Chagas disease kills more than 50,000 people each year in Central and South America and is a growing threat in the United States and Europe. UGA researchers have discovered one reason why: The parasite that causes the disease can go dormant, effectively “hiding out” from drug treatment regimens and re-establishing the infection once it re-emerges.
The disease infects an estimated 6 million to 7 million people, according to the World Health Organization, although some scientists estimate the number could be as high as 20 million. Chagas disease damages the heart and digestive system, and effective prevention and treatment methods are virtually nonexistent.
In a study published in eLife, Rick Tarleton and his team at the Center for Tropical and Emerging Global Diseases sought to determine why drug treatments frequently fail.
“Benzimidazole has been shown to be particularly effective in reducing parasite infection,” says Tarleton, Regents’ Professor in the department of cellular biology. “A single dose can eliminate nearly 90 percent of parasites within 48 hours, but we didn’t know why it didn’t kill 100 percent of the parasites.”
For the first time, they show that a small proportion of Trypanosoma cruzi parasites halt replication within 24 hours of invading the host cell. These dormant parasites are resistant to extended drug treatment and can resume replication after treatment ends, thus re-establishing a growing infection.
The researchers don’t know why some of the parasites exhibit this behavior, but they are hopeful that future studies into this mechanism will shed more light on the way T. cruzi evades the host’s immune response.
“This isn’t drug resistance in the classical way we think of resistance,” Tarleton says. “The parasites aren’t dormant because of the presence of the drug.”
In fact, while treatment continued, researchers saw some of the dormant parasites “wake up” and then become susceptible to the treatment. The team believes the key to effective treatment will be to catch the parasites as they resume replication, continuing medication until no parasites remain in the host.
“This discovery really offers a solution for current drugs to be used in a more effective way,” he says. “A longer, less concentrated dosing schedule could lead to a cure.”
Life cycle of Trypanosoma cruzi, the cause of Chagas disease
(Graphic by Lindsay Robinson)
This story appeared in the fall 2018 issue of Research Magazine. The original press release is available at https://news.uga.edu/study-reveals-key-cause-treatment-failure-chagas-disease/.
