A major new research project at Africa Health Research Institute (AHRI) is set to tackle asymptomatic TB, one of the most complex issues hindering progress in the fight against the tuberculosis (TB) epidemic. The R58-million ($3,236,622), multi-site, three-year project, led by AHRI faculty member Dr Emily Wong and funded by the Gates Foundation, will use cutting-edge technologies to improve understanding of asymptomatic TB and identify signals that may lead to useful screening tests.

TB is the leading cause of death by infectious disease globally. In South Africa, the World Health Organisation estimates 56,000 people died from TB and around 270,000 people fell ill with TB in 2023. However, recent evidence has indicated that half of all people who have active pulmonary TB are unaware of their status – because they have no symptoms. This condition, known as asymptomatic TB, damages lung tissue but does not trigger signs of illness. Some research suggests that people with asymptomatic TB may also contribute to spreading TB to others. There are still many knowledge gaps about asymptomatic TB, and its contribution to the global TB burden. There are also many challenges to addressing the issue at an international level. These include:

  • there is currently no cost-effective diagnostic method to screen large numbers of asymptomatic patients
  • a lack of understanding of the wide range of disease states within the ‘asymptomatic’ category – including who may contribute to spreading TB, and who may not
  • the difference between those who are likely to develop to more advanced disease and those who are likely to recover without treatment

The AHRI study will focus on these unanswered questions by analysing a unique cohort of people with asymptomatic TB, who were initially enrolled during AHRI’s Vukuzazi project in rural KwaZulu-Natal between 2018 and 2020. Using advanced scientific methods, including multi-omic and high-dimensional analyses, the research team will investigate blood samples to identify biological markers that distinguish the different subtypes of asymptomatic TB. The study will also include clinical follow-ups over five years with people who had confirmed or suspected asymptomatic TB during Vukuzazi.

(Above: Inside the digital x-ray truck at one of Africa Health Research Institute’s Vukuzazi mobile screening camps)

“This project will use a discovery strategy to better understand the full spectrum of asymptomatic TB and will include a large proportion of people living with HIV – a crucially important population that is often overlooked in biomarker studies,” said Dr Wong.

“Definition of these asymptomatic TB ‘sub-types’ and their biological characteristics will allow public health strategies to focus on detecting and treating the people with asymptomatic TB who require intervention.”

 *This study is led by Dr Emily Wong, an infectious disease physician-scientist based at the Africa Health Research Institute and the University of Alabama at Birmingham. Collaborators include teams from the South African TB Vaccine Initiative (SATVI, led by Prof Tom Scriba) and the Harvard School of Public Health (led by Prof Sarah Fortune). Additional partners have been engaged through the Gates Foundation-funded Global Health Discovery Collaboratory  Platforms (ghdiscoverycollaboratory.org), including: the Center for Human Systems Immunology at Stanford University, the Vaccine Immunology Statistical Center (VISC) at Fred Hutchinson Cancer Center and Metabolic Biomarker Discovery and Sapient.