Investigating the potential impact and suitability of tuberculosis active case-finding approaches in the rapidly changing environment of urban Blantyre, Malawi.

Millions of cases of Tuberculosis (TB) go undiagnosed each year. Several approaches are recommended to fill this gap, including community-based active case-finding (ACF). This PhD investigates undiagnosed TB in communities and primary care health clinics in Blantyre, Malawi, and the potential direct and indirect (health promotion) impact of community-based ACF in identifying people with undiagnosed TB. It includes: • A prospective cohort analysis of outpatients at a primary health-care clinic using linked entry and exit interviews. Patients were lost at every stage of the TB diagnosis cascade, with same-day sputum submission only achieved in 4.7% of those clinically indicated to test for TB. • A tuberculosis prevalence survey in Blantyre. A prevalence of 150-189 per 100,000 adult residents was identified, consistent with a several-fold reduction from levels identified in a 2013-14 National TB Programme prevalence survey. Some groups, notably men, remain disproportionately affected. • A systematic review of the impact of ACF beyond directly diagnosed patients for TB, using routine case-notification rate (CNR) ratios as a measure of indirect effect. Twelve studies were identified, with two linked qualitative studies, but these provided insufficient evidence to reach firm conclusions, mainly due to study design issues. • A cluster-randomised trial of door-to-door ACF in Blantyre to assess both direct and indirect impact of ACF on TB case-notifications. No detectable impact was found, with adjusted 91-day CNR ratios 1.12 (95% CI: 0.61-2.07) for bacteriologically-confirmed TB and 0.86 (95%CI: 0.63-1.16) for non-ACF (routinely) diagnosed TB patients. Lack of impact was likely due to several previous years of TB ACF screening activity and rapid declines in TB burden. These results highlight the need for resources to be targeted most effectively to reach those with undiagnosed TB in an environment with rapidly changing TB epidemiology. In Blantyre, approaches likely to bring the highest yield are optimised facility-based screening and ACF targeted to high-risk groups, such as men, or geographic hotspots.