STOOL4TB

The challenge

Many cases of tuberculosis go undetected, so patients do not receive treatment, and the disease has more opportunity to spread. This issue is particularly acute for groups such as children and people living with HIV, where it can be difficult to obtain a sputum sample for analysis, and diagnostics may not pick up the relatively small numbers of bacteria in many infections.

In children, TB treatment is generally empirical, without firm diagnosis. This means that many children with TB are missed, and some children receive powerful drugs unnecessarily when they do not have TB infections. It is estimated that more than 96% of paediatric TB deaths occur in children who are not treated for TB.

Great strides have been made in developing easier-to-use tests for TB, including molecular platforms such as Xpert. However, obtaining a sputum sample for analysis using such tools can still be a major barrier in groups such as children and people living with HIV.

The project

Funded by the EDCTP2 programme, the STOOL4TB project has been exploring an alternative approach based on detecting TB bacteria in stool samples. When people with TB disease cough, some bacteria end up being swallowed and pass through the intestinal tract. Stool samples are relatively easy to collect from all patients and can be shipped to laboratories for high-throughput molecular (PCR) analysis.

Initial small-scale studies showed that this approach could increase confirmed case detection (by 12% in Eswatini adults and 19% in Tanzanian children). Stool samples could be collected from at least 87% of patients. The WHO recommends the use of stool samples for detecting TB in children. 

The STOOL4TB project is conducting a larger-scale study to confirm these encouraging findings, focusing on around 1,500 children less than 8 years old and 650 adults living with HIV (15 years and older) in high-burden settings in Eswatini, Mozambique and Uganda. The project was hit by delays in regulatory approvals and recruitment difficulties during the COVID-19 pandemic, and additional Global Health EDCTP3 funding will enable it to complete its important work.

As well as demonstrating whether the stool-based approach identifies more cases than alternative detection methods, the project is also investigating the feasibility and acceptability of this approach through consultations with patients, caregivers, health workers, and health system officials.

It is also exploring whether the approach could be used to monitor responses to treatment, which could help to identify drug-resistant infections and the need to change treatments if patients are not responding.

Impact

The STOOL4TB project could have a major impact on the diagnosis of tuberculosis in children and people living with HIV. It will:

• Provide high-quality evidence on the potential of stool-based approaches to detect TB cases.
• Potentially facilitate task shifting in primary care, as stool collection can be carried out by a broader range of health workers.
• Support the development of a point-of-care test based on stool samples (manufacturers of the Xpert platform have expressed interest in developing a stool-specific test).
• Potentially provide a tool for monitoring responses to treatment.
• Create a platform for additional studies – more than 10 further studies are drawing on the study’s data and sample biorepository.

If the advantages of the stool-based approach are confirmed, this could have a major impact on TB case detection in two critical groups, children and people living with HIV, where many avoidable deaths are currently occurring because of the failure to identify TB.