Intermittent or Daily Short Course Chemotherapy for Tuberculosis in Children: Meta-analysis of Randomized Controlled Trials.

ABSTRACT

Objective: To compare the effectiveness of intermittent with daily chemotherapy (both containing rifampicin) in childhood tuberculosis (age ≤16yrs) in achieving cure/ significant improvement. Design: Systematic Review and Meta-analysis. Methods: MEDLINE and the Cochrane Library were searched for randomized trials of antitubercular regimens containing rifampicin, in children 16 yrs or less with tuberculosis. Two reviewers independently assessed trial eligibility and quality. Data from full articles of selected studies were independently extracted by two authors and analyzed. The odds ratio was obtained for the pooled data in two groups (intermittent and daily therapy). Outcome variables Cure/significant improvement, relapse rate and adverse events. Results: Four randomized controlled trials comparing twice weekly and daily therapy including 466 children (pulmonary 439; extrapulmonary 27) met the inclusion criteria. Baseline data were comparable. On quality assessment, 3 studies scored 2 and one study scored 3 out of 5 points. Per protocol analysis showed that children receiving intermittent regimen were less likely to be cured than those receiving daily therapy (OR 0.27; 95% CI 0.14, 0.51). The results of intention to treat analysis suggest similar trend towards lower cure rates with twice weekly regimen (OR 0.66; 95% CI 0.23-1.84). Conclusion: Twice weekly intermittent short course therapy is less likely to cure tuberculosis in children as compared to daily therapy. There is a need for better quality randomized controlled trials for assessing efficacy of alternate schedule for intermittent therapy for childhood tuberculosis.