title: A molecular epidemiological study of var gene diversity to characterize the reservoir of Plasmodium falciparum in humans in Africa.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Medical Parasitology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Chen
authors.forename: Alyssa E
authors.initials: AE
authors.lastname: Barry
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Leliwa-Sytek
authors.forename: Terry-Ann
authors.initials: TA
authors.lastname: Smith
authors.forename: Ingrid
authors.initials: I
authors.lastname: Peterson
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Brown
authors.forename: Florence
authors.initials: F
authors.lastname: Migot-Nabias
authors.forename: Philippe
authors.initials: P
authors.lastname: Deloron
authors.forename: Moses M
authors.initials: MM
authors.lastname: Kortok
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Johanna P
authors.initials: JP
authors.lastname: Daily
authors.forename: Daouda
authors.initials: D
authors.lastname: Ndiaye
authors.forename: Ousmane
authors.initials: O
authors.lastname: Sarr
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
authors.forename: Karen P
authors.initials: KP
authors.lastname: Day
mesh_terms: D000349:Africa / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D018503:Genome, Protozoan / Q000235:genetics; D005843:Geography; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000635:transmission; D018895:Microsatellite Repeats / Q000235:genetics; D017720:Molecular Epidemiology; D010963:Plasmodium falciparum / Q000235:genetics* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics*
chemical_list: D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum