Mycobacterium w Immunotherapy for Treating Pulmonary Tuberculosis - a Systematic Review.

BACKGROUND:Tuberculosis (TB) remains a global health catastrophe. Mycobacterium w is a heat-killed immune-modulating vaccine designed to attenuate the effects of TB, reduce time to sputum conversion, and thereby decrease transmission and improve cure rates. OBJECTIVES:To evaluate Mycobacterium w (M w) immunotherapy as an adjunct to chemotherapy in participants with pulmonary TB (PTB). SEARCH STRATEGY:In January 2012, we performed both a database search, a handsearch and corresponded with experts in the field. SELECTION CRITERIA:Randomised and quasi-randomised controlled trials of M w immunotherapy versus placebo (or no control) for participants with PTB. DATA COLLECTION AND ANALYSIS:Two of the authors (SP and ZK) independently extracted data. Dichotomous outcomes were analysed using risk ratios (RR) and 95% confidence intervals (CI). OUTCOMES:The primary outcome was to determine the effect of M w therapy on sputum conversion. Secondary outcomes were to determine the frequency of adverse reactions. MAIN RESULTS:Three trials (four papers) involving 368 participants were included. All four papers had methodological flaws. Overall, 173 participants received M w and 168 participants received placebo or no control. M w immunotherapy was effective at reducing time to sputum conversion at days 15 (RR 2.31; 95% CI 1.75 to 3.06; P < 0.001) and 30 (RR 1.83; 95% CI 1.12 to 2.98; P = 0.02). After day 30, benefit was only demonstrated in the category II TB (re-treatment). CONCLUSIONS:The meta-analysis suggests benefit as regards the time to sputum conversion. The available data on M w immunotherapy for participants with PTB are however methodologically flawed. We advise that M w be investigated in a well-structured, randomised controlled trial.