Veterinary endectocides for malaria control and elimination: prospects and challenges

Chaccour, Carlos

doi:10.1098/rstb.2019.0810

Cited by 19 publications

(14 citation statements)

References 48 publications

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“…Our study was designed to establish the proof of concept that a long-lasting formulation of ivermectin could allow the release, in a single injection, of mosquitocidal plasma concentrations of ivermectin to kill malaria vector mosquitoes for up to 6 months. This sustained effect and the associated logistical advantages for mass administration to domesticated animals reinforce the perspectives for the One Health approach and the fight against malaria in different field contexts [ 42 ].…”

Section: Discussionmentioning

confidence: 86%

Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool

et al. 2023

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Background Domesticated animals play a role in maintaining residual transmission of Plasmodium parasites of humans, by offering alternative blood meal sources for malaria vectors to survive on. However, the blood of animals treated with veterinary formulations of the anti-helminthic drug ivermectin can have an insecticidal effect on adult malaria vector mosquitoes. This study therefore assessed the effects of treating cattle with long-acting injectable formulations of ivermectin on the survival of an important malaria vector species, to determine whether it has potential as a complementary vector control measure. Methods Eight head of a local breed of cattle were randomly assigned to either one of two treatment arms (2 × 2 cattle injected with one of two long-acting formulations of ivermectin with the BEPO® technology at the therapeutic dose of 1.2 mg/kg), or one of two control arms (2 × 2 cattle injected with the vehicles of the formulations). The lethality of the formulations was evaluated on 3–5-day-old Anopheles coluzzii mosquitoes through direct skin-feeding assays, from 1 to 210 days after treatment. The efficacy of each formulation was evaluated and compared using Cox proportional hazards survival models, Kaplan–Meier survival estimates, and log-logistic regression on cumulative mortality. Results Both formulations released mosquitocidal concentrations of ivermectin until 210 days post-treatment (hazard ratio > 1). The treatments significantly reduced mosquito survival, with average median survival time of 4–5 days post-feeding. The lethal concentrations to kill 50% of the Anopheles (LC50) before they became infectious (10 days after an infectious blood meal) were maintained for 210 days post-injection for both formulations. Conclusions This long-lasting formulation of ivermectin injected in cattle could complement insecticide-treated nets by suppressing field populations of zoophagic mosquitoes that are responsible, at least in part, for residual malaria transmission. The impact of this approach will of course depend on the field epidemiological context. Complementary studies will be necessary to characterize ivermectin withdrawal times and potential environmental toxicity. Graphical Abstract

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Section: Discussionmentioning

confidence: 86%

Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool

et al. 2023

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“…Our study has been designed to establish the proof of concept that long-lasting formulation of ivermectin using the BEPO® technology could allow the release, in a single injection, of mosquitocidal plasma concentrations of ivermectin in order to kill malaria vector mosquitoes during at least 6 months. This signi cant and sustained and the associated logistical advantages for mass administration, open up new perspectives for the One-Health approach and the ght against malaria in different eld contexts [34].…”

Section: Discussionmentioning

confidence: 99%

Proof-of-concept study for a long-acting formulation of ivermectin injected to cattle as a complementary malaria vector control tool

Pooda

Moiroux

Porciani

et al. 2022

Preprint

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Background: Peridomestic animals play a role in maintaining residual transmission of Plasmodium, being alternative blood meal sources for malaria vectors. The blood of animals treated with veterinary formulations of ivermectin show a mosquitocidal effect on malaria vectors, but for a too short period of time to impact Plasmodium transmission. This study proposes to treat cattle with innovative long-acting (six months) injectable formulations of ivermectin as a complementary vector control measure.Methods: The local breeds of cattle were used in two treatment arms (Four cattle injected with two long-acting formulations of ivermectin with the BEPO® technology at the therapeutic dose of 1.2 mg/kg, and two control arms (Four cattle injected with the vehicles of the formulations). The lethality of the formulations was evaluated on 3-5 days old Anopheles coluzzii mosquitoes through direct-skin feeding assays, from one to 210 days after treatments. Formulations’ efficacy was evaluated and compared using Cox proportional hazards survival models, Kaplan-Meier estimates and 4 parameters log-logistic regression on cumulative mortalities. These results were extrapolated to field scenarii using entomological and transmission models, considering different mosquito feeding preferences, hosts abundances, and bed nets uses ratios. Results: Both formulations released mosquitocidal concentrations of ivermectin until 210 days post-treatment (Hazard ratios > 1). The treatments significantly reduced mosquito survival, with the average median survival times of 4-5 days post-feeding. The Lethal Concentrations to kill 50% of the Anopheles (LC50) before they become infectious (10 days after infectious blood meal) were reached until 210 days post injection for both formulations. Modeling showed that administering long-acting ivermectin formulations to calves would significantly decrease Anopheles populations in the fields. The population of infectious vectors may decrease from 35% to 75% depending mostly on the mosquito feeding preference and on the hosts species relative availability.Conclusions: This study shows that, in complement to bed nets, a long-lasting BEPO® formulation of ivermectin injected to cattle could help to decrease field populations of malaria mosquitoes and residual transmission, the impact of this approach being dependant on the field epidemiological context.

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“…The side effect could be the indirect selection of resistant arthropods being able to bite or infest humans. The project of using mass drug administration (MDA) of ivermectin for humans and cattle as a malaria vector control combined with the classical use of macrocyclic lactones in ruminants for their endectocide activity has the potential to enhance the risk of generating resistance in mosquitoes as well as in soil-transmitted helminth infections of humans and livestock [ 31 , 32 ]. While there is not yet evidence of mosquito tolerance or resistance to ivermectin, risks mitigation strategies should take into account the doses and regimen proposed as MDA in humans, the residency time of the drug in treated humans or animals, and the persistence in the environmental water up to 4 months [ 33 ].…”

Section: Insecticides-acaricidesmentioning

confidence: 99%

Drug resistant parasites and fungi from a one-health perspective: A global concern that needs transdisciplinary stewardship programs

et al. 2022

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Antimicrobials including antibiotics, antiparasitic, and antifungals, are subjected to resistance. In this context, Public Health Organizations called for a One Health approach because antimicrobials used to treat different infectious diseases in animals and plants may be the same than those used in humans. Whereas mechanisms of resistance transmission from animals or environment to humans should be considered differently if related to prokaryotic or eukaryotic pathogens, their impact can be considered as a whole. In that respect, we discussed the use of anti-parasitic in animals including anticoccidials, anthelmintics, and insecticides-acaricides, and the use of azoles in the environment that may both favor the development of drug resistance in humans. In light of the current situation, there is an urgent need for a transdisciplinary approach through anti-parasitic and antifungal stewardship programs in humans, animals, and environment, especially in the era of COVID-19 pandemic that will probably aggravate antimicrobial resistance.

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Veterinary endectocides for malaria control and elimination: prospects and challenges

Cited by 19 publications

References 48 publications

Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool

Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool

Proof-of-concept study for a long-acting formulation of ivermectin injected to cattle as a complementary malaria vector control tool

Drug resistant parasites and fungi from a one-health perspective: A global concern that needs transdisciplinary stewardship programs

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