# Development of a rodent model for anthelmintic testing against multidrug resistant hookworms

> **NIH NIH R21** · GEORGE WASHINGTON UNIVERSITY · 2023 · $242,250

## Abstract

Hookworms are serious parasites of humans and animals, causing anemia and even death in heavy infections
and vulnerable populations. Nearly 500 million people are infected with hookworms, primarily in developing
countries lacking sanitation infrastructure. Canine hookworms are the most important gastrointestinal parasite
of dogs. Hookworms can be controlled using several anthelmintics, which in the absence of a vaccine, remain
the only available control for hookworm infections. However, heavy use of anthelmintics has led to the
development of genetic resistance to all the major anthelmintics used to treat parasitic nematodes in livestock.
Increased use of anthelmintics to treat humans is predicted to lead to anthelmintic resistance (AR) in
hookworms as well. Indeed, heavy use of anthelmintics in racing greyhounds has led to the emergence of
multidrug resistant (MDR) canine hookworms (Ancylostoma caninum). These MDR isolates are resistant to all
classes of anthelmintics approved for use in dogs in the US. Recently, MDR hookworms have spread from
greyhounds into the general pet dog population and are predicted to continue this spread in the future. Not only
will MDR hookworms negatively affect the ability to treated infected dogs, they will also severely limit treatment
options for zoonotic hookworm infections in humans such as cutaneous larva migrans, eosinophilic enteritis
and diffuse unilateral subacute neuroretinitis. Therefore, there is an urgent need to develop new drugs to treat
infections with MDR hookworms. Development of anthelmintics requires adult parasites to test potential
compounds for activity in vitro, and infected hosts to test the efficacy of potential drugs. This is hampered by
the lack of a small animal model for hookworm infections in which to test new drugs. Ancylostoma caninum can
currently only be maintained in dogs, making anthelmintic development and testing costly and ethically
problematic. Therefore, we propose a two-pronged approach to developing a rodent model for canine
hookworm infection. In Aim 1, we will use drugs to immunosuppress potential rodent hosts before and during
infection to determine if the animals can be permissive to MDR hookworm infection. We will also test
immunodeficient rodents for their ability to host A. caninum. In Aim 2, we will use the rodent model to test
current anthelmintics as a proof of principle. A small animal model of canine hookworm infection would greatly
facilitate the development of anthelmintics effective against MDR worms and would provide insights into the
development of AR in hookworms that are applicable to hookworm infections of humans.

## Key facts

- **NIH application ID:** 10569256
- **Project number:** 1R21AI173403-01
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** JOHN M HAWDON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $242,250
- **Award type:** 1
- **Project period:** 2023-09-11 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10569256

## Citation

> US National Institutes of Health, RePORTER application 10569256, Development of a rodent model for anthelmintic testing against multidrug resistant hookworms (1R21AI173403-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10569256. Licensed CC0.

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