A Plasmodium vivax experimental human infection model for evaluating efficacy of interventions
Autor: | Joerg J. Moehrle, Emma Ballard, Stephan Chalon, Leonardo Lucantoni, Vicky M. Avery, Matthew Adams, James S. McCarthy, Todd Shelper, Anand Odedra, Katharine A. Collins, Greg Robinson, Melanie Rampton, Claire Y. T. Wang, David S. Khoury, Hayley Mitchell, Suzanne L. Elliott |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Infectivity biology business.industry Plasmodium vivax lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Psychological intervention General Medicine medicine.disease biology.organism_classification Virology 03 medical and health sciences All institutes and research themes of the Radboud University Medical Center 030104 developmental biology 0302 clinical medicine Chloroquine Infectious disease (medical specialty) 030220 oncology & carcinogenesis parasitic diseases Gametocyte Medicine business Adverse effect Malaria medicine.drug |
Zdroj: | Journal of Clinical Investigation, 130, 6, pp. 2920-2927 Journal of Clinical Investigation, 130, 2920-2927 |
ISSN: | 1558-8238 0021-9738 |
Popis: | BACKGROUNDInterventions 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.METHODSHealthy, 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.RESULTSParasitemia 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.CONCLUSIONWe 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.TRIAL REGISTRATIONACTRN12614000930684 and ACTRN12616000174482.FUNDING(Australian) National Health and Medical Research Council Program Grant 1132975 (Study 1). Bill and Melinda Gates Foundation (OPP1111147) (Study 2). |
Databáze: | OpenAIRE |
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