PROJECT 1 SUMMARY: The north-east corridor of South Asia has regions with high level of P. falciparum, high levels of pathogenesis, and high levels of drug failures. In complete contrast, southern regions of India still carry predominantly P. vivax. In these regions malaria presentations appear more benign. Interestingly, profiles of malaria cases in central India are changing rapidly thus providing an extraordinary opportunity to study the factors that may be driving the evolution of malaria. The most obvious explanation for higher levels of P. falciparum in central India is that specific parasite strains are moving from "source" sites (involving high levels of virulence) to new "sink" sites, which historically presented more benign P. vivax infections. Another, more intriguing explanation is that the "whole parasite" does not need to move;specific virulence traits, coded by specific genes, may propagate by recombination across regions. Local parasites that have acquired new virulence traits may compete more effectively against local P. vivax parasite populations. In order to investigate this, one general goal of Project 1 is to systematically and carefully define the population structures of P. falciparum and P. vivax in South Asia. A second general goal is to determine if detailed genotypic analysis of parasites allow us to correlate parasite genotypes to specific disease outcomes.