Gates combination chemotherapy - Co-Administration Drug Therapy against Soil-Transmitted Helminthiasis: from Efficacy and Safety to Community Effectiveness

Soil-transmitted helminths (STHs) – roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura), the hookworms (Ancylostoma duodenale and Necator americanus), and threadworm (Strongyloides stercoralis) – affect more than 1 billion people worldwide with the highest infection rates usually observed in marginalized communities in low- and middle-income countries. The global strategy to control morbidity due to STH infections is preventive chemotherapy (PC) with one of the two benzimidazole drugs (albendazole and mebendazole) that are donated by pharmaceutical companies to the World Health Organization (WHO). However, both drugs have shortcomings, most notably low cure and egg reduction rates against T. trichiura infections. Optimized dosages and drug combinations can overcome this shortcoming; they result in higher efficacy than monotherapy and lower the risk of developing anthelmintic resistance against the current armamentarium of deworming drugs.
Goal and specific objectives:
The overarching goal of this proposal and supplemental amendments is to assemble and analyze available data on albendazole and ivermectin for the treatment of STHs and to conduct studies on the efficacy of albendazole and ivermectin, pharmacokinetic (PK) properties of ivermectin and the co-administration of albendazole-ivermectin.
Assembling and generating the evidence to inform recommendations on co-administration of drugs in STH control programs will be done with two activities. First, we will systematically review and analyze available efficacy and safety data on albendazole-ivermectin combination therapy (i.e. Tier 1 combination) in order to prepare the dossier for the Essential Medicine List (EML). Second, we propose dose-finding studies with albendazole and ivermectin in preschool-aged children, school-aged children, and adults. PK studies on ivermectin will complement this research. We hypothesize that treatment dosages of albendazole and ivermectin can be optimized. Ideally, a weight-independent dosage for ivermectin can be applied. On top, the identification of a safe and efficacious dose of ivermectin is crucial for the use of albendazole-ivermectin in preschool-aged children. Moreover, the safety and efficacy of the co-administration of albendazole-ivermectin will be evaluated in 3 countries 3 weeks as well as 6 months and 12 months pots-treatment.
Expected outcomes:
We expect that we will have assembled new knowledge on the safety, efficacy of albendazole, ivermectin, and albendazole-ivermectin, and PK properties of ivermectin to improve treatment of soil-transmitted helminthiasis.


Jennifer Keiser

Jennifer Keiser, Associate Professor, PhD
Head of Unit


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