expressed by Streptococcus pyogenes that opacifies mammalian serum. SOF is also a virulence factor of S. pyogenes, but it has not been previously shown to elicit a protective immune response. Herein, we report that SOF evokes bactericidal antibodies against S. pyogenes in humans, rabbits, and mice. Rabbit antiserum against purified recombinant SOF2 opsonized SOF-positive M type 2, 4, and 28 S. pyogenes in human blood but had no effect on SOF-negative M type 5 S. pyogenes. Furthermore, affinity-purified human antibodies against SOF2 also opsonized SOF-positive streptococci. A combination of antisera against M2 and SOF2 proteins was dramatically more effective in killing streptococci than either antiserum alone, indicating that antibodies against SOF2 enhance the opsonic efficiency of M protein antibodies. Mice tolerated an intravenous injection of 100 μg of SOF without overt signs of toxicity, and immunization with SOF protected mice against challenge infections with M type 2 S. pyogenes. These data indicate that SOF evokes opsonic antibodies that may protect against infections by SOF-positive serotypes of group A streptococci and suggest that different serotypes of SOF have common epitopes that may be useful vaccine candidates to protect against group A streptococcal infections.

scholarly journals STUDIES ON THE PATHOGENICITY OF GROUP A STREPTOCOCCI

1959 ◽  
Vol 110 (4) ◽  
pp. 617-628 ◽  
Author(s):  
Marie Judith Foley ◽  
W. Barry Wood
Keyword(s):  
Hyaluronic Acid ◽  
Virulent Strain ◽  
Critical Role ◽  
M Protein ◽  
Group A Streptococci ◽  
Streptococcal Infections ◽  
Full Complement ◽  
Group A ◽  
Hyaluronic Acid Capsule

A quantitative study of the combined antiphagocytic effects of the M protein and the hyaluronic acid capsules of four strains of Group A streptococci revealed the following facts relating to their intraperitoneal virulence in mice and rats: 1. The most virulent strain, S23M (matt), produced both a large hyaluronic acid capsule and a full complement of M protein, the combined effects of which rendered the organism highly resistant to surface phagocytosis. 2. The slightly less virulent strain, T14/46 (matt virulent) was somewhat more susceptible to surface phagocytosis owing to the fact that its smaller capsule was less antiphagocytic than that of the S23M organism. 3. The glossy variant of the S23 strain (S23G), which ranked third in virulence, was still more susceptible to surface phagocytosis because of its lack of detectable M substance. Its large hyaluronic acid capsule, however, was capable of protecting it against phagocytosis on glass. 4. The least virulent strain, T14 (matt avirulent), was the most susceptible of all to phagocytosis. Though it possessed both M substance and capsule, which together prevented its phagocytosis on glass, each of them was shown to be quantitatively and functionally deficient as compared to Strain S23M. The differences in phagocytability, which appear to be directly related to the pathogenicity of the organisms, could be adequately demonstrated in vitro only by phagocytic tests designed to measure surface phagocytosis in the absence of opsonins. This fact is in keeping with the observation, previously reported, that surface phagocytosis plays a critical role in the defense of the host, particularly during the earliest stages of experimental streptococcal infections. Its possible relation to suppuration during the later stages of infection is also discussed.

scholarly journals Clinical and epidemiological features of group A streptococcal bacteraemia in a region with hyperendemic superficial streptococcal infection

1999 ◽  
Vol 122 (1) ◽  
pp. 59-65 ◽  
Author(s):  
J. R. CARAPETIS ◽  
A. M. WALKER ◽  
M. HIBBLE ◽  
K. S. SRIPRAKASH ◽  
B. J. CURRIE
Keyword(s):  
Streptococcal Infection ◽  
Northern Territory ◽  
Streptococcal Infections ◽  
Invasive Group ◽  
Genetic Typing ◽  
Aboriginal Population ◽  
Epidemiological Features ◽  
Significant Difference ◽  
Group A ◽  
Study Population

Reports of increasing incidence and severity of invasive group A streptococcal (GAS) infections come mainly from affluent populations where exposure to GAS is relatively infrequent. We conducted a 6-year retrospective review of GAS bacteraemia in the Northern Territory of Australia, comparing the Aboriginal population (24% of the study population), who have high rates of other streptococcal infections and sequelae, to the non-Aboriginal population. Of 72 episodes, 44 (61%) were in Aboriginal patients. All 12 cases in children were Aboriginal. Risk factors were implicated in 82% of episodes (91% in adults) and there was no significant difference in the proportion of Aboriginal compared to non-Aboriginal patients with at least one risk factor. Genetic typing of isolates revealed no dominant strains and no evidence of a clone which has been a common cause of these infections elsewhere.

scholarly journals Risk Factors in the Pathogenesis of Invasive Group A Streptococcal Infections: Role of Protective Humoral Immunity

1999 ◽  
Vol 67 (4) ◽  
pp. 1871-1877 ◽  
Author(s):  
Hesham Basma ◽  
Anna Norrby-Teglund ◽  
Yajaira Guedez ◽  
Allison McGeer ◽  
Donald E. Low ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Streptococcal Infection ◽  
Host Susceptibility ◽  
Streptococcal Toxic Shock Syndrome ◽  
Invasive Infection ◽  
Streptococcal Infections ◽  
Invasive Group ◽  
Invasive Infections ◽  
Protective Antibodies ◽  
Group A

ABSTRACT An impressive change in the epidemiology and severity of invasive group A streptococcal infections occurred in the 1980s, and the incidence of streptococcal toxic shock syndrome cases continues to rise. The reason for the resurgence of severe invasive cases remains a mystery—has there been a change in the pathogen or in host protective immunity? To address these questions, we have studied 33 patients with invasive infection caused by genotypically indistinguishable M1T1 strains of Streptococcus pyogenes who had different disease outcomes. Patients were classified as having severe (n= 21) and nonsevere (n = 12) invasive infections based on the presence or absence of shock and organ failure. Levels of anti-M1 bactericidal antibodies and of anti-streptococcal superantigen neutralizing antibodies in plasma were significantly lower in both groups than in age- and geographically matched healthy controls (P < 0.01). Importantly, the levels of these protective antibodies in plasma samples from severe and nonsevere invasive cases were not different. Together the data suggest that low levels of protective antibodies may contribute to host susceptibility to invasive streptococcal infection but do not modulate disease outcome. Other immunogenetic factors that regulate superantigen responses may influence the severity of systemic manifestations associated with invasive streptococcal infection.

scholarly journals Invasive Group A Streptococcal Infections: Benefit of Clindamycin, Intravenous Immunoglobulins and Secondary Prophylaxis

2021 ◽  
Vol 9 ◽  
Author(s):  
Delphine Laho ◽  
Sophie Blumental ◽  
Anne Botteaux ◽  
Pierre R. Smeesters
Keyword(s):  
Clinical Studies ◽  
Secondary Infection ◽  
Secondary Prophylaxis ◽  
Added Value ◽  
Streptococcal Toxic Shock Syndrome ◽  
Streptococcal Infections ◽  
Invasive Group ◽  
Household Contacts ◽  
Increased Risk ◽  
Group A

Introduction: Mortality associated with invasive group A streptococcal infections (iGAS) remains high among adults, with lower mortality in children. The added value of both clindamycin and immunoglobulins in such treatment is still controversial, as is the need for antibiotic secondary prophylaxis. It is unlikely that conclusive randomized clinical studies will ever definitively end these controversies.Materials and Methods: A clinical and experimental literature review was conducted in Pubmed, Cochrane, and lay literature to determine the benefit of adding clindamycin and immunoglobulins to β-lactams in the management of iGAS, as well as the need for secondary prophylaxis measures in close contacts.Results: This review includes two meta-analyses, two randomized controlled trials, four prospective studies, five retrospective studies, and microbiological studies. To reduce mortality and morbidity, it appears useful to add clindamycin to β-lactams in severe clinical presentations, including necrotizing fasciitis or streptococcal toxic shock syndrome, and immunoglobulins for the latter two presentations. The high risk of secondary infection in household contacts justifies the need of taking preventive measures.Conclusions: Both clinical studies and available experimental evidence suggest that adding clindamycin and immunoglobulins as adjunctive therapies in the management of invasive group A streptococcal infections may reduce mortality. Household contacts should be warned about the increased risk of secondary infection, and chemoprophylaxis may be considered in certain situations.

Invasive Group A Streptococcal infections in children

2020 ◽  
Vol 16 ◽  
Author(s):  
Molla Imaduddin Ahmed ◽  
Rosalind V Saunders ◽  
Srini Bandi
Keyword(s):  
Early Diagnosis ◽  
Management Practices ◽  
Clinical Presentation ◽  
Streptococcal Infections ◽  
Invasive Group ◽  
Children's Hospital ◽  
Good Outcome ◽  
Children’S Hospital ◽  
Group A

: We reviewed the clinical presentation and management of children with Invasive group A streptococcal infections admitted to our tertiary Children’s Hospital in the last eight years. Our study highlighted the varied symptomatology and management practices in children with iGAS and showed that early diagnosis and prompt initiation of appropriate antibiotics for iGAS can help in resolution of symptoms and good outcome.

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