Shifting the paradigm in Dirofilaria immitis prevention: blocking transmission from mosquitoes to dogs using repellents/insecticides and macrocyclic lactone prevention as part of a multimodal approach

McCall, John W.; Varloud, Marie; Hodgkins, Elizabeth; Mansour, Abdelmoneim; DiCosty, Utami; McCall, Scott; Carmichael, James; Carson, Ben; Carter, Justin

doi:10.1186/s13071-017-2438-4

Cited by 23 publications

(13 citation statements)

References 26 publications

(27 reference statements)

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“… a Day of first treatment is designated as Day 0. All dogs inoculated with 50 L3 unless otherwise specified b Geometric means (arithmetic means for McCall et al [55]) c Less than 100% efficacy was obtained with 2.5 mg/kg topical moxidectin in a similar study (Dr John McCall, personal communication) d Dogs infected with an estimated total of 78 ± 14 L3 via two exposures to infected mosquitoes e Mean dose administered Abbreviations : EPAR, European Public Assessment Report; na, data not available…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…Other less common topics were: the use of PPF in novel products (bed nets [65,91], paints [92], release blocks [93], sugar baits [94,95], candles [96], topical treatments [97][98][99] ovitraps [100,101], resin sticks [102][103][104], and controlled release mesh [105]; the effect of PPF on the termination of the diapause process [106]; and PPF's environmental persistence and effect on non-target organisms [107]. There was also a review written in 2008 by a PPF manufacturer that focused on the different uses for PPF as a larvicide against nuisance mosquitoes and vectors of dengue and malaria [108].…”

Section: Study Characteristicsmentioning

confidence: 99%

Use of pyriproxyfen in control of Aedes mosquitoes: A systematic review

et al. 2020

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Background Dengue is the most rapidly spreading arboviral disease in the world. The current lack of fully protective vaccines and clinical therapeutics creates an urgent need to identify more effective means of controlling Aedes mosquitos, principally Aedes aegypti, as the main vector of dengue. Pyriproxyfen (PPF) is an increasingly used hormone analogue that prevents juvenile Aedes mosquitoes from becoming adults and being incapable of transmitting dengue. The objectives of the review were to (1) Determine the effect of PPF on endpoints including percentage inhibition of emergence to adulthood, larval mortality, and resistance ratios; and (2) Determine the different uses, strengths, and limitations of PPF in control of Aedes. A systematic search was applied to Pubmed, EMBASE, Web of Science, LILACS, Global Health, and the Cochrane database of Systematic Reviews. Out of 1,369 records, 90 studies met the inclusion criteria. Nearly all fit in one of the following four categories 1) Efficacy of granules, 2) Auto-dissemination/horizontal transfer, 3) use of ultra-low volume thermal fogging (ULV), thermal fogging (TF), or fumigant technologies, and 4) assessing mosquito resistance. PPF granules had consistently efficacious results of 90-100% inhibition of emergence for up to 90 days. The evidence is less robust but promising regarding PPF dust for auto-dissemination and the use of PPF in ULV, TF and fumigants. Several studies also found that while mosquito populations were still susceptible to PPF, the lethal concentrations increased among temephos-resistant mosquitoes compared to reference strains. The evidence is strong that PPF does increase immature mortality and adult inhibition in settings represented in the included studies, however future research should focus on areas where there is less evidence (e.g. auto-dissemination, sprays) and new use cases for PPF. A better understanding of the biological mechanisms of cross-resistance between PPF, temephos, and other insecticides will allow control programs to make better informed decisions.

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“…Apart from this, mosquito control measurements in the surroundings where dogs are present have prevented mosquito bites. After very important research on the efficacy of prophylactic agents against D. immitis (McCall et al, 2017a;2017b), a new preventive measure, i.e. the multimodal prophylactic approach, was established.…”

Section: O N L I N E F I R S Tmentioning

confidence: 99%

Dog heartworm disease is here to stay: The most important aspects of clinical relevance

Spasojevic-Kosic

Lalošević

2020

VET GLASNIK

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Background. Heartworm disease (HWD) is a clinically important parasitic disease of the cardiovascular system in dogs, and is caused by Dirofilaria immitis (D. immitis), which resides in pulmonary arteries. Infected domestic and wild canids as hosts, and mosquitoes as intermediate hosts, are the main reservoirs of D. immitis. Because D. immitis does not reach complete development in humans, HWD is considered to be a disease with zoonotic potential. In addition to its veterinary relevance and zoonotic potential, the disease is distributed worldwide, and thus, a multidisciplinary approach is necessary to control this disease on the global level. Scope and Approach. The life cycle of D. immitis explains the pathogenesis and clinical signs of HWD in dogs, and determines its diagnosis, therapy and prophylactic measures. In this review, the most important aspects of HWD in canine patients are emphasized: establishment of correct diagnosis of the disease, proper diagnostic procedures for monitoring the clinical condition of an infected dog, different therapeutic protocols and how efficient they are and finally, recommendations for adequate prophylactic measures. Key Findings and Conclusions. Dogs with and without clinical signs of HWD should be tested for both microfilariae and adults of D. immitis at appropriate times. If positive for heartworm, the pathological changes in relevant organs, mainly lungs and heart, should be assessed in the dog. Their extent and severity determine therapeutic protocol. For dogs cured from HWD and non-infected ones, adequate preventive measures should be applied.

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Shifting the paradigm in Dirofilaria immitis prevention: blocking transmission from mosquitoes to dogs using repellents/insecticides and macrocyclic lactone prevention as part of a multimodal approach

Cited by 23 publications

References 26 publications

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

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

Use of pyriproxyfen in control of Aedes mosquitoes: A systematic review

Dog heartworm disease is here to stay: The most important aspects of clinical relevance

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