Abstract
Sensitive tools are needed to accurately establish the diagnosis of tuberculosis (TB) at death, especially in low-income countries. The objective of this study was to evaluate 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.
Complete diagnostic autopsies were performed in a series of 223 deaths (56.5% being HIV-positive), including 54 children, 57 maternal deaths and 112 other adults occurring at the Maputo Central Hospital, Mozambique. TB-PCR was performed in all lung, cerebrospinal fluid and central nervous system samples in HIV-positive patients. All samples positive for TB-PCR or showing histological findings suggestive of TB were analysed with the Xpert Ultra assay.
TB was identified as the cause of death in 31 patients: three out of 54 (6%) children, five out of 57 (9%)maternal deaths and 23 out of 112 (21%) other adults. The sensitivity of the main clinical diagnosis to detect TB as the cause of death was 19.4% (95% CI 7.5–37.5) and the specificity was 97.4% (94.0–99.1) compared to autopsy findings. Concomitant TB (TB disease in a patient dying of other causes) was found in 31 additional cases. Xpert Ultra helped to identify 15 cases of concomitant TB. In 18 patients, Mycobacterium tuberculosis DNA was identified by TB-PCR and Xpert Ultra in the absence of histological TB lesions. Overall, 62 (27.8%) cases had TB disease at death and 80 (35.9%) had TB findings.
The use of highly sensitive, easy to perform molecular tests in complete diagnostic autopsies may contribute to identifying TB cases at death that would have otherwise been missed. Routine use of these tools in certain diagnostic algorithms for hospitalised patients needs to be considered. Clinical diagnosis showed poor sensitivity for the diagnosis of TB at death.
Abstract
This study shows the usefulness of molecular assays in ascertaining TB diagnosis at death. It questions the information of clinical diagnoses obtained from hospital registries as a reliable tool for TB mortality estimation. http://bit.ly/2KrzTBJ
Footnotes
Support statement: The CaDMIA research project (Validation of the minimally invasive autopsy tool for cause of death investigation in developing countries) was funded by the Bill and Melinda Gates Foundation (global health grant numbers OPP1067522; Q. Bassat) (www.gatesfoundation.org/) and by the Spanish Instituto de Salud Carlos III (FIS, PI12/00757; C. Menendez) (https://portalfis.isciii.es). Data analysis was supported by the CaDMIA plus research project, funded by the Bill and Melinda Gates Foundation (global health grant numbers OPP1128001; J. Ordi) (www.gatesfoundation.org/) and the Spanish Instituto de Salud Carlos III (Acciones CIBER; C. Menendez) (www.ciberisciii.es/). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya (http://cerca.cat/en/suma/). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was also partially supported by grant 2017 SGR 794 from the Agència de gestió Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) – Departament d'Empresa i Coneixement, Generalitat de Catalunya. Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: A.L. Garcia-Basteiro has nothing to disclose.
Conflict of interest: J.C. Hurtado has nothing to disclose.
Conflict of interest: P. Castillo has nothing to disclose.
Conflict of interest: F. Fernandes has nothing to disclose.
Conflict of interest: M. Navarro has nothing to disclose.
Conflict of interest: L. Lovane has nothing to disclose.
Conflict of interest: I. Casas has nothing to disclose.
Conflict of interest: L. Quinto has nothing to disclose.
Conflict of interest: D. Jordao has nothing to disclose.
Conflict of interest: M.R. Ismail has nothing to disclose.
Conflict of interest: C. Lorenzoni has nothing to disclose.
Conflict of interest: C. Carrilho has nothing to disclose.
Conflict of interest: A. Sanz has nothing to disclose.
Conflict of interest: N. Rakislova has nothing to disclose.
Conflict of interest: A. Mira has nothing to disclose.
Conflict of interest: M.J. Alvarez-Martinez has nothing to disclose.
Conflict of interest: A. Cossa has nothing to disclose.
Conflict of interest: F. Cobelens has nothing to disclose.
Conflict of interest: I. Mandomando has nothing to disclose.
Conflict of interest: J. Vila has nothing to disclose.
Conflict of interest: Q. Bassat has nothing to disclose.
Conflict of interest: C. Menendez has nothing to disclose.
Conflict of interest: J. Ordi has nothing to disclose.
Conflict of interest: M.J. Martinez has nothing to disclose.
- Received February 13, 2019.
- Accepted June 17, 2019.
- Copyright ©ERS 2019
This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.