Over the past two years, the COVID-19 pandemic has been at the centre of health research. This has stymied progress in the management of another global health crisis – tuberculosis (TB), which remains a major health threat in South Africa.
World Tuberculosis Awareness Month, during which World Tuberculosis Day is observed on 24 March, is an opportunity to renew our commitment to excellence in the epidemiology, and timely diagnosis and treatment of the disease.
According to the World Health Organisation’s (WHO) 2021 Global Tuberculosis Report, TB claimed the lives of 1.5 million people in 2020. The same report indicates an 18% drop in new TB diagnoses in the first year of the pandemic (2020) and a 21% drop in the number of people receiving treatment for the disease. The report also shows the first year-on-year increase in the global number of TB-related deaths since 2015, and marks a massive setback for the WHO’s End TB goals.
Several factors have contributed to this setback, including reduced access to healthcare facilities during the pandemic; a significant drop-off in diagnostic testing; the similarity in symptomatology between pulmonary TB and COVID-19, causing the former to be missed; and the diversion of resources as a consequence of the pandemic.
The pandemic has highlighted the need to recentre our focus when it comes to the treatment of TB in South Africa: we need to improve on our ability to provide remote care and expand our use of digital technology; bring treatment to the community and limit the number of healthcare service visits; support the provision of preventative TB treatment; and proactively plan for future pandemics. The consequences of the sudden halt in progress towards TB elimination will be felt for years to come in terms of mortality, advanced presentation of disease and lifelong disability for some patients.
However, the pandemic years have not been completely lost to TB research, and there have been significant contributions to the understanding of transmission and treatment. The basic sciences have improved our understanding of the pathophysiology of the disease, with 3D printing technology creating the first model of a granuloma (a cluster of white blood cells and other tissue produced in response to an infection), thus providing insight into the spatial organisation of the TB granuloma and its relation to the airways and vasculature of the lungs. We also learned that 90% of aerosolised TB occurs as a result of normal breathing; this is in stark contrast to the widely accepted idea that coughing is the main contributor. This influences our practices in infection control and transmission prevention. Additionally, University of Pretoria (UP) researchers have mapped the lung microbiome in patients with HIV and TB co-infection, and demonstrated that there is a loss of microbial diversity when compared with HIV-positive controls.
Furthermore, there has been a shift in our understanding of the spectrum of the disease. We used to consider TB as either “latent” or “active”. The former refers to people who are infected but have no symptoms and whose immune systems have things in check, while the latter refers to those who have clinical manifestations of the disease. The paradigm is shifting towards a continuum of disease, where “subclinical TB” is emerging as a disease entity. In subclinical TB, disease is present, and can be diagnosed by microbiological and radiological means, but there is no obvious clinical disease. It is estimated that subclinical TB accounts for about 50% of disease prevalence globally, and contributes to transmission and spread of the disease.
Important research questions have arisen, particularly around whether and how people with subclinical TB should be treated. UP and Leicester University are collaborating to investigate the prevalence of subclinical TB, phenotype people with subclinical disease (determine their biochemical traits) and monitor them to understand disease progression and spread.
In terms of TB diagnostics, there has been renewed interest in novel biomarkers such as T-cell activation assays and RNA signatures to diagnose TB, and to aid stratification of patients into those who require longer and shorter treatment courses. Most of these studies are still in the experimental phase. The discovery of a protein CFP-10 that can be detected in the blood of neonates with TB infection offers new hope for earlier diagnosis in this vulnerable group.
A wonderful example in which science and community health come together to improve outcomes is a collaborative study between UP and Leicester University which showed that face-mask sampling in the community offered an efficient, non-invasive method to detect Mycobacterium tuberculosis. Another UP diagnostic study described computed tomography (CT) findings that suggest residual disease in patients who have completed TB treatment, using fluorine-18 fluorodeoxyglucose positron emission tomography/CT scanning to detect residual metabolic activity in the lungs.
Although progress in the development of a TB vaccine took a back seat to the production of SARS-CoV-2 vaccines, the technology, networks and experience gleaned by the latter are likely to strengthen TB vaccine research in the future. In terms of the treatment of TB, various important advances have been made. In drug-resistant TB, the recently developed anti-tuberculosis drugs bedaquiline and pretomanid have been significant treatment developments in recent years. The so-called BPaL regimen (bedaquiline, pretomanid and linezolid) has also shown favourable outcomes in the treatment of resistant TB.
As we start to emerge from the COVID-19 pandemic, there is an opportunity to rethink the way in which we prevent and manage TB in our communities. South Africa is uniquely positioned because of its high prevalence of the disease coupled with its research capabilities to study all aspects of the disease and translate high-level science into tangible patient outcomes at community level. It is time to regain the momentum lost in our fight towards the eradication of TB.
Professor Veronica Ueckermann is Adjunct Professor of Internal Medicine at the University of Pretoria’s Faculty of Health.
This article first appeared on news24 on 24 March 2022.