The effect of treatment with a large dose of isoniazid on an established tuberculous infection in mice.

Mice were infected intracorneally with Mycobacterium tuberculosis var. bovis and the infection allowed to develop for a period of 2 weeks. At this stage the animals were divided into two main groups; one received no treatment, the other was treated with large doses of isoniazid (3.0 mg./mouse/day). The effect of treatment on the primary lesion, the viability of the bacilli, the systemic spread of infection, and the production of immunity were observed. Treatment was continued for 11 months, after which the animals were observed for another 8 months. Within a few days of starting isoniazid treatment the primary lesion stopped increasing in size, regressed slightly and stabilized at a size of about one-third of that of the controls. There was little evidence of any clearing of the bacilli from the lesions; they remained strongly acid-fast and morphologically normal for many months after infection, although by 13 months about half of the organisms in both groups had become very granular. The evidence suggests that in control and treated animals the bacilli in the cornea had usually all died within 8 months after infection. In two treated corneas, living virulent bacilli were demonstrated 15 months after inoculation. In the untreated animals, the disease spread systemically to involve the lungs, liver, and spleen, and by one year after inoculation the systemic tuberculous infection was very heavy, though not enough to kill the animals. The lesions in these animals contained many acid-fast bacilli. In the treated group, systemic spread of infection as judged by the development of small macroscopic lung foci was slight; acid-fast bacilli were found in only one animal. In the treated animals, practically no immunity could be detected 5 months after inoculation and had not reappeared 2 months after cessation of treatment; in the untreated animals immunity was present.