Chagas disease: half the benznidazole course, the same clearance, fewer side effects

Design

Phase 2b, open-label, randomised, non-inferiority, six arms

Population

450 adults aged 18–50 with chronic T. cruzi infection, Bolivia

Primary outcome

Sustained parasitological clearance by PCR, 4–36 months

Effect

BZN 30-day 94% vs 60-day 95%, RD −2.0 (97.5% CI −5.4 to 1.5); adverse events 37% vs 60%

TESEO, published in Lancet Infectious Diseases on 22 September, randomised 450 adults aged 18–50 with chronic Trypanosoma cruzi infection (indeterminate or early cardiac form) at three sites in Bolivia to six regimens: benznidazole 150 mg twice daily for 60 days (standard), 150 mg once daily for 30 days or 90 days, and nifurtimox 240 mg twice daily for 60 days (standard), twice daily for 30 days or once daily for 90 days. It was open-label, and the primary outcome was sustained negative PCR over 4 to 36 months.

All four experimental regimens were non-inferior to their drug's standard. Clearance was 94% with 30-day once-daily benznidazole versus 95% with the standard 60-day course (risk difference −2.0 points, 97.5% CI −5.4 to 1.5). Only the 30-day benznidazole arm reduced drug-related adverse events — 37% against 60% (risk difference −23 points, 95% CI −38 to −7). Most adverse events began within 10 to 14 days regardless of how long treatment lasted.

Practically, a quarter of the standard total dose kept efficacy and made treatment easier to finish, which is the main reason Chagas therapy fails. The authors call for phase 3 confirmation across parasite strains before guidelines change, and PCR clearance is a surrogate, not a clinical outcome.

• Discuss the 30-day once-daily regimen with a specialist centre while guidelines catch up
• Warn patients that rash and gastrointestinal effects usually appear in the first two weeks
• Review patients at day 10–14, when most adverse events surfaced
• Screen Latin American-born patients, and women of childbearing age before pregnancy, for T. cruzi
• In India Chagas is seen only in migrants and returning travellers; seek tropical medicine advice

Why it matters

Chagas treatment usually fails because patients stop it; a shorter, better-tolerated course attacks that directly.

Don't overread it

This is a phase 2b, open-label trial with a PCR surrogate outcome — it does not show fewer cardiac complications.

The statistics, in plain English

Non-inferiority means the new regimen was not worse than the standard by more than a pre-set margin, here 9.5 percentage points. The lower bound of the benznidazole 30-day interval was −5.4, inside that margin. The adverse-event reduction is a true superiority result, with an interval well clear of zero.

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