Heritability of the Human Infectious Reservoir of Malaria Parasites

Abstract

BackgroundStudies 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.Methods and FindingsWe 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.ConclusionsThe 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.

Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

“…Gametocyte carriage and malaria transmission potential were also related to human genetic variation at the ␤-globin locus, with a higher gametocyte density and/or higher infection rate for individuals with the HbAS, HbAC, or HbCC genotype than for those with the HbAA ␤-globin genotype (164,387). Further evidence of a genetic component of gametocyte carriage was provided by Lawaly et al (240). They demonstrated a significant heritable contribution to gametocyte prevalence in individuals from Senegal and Thailand.…”

Impact of Mosquito Bites on Asexual Parasite Density and Gametocyte Prevalence in Asymptomatic Chronic Plasmodium falciparum Infections and Correlation with IgE and IgG Titers

“…The extracted RNA was directly analyzed or stored at Ϫ80°C. RT-PCR was carried out as described previously (26). Briefly, the "Plasmodium falciparum meiotic recombination protein DMC1-like protein" gene (GenBank accession number AF356553) was selected because it is expressed exclusively in gametocytes (27) and contains introns.…”

Human Genetic Contribution to the Outcome of Infection with Malaria Parasites

“…By contrast, there was no heritability associated with the production of gametocytes for P. falciparum or P. vivax symptomatic infections. Increased gametocyte carriage has been observed in individuals with HbC (Gouagna et al, 2010) and HbS, although its contribution was small (Lawaly et al, 2010). Clearly there are other genes implicated in eliciting gametocyte production by the parasite.…”