World TB Day 2024: focus on long-term effects

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On 24 March 1882, bacteriologist Robert Koch announced that he had successfully isolated the tuberculosis (TB) pathogen, a discovery commemorated on World Tuberculosis Day. The disease is caused by mycobacteria. Tuberculosis remains a scourge of humanity 142 years later. According to the World Health Organization (WHO), some 10.6 million people fell ill with the disease in 2022, with almost 1.3 million people dying from it. Doctor of Medicine Andrea Rachow researches the late effects of TB in people who have survived infection, with a particular focus on post-tuberculosis lung disease (PTLD). As well as heading the TB Epidemiology and Clinical Cohorts research group at the Division of Infectious Diseases and Tropical Medicine at University of Munich Hospital, Rachow is co-director of the TB Sequel Network and co-head of the Unit Global Health (UGH) at Helmholtz Munich.

“In the fight against tuberculosis, the main focus of attention has been on diagnosis and treating the disease,” says Rachow. “By contrast, the long-term effects of the disease have remained largely unknown.” The SARS-CoV-2 pandemic has gone a long way to changing people’s perspective on this. “Although the pathophysiological symptoms of pulmonary post-Covid are very different from the ones of PTLD, the pandemic raised awareness at all levels that infections can have long-term health implications.”

What are the effects of post-tuberculosis lung disease?

“Patients with PTLD are no longer infectious,” explains Rachow. “But they suffer from considerable long-term consequences, medically and socially.” Tuberculosis can leave scars in the lungs, which lead to restricted lung volume and increase the risk of respiratory problems. Post-tuberculosis can also manifest as a persistent cough, phlegm, and shortness of breath. For many people, these complaints mean they can no longer work or participate in social life to the same extent as they did before. Children of parents with post-tuberculosis suffer a drop in educational performance, affecting their future prospects. These are key findings of the TB Sequel I study.

But how can we help those affected? TB Sequel I and TB Sequel II seek to address precisely this question. These projects are being carried out by Rachow and colleagues together with the Aurum Institute in South Africa and six other research institutions in Germany and sub-Saharan Africa. "When we started out planning the first study, there wasn’t even a standard term for post-tuberculosis complaints,” recalls Rachow. “We wanted to understand what long-term pulmonary consequences the disease has.” Further questions include: What complications – for example, superinfections – are there? Do patients with this condition require more frequent medical treatment? Do some of them die from the effects of PTLD?

A total of 1,500 participants were admitted to the cohort at the time of their TB diagnosis. “We’re now in the fifth to the seventh year of observing them,” reports Rachow. The team was able to confirm that up to 25 percent of the study participants had moderate to severe impairments of lung function even several years after their acute illness. “In addition, we’re collecting blood or sputum samples in order to determine immunological parameters and understand what inflammatory processes are involved in the pathological process, especially when the disease takes a chronic course.”

In this context, the researchers are investigating whether N-acetylcysteine (NAC), an active ingredient that is approved for use as a cough expectorant, could also be beneficial for PTLD. A small pilot study has furnished indications to support this possibility. NAC has anti-inflammatory effects and traps harmful oxygen radicals. Rachow: “We hope that giving TB patients NAC therapy will lead to less tissue damage and the resulting lung function impairment.” In addition to the medical aspects, TB Sequel II is also about better understanding economic effects, such as the increase in severe poverty among patients and families affected by TB and PTLD. The study will also investigate sociological consequences, such as stigma and discrimination of patients with PTLD. And last but not least, it will analyze the costs associated with PTLD for health systems.

New knowledge to quickly benefit people affected

At the heart of the enterprise is the question of how to care for patients with PTLD. The evidence currently available is not robust enough to create guidelines. But the results of Rachow’s research group could help pave the way for better care for people affected by PTLD. “We’re working with our partners in various African countries to devise initial recommendations for action for the responsible health authorities and systems,” says Rachow. This is an important aspect of the funding granted by the German Federal Ministry of Education and Research (BMBF): swift translation of the insights obtained by research into improved medical care for patients. “The same goes for RHISSA, Research Networks for Health Innovations in Sub-Saharan Africa, where the ministry is particularly interested in the direct transfer of research results into medical care locally – among other things, through the active integration of political decision-makers into the planning and implementation of these projects – alongside the training of African scientists and the development of high-class research infrastructure and networks.”

The Global Fund to Fight AIDS, Tuberculosis and Malaria is another of the principal sponsors, funding programs for TB diagnostics and therapy. As part of a tender, African countries had the opportunity to apply for funding last year, and this included TB-associated diseases such as PTLD for the first time. “It’s important to realize that the main bulk of the activities the Global Fund currently supports are related to the care of patients with active tuberculosis. But of course you can prevent PTLD during this period – and this provides us with our opportunity,” emphasizes Rachow.

At the same time, the WHO is engaged in activities with international experts, including researchers from the TB Sequel consortium, aimed at developing an international guideline for PTLD. Post-TB is also beginning to feature in expert panels and scientific research groups. The road to better care for patients is slowly but surely being paved.