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Background The heritable haemoglobinopathy [α.sup.+]-thalassaemia is caused by the reduced synthesis of α-globin chains that form part of normal adult haemoglobin (Hb). Individuals homozygous for [α.sup.+]-thalassaemia have microcytosis and an increased erythrocyte count. [α.sup.+]-Thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration, 50 g/l), but does not influence parasite count. We tested the hypothesis that the erythrocyte indices associated with [α.sup.+]-thalassaemia homozygosity provide a haematological benefit during acute malaria. Methods and Findings Data from children living on the north coast of Papua New Guinea who had participated in a case-control study of the protection afforded by [α.sup.+]-thalassaemia against severe malaria were reanalysed to assess the genotype-specific reduction in erythrocyte count and Hb levels associated with acute malarial disease. We observed a reduction in median erythrocyte count of ~1.5 x [10.sup.12]/l in all children with acute falciparum malaria relative to values in community children (p < 0.001). We developed a simple mathematical model of the linear relationship between Hb concentration and erythrocyte count. This model predicted that children homozygous for [α.sup.+]-thalassaemia lose less Hb than children of normal genotype for a reduction in erythrocyte count of >1.1 x [10.sup.12]/l as a result of the reduced mean cell Hb in homozygous [α.sup.+]-thalassaemia. In addition, children homozygous for [α.sup.+]-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA. We estimated that the haematological profile in children homozygous for [α.sup.+]-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09). Conclusions The increased erythrocyte count and microcytosis in children homozygous for [α.sup.+]-thalassaemia may contribute substantially to their protection against SMA. A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum. This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia. Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage., Introduction The heritable haemoglobinopathy a-thalassaemia is one of the most common monogenic disorders of humans [1]. The different forms of [α.sup.+]-thalassaemia result from deletions (3.7 or 4.2 kb) or point [...]

Over the past decade, there has been a substantial increase globally in the coverage of effective interventions to reduce morbidity and mortality from malaria. Insecticide-treated bed nets (ITNs), indoor residual [...]

Background: One of the criteria to objectively prioritize merozoite antigens for malaria vaccine development is the demonstration that naturally acquired antibodies are associated with protection from malaria. However, published evidence of the protective effect of these antibodies is conflicting. Methods and Findings: We performed a systematic review with meta-analysis of prospective cohort studies examining the association between anti-merozoite immunoglobin (Ig) G responses and incidence of Plasmodium falciparum malaria. Two independent researchers searched six databases and identified 33 studies that met predefined inclusion and quality criteria, including a rigorous definition of symptomatic malaria. We found that only five studies were performed outside subSaharan Africa and that there was a deficiency in studies investigating antibodies to leading vaccine candidates merozoite surface protein [(MSP)-1.sub.42] and erythrocyte binding antigen (EBA)-175. Meta-analyses of most-studied antigens were conducted to obtain summary estimates of the association between antibodies and incidence of P. falciparum malaria. The largest effect was observed with IgG to MSP-3 C terminus and [(MSP)-1.sub.19] (responders versus nonresponders, 54%, 95% confidence interval [CI] [33%-68%] and 18% [4%-30%] relative reduction in risk, respectively) and there was evidence of a dose-response relationship. A tendency towards protective risk ratios (RR Conclusions: These findings are valuable for advancing vaccine development by providing evidence supporting merozoite antigens as targets of protective immunity in humans, and to help identify antigens that confer protection from malaria. Further prospective cohort studies that include a larger number of lead antigens and populations outside Africa are greatly needed to ensure generalizability of results. The reporting of results needs to be standardized to maximize comparability of studies. We therefore propose a set of guidelines to facilitate the uniform reporting of malaria immuno-epidemiology observational studies., Introduction Malaria caused by Plasmodium falciparum is a leading cause of mortality and morbidity globally, particularly among young children. After repeated exposure, individuals develop effective immunity that controls blood-stage parasitaemia, [...]