Individual variation in malaria risk: causes and consequences in Amazonian populations

• Grant number: 22/11963-3
• Support Opportunities: Research Projects - Thematic Grants
• Start date: October 01, 2023
• End date: September 30, 2028
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Marcelo Urbano Ferreira
• Grantee: Marcelo Urbano Ferreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Paulo Eduardo Martins Ribolla
• Associated researchers: Ana Paula Martins dos Reis Arez ; Júlia Maria Pavan Soler ; Rodrigo Malavazi Corder ; Sergio Muniz Oliva Filho ; Tais Nobrega de Sousa
• Associated research grant(s): 25/06122-8 - Developing Conditional Independence Tests for Causal Discovery with Multiple (Co)Variance Components and Heterogeneous Variables: Application to Understanding Variability in Malaria Risk in the Brazilian Amazon, AV.EXT; 24/00293-2 - Pyruvate kinase deficiency: optimizing pkrl gene sequencing and analysis of genotypic data in relation to malaria risk, AV.EXT
• Associated scholarship(s): 24/21891-5 - Polymorphism in the pklr gene, pyruvate kinase deficiency in red blood cells, and malaria risk in the Brazilian Amazon, BP.MS; 24/10682-6 - Individual variation in malaria risk: causes and consequences in Amazonian populations, BP.PD; 24/02290-0 - Naturally acquired anti-RBP2b antibodies, red bllod cell invasion blockade, and protection from Plasmodium vivax Malaria, BP.PD; 23/15369-1 - Superspreaders and residual malaria transmission in the main urban hotspot of Brazil, BP.DR

Abstract

Extensive research has examined why some people have repeated Plasmodium falciparum malaria attacks in Sub-Saharan Africa while others remain free of disease most of the time. In contrast, malaria risk heterogeneity remains little studied in regions where P. vivax is the dominant species. Are repeatedly infected people in vivax malaria settings such as the Amazon just unlucky? Here we aim to explore specific factors - including human and vector genetic polymorphism, acquired antibody-mediated immunity, and variation in parasite virulence - that can modulate the individual risk of P. vivax infection and disease in well characterized malaria-endemic Amazonian communities. We combine classical epidemiological approaches, molecular genotyping of humans, vectors and parasites, and functional antibody assays with quantitative genetics, mathematical modeling and vector biology to explore longitudinally collected data and samples from a unique population-based cohort study carried out in the main malaria transmission hotspot of Brazil. We aim to: (a) estimate the contribution of human genetics, not limited to known or suspected "malaria resistance genes", to individual malaria risk variation in Brazil; (b) to compare the differential impact of a specific human genetic polymorphism, pyruvate kinase deficiency, on P. falciparum and P. vivax malaria risk; (c) to investigate the association between naturally acquired antibodies to a key asexual blood-stage of P. vivax antigen and malaria risk; (d) to test the hypothesis that less virulent P. vivax lineages are positively selected as malaria vectors become less abundant and transmission declines; (e) to estimate the population-wide impact of specific malaria control interventions targeted at high-risk individuals; and (f) to determine how the biological heterogeneity of vectors affects the transmission dynamics of malaria considering its population structure and its preference for certain individuals (e.g., infected people). We argue that individual risk variation must be considered when designing and implementing strategies for malaria control and elimination. (AU)