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dc.contributor.authorCollins, Katharine A
dc.contributor.authorWang, Claire YT
dc.contributor.authorAdams, Matthew
dc.contributor.authorMitchell, Hayley
dc.contributor.authorRobinson, Greg J
dc.contributor.authorRampton, Melanie
dc.contributor.authorElliott, Suzanne
dc.contributor.authorOdedra, Anand
dc.contributor.authorKhoury, David
dc.contributor.authorBallard, Emma
dc.contributor.authorShelper, Todd B
dc.contributor.authorLucantoni, Leonardo
dc.contributor.authorAvery, Vicky M
dc.contributor.authorChalon, Stephan
dc.contributor.authorMoehrle, Joerg J
dc.contributor.authorMcCarthy, James S
dc.date.accessioned2020-09-16T04:42:21Z
dc.date.available2020-09-16T04:42:21Z
dc.date.issued2020
dc.identifier.issn0021-9738
dc.identifier.doi10.1172/JCI134923
dc.identifier.urihttp://hdl.handle.net/10072/397569
dc.description.abstractBACKGROUND. 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society for Clinical Investigation (ASCI)
dc.relation.ispartofpagefrom2920
dc.relation.ispartofpageto2927
dc.relation.ispartofissue6
dc.relation.ispartofjournalJournal of Clinical Investigation
dc.relation.ispartofvolume130
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchHealth sciences
dc.subject.fieldofresearchcode32
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode42
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsMedicine, Research & Experimental
dc.subject.keywordsResearch & Experimental Medicine
dc.subject.keywordsMALARIA
dc.titleA Plasmodium vivax experimental human infection model for evaluating efficacy of interventions
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationCollins, 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
dcterms.dateAccepted2020-02-04
dc.date.updated2020-09-16T04:39:36Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 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.
gro.hasfulltextFull Text
gro.griffith.authorAvery, Vicky M.


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