title: The emergence of macrocyclic lactone resistance in the canine heartworm, Dirofilaria immitis.
abstract: Prevention of heartworm disease caused by Dirofilaria immitis in domestic dogs and cats relies on a single drug class, the macrocyclic lactones (MLs). Recently, it has been demonstrated that ML-resistant D. immitis are circulating in the Mississippi Delta region of the USA, but the prevalence and impact of these resistant parasites remains unknown. We review published studies that demonstrated resistance in D.immitis, along with our current understanding of its mechanisms. Efforts to develop in vitro tests for resistance have not yet yielded a suitable assay, so testing infected animals for microfilariae that persist in the face of ML treatment may be the best current option. Since the vast majority of D. immitis populations continue to be drug-sensitive, protected dogs are likely to be infected with only a few parasites and experience relatively mild disease. In cats, infection with small numbers of worms can cause severe disease and so the clinical consequences of drug resistance may be more severe. Since melarsomine dihydrochloride, the drug used to remove adult worms, is not an ML, the ML-resistance should have no impact on our ability to treat diseased animals. A large refugium of heartworms that are not exposed to drugs exists in unprotected dogs and in wild canids, which may limit the development and spread of resistance alleles.
authors.affiliation: Department of Infectious Diseases,College of Veterinary Medicine,University of Georgia,Athens,GA 30602,USA.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Wolstenholme
authors.affiliation: Department of Infectious Diseases,College of Veterinary Medicine,University of Georgia,Athens,GA 30602,USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Evans
authors.affiliation: Calle 169 B No. 75-73 casa 130,Bogotá,Colombiaand European Scientific Counsel for Companion Animal Parasites,The Mews Studio,Portland Road,Malvern,Worcestershire,WR14 2TA,United Kingdom.
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Jimenez
authors.affiliation: Department of Infectious Diseases,College of Veterinary Medicine,University of Georgia,Athens,GA 30602,USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Moorhead
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology / Q000627:therapeutic use; D004183:Dirofilaria immitis / Q000187:drug effects / Q000502:physiology*; D004184:Dirofilariasis / Q000188:drug therapy / Q000469:parasitology* / Q000517:prevention & control; D004283:Dog Diseases / Q000188:drug therapy / Q000469:parasitology* / Q000517:prevention & control; D004285:Dogs; D004351:Drug Resistance; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000977:Antiparasitic Agents; D007783:Lactones
keywords: Dirofilaria immitis; ivermectin; refugia; resistance