LITTLEROCK, California — In Uganda, with a population of 46 million people, one person contracts tuberculosis (TB) every six minutes while another dies from TB every 42 minutes, according to the World Health Organization (WHO). The deadly infectious disease can affect any body part but primarily affects the lungs because it spreads easily through the air.
WHO data points to HIV as the prime factor for people in Uganda becoming ill with TB. Other factors include malnourishment, smoking, alcohol use disorders and diabetes. TB presents a series of challenges for medical practitioners and health agencies combatting its prevalence.
Early detection, diagnosis and treatment are vital in stopping the spread of tuberculosis in Uganda. Researchers in the academic-public health partnership Uganda Tuberculosis Implementation Research Consortium (U-TIRC) and its parent NGO Walimu are developing more efficient TB diagnostic tests and management strategies.
Framing the Challenges
Eradication of tuberculosis in Uganda and halting infection transmission is often an uphill battle. On a global scale, lack of funding and outdated methods of diagnosis and/or screening are significant barriers to eliminating TB. Dr. Luke Davis, an associate professor of Epidemiology and Medicine at the Yale School of Public Health, principal investigator at U-TIRC and a board director at Walimu, explained the issue to The Borgen Project by saying that “It is very expensive to provide TB services and it’s hard to find TB, it’s like finding a needle in a haystack sometimes.” A quick, low-cost method of screening is needed to locate this elusive culprit. The general public may be familiar with the TB skin test. However, this test only detects the potential infection with TB (latent TB) and not active TB disease.
The standard for diagnosing active TB is a sputum (phlegm) culture test, but the consensus is that this method is time-consuming, costly, potentially hazardous and inapplicable to individuals who cannot produce sputum. There is less capacity for Ugandan health care systems to manage TB and deliver care because of limited resources, health care workers and optimally designed facilities, according to Davis. Another barrier present he mentioned that contributes to this is the lack of education on TB within local communities which can perpetuate stigma or misconceptions. Walimu, a research and policy advocacy organization, identifies these barriers and develops strategies to overcome them. Its mission is to improve and scale-up tuberculosis care and prevention nationwide.
Research in Uganda
Davis, who is a physician, saw first-hand how challenging the TB situation was when he trained years ago at a hospital in Kenya. This led him to later collaborate with Uganda’s oldest and most prestigious university – Makerere University. The Makerere University College of Health Sciences is a leading research institution and has a memorandum of understanding with Walimu, which hosts U-TIRC. It is a collaborative effort between local and international investigators at U-TIRC and Uganda’s Ministry of Health to integrate new evidence and strategies into TB public health care and support frontline healthcare workers. The consortium also works diligently to address social and economic barriers to TB care and elimination.
The Development of Molecular Testing
“The biggest revolution that’s happened in TB diagnosis over the last 30 years, especially over the last 15 years, is the development of molecular testing,” Davis stated. An exploration into the application of molecular diagnostics is present in a 2022 pilot study, in which Davis is a senior author, that took place in Uganda’s capital, Kampala. The study examined if testing saliva samples using Cepheid’s GeneXpert could be an alternative to sputum. Coughing is a common symptom of TB and can bring up TB bacteria (Mycobacterium tuberculosis) from the lungs into saliva. The research team found that the saliva test is feasible and it correctly diagnosed 90% of participants with confirmed TB. Saliva, however, may only contain small amounts of the bacteria and has limitations. Still, participants were more comfortable giving saliva samples than sputum.
The next phase of research is to test larger groups, such as populations with advanced TB, and improve test performance. The test could also potentially pair with new molecular platforms that were innovative tools for diagnosing COVID-19. “So something like the CRISPR technologies, a new molecular technology recognized with the Nobel Prize in Chemistry in 2020,” Davis said, “might be appealing because the tests might be successful, let’s say without electricity, or with a minimum amount of electricity (i.e. solar panels) compared to the molecular tests now that we now have.”
Education and Counseling
Also taking place in Kampala, Davis is one of the principal investigators for U-TIRC’s Theory Informed Education and Counseling Intervention for HIV-TB Treatment Adherence (TEACH) project. The project evaluates an innovative TB education and counseling intervention for newly diagnosed TB patients that uses peers who have or had TB as educators. Davis believes these are the best messengers because they can share their journeys and what the practical effects of contracting TB may be. This strategy can help lessen the burden placed on healthcare workers and combat the lack of standardized education on TB.
U-TIRC is additionally evaluating the effectiveness of an intervention strategy aiming to improve contact investigation across 12 clinics in Uganda.
Artificial Intelligence
Other principal investigators at U-TIRC are studying TB with the help of artificial intelligence (AI) Davis shared. Dr. Emily Kendall from Johns Hopkins and Dr. Achilles Katamba from Makerere University are studying the use of artificial intelligence to interpret chest X-rays, Davis explained. Dr. Adithya Cattamanchi and others are authors of a recent study this year that tested whether monitoring cough sounds can help diagnose TB and track treatment response using acoustic AI. Such technology can help collect data on the pitch, frequency and number of coughs.
The study used the Hyfe Research smartphone app to monitor participants with presumed TB over 14 days at health centers in Uganda and other countries. Using this data, researchers identified a distinct cough frequency in participants with TB early in treatment. The results support cough-based monitoring as a possible treatment and diagnostic tool and qualify for further study. This method could be invaluable for low-income populations displaying TB-like symptoms and those living far from healthcare facilities.
Breaking the Chains of TB
Eliminating tuberculosis in Uganda by 2050 may not be a realistic goal from an epidemiologist’s perspective. “Reducing TB incidence below one case per 100,000 population per year would eliminate TB as a public health problem [and]may be achievable in low TB burden countries,” Davis said, “but we will need a transformative technology like an effective TB vaccine to achieve this in high-burden countries like Uganda.” It is therefore beneficial for Uganda to still strive towards this goal. With expanded funding, international research holds the potential to make this transformative technology a reality.
– Clare Calzada
Photo: Flickr