ISONIAZID PROPHYLAXIS OF TUBERCULOUS INFECTION IN MICE

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Abstract
Isoniazid, 3 mg/kg/day, for 4.5 weeks exerted a prophylactic effect in experimentally infected tuberculous mice. The resistance to infection was demonstrable even after the drug had been discontinued. During the period of observation, the mortality in the isoniazid groups was 14.8 to 17.7%, while that in the control group was 36.7%. Fourteen weeks after the second challenge, the previously and newly infected control animals showed higher mortality rates of 53.9 to 68.3%. By contrast, in the prophylactic groups the mortality rates were 17.3 to 25.2%. Infected mice that received the same doses of isoniazid for 4.5 weeks before challenge and 10 weeks thereafter acquired some degree of immunity against rechallenge. Fourteen weeks after rechallenge, in more than half of the prophylactic group the lungs were normal. The histopathologic changes in lungs, liver, spleen, and kidney were considerably less in the mice that received isoniazid than among the control animals. At the end of the experiment, no isoniazid-resistant strains of Mycobacterium tuberculosis were isolated from any of the animals.