Background

Southern Africa has had an unprecedented increase in the burden of tuberculosis, driven by the HIV epidemic. The Zambia, South Africa Tuberculosis and AIDS Reduction (ZAMSTAR) trial examined two public health interventions that aimed to reduce the burden of tuberculosis by facilitating either rapid sputum diagnosis or integrating tuberculosis and HIV services within the community.

Methods

ZAMSTAR was a community-randomised trial done in Zambia and the Western Cape province of South Africa. Two interventions, community-level enhanced tuberculosis case-finding (ECF) and household level tuberculosis—HIV care, were implemented between Aug 1, 2006, and July 31, 2009, and assessed in a 2×2 factorial design between Jan 9, 2010, and Dec 6, 2010. All communities had a strengthened tuberculosis—HIV programme implemented in participating health-care centres. 24 communities, selected according to population size and tuberculosis notification rate, were randomly allocated to one of four study groups using a randomisation schedule stratified by country and baseline prevalence of tuberculous infection: group 1 strengthened tuberculosis—HIV programme at the clinic alone; group 2, clinic plus ECF; group 3, clinic plus household intervention; and group 4, clinic plus ECF and household interventions. The primary outcome was the prevalence of culture-confirmed pulmonary tuberculosis in adults (≥18 years), defined as Mycobacterium tuberculosis isolated from one respiratory sample, measured 4 years after the start of interventions in a survey of 4000 randomly selected adults in each community in 2010. The secondary outcome was the incidence of tuberculous infection, measured using tuberculin skin testing in a cohort of schoolchildren, a median of 4 years after a baseline survey done before the start of interventions. This trial is registered, number ISRCTN36729271.

Findings

Prevalence of tuberculosis was evaluated in 64 463 individuals randomly selected from the 24 communities; 894 individuals had active tuberculosis. Averaging over the 24 communities, the geometric mean of tuberculosis prevalence was 832 per 100 000 population. The adjusted prevalence ratio for the comparison of ECF versus non-ECF intervention groups was 1·09 (95% CI 0·86—1·40) and of household versus non-household intervention groups was 0·82 (0·64—1·04). The incidence of tuberculous infection was measured in a cohort of 8809 children, followed up for a median of 4 years; the adjusted rate ratio for ECF versus non-ECF groups was 1·36 (95% CI 0·59—3·14) and for household versus non-household groups was 0·45 (0·20—1·05).

Interpretation

Although neither intervention led to a statistically significant reduction in tuberculosis, two independent indicators of burden provide some evidence of a reduction in tuberculosis among communities receiving the household intervention. By contrast the ECF intervention had no effect on either outcome.

We assessed prevalence of tuberculosis in 24 communities in Zambia and South Africa, after 3 years of ECF or household interventions for tuberculosis control. Of 64 463 randomly selected individuals, 894 individuals had active tuberculosis. Averaging over 24 communities the geometric mean of tuberculosis prevalence was 832 per 100 000 population. We also measured the incidence of tuberculous infection in a cohort of 8809 children, followed up for a median of 4 years. The adjusted prevalence ratio for prevalence and the adjusted rate ratio for incidence did not differ significantly for the ECF versus non-ECF or for the household versus non household groups. However, for the household versus non-household groups the upper bounds of the CI for both prevalence ratio and incidence rate ratio were close to unity. The concordance of two robust outcome measures, measured in different population groups and with different methods suggests that the household intervention did have some effect on the burden of tuberculosis in these communities.

The convergence of HIV and tuberculosis has led to an urgent need for an evidence-based public health response to reduce the burden of tuberculosis at the community level. Cluster-randomised trials should provide the gold standard for evidence-based policy making.

A systematic review of published work identified five studies that provided evidence for the effect of interventions on the epidemiology of tuberculosis at community level . Apart from preliminary data from the ZAMSTAR trial, two were randomised trials—the DETECTB trial of enhanced case-finding strategies in Zimbabwe and a trial of a household-level intervention in Brazil. The ZAMSTAR trial is the only study to measure the effect of public health interventions on tuberculosis with a randomised design and direct measurements of the burden of disease as the endpoint. The ZAMSTAR trial covered a population of almost 1 million people and was designed to detect reductions in prevalence of tuberculosis, and incidence of tuberculous infection, of 30%. Our study identified no evidence that the ECF intervention had an effect on the burden of tuberculosis at community level. However, despite not reaching statistical significance, there is plausible evidence that the household intervention did reduce the burden of tuberculosis in these communities.

Source: Lancet

Bill & Melinda Gates Foundation.