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We conducted a retrospective cohort study of children who had chronic fascioliasis in the highlands of Peru to determine triclabendazole treatment efficacy. Children passing Fasciola eggs in stool were offered directly observed triclabendazole treatment (>1 doses of 10 mg/kg). Parasitologic cure was evaluated by using microscopy of stool 1–4 months after each treatment. A total of 146 children who had chronic fascioliasis participated in the study; 53% were female, and the mean ± SD age was 10.4 ± 3.1 years. After the first treatment, 55% of the children achieved parasitologic cure. Cure rates decreased after the second (38%), third (30%), and fourth (23%) treatments; 17 children (11.6%) did not achieve cure after 4 treatments. Higher baseline egg counts and lower socioeconomic status were associated with triclabendazole treatment failure. Decreased triclabendazole efficacy in disease-endemic communities threatens control efforts. Further research on triclabendazole resistance and new drugs to overcome it are urgently needed.

Fascioliasis is a neglected zoonosis with major public health implications in humans. Although triclabendazole (TCBZ) is the drug of choice, there are records of TCBZ failure worldwide. TCBZ-resistant fascioliasis is treated with alternative approved drugs including nitazoxanide (NTZ), with varying levels of efficacy. Data on NTZ efficacy after TCBZ failure in Egypt is scarce. This study evaluated the efficacy of NTZ in cases of TCBZ failure during an outbreak of fascioliasis in Assiut governorate of Upper Egypt. This prospective study included 67 patients from the outpatient clinic in Manfalout locality of Assiut governorate with clinical manifestations of acute fascioliasis. These included high eosinophilia (> 6% eosinophils in peripheral blood), positive anti-Fasciola antibodies, and hepatic focal lesions (HFL) or ascites on abdominal ultrasound or computed tomography. All patients initially received TCBZ at recommended doses. Patients were followed up after 1 month to assess response. According to the responses, patients were categorized as non-responders and responders. The non-responders received a trial of NTZ and were re-assessed for response based on clinical manifestations, eosinophil count, and abdominal ultrasound. Patients not responding to NTZ received additional doses of TCBZ. One month after initial TCBZ treatment, 37 patients responded well to TCBZ, while 30 patients failed to respond with persistence of fever, abdominal pain, high eosinophilia, and HFL. Most non-responders were male (56.7%); females predominated among TCBZ responders (62.2%). The mean age of the non-responders was relatively lower, at 20.57 ± 14.47 years (p = 0.004). Following NTZ therapy, HFL disappeared in 9/30 (30%) patients and eosinophil counts normalized in only 2 (6.7%) patients, indicating an overall efficacy of 36.6%. The remaining cases received additional doses of TCBZ with complete clinical, pathological, and radiological resolution. Nitazoxanide was partially effective in TCBZ failure in acute human fascioliasis in Upper Egypt. Further studies with larger samples are highly encouraged and further research is urgently needed to find new therapeutic alternatives to TCBZ.

Triclabendazole (TCBZ) is the gold standard treatment for fascioliasis. However, reports on resistance are increasing, emphasizing the need for alternative therapy. Combining TCBZ with ivermectin (IVM) was found to be effective for treating animal fascioliasis. Building on this, we aimed to evaluate the efficacy of the TCBZ/IVM combination therapy for human fascioliasis. This study enrolled 136 patients with Fasciola from Upper Egypt, and they were divided into the first group (n = 65), who received TCBZ monotherapy, and the second group (n = 71), who received the TCBZ/IVM combination. Assessments were to evaluate treatment response based on clinical, eosinophilic, and radiological parameters. Chronic fasciolosis was diagnosed in 17 patients (12.5%). No differences were observed in age and sex. Significant improvements were noted in all parameters in both groups, with more pronounced effects observed in the second group. A significantly higher complete response, including clinical, eosinophilic, and radiological improvements, was reported in the combined therapy group, with 53.3% compared to 26.2% in the monotherapy group (p < 0.001). A high baseline eosinophilic count was significantly associated with response. The efficacy of the TCBZ/IVM combination for treating human fascioliasis suggested a possible boosting effect, which can benefit regions of TCBZ failure. Further large-scale randomized studies are warranted to confirm these findings.

Triclabendazole is reported to be highly effective in treatment of human fascioliasis. We present 7 of 19 selected cases of human fascioliasis referred to our center in the Cusco region of Peru that failed to respond to triclabendazole. These were mostly symptomatic adults of both sexes that continued passing Fasciola eggs in the stool despite multiple treatments with 2 doses of triclabendazole at 10 mg/kg per dose. We documented the presence of eggs by rapid sedimentation and Kato Katz tests after each treatment course. We found that repeated triclabendazole courses were not effective against fascioliasis in this group of people. These findings suggest that resistance to triclabendazole may be an emerging problem in the Andes.

Fascioliasis is a trematode flatworm infection caused by Fasciola hepatica. Humans are incidental hosts, and the infection is most often acquired by eating watercress grown in contaminated water in livestock-rearing areas. Triclabendazole is the only highly effective treatment, with a reported cure rate of >90%. Treatment failure may be due to several factors, though resistance is rare in humans and scarcely reported, most probably a reflection of the widespread use of anthelmintics in livestock. There are three papers describing cases of treatment failure, possibly due to resistance, in the Netherlands, Chile and Peru. We document for the first time one case of failure after multiple treatment courses with triclabendazole in Portugal, probably due to resistance to the anthelmintic. Our aim is to alert for the emergence of resistance across continents, with consequent predictable difficulties in the management of the disease and encourage more investigation in the field.