Primary pneumonic plague in the African Green monkey as a model for treatment efficacy evaluation.

Abstract

BACKGROUND: Primary pneumonic plague is rare among humans, but treatment efficacy may be tested in appropriate animal models under the FDA 'Animal Rule'. METHODS: Ten African Green monkeys (AGMs) inhaled 44-255 LD(50) doses of aerosolized Yersinia pestis strain CO92. Continuous telemetry, arterial blood gases, chest radiography, blood culture, and clinical pathology monitored disease progression. RESULTS: Onset of fever, >39°C detected by continuous telemetry, 52-80 hours post-exposure was the first sign of systemic disease and provides a distinct signal for treatment initiation. Secondary endpoints of disease severity include tachypnea measured by telemetry, bacteremia, extent of pneumonia imaged by chest x-ray, and serum lactate dehydrogenase enzyme levels. CONCLUSIONS: Inhaled Y. pestis in the AGM results in a rapidly progressive and uniformly fatal disease with fever and multifocal pneumonia, serving as a rigorous test model for antibiotic efficacy studies.