Restif Olivier, Grenfell Bryan T
Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
Proc Biol Sci. 2006 Feb 22;273(1585):409-16. doi: 10.1098/rspb.2005.3335.
Models for the diversity and evolution of pathogens have branched into two main directions: the adaptive dynamics of quantitative life-history traits (notably virulence) and the maintenance and invasion of multiple, antigenically diverse strains that interact with the host's immune memory. In a first attempt to reconcile these two approaches, we developed a simple modelling framework where two strains of pathogens, defined by a pair of life-history traits (infectious period and infectivity), interfere through a given level of cross-immunity. We used whooping cough as a potential example, but the framework proposed here could be applied to other acute infectious diseases. Specifically, we analysed the effects of these parameters on the invasion dynamics of one strain into a population, where the second strain is endemic. Whereas the deterministic version of the model converges towards stable coexistence of the two strains in most cases, stochastic simulations showed that transient epidemic dynamics can cause the extinction of either strain. Thus ecological dynamics, modulated by the immune parameters, eventually determine the adaptive value of different pathogen genotypes. We advocate an integrative view of pathogen dynamics at the crossroads of immunology, epidemiology and evolution, as a way towards efficient control of infectious diseases.
定量生活史特征(尤其是毒力)的适应性动态,以及与宿主免疫记忆相互作用的多种抗原性不同菌株的维持和入侵。作为调和这两种方法的首次尝试,我们开发了一个简单的建模框架,其中由一对生活史特征(感染期和感染力)定义的两种病原体菌株,通过给定水平的交叉免疫相互干扰。我们以百日咳为例,但这里提出的框架可应用于其他急性传染病。具体而言,我们分析了这些参数对一种菌株入侵另一种菌株为地方病的人群的动态影响。虽然模型的确定性版本在大多数情况下趋向于两种菌株的稳定共存,但随机模拟表明,短暂的流行动态可能导致任何一种菌株灭绝。因此,由免疫参数调节的生态动态最终决定了不同病原体基因型的适应值。我们主张在免疫学、流行病学和进化的交叉点上对病原体动态进行综合观察,以此作为有效控制传染病的一种方式。