A recent study by the Barcelona Institute for Global Health (ISGlobal) shows that the Xpert MTB/RIF Ultra molecular test, usually used on stool samples, might also work well for diagnosing tuberculosis (TB) in adults with HIV. This test has previously been recommended solely for children who have difficulty producing sputum. The research, conducted under the Stool4TB Alliance project, included multiple collaborators. The entities involved are the Manhiça Health Research Centre (CISM), the Research Centre Borstel, Makerere University, Baylor College of Medicine Children’s Foundation—Eswatini, and the Amsterdam Institute for Global Health and Development. The findings were released in The Lancet Microbe and have the potential to alter the diagnostic approach for tuberculosis in individuals with HIV. 

Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. In the year 2023, tuberculosis resulted in 1.25 million fatalities. Approximately 13% of these fatalities occurred among individuals diagnosed with HIV. The standard method of testing tuberculosis involves analysing sputum, which is produced through deep coughing. The World Health Organisation (WHO) has issued a recommendation for the use of sputum and urine tests (TB-LAM) for individuals living with HIV. Many individuals living with HIV are unable to produce sputum. Over fifty percent of individuals with advanced HIV face challenges in managing their condition. The quantity of TB bacteria present in sputum is frequently minimal, resulting in a diminished utility of the test. 

The Stool4TB project, funded by EDCTP, conducted tests on stool samples using the Xpert MTB/RIF Ultra to address these issues. Children, who struggle to produce sputum through coughing, currently use this test. The research was conducted from December 2021 to August 2024 across three African nations: Eswatini, Mozambique, and Uganda. The study involved 677 patients aged 15 and older, all of whom were diagnosed with HIV and suspected of having tuberculosis. Samples of sputum, urine, stool, and blood were provided by these patients. 

George William Kasule, a PhD student at ISGlobal and the University of Barcelona and the first author of the study, states that individuals living with HIV face an increased risk of developing pulmonary tuberculosis. He notes that diagnosing this condition in such cases is particularly difficult because conventional tests have low sensitivity. He stated, “The variety of samples obtained in this study enabled a comparison of the sensitivity and specificity of the Stool Ultra test against a microbiological reference standard that includes three WHO-recommended tests: TB-LAM in urine, liquid culture, and Xpert Ultra from sputum.” 

The research indicated that the stool test demonstrated a sensitivity of 23.7% and a specificity of 94.0% in relation to the reference standard. In patients exhibiting CD4 counts below 200 cells/?l, the sensitivity was observed to rise to 45.5%. CD4 cells play a crucial role in the immune system and are impacted by HIV. Individuals with low CD4 counts exhibit an increased susceptibility to infections such as tuberculosis. 

Alberto L. García-Basteiro, a researcher at ISGlobal and head of the Vaccine and Immune Response to Infections Unit at Hospital Clínic de Barcelona, stated that the findings of the study endorse the Stool Ultra test as a supplementary method for diagnosing tuberculosis in individuals with HIV, particularly among those with advanced AIDS, who are at an increased risk for the disease. He states that in these patients, the sensitivity of standard tests is significantly lower compared to the HIV-negative population. Our findings indicate that in patients with advanced AIDS, stool molecular detection demonstrates effectiveness comparable to that of sputum testing. The method is capable of confirming the disease in numerous instances where respiratory tests yield negative results. This indicates the potential of this sample for diagnosing tuberculosis in individuals with HIV, particularly in situations where respiratory samples are not accessible. 

In low- and middle-income countries (LMICs), where health resources are constrained and access to advanced diagnostic tests poses significant challenges, the introduction of this new stool test may represent a significant advancement. The method provides a straightforward and minimally invasive approach to identify tuberculosis in at-risk adults living with HIV, which may lead to quicker treatment initiation and enhanced survival outcomes.