Malaria, erythrocytic infection, and anemia.
Malaria, erythrocytic infection, and anemia.
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DOI：
10.1182/asheducation-2009.1.87
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Mohandas N
中科院分区：
文献类型：
--
作者：
Haldar K;Mohandas N
疟疾是一个主要的世界卫生问题。它由疟原虫属寄生虫感染引起。恶性疟原虫和间日疟原虫引起主要的人类疟疾，其中恶性疟原虫毒性更强。在它们的血液感染阶段，恶性疟原虫和间日疟原虫都引起贫血。由恶性疟原虫引起的严重疟疾性贫血造成了约三分之一的与疾病相关的死亡。疟疾性贫血似乎是多因素的。它涉及循环红细胞的清除增加以及骨髓中红细胞的产生减少。疟疾性贫血的分子机制在很大程度上是未知的。在过去的五年中，疟疾寄生虫配体已被研究其重塑红细胞和成熟红细胞的破坏中的可能作用。细胞因子的多态性与严重疟疾性贫血的易感性有关：这些细胞因子和疟疾“毒素”可能通过干扰红细胞生成发挥作用。最后，一些合并感染增加了对疟疾贫血的易感性，可能是因为它们加剧了疟疾引起的炎症。由于所涉及的复杂性，严重疟疾贫血的研究可能需要一种“系统方法”，以全面了解与疾病相关的红细胞生成和免疫缺陷。新的和正在出现的工具，如（i）疟疾感染的宿主控制动力学的数学建模，（ii）人脾的离体灌注以测量感染和未感染的红细胞保留，和（iii）红系祖细胞的体外发育以剖析对细胞因子失衡或疟疾毒素的反应，可能特别有助于开发综合的机制见解和治疗方法来控制这种主要和致命的疾病病理。
Malaria is a major world health problem. It results from infection of parasites belonging to the genus Plasmodium. Plasmodium falciparum and Plasmodium vivax cause the major human malarias, with P falciparum being the more virulent. During their blood stages of infection, both P falciparum and P vivax induce anemia. Severe malarial anemia caused by P falciparum is responsible for approximately a third of the deaths associated with disease. Malarial anemia appears to be multi-factorial. It involves increased removal of circulating erythrocytes as well as decreased production of erythrocytes in the bone marrow. The molecular mechanisms underlying malarial anemia are largely unknown. Over the last five years, malaria parasite ligands have been investigated for their remodeling of erythrocytes and possible roles in destruction of mature erythrocytes. Polymorphisms in cytokines have been associated with susceptibility to severe malarial anemia: these cytokines and malaria “toxins” likely function by perturbing erythropoiesis. Finally a number of co-infections increase susceptibility to malarial anemia, likely because they exacerbate inflammation caused by malaria. Because of the complexities involved, the study of severe malarial anemia may need a “systems approach” to yield comprehensive understanding of defects in both erythropoiesis and immunity associated with disease. New and emerging tools such as (i) mathematical modeling of the dynamics of host control of malarial infection, (ii) ex vivo perfusion of human spleen to measure both infected and uninfected erythrocyte retention, and (iii) in vitro development of erythroid progenitors to dissect responsiveness to cytokine imbalance or malaria toxins, may be especially useful to develop integrated mechanistic insights and therapies to control this major and fatal disease pathology.