Institutions based in two malaria-endemic countries, Brazil and Peru, are partnering with a leading research group in the USA with the long-term goal of providing scientific evidence that can be translated into effective public health interventions for malaria control in Amazonia. To determine whether asymptomatic parasite carriage is a major contributor to malaria transmission across the region, we aim: (a) to estimate the prevalence, incidence and risk factors for asymptomatic malaria parasite carriage in rural Amazonia;(b) to estimate the prevalence, incidence, average duration and risk factors for gametocyte carriage;(c) to compare the ability of symptomatic and asymptomatic carriers of gametocytes to experimentally infect wild caught local vectors;(d) to compare prospectively the risk of subsequent clinical malaria among asymptomatic parasite carriers and non-infected controls living in the same communities and to determine whether these episodes are due to persistent parasite lineages or to new infections;and (e) to test whether intra-host competition of genetically distinct parasite clones contributes to increased parasite virulence, greater risk of disease, and increased gametocyte production.
These aims will be achieved with population based surveys, using uniformized clinical and laboratory protocols, in three epidemiologically diverse Amazonian settings: (a) a typical agricultural settlement with endemic malaria transmission in Brazil, (b) periurban villages in Peru that became recently exposed to epidemic malaria, and (c) gold-mining enclaves in Peru with explosive malaria outbreaks due to P. vivax. The field-based clinical and epidemiological analysis will be complemented with measurements of immunological parameters, extensive parasite genotyping and experimental infections of mosquitoes through membrane-feeding assays, providing a unique multidisciplinary perspective on the public health significance of asymptomatic parasite carriage in the Amazon Basin. Of crucial importance, the infrastructure and the data resulting of seven years of active malaria surveillance in the field sites will establish the bases for the vector biology and pathogenesis components of this proposal and for implementing future malaria vaccine trials in the Amazon region.

Public Health Relevance

At a time when eradication is advocated as the ultimate goal of malaria control strategies worldwide, it remains unclear why malaria proved so difficult to control in areas of relatively low levels of transmission across the Amazon Basin. We hypothesize that asymptomatic infections may represent a major reservoir of parasites in this region, which is not addressed by traditional malaria control strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI089681-05
Application #
8686723
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
Ferreira, Marcelo U; Castro, Marcia C (2016) Challenges for malaria elimination in Brazil. Malar J 15:284
Conn, Jan E (2016) News from Africa: Novel Anopheline Species Transmit Plasmodium in Western Kenya. Am J Trop Med Hyg 94:251-2
Nicolete, Vanessa C; Frischmann, Sarah; Barbosa, Susana et al. (2016) Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein and Clinical Immunity to Malaria in Rural Amazonians. J Infect Dis 214:1539-1546
Shaw-Saliba, Kathryn; Clarke, David; Santos, Jorge M et al. (2016) Infection of laboratory colonies of Anopheles mosquitoes with Plasmodium vivax from cryopreserved clinical isolates. Int J Parasitol 46:679-83
Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo et al. (2016) Epidemiology of Plasmodium vivax Malaria in Peru. Am J Trop Med Hyg :
Gonçalves-Lopes, Raquel M; Lima, Nathália F; Carvalho, Karina I et al. (2016) Surface expression of inhibitory (CTLA-4) and stimulatory (OX40) receptors by CD4(+) regulatory T cell subsets circulating in human malaria. Microbes Infect 18:639-648
Llanos-Chea, Fiorella; Martínez, Dalila; Rosas, Angel et al. (2015) Characteristics of Travel-Related Severe Plasmodium vivax and Plasmodium falciparum Malaria in Individuals Hospitalized at a Tertiary Referral Center in Lima, Peru. Am J Trop Med Hyg 93:1249-53
Bickersmith, Sara A; Lainhart, William; Moreno, Marta et al. (2015) A sensitive, specific and reproducible real-time polymerase chain reaction method for detection of Plasmodium vivax and Plasmodium falciparum infection in field-collected anophelines. Mem Inst Oswaldo Cruz 110:573-6
Kobayashi, Tamaki; Gamboa, Dionicia; Ndiaye, Daouda et al. (2015) Malaria Diagnosis Across the International Centers of Excellence for Malaria Research: Platforms, Performance, and Standardization. Am J Trop Med Hyg 93:99-109
Cui, Liwang; Mharakurwa, Sungano; Ndiaye, Daouda et al. (2015) Antimalarial Drug Resistance: Literature Review and Activities and Findings of the ICEMR Network. Am J Trop Med Hyg 93:57-68

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