Transmission dynamics of the malaria parasite Plasmodium falciparum have been proposed to be largely driven by immune selection to the major surface antigen of the blood stages known as erythrocyte membrane protein 1 (PfEMP1) encoded by up to 60 members of the var multigene family per haploid genome. Emerging population genetic data have revealed that the malaria transmission system is remarkably complex necessitating a much deeper molecular sampling of parasite populations and the development of computational approaches that extend previous 'strain theory'through the lens of var genetics. This project aims to define the population structure of P. falciparum in the context of var gene diversity and explore epidemiological dynamics in this framework. A team project has been created that brings together mathematical modelers, epidemiologists, entomologists, bioinformaticians, population geneticists and malaria epidemiologists from Ghana and US. Our approach combines both modeling and empirical studies to explore malaria transmission dynamics of P. falciparum at the level of local parasite populations in northern Ghana in the context of var genetics. Specific objectives are: (1) An individual-based, stochastic modeling framework that couples within and between-host transmission and describes the individual-host immunological history of exposure to different var gene repertoires to explore strain dynamics of P. falciparum in relation to age, seasonality and vector intervention. (2): For the first time in malaria epidemiology research, the longitudinal seasonal sampling of entire asymptomatic P. falciparum populations in human communities using deep 454 sequencing of var genes. (3): The quantitative description of var gene diversity and of var repertoires in wet and dry seasons, as well as across a major vector control intervention using indoor residual spraying (IRS), in comparison to microsatellite diversity. Through these objectives',-we-will address the fundamental question of strain structure despite extensive recombination and driven by immune selection, competitive interactions between parasites for hosts in the transmission dynamics. In turn, we will also ask how this structure and associated parasite diversity influence transmission dynamics.

Public Health Relevance

This project will create a conceptual shift in malaria control and practice if we prove that P. falciparum has a strain structure as current theory ignores parasite diversity and potentially overestimates the transmissibility of malaria (Ro). This outcome of the project could lead to real innovation in malaria surveillance, control and elimination strategies.

National Institute of Health (NIH)
Fogarty International Center (FIC)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IDM-U (55))
Program Officer
Jessup, Christine
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Arts and Sciences
Ann Arbor
United States
Zip Code
Rorick, Mary M; Baskerville, Edward B; Rask, Thomas S et al. (2018) Identifying functional groups among the diverse, recombining antigenic var genes of the malaria parasite Plasmodium falciparum from a local community in Ghana. PLoS Comput Biol 14:e1006174
Rorick, Mary M; Artzy-Randrup, Yael; Ruybal-Pesántez, Shazia et al. (2018) Signatures of competition and strain structure within the major blood-stage antigen of Plasmodium falciparum in a local community in Ghana. Ecol Evol 8:3574-3588
He, Qixin; Pilosof, Shai; Tiedje, Kathryn E et al. (2018) Networks of genetic similarity reveal non-neutral processes shape strain structure in Plasmodium falciparum. Nat Commun 9:1817
Perez-Saez, Javier; King, Aaron A; Rinaldo, Andrea et al. (2017) Climate-driven endemic cholera is modulated by human mobility in a megacity. Adv Water Resour 108:367-376
Ruybal-Pesántez, Shazia; Tiedje, Kathryn E; Tonkin-Hill, Gerry et al. (2017) Population genomics of virulence genes of Plasmodium falciparum in clinical isolates from Uganda. Sci Rep 7:11810
Day, Karen P; Artzy-Randrup, Yael; Tiedje, Kathryn E et al. (2017) Evidence of strain structure in Plasmodium falciparum var gene repertoires in children from Gabon, West Africa. Proc Natl Acad Sci U S A 114:E4103-E4111
Rask, Thomas S; Petersen, Bent; Chen, Donald S et al. (2016) Using expected sequence features to improve basecalling accuracy of amplicon pyrosequencing data. BMC Bioinformatics 17:176
Artzy-Randrup, Yael; Dobson, Andrew P; Pascual, Mercedes (2015) Synergistic and antagonistic interactions between bednets and vaccines in the control of malaria. Proc Natl Acad Sci U S A 112:3014-9