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New literature on heartworm preventative resistance


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

Veterinary Parasitology
15 June 2015, Vol.210(3):167178, doi:10.1016/j.vetpar.2015.04.002

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.

Abbreviations
ML, macrocyclic lactones

LOE, loss of efficacy

SUS, susceptible

RES, survivor/resistant

mf, microfilariaI

VM, ivermectin

MO, milbemycin oxime

MOX, moxidectin

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While resistance has been confirmed in heartworms the spread of the alleles that confer resistance is expected to be slow and the drugs used to treat heartworm infections are sill effective. (see attached review).

Additionally, there are ongoing studies to determine the mode of resistance which will allow for developing new preventatives which work around this mode of resistance.
ABC-B transporter genes in Dirofilaria immitis

The emergence of macrocyclic lactone resistance in the.pdf

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