Patients with presumed tuberculosis in sub-Saharan Africa that are not diagnosed with tuberculosis: a systematic review and meta-analysis

Background: Many patients in sub-Saharan Africa whom a diagnosis of tuberculosis is considered are subsequently not diagnosed with tuberculosis. The proportion of patients this represents, and their alternative diagnoses, have not previously been systematically reviewed. Methods: We searched four databases from inception to April 27, 2020, without language restrictions (PROSPERO: CRD42018100004). We included all adult pulmonary tuberculosis diagnostic studies from sub-Saharan Africa, excluding case series and inpatient studies. We extracted the proportion of patients with presumed tuberculosis subsequently not diagnosed with tuberculosis and any alternative diagnoses received. We conducted a random-effects meta-analysis to obtain pooled estimates stratified by passive and active case finding. Results: Our search identified 1799 studies, of which 18 studies with 14527 participants from 10 African countries were included. The proportion of patients with presumed tuberculosis subsequently not diagnosed with tuberculosis was 48.5% (95% CI 38.4-56.7) in passive and 92.7% (95% CI 83.1-97.0) in active case finding studies. This proportion increased with declining numbers of clinically diagnosed tuberculosis cases. Past history of tuberculosis was documented in only 55% of studies, with just five out of 18 reporting any alternative diagnoses. Discussion: Nearly half of all patients with presumed tuberculosis in sub-Saharan Africa do not have a final diagnosis of active tuberculosis. This proportion may be higher when active case finding strategies are used. Little is known about the healthcare needs of these patients. Research is required to better characterise these patient populations and plan health system solutions that meet their needs. Funding NIHR, UK MRC