Heritability of the human infectious reservoir of malaria parasites.
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.
Lawaly
Yaye Ramatoulaye
YR
Institut Pasteur de Dakar, Laboratoire d'Entomologie Médicale, Dakar, Senegal.
Sakuntabhai
Anavaj
A
Marrama
Laurence
L
Konate
Lassana
L
Phimpraphi
Waraphon
W
Sokhna
Cheikh
C
Tall
Adama
A
Sarr
Fatoumata Diène
FD
Peerapittayamongkol
Chayanon
C
Louicharoen
Chalisa
C
Schneider
Bradley S
BS
Levescot
Anaïs
A
Talman
Arthur
A
Casademont
Isabelle
I
Menard
Didier
D
Trape
Jean-François
JF
Rogier
Christophe
C
Kaewkunwal
Jaranit
J
Sura
Thanyachai
T
Nuchprayoon
Issarang
I
Ariey
Frederic
F
Baril
Laurence
L
Singhasivanon
Pratap
P
Mercereau-Puijalon
Odile
O
Paul
Rick
R
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