Three chemotherapy studies of tuberculous meningitis in children

Chemotherapy studies were undertaken in 180 patients with tuberculous meningitis. They were treated for 12 months with 1 of 3 regimens: the first consisted of streptomycin, isoniazid and rifampicin daily for the first 2 months, followed by ethambutol plus isoniazid for 10 months; in the second, pyrazinamide was added for the first 2 months, and in the third, rifampicin was reduced to twice weekly in the first 2 months. Steroids were prescribed for all the patients in the initial weeks of treatment. Approximately 50% of the patients were aged less than 3 years. On admission, 13% of the patients were classified as stage I, 77% as stage II and 9% as stage III. Cerebrospinal fluid (CSF) culture results were available for all the 180 patients and M. tuberculosis was isolated in 59 (33%). CSF smear results for acid fast bacilli were available only for the 103 patients admitted to the second and the third studies, and of these in 60 (58%) the CSF was positive either by smear or culture. The response to therapy was similar in the 3 studies. Despite administration of rifampicin for 2 months, the mortality was high. In all, 27% of the patients died of tuberculous meningitis, 39% had neurological sequelae and 34% recovered completely. There was a strong association between the stage on admission and the mortality rate, the deaths being highest in stage III. In the first study, when isoniazid was prescribed daily in a dosage of 20 mg/kg, 39% of the patients developed jaundice; however, when the dosage was reduced to 12 mg/kg, the incidence fell to 16%. In the third study, where rifampicin was administered twice a week, the incidence of jaundice was much lower (5%).