Macrocyclic lactone resistance in Dirofilaria immitis: Failure of heartworm preventives and investigation of genetic markers for resistance

Catherine Bourguinat*, Alice C.Y. Lee, Regina Lizundia, Byron L. Blagburn, Janice L. Liotta, Marc S. Kraus, Kathy Keller, Christian Epe, Louis Letourneau, Claudia L. Kleinman, Tara Paterson, Elena Carretón, José Alberto Montoya-Alonso, Hubert Smith, Aron Bhan, Andrew S. Peregrine, James Carmichael, Jason Drake, Rudolf Schenker, Ronald KaminskyDwight D. Bowman, Timothy G. Geary, Roger K. Prichard

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)

Abstract

Macrocyclic lactone (ML) endectocides are used as chemoprophylaxis for heartworm infection (Dirofilaria immitis) in dogs and cats. Claims of loss of efficacy (LOE) of ML heartworm preventives have become common in some locations in the USA. We directly tested whether resistance to MLs exists in LOE isolates of D. immitis and identified genetic markers that are correlated with, and therefore can predict ML resistance. ML controlled studies showed that LOE strains of D. immitis established infections in dogs despite chemoprophylaxis with oral ivermectin or injectable moxidectin. A whole genome approach was used to search for loci associated with the resistance phenotype. Many loci showed highly significant differences between pools of susceptible and LOE D. immitis. Based on 186 potential marker loci, Sequenom® SNP frequency analyses were conducted on 663 individual parasites (adult worms and microfilariae) which were phenotypically characterized as susceptible (SUS), confirmed ML treatment survivors/resistant (RES), or suspected resistant/loss of efficacy (LOE) parasites. There was a subset of SNP loci which appears to be promising markers for predicting ML resistance, including SNPs in some genes that have been associated with ML resistance in other parasites. These data provide unequivocal proof of ML resistance in D. immitis and identify genetic markers that could be used to monitor for ML resistance in heartworms.

Original languageEnglish
Pages (from-to)167-178
Number of pages12
JournalVeterinary Parasitology
Volume210
Issue number3-4
DOIs
Publication statusPublished - 15 Jun 2015

Keywords

  • Dirofilaria immitis
  • Genetic markers
  • Ivermectin
  • Macrocyclic lactones
  • Moxidectin
  • Resistance

ASJC Scopus subject areas

  • Parasitology
  • veterinary(all)

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