BACKGROUND Multiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear. METHODS Data from a longitudinal cohort study conducted in 3 sub-counties in Uganda was used to quantify associations between three red blood cell variants Hb [AA, AS, S (rs334)], alpha thalassaemia 3.7 kb deletion, and glucose-6-phosphate dehydrogenase deficiency A-(G6PD 202A genotype) and malaria incidence, parasite prevalence, parasite density (a measure of anti-parasite immunity) and body temperature adjusted for parasite density (a measure of anti-disease immunity). All analyses were adjusted for age, average household entomological inoculation rate, and study site. Results for all variants were compared to those for wild type genotypes. RESULTS In children, HbAS was associated, compared to wild type, with a lower incidence of malaria (IRR = 0.78, 95% CI 0.66-0.92, p = 0.003), lower parasite density upon infection (PR = 0.66, 95% CI 0.51-0.85, p = 0.001), and lower body temperature for any given parasite density (- 0.13 ℃, 95% CI - 0.21, - 0.05, p = 0.002). In children, HbSS was associated with a lower incidence of malaria (IRR = 0.17, 95% CI 0.04-0.71, p = 0.02) and lower parasite density upon infection (PR = 0.31, 95% CI 0.18-0.54, p < 0.001). α-/αα thalassaemia, was associated with higher parasite prevalence in both children and adults (RR = 1.23, 95% CI 1.06-1.43, p = 0.008 and RR = 1.52, 95% CI 1.04-2.23, p = 0.03, respectively). G6PD deficiency was associated with lower body temperature for any given parasite density only among male hemizygote children (- 0.19 ℃, 95% CI - 0.31, - 0.06, p = 0.003). CONCLUSION RBC variants were associated with non-severe malaria outcomes. Elucidation of the mechanisms by which they confer protection will improve understanding of genetic protection against malaria.

中文翻译：

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乌干达三个地区儿童和成年人中红细胞变异与疟疾之间的关联：一项前瞻性队列研究。

背景技术多种红细胞（RBC）变体似乎提供针对最严重形式的恶性疟原虫疟疾的保护。这些变体与单纯性疟疾之间的关联尚不清楚。方法在乌干达的三个子县进行的纵向队列研究数据用于量化三种红细胞变异株Hb [AA，AS，S（rs334）]，α地中海贫血3.7 kb缺失和6磷酸葡萄糖之间的关联脱氢酶缺乏症A-（G6PD 202A基因型）和疟疾发病率，寄生虫患病率，寄生虫密度（衡量抗寄生虫免疫力）和针对寄生虫密度调整的体温（衡量抗疾病免疫力）。所有分析均根据年龄，平均家庭昆虫接种率和研究地点进行了调整。将所有变体的结果与野生型基因型的结果进行比较。结果在儿童中，与野生型相比，HbAS与疟疾发病率较低（IRR = 0.78，95％CI 0.66-0.92，p = 0.003），感染后的寄生虫密度较低（PR = 0.66，95％CI 0.51）相关。 -0.85，p = 0.001），并在任何给定的寄生虫密度下降低体温（-0.13℃，95％CI-0.21，-0.05，p = 0.002）。在儿童中，HbSS与较低的疟疾发病率（IRR = 0.17，95％CI 0.04-0.71，p = 0.02）和较低的感染后寄生虫密度（PR = 0.31，95％CI 0.18-0.54，p <0.001） 。α-/αα地中海贫血与儿童和成人中较高的寄生虫患病率相关（分别为RR = 1.23，95％CI 1.06-1.43，p = 0.008和RR = 1.52，95％CI 1.04-2.23，p = 0.03） 。对于任何给定的寄生虫密度，仅在男性半合子儿童中，G6PD缺乏与较低的体温相关（-0.19℃，95％CI-0.31，-0.06，p = 0.003）。结论RBC变异与非严重疟疾预后相关。阐明它们赋予保护的机制将增进人们对疟疾遗传保护的了解。