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Background  The reservoir of  Plasmodium  infection in humans has traditionally been defined by blood slide positivity. This study was designed to characterize the local reservoir of infection in relation to the diverse  var  genes that encode the major surface antigen of  Plasmodium falciparum  blood stages and underlie the parasite's ability to establish chronic infection and transmit from human to mosquito.    Methodology/Principal Findings  We investigated the molecular epidemiology of the  var  multigene family at local sites in Gabon, Senegal and Kenya which differ in parasite prevalence and transmission intensity. 1839 distinct  var  gene types were defined by sequencing DBLα domains in the three sites. Only 76 (4.1%)  var  types were found in more than one population indicating spatial heterogeneity in  var  types across the African continent. The majority of  var  types appeared only once in the population sample. Non-parametric statistical estimators predict in each population at minimum five to seven thousand distinct  var  types. Similar diversity of  var  types was seen in sites with different parasite prevalences.    Conclusions/Significance    Var  population genomics provides new insights into the epidemiology of  P. falciparum  in Africa where malaria has never been conquered. In particular, we have described the extensive reservoir of infection in local African sites and discovered a unique  var  population structure that can facilitate superinfection through minimal overlap in  var  repertoires among parasite genomes. Our findings show that  var  typing as a molecular surveillance system defines the extent of genetic complexity in the reservoir of infection to complement measures of malaria prevalence. The observed small scale spatial diversity of  var  genes suggests that  var  genetics could greatly inform current malaria mapping approaches and predict complex malaria population dynamics due to the import of  var  types to areas where no widespread pre-existing immunity in the population exists.

A Molecular Epidemiological Study of var Gene Diversity to Characterize the Reservoir of Plasmodium falciparum in Humans in Africa