Development of tools to detect deworming drug resistance in children with hookworm infection
BACKGROUND: Hookworm and other Soil-Transmitted Helminth (STH) infections represent a leading cause of anemia, malnutrition, and growth delay in children from low and middle-income countries. Global control efforts rely heavily on mass drug administration (MDA) with benzimidazole (BZ) anthelminthics, most often albendazole, to control hookworm infection.
GAP: With considerable evidence highlighting variable effectiveness of albendazole against hookworm in endemic countries, there is a growing concern on emergence of drug resistant strains. However, the present copro-microscopic and molecular tools fail to truly assess the emergence of these drug resistance strains.
HYPOTHESIS: Hypothesis 1: The mechanisms of deworming treatment failure include increased drug tolerance and the emergence of genetically mediated BZ resistance in hookworm.
Hypothesis 2: Repeated exposure to BZ drugs is associated with an increase in the allele frequency of genetic markers of resistance within hookworm populations.
METHODS: We will carry out a cross-sectional study among school-age children in Ghana, where we have previously reported high prevalence and variable effectiveness of albendazole against hookworm and enroll 300 school age children to field test a novel deep-sequencing method that is capable of detecting benzimidazole resistance mutations in hookworms at a level more sensitive than currently available diagnostic tools. The frequency of resistance associated mutations will be correlated with response to albendazole treatment among hookworm infected subjects.
IMPACT: These studies will increase our understanding of the genetics of BZ resistance, and implementation of the methods developed will provide valuable tools to monitor the effectiveness of control programs for hookworm and other STHs.
Website Link: https://medicine.yale.edu/lab/cappello/