Shorter benznidazole course cuts Chagas treatment side effects by 40%

More than seven million people worldwide carry Trypanosoma cruzi in their blood, the parasite that causes Chagas disease. Most live in Latin America, though the infection is spreading in the United States, Europe, and Japan. Between 30 and 40 percent of those infected will develop serious complications—heart damage, digestive problems—yet fewer than one in a hundred ever receive a diagnosis or treatment. For decades, the two drugs available to treat the infection have been given in regimens designed over fifty years ago, regimens so punishing that roughly a third of patients simply stop taking them, unable to tolerate the headaches, nausea, joint pain, and fever.

A seven-year clinical trial called TESEO, led by researchers at the University of Texas at El Paso, the CEADES Foundation in Bolivia, and the Barcelona Institute for Global Health, has now found a way to cut that burden substantially. The trial enrolled 450 adults at three centers in Bolivia and tested six different treatment strategies, comparing two drugs—benznidazole and nifurtimox—across different doses and durations. The results, published in The Lancet Infectious Diseases, show that a single daily pill of benznidazole taken for just thirty days works as well as the standard two pills a day for sixty days, while causing far fewer side effects.

The difference is striking. Among patients taking the standard regimen, sixty percent experienced drug-related adverse events. Among those on the shorter course, that number dropped to thirty-seven percent—a reduction of nearly forty percent. More importantly, eighty-three percent of patients on the thirty-day regimen completed their treatment without interruption, compared to sixty percent on the standard protocol. Most side effects appeared within the first two weeks regardless of how long treatment lasted, and nearly all resolved on their own.

Three years after treatment ended, researchers tested participants' blood for parasite DNA using PCR, the most sensitive detection method available. In the thirty-day group, ninety-four percent had undetectable parasites. In the standard group, ninety-five percent did. The difference was negligible—the shorter course was just as effective. The nifurtimox regimens tested in the trial were less effective overall, making benznidazole the clearer choice.

There is another advantage that extends beyond individual patients. The thirty-day regimen uses one-quarter of the drug required by the standard treatment. As one of the trial's senior authors noted, the same amount of medication that previously treated one patient can now treat four. For countries with limited resources and millions of infected people, that mathematics matters enormously.

The trial was funded by an approximately eight million dollar award from the National Institute of Allergy and Infectious Diseases and was completed despite the disruptions of the COVID-19 pandemic. It represents the first clinical trial sponsored by the University of Texas at El Paso, a milestone that university leadership emphasized as significant for both the institution and the field.

Before the thirty-day regimen can be incorporated into official treatment guidelines, larger phase 3 trials will be needed to confirm these results in broader populations. Researchers emphasized that people currently receiving treatment for Chagas disease should continue with the regimen their doctor prescribed. But if the next phase of testing confirms what TESEO has shown, the way millions of people are treated for one of the world's most neglected tropical diseases could change fundamentally—making treatment safer, easier to complete, and far more efficient to deliver.