Hastings I M, Mackinnon M J
Institute of Cell, Animal and Population Biology, University of Edinburgh, UK. I.Hastings@.ed.ac.uk
Parasitology. 1998 Nov;117 ( Pt 5):411-7. doi: 10.1017/s0031182098003291.
Stochastic processes play a vital role in the early stages of the evolution of drug-resistant malaria. We present a simple and flexible method for investigating these processes and understanding how they affect the emergence of drug-resistant malaria. Qualitatively different predictions can be made depending on the biological and epidemiological factors which prevail in the field. Intense intra-host competition between co-infecting clones, low numbers of genes required to encode resistance, and high drug usage all encourage the emergence of drug resistance. Drug-resistant forms present at the time drug application starts are less likely to survive than those which arise subsequently; survival of the former largely depends on how rapidly malaria population size stabilizes after drug application. In particular, whether resistance is more likely to emerge in areas of high or low transmission depends on malaria intra-host dynamics, the level of drug usage, the population regulation of malaria, and the number of genes required to encode resistance. These factors are discussed in relation to the practical implementation of drug control programmes.
随机过程在耐药性疟疾演变的早期阶段起着至关重要的作用。我们提出了一种简单灵活的方法来研究这些过程，并了解它们如何影响耐药性疟疾的出现。根据该领域中普遍存在的生物学和流行病学因素，可以做出定性不同的预测。共同感染克隆之间激烈的宿主内竞争、编码抗性所需的基因数量少以及药物使用量大，都促使耐药性的出现。药物应用开始时存在的耐药形式比随后出现的耐药形式存活的可能性小；前者的存活很大程度上取决于药物应用后疟疾种群数量稳定的速度。特别是，耐药性在高传播或低传播地区更有可能出现，这取决于疟疾宿主内动态、药物使用水平、疟疾的种群调节以及编码抗性所需的基因数量。结合药物控制计划的实际实施对这些因素进行了讨论。
