Malaria, caused by both Plasmodium falciparum and P. vivax in the Amazon region, is responsible for enormous human suffering and human economic loss worldwide. The long-term objective of the research proposed here is to contribute towards the global control of malaria by understanding human, parasite and mosquito factors that modulate the transmission of malaria parasites from the human reservoir to mosquitoes. Despite eradication efforts since the 1950s, malaria has rebounded to levels of morbidity and mortality that are higher than ever. There is no effective malaria vaccine. Drug-resistant malaria is common and increasing not only in the lethal human malaria parasite, Plasmodium falciparum but also in the even more widespread human malaria parasite, P. vivax. A key observation we seek to explain is why patients infected with P. vivax that have patent gametocytemia only inefficiently (-50%) infected wild-caught Anopheles darlingi mosquitoes under experimental conditions. The central hypotheses ofthis project are that that human antibody responses, cell-mediated immunity, and P. vivax maturity and sex ratios may modulate parasite infectivity to mosquitoes;and that different species of neotropical anopheles mosquitoes differ in their sensitivity to P. vivax. These hypotheses will be tested in the following Specific Aims: 1) To determine the contributions and associations ofhuman humoral responses, human cell-mediated immune responses, and P. vivax gametocyte maturity and sex ratio with parasite transmission to Anopheles darlingi, in both symptomatic and asymptomatic patient populations;2) To assess the susceptibility of colonized Anopheles darlingi and non-An darlingi potential malaria vector mosquitoes to infection by Plasmodium vivax;and 3) To determine mechanisms of transmission blocking activity in patients with naturally acquired transmission blocking antibodies. This project will provide new insights into fundamental mechanisms affecting the transmission of P. vivax from the human reservoir to natural, wild type neotropical Anopheles mosquito vectors in the Amazonian hypoendemic setting.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI089681-04
Application #
8512545
Study Section
Special Emphasis Panel (ZAI1-AWA-M)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$509,756
Indirect Cost
$39,490
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Torres, Katherine J; Villasis, Elizabeth; Bendez├║, Jorge et al. (2014) Relationship of regulatory T cells to Plasmodium falciparum malaria symptomatology in a hypoendemic region. Malar J 13:108
Moreno, Marta; Tong, Carlos; Guzmán, Mitchel et al. (2014) Infection of laboratory-colonized Anopheles darlingi mosquitoes by Plasmodium vivax. Am J Trop Med Hyg 90:612-6
Abeles, Shira R; Chuquiyauri, Raul; Tong, Carlos et al. (2013) Human host-derived cytokines associated with Plasmodium vivax transmission from acute malaria patients to Anopheles darlingi mosquitoes in the Peruvian Amazon. Am J Trop Med Hyg 88:1130-7
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Yalcindag, Erhan; Elguero, Eric; Arnathau, Celine et al. (2012) Multiple independent introductions of Plasmodium falciparum in South America. Proc Natl Acad Sci U S A 109:511-6
Chuquiyauri, Raul; Paredes, Maribel; Penataro, Pablo et al. (2012) Socio-demographics and the development of malaria elimination strategies in the low transmission setting. Acta Trop 121:292-302
Kosek, Margaret; Yori, Pablo P; Gilman, Robert H et al. (2012) High degree of Plasmodium vivax diversity in the Peruvian Amazon demonstrated by tandem repeat polymorphism analysis. Am J Trop Med Hyg 86:580-6

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