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

Vinetz, Joseph Michael; Orjuela-Sanchez, Pamela; Tong-Rios, Carlos; Winzeler, Elizabeth A.; Villa, Zaira Hellen; Moreno, Marta; Meister, Stephan; Campo, Brice; LaMonte, Gregory M.

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.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