TEST4TPT

The challenge

Approximately one in four people globally have been infected with the bacteria causing tuberculosis (TB), Mycobacterium tuberculosis (Mtb). However, only a proportion of those exposed to Mtb will progress to active TB disease, and the risk can be significantly reduced through a short course of anti-TB medications, known as TB preventive treatment (TPT).

Although TPT is recommended by the World Health Organization, its implementation in routine practice remains challenging. The main barrier is identifying people who have been exposed to Mtb but do not have TB disease. The tuberculin skin test (TST) requires repeated visits to healthcare facilities and assessment by healthcare workers; it also gives false-positive results in those who have been vaccinated with BCG. An IGRA test is more reliable but also more expensive; it requires laboratory infrastructure and is not easily deployable at scale.

A possible alternative is the Cy-TB skin test, which detects allergic responses to Mtb antigens. A preparation containing Mtb proteins is applied to the skin, generating a localised swelling that is significantly larger in people exposed to Mtb. This is as reliable as the IGRA test, is not affected by BCG vaccination or HIV status, and an affordable product is available (SIILTIBCY).

The project

The TEST4TPT project is assessing whether routine SIILTIBCY testing, potentially augmented with new AI-based tools to automatically assess skin reactions, can increase the number of people exposed to Mtb who receive and complete preventive treatment.

One drawback of the SIILTIBCY test is that it still requires a return trip to health facilities for an assessment after 2–3 days. However, assessment of skin reactions could potentially be carried out in the community by community health workers, reducing loss to follow-up.

A community-based approach could be facilitated by two new innovations: a specially designed QR-coded skin patch to guide test administration (SmartPatch), and an AI-driven assessment app that provides a test result and links results to a patient record (using the QR code on the patch). Supported by facility-based TB focal points, community health workers could then ensure that people who test positive start preventive treatment.

The TEST4TPT project is carrying out field-based studies to assess a new SIILTIBCY-based testing pathway. In a first step, reliability and inter-user consistency are being assessed at sites in Mozambique, Tanzania and Uganda. Results from the AI-based app generated by community health workers will be compared with the interpretations made by healthcare workers based on visual assessment, focusing on a mix of age ranges (adults, older children and young children).

Depending on the results obtained in this study, a combined effectiveness/implementation study will then be organised, comparing standard assessment procedures with the use of the SmartPatch and app by community health workers. Participants will be the household and other close contacts of patients newly diagnosed with TB, who are at increased risk of Mtb infection. If they are already showing signs of TB disease, they will be started on TB treatment and excluded from the study. The key outcome measures will be the numbers and proportions of participants who start and complete TPT.

In parallel, the team will carry out acceptability and feasibility studies to identify factors that could accelerate or hinder programmatic use of the new tools. A cost-effectiveness analysis will also be carried out for a range of implementation strategies.

Impact

The TEST4TPT project could lead to accelerated change in tuberculosis care and prevention. It will:

• Demonstrate whether detection of exposure to Mtb by SmartPatch/app use in the community can increase use of TB preventive treatment.
• Identify potential practical barriers to the new approach and its financial implications for TB care and prevention programmes.
• As an additional benefit, provide information on transmission in the community and the annual risk of infection in different age groups.

Tuberculosis preventive treatment (TPT) is an underexploited tool in TB care and prevention. More efficient detection of exposure to Mtb among contacts of new people with TB could facilitate greater TPT use, thereby reducing the number of people progressing to TB disease, limiting further transmission of Mtb, and reducing financial impacts on both households and health systems.