Heritability of the human infectious reservoir of malaria parasites.

Yaye Ramatoulaye Lawaly,Fatoumata Diène Sarr,Jaranit Kaewkunwal,Adama Tall,Thanyachai Sura,Laurence Baril,Pratap Singhasivanon,Anavaj Sakuntabhai,Christophe Rogier,Cheikh Sokhna,Chalisa Louicharoen,Bradley S Schneider,Anaïs Levescot,Issarang Nuchprayoon,Laurence Marrama,Chayanon Peerapittayamongkol,Waraphon Phimpraphi,Arthur M Talman ,Isabelle Casadémont ,Didier Ménard ,Jean‐François Trape ,Frédéric Ariey ,Odile Mercereau−Puijalon ,Lassana Konaté ,R E L Paul

doi:10.1371/journal.pone.0011358

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.

Highlights

Transmission of malaria parasites from man to mosquito depends on the production of gametocyte sexual parasite stages in the human host that are subsequently taken up by a mosquito during a bloodmeal
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
Such cues are associated with symptomatic episodes of malaria and it is well established that asymptomatic infections can generate gametocytes and infect mosquitoes [8,9,10]

Summary

Introduction

Transmission of malaria parasites from man to mosquito depends on the production of gametocyte sexual parasite stages in the human host that are subsequently taken up by a mosquito during a bloodmeal. For Plasmodium falciparum, the etiological agent of malignant tertian malaria, sexual stage differentiation (gametocytogenesis) from asexual parasites occurs in the blood of the human host. Both in vitro and in vivo studies emphasise the importance of environmental stimuli in modulating gametocytogenesis [1,2]. Gametocyte carriage has been associated with a worsening blood environment for the parasite (e.g. fever responses, anaemia, and the presence of reticulocytes) [5,6,7] Such cues are associated with symptomatic episodes of malaria and it is well established that asymptomatic infections can generate gametocytes and infect mosquitoes [8,9,10]. Virtually no attention has been paid to the role of human genetics in eliciting the production of parasite transmission stages, the gametocytes, and enhancing the spread of disease

Methods

Results

Discussion

Conclusion