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

Abstract 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 iv...

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Main Authors: Sié Hermann Pooda, Nicolas Moiroux, Angélique Porciani, Anne-Laure Courjaud, Christophe Roberge, Georges Gaudriault, Issa Sidibé, Adrien Marie Gaston Belem, Jean-Baptiste Rayaissé, Roch K. Dabiré, Karine Mouline
Format: Article
Language:English
Published: BMC 2023-02-01
Series:Parasites & Vectors
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Online Access:https://doi.org/10.1186/s13071-022-05621-z
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author Sié Hermann Pooda
Nicolas Moiroux
Angélique Porciani
Anne-Laure Courjaud
Christophe Roberge
Georges Gaudriault
Issa Sidibé
Adrien Marie Gaston Belem
Jean-Baptiste Rayaissé
Roch K. Dabiré
Karine Mouline
author_facet Sié Hermann Pooda
Nicolas Moiroux
Angélique Porciani
Anne-Laure Courjaud
Christophe Roberge
Georges Gaudriault
Issa Sidibé
Adrien Marie Gaston Belem
Jean-Baptiste Rayaissé
Roch K. Dabiré
Karine Mouline
author_sort Sié Hermann Pooda
collection DOAJ
description Abstract 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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spelling doaj.art-521fda24d64a432186b2822ed829a76c2023-03-22T10:33:28ZengBMCParasites & Vectors1756-33052023-02-0116111210.1186/s13071-022-05621-zProof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control toolSié Hermann Pooda0Nicolas Moiroux1Angélique Porciani2Anne-Laure Courjaud3Christophe Roberge4Georges Gaudriault5Issa Sidibé6Adrien Marie Gaston Belem7Jean-Baptiste Rayaissé8Roch K. Dabiré9Karine Mouline10Université de DédougouMIVEGEC, Université de Montpellier-CNRS-IRDMIVEGEC, Université de Montpellier-CNRS-IRDMedinCell S.A.MedinCell S.A.MedinCell S.A.Insectarium de Bobo Dioulasso – Campagne d’éradication de la mouche Tsé Tsé et des TrypanosomosesUniversité Nazi BoniCentre International de Recherche et Développement pour l’Élevage en zones Sub-humidesInstitut de Recherche en Sciences de la SantéMIVEGEC, Université de Montpellier-CNRS-IRDAbstract 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 Abstracthttps://doi.org/10.1186/s13071-022-05621-zAnophelesMalariaResidual transmissionIvermectinLong-acting formulationCattle
spellingShingle Sié Hermann Pooda
Nicolas Moiroux
Angélique Porciani
Anne-Laure Courjaud
Christophe Roberge
Georges Gaudriault
Issa Sidibé
Adrien Marie Gaston Belem
Jean-Baptiste Rayaissé
Roch K. Dabiré
Karine Mouline
Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool
Parasites & Vectors
Anopheles
Malaria
Residual transmission
Ivermectin
Long-acting formulation
Cattle
title Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool
title_full Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool
title_fullStr Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool
title_full_unstemmed Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool
title_short Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool
title_sort proof of concept study for a long acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool
topic Anopheles
Malaria
Residual transmission
Ivermectin
Long-acting formulation
Cattle
url https://doi.org/10.1186/s13071-022-05621-z
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