Despite major progress in malaria reduction in Latin America from 2005-2015, malaria cases have again increased to nearly one million in the last few years, with 75% of these cases reported in Venezuela and Brazil. We emphasize that ecological variables (such as ecotones and land use classes) that impact the primary neotropical vector Anopheles darlingi (in Brazil and Venezuela) and the regional vector An. albitarsis s.l. (equal in importance to An. darlingi in Venezuela) are largely unquantified or unidentified, constituting a major information gap. The premise of the proposed study is that human-modified landscape types (riverine, mining, agricultural) in persistent malaria hotspots differ significantly in measurable determinants of transmission (ecological, entomological, socioeconomic). Quantification of these determinants in landscape types in Venezuela and Brazil is essential for malaria surveillance to facilitate local targeted interventions to most effectively reduce transmission. Coupling these measures with landscape genomics, we propose to identify and quantify, in a spatially explicit way, landscape features affecting microevolution of malaria vectors. This will provide new insights into local vector adaptation in heterogeneous landscapes, and will help determine why neotropical malaria hotspots persist, at times over multiple years, in certain geographic locations. We hypothesize that the ecological drivers of abundance, proliferation and survival in An. darlingi and An. albitarsis s.l. will differ significantly due to unique ecological signatures (niches) of each species. We anticipate that our findings will provide new information about differential habitat suitability that can be applied throughout the broad and largely overlapping distributions of An. darlingi and An. albitarsis s.l. Polymorphism discovery through whole genome resequencing, integrated with measures of entomological and socioeconomic factors that intensify human-vector contact, will reveal the evolutionary genetic basis of factors promoting vector proliferation and connectivity among vector populations, allowing for more effective vector surveillance. A key remaining issue in our understanding of the role of An. darlingi landscape genomics in malaria transmission is whether gene flow contributes to rapid adaptation and colonization of deforested/degraded habitats throughout the Amazon Basin. We will employ landscape genomics at a regional scale in both Brazil and Venezuela to test whether An. darlingi maintains genetic connectivity or is isolated by resistance across ecotones punctuated by high forest cover. Whereas population genetic surveys based on RADseq or individual genes can detect overall population structure, whole genome sequencing studies have shown that these limited surveys may miss important patterns of ancestry, gene flow and evidence of adaptation (Anopheles gambiae 1000 Genomes Consortium 2017). Herein we present an integrated approach to identify and quantify ecological, entomological and socioeconomic drivers of malaria transmission, based on multi-scale analysis of An. darlingi and An. albitarsis s.l. collected under natural field conditions.

Public Health Relevance

? Public Health Relevance Malaria remains the major mosquito-borne parasitic disease worldwide, and Venezuela and Brazil combined are currently responsible for an estimated 720,000 malaria cases, 75% of all those reported in South America. Our studies will provide the first regional comparison of key understudied ecological mechanisms and landscape genetics directly linked to malaria risk from the primary malaria vectors in endemic hotspots: gold mining settlements in Venezuela and rainforest riverine, mining, and agricultural settlements in Brazil. This field-based study at multiple spatial scales will provide evidence to improve control strategies that maximally impact malaria transmission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI110112-06A1
Application #
10071331
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2014-06-15
Project End
2025-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Wadsworth Center
Department
Type
DUNS #
153695478
City
Menands
State
NY
Country
United States
Zip Code
12204
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