Unmasking the hidden tuberculosis mortality burden in a large postmortem study in Mozambique

Abstract

Introduction: Refined tools are needed to precisely ascertain the diagnosis of tuberculosis (TB) at death, especially in low-income countries. This study evaluated the burden of TB in a series of patients who died in a tertiary referral hospital in sub-Saharan Africa using an in-house real-time PCR (TB-PCR) and the Xpert MTB/RIF Ultra (Xpert Ultra) assay. Methods: Complete diagnostic autopsies were performed to a series of 54 children, 57 maternal deaths and 112 other adults occurring at the Maputo Central Hospital, Mozambique. TB-PCR was performed in all lung samples and all cerebrospinal fluid and central nervous system in HIV-positive patients. All samples testing positive for TB-PCR or showing histological findings suggestive of TB were analyzed with the Xpert Ultra assay. Results: The post-mortem evaluations identified TB as the cause of death in 31/223 (13.9%) patients: 3/54 (6%) children, 5/57 (9%) maternal deaths and 23/112 (21%) other adults. The main clinical diagnosis given by the clinician in charge of the patient had a sensitivity to detect TB as cause of death of 19.4% (95% CI: 7.5-37.5) and a specificity of 97.4% (94.0-99.1). Concomitant TB (TB disease in a patient dying of other causes) was found in 31 additional cases. In 18 patients, M. tuberculosis DNA was identified by TB-PCR and Xpert Ultra in the absence of histological TB lesions. Conclusions: The use of highly sensitive and easy to perform molecular tests in complete diagnostic autopsies may contribute to identify TB cases at death that would otherwise have been missed. The clinical diagnosis made by physicians has a poor sensitivity for the diagnosis of TB at death.