Large cohort study published on recurrent TB is first of its kind

“It’s been a long time coming,” said Dr. Sabine Hermans when discussing the recently published article in the journal of Clinical Infectious Diseases. The study, completed in 2016, was part of Hermans’ Marie Curie post-doctoral fellowship. It focused on recurrent tuberculosis in the population of Cape Town, South Africa. The results of the study not only surprised Dr. Hermans, but also left her asking more questions about what the best approach would be to improve TB control for patients with a history of TB.

The project, funded by the European Union, was titled the Epidemiology and control of TB in the antiretroviral therapy era: Towards a mathematical model for Cape Town. The funding allowed Asst. Prof. Hermans to spend 3 years in South Africa looking at all episodes of TB disease in the entire city’s population from 2003-2016. This cohort included 260,000 people and 290,000 episodes of TB disease, 9% of which had recurring TB within the 13-year span. Additionally, there were some instances of people who acquired recurrent TB up to 9 times in 13 years. How does this happen and how long does it take before another TB episode appears?

In Cape Town, TB is the largest cause of death of any single infectious disease. The burden of recurrent TB is also extremely high. Every year in South Africa, 30% of treated TB patients would have previously had TB. The data that Dr. Hermans analyzed showed that if a patient had TB once, they were at a much higher risk of getting it again. Also, she was able to show that this risk increased substantially with every subsequent TB episode.

The recent publication on this study, High rates of recurrent TB disease: a population-level cohort study, is unique because up until the release of this publication, there had not been such a large cohort of TB patients with long enough follow-up to allow for such a study. There have been smaller cohorts in high-income settings looking at recurrent TB, but there were lower rates of TB in those settings.

In order to look into this escalating risk of TB further, Dr. Hermans would like to do a more targeted project where she can look in-depth into the potential causes of risks of recurrent TB in patients. “This would entail setting up a prospective cohort study where I can test and follow-up patients from their second to their third episode, taking sputum and blood samples and collecting other indicators that can tell us more about why people get recurrent TB. Maybe they have certain underlying risk factors that make them more susceptible to another episode, which would be important to understand to be able to determine what the best approach would be to reduce their risk of acquiring TB again. Perhaps patients need to be screened for TB regularly or treated for a longer period of time.”

How could these discoveries change TB control policy in the future?

There is a lot in interest in the field of recurrent TB from a vaccine development perspective, as this population is very attractive for TB vaccine testing because it is much less time-consuming. If people with a previous history of TB are immunologically different from those who have never had TB, the vaccine outcome may be different from those who have TB for the first time. Furthermore, the people who get TB for a second, third, or fourth time may have different characteristics that require the formation of a new screening or treatment regimen.