Evaluation of Oxfendazole, Praziquantel and Albendazole against Cystic Echinococcosis: A Randomized Clinical Trial in Naturally Infected Sheep

Abstract

BackgroundCystic Echinococosis (CE) is a zoonotic disease caused by larval stage Echinococcus granulosus. We determined the effects of high dose of Oxfendazole (OXF), combination Oxfendazole/Praziquantel (PZQ), and combination Albendazole (ABZ)/Praziquantel against CE in sheep.Methodology/Principal FindingsA randomized placebo-controlled trial was carried out on 118 randomly selected ewes. They were randomly assigned to one of the following groups: 1) placebo; 2) OXF 60 mg/Kg of body weight (BW) weekly for four weeks; 3) ABZ 30 mg/Kg BW + PZQ 40 mg/Kg BW weekly for 6 weeks, and 4) OXF 30 mg/Kg BW+ PZQ 40 mg/Kg BW biweekly for 3 administrations (6 weeks). Percent protoscolex (PSC) viability was evaluated using a 0.1% aqueous eosin vital stain for each cyst. “Noninfective” sheep were those that had no viable PSCs; “low-medium infective” were those that had 1% to 60% PSC viability; and “high infective” were those with more than 60% PSC viability. We evaluated 92 of the 118 sheep. ABZ/PZQ led the lowest PSC viability for lung cysts (12.7%), while OXF/PZQ did so for liver cysts (13.5%). The percentage of either “noninfective” or “low-medium infective” sheep was 90%, 93.8% and 88.9% for OXF, ABZ/PZQ and OXF/PZQ group as compared to 50% “noninfective” or “low-medium infective” for placebo. After performing all necropsies, CE prevalence in the flock of sheep was 95.7% (88/92) with a total number of 1094 cysts (12.4 cysts/animal). On average, the two-drug-combination groups resulted pulmonary cysts that were 6 mm smaller and hepatic cysts that were 4.2 mm smaller than placebo (p<0.05).Conclusions/SignificanceWe demonstrate that Oxfendazole at 60 mg, combination Oxfendazole/Praziquantel and combination Albendazole/Praziquantel are successful schemas that can be added to control measures in animals and merits further study for the treatment of animal CE. Further investigations on different schedules of monotherapy or combined chemotherapy are needed, as well as studies to evaluate the safety and efficacy of Oxfendazole in humans.

Safety of the Combined Use of Praziquantel and Albendazole in the Treatment of Human Hydatid Disease

“…Although there are no comparative randomized studies exploring treatment with albendazole in monotherapy versus combined therapy with albendazole plus praziquantel in patients without surgery, it appears that the combined therapy could improve the results obtained with albendazole alone. 17,18,[23][24][25][26]38 In addition, treatment with praziquantel plus albendazole before surgery could be more efficient as regards reducing relapse rates in comparison with albendazole monotherapy. 23 To date, there are no published randomized clinical trials comparing both therapeutic strategies.…”

Efficacy of a Single Oral Dose of Oxfendazole against Fasciola hepatica in Naturally Infected Sheep

“…Gonzalez and others 16 showed that oxfendazole is effective against T. solium cysticercosis in naturally infected pigs. Likewise, Gavidia and others 15 showed that oxfendazole in combination with praziquantel is effective against hydatid disease (Echinococcus granulosus) in naturally infected sheep. Oxfendazole has also been previously used for the treatment of fascioliasis.…”

“…The control group did not receive treatment, whereas the treatment group was treated orally with a single dose of 30 mg/kg of body weight of oxfendazole (Synanthic, Fort Dodge, Mexico), adapted from the studies from Gavidia and others 15 and Gonzalez and others. 16 A drench dosing gun was used for oxfendazole administration, with the animal in standing position.…”

In vitro viability test for the eggs of Echinococcus granulosus: a rapid method

“…Eosin (0.1%) has been frequently used for the in vitro viability test of protoscolices of hydatid cyst by many researchers (Diker et al 2007;Ciftci et al 2007;Esme et al 2007;Moazeni and Larki 2010;Gavidia et al 2010;Moazeni and Nazer 2010;Moazeni and AlipourChaharmahali 2011). They have exposed the protoscolices to 0.1% eosin for 15 min, however we obtained the best results after 30 min of exposure time.…”