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

被引：107

作者：

Bourguinat, Catherine ^{[1
]}

Lee, Alice C. Y. ^{[2
]}

Lizundia, Regina ^{[3
]}

Blagburn, Byron L. ^{[4
]}

Liotta, Janice L. ^{[2
]}

Kraus, Marc S. ^{[2
]}

Keller, Kathy ^{[1
]}

Epe, Christian ^{[3
]}

Letourneau, Louis ^{[5
,6
]}

Kleinman, Claudia L. ^{[7
,8
]}

Paterson, Tara ^{[9
]}

Carreton Gomez, Elena ^{[10
]}

Alberto Montoya-Alonso, Jose ^{[10
]}

Smith, Hubert ^{[11
]}

Bhan, Aron ^{[12
]}

Peregrine, Andrew S. ^{[13
]}

Carmichael, James ^{[14
]}

Drake, Jason ^{[14
]}

Schenker, Rudolf ^{[3
]}

Kaminsky, Ronald ^{[3
]}

Bowman, Dwight D. ^{[2
]}

Geary, Timothy G. ^{[1
]}

Prichard, Roger K. ^{[1
]}

机构：

[1] McGill Univ, Inst Parasitol, Ste Anne De Bellevue, PQ H9X 3V9, Canada

[2] Cornell Univ, Coll Vet Med, Ithaca, NY 14853 USA

[3] Novartis Anim Hlth, CH-1566 St Aubin, Switzerland

[4] Auburn Univ, Coll Vet Med, Auburn, AL 36849 USA

[5] McGill Univ, Montreal, PQ H3A 0G1, Canada

[6] Genome Quebec Innovat Ctr, Quebec City, PQ H3A 0G1, Canada

[7] McGill Univ, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada

[8] McGill Univ, Dept Human Genet, Montreal, PQ H3T 1E2, Canada

[9] St Georges Univ, Sch Vet Med, True Blue, St Georges, Grenada

[10] Univ Las Palmas Gran Canaria, Fac Vet, Las Palmas Gran Canaria 35001, Spain

[11] Haywood Anim Hosp, Brownsville, TN 38012 USA

[12] Main West Anim Hosp, Welland, ON L3C 5L2, Canada

[13] Univ Guelph, Ontario Vet Coll, Guelph, ON N1G 2W1, Canada

[14] Novartis Anim Hlth, Greensboro, NC 27408 USA

来源：

VETERINARY PARASITOLOGY | 2015年 / 210卷 / 3-4期

基金：

加拿大自然科学与工程研究理事会;

关键词：

Macrocyclic lactones; Resistance; Dirofilaria immitis; Genetic markers; Ivermectin; Moxidectin; ONCHOCERCIASIS-ENDEMIC FOCI; ANTHELMINTIC RESISTANCE; MULTIPLE TREATMENTS; MILBEMYCIN OXIME; IVERMECTIN; INFECTION; EFFICACY; VOLVULUS; GHANA; DOGS;

D O I：

10.1016/j.vetpar.2015.04.002

中图分类号：

R38 [医学寄生虫学]; Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ; 100103 ;

摘要：

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((R)) 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. (C) 2015 Elsevier B.V. All rights reserved.

引用

页码：167 / 178

页数：12

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