Estimating sequestered parasite population dynamics in cerebral malaria
Estimating sequestered parasite population dynamics in cerebral malaria
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DOI：
10.1073/pnas.95.13.7620
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发表时间：
1998-06-23
影响因子：
11.1
通讯作者：
Kwiatkowski, D
中科院分区：
文献类型：
--
作者：
Gravenor, MB;van Hensbroek, MB;Kwiatkowski, D
疟疾的临床研究由于缺乏估计隔离在组织中的寄生虫数量的方法而受到阻碍，因为这些寄生虫被认为是危及生命的并发症如脑型疟疾的发病机制的关键。我们提出了一种方法，估计这个隐藏的人口通过使用临床观察外周寄生虫血症结合年龄结构的数学模型的寄生虫红细胞周期，应用该模型的数据，从217冈比亚儿童接受治疗的脑型疟疾的结论是，虽然蒿甲醚清除寄生虫血症更迅速地比奎宁，隔离的寄生虫的清除是类似的tno药物。估计的隔离质量，被发现是一个更直接的预测致命的结果比临床观察到的寄生虫血症，这种方法允许一个连续的分析隔离寄生虫种群动态的儿童患有脑型疟疾，和结果提供了一个可能的解释，为什么蒿甲醚提供的优势不如预期的奎宁在降低死亡率，尽管它对循环寄生虫的快速影响。
Clinical investigation of malaria is hampered by the lack of a method for estimating the number of parasites that are sequestered in the tissues, for it is these parasites that are thought to be crucial to the pathogenesis of life-threatening complications such as cerebral malaria. We present a method of estimating this hidden population by using clinical observations of peripheral parasitemia combined with an age-structured mathematical model of the parasite erythrocyte cycle, Applying the model to data from 217 Gambian children undergoing treatment for cerebral malaria ne conclude that although artemether clears parasitemia more rapidly than quinine, the clearance of sequestered parasites is similar for the tno drugs. The estimated sequestered mass,vas found to be a more direct predictor of fatal outcome than clinically observed parasitemia, This method allows a sequential analysis of sequestered parasite population dynamics in children suffering from cerebral malaria, and the results offer a possible explanation for why artemether provides less advantage than might have been expected over quinine in reducing mortality despite its rapid effect on circulating parasites.