# Emerging benzimidazole resistance in human hookworms

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $418,750

## Abstract

Project Summary
Hookworm infection is a leading cause of anemia and malnutrition in poor countries, especially in sub-Saharan
Africa. The World Health Organization recommends repeated Mass Drug Administration of benzimidazole
anthelminthics to high risk groups, including school age children, as a way to control morbidity and reduce
transmission of hookworm and other Soil Transmitted Helminths. Although it is anticipated that hookworm
resistance to benzimidazoles will eventually emerge, little is known about the frequency or distribution of
resistant genotypes, as well as the potential for repeated anthelminthic exposure to reduce the effectiveness of
deworming in human populations. Since 2007, the Ghana-Yale Partnership for Global Health has carried out
collaborative field studies on hookworm epidemiology and deworming response, first in Kintampo North
Municipality (KNM) and more recently Kpandai District (KD). Studies in adults and school age children (2007-
2015) have demonstrated reduced efficacy of albendazole, and preliminary data confirm the presence of
putative benzimidazole resistance markers in N. americanus hookworms. We hypothesize that the mechanism
of hookworm treatment failure in Kintampo involves genetically mediated resistance to albendazole. In Specific
Aim 1, deworming effectiveness will be correlated with albendazole susceptibility using N. americanus isolates
from KNM and KD in a field adapted in vitro assay. In Specific Aim 2, genomic DNA from hookworm field
isolates will be used to define the temporal and spatial distribution of known benzimidazole resistance markers,
as well as the genotypes associated with in vitro resistance and treatment failure. Studies in Specific Aim 3 will
establish the structural basis of benzimidazole binding to hookworm β tubulin, as well as map the functional
significance of putative resistance associated mutations. Finally, in Specific Aim 4 the effect of benzimidazole
exposure on hookworm gene expression will be characterized using stage specific cultures of field adapted
and laboratory strains of human parasites. In addition to creating new knowledge to promote Neglected
Tropical Disease control, this project will provide a framework for ongoing collaborative research and training,
building on the record of the Ghana-Yale Partnership for Global Health. Ultimately, development of molecular
methods to elucidate the mechanisms of deworming treatment failure will bridge a pressing technological gap
and fill a critical public health need in Ghana and other resource limited countries.

## Key facts

- **NIH application ID:** 10159191
- **Project number:** 5R01AI132452-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** MICHAEL CAPPELLO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2017-06-09 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159191

## Citation

> US National Institutes of Health, RePORTER application 10159191, Emerging benzimidazole resistance in human hookworms (5R01AI132452-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159191. Licensed CC0.

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