# Current issues in heartworm chemotherapy

## TL;DR

Heartworm infections are increasing in the USA, and challenges like drug resistance and climate change require further research and careful treatment approaches.

## Contribution

The paper highlights the need for research into ML resistance mechanisms and the cautious use of emodepside in treating drug-resistant hookworms in dogs.

## Key findings

- Genomic markers associated with macrocyclic lactone resistance are increasing in frequency.
- Emodepside, though not approved for dogs, is being used off-label for drug-resistant hookworms.
- More research is needed to confirm the phenotypic relevance of resistance markers and to develop inbred ML-resistant heartworm strains.

## Abstract

Several issues that affect prevention and treatment of heartworm infections require more intensive research. The incidence of heartworm infection in the USA is increasing, but the factors that underlie this trend remain incompletely understood. The contributions of climate change, vector range expansion, client compliance and resistance to macrocyclic lactones (ML) are likely interrelated and require investigation. Molecular-level research has not yet identified the causative mechanisms underlying ML resistance (MLR), but surveys of genomic markers associated with the trait reveal worrying trends in the presence and frequency of these resistance alleles. Research is needed to confirm the phenotypic relevance of these markers and to identify the gene(s) responsible for it. Developing highly inbred strains of MLR heartworms may be necessary but would require multigenerational studies of targeted breeding of selected parasites in dogs. A second issue of concern for veterinarians is the increasing extra-label use of emodepside products for the treatment of multiple anthelmintic drug resistant (MADR) canine hookworms (Ancylostoma caninum), which are already common throughout the USA. Emodepside is not approved for use in dogs in the USA, but a cat topical product containing the drug is, and is being used orally in hookworm-infected dogs. Emodepside has activity against larval and adult stages of many filarial parasites and the safety of this drug in heartworm-infected dogs has not been reported. It is perhaps unlikely that such studies will be undertaken, given the lack of economic motivation. Nonetheless, a review of the relevant literature leads to the conclusion that the status of heartworm infection in a dog bearing an apparently MADR hookworm infection be determined before starting treatment with emodepside, with caution exercised should it ensue.