Why is tuberculosis still a major cause of death? An interview with Dr. Hmwe Hmwe Kyu

Associate Professor Hmwe Hmwe Kyu, PhD, discusses the recently published article “Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy: a systematic analysis for the Global Burden of Disease Study,” published in The Lancet Infectious Diseases in March 2024. Dr. Kyu leads a research team focused on modeling the burden of HIV/AIDS, tuberculosis, diarrheal diseases, upper and lower respiratory infections, otitis media, meningitis, and encephalitis for the GBD study.

This transcript has been lightly edited for length and clarity.

Katherine Leach-Kemon: In your paper, I was really struck by the quote that said tuberculosis is a preventable and largely curable disease. Why are more than 1 million people still dying each year from tuberculosis?

Hmwe Hmwe Kyu: That’s a very good question. Challenges remain in the prevention, diagnosis, and treatment of TB. About a quarter of the global population carries a latent TB infection, and of these, over 9 million develop active TB disease, with over a million dying from the disease each year. Despite TB having different stages, from latent TB infection to active TB disease, the ability of current diagnostic tools to predict who will progress to active TB is limited. Additionally, delayed diagnosis and treatment of TB disease can result from several factors, including a lack of patient awareness of TB symptoms, limited access to health care services, and health system challenges such as staff shortages and limited diagnostic tools, all of which may contribute to poor outcomes. Non-adherence to TB treatment, drug resistance, comorbidities, and risk factors further complicate TB prevention and control.

Let’s consider one of the high-risk groups, which is older adults. They have weakened immunity and are at high risk of progressing from latent to active TB. Often, they do not exhibit typical TB symptoms such as coughing up blood, weight loss, or night sweats, which contributes to the delay in diagnosis and treatment. Older adults are also prone to adverse drug reactions, potentially contributing to treatment interruptions and poor outcomes. Furthermore, they tend to have comorbidities that increase their risk of poor treatment outcomes and mortality.

Despite these challenges, studies have demonstrated a number of promising strategies that may help reduce the TB burden. Some of these strategies include strengthening TB diagnostics by forming partnerships with private laboratories, conducting active case-finding in areas known for high occurrences of TB, integrating health care services to simultaneously address TB and other comorbid conditions such as HIV/AIDS, and implementing monetary incentive programs to encourage patients to adhere to their TB treatment regimens. The way forward includes learning from successful strategies and adapting interventions to suit local needs.

Katherine Leach-Kemon: You mentioned that smoking, alcohol use, and diabetes were risk factors for TB. Why do these different risk factors put people at a greater likelihood of dying from TB?

Hmwe Hmwe Kyu: There are several potential mechanisms through which these risk factors can put people at higher risk of dying from TB. A commonly cited mechanism is that, by impairing the body’s immune response, these risk factors not only increase the risk of developing active TB but can also lead to poorer outcomes in TB treatment, including a higher risk of mortality. Beyond weakening the immune response, alcohol consumption and smoking are associated with poor adherence to TB treatment, an increased risk of treatment failure, and higher rates of patients being lost to follow-up. Additionally, research has shown that individuals with diabetes face a heightened risk of death during TB treatment and an increased likelihood of TB relapse after successfully completing treatment. Studies have shown the promising benefits of integrated care services. For example, collaborations between TB and diabetes care programs have been shown to manage both conditions more effectively and concurrently, resulting in better outcomes.

Katherine Leach-Kemon: How big a threat are antibiotic-resistant TB infections?

Hmwe Hmwe Kyu: The fraction of TB deaths attributable to multidrug-resistant TB (MDR-TB) was about 9%, whereas the fraction attributable to extensively drug-resistant TB (XDR-TB) was less than 1% in 2021. From 2015 to 2021, the mortality rates for both MDR-TB and XDR-TB declined more slowly compared to those for drug-susceptible TB.

The challenge with MDR-TB and XDR-TB lies not only in their resistance to standard treatments but also in the complex, expensive, and often less effective treatment options available. These treatments can take a much longer time, sometimes up to two years, and have more severe side effects. They are also more costly, which places a heavy burden on both patients and health systems.

Katherine Leach-Kemon: I’d love to hear more about what led you to become an expert in measuring the burden of disease from conditions such as TB.

Hmwe Hmwe Kyu: My personal connection to TB likely originated from my childhood experiences, when my daily walk to school took me past the grounds of a TB hospital. The windows of the hospital were always closed. Occasionally, passing by across the way, I caught sight of TB patients stepping out for a brief exposure to sunlight. This was my first, although indirect, encounter with TB, which I knew very little about except for its contagious nature.

Later, through medical school and my medical practice, I witnessed firsthand the impact of TB and HIV/TB co-infection on patients, many of whom were unaware of their condition until it had progressed significantly. These experiences may have laid the foundation for my lifelong interest in infectious diseases, including TB. Joining IHME provided me with an exciting opportunity to further pursue my interest. TB research is complex and fascinating, requiring ongoing learning and adaptation to keep pace with new developments. I often say, “I’m still learning,” because the field is constantly evolving.

Katherine Leach-Kemon: Thank you for your time. This was so informative.