A Plasmodium vivax experimental human infection model for evaluating efficacy of interventions
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Wang, Claire YT
Adams, Matthew
Mitchell, Hayley
Robinson, Greg J
Rampton, Melanie
Elliott, Suzanne
Odedra, Anand
Khoury, David
Ballard, Emma
Shelper, Todd B
Lucantoni, Leonardo
Avery, Vicky M
Chalon, Stephan
Moehrle, Joerg J
McCarthy, James S
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Abstract
BACKGROUND. Interventions that interrupt Plasmodium vivax transmission or eliminate dormant P. vivax liver-stage parasites will be essential for malaria elimination. Development of these interventions has been hindered by the lack of P. vivax in vitro culture and could be accelerated by a safe and reproducible clinical model in malaria-naive individuals.
METHODS. Healthy, malaria-naive adults were enrolled in 2 studies to assess the safety, infectivity, and transmissibility of a new P. vivax isolate. Participants (Study 1, n = 2; Study 2, n = 24) were inoculated with P. vivax–infected red blood cells to initiate infection, and were treated with artemether-lumefantrine (Study 1) or chloroquine (Study 2). Primary endpoints were safety and infectivity of the new isolate. In Study 2, transmission to mosquitoes was also evaluated using mosquito feeding assays, and sporozoite viability was assessed using in vitro cultured hepatocytes.
RESULTS. Parasitemia and gametocytemia developed in all participants and was cleared by antimalarial treatment. Adverse events were mostly mild or moderate and none were serious. Sixty-nine percent of participants (11/16) were infectious to Anopheles mosquitoes at peak gametocytemia. Mosquito infection rates reached 97% following membrane feeding with gametocyte-enriched blood, and sporozoites developed into liver-stage schizonts in culture.
CONCLUSION. We have demonstrated the safe, reproducible, and efficient transmission of P. vivax gametocytes from humans to mosquitoes, and have established an experimental model that will accelerate the development of interventions targeting multiple stages of the P. vivax life cycle.
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Journal of Clinical Investigation
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130
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6
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© 2020 American Society for Clinical Investigation (ASCI). The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
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Biomedical and clinical sciences
Biological sciences
Health sciences
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
MALARIA
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Collins, KA; Wang, CYT; Adams, M; Mitchell, H; Robinson, GJ; Rampton, M; Elliott, S; Odedra, A; Khoury, D; Ballard, E; Shelper, TB; Lucantoni, L; Avery, VM; Chalon, S; Moehrle, JJ; McCarthy, JS, A Plasmodium vivax experimental human infection model for evaluating efficacy of interventions, Journal of Clinical Investigation, 2020, 130 (6), pp. 2920-2927