A shorter benznidazole course cleared Chagas as well as the standard 60 days

A 30-day course of benznidazole cleared the parasite that causes Chagas disease as well as the standard 60-day course, and caused fewer side effects, in the randomised TESEO trial [s1]. The result points toward a shorter, better-tolerated treatment for a neglected infection that, by the World Health Organization's estimate, affects about 8 million people worldwide [s2].

For a disease whose main drugs are effective but hard to finish, a regimen that is half as long and gentler is a meaningful practical gain.

Why the length of treatment matters

Chagas disease is caused by the parasite Trypanosoma cruzi, spread mainly by blood-sucking triatomine bugs and classed by the WHO as a neglected tropical disease since 2005 [s2]. It is concentrated in 21 continental Latin American countries but has been detected in 44 countries as people move, and the WHO records more than 10,000 deaths a year and more than 100 million people at risk [s2]. Untreated, up to a third of people with chronic infection go on to develop heart disease, and about 1 in 10 develop digestive, neurological or mixed complications, often decades later [s2].

The two drugs that kill the parasite, benznidazole and nifurtimox, work best when given early, but treatment is long and hard to tolerate: the WHO notes courses of up to two months and adverse reactions in up to 40% of adults, which drives many patients to stop before finishing [s2]. Anything that shortens the course or reduces side effects without sacrificing efficacy therefore addresses one of the biggest obstacles to actually treating the disease. That obstacle is one reason Chagas remains a leading cause of premature death in endemic populations.

How the trial was run

TESEO was an open-label, randomised, non-inferiority, phase 2b trial in adults with chronic T. cruzi infection confirmed by quantitative PCR, in the indeterminate or early cardiac form of the disease [s1]. Participants were randomly assigned in equal proportions to one of six regimens, with 75 people per group: benznidazole 150 mg twice daily for 60 days (the standard of care), benznidazole 150 mg once daily for 30 days, benznidazole 150 mg once daily for 90 days, nifurtimox 240 mg twice daily for 60 days (the standard of care), nifurtimox 240 mg twice daily for 30 days, and nifurtimox 240 mg once daily for 90 days [s1].

The primary outcome was sustained parasitological clearance — all-negative qPCR results for at least four of seven timepoints between 4 and 36 months — in a modified intention-to-treat population [s1]. Each experimental regimen was tested for non-inferiority against the standard-of-care course of the same drug, at a prespecified margin of -9.5 percentage points on the risk difference [s1]. Between 18 December 2019 and 20 May 2021, 890 people were screened and 450 were enrolled and randomly assigned [s1].

What it found

Sustained clearance was seen in 69 of 73 participants (95%) in the benznidazole 60-day standard-of-care group, 68 of 72 (94%) in the benznidazole 30-day group, and 69 of 75 (92%) in the benznidazole 90-day group [s1]. In the nifurtimox arms it was 58 of 72 (81%) for the 60-day standard of care, 63 of 71 (89%) for the 30-day course, and 65 of 72 (90%) for the 90-day course [s1].

All four experimental regimens met the bar for non-inferiority against their within-drug standard of care [s1]. The risk differences, experimental minus standard, were -2.0 percentage points for benznidazole 30 days (97.5% CI, -5.41 to 1.45), -2.0 for benznidazole 90 days (-5.45 to 1.49), 3.3 for nifurtimox 30 days (-3.84 to 10.48) and 1.5 for nifurtimox 90 days (-6.76 to 9.70) [s1].

Side effects, the practical crux, favoured the shorter benznidazole course. Overall, 273 of 449 participants in the safety analysis (61%) had at least one drug-related adverse event [s1]. Fewer people in the benznidazole 30-day group had a drug-related adverse event — 28 of 75 (37%) — than in the benznidazole 60-day standard-of-care group, 45 of 75 (60%), a risk difference of -23 percentage points (95% CI, -38 to -7; adjusted p=0.022); no other comparison between arms was significant [s1].

What it does and does not establish

The trial's own conclusion is specific: benznidazole 150 mg once daily for 30 days showed non-inferior efficacy to the 60-day standard while causing fewer side effects, supporting its adoption as the preferred benznidazole regimen [s1]. It was funded by the US National Institutes of Health, not by a drug manufacturer [s1].

The limits are those of an early-phase trial. This is a phase 2b study, and its endpoint is parasite clearance measured by PCR — a biological marker, not a count of the heart and digestive complications that make Chagas dangerous, which take decades to appear [s1]. The trial was open-label, meaning participants and staff knew which regimen was given, and its groups of 75 are modest [s1]. A shorter course that clears the parasite as reliably is a strong lead, but confirmation that it also prevents long-term organ damage would need longer, larger follow-up.

What to watch

The immediate question is whether guideline bodies and national programmes adopt the 30-day benznidazole regimen, which would ease the treatment burden for patients and health systems alike. The longer one is whether shorter courses hold up on clinical outcomes, not just parasite clearance — the test any surrogate must eventually pass.

This article describes trial results. It is not medical advice, and nothing here should be used to start, stop or change treatment.

Sources

• Efficacy and safety of alternative benznidazole and nifurtimox regimens for adults with chronic Trypanosoma cruzi infection (TESEO), The Lancet Infectious Diseases, 22 September 2026
• Chagas disease (American trypanosomiasis) — fact sheet, World Health Organization, 8 April 2026