Cure for ‘silent killer’ remains elusive

Barbara Burleigh Chagas disease Big 3 banner

April 30, 2014 — Barbara Burleigh, associate professor of immunology and infectious diseases, studies Chagas disease, a leading cause of infectious heart failure. The disease is a major health and economic burden in Latin America, where it’s endemic, with roughly 8 million people infected and another 100 million individuals at risk of infection, mostly in rural, resource-poor settings.

How does Chagas disease cause infectious heart failure, and does it affect many people in the U.S?

Chagas is one of a group of so-called “neglected tropical diseases”—diseases that mainly affect the poorest countries and that have typically been overlooked because of the world’s focus on the “big three” diseases with the highest mortality rates: HIV/AIDS, malaria, and tuberculosis.In people with Chagas disease, it takes decades after the initial infection for severe symptoms to appear—which is why the disease is sometimes referred to as “the silent killer.” Symptoms include heart failure as well as severe swelling of the esophagus and/or colon, which greatly interferes with digestion. Chagas appears in people chronically infected with Trypanosoma cruzi, typically transmitted via contact with the feces of a blood-sucking insect called the triatomine, or “kissing bug.” Although triatomine bugs are found in the U.S.—mostly in the southern half of the country—people here have rarely been infected through bug bites, because the bugs thrive mainly in cracks and holes in houses made of mud or adobe or thatch—the kind of housing you’ll find in poorer countries. So, in the U.S., Chagas infections come mostly from infected blood or from mother-to-baby transmission, and are on the rise because of new immigration from Latin America. About 300,000 are infected in the U.S., and it’s estimated that Chagas-related health care costs top $100 million annually. While insect control measures in Latin America and donor blood screening both there and in the U.S. have helped lower the incidence of new cases of Chagas disease, more needs to be done. There’s no vaccine for the disease and the two Chagas drugs available—nifurtimox and benznidazole—can provide a cure only if taken very soon after the initial infection. That means that costs will continue to rise for those with Chagas disease, who are often infected as children, develop heart failure at relatively young ages (40s and 50s), and who may require extensive cardiac care, including heart transplants.

What sparked your interest in studying this “neglected” disease?

Since I was a graduate student, I have gravitated toward parasitic diseases that impact populations in the developing world. It is the fascinating biology of the Chagas disease parasite, T. cruzi, that attracted me initially, but the fact that this is a neglected disease afflicting millions motivates me to find ways to combat it. There is still so much to learn about how this pathogen establishes and maintains infection that persists for decades, and about the cellular and metabolic processes involved. Gaining insights into these processes at the molecular level will have significant implications for the understanding and treatment of chronic Chagas disease.

How close do you think we are to finding an effective way to combat this disease?

It’s hard to say. For a long time, Chagas was neglected because pharmaceutical companies don’t see poverty-stricken populations as a market. Now, with increased emphasis on developing drugs to combat neglected tropical diseases—supported by the U.S. government, the World Health Organization, and other nongovernmental organizations and nonprofits—the Chagas disease agenda has gained traction. While some new compounds look promising, recent clinical trials in humans have been disappointing. These failures suggest a complexity associated with persistent human infection that we do not understand. It’s possible that the parasite is able to adapt in order to avoid harm from the medications being used. By studying this possibility at the molecular level, we might be able to pinpoint the mechanisms at play in Chagas disease—which could lead to the development of more effective drugs to fight it.

Karen Feldscher