Abstract
SummaryAn essential element for continuing transmission of Plasmodium falciparum is the availability of mature gametocytes in human peripheral circulation for uptake by mosquitoes. Natural immune responses to circulating gametocytes may play a role in reducing transmission from humans to mosquitoes. Here, antibody recognition of the surface of mature intra‐erythrocytic gametocytes produced either by a laboratory‐adapted parasite, 3D7, or by a recent clinical isolate of Kenyan origin (HL1204), was evaluated longitudinally in a cohort of Ghanaian school children by flow cytometry. This showed that a proportion of children exhibited antibody responses that recognized gametocyte surface antigens on one or both parasite lines. A subset of the children maintained detectable anti‐gametocyte surface antigen (GSA) antibody levels during the 5 week study period. There was indicative evidence that children with anti‐GSA antibodies present at enrolment were less likely to have patent gametocytaemia at subsequent visits (odds ratio = 0·29, 95% CI 0·06–1·05; P = 0·034). Our data support the existence of antigens on the surface of gametocyte‐infected erythrocytes, but further studies are needed to confirm whether antibodies against them reduce gametocyte carriage. The identification of GSA would allow their evaluation as potential anti‐gametocyte vaccine candidates and/or biomarkers for gametocyte carriage.
Highlights
Malaria is a major global health problem accounting for 198 million cases in 2014, and an estimated 584 000 deaths worldwide, 78% of which are thought to occur in African children under 5 years [1]
In a study of plasma antibodies from Gambian children with a known history of gametocyte carriage and mosquito infectivity, we found some evidence that surface antigens, identity unknown, on erythrocytes harbouring mature gametocytes (GSA) of P. falciparum clone 3D7 were recognized by a subset of children [24]
Children harboured IgG which recognized erythrocytes infected with mature gametocytes, but the level of recognition varied among individuals, and among the three time points in some individuals (Figure 4; Tables 2 and 3)
Summary
Malaria is a major global health problem accounting for 198 million cases in 2014, and an estimated 584 000 deaths worldwide, 78% of which are thought to occur in African children under 5 years [1]. Of the six parasite species causing malaria in humans, Plasmodium falciparum is the most virulent and the leading cause of morbidity and mortality among children under 5 [2]. The development of resistance to antimalarials by malaria parasites and to insecticides by mosquitoes is increasing challenges [4]. There has been renewed interest in the sexual stages of the life cycle of malaria parasites, which involve distinctive parasite forms with specific morphology, metabolism and biochemical profiles needed to establish infection in the mosquito host [5,6,7]. The sexual cycle begins with the development of gametocytes during human blood stage infection in all species, but a specific feature of P. falciparum is that only mature stage V gametocytes are seen in the peripheral circulation of infected individuals. It had been assumed that this is mediated by endothelium
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