Previous work has suggested that triclabendazole, a member of the benzimidazole group of compounds, possessed efficacy against Schistosoma mansoni. In view of recent indications in praziquantel treatment failures and loss of sensitivity, it is imperative that new anti-schistosomals are developed as contingent treatment options, while resistance alleles, if any, remain at low frequencies. While recent studies have indicated that triclabendazole monotherapy exert weak anti-schistosomal effects, the combinatorial application of triclabendazole with praziquantel has not been explored. To assess this hypothesis, triclabendazole and its metabolites were initially assessed against the many life-stages of Schistosoma mansoni in vitro. Combinatorial drug and isobologram analyses against adult Schistosoma mansoni was also performed, and subsequently applied against other parasitic models (Giardia duodenalis and Haemonchus contortus) to assess the specificity of such effects. Subsequently, the drug combinations were assessed against Schistosoma mansoni in vivo. To further assess the suitability of combinatorial drug applications, an economic model was developed to project the cost-efficacy of praziquantel-triclabendazole drug combinations in a global focus. It was concluded that triclabendazole and its metabolites possessed good efficacy against immature schistosomula, albeit weak efficacy against adult Schistosoma mansoni. Upon combination with praziquantel, however, a strong synergistic effect against adult worms were observed in vitro. Praziquantel and triclabendazole were also shown to possess unique and independent ovicidal modes of action that can be of clinical significance. More importantly, in vivo drug trials concluded that the combinations exerted additive effects against Schistosoma mansoni harbored in mice. Economic modeling and cost-effectiveness analyses further demonstrated the feasibility of this drug combination, and may represent a new line of treatment against mansonial schistosomiasis

Die Effektivität und Verträglichkeit von Triclabendazol wurde in einer klinischen Phase 2 Studie untersucht. 81 Patienten (51 weiblich, 30 männlich, Alter 15-81 Jahre) mit chronischer oder latenter Fasciola hepatica Infektion, bei denen mindestens eine antihelminthische Therapie fehlgeschlagen war wurde in die Studie aufgenommen. Die Patienten erhielten 20mg/Kg Triclabendazol in 2 Dosierungen a 10 mg/Kg im Abstand von 12 h postprandial. Der Therapieerfolg wurde durch mikroskopische Stuhluntersuchungen, Bestimmung exkretorisch-sekretorischer Antigene im Stuhl und Ultraschall überprüft. Bei Siebzig (92%) von 76 Patienten konnten in der Nachuntersuchungsperiode (60 Tage) keine Fasciola hepatica-Eier in den mikroskopischen Stuhluntersuchungen nachgewiesen werden. Die häufigsten unerwünschten Wirkungen waren kolikartige Oberbauchbeschwerden, die bei 40 Patienten (49%) zeitgleich mit der Passage der Parasiten durch die Gallengänge beobachtet wurden. Triclabendazol ist eine effektive Therapie für Patienten mit Fasziolose bei denen andere antihelmithische Therapien nicht wirksam sind. / The efficacy and tolerability of triclabendazole (TCZ) was assessed in a clinical phase 2 study. Eighty-one patients (51 female, 30 male, age 15- 81 years) with chronic or latent F. hepatica infection refractory to previous anti-helminthic chemotherapy were enrolled in a 60 day open, non-comparative trial. Patients received 20 mg/kg TCZ as two doses of 10 mg/kg administered after food 12 hr apart. Efficacy of treatment was assessed by stool microscopy, determination of fasciola excretory-secretory antigen in feces, and by ultrasonography. Seventy (92%) of the 76 patients who completed the 60 day follow up period became egg negative. The most important adverse event was colic-like abdominal pain (40 patients [49%]) consistent with the expulsion of the parasite through the bile ducts as confirmed by US on Days 2 - 7. Triclabendazole is an effective therapy for the treatment of F. hepatica infection in patients who have failed to respond to other antihelminthic agents.