Effect of red blood cell variants on childhood malaria in Mali: a prospective cohort study
Effect of red blood cell variants on childhood malaria in Mali: a prospective cohort study
复制标题
DOI：
10.1016/s2352-3026(15)00043-5
复制
发表时间：
2015-04-01
影响因子：
24.7
通讯作者：
Fairhurst, Rick M.
中科院分区：
文献类型：
--
作者：
Lopera-Mesa, Tatiana M.;Doumbia, Saibou;Fairhurst, Rick M.
背景红细胞变异体保护非洲儿童免受严重恶性疟疾的侵袭。然而，它们对轻度疾病和寄生虫密度的个体和相互作用的影响，以及它们被年龄相关免疫所改变的情况，人们知之甚少。在这项研究中，我们解决了马里儿童疟疾风险和恶性疟原虫密度的前瞻性队列研究中的这些知识差距。方法肯涅罗巴疟疾先天防御研究(儿童疟疾)是一项为期4年的前瞻性队列研究，对象是2008至2011年间在马里进行的6个月至17岁的儿童。红细胞变异包括血红蛋白S(HBs)、血红蛋白C(Hbc)、α地中海贫血症、ABO血型和由X连锁A等位基因编码的葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症。主要结果是疟疾发病率，以一段时间内无并发症或严重疟疾发作的数量来衡量。次要结果是疟疾发作时的寄生虫密度。我们用准泊松回归对发病率比率进行建模，并使用广义估计方程分析寄生虫密度。这项研究在ClinicalTrials.gov注册，编号为NCT00669084。在2008年5月1日至2011年12月29日期间，我们招募了1586名儿童参加这项研究。我们成功地为其中1543名儿童输入了所有五种红细胞变异体，因此他们构成了可评估的人群，在2656个儿童年的跟踪调查中，我们诊断出4091例疟疾发作。在这1543名儿童中，红细胞变异很常见，出现频率如下：镰状细胞性状(HbAS)220(14%)，HbAC杂合性(HbAC)103(7%)，地中海贫血438(28%)，O型621(40%)，G6PD缺乏症72(9%)男孩和158(20%)776女孩。疟疾总发病率为1.54次/儿童年，3岁时为2.78次/儿童年，17岁时为0.40次/年。HbAS儿童疟疾发病率低于HbAA正常儿童(校正发病率比[aIRR]0.66[95%CI 0.59~0.75]，P<0.05)。
Background Red blood cell variants protect African children from severe falciparum malaria. However, their individual and interactive effects on mild disease and parasite density, and their modification by age-dependent immunity, are poorly understood. In this study, we address these knowledge gaps in a prospective cohort study of malaria risk and Plasmodium falciparum densities in Malian children.Methods The Kenieroba Innate Defense Study for Malaria (KIDS-Malaria) was a 4-year prospective cohort study of children aged 6 months to 17 years undertaken in Mali between 2008 and 2011. Red blood cell variants were haemoglobin S (HbS), haemoglobin C (HbC), alpha thalassaemia, ABO blood groups, and glucose-6-phosphate dehydrogenase (G6PD) deficiency encoded by the X-linked A-allele. The primary outcome was malaria incidence, measured as the number of uncomplicated or severe malaria episodes over time. The secondary outcome was parasite density at the time of a malaria episode. We modelled incidence rate ratios with quasi-Poisson regression and we analysed parasite densities using generalised estimating equations. This study is registered with ClinicalTrials.gov, number NCT00669084.Findings Between May 1, 2008, and Dec 29, 2011, we enrolled 1586 children into the study. We successfully typed all five red blood cell variants for 1543 of these children, who therefore constituted the evaluable population and in whom we diagnosed 4091 malaria episodes over 2656 child-years of follow-up. In these 1543 children, red blood cell variants were common, and occurred at the following frequencies: sickle cell trait (HbAS) 220 (14%), HbC heterozygosity (HbAC) 103 (7%), a thalassaemia 438 (28%), type O blood group 621 (40%), and G6PD deficiency 72 (9%) in 767 boys and 158 (20%) in 776 girls. The overall incidence of malaria was 1.54 episodes per child-year of follow-up, ranging from 2.78 episodes per child-year at age 3 years to 0.40 episodes per child-year at age 17 years. The malaria incidence was lower in HbAS children than in HbAA children with normal haemoglobin (adjusted incidence rate ratio [aIRR] 0.66 [95% CI 0.59-0.75], p