Soil-transmitted helminths infect more than 1.5 billion people worldwide, and Trichuris spp. infections remain notoriously difficult to treat. The widely used benzimidazoles albendazole and mebendazole achieve cure rates of only about 30.7% and 42.1% respectively against whipworm in single-dose regimens, even though they are highly effective against roundworm and reasonably effective against hookworm. Untreated, repeated Trichuris infections can contribute to malnutrition and impair physical and cognitive development in children. The World Health Organization has set a goal of eliminating soil-transmitted helminthiasis as a public health problem by 2030, defined as fewer than 2% of at-risk individuals harbouring moderate or heavy intensity infections, and the trial’s authors argue that reaching that target will require more effective medicines.

Oxfendazole, a benzimidazole approved since 1990 for treating cestodes and nematodes in dogs, horses and cattle, works by degenerating parasite microtubules, blocking glucose uptake and depleting the parasite’s energy reserves while leaving glucose metabolism in mammals unaffected. Three phase 1 trials conducted between 2014 and 2022 in healthy volunteers, including a 2022 Tanzanian study of the same tablet formulation used in the new trial, found the drug well tolerated with no major safety concerns and a long elimination half-life. Within the EU-funded eWHORM consortium, an adaptive basket-design platform was set up across four sub-Saharan African countries to evaluate oxfendazole against onchocerciasis, loiasis, mansonellosis and trichuriasis under a unified protocol.

The new trial ran from April 29 to July 16, 2025 in two villages in the shehia of Ndagoni on Pemba Island. Researchers screened 229 individuals for Trichuris spp. infection using quadruplicate Kato-Katz thick smears, and 127 adults aged 18 to 65 who tested positive in at least two of four smears were randomised 1:1:1:1 to receive placebo on three consecutive days, a single 400 mg dose of oxfendazole, a single 800 mg dose, or 800 mg on three consecutive days, with matching placebos used to preserve blinding. Participants, investigators, physicians and the outcome assessor all remained masked to treatment allocation. The primary endpoint was egg count at day 18, expressed as eggs per gram of stool, measured among participants infected at baseline.

The results showed a clear dose-duration effect. The observed cure rate for Trichuris spp. was 75.9% (95% CI 57.9–87.8) in the three-dose 800 mg arm, compared with 31.0% (95% CI 17.3–49.2) for a single 400 mg dose, 35.3% (95% CI 21.5–52.1) for a single 800 mg dose, and 20.0% (95% CI 9.5–37.3) for placebo. Egg counts at day 18 differed significantly between the placebo group and the three-dose arm (p < 0.001; probabilistic index 0.81), but not between placebo and either single-dose arm. Geometric egg reduction rates followed the same pattern: 99.7% (99.2–99.9) for the three-dose regimen, 90.2% (78.2–95.9) for single 800 mg, 91.3% (81.9–96.1) for single 400 mg, and 66.4% (28.3–84.7) for placebo.

A post hoc analysis stratified by baseline infection intensity added nuance. In the three-dose arm, 85.0% of participants with light infections (17/20) and 55.6% of those with moderate-to-heavy infections (5/9) were cured. By contrast, the single 400 mg dose cured no participants with moderate-to-heavy infections (0/6) and 39.1% of light infections (9/23), while the single 800 mg dose cured 25.0% (1/4) of moderate-to-heavy and 36.7% (11/30) of light infections. The placebo arm cured 24.0% of light infections (6/25) and none of the moderate-to-heavy ones. The authors note that the 20.0% placebo cure rate may reflect well-described variability in egg shedding, low worm burden, natural fluctuations in female worm fertility and the diagnostic limitations of the Kato-Katz method, particularly as the placebo arm had the lowest baseline infection intensity, with a geometric mean of 207.7 eggs per gram compared with 527.6 in the three-dose arm.

Against co-infecting parasites, oxfendazole performed strikingly well. Complete clearance of Ascaris lumbricoides and hookworm infections was observed in all participants who received oxfendazole, regardless of dose, corresponding to cure rates of 100%. However, the authors caution that co-infection prevalence was low in the study population, ranging from 18.8% to 40.0% across arms, and that hookworm cure rates in the placebo arm were high at 40.0% (4/10), so further studies are needed to confirm the observed efficacy. No participants with Ascaris infection who received placebo were cured (0/6).

Safety findings were reassuring. No serious adverse events were reported during the study. In total, 37 adverse events were recorded: 10 among participants receiving the three-dose regimen, 12 in the single 800 mg arm, five in the single 400 mg arm and 10 among placebo recipients. All observed adverse events were mild except one moderate event, a panic attack in the single 800 mg arm judged unrelated to the study drug. The most common adverse event was abdominal discomfort or pain, reported in 12 of 37 cases, which the authors note may also be attributable to the underlying disease itself. All adverse events were self-limiting within one to 17 days after the first dose, apart from five with unknown start or stop dates. No clinically relevant changes in vital signs, physical or neurological examinations, or urinalysis were observed, and three participants with elevated liver enzymes at day 18, two in the three-dose arm and one in the single 400 mg arm, had values that remained below three times the upper limit of normal and returned to the normal range by day 47. Two participants tested positive for pregnancy at day 47 despite negative tests at day 18, and both delivered healthy infants; unblinding showed both had received a single 800 mg dose.

The authors acknowledge several limitations. The trial enrolled 127 participants rather than the anticipated 160, owing to an unexpectedly high number of exclusions at clinical examination, and primary endpoint data were collected for 122 of them. Randomisation was not stratified by infection intensity, which left the three-dose arm with the highest baseline egg counts and may have led to an underestimation of that arm’s efficacy. In addition, clinical chemistry assessments were not performed at an earlier time point after drug administration, so earlier transient laboratory abnormalities may have gone undetected.

Placed in context, the findings suggest that single-dose oxfendazole is unlikely to offer an advantage over existing single-dose albendazole or mebendazole for whipworm, given similarly low cure rates, and that because oxfendazole shares the benzimidazole mode of action, its introduction may not overcome potential resistance mechanisms. However, oxfendazole achieved higher egg reduction rates than the figures reported for albendazole and mebendazole, and the three-dose regimen delivered a cure rate and egg reduction that compare favourably with published multi-dose results for the older drugs, including cure rates of 56.2% for three-dose albendazole and 70.7% for three-dose mebendazole in a prior study. The authors suggest that a 3 × 400 mg oxfendazole regimen, which would halve the tablet burden, is worth evaluating, and note that higher doses and longer schedules are currently being tested within the eWHORM basket trial for onchocerciasis, loiasis and mansonellosis. While multiple-dose regimens are less suitable for mass drug administration, they could become valuable for targeted test-and-treat strategies if drug donations cease, and may offer the added benefit of treating multiple co-endemic helminth infections simultaneously.

Subject of Research: Efficacy and safety of oxfendazole against Trichuris spp. infection in adults in a phase 2a randomised controlled trial in Tanzania

Article Title: Efficacy and safety of oxfendazole in adults with Trichuris spp. infection in Pemba Island, Tanzania: a double-blind, phase 2a, randomised controlled trial

Article References: Schnoz, A., Jeanguenat, H., Msellem, A. S., Mohammed, I. S., Abdalla, R. S., Seif, S. N., Amour, A. K., Khamis, M. J., Mougeni, F. L., Volotko, O., Sieradzan, O., Cheeseman, K. D., Nyangweso, G. M., Egondi, T. W., Barreira, F., Hübner, M. P., Zehetmayer, S., Ali, S. M., & Keiser, J. (2026). Efficacy and safety of oxfendazole in adults with Trichuris spp. infection in Pemba Island, Tanzania: a double-blind, phase 2a, randomised controlled trial. eClinicalMedicine, 101, Article 104273. https://doi.org/10.1016/j.eclinm.2026.104273

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104273

Keywords: oxfendazole, Trichuris spp, soil-transmitted helminths, phase 2a trial, Tanzania, Pemba Island, anthelminthics, cure rate, egg reduction rate, albendazole, mebendazole, eWHORM