Molecular Stool Testing Enhances Tuberculosis Detection in HIV-Positive Adults

The innovative research regarding the Xpert MTB/Ultra molecular diagnostic test has unveiled transformational possibilities in tuberculosis (TB) diagnostics, particularly for adults living with HIV. Traditionally, the application of this test has been limited to pediatric cases, primarily due to the challenges children face in providing sputum samples. However, recent findings from the Stool4TB Alliance study, conducted by esteemed researchers from the Barcelona Institute for Global Health and other prestigious institutions, highlight the potential for using stool samples to broaden diagnostic testing in adults. The implications of this advancement could signify a substantial shift in the way TB is diagnosed in this high-risk population.

Tuberculosis remains a significant global health challenge. In 2023 alone, TB accounted for 1.25 million deaths worldwide, with a concerning 13% of those fatalities occurring among individuals living with HIV. The traditional diagnostic approach hinges fundamentally on the collection and analysis of sputum samples, which involve a physically demanding process of deep coughing to expectorate lung secretions. This method has been the cornerstone of TB diagnosis as recommended by international health organizations like the World Health Organization (WHO). However, as the research highlights, such techniques are fraught with limitations, especially for individuals battling advanced stages of HIV.

One of the central tenets of the study emphasizes that many individuals living with HIV often face difficulties in producing adequate sputum samples. It has been observed that over half of patients with advanced AIDS are unable to provide these crucial samples. Moreover, even when sputum samples are obtained, the concentration of Mycobacterium tuberculosis can be prohibitively low, rendering standard diagnostic tests ineffective. In light of these challenges, researchers sought an alternative that could offer a reliable diagnostic avenue for this vulnerable demographic.

The Stool4TB project, supported by the European and Developing Countries Clinical Trials Partnership (EDCTP), aimed to explore the feasibility of employing the Xpert MTB/RIF Ultra test on stool samples. This molecular diagnostic tool, currently in use for respiratory samples, has already been notably beneficial for pediatric patients who also struggle with sputum production. The backdrop for this research involved extensive fieldwork, with trials taking place across three African nations – Eswatini, Mozambique, and Uganda – between December 2021 and August 2024. A substantial cohort of 677 patients aged 15 and older was enlisted, all living with HIV and suspected of having TB, allowing researchers to gather a diverse array of biological samples, including sputum, urine, stool, and blood.

Amidst the clinical landscape, the challenges associated with diagnosing TB in patients with HIV infections are particularly pronounced. As George William Kasule, a promising doctoral candidate at ISGlobal, points out, individuals living with HIV exhibit a heightened susceptibility to pulmonary tuberculosis, yet conventional diagnostic tests often fall short in sensitivity. This discrepancy underlines the necessity for alternative testing methods that can capture a broader spectrum of potential TB cases. The research team utilized a microbiological reference standard based on three WHO-recommended tests to establish a comparison with the results from the Stool Ultra test.

The findings from this comprehensive study reveal critical insights. The sensitivity of the stool-based Xpert Ultra test was observed to be 23.7%, with an impressive specificity rate of 94%. However, what is particularly striking is how sensitivity escalated to 45.5% among patients with CD4 counts falling below 200 cells/μl. This marker is indicative of advanced HIV disease, and it is within this population where the risk of contracting opportunistic infections such as tuberculosis intensifies. The results prompt a broad re-evaluation of existing diagnostic practices, advocating for the integration of stool testing as an adjunctive tool for TB diagnosis.

Dr. Alberto L. García-Basteiro, a leading researcher at ISGlobal and the head of the Vaccine and Immune Response to Infections Unit at Hospital Clínic de Barcelona, emphasizes the transformative nature of these findings. The Stool Ultra test can not only identify additional TB cases that standard tests like TB-LAM, sputum Ultra, or culture may overlook, but it also offers a level of efficacy that is comparable to conventional sputum tests for patients in advanced AIDS stages. This insight brings to light a crucial benefit of utilizing stool samples – the ability to affirm a diagnosis even in scenarios where respiratory specimen collection is not feasible or fails to provide conclusive results.

As such, the potential of utilizing stool samples for TB detection, particularly in populations with HIV, is underscored by the pressing need for improved diagnostic strategies. The study demonstrates that such non-invasive methods can play a pivotal role in enhancing TB diagnosis in adults facing significant health challenges. This paradigm shift could usher in a new era of TB diagnostics, underscoring a glaring need for accessible and reliable testing methods that cater to the unique needs of populations traditionally marginalized in clinical diagnostics.

In summary, the findings from the Stool4TB project illuminate the viability of stool samples as an essential component in the diagnostic toolkit for tuberculosis, especially for individuals living with HIV. With substantial data backing this approach, healthcare providers and policymakers are urged to reconsider existing diagnostic frameworks that primarily rely on sputum samples. The emerging evidence from this research supports the notion that by embracing innovative testing methods, significant strides can be made toward combating the global TB epidemic—ultimately reducing morbidity and mortality in one of the most vulnerable populations today.

The significance of these findings cannot be overstated. As researchers continue to refine and expand upon the application of the Xpert MTB/Ultra test for stool samples, the overarching goal remains clear: to enhance accuracy in TB diagnosis, particularly for those who face barriers to traditional testing methods. The landscape of TB diagnostics is poised for a substantial evolution, and the implications of this research hold the promise of saving lives and improving health outcomes for countless individuals worldwide.

Subject of Research: People Living with HIV and Tuberculosis
Article Title: Stool Tests Could Revolutionize Tuberculosis Diagnosis in HIV-Positive Adults
News Publication Date: October 2023
Web References: https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(25)00013-8/fulltext
References: Kasule, G., Hermans, S., Acacio, S., et al, Performance of stool Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis among adult people living with HIV: a prospective multicentre diagnostic study. Lancet Microbe (2025).
Image Credits: Not Available

Keywords: Tuberculosis, HIV, Diagnostic Testing, Public Health, Molecular Diagnostics, Stool Sample Analysis, CD4 Count, Xpert MTB/RIF Ultra.

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