Mathematical Modeling of Malaria Infection with Innate and Adaptive Immunity in Individuals and Agent-Based Communities
Mathematical Modeling of Malaria Infection with Innate and Adaptive Immunity in Individuals and Agent-Based Communities
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DOI：
10.1371/journal.pone.0034040
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发表时间：
2012-03-28
期刊：
影响因子：
3.7
通讯作者：
Davis, Timothy M. E.
中科院分区：
文献类型：
--
作者：
Gurarie, David;Karl, Stephan;Davis, Timothy M. E.
背景资料：基于代理的建模恶性疟原虫感染提供了一个有吸引力的替代传统的罗斯-麦克唐纳方法，因为它允许模拟异质社区进行现实的transmission（接种模式）。方法/主要发现：我们开发了一个新的，代理的模型，占基本的在主机的过程：寄生虫复制和其调节先天性和适应性免疫。该模型还纳入了一个简化版本的恶性疟原虫抗原变异。我们使用疟疾治疗（MT）研究的数据校准了模型，并开发了一种新的校准程序，该程序考虑了所观察到的寄生虫密度模式中的确定性和伪随机成分。使用122 MT患者的寄生虫密度模式，我们生成了大量的校准参数。由此产生的数据集作为构建和模拟异构的基于代理（AB）的MT类主机社区的基础。我们进行了几个数值实验，AB社区从以前的实地研究报告的现实接种模式，并比较了模型输出到实地观察到的疟疾流行率。总体上具有一致性，支持这种基于代理的方法在现实社区中代表传播的潜力。结论/意义：我们的方法代表了一种新型、方便且通用的恶性疟原虫感染模型方法。
Background: Agent-based modeling of Plasmodium falciparum infection offers an attractive alternative to the conventional Ross-Macdonald methodology, as it allows simulation of heterogeneous communities subjected to realistic transmission (inoculation patterns).Methodology/Principal Findings: We developed a new, agent based model that accounts for the essential in-host processes: parasite replication and its regulation by innate and adaptive immunity. The model also incorporates a simplified version of antigenic variation by Plasmodium falciparum. We calibrated the model using data from malaria-therapy (MT) studies, and developed a novel calibration procedure that accounts for a deterministic and a pseudo-random component in the observed parasite density patterns. Using the parasite density patterns of 122 MT patients, we generated a large number of calibrated parameters. The resulting data set served as a basis for constructing and simulating heterogeneous agent-based (AB) communities of MT-like hosts. We conducted several numerical experiments subjecting AB communities to realistic inoculation patterns reported from previous field studies, and compared the model output to the observed malaria prevalence in the field. There was overall consistency, supporting the potential of this agent-based methodology to represent transmission in realistic communities.Conclusions/Significance: Our approach represents a novel, convenient and versatile method to model Plasmodium falciparum infection.