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

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.

Diagnosing adult and pediatric extrapulmonary tuberculosis by MPT64 antigen detection with immunohistochemistry and immunocytochemistry using reproduced polyclonal antibodies

“…The sensitivity of the MPT64 test in cytology specimens was low in our study (36%), contrasting the results of our previous studies, which showed sensitivities of 69–92% [ 18 , 19 , 20 ]. This could be explained by the difference in primary polyclonal antibodies.…”

“…The test method is rapid and robust, and its relative simplicity makes it suitable for implementation in low‐resource settings with modest laboratory facilities. Recent results from validation of the MPT64 test in routine diagnostics in the resource‐limited and high TB burden areas of Zanzibar and Tanzania show sensitivity and specificity of 69–92% and 78–95%, respectively, against a composite reference standard (CRS) [ 18 , 19 , 20 ]. However, the antibodies evaluated in previous studies were in limited supply.…”

Mortality among extrapulmonary tuberculosis patients in the HIV endemic setting: lessons from a tertiary level hospital in Mbeya, Tanzania

“…In our study, a negative MPT64 test result led to a less frequent initiation of ATT. The finding that fewer patients with a negative MPT64 test result received ATT could imply that clinicians had higher confidence in this new test modality and corresponds well with our previously reported high negative predictive value of the MPT64 test 11 , 12 , 27 . The poor negative predictive value of both mycobacterial culture and GeneXpert means that clinicians really cannot trust negative results.…”

“…In addition, 22% of the non-TB patients received ATT incorrectly. Our patients were classified based on a composite reference standard, which mimicked clinical practice in the low resource setting, where patients are often treated for presumptive EPTB without microbiological confirmation 11 , 12 , 27 . The clinicians did not, however, use our case definition when diagnosing patients, but followed national guidelines.…”

“…The study participants were classified into TB and non-TB groups. The TB case definition relied on a composite reference standard 11 , 12 . A confirmed TB case was positive on mycobacterial culture.…”