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

Abstract

IntroductionAccurate 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.MethodsIn 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.Results4382 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).ConclusionWe 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.

Identification of incipient tuberculosis in household contacts. The relevance of tuberculosis exposure scores and contact investigations.

“…in the same study area reported a birthweight of ≤2500g in 29% of 4382 neonates(44) which taken together suggests an explanation for the low BCG scar rate in the present study. Surprisingly, neither the TB exposure scores or other well-established TB risk factors had a clear association with incipient TB in multivariate analysis.…”

Does tuberculosis screening improve individual outcomes? A systematic review

“…However, these require large sample sizes, long term follow-up and are resource intensive. We only identified three RCTs, conducted over relatively short time-periods (1-2 years) [28,36,37]. Therefore, insights from routine programme implementation are essential.…”

“…From 27,270 articles, 18 were eligible [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] (Figure 1 and Table 2); seven were not reported in the previous review [20,[29][30][31][32]36,37]. We only identified n=12/23 (52%) of the outcome indicators sought (Table 1); no studies reported on the remainder.…”

“…Two CRTs were identified (Table 2, Table 5 and Appendix 2) [36,37]. One among Indian neonates compared fortnightly ACF over 2 years, in 297 intervention communities to PCF in 295 control communities [36].…”

“…Two CRTs were identified (Table 2, Table 5 and Appendix 2) [36,37]. One among Indian neonates compared fortnightly ACF over 2 years, in 297 intervention communities to PCF in 295 control communities [36]. Screening was associated with lower all-cause mortality compared to PCF (adjusted OR 0.68 [95%CI 0.47-0.98]), which was attributed to decreases in pneumonia/respiratory infections.…”