1. Using an antimalarial in mosquitoes overcomes Anopheles and Plasmodium resistance to malaria control strategies
- Author
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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, Prislaure S. L. Paré, Rakiswendé S. Yerbanga, Abdoullaye Diabaté, Roch K. Dabiré, Thierry Lefèvre, Dyann F. Wirth, Flaminia Catteruccia, Harvard T.H. Chan School of Public Health, Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Transmission-Interactions-Adaptations hôtes/vecteurs/pathogènes (MIVEGEC-TRIAD), Evolution des Systèmes Vectoriels (ESV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Centre de Recherche en Ecologie et Evolution de la Santé (CREES), Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and ANR-16-CE35-0007,STORM,Stratégies de transmission des parasites à vecteur : variation génétique, plasticité phénotypique et conséquences pour les mesures de contrôle(2016)
- Subjects
Plasmodium ,Immunology ,Plasmodium falciparum ,Microbiology ,Malaria ,[SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology ,Antimalarials ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Virology ,Anopheles ,Genetics ,Animals ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Parasitology ,Female ,Malaria, Falciparum ,Molecular Biology ,Atovaquone - Abstract
The spread of insecticide resistance in Anopheles mosquitoes and drug resistance in Plasmodium parasites is contributing to a global resurgence of malaria, making the generation of control tools that can overcome these roadblocks an urgent public health priority. We recently showed that the transmission of Plasmodium falciparum parasites can be efficiently blocked when exposing Anopheles gambiae females to antimalarials deposited on a treated surface, with no negative consequences on major components of mosquito fitness. Here, we demonstrate this approach can overcome the hurdles of insecticide resistance in mosquitoes and drug resistant in parasites. We show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistant Anopheles are exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistant P. falciparum parasites (Kelch13 C580Y mutant), proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions, including in ongoing infections. These data support the use of mosquito-targeted antimalarials as a promising tool to complement and extend the efficacy of current malaria control interventions.
- Published
- 2022
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