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Title: Macrocyclic lactone resistance in Dirofilaria immitis: Failure of heartworm preventives and investigation of genetic markers for resistance
Authors: Bourguinat, Catherine
Lee, Alice C.Y.
Lizundia, Regina
Blagburn, Byron L.
Liotta, Janice L.
Kraus, Marc S.
Keller, Kathy
Epe, Christian
Letourneau, Louis
Kleinman, Claudia L.
Paterson, Tara
Carretón Gomez, Elena 
Montoya Alonso, José Alberto 
Smith, Hubert
Bhan, Aron
Peregrine, Andrew S.
Carmichael, James
Drake, Jason
Schenker, Rudolf
Kaminsky, Ronald
Bowman, Dwight D.
Geary, Timothy G.
Prichard, Roger K.
UNESCO Clasification: 310907 Patología
240112 Parasitología animal
Keywords: Macrocyclic lactones
Dirofilaria immitis
Genetic markers
Ivermectin, et al
Issue Date: 2015
Publisher: 0304-4017
Journal: Veterinary Parasitology 
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.
ISSN: 0304-4017
DOI: 10.1016/j.vetpar.2015.04.002
Source: Veterinary Parasitology [ISSN 0304-4017], v. 210, p. 167-178
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