ANIMAL MODEL FOR TOXIC SHOCK SYNDROME (TSS)

Abstract

TSS Antigen (TSS Ag), the protein marker identifying TSS associated staphylococci, can be detected in blood, urine and tissues of patients with TSS but has not been proven to be the toxin responsible for shock and multisystem dysfunction. To assess pathogenicity we developed an animal model. Rabbits given I.V. bolus of 60 μg/kg of purified TSS Ag were unaffected but 100 μg/kg bolus dose → rapid ↑ in BUN, creatinine and SGOT, lymphopenia, profound hypotension by 12 hours and death by 24 hours. Baboons given 100 μg/kg by I.V. bolus showed no hypotension or chemical change but doses of 150-400 μg/kg given by infusion over 1-16 hours → azotemia, lymphopenia, moderate to profound hypotension in all and spontaneous mortality in 2/3. The profile of TSS Ag in serum and urine was followed by radioimmunoassay. In baboons TSS Ag was detected in serum immediately after 100 μg/kg bolus injection (ineffective dose) with peak concentration of >1300 ng/ml but was cleared rapidly. Infusion of 400 μg/kg over 4 hours → shock and death with peak concentration 110 ng/ml and persistence for 32 hours. Plasma levels of TSS Ag in rabbits and baboons with hypotension, azotemia, liver damage and lymphopenia are similar to those in experimental infection with TSS staphylococci (> 80 ng/ml sustained over several hours.) Autopsy resembled fatal human TSS. This animal model reproduces the major pathological features of TSS, suggesting that TSS Ag is the mediator of renal and hepatic dysfunction, shock and death either by direct action or through endogenous host response.

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