Improved diagnosis of extrapulmonary tuberculosis in adults with and without HIV in Mbeya, Tanzania using the MPT64 antigen detection test

Erlend Grønningen; Marywinnie Nanyaro; Lisbet Sviland; Esther Ngadaya; William Muller; Lisete Torres; Sayoki Mfinanga; Tehmina Mustafa

doi:10.1371/journal.pgph.0001317

Improved diagnosis of extrapulmonary tuberculosis in adults with and without HIV in Mbeya, Tanzania using the MPT64 antigen detection test

PLOS Glob Public Health. 2022 Nov 29;2(11):e0001317. doi: 10.1371/journal.pgph.0001317. eCollection 2022.

Authors

Erlend Grønningen^{1

2}, Marywinnie Nanyaro³, Lisbet Sviland^{4

5}, Esther Ngadaya³, William Muller^{3

6}, Lisete Torres^{3

6}, Sayoki Mfinanga³, Tehmina Mustafa^{1

2}

Affiliations

¹ Department of Global Public Health and Primary Care, Centre for International Health, University of Bergen, Bergen, Vestland, Norway.
² Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Vestland, Norway.
³ National Institute for Medical Research, Dar es Salaam, The United Republic of Tanzania.
⁴ Faculty of Medicine, Department of Clinical Medicine, University of Bergen, Bergen, Vestland, Norway.
⁵ Department of Pathology, Haukeland University Hospital, Bergen, Vestland, Norway.
⁶ Mbeya Zonal Referral Hospital, Mbeya, The United Republic of Tanzania.

Abstract

Extrapulmonary tuberculosis (EPTB) in People Living with HIV (PLWHIV) is a diagnostic challenge. Our immunochemistry based MPT64 antigen detection test has shown improved sensitivity compared to current laboratory tests in the resource limited diagnostic setting. The aim of this study was to validate the implementability and diagnostic performance of the test in PLWHIV and HIV negative adults in a HIV endemic Tanzanian setting. Adult (>18 y) presumptive EPTB patients were prospectively enrolled at Mbeya Zonal Referral Hospital and followed to the end of treatment or until an alternative diagnosis was reached. Suspected sites of infection were sampled and were subject to routine diagnostics, GeneXpert MTB/RIF assay and the MPT64 test. The performance of the diagnostics tests was assessed using a composite reference standard that included clinical suspicion, mycobacterial culture, response to anti-tuberculosis (TB) therapy, cytological and radiological findings. Patients (N = 168) were categorized as 21 confirmed TB, 23 probable TB and 44 possible TB cases, 69 patients were categorized as non-TB cases and 11 were uncategorized. In the TB group, the three most common infections were adenitis (41%), peritonitis (19%) and pleuritis (14%). The TB and non-TB groups did not differ in HIV seropositivity (46% vs 42%) Among HIV negative and PLWHIV, the MPT64 test had a sensitivity of (91% vs 78%), specificity (75% vs 86%), positive predictive value (80% vs 88%), negative predictive value (89% vs 74%), and accuracy (84% vs 81%), respectively. Performance was not significantly reduced in PLWHIV, and sensitivity was higher than in the currently used tests, including the GeneXpert MTB/RIF assay. The MPT64 test improved the diagnosis of EPTB, irrespective of HIV status. The test performed better than currently used diagnostic test. The test was implementable in a tertiary level hospital with basic pathology services in a HIV endemic Tanzanian setting.

Copyright: © 2022 Grønningen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Grants and funding

This work was partly supported by the Research Council of Norway through the Global Health and Vaccination Programme [project number 234457]. This project is part of the EDCTP2 programme supported by the European Union. The first author (EG) received a grant from the Norwegian Medical Association to cover expenses relating to travels and the gathering of data in Tanzania. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.