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 #
1U19AI089681-01
Application #
8005410
Study Section
Special Emphasis Panel (ZAI1-AWA-M (M1))
Project Start
2010-07-01
Project End
2017-06-30
Budget Start
2010-09-01
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$289,409
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Moreno, Marta; Tong-Rios, Carlos; Orjuela-Sanchez, Pamela et al. (2018) Continuous Supply of Plasmodium vivax Sporozoites from Colonized Anopheles darlingi in the Peruvian Amazon. ACS Infect Dis 4:541-548
Prussing, Catharine; Moreno, Marta; Saavedra, Marlon P et al. (2018) Decreasing proportion of Anopheles darlingi biting outdoors between long-lasting insecticidal net distributions in peri-Iquitos, Amazonian Peru. Malar J 17:86
Martin, Thomas C S; Vinetz, Joseph M (2018) Asymptomatic Plasmodium vivax parasitaemia in the low-transmission setting: the role for a population-based transmission-blocking vaccine for malaria elimination. Malar J 17:89
Junqueira, Caroline; Barbosa, Camila R R; Costa, Pedro A C et al. (2018) Cytotoxic CD8+ T cells recognize and kill Plasmodium vivax-infected reticulocytes. Nat Med 24:1330-1336
Cowell, Annie N; Valdivia, Hugo O; Bishop, Danett K et al. (2018) Exploration of Plasmodium vivax transmission dynamics and recurrent infections in the Peruvian Amazon using whole genome sequencing. Genome Med 10:52
Schrum, Jacob E; Crabtree, Juliet N; Dobbs, Katherine R et al. (2018) Cutting Edge: Plasmodium falciparum Induces Trained Innate Immunity. J Immunol 200:1243-1248
White, Sara E; Harvey, Steven A; Meza, Graciela et al. (2018) Acceptability of a herd immunity-focused, transmission-blocking malaria vaccine in malaria-endemic communities in the Peruvian Amazon: an exploratory study. Malar J 17:179
Hirako, Isabella Cristina; Assis, Patrícia Aparecida; Hojo-Souza, Natália Satchiko et al. (2018) Daily Rhythms of TNF? Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle. Cell Host Microbe 23:796-808.e6
Prussing, Catharine; Bickersmith, Sara A; Moreno, Marta et al. (2018) Nyssorhynchus dunhami: bionomics and natural infection by Plasmodium falciparum and P. vivax in the Peruvian Amazon. Mem Inst Oswaldo Cruz 113:e180380
Rodrigues, Priscila T; Valdivia, Hugo O; de Oliveira, Thais C et al. (2018) Human migration and the spread of malaria parasites to the New World. Sci Rep 8:1993

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