UVA School of Medicine

2 VIRGINIA MEDICINE A s headlines focus on COVID-19 and monkeypox, tuberculosis remains one of the great scourges of infectious disease around the world. Approximately 1.5 million people died of tuberculosis in 2020, according to the World Health Organization. Alarmingly, that year marked the first increase in TB deaths in more than a decade. But doctors and scientists at the University of Virginia School of Medicine are making important progress in their longstanding efforts to better understand, prevent, and treat tuberculosis, and they recently received a $1.25 million boost for a partnership with colleagues in Tanzania to train the next generation of front-line soldiers in the war against the disease. Malnutrition's Role in Tuberculosis New discoveries from the researchers highlight the crucial role of malnutrition in global tuberculosis. In a paper in the scientific journal The Lancet Microbe, the UVA researchers and their collaborators in Tanzania reveal how malnutrition and gut infections impair tuberculosis treatments for young children. The scientists found that children with these common gut infections have lower concentrations of the critical TB drugs in their bodies — and the more infections they have, the lower the concentration of the drugs. Based on these findings, researchers say that doctors may be able to target the gut pathogens to improve tuberculosis treatment outcomes. "Blame for failure of tuberculosis treatment historically was placed on the patient and a lack of adherence to medicines," says researcher Scott Heysell, MD, MPH, of UVA's Division of Infectious Diseases and International Health. "Instead, the other germs in the gut of children from impoverished areas are leading to suboptimal levels of key medicines even if taken as directed. Some of the same pathogens in the gut that lead to malnutrition and predispose to malnutrition-related tuberculosis make tuberculosis even harder to treat." Malnutrition is a vastly underappreciated contributor to tuberculosis, the researchers say. In a paper in the scientific journal The Lancet Infectious Diseases, the authors call malnutrition a "leading risk factor" for contracting the disease. There is an urgent need, they say, to better understand how nutritional deficiencies compromise the body's immune system. This understanding would shed important light on how malnutrition and "undernutrition" affect the effectiveness of both tuberculosis vaccines and treatments. In the paper, Heysell and his co-authors urge dramatic action against malnutrition and undernutrition: "It is time for governments, non-governmental organizations, philanthropic foundations, and researchers to be invigorated by the challenge and not daunted by it. A rapid scale-up in funding and research is needed," they write. "The payoff could be monumental. Investments in eradicating undernutrition will probably have long- reaching benefits, far beyond their impact on tuberculosis, and can be transformative, especially for low-income regions. We should consider a Haitian saying: 'Giving people medicine for tuberculosis and not giving them food is like washing your hands and drying them in the dirt.'" Training the Next Generation Based in part on the new tuberculosis findings, the National Institutes of Health's Fogarty International Center awarded the UVA scientists a $1.25 million grant that will bolster a longstanding training partnership with their collaborators in Tanzania. The crucial funding will allow the partnership to train Tanzanian postdoctoral researchers Progress in the Global Battle Against Tuberculosis D I S C O V E R Y Scott Heysell, MD, MPH, and Stellah Mpagama, MD, PhD "This program will enable Tanzanians to develop research leaders that will take forward the agenda of 'End TB' in the country."

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