Twice weekly vs. daily chemotherapy for childhood tuberculosis
Background. Treating childhood tuberculosis places a large burden on health services, and ways of lessening this were sought. Methods. A randomized controlled trial was conducted to determine the effectiveness of fully intermittent twice weekly treatment for intrathoracic childhood tuberculosis and its effect on adherence to treatment, in comparison with daily (weekday) treatment. The setting was a district of Cape Town, South Africa, an area of high incident tuberculosis. We randomized 206 children with confirmed (4%), probable (94%) and suspected (2%) intrathoracic tuberculosis: 89 (median age, 25 months) received intermittent treatment; and 117 (median age, 28 months) received daily treatment. Intermittent treatment (twice weekly for 6 months) was isoniazid 15 mg/kg/dose, rifampin 15 mg/kg/dose and pyrazinamide 55 mg/kg/dose for 2 months, followed by isoniazid and rifampin only for 4 months. Daily treatment was isoniazid 10 mg/kg/day, rifampin 10 mg/kg/day and pyrazinamide 25 mg/kg/day on weekdays for 6 months. Results. At 6 months 97% of subjects were discharged, with treatment outcomes in the two groups equivalent at that time (P = 0.90) and at the 18- to 30- month follow-up. One relapse occurred in the twice weekly group (P = 0.25). Adherence was equivalent; 70 children (79%) on intermittent and 90 (77%) on daily treatment took 75% or more of the prescribed doses (P = 0.90). Nonadherence over the full course of therapy was significantly associated with nonadherence during the first month of treatment (P = 0.0002) and household crowding (P = 0.002). Conclusions. Six month fully intermittent antituberculosis treatment is an effective and acceptable alternative to daily treatment.