AAVP Hookworm Research Initiative

AAVP Hookworm Research Initiative

Multiple Anthelmintic Drug Resistant (MADR) infections with the canine hookworm Ancylostoma caninum are increasingly common and present therapeutic challenges to veterinarians and their clients across the continental USA. Although research has revealed some information about the derivation and distribution of these parasite populations, much remains to be learned. Diagnostic and treatment options remain suboptimal and negatively affect the health of dogs and the practice of companion animal veterinary medicine. This parasite species has zoonotic potential, capable of causing cutaneous larva migrans and more serious complications in humans, making the need for improved knowledge increasingly urgent.

A similar situation arose about 15 years ago with the realization that macrocyclic lactone (ML)-resistant canine heartworms (Dirofilaria immitis) had arisen in the southern USA, again providing a therapeutic challenge for veterinarians and their clients. In 2008, Novartis Animal Health funded a consortium of academic researchers in the USA and Canada with $400,000 over 4 years to investigate these parasites to better understand the problem. That work led to confirmation of ML resistance, the creation of an in vivo assay for resistance and a molecular test that could detect resistance markers, although the mechanism of resistance still has not been identified.

Recently, the AAVP commissioned a Hookworm Task Force to address this issue by identifying research priorities and providing diagnostic and treatment guidance to practitioners. A manuscript supporting the first aim has been published and a manuscript for the second aim has been accepted for publication. We believe the next step is for the AAVP to advocate an effort similar to that for heartworms, supporting research on MADR hookworms. This urgently needed initiative should be based on a consortium of animal health companies and academic researchers. MADR hookworms affect products from every AH company and new drugs for these parasites are not on the immediate horizon.

Organization of the effort

To facilitate establishing this initiative, we propose that Professors Ray Kaplan, Tim Geary and Andy Moorhead serve as the AAVP Leadership Team. They will oversee and administer the initiative but will not receive funding from it. Management of funds will be handled by the Rees Company as part of their arrangement with AAVP, minimizing administrative costs. In addition, we will establish a Management Council that includes the AAVP leadership team as well as a representative from each Animal Health (AH) company that contributes to the initiative.

Similar to the initiative that supported research in heartworm drug resistance, we propose to raise funds for a 3-year multi-institutional research project to address several of the most important and achievable research goals for improving our understanding of MADR A. caninum. We set  a goal of US $1,000,000 for a 3-year project, to be raised from AH companies. Any donation level will be accepted and acknowledged; however, AH companies that donate at the Platinum level of US $100,000 per year or more will be provided with a voice on the Management Council and allowed to have input on proposals (but not vote). AH companies that donate at the Gold level (less than US $100,000 per year) will be acknowledged for their contribution, but will not be involved in the discussion of proposal selection.

The Management Council will develop a prioritized list of research topics based on their importance to the clinical situation, feasibility in terms of time and cost, and availability of academic researchers with suitable expertise to conduct the studies. This effort will form the basis for a call for proposals from the academic community. As a starting point for discussion, we propose 4 aims as an initial set of priority areas for research support:

1. Develop improved diagnostic platforms to detect ML and pyrantel resistance at the phenotypic and molecular levels to improve our understanding of the epidemiology and spread of MADR hookworms.
2. Develop a laboratory animal model for caninum to facilitate characterization of the pharmacology of MADR hookworms and testing of new therapeutic approaches, resolving the current requirement for the intensive use of dogs.
3. Generate a highly contiguous genome assembly for caninum drug-sensitive and MADR isolates to enable identification of molecular markers for resistance.
4. Establish repositories to collect and share data relevant for understanding MADR hookworm biology and epidemiology.

If sufficient funds are provided by AH companies to support this initiaitve, proposals will be solicited from academic consortia to address the jointly identified priority research topics. This process will be administered by the Leadership Team under the auspices of AAVP. The goal is not to solicit single-PI grants, but instead, as for the Novartis-funded heartworm initiative, to fund a consortium of academic scientists who will work collaboratively.  We envision a consortium with a senior leader, who would lead the effort to assemble and oversee the research group in collaboration with the Management Council.