Lead Institution: Yale University
Although the overall burden of malaria in Latin America and the Caribbean has decreased dramatically over the past two decades, transmission persists in 21 countries in the region, where 120 million people are exposed to some risk of infection. The Amazon Basin, a vast territory that extends over nine countries in South America, contributes approximately 90 percent of the region’s malaria burden. Plasmodium vivax is the dominant human malaria parasite, found in nearly 76 percent of cases in the region. Malaria infections are predominantly acquired in remote riverine villages, frontier farming settlements, gold mining camps, and Amerindian reserves. More recently, malaria transmission has been increasingly documented within and near urban centers in the region.
The overall research aim of the Amazonia ICEMR is to implement a comprehensive approach to understanding the biological features of Amazonian malaria. The ICEMR focuses on malaria epidemiology, vector biology and ecology, diagnostics, transmission biology, and clinical pathogenesis.
Malaria epidemiology, diagnostics, and transmission
Significant findings on malaria epidemiology from the Amazonia ICEMR include the following:
- Malaria transmission in the Peruvian Amazon is highly heterogeneous at the micro-geographical level and over time. Therefore, public health interventions should take into account contrasting contexts (e.g., riverine, road construction/deforestation, and gold mining) to carry out effective anti-malaria control and elimination efforts.
- High prevalence of very-low parasitaemias were observed in the Amazon region, with findings that asymptomatic and subpatent infections predominated. In addition, plasmodium gametocyte reservoirs in the Amazon region are predominately asymptomatic and submicroscopic. Sensitive molecular tools will be needed to detect these infections that would otherwise escape routine malaria surveillance and may threaten control and elimination strategies in the Amazon region.
- Individuals living near a confirmed malaria case have increased risk of symptomatic or asymptomatic infections. It is unknown whether the subpatent and asymptomatic carriers who remain outside the identified clusters of symptomatic infections beyond the reach of reactive case detection (RCD) represent a significant parasite reservoir. These findings suggest that RCD may be a useful strategy to address these high-risk subjects.
- Researchers reported the presence of malaria gene corridors connecting geographically distant transmission zones of Plasmodium vivax in the Peruvian Amazon likely due to human mobility. Introduction of a new parasite clone or reintroduction of parasites in areas where malaria has already been controlled sustains disease transmission, hindering the success of control and elimination measures.
Molecular entomology and vector biology
The ICEMR’s findings on vector behavior and ecology in the Amazon include the following:
- Over several years and localities in the Peruvian Amazon, ICEMR researchers demonstrated a novel pattern of host choice in the primary Amazonian malaria vector Ny. darlingi (also known as Anopheles darlingi) of mosquitoes feeding exclusively on humans, exclusively on Galliformes, or on both. The findings suggest that biomass and availability of alternate hosts when humans are protected facilitates opportunistic feeding that ensures survival of malaria vectors.
- The ICEMR detected microgeographic structures of Ny. darlingi populations by habitat (highway/riverine) using microsatellites. Different molecular markers and interpretations detected subpopulations based on degree of anthropogenic disturbance (old/new settlements), locality (indoor/outdoor), and time (dawn/dusk) in Brazilian localities but not in Peruvian ones. These findings suggest that distinctive vector subpopulations may require a range of local vector controls. One size does not fit all.
- High outdoor (residual) malaria transmission by Ny. darlingi was found in Brazil and Peru. Researchers also documented behavioral plasticity of Ny. darlingi in Peru towards increased exophagy (outdoor biting), due to repellence by insecticides used on long-lasting insecticidal nets (LLINs), and subsequent reversion to increased endophagy (indoor biting) as nets aged. These results indicate that LLINs require routine replacement. Additional control methods and/or personal protections are essential in outdoor settings during the evening.
- Researchers discovered that Ny. darlingi breeding sites in the Peruvian Amazon are significantly correlated with low forest coverage, low sunlight exposure and emergent vegetation. The ICEMR team was the first to use high accuracy multispectral imagery with drones to consistently and accurately detect water bodies that have a high probability of Ny. darlingi presence. This work demonstrates that drones could be employed in high-risk malaria sites to help locate breeding sites of Ny. darlingi that could then be treated.
- Researchers established the first Ny. darlingi colony derived from wild-caught mosquitoes in Peru and Brazil and developed a P. vivax sporozoite production in a malaria-endemic setting using this colony.
Immunology and clinical pathogenesis
In the Peruvian Amazon, the ICEMR developed a protein microarray of asexual-stage P. vivax and P. falciparum to identify antigens for potential use as serological markers for the accurate detection of recent malaria exposure to guide and monitor malaria control efforts. In a low transmission setting such as the Peruvian Amazon, researchers were able to associate only a few sets of P. falciparum protein antigens with the development of naturally acquired clinical immunity, which represents an obstacle for a vaccine design.
The ICEMR also aims to characterize these novel proteins in functional studies such as P. vivax and P. falciparum invasion assays and continue to evaluate their applications in epidemiological studies. Currently, this protein production system is being used in a multidisciplinary collaboration at Universidad Peruana Cayetano Heredia (UPCH), with the goal to expand the implementation of this technology.
The long-term goal of the Amazonia ICEMR is to provide scientific evidence that can be translated into effective public health interventions for malaria control and elimination. The ICEMR seeks to 1) understand the basis for two contrasting epidemiological situations in the Amazon: residual malaria with low transmission and hotspots of high transmission; 2) target vector control interventions to the behavior, ecology, and genetics of local vectors; and 3) to perform a comparative analysis of the immune response of both asymptomatic and symptomatic malaria, aiming to identify immunological markers that predict disease outcome and infectivity of malaria parasites to Ny. Darlingi (the primary malaria vector in the region).
View Associated Sites for the Amazonia ICEMR in a larger map
Principal Investigator: Joseph Vinetz, M.D.
- Marcelo Ferreira, University of Sao Paulo, Institute of Biomedical Sciences
- Dionicia Gamboa, Universidad Peruana Cayetano Heredia, Faculty of Sciences and Philosophy, Alexander von Humboldt Institute of Tropical Medicine
- Jan Conn, Wadsworth Center, New York State Department of Health
- Ricardo Gazzinelli, University of Massachusetts Medical School
- Fundação Oswaldo Cruz (FIOCRUZ)– Bel Horizonte, Brazil
- Instituto de Biociencias, Universidade Estadual Paulista, Botucatu, Sao Paulo, Brazil
- Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
- Universidad Peruana Cayetano Heredia, Lima, Peru
- Liverpool School of Tropical Medicine, Liverpool, UK
- Wadsworth Center, New York State Department of Health, Albany, NY and School of Public Health, University at Albany, State University of New York
- President and Fellows of Harvard College, Boston, MA
- Harvard School of Public Health, Boston, MA
- University of Massachusetts Medical School, Boston, MA
- Temple University of the Commonwealth, Philadelphia, PA
- Scripps Research Institute, La Jolla, CA