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Severe group A streptococcal infections associated with early onset shock and multiorgan failure define the streptococcal toxic shock syndrome. In the United States, group A streptococcal strains most commonly isolated are M types 1 and 3, which produce pyrogenic exotoxin type A. The role of tumor necrosis factor (TNF)-alpha and the dynamics of cardiovascular and laboratory abnormalities were investigated in a baboon model of group A Streptococcal bacteremia that mimics human Streptococcal toxic shock syndrome. Profound hypotension, leukopenia, metabolic acidosis, renal impairment, thrombocytopenia, and disseminated coagulopathy developed within 3 h after intravenous infusion of M type 3, pyrogenic exotoxin A-producing group A streptococci. Serum TNF-alpha peaked at 3 h and returned to baseline by 10 h. Mortality was 100%. Anti-TNF-alpha monoclonal antibody treatment markedly improved mean arterial blood pressure, tissue perfusion, and survival, suggesting that TNF-alpha plays an important role in the induction of shock and organ failure in group A streptococcal bacteremia.

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