Investigating antigenic variation and other parasite-host interactions in Plasmodium falciparum infections in naive hosts
Investigating antigenic variation and other parasite-host interactions in Plasmodium falciparum infections in naive hosts
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DOI：
10.1017/s0031182003004608
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发表时间：
2004-04-01
期刊：
影响因子：
2.4
通讯作者：
Cheng, Q
中科院分区：
文献类型：
--
作者：
Gatton, ML;Cheng, Q
疟疾感染在宿主内动态的数学模型为探索宿主-寄生虫相互作用的各个方面提供了一个有价值的工具，这些方面无法通过实验进行研究。本文预测了2种寄生虫品系/类群的几个重要参数值：寄生虫PfEMP1转换率、宿主抗PfEMP1抗体的动态以及与特异性和非特异性宿主免疫反应相关的参数。一个随机模拟模型的恶性疟原虫感染的宿主动力学在幼稚的宿主被用来作出这些预测。该模型结合了一个新的过程来模拟寄生虫的抗原变异，以及宿主的特异性和非特异性免疫反应。将模型输出与一系列已发表的统计数据进行比较，表明该模型能够再现临床恶性疟原虫感染的特征，包括典型的复发行为。利用该模型，我们探索了在感染早期快速总体抗原变异率的假设开关机制，并发现当var基因分成两组时，它与慢性感染兼容；快慢切换。
Mathematical models of the in-host dynamics of malaria infections provide a valuable tool to explore aspects of the host-parasite interaction that are not possible to investigate experimentally. This paper presents predictions of several important parameter values for 2 parasite strains/groups: parasite PfEMP1 switching rates, dynamics of host anti-PfEMP1 antibodics and parameters related to specific and non-specific host immune responses. A stochastic simulation model of the in-host dynamics of Plasmodium falciparum infections in naive hosts was used to make these predictions. This model incorporates a novel process to simulate antigenic variation by the parasite, and specific and non-specific immune responses by the host. Comparison of model output to a range of published statistics indicated that the model is capable of reproducing the features of clinical P. falciparum infections, including the characteristic recrudescent behaviour. Using the model, we explored the hypothesized switching mechanism of a fast overall rate of antigenic variation early in an infection and found that it is compatible with chronic infections when the var genes are split into 2 groups; fast and slow switching.