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Cord blood IgG and the risk of severe Plasmodium falciparum malaria in the first year of life.

机译:生命第一年的脐带血IgG和严重恶性疟原虫疟疾的风险。

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摘要

Young infants are less susceptible to severe episodes of malaria but the targets and mechanisms of protection are not clear. Cord blood antibodies may play an important role in mediating protection but many studies have examined their association with the outcome of infection or non-severe malaria. Here, we investigated whether cord blood IgG to Plasmodium falciparum merozoite antigens and antibody-mediated effector functions were associated with reduced odds of developing severe malaria at different time points during the first year of life. We conducted a case-control study of well-defined severe falciparum malaria nested within a longitudinal birth cohort of Kenyan children. We measured cord blood total IgG levels against five recombinant merozoite antigens and antibody function in the growth inhibition activity and neutrophil antibody-dependent respiratory burst assays. We also assessed the decay of maternal antibodies during the first 6months of life. The mean antibody half-life range was 2.51months (95% confidence interval (CI): 2.19-2.92) to 4.91months (95% CI: 4.47-6.07). The rate of decline of maternal antibodies was inversely proportional to the starting concentration. The functional assay of antibody-dependent respiratory burst activity predicted significantly reduced odds of developing severe malaria during the first 6months of life (Odds ratio (OR) 0.07, 95% CI: 0.007-0.74, P=0.007). Identification of the targets of antibodies mediating antibody-dependent respiratory burst activity could contribute to the development of malaria vaccines that protect against severe episodes of malaria in early infancy.
机译:幼儿不太容易患上严重的疟疾,但保护的目标和机制尚不清楚。脐带血抗体可能在介导保护中起重要作用,但是许多研究已经检查了它们与感染或非严重疟疾结局的关系。在这里,我们研究了在生命的第一年中不同时间点,针对恶性疟原虫裂殖子抗原的脐带血IgG和抗体介导的效应子功能是否与降低患上严重疟疾的几率降低有关。我们对肯尼亚儿童的纵向出生队列中嵌套的明确的严重恶性疟疾进行了病例对照研究。我们在生长抑制活性和中性粒细胞抗体依赖性呼吸爆发试验中测量了针对五个重组裂殖子抗原的脐血总IgG水平和抗体功能。我们还评估了生命头6个月中母源抗体的衰减。平均抗体半衰期范围为2.51个月(95%置信区间(CI):2.19-2.92)至4.91个月(95%CI:4.47-6.07)。母源抗体的下降速度与起始浓度成反比。抗体依赖性呼吸爆发活性的功能测定可预测出生后头6个月内发生严重疟疾的几率显着降低(几率(OR)0.07,95%CI:0.007-0.74,P = 0.007)。鉴定介导抗体依赖性呼吸爆发活性的抗体靶标可有助于开发疟疾疫苗,以预防婴儿期早期的严重疟疾发作。

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