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Antimalarials in mosquitoes overcome Anopheles and Plasmodium resistance to malaria control strategies

Douglas G. Paton, Alexandra S. Probst, Erica Ma, Kelsey L. Adams, W. Robert Shaw, Naresh Singh, Selina Bopp, Sarah K. Volkman, Domombele F. S. Hien, Rakiswendé S. Yerbanga, Thierry Lefèvre, Abdoullaye Diabaté, Roch K. Dabiré, Dyann F. Wirth, Flaminia Catteruccia
doi: https://doi.org/10.1101/2021.03.12.435188
Douglas G. Paton
1Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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  • For correspondence: fcatter@hsph.harvard.edu dpaton@hsph.harvard.edu
Alexandra S. Probst
1Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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Erica Ma
1Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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Kelsey L. Adams
1Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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W. Robert Shaw
1Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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Naresh Singh
1Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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Selina Bopp
1Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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Sarah K. Volkman
1Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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Domombele F. S. Hien
2Institut de Recherche en Sciences de la Santé/Centre Muraz, Bobo-Dioulasso, Burkina Faso
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Rakiswendé S. Yerbanga
2Institut de Recherche en Sciences de la Santé/Centre Muraz, Bobo-Dioulasso, Burkina Faso
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Thierry Lefèvre
3MIVEGEC, IRD, CNRS, University of Montpellier, Montpellier, France
4Laboratoire mixte international sur les vecteurs (LAMIVECT), Bobo Dioulasso, Burkina Faso
5Centre de Recherche en Écologie et Évolution de la Santé (CREES), Montpellier, France
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Abdoullaye Diabaté
2Institut de Recherche en Sciences de la Santé/Centre Muraz, Bobo-Dioulasso, Burkina Faso
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Roch K. Dabiré
2Institut de Recherche en Sciences de la Santé/Centre Muraz, Bobo-Dioulasso, Burkina Faso
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Dyann F. Wirth
1Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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Flaminia Catteruccia
1Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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  • For correspondence: fcatter@hsph.harvard.edu dpaton@hsph.harvard.edu
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Abstract

The spread of insecticide resistance in Anopheles mosquitoes and drug resistance in malaria parasites is contributing to a global resurgence of malaria, and the generation of control tools that can overcome these issues is an urgent public health priority. We recently demonstrated that the transmission of Plasmodium falciparum parasites by Anopheles gambiae can be efficiently blocked when female mosquitoes contact the antimalarial atovaquone deposited on a treated surface, with no negative consequences on mosquito fitness. Here, we demonstrate that the transmission-blocking efficacy of mosquito-targeted atovaquone is maintained when highly insecticide resistant, field-derived Anopheles mosquitoes are exposed to this antimalarial, indicating that insecticide resistance mechanisms do not interfere with drug function. Moreover, this approach prevents transmission of field P. falciparum isolates, including an artemisinin resistant Kelch13 C580Y mutant, demonstrating that this strategy could prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Finally, we show that ingestion of atovaquone in sugar solution is highly effective at limiting parasite development, including in ongoing infections. These data support the use of mosquito-targeted antimalarial interventions to potentiate and extend the efficacy of our best malaria control tools.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 12, 2021.
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Antimalarials in mosquitoes overcome Anopheles and Plasmodium resistance to malaria control strategies
Douglas G. Paton, Alexandra S. Probst, Erica Ma, Kelsey L. Adams, W. Robert Shaw, Naresh Singh, Selina Bopp, Sarah K. Volkman, Domombele F. S. Hien, Rakiswendé S. Yerbanga, Thierry Lefèvre, Abdoullaye Diabaté, Roch K. Dabiré, Dyann F. Wirth, Flaminia Catteruccia
bioRxiv 2021.03.12.435188; doi: https://doi.org/10.1101/2021.03.12.435188
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Antimalarials in mosquitoes overcome Anopheles and Plasmodium resistance to malaria control strategies
Douglas G. Paton, Alexandra S. Probst, Erica Ma, Kelsey L. Adams, W. Robert Shaw, Naresh Singh, Selina Bopp, Sarah K. Volkman, Domombele F. S. Hien, Rakiswendé S. Yerbanga, Thierry Lefèvre, Abdoullaye Diabaté, Roch K. Dabiré, Dyann F. Wirth, Flaminia Catteruccia
bioRxiv 2021.03.12.435188; doi: https://doi.org/10.1101/2021.03.12.435188

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