Park Andrew W, Haven James, Kaplan Ray, Gandon Sylvain
Odum School of Ecology, University of Georgia, Athens, GA 30602, USA Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
Odum School of Ecology, University of Georgia, Athens, GA 30602, USA.
Biol Lett. 2015 Nov;11(11). doi: 10.1098/rsbl.2015.0783.
Drug resistance is a long-standing economic, veterinary and human health concern in human and animal populations. Efficacy of prophylactic drug treatments targeting a particular pathogen is often short-lived, as drug-resistant pathogens evolve and reach high frequency in a treated population. Methods to combat drug resistance are usually costly, including use of multiple drugs that are applied jointly or sequentially, or development of novel classes of drugs. Alternatively, there is growing interest in exploiting untreated host populations, refugia, for the management of drug resistance. Refugia do not experience selection for resistance, and serve as a reservoir for native, drug-susceptible pathogens. The force of infection from refugia may dilute the frequency of resistant pathogens in the treated population, potentially at an acceptable cost in terms of overall disease burden. We examine this concept using a simple mathematical model that captures the core mechanisms of transmission and selection common to many host-pathogen systems. We identify the roles of selection and gene flow in determining the utility of refugia.
耐药性是人类和动物群体中长期存在的经济、兽医和人类健康问题。针对特定病原体的预防性药物治疗效果往往是短暂的，因为耐药病原体不断进化并在接受治疗的群体中达到高频率。对抗耐药性的方法通常成本高昂，包括联合或序贯使用多种药物，或开发新型药物类别。另外，利用未接受治疗的宿主群体（避难所）来管理耐药性的兴趣日益浓厚。避难所不会经历耐药性选择，并且作为天然的、对药物敏感的病原体的储存库。来自避难所的感染压力可能会稀释接受治疗群体中耐药病原体的频率，就总体疾病负担而言，这可能以可接受的成本实现。我们使用一个简单的数学模型来研究这一概念，该模型捕捉了许多宿主-病原体系统共有的传播和选择核心机制。我们确定了选择和基因流动在确定避难所效用方面的作用。
