Aerosol-Induced Tuberculosis in Subhuman Primates and the Course of the Disease After Intravenous BCG Vaccination

Abstract

Suitability of the rhesus monkey (Macaca mulatta) as an experimental host for evaluation of vaccines against airborne infection with Mycobacterium tuberculosis strain H37Rv was investigated. Nonvaccinated monkeys were exposed to estimated doses of 12, 25, or 49 units of H37Rv in a modified Henderson apparatus, and the course of the disease was followed by chest X rays, skin testing with purified protein derivative, body-weight determinations, and autopsy 8 weeks postinfection. These animals developed progressive and extensive tuberculosis with pathological changes proportional to the infecting dose. Four of seven monkeys vaccinated intravenously with 1 mg of live BCG 8 weeks prior to challenge with 40 units of H37Rv had no gross evidence of disease at autopsy 13 weeks postinfection; the other three monkeys had minimal disease. These data demonstrated that (i) reproducible and progressive infection could be induced in rhesus monkeys infected in a manner which simulated natural infection of man and (ii) a high level of resistance to infection could be induced by BCG vaccine in the rhesus monkey, which in nature is highly susceptible to tuberculous infection.