Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the most devastating infectious diseases worldwide. Despite significant advancements in diagnosis and treatment, TB continues to pose a substantial global health burden. According to the World Health Organisation’s 2023 Global TB Report, 10.6 million people were diagnosed with TB in 2022, and 1.3 million people died from the disease, including approximately 167,000 individuals living with HIV.
Developing an effective TB vaccine is one of the most promising long-term solutions to this epidemic. However, conducting vaccine trials requires identifying areas where TB is common, to ensure statistically reliable results within a reasonable timeframe and sample size. Finding such locations can be difficult, especially in countries with limited data and clinical research infrastructure.
In response to this challenge, researchers at the MRC Unit The Gambia took part in a multi-country study to evaluate the prevalence of TB infection. The study was conducted in 14 high-burden countries, including The Gambia, Bangladesh, Brazil, the Democratic Republic of Congo (DRC), India, Indonesia, Kenya, Mozambique, Peru, the Philippines, South Africa, Uganda, Vietnam, and Zambia. To estimate the TB infection rates in these areas, the researchers used a test called IGRA (Interferon-Gamma Release Assay), which detects whether a person has been infected with the TB bacteria, even if they do not have symptoms. By measuring how many people in each area tested positive, researchers could identify populations at highest risk of TB infection and build local clinical research capacity in preparation for the phase 3 clinical trial of a TB vaccine.
Concluded in February 2025, the study revealed that rates of IGRA positivity varied greatly from one country to another and even between different sites within the same country. This reinforces the importance of using detailed localised data when selecting sites for TB vaccine trials. Because the IGRA test reveals whether a person has been priorly infected with TB, it gives researchers a clearer picture of where new cases are likely to occur, which is a critical factor for vaccine trial site selection.
This data is vital for ensuring that future TB vaccine trials can be conducted efficiently, with recruitment of study participants focused on the highest-risk populations. Such precision optimises the chances of detecting a vaccine’s protective effect, which is especially crucial given the long and resource-intensive nature of TB vaccine trials.
The outcomes of this study have implications beyond vaccine development. By mapping the landscape of IGRA positivity and investing in site capacity, the initiative contributes to a broader understanding of TB epidemiology in diverse settings. This knowledge can inform public health strategies, guide resource allocation, and improve early intervention programs in high-burden areas.
Moreover, the capacity-building efforts associated with the study have laid the groundwork for future TB research, fostering stronger global collaboration and equipping local institutions with the tools needed for sustained TB control efforts.
According to Professor Jayne Sutherland, Head of the TB Research Group at MRCG at LSHTM, “There is an urgent need for a new TB vaccine. This project, funded by Gates MRI, was the precursor to one of the first Phase 3 TB vaccine trials in decades. The M72 vaccine was shown to have 50% efficacy in a Phase 2b trial in South Africa. This next step was to ‘prime’ the sites to ensure excellence of results. It was a steep learning curve for our team, but they performed exemplary and developed new levels of skills for clinical trials. Special thanks go to the TB clinic team led by Dr Owolabi, our excellent field team responsible for enrolment and follow-up of participants, and the laboratory team, led by Ms. Georgetta K. Daffeh, for the extensive sample analysis, data entry and shipping requirements. This project has not only set the scene for future TB vaccine trials but also put us in good stead to conduct a clinical trial on an adjunctive therapy to reduce the burden of post-TB lung disease.”
As the global community works toward ending the TB epidemic, strategic, data-driven, and inclusive approaches such as this multi-country study will represent a significant step toward the development and implementation of more effective TB prevention tools, including vaccines.
The Bill & Melinda Gates Medical Research Institute sponsored the study.
