Universidad Peruana Cayetano Heredia

Developing Plasmodium vivax Resources for Liver Stage Study in the Peruvian Amazon Region

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dc.contributor.author Orjuela-Sanchez, Pamela
dc.contributor.author Villa, Zaira Hellen
dc.contributor.author Moreno, Marta
dc.contributor.author Tong-Rios, Carlos
dc.contributor.author Meister, Stephan
dc.contributor.author LaMonte, Gregory M.
dc.contributor.author Campo, Brice
dc.contributor.author Vinetz, Joseph Michael
dc.contributor.author Winzeler, Elizabeth A.
dc.date.accessioned 2018-11-30T03:10:44Z
dc.date.available 2018-11-30T03:10:44Z
dc.date.issued 2018
dc.identifier.uri https://hdl.handle.net/20.500.12866/4040
dc.description.abstract To develop new drugs and vaccines for malaria elimination, it will be necessary to discover biological interventions, including small molecules that act against Plasmodium vivax exoerythrocytic forms. However, a robust in vitro culture system for P. vivax is still lacking. Thus, to study exoerythrocytic forms, researchers must have simultaneous access to fresh, temperature-controlled patient blood samples, as well as an anopheline mosquito colony. In addition, researchers must rely on native mosquito species to avoid introducing a potentially dangerous invasive species into a malaria-endemic region. Here, we report an in vitro culture system carried out on site in a malaria-endemic region for liver stage parasites of P. vivax sporozoites obtained from An. darlingi, the main malaria vector in the Americas. P. vivax sporozoites were obtained by dissection of salivary glands from infected An. darlingi mosquitoes and purified by Accudenz density gradient centrifugation. HC04 liver cells were exposed to P. vivax sporozoites and cultured up to 9 days. To overcome low P. vivax patient parasitemias, potentially lower mosquito vectorial capacity, and humid, nonsterile environmental conditions, a new antibiotic cocktail was included in tissue culture to prevent contamination. Culturing conditions supported exoerythrocytic (EEF) P. vivax liver stage growth up to 9 days and allowed for maturation into intrahepatocyte merosomes. Some of the identified small forms were resistant to atovaquone (1 μM) but sensitive to the phosphatidylinositol 4-kinase inhibitor, KDU691 (1 μM). This study reports a field-accessible EEF production process for drug discovery in a malaria-endemic site in which viable P. vivax sporozoites are used for drug studies using hepatocyte infection. Our data demonstrate that the development of meaningful, field-based resources for P. vivax liver stage drug screening and liver stage human malaria experimentation in the Amazon region is feasible. en_US
dc.language.iso eng
dc.publisher American Chemical Society
dc.relation.ispartofseries ACS Infectious Diseases
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Anopheles darlingi en_US
dc.subject drug evaluation en_US
dc.subject exoerythrocytic stage en_US
dc.subject in vitro culture en_US
dc.subject Peruvian Amazon region en_US
dc.subject Plasmodium vivax en_US
dc.subject sporozoite en_US
dc.title Developing Plasmodium vivax Resources for Liver Stage Study in the Peruvian Amazon Region en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1021/acsinfecdis.7b00198
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.relation.issn 2373-8227


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