title: Heritability of the human infectious reservoir of malaria parasites.
abstract: BACKGROUND
  Studies on human genetic factors associated with malaria have hitherto concentrated on their role in susceptibility to and protection from disease. In contrast, virtually no attention has been paid to the role of human genetics in eliciting the production of parasite transmission stages, the gametocytes, and thus enhancing the spread of disease.
  
  
  RESULTS
  We analysed four longitudinal family-based cohort studies from Senegal and Thailand followed for 2-8 years and evaluated the relative impact of the human genetic and non-genetic factors on gametocyte production in infections of Plasmodium falciparum or P. vivax. Prevalence and density of gametocyte carriage were evaluated in asymptomatic and symptomatic infections by examination of Giemsa-stained blood smears and/or RT-PCR (for falciparum in one site). A significant human genetic contribution was found to be associated with gametocyte prevalence in asymptomatic P. falciparum infections. By contrast, there was no heritability associated with the production of gametocytes for P. falciparum or P. vivax symptomatic infections. Sickle cell mutation, HbS, was associated with increased gametocyte prevalence but its contribution was small.
  
  
  CONCLUSIONS
  The existence of a significant human genetic contribution to gametocyte prevalence in asymptomatic infections suggests that candidate gene and genome wide association approaches may be usefully applied to explore the underlying human genetics. Prospective epidemiological studies will provide an opportunity to generate novel and perhaps more epidemiologically pertinent gametocyte data with which similar analyses can be performed and the role of human genetics in parasite transmission ascertained.
authors.affiliation: Institut Pasteur de Dakar, Laboratoire d'Entomologie Médicale, Dakar, Senegal.
authors.forename: Yaye Ramatoulaye
authors.initials: YR
authors.lastname: Lawaly
authors.forename: Anavaj
authors.initials: A
authors.lastname: Sakuntabhai
authors.forename: Laurence
authors.initials: L
authors.lastname: Marrama
authors.forename: Lassana
authors.initials: L
authors.lastname: Konate
authors.forename: Waraphon
authors.initials: W
authors.lastname: Phimpraphi
authors.forename: Cheikh
authors.initials: C
authors.lastname: Sokhna
authors.forename: Adama
authors.initials: A
authors.lastname: Tall
authors.forename: Fatoumata Diène
authors.initials: FD
authors.lastname: Sarr
authors.forename: Chayanon
authors.initials: C
authors.lastname: Peerapittayamongkol
authors.forename: Chalisa
authors.initials: C
authors.lastname: Louicharoen
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Schneider
authors.forename: Anaïs
authors.initials: A
authors.lastname: Levescot
authors.forename: Arthur
authors.initials: A
authors.lastname: Talman
authors.forename: Isabelle
authors.initials: I
authors.lastname: Casademont
authors.forename: Didier
authors.initials: D
authors.lastname: Menard
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Trape
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkunwal
authors.forename: Thanyachai
authors.initials: T
authors.lastname: Sura
authors.forename: Issarang
authors.initials: I
authors.lastname: Nuchprayoon
authors.forename: Frederic
authors.initials: F
authors.lastname: Ariey
authors.forename: Laurence
authors.initials: L
authors.lastname: Baril
authors.forename: Pratap
authors.initials: P
authors.lastname: Singhasivanon
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Rick
authors.initials: R
authors.lastname: Paul
mesh_terms: D000755:Anemia, Sickle Cell / Q000469:parasitology; D000818:Animals; D015331:Cohort Studies; D004197:Disease Reservoirs; D006801:Humans; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D010966:Plasmodium vivax / Q000472:pathogenicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017085:alpha-Thalassemia / Q000469:parasitology