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Recent findings indicate that the Xpert MTB/Ultra molecular diagnostic test, previously advised for pediatric use, may serve as a significant resource for diagnosing tuberculosis (TB) in HIV-positive adults. This assertion stems from the Stool4TB Alliance study, spearheaded by the Barcelona Institute for Global Health (ISGlobal) and supported by the “la Caixa” Foundation, in partnership with a range of research entities, including the Manhiça Health Research Centre, the Research Center Borstel, Makerere University, the Baylor College of Medicine Children’s Foundation — Eswatini, and The Amsterdam Institute for Global Health and Development. The study’s outcomes, featured in The Lancet Microbe, could revolutionize TB diagnosis methodologies for this vulnerable demographic.
Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, was linked to 1.25 million fatalities in 2023, representing 13% of deaths among those living with HIV. The predominant diagnostic approach today relies on sputum samples collected through deep coughing, but this method has proven challenging for many HIV-positive individuals. Despite the World Health Organization’s endorsement of sputum tests, including molecular tests and urine antigen detection (TB-LAM), access and efficiency are inadequate in numerous regions. Many individuals with HIV face difficulties producing sputum; over 50% of those in advanced stages of the disease are unable to produce satisfactory samples, compounded by low bacterial concentrations making detection problematic.
To mitigate these diagnostic hurdles, the EDCTP-funded Stool4TB initiative investigated the feasibility of applying the Xpert MTB/RIF Ultra test, already effective for respiratory analyses, to stool samples. Recognizing that children typically struggle to provide sputum, the test has gained recommendations for this younger age group. The study, which unfolded from December 2021 to August 2024, involved 677 HIV-positive participants over the age of 15 across medical facilities in Eswatini, Mozambique, and Uganda. Subjects contributed samples—sputum, urine, stool, and blood—for comprehensive analysis.
The challenge of diagnosing TB in vulnerable populations
George William Kasule, a PhD researcher at ISGlobal and the University of Barcelona, underscores the difficulties faced in diagnosing pulmonary tuberculosis in HIV-positive individuals. He states, “People living with HIV are at higher risk, yet the conventional tests often lack sensitivity. This study evaluated various sample types, allowing us to analyze the Stool Ultra test against a microbiological standard comprising three WHO-endorsed tests: urine TB-LAM, liquid culture, and sputum Xpert Ultra.”
A more sensitive test in advanced stages of HIV
The results revealed that the stool test offered a sensitivity rate of 23.7% and a specificity of 94.0% in relation to the reference standard. Notably, for patients with CD4 counts below 200 cells/μl, the sensitivity rose to 45.5%, as these lymphocytes are crucial for immune response, with lower counts indicating a higher risk of serious opportunistic infections, including TB.
Alberto L. GarcÃa-Basteiro, an ISGlobal researcher and head of the Vaccine and Immune Response to Infections Unit at Hospital ClÃnic de Barcelona, emphasizes the implications of the findings: “Our research supports the inclusion of the Stool Ultra test as a supplementary diagnostic tool for TB in people living with HIV, particularly those with advanced AIDS where tuberculosis risks are notably elevated.”
Crucially, the Stool Ultra test identified additional TB cases overlooked by conventional methods, including TB-LAM, sputum Xpert Ultra, or bacterial culture. The low sensitivity of standard tests in patients with advanced AIDS highlights the effectiveness of stool molecular detection; in fact, it can match sputum test efficacy. GarcÃa-Basteiro concludes that this alternative approach offers valuable diagnostic potential for those unable to furnish respiratory samples.
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