Tuberculosis (TB) remains a significant global health threat, especially for individuals co-infected with HIV. In 2023, TB caused 1.25 million deaths globally. Of those deaths, 13% were among people living with HIV, according to the study published in The Lancet Microbe. For years,diagnosing TB in HIV-positive adults has been a challenge,frequently enough relying on sputum samples that are tough to obtain and may yield inaccurate results,especially in later stages of HIV. But a new study offers a potential breakthrough: using stool samples and the Xpert MTB/RIF Ultra molecular test.

The Stool4TB Alliance study, conducted across medical centers in Eswatini, Mozambique, and Uganda between December 2021 and august 2024, suggests that the Xpert MTB/RIF Ultra test, typically used on respiratory samples, could be an effective additional tool for diagnosing TB in adults living with HIV. The study involved 677 patients over the age of 15 with HIV and suspected TB, who provided sputum, urine, stool, and blood samples.

The Sputum Stalemate: Why Current TB Tests Fall Short

The standard method for TB diagnosis involves analyzing sputum, a thick mucus coughed up from the lungs. However, this approach presents several problems for people with HIV.

• Difficulty Producing Sputum: More than half of HIV-positive individuals in advanced stages of the disease struggle to produce enough sputum for testing.
• Low Bacterial Concentration: Even when sputum is available, the concentration of TB bacteria is frequently enough too low to be detected by conventional methods.

These challenges highlight the urgent need for alternative diagnostic approaches. In the United States, where TB rates are generally low compared to other parts of the world, these diagnostic difficulties can lead to delayed treatment and potentially contribute to the spread of the disease, particularly within vulnerable populations. consider, for example, homeless populations in major cities like Los Angeles or New York, where HIV and TB co-infection can present significant public health challenges.

Stool Ultra Test: A New Hope for TB Diagnosis

The Stool4TB project proposed using the Xpert MTB/RIF Ultra test on stool samples.this test is already recommended for children, who often struggle to produce sputum. The central finding is that the Xpert MTB/RIF Ultra test on stool samples could be a powerful tool in the fight against TB, providing a more accessible and accurate diagnostic method, particularly for those hardest to reach with traditional techniques.

George William Kasule, a PhD student, explains the study’s methodology:

The variety of samples obtained in this study allowed us to compare the sensitivity and specificity of the Stool Ultra test with a microbiological reference standard consisting of three WHO-recommended tests: TB-LAM in urine, liquid culture, and Xpert Ultra from sputum.
George William Kasule,PhD Student

The results showed the stool test had a sensitivity of 23.7% and a specificity of 94.0% when compared to the reference standard. Notably,in patients with CD4 counts below 200 cells/μl,the sensitivity increased to 45.5%. CD4 lymphocytes are immune system cells depleted by HIV, making individuals with low CD4 counts particularly vulnerable to opportunistic infections like TB.

What does this meen for the average American reader? Imagine a scenario in a major U.S. city with a significant HIV-positive population. The Stool Ultra test could offer a non-invasive and more reliable diagnostic tool, potentially leading to earlier detection and treatment of TB, ultimately improving patient outcomes and reducing the burden on public health resources.

The Science Behind the Stool: How the Test Works

The Xpert MTB/RIF Ultra test is a molecular diagnostic test that detects the presence of Mycobacterium tuberculosis DNA in a sample. Unlike traditional methods that rely on culturing the bacteria, this test can provide results within hours. Here’s a simplified explanation:

1. Sample Collection: A stool sample is collected from the patient.
2. Sample Readiness: the sample is processed to isolate and concentrate any TB bacteria present.
3. DNA Amplification: The test uses a process called polymerase chain reaction (PCR) to amplify the DNA of Mycobacterium tuberculosis. This makes it easier to detect even small amounts of the bacteria.
4. Detection: The amplified DNA is then detected using specific probes that bind to the TB DNA.
5. Result Interpretation: the test provides a result indicating weather TB bacteria were detected in the sample.

The ability to detect even small amounts of TB DNA is crucial, especially in HIV-positive individuals, where the bacterial load in sputum can be low.

Implications for the U.S. healthcare System

The findings of the Stool4TB study have significant implications for the U.S. healthcare system, particularly in areas with high rates of HIV and TB co-infection. Here’s how the implementation of stool-based TB testing could benefit the U.S.:

• Improved Diagnostic Accuracy: Stool testing could provide a more accurate diagnosis, especially in patients who have difficulty producing sputum.
• Earlier Detection and Treatment: Earlier detection of TB can lead to prompt treatment, preventing the spread of the disease and improving patient outcomes.
• Reduced Healthcare Costs: By improving diagnostic accuracy and enabling early treatment, stool testing could potentially reduce healthcare costs associated with TB management.
• Enhanced Public Health Efforts: stool testing could enhance public health efforts to control TB transmission, particularly in vulnerable populations.

However, several factors could hinder the implementation of stool-based TB testing in the U.S., including cost, infrastructure requirements, and potential regulatory hurdles. Addressing these challenges will be crucial to maximizing the benefits of this innovative diagnostic approach.

Addressing Counterarguments

While the Stool Ultra test shows promise, some argue that its sensitivity, even at 45.5% in patients with low CD4 counts, is still not high enough to replace sputum testing entirely. Also, the specificity of 94% means there is a small chance of false positives, which could lead to unnecessary treatment and anxiety for patients.

However, proponents emphasize that the stool test is not intended to replace sputum testing, but rather to serve as a complementary tool, especially in situations where sputum samples are difficult to obtain or unreliable. The test’s ability to identify additional cases missed by other methods highlights its potential value in improving TB diagnosis in vulnerable populations.Furthermore, confirmatory testing can be performed to address any concerns about false positives.

The future of TB Diagnostics

The research builds momentum for development in TB diagnostics. this new approach holds considerable promise.

Alberto L. García-Basteiro stated:

The results of our study support the use of the Stool Ultra test as a complementary tool for diagnosing tuberculosis in people living with HIV, especially in those with advanced AIDS, where the risk of tuberculosis is higher.
alberto L. García-Basteiro

García-Basteiro further elaborated on the potential of stool samples in diagnosing TB:

This demonstrates the potential of this sample,perhaps counterintuitively,for diagnosing tuberculosis in people with HIV,especially when respiratory samples are not available.
Alberto L. García-Basteiro

The xpert MTB/Ultra molecular diagnostic test for stool samples represents a significant advancement in the fight against TB, particularly in HIV co-infected individuals. While further research and implementation strategies are needed, this innovative approach holds the potential to transform TB diagnosis and improve patient outcomes globally.