Hastings I M
Laboratoire Génétique Moléculaire des Parasites et des Vecteurs, ORSTOM, Montpellier, France.
Parasitology. 1997 Aug;115 ( Pt 2):133-41. doi: 10.1017/s0031182097001261.
A general method of investigating parasite population genetics is presented and used to investigate the evolution of drug resistance in Plasmodium. The most important biological factor is the nature of the control, presumably through host immunity, of the malarial infection. Two models are examined: a 'generalized immunity' (GI) model in which immunity regulates the overall level of infection, and a 'specific immunity' (SI) model in which each clone within the infection is regulated independently. These models are used to investigate 3 critical factors in the evolution of resistance: (i) the frequency of resistant alleles in the population prior to drug use, (ii) the dynamics of resistance following drug application and (iii) the magnitude of threshold frequencies below which resistance will not evolve. These analyses also identify the implicit assumptions made in several previous models, reconcile their differing conclusions and allow a more informed debate about the practical application of drugs.
本文提出了一种研究寄生虫种群遗传学的通用方法，并将其用于研究疟原虫耐药性的演变。最重要的生物学因素是疟疾感染控制的本质，推测是通过宿主免疫来实现的。研究了两种模型：一种是“广义免疫”（GI）模型，其中免疫调节感染的总体水平；另一种是“特异性免疫”（SI）模型，其中感染内的每个克隆都被独立调节。这些模型用于研究耐药性演变中的三个关键因素：（i）用药前种群中耐药等位基因的频率，（ii）用药后耐药性的动态变化，以及（iii）低于该频率耐药性不会演变的阈值频率大小。这些分析还确定了先前几个模型中隐含的假设，调和了它们不同的结论，并为关于药物实际应用的更明智辩论提供了依据。
