This proposal seeks to apply concepts from evolutionary biology to the study of both human and non-human malaria parasites, with the broad goal of gaining analyzing their phylogenetic relationships and of characterizing the amount, origin and manner of maintenance of genetic diversity in various genes encoding human candidate immunogens. Four primary aims are to be pursued, including: (1) to establish phylogenetic relationships relating the various mammalian malaria parasites to each other and to those of other Haemosporina, emphasizing the origins and evolutionary history of P. falciparum and P. vivax; (2) using this phylogenetic tree as a base, to identify factors affecting the evolution of major candidate vaccine immunogens; 3) to compare the extent, origin and maintenance of genetic diversity among candidate immunogens from geographically diverse samples of P. falciparum and of P. vivax; and 4) to correlate intra-host parasite genetic diversity and clinical manifestations of disease in P. falciparum-infected children in western Kenya. Overall, the proposed body of work seeks to establish the origins of the malaria parasites, to provide a basis for developing a multivalent malaria vaccine and to define the distribution of genetic diversity among malaria parasites across a broad geographic area.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-GEN (01))
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Eckstrand, Irene A
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Emory University
Schools of Arts and Sciences
United States
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Hamel, Mary J; Greene, Carolyn; Chiller, Tom et al. (2008) Does cotrimoxazole prophylaxis for the prevention of HIV-associated opportunistic infections select for resistant pathogens in Kenyan adults? Am J Trop Med Hyg 79:320-30
Nishimoto, Yuriko; Arisue, Nobuko; Kawai, Satoru et al. (2008) Evolution and phylogeny of the heterogeneous cytosolic SSU rRNA genes in the genus Plasmodium. Mol Phylogenet Evol 47:45-53
Hamel, Mary J; Poe, Amanda; Bloland, Peter et al. (2008) Dihydrofolate reductase I164L mutations in Plasmodium falciparum isolates: clinical outcome of 14 Kenyan adults infected with parasites harbouring the I164L mutation. Trans R Soc Trop Med Hyg 102:338-45
Pacheco, M Andreina; Poe, Amanda C; Collins, William E et al. (2007) A comparative study of the genetic diversity of the 42kDa fragment of the merozoite surface protein 1 in Plasmodium falciparum and P. vivax. Infect Genet Evol 7:180-7
McCollum, Andrea M; Mueller, Kristen; Villegas, Leopoldo et al. (2007) Common origin and fixation of Plasmodium falciparum dhfr and dhps mutations associated with sulfadoxine-pyrimethamine resistance in a low-transmission area in South America. Antimicrob Agents Chemother 51:2085-91
Cornejo, Omar E; Escalante, Ananias A (2006) The origin and age of Plasmodium vivax. Trends Parasitol 22:558-63
McCollum, Andrea M; Poe, Amanda C; Hamel, Mary et al. (2006) Antifolate resistance in Plasmodium falciparum: multiple origins and identification of novel dhfr alleles. J Infect Dis 194:189-97
Takala, S L; Escalante, A A; Branch, O H et al. (2006) Genetic diversity in the Block 2 region of the merozoite surface protein 1 (MSP-1) of Plasmodium falciparum: additional complexity and selection and convergence in fragment size polymorphism. Infect Genet Evol 6:417-24
Escalante, Ananias A; Cornejo, Omar E; Freeland, Denise E et al. (2005) A monkey's tale: the origin of Plasmodium vivax as a human malaria parasite. Proc Natl Acad Sci U S A 102:1980-5
Escalante, Ananias A; Cornejo, Omar E; Rojas, Ascanio et al. (2004) Assessing the effect of natural selection in malaria parasites. Trends Parasitol 20:388-95

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