Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation.
Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation.
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DOI：
10.1016/j.ebiom.2016.11.011
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发表时间：
2016-12
期刊：
影响因子：
11.1
通讯作者：
Cerami, C.
中科院分区：
文献类型：
--
作者：
Goheen, M. M.;Wegmueller, R.;Bah, A.;Darboe, B.;Danso, E.;Affara, M.;Gardner, D.;Patel, J. C.;Prentice, A. M.;Cerami, C.
缺铁会对儿童造成长期不良后果，是全世界最常见的营养缺乏症。观察性研究表明，缺铁性贫血可以预防恶性疟原虫疟疾，并且一些干预试验表明，补充铁剂会通过未知的机制增加疟疾风险。这对卫生政策提出了重大挑战。我们研究了贫血如何抑制血期疟疾感染以及铁补充剂如何消除这种保护。这项观察性队列研究发生在疟疾流行地区，镰状细胞性状也很常见。我们研究了参加铁补充剂试验（ISRCTN 登记处，编号 ISRCTN07210906）的贫血儿童（135 名儿童；年龄 6-24 个月；血红蛋白 < 11 g/dl）的新鲜红细胞，其中他们接受铁（12 毫克/天）作为微量营养素粉的一部分，为期 84 天。儿童在基线、第 49 天和第 84 天捐赠红细胞，用于恶性疟原虫实验室和现场菌株的基于流式细胞术的体外生长和侵袭测定。受试者红细胞中的体外寄生虫生长是主要终点。贫血显着降低了实验室和野外恶性疟原虫菌株的体外侵袭和生长（血红蛋白每标准差变化约生长减少 10%）。贫血对红细胞期疟疾的人群影响为 15.9%，而镰状细胞性状为 3.5%。补铁 49 天后，寄生虫的生长相对于基线增加了 2.4 倍（p < 0.001），与红细胞生成的增加平行。这些结果证实并量化了贫血保护非洲儿童免受恶性疟疾的一种合理机制，这种作用远远大于镰状细胞性状所提供的保护。补充铁剂完全逆转了观察到的保护作用，因此应同时预防疟疾。非洲裔人群中常见的较低血红蛋白水平可能反映了疟疾过去的遗传选择。国家儿童健康与发展研究所、比尔和梅琳达·盖茨基金会、英国医学研究理事会 (MRC) 以及 MRC/DFID 协约下的国际发展部 (DFID)。恶性疟原虫实验室和野外菌株侵入贫血儿童的红细胞并在其中生长的效率较低。当使用接受铁补充剂 49 和 84 天的贫血儿童的红细胞时，恶性疟原虫红细胞阶段的侵袭和生长缺陷得到逆转。预防疟疾和贫血对人群水平的影响大于镰状细胞性状的影响。贫血的长期后果很严重，但很容易治疗。然而，人们仍然对铁补充剂的安全性感到担忧，特别是对于疟疾流行国家中缺乏充分医疗服务的儿童而言。我们在每日补铁 12 周之前、期间和之后使用冈比亚儿童的红细胞进行体外恶性疟原虫检测。与基线相比，贫血红细胞中恶性疟原虫的入侵和生长有所减少，而在补铁 49 天后则有所增加 (p < 0.001)，与疟原虫所喜欢的年轻红细胞的增加平行。寄生虫生长对贫血的保护作用是显着的，比镰状细胞性状提供了更大的群体水平影响。
Iron deficiency causes long-term adverse consequences for children and is the most common nutritional deficiency worldwide. Observational studies suggest that iron deficiency anemia protects against Plasmodium falciparum malaria and several intervention trials have indicated that iron supplementation increases malaria risk through unknown mechanism(s). This poses a major challenge for health policy. We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection. This observational cohort study occurred in a malaria-endemic region where sickle-cell trait is also common. We studied fresh RBCs from anemic children (135 children; age 6–24 months; hemoglobin < 11 g/dl) participating in an iron supplementation trial (ISRCTN registry, number ISRCTN07210906) in which they received iron (12 mg/day) as part of a micronutrient powder for 84 days. Children donated RBCs at baseline, Day 49, and Day 84 for use in flow cytometry-based in vitro growth and invasion assays with P. falciparum laboratory and field strains. In vitro parasite growth in subject RBCs was the primary endpoint. Anemia substantially reduced the invasion and growth of both laboratory and field strains of P. falciparum in vitro (~ 10% growth reduction per standard deviation shift in hemoglobin). The population level impact against erythrocytic stage malaria was 15.9% from anemia compared to 3.5% for sickle-cell trait. Parasite growth was 2.4 fold higher after 49 days of iron supplementation relative to baseline (p < 0.001), paralleling increases in erythropoiesis. These results confirm and quantify a plausible mechanism by which anemia protects African children against falciparum malaria, an effect that is substantially greater than the protection offered by sickle-cell trait. Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria. National Institute of Child Health and Development, Bill and Melinda Gates Foundation, UK Medical Research Council (MRC) and Department for International Development (DFID) under the MRC/DFID Concordat. P. falciparum laboratory and field strains invade and grow less efficiently in RBCs from anemic children. Deficits in invasion and growth for erythrocytic stage P. falciparum are reversed when RBCs are used from anemic children receiving iron supplementation for 49 and 84 days. The population level impact of protection against malaria from anemia was greater than that for sickle-cell trait. The long-term consequences of anemia are severe, and it is easily treatable. However, concerns remain about the safety of iron supplements, particularly for children in malaria-endemic countries lacking adequate access to health services. We used RBCs from Gambian children before, during, and after 12 weeks of daily iron supplementation for in vitro P. falciparum assays. P. falciparum invasion and growth was decreased in anemic RBCs and increased after 49 days of iron supplementation relative to baseline (p < 0.001), paralleling increases in young RBCs, which the parasite prefers. The parasite growth protection from anemia was substantial, providing greater population level impact than sickle-cell trait.
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影响因子：
6.4
作者：
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通讯作者：
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Cerami C
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