The rhesus monkey as a model for the study of infectious disease

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Abstract
Models for bacterial and viral infections and intoxication were developed in rhesus macaques (Macaca mulatta). Manifestations of acute‐phase illnesses, e.g., temperature, white blood cell (WBC) counts, blood cultures, etc., were monitored at regular intervals. Viral infection was established by inoculating subcutaneously 412 plaque‐forming units of Trinidad strain, Venezuelan equine encephalomyelitis virus. A diphasic febrile response developed, with the first fever peak on days 1 to 2 and a second peak on days 3 to 5. Viremia occurred within 12 hours and persisted in some animals for as long as five days. WBC responses were typical of viral infection. Gram‐positive infections were induced by intravenous (IV) inoculation of 108 Type I Diplococcus pneumoniae. Peak febrile response and bacteremia (102 to 106 pneumococci per milliliter) occurred within 48 hours. Gram‐negative infections, obtained by IV inoculation with 109 Salmonella typhimurium, induced maximal febrile responses within 24 to 48 hours. Leukopenia occurred in 75% of animals; all were bacteremic. Mortality was 40% at 72 hours. Manifestations of intoxication following IV administration of purified staphylococcal enterotoxin B (10 μg per kg body weight) consisted of vomiting, diarrhea, leukopenia, and fever within one to three hours and resembled nonlethal staphylococcal food poisoning of man. These studies indicate that the rhesus macaque has reproducible and characteristic responses to a variety of microbial stimuli and therefore is eminently suitable for studying pathophysiologic, metabolic, and immunologic parameters of infectious or toxic disease processes.