Dose-response assay templates for in vitro assessment of resistance to benzimidazole and nicotinic acetylcholine receptor agonist drugs in human hookworms.

With the implementation of mass drug administration programs for the control of human hookworms, there is a need to monitor for the emergence of drug resistance. We have therefore examined in vitro assays for monitoring sensitivity to benzimidazoles (egg hatch assay) and nicotinic acetylcholine receptor agonist drugs (motility and morphology assays), with a view to developing tools for monitoring drug sensitivity in the field. We have performed assays with Necator americanus and Ancylostoma ceylanicum, and combined this with published data on N. americanus and Ancylostoma caninum, to indicate the breadth of the responses of various hookworm species and isolates in these in vitro assays. This has allowed us to generate assay templates covering the known range of responses, with scope to cover any shift in response that may be indicative of resistance. These assays will have immediate applicability in monitoring for the emergence of drug resistance in human hookworm populations.