Dataset Information

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. METHODS AND FINDINGS: 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.

SUBMITTER: Lawaly YR

PROVIDER: S-EPMC2894056 | biostudies-other | 2010

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Heritability of the human infectious reservoir of malaria parasites.

Lawaly Yaye Ramatoulaye YR 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

PloS one 20100629 6

<h4>Background</h4>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.<h4>Methods and findings</h4>We analysed four longitudinal family-based cohort studies from Senegal and Thailand followed for 2-8 year ...[more]

PMID: 20613877

Similar Datasets

Project description:Malaria transmission remains high in Sub-Saharan Africa despite large-scale implementation of malaria control interventions. A comprehensive understanding of the transmissibility of infections to mosquitoes may guide the design of more effective transmission reducing strategies. The impact of P. falciparum sexual stage immunity on the infectious reservoir for malaria has never been studied in natural settings. Repeated measurements were carried out at start-wet, peak-wet and dry season, and provided data on antibody responses against gametocyte/gamete antigens Pfs48/45 and Pfs230 as anti-gametocyte immunity. Data on high and low-density infections and their infectiousness to anopheline mosquitoes were obtained using quantitative molecular methods and mosquito feeding assays, respectively. An event-driven model for P. falciparum sexual stage immunity was developed and fit to data using an agent based malaria model infrastructure. We found that Pfs48/45 and Pfs230 antibody densities increased with increasing concurrent gametocyte densities; associated with 55-70% reduction in oocyst intensity and achieved up to 44% reduction in proportions of infected mosquitoes. We showed that P. falciparum sexual stage immunity significantly reduces transmission of microscopic (p < 0.001) but not submicroscopic (p = 0.937) gametocyte infections to mosquitoes and that incorporating sexual stage immunity into mathematical models had a considerable impact on the contribution of different age groups to the infectious reservoir of malaria. Human antibody responses to gametocyte antigens are likely to be dependent on recent and concurrent high-density gametocyte exposure and have a pronounced impact on the likelihood of onward transmission of microscopic gametocyte densities compared to low density infections. Our mathematical simulations indicate that anti-gametocyte immunity is an important factor for predicting and understanding the composition and dynamics of the human infectious reservoir for malaria.

Dataset Information

Heritability of the human infectious reservoir of malaria parasites.

Publications

Heritability of the human infectious reservoir of malaria parasites.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets