Abstract

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.

Aim
The aim of this study was to undertake a systematic review of the evidence describing the number and nature of alternative final diagnoses among patients with presumed tuberculosis in sSA.

Methods
We searched four databases from inception to April 27, 2020, without language restrictions. We included all general population adult pulmonary tuberculosis diagnostic studies from sub-Saharan Africa, excluding case series and in-patient studies. Data including the proportion of patients with presumed tuberculosis subsequently found not to have tuberculosis and any alternative diagnoses received were extracted. We conducted a random-effects meta-analysis to obtain pooled estimates. We stratified meta-analyses by passive and active case finding. PROSPERO registration: CRD42018100004.

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 found not to have tuberculosis in passive and active case finding studies was 48.5% (CI: 38.4-56.7) and 92.7% (CI: 83.1-97.0), respectively. The proportion of patients with presumed tuberculosis subsequently found not to have tuberculosis increased with declining numbers of clinically diagnosed tuberculosis cases. Only 5/18 studies reported alternative diagnoses.

Conclusions
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 an active case finding approach is adopted. Research is required to better characterise these patient populations in sub-Saharan Africa and plan health system solutions that meet their needs.