Intermittent versus daily therapy for treating tuberculosis in children: Summary of the evidence and implications for public health programmes

A Cochrane systematic review summarized the evidence for the effects of intermittent versus daily short-course anti-tuberculosis (TB) treatment regimens (containing rifampicin in the intensive treatment phase) on cure rates, deaths, relapses, adherence, and adverse events in children with TB not known to have drug resistance. The review included four randomized controlled trials published between 1996 and 2000 and conducted in India (two trials), South Africa and Turkey that included 563 (465 evaluable) children aged five months to 15 years. Children were recruited from the community in one trial and from hospital clinics in the others; their HIV status was not reported. All trials used a combination of clinical and radiological criteria to diagnose childhood TB.The four trials compared twice-weekly versus daily anti-TB regimens. No trials comparing thrice-weekly versus daily anti-TB regimens in children were identified. The review did not find significant differences between the intermittent twice-weekly and the daily treatment regimens in the proportions of children who were cured, who died, who relapsed over 12–30 months of follow-up, or who had treatment limiting adverse events. Adherence to the intermittent and daily treatments was also similar (87% and 84%). The trials were underpowered to detect significant differences in many of the outcomes, were at high risk of bias, and the regimens used in these trials were not the standard recommended regimens in use today. The review concluded that the evidence was in sufficient to “support or refute the use of intermittent twice- or thrice-weekly, short-course treatment regimens over daily short-course treatment in children with TB”. The review called for adequately powered, well conducted and reported randomized trials comparing intermittent versus daily regimens conducted in high TB-transmission settings to provide evidence to inform policy and practice.