Preventive efficacy of oral moxidectin at various doses and dosage regimens against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs.

Autor: McTier TL; Zoetis, Veterinary Medicine Research and Development, 333 Portage St, Kalamazoo, MI, 49007, USA. tom.mctier@zoetis.com., Six RH; Zoetis, Veterinary Medicine Research and Development, 333 Portage St, Kalamazoo, MI, 49007, USA., Pullins A; Zoetis, Veterinary Medicine Research and Development, 333 Portage St, Kalamazoo, MI, 49007, USA., Chapin S; Zoetis, Veterinary Medicine Research and Development, 333 Portage St, Kalamazoo, MI, 49007, USA., Kryda K; Zoetis, Veterinary Medicine Research and Development, 333 Portage St, Kalamazoo, MI, 49007, USA., Mahabir SP; Zoetis, Veterinary Medicine Research and Development, 333 Portage St, Kalamazoo, MI, 49007, USA., Woods DJ; Zoetis, Veterinary Medicine Research and Development, 333 Portage St, Kalamazoo, MI, 49007, USA., Maeder SJ; Zoetis, Veterinary Medicine Research and Development, 333 Portage St, Kalamazoo, MI, 49007, USA.
Jazyk: angličtina
Zdroj: Parasites & vectors [Parasit Vectors] 2019 Sep 11; Vol. 12 (1), pp. 444. Date of Electronic Publication: 2019 Sep 11.
DOI: 10.1186/s13071-019-3685-3
Abstrakt: Background: Moxidectin has previously shown limited efficacy (≤ 44.4%) against confirmed macrocyclic lactone (ML)-resistant Dirofilaria immitis strains at 3 µg/kg after single and multiple oral dosages. Three studies were conducted to evaluate higher oral moxidectin doses for efficacy against confirmed ML-resistant D. immitis strains.
Methods: Dogs were inoculated with 50 D. immitis L3 and randomly allocated to treatments. Study 1: 6 groups of dogs (n = 8) were inoculated with JYD-34 (Day - 30) and treated as follows: T01, negative control; T02-T05, moxidectin at 3, 6, 12 or 24 µg/kg, respectively, on Day 0 only; T06, moxidectin at 3 µg/kg on Days 0, 30 and 60. Study 2: 10 groups of dogs (n = 5) were inoculated (Day - 30) with either JYD-34 (T01, T03-05) or ZoeLA (T02, T06-T10) and treated as follows: T01 and T02, negative controls; T03-T05, moxidectin at 24, 40 or 60 µg/kg, respectively, on Days 0, 28 and 56; T06 and T09, moxidectin at 3 or 60 µg/kg on Day 0 only; T07, T08 and T10, moxidectin at 24, 40 or 60 µg/kg, respectively, on Days 0, 28 and 56. Study 3: 5 groups of dogs (n = 5) were inoculated with ZoeMO (Day - 28) and treated as follows: T01, negative control; T02, moxidectin at 3 µg/kg moxidectin on Day 0 only; T03-T05, moxidectin at 24, 40 or 60 µg/kg, respectively, on Days 0, 28 and 56. All dogs were necropsied for adult heartworm recovery ~ 4-5 months post-inoculation.
Results: All moxidectin-treated dogs showed significantly lower worm counts than controls. The efficacy of moxidectin administered once at 3 µg/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 µg/kg (JYD-34, ZoeMO) or 60 µg/kg (ZoeLA). Three dosages of 24 µg/kg were also highly effective, providing ≥ 98.8% efficacy for all three strains.
Conclusions: 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 µg/kg dose was considered the optimal dose for further commercial development.
Databáze: MEDLINE
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