A Shorter, Better-Tolerated Treatment for Chagas Disease Is Possible

A 30-day course of benznidazole taken once a day could offer people with chronic Trypanosoma cruzi  infection a safer and more practical option than the current standard treatment, taken twice a day for 60 days. The TESEO trial, co-led by The Barcelona Institute for Global Health (ISGlobal), an institution supported by the “la Caixa” Foundation, the University of Texas at El Paso (UTEP, USA), and CEADES (Bolivia), reports these results today in The Lancet Infectious Diseases.

A neglected disease with limited treatment options

Trypanosoma cruzi infection affects more than seven million people worldwide, mainly in Latin America, and is now also a public health concern in the United States, Europe and Japan. About 30–40% of infected people develop Chagas disease, with serious heart or digestive complications, yet fewer than 1% are diagnosed and treated. The only two drugs, benznidazole and nifurtimox, are given in regimens set more than 50 years ago that frequently cause side effects, and up to 31% of patients stop treatment early.

Six treatment strategies compared over three years

“TESEO is the first randomized clinical trial to evaluate benznidazole and nifurtimox head-to-head under identical conditions, with sustained follow-up to detect parasites in the blood by PCR for three years,” says Igor Almeida (UTEP), co-senior author of the study with Joaquim Gascón (ISGlobal) and Faustino Torrico (CEADES).

The phase 2b trial enrolled 450 adults at three centers in Bolivia and randomly assigned them to six groups: three benznidazole regimens (the 60-day standard, 30 days and 90 days) and three nifurtimox regimens (the 60-day standard, 30 days and 90 days). The researchers recorded drug-related adverse events and tested participants’ blood for parasite DNA by qPCR over three years.

Fewer side effects with 30 days of benznidazole

Only the 30-day benznidazole regimen significantly reduced side effects: 37% of participants had a drug-related adverse event, compared with 60% on the standard regimen, a reduction of nearly 40%. It was also easier to follow, with 83% of patients completing treatment without interruption, compared with 60%. Most side effects appeared within the first two weeks, regardless of treatment length, and almost all resolved.

Without compromising efficacy

Three years after treatment, the parasite remained undetectable in the blood of 94% of participants in the 30-day group, compared with 95% in the standard group, meeting the prespecified criterion for non-inferiority. The 30-day regimen therefore offered the best balance between benefits and harms of the six strategies tested. The nifurtimox regimens were less effective overall (81% to 90%).

“The improved safety profile of the shorter benznidazole regimen, combined with once-daily dosing, has the potential to substantially increase the proportion of patients who complete treatment,” says Gascón. The 30-day course also uses a quarter of the drug: “We can treat four patients with the same amount of drug we previously used for one,” adds Torrico.

Larger phase 3 trials are needed to confirm these results before the 30-day regimen can be incorporated into treatment guidelines. People currently receiving treatment for Chagas disease should continue the regimen prescribed by their doctor.

Reference

Alonso-Vega C, Pinto Rocha JJ, Rojas Delgadillo LG, García Ruiloba W, Palacios López A, Pinto Rocha LV, Méndez Bartolomé S, González VR, Laserna M, Ribeiro I, Pinazo MJ, Thomas MC, López MC, Losada Galván I, Ortiz L, Schijman AG, Urbina JA, Sanz Bravo S, Gascón J, Torrico F, Almeida IC. Efficacy and safety of alternative benznidazole and nifurtimox regimens for adults with chronic Trypanosoma cruzi infection (TESEO): an open-label, randomised, non-inferiority phase 2b trial. Lancet Infect Dis 2026; published online September 22. https://doi.org/10.1016/S1473-3099(26)00436-6.