{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:54:31Z","timestamp":1792652071693,"version":"4.5.0"},"reference-count":91,"publisher":"Cambridge University Press (CUP)","issue":"10","license":[{"start":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T00:00:00Z","timestamp":1433376000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["journals.cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>Prevention of heartworm disease caused by<jats:italic>Dirofilaria immitis<\/jats:italic>in domestic dogs and cats relies on a single drug class, the macrocyclic lactones (MLs). Recently, it has been demonstrated that ML-resistant<jats:italic>D. immitis<\/jats:italic>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<jats:italic>D.immitis<\/jats:italic>, along with our current understanding of its mechanisms. Efforts to develop<jats:italic>in vitro<\/jats:italic>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<jats:italic>D. immitis<\/jats:italic>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.<\/jats:p>","DOI":"10.1017\/s003118201500061x","type":"journal-article","created":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T12:39:54Z","timestamp":1433421594000},"page":"1249-1259","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":88,"title":["The emergence of macrocyclic lactone resistance in the canine heartworm,<i>Dirofilaria immitis<\/i>."],"prefix":"10.1017","volume":"142","author":[{"given":"ADRIAN J.","family":"WOLSTENHOLME","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CHRISTOPHER C.","family":"EVANS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PABLO D.","family":"JIMENEZ","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANDREW R.","family":"MOORHEAD","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2015,6,4]]},"reference":[{"key":"S003118201500061X_ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2010.02.004"},{"key":"S003118201500061X_ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2005.10.016"},{"key":"S003118201500061X_ref39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095072"},{"key":"S003118201500061X_ref42","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.2460\/ajvr.1982.43.12.2199","article-title":"Developmental stages of Dirofilaria immitis in the dog","volume":"43","author":"Kotani","year":"1982","journal-title":"American Journal of Veterinary Research"},{"key":"S003118201500061X_ref77","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2014.08.005"},{"key":"S003118201500061X_ref82","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-010-2142-1"},{"key":"S003118201500061X_ref11","doi-asserted-by":"publisher","DOI":"10.1006\/expr.1998.4316"},{"key":"S003118201500061X_ref21","doi-asserted-by":"publisher","DOI":"10.1053\/j.tcam.2011.07.001"},{"key":"S003118201500061X_ref5","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182005008991"},{"key":"S003118201500061X_ref53","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-015-0771-z"},{"key":"S003118201500061X_ref2","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.572"},{"key":"S003118201500061X_ref68","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2885.2002.00415.x"},{"key":"S003118201500061X_ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2014.08.013"},{"key":"S003118201500061X_ref51","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2014.01.007"},{"key":"S003118201500061X_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(96)00183-X"},{"key":"S003118201500061X_ref34","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182007000066"},{"key":"S003118201500061X_ref52","first-page":"235","article-title":"Studies of reproductive competence in male Dirofilaria immitis treated with milbemycin oxime","volume":"46","author":"Lok","year":"1995","journal-title":"Tropical Medicine and Parasitology"},{"key":"S003118201500061X_ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cvsm.2009.06.003"},{"key":"S003118201500061X_ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2010.12.049"},{"key":"S003118201500061X_ref85","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2011.09.003"},{"key":"S003118201500061X_ref7","doi-asserted-by":"publisher","DOI":"10.1186\/1746-6148-8-55"},{"key":"S003118201500061X_ref12","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(03)00201-9"},{"key":"S003118201500061X_ref69","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-014-3970-1"},{"key":"S003118201500061X_ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2013.05.001"},{"key":"S003118201500061X_ref1","doi-asserted-by":"publisher","DOI":"10.1007\/s10158-012-0129-6"},{"key":"S003118201500061X_ref49","doi-asserted-by":"publisher","DOI":"10.2460\/javma.238.3.311"},{"key":"S003118201500061X_ref45","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2005.04.006"},{"key":"S003118201500061X_ref66","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-014-0494-6"},{"key":"S003118201500061X_ref91","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2004.04.010"},{"key":"S003118201500061X_ref35","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-205096"},{"key":"S003118201500061X_ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2007.12.001"},{"key":"S003118201500061X_ref87","doi-asserted-by":"publisher","DOI":"10.2174\/138920112800399239"},{"key":"S003118201500061X_ref10","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(98)00087-5"},{"key":"S003118201500061X_ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2008.03.002"},{"key":"S003118201500061X_ref79","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2014.02.004"},{"key":"S003118201500061X_ref59","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1011983107"},{"key":"S003118201500061X_ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2011.01.024"},{"key":"S003118201500061X_ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2005.11.019"},{"key":"S003118201500061X_ref55","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2014.09.023"},{"key":"S003118201500061X_ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2008.10.093"},{"key":"S003118201500061X_ref76","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2014.04.004"},{"key":"S003118201500061X_ref33","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182013001145"},{"key":"S003118201500061X_ref80","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2004.06.024"},{"key":"S003118201500061X_ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2011.01.023"},{"key":"S003118201500061X_ref19","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-5-138"},{"key":"S003118201500061X_ref24","doi-asserted-by":"publisher","DOI":"10.2478\/s11686-013-0177-z"},{"key":"S003118201500061X_ref84","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-7-264"},{"key":"S003118201500061X_ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2010.08.020"},{"key":"S003118201500061X_ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2013.04.002"},{"key":"S003118201500061X_ref67","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2009.02.011"},{"key":"S003118201500061X_ref72","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2011.03.034"},{"key":"S003118201500061X_ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2006.08.007"},{"key":"S003118201500061X_ref31","doi-asserted-by":"publisher","DOI":"10.1645\/13-443.1"},{"key":"S003118201500061X_ref32","doi-asserted-by":"publisher","DOI":"10.1053\/j.tcam.2011.09.004"},{"key":"S003118201500061X_ref36","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2005.10.002"},{"key":"S003118201500061X_ref37","doi-asserted-by":"publisher","DOI":"10.1079\/9780851996172.0353"},{"key":"S003118201500061X_ref38","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2005.04.004"},{"key":"S003118201500061X_ref41","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-2867(98)80010-8"},{"key":"S003118201500061X_ref43","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2006.01.017"},{"key":"S003118201500061X_ref44","doi-asserted-by":"publisher","DOI":"10.1124\/mol.53.2.283"},{"key":"S003118201500061X_ref48","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2010.01.003"},{"key":"S003118201500061X_ref50","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-7-257"},{"key":"S003118201500061X_ref56","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182007000042"},{"key":"S003118201500061X_ref57","doi-asserted-by":"publisher","DOI":"10.1603\/ME12197"},{"key":"S003118201500061X_ref60","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e3282f4711d"},{"key":"S003118201500061X_ref61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02379.x"},{"key":"S003118201500061X_ref62","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-6-16"},{"key":"S003118201500061X_ref46","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-014-0493-7"},{"key":"S003118201500061X_ref63","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-014-3991-9"},{"key":"S003118201500061X_ref64","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4922(01)01983-3"},{"key":"S003118201500061X_ref65","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2005.04.008"},{"key":"S003118201500061X_ref70","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02831.x"},{"key":"S003118201500061X_ref73","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2010.0657.x"},{"key":"S003118201500061X_ref74","first-page":"233","article-title":"Utilization of computer processed high definition video imaging for measuring motility of microscopic nematode stages on a quantitative scale: \u2018The Worminator\u2019","volume":"4","author":"Storey","year":"2014","journal-title":"International Journal for Parasitology: Drugs and Drug Resistance"},{"key":"S003118201500061X_ref75","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2003.09.016"},{"key":"S003118201500061X_ref78","first-page":"55","article-title":"Refugia \u2013 overlooked as perhaps the most potent factor concerning the development of anthelmintic resistance","volume":"68","author":"Van Wyk","year":"2001","journal-title":"Onderstepoort Journal of Veterinary Research"},{"key":"S003118201500061X_ref81","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2010.10.046"},{"key":"S003118201500061X_ref83","doi-asserted-by":"publisher","DOI":"10.1017\/S003118200800543X"},{"key":"S003118201500061X_ref54","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2005.04.005"},{"key":"S003118201500061X_ref86","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R112.406280"},{"key":"S003118201500061X_ref88","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182005008218"},{"key":"S003118201500061X_ref89","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2004.07.010"},{"key":"S003118201500061X_ref90","doi-asserted-by":"publisher","DOI":"10.1089\/vbz.2014.1592"},{"key":"S003118201500061X_ref47","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2885.2007.00878.x"},{"key":"S003118201500061X_ref71","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2009.06.003"},{"key":"S003118201500061X_ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2011.04.012"},{"key":"S003118201500061X_ref30","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4017(02)00321-7"},{"key":"S003118201500061X_ref15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000072"},{"key":"S003118201500061X_ref40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2007.01.001"},{"key":"S003118201500061X_ref27","doi-asserted-by":"publisher","DOI":"10.1023\/B:VERC.0000034993.87007.f8"},{"key":"S003118201500061X_ref58","doi-asserted-by":"publisher","DOI":"10.2174\/138920112800399194"}],"container-title":["Parasitology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S003118201500061X","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T09:38:55Z","timestamp":1748425135000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S003118201500061X\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,4]]},"references-count":91,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["S003118201500061X"],"URL":"https:\/\/doi.org\/10.1017\/s003118201500061x","relation":{},"ISSN":["0031-1820","1469-8161"],"issn-type":[{"value":"0031-1820","type":"print"},{"value":"1469-8161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,4]]},"assertion":[{"value":"Copyright \u00a9 Cambridge University Press 2015\u00a0","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}