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Apr 8, 2025
Tuberculosis (TB), caused by Mycobacterium tuberculosis, claimed approximately 1.25 million lives in 2023, with 13% of those deaths occurring among people living with HIV. Traditionally, TB diagnosis relies on sputum samples, which are collected through deep coughing to retrieve lung secretions. However, this method poses challenges for people with HIV, who often struggle to produce sputum particularly in advanced stages of the disease and when they can, the bacterial load may be too low for detection.
To overcome these limitations, researchers from the EDCTP-funded Stool4TB project explored an alternative: using the Xpert MTB/RIF Ultra molecular test, typically used on respiratory samples, on stool samples. This test is already recommended for children due to similar sputum collection challenges.
Between December 2021 and August 2024, the study enrolled 677 HIV-positive individuals over the age of 15 suspected of having TB across sites in Eswatini, Mozambique, and Uganda.
Each participant provided sputum, urine, stool, and blood samples. The performance of the stool-based test was then compared against a composite reference standard comprising WHO-recommended diagnostics: TB-LAM (urine), liquid culture, and sputum-based Xpert Ultra.
Lead author George William Kasule, a PhD student at ISGlobal and the University of Barcelona, highlighted the diagnostic difficulty of TB in people living with HIV due to reduced sensitivity of conventional tests.
The study found that the stool test demonstrated 23.7% sensitivity and 94.0% specificity overall, with sensitivity rising to 45.5% in individuals with CD4 counts below 200 cells/μl indicating more advanced HIV infection and a higher susceptibility to opportunistic infections like TB.
According to ISGlobal researcher Alberto L. García-Basteiro, the stool-based test shows promise as a complementary diagnostic tool, especially in advanced HIV/AIDS cases where TB risk is elevated and conventional diagnostics fall short. Notably, the Stool Ultra test detected TB in several cases where sputum-based or urine-based diagnostics failed, underscoring its value when respiratory samples are inadequate or unavailable.
This research not only supports the expanded use of stool molecular diagnostics for TB in adults with HIV but also highlights a potentially game-changing approach for improving TB detection in vulnerable populations.