Liver cystic echinococcosis: pre-clinical assessment of a novel, single step percutaneous treatment procedure (intracystic albendazole sulfoxide injection)

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 DESCRIPTION (provided by applicant): Cystic echinococcosis (CE), a zoonotic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus, is endemic to areas where livestock are raised including Eurasia, UK, Australia, South America and North and East Africa, and considered a serious and costly public health problem in endemic regions. Liver CE is the most common clinical presentation, representing around 70% of human CE cases. Treatment procedures for liver CE have evolved over the past four decades. Currently, four treatment modalities are used: (1) medical treatment with albendazole (ABZ), (2) PAIR (Puncture, Aspiration, Injection of protoscolicidal agent; Reaspiration), (3) surgery to remove the cyst and (4) watch and wait for inactive, clinically silent cysts. In most endemic countries, surgery is the main treatment approach for liver cysts. PAIR has gained ground in the treatment of liver CE and can be performed in centers with limited resources as much as ultrasound guiding is available. PAIR however has some technical drawbacks that include the need to rule out the presence of a cysto-biliary fistula, and is not completely efficacious. A simpler, safer an more effective treatment approach would be of great benefit for patients in endemic regions. The current proposal will evaluate a new treatment approach that consists on a single step injection of albendazole sulfoxide (ABZ-SF), the active metabolite of ABZ, into the cyst. This procedure is less resource and time demanding than PAIR, should not be hampered by the presence of cysto-biliary fistula, and should also be safer than oral ABZ therapy since it avoids the systemic toxicity associated with a prolonged therapy with oral ABZ. The first project is a pilot placebo controlled experimental / interventional animal safety study comparing two different doses of ABZ-SF to determine the higher safe doses as well as to provide preliminary information about efficacy of the antiparasitic drug injection. The second study is a blind, placebo controlled randomized trial testing the highest safe dose of ABZ-SF identified in study 1. Finally, in a third study, which is also a blind, controlled randomized trial, we will determine the minimal needed concentration of intracystic ABZ-SF to achieve treatment success. This proposal can eventually provide a new therapeutic approach for human liver CE, and should result in an R34 application for a future human trial.