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Three studies were conducted to evaluate higher oral moxidectin doses for efficacy against confirmed ML-resistant\n                      <jats:italic>D. immitis<\/jats:italic>\n                      strains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Dogs were inoculated with 50\n                      <jats:italic>D. immitis<\/jats:italic>\n                      L3 and randomly allocated to treatments. Study 1: 6 groups of dogs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098) were inoculated with JYD-34 (Day \u2212\u200930) and treated as follows: T01, negative control; T02\u2013T05, moxidectin at 3, 6, 12 or 24 \u00b5g\/kg, respectively, on Day 0 only; T06, moxidectin at 3 \u00b5g\/kg on Days 0, 30 and 60. Study 2: 10 groups of dogs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095) were inoculated (Day \u2212\u200930) with either JYD-34 (T01, T03\u201305) or ZoeLA (T02, T06\u2013T10) and treated as follows: T01 and T02, negative controls; T03\u2013T05, moxidectin at 24, 40 or 60 \u00b5g\/kg, respectively, on Days 0, 28 and 56; T06 and T09, moxidectin at 3 or 60 \u00b5g\/kg on Day 0 only; T07, T08 and T10, moxidectin at 24, 40 or 60 \u00b5g\/kg, respectively, on Days 0, 28 and 56. Study 3: 5 groups of dogs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095) were inoculated with ZoeMO (Day \u2212\u200928) and treated as follows: T01, negative control; T02, moxidectin at 3 \u00b5g\/kg moxidectin on Day 0 only; T03\u2013T05, moxidectin at 24, 40 or 60 \u00b5g\/kg, respectively, on Days 0, 28 and 56. All dogs were necropsied for adult heartworm recovery ~\u20094\u20135 months post-inoculation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All moxidectin-treated dogs showed significantly lower worm counts than controls. The efficacy of moxidectin administered once at 3 \u00b5g\/kg was 19% (JYD-34), 44.4% (ZoeLA) and 82.1% (ZoeMO). Increasing both the dose and the number of dosages of moxidectin improved efficacy, with 100% protection obtained using three dosages of moxidectin at either 40 \u00b5g\/kg (JYD-34, ZoeMO) or 60 \u00b5g\/kg (ZoeLA). Three dosages of 24 \u00b5g\/kg were also highly effective, providing \u2265\u200998.8% efficacy for all three strains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Increasing both the dose and number of consecutive monthly dosages of moxidectin improved the efficacy against ML-resistant heartworms. Based on these data and other technical considerations, the 24 \u00b5g\/kg dose was considered the optimal dose for further commercial development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13071-019-3685-3","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T19:04:57Z","timestamp":1568142297000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Preventive efficacy of oral moxidectin at various doses and dosage regimens against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs"],"prefix":"10.1186","volume":"12","author":[{"given":"Tom L.","family":"McTier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Six","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleah","family":"Pullins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Chapin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Kryda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P.","family":"Mahabir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra J.","family":"Woods","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Maeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,11]]},"reference":[{"issue":"Suppl. 1","key":"3685_CR1","doi-asserted-by":"publisher","first-page":"S76","DOI":"10.1007\/s00436-005-1448-x","volume":"97","author":"RG Arther","year":"2005","unstructured":"Arther RG, Bowman DD, Slone RL, Travis LE. 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