Incidence of tuberculosis and the influence of surveillance strategy on tuberculosis case-finding and all-cause mortality: a cluster randomised trial in Indian neonates vaccinated with BCG.

Introduction: Accurate tuberculosis (TB) incidence and optimal surveillance strategies are pertinent to TB vaccine trial design. Infants are a targeted population for new TB vaccines, but data from India, with the highest global burden of TB cases, is limited.

Methods: In a population-based prospective trial conducted between November 2006 and July 2008, BCG-vaccinated neonates in South India were enrolled and cluster-randomised to active or passive surveillance. We assessed the influence of surveillance strategy on TB incidence, case-finding rates and all-cause mortality. Predefined criteria were used to diagnose TB. All deaths were evaluated using a verbal autopsy.

Results: 4382 children contributed to 8164 person-years (py) of follow-up (loss to follow-up 6.9%); 749 children were admitted for TB evaluation (active surveillance: 641; passive surveillance: 108). The TB incidence was 159.2/100 000 py and the overall case-finding rate was 3.19 per 100 py (95% CI 0.82 to 18.1). Whereas, the case-finding rate for definite TB was similar using active or passive case finding, the case-finding rate for probable TB was 1.92/100 py (95% CI 0.83 to 3.78) with active surveillance, significantly higher than 0.3/100 py (95% CI 0.01 to 1.39, p=0.02) with passive surveillance. Compared to passive surveillance, children with active surveillance had decreased risk of dying (OR 0.68, 95%CI 0.47 to 0.98) which was mostly attributable to reduction of death from pneumonia/respiratory infections (OR 0.34, 95%CI 0.14 to 0.80).

Conclusion: We provide reliable estimates of TB incidence in South Indian children <2 years of age. Active surveillance increased the case-finding rates for probable TB and was associated with reduced all-cause mortality.