Malaria parasite diversity and transmission intensity affect development of parasitological immunity in a mathematical model.
Malaria parasite diversity and transmission intensity affect development of parasitological immunity in a mathematical model.
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DOI：
10.1186/1475-2875-11-419
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发表时间：
2012-12-15
期刊：
影响因子：
3
通讯作者：
Eckhoff PA
中科院分区：
文献类型：
--
作者：
Eckhoff PA
针对疟疾的寄生虫免疫的发展影响检测感染的能力、当地人类寄生虫宿主感染蚊子的效率以及对寄生虫重新引入先前清理区域的反应。在检测到的患病率和平均寄生虫血症中观察到相似的年龄趋势，基线传播的变化超过一个数量级，这使得简单的暴露驱动解释变得复杂。数学模型通常采用年龄依赖性免疫因素来匹配观察到的趋势，而本模型使用寄生虫传播动力学的新详细机制模型，通过寄生虫多样性机制来解释年龄趋势。对坦桑尼亚和尼日利亚的多个现场进行了说明性模拟，并在计算机中重新创建了观察到的寄生虫流行的年龄趋势和季节性，为观测数据提供了可能的机制解释。为每个位置重新创建了测量的寄生虫血症中观察到的时间动态，并研究了年龄流行率输出。疟疾表面抗原的人群水平多样性的增加延迟了广泛的寄生虫免疫的发展。具有高度多样性的当地寄生虫种群可以在传播强度变化超过一个数量级的情况下重现观察到的年龄流行趋势。人类免疫和寄生虫抗原多样性的机制模型可以重建观察到的时间模式，以在广泛的传播强度范围内发展寄生虫免疫。这对于疾病负担在人群中的分布、人类传播媒介、消除运动的设计以及潜在疫苗的开发和推广都有影响。
The development of parasitological immunity against malaria affects the ability to detect infection, the efficiency of the local human parasite reservoir at infecting mosquitoes, and the response to reintroduction of parasites to previously cleared areas. Observations of similar age-trends in detected prevalence and mean parasitaemia across more than an order-of-magnitude of variation in baseline transmission complicate simple exposure-driven explanations. Mathematical models often employ age-dependent immune factors to match the observed trends, while the present model uses a new detailed mechanistic model of parasite transmission dynamics to explain age-trends through the mechanism of parasite diversity. Illustrative simulations are performed for multiple field sites in Tanzania and Nigeria, and observed age-trends and seasonality in parasite prevalence are recreated in silico, proffering possible mechanistic explanations of the observational data. Observed temporal dynamics in measured parasitaemia are recreated for each location and age-prevalence outputs are studied. Increasing population-level diversity in malaria surface antigens delays development of broad parasitological immunity. A local parasite population with high diversity can recreate the observed trends in age-prevalence across more than an order of magnitude of variation in transmission intensities. Mechanistic models of human immunity and parasite antigen diversity can recreate the observed temporal patterns for the development of parasitological immunity across a wide range of transmission intensities. This has implications for the distribution of disease burden across the population, the human transmission reservoir, design of elimination campaigns, and development and roll-out of potential vaccines.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3
作者：
Eckhoff PA
通讯作者：
Eckhoff PA
影响因子：
3
作者：
Depinay, JMO;Mbogo, CM;McKenzie, FE
通讯作者：
McKenzie, FE
DOI：
10.4269/ajtmh.2004.71.103
发表时间：
2004-08-01
影响因子：
3.3
作者：
De Castro, MC;Yamagata, Y;Singer, BH
通讯作者：
Singer, BH
影响因子：
15.8
作者：
Griffin, Jamie T.;Hollingsworth, T. Deirdre;Ghani, Azra C.
通讯作者：
Ghani, Azra C.