Date Published: January 25, 2016
Publisher: Public Library of Science
Author(s): Miguel M. Cabada, Martha Lopez, Maria Cruz, Jennifer R. Delgado, Virginia Hill, A. Clinton White, Hector H Garcia. http://doi.org/10.1371/journal.pntd.0004361
Abstract: 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.
Partial Text: Fascioliasis is a worldwide zoonotic infection caused by the trematode parasite Fasciola hepatica. Livestock infection causes large economic losses in developed and developing countries. Even in some wealthy countries, up to 50% of the dairy and meat herds may be infected; but data from resource-poor countries are limited.[2–4] Heavily infected cattle have significantly decreased milk (≥ 1.5 L daily) and meat (≥ 3 kg) production.[5,6] Human infection has been reported in more than 70 countries, but the highest burden occurs in the Andes and parts of the Middle East. School-age children have the highest prevalence of fascioliasis and bear most of its severe consequences. Lopez et al. described a threefold increase in anemia risk among children with fascioliasis compared with children without infection. Significant weight loss during the acute and chronic infections has been described in other studies.[9,10] Thus, the long term effects of fascioliasis complications have motivated significant efforts to tackle livestock and human infection.
The Cusco region in the south highlands of Peru is an endemic area for fascioliasis. In rural areas of this region the prevalence of Fasciola hepatica infection among children is 11%. The Universidad Peruana Cayetano Heredia and University of Texas Medical Branch Collaborative Research Center in Cusco is a referral center for research and management of Fasciola infection. Patients referred to us with diagnosed or suspected fascioliasis are evaluated with up to three Lumbreras rapid sedimentation and Kato Katz stool tests. Subjects with negative stool tests and significant eosinophilia are evaluated with Fas2 ELISA for serum antibodies against Fasciola hepatica. Except when noted, treatment courses for patients with stool or serologic evidence of fascioliasis consisted of 2 doses of triclabendazole at 10 mg/kg every 12 hours preceded by a meal rich in fat. All subjects received counseling on avoidance of vegetables that might put them at risk for reinfection. Treatment response was assessed with Lumbreras rapid sedimentation and Kato Katz stool tests between 1 and 3 months after treatment.[18,19] Those found to remain infected received repeated courses of triclabendazole.
Although triclabendazole resistance in veterinary medicine is well known, resistant human infections have only rarely been reported. In this manuscript, we report 7 cases of Fasciola hepatica infection that failed to respond to multiple treatment courses with recommended doses of triclabendazole. Two other case reports of failure of triclabendazole treatment for fascioliasis have been published. In 2012, Winkelhagen et al. from the Netherlands reported a single case of multiple treatment failures with triclabendazole and nitazoxanide. In 2014, Gil et al. reported 4 cases of triclabendazole failure in Chile. However, in 3 of those cases the timeline between symptoms, treatment, and evaluation of response suggest reinfection rather than treatment failures. Of note, none of the reported cases had quantitative tests to evaluate the response of egg burden to treatment. Most of our patients had low egg burdens and the egg counts did not showed significant reductions after treatment.