Superinfection and the evolution of resistance to antimalarial drugs
Superinfection and the evolution of resistance to antimalarial drugs
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DOI：
10.1098/rspb.2012.1064
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发表时间：
2012-09-22
影响因子：
4.7
通讯作者：
Levin, Simon
中科院分区：
文献类型：
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作者：
Klein, Eili Y.;Smith, David L.;Levin, Simon
控制疟疾的一个主要问题是耐药性的演变。生态学理论表明，病原体的重叠感染和由此产生的宿主内竞争影响了特定性状的进化。感染恶性疟原虫的个体经常感染多种寄生虫；然而，虽然这可能会改变耐药性进化的动态，但很少有可靠的数学模型来研究这一问题。我们开发了一种一般理论来模拟宿主重复感染的耐药性进化，并检查：(i)传播强度对耐药性进化速度的影响；（ii）抗性的不同生物成本的重要性；（三）电阻的最佳测量频率。我们发现，宿主内的竞争阻碍了耐药寄生虫入侵的能力和速度，特别是在传播率增加的情况下。我们还发现，减少传播的耐药生物成本不如缩短耐药感染的持续时间重要。最后，我们发现对耐药寄生虫种群的随机抽样很可能大大低估了耐药的频率。因此，在抗疟药物耐药的数学模型中考虑重复感染，对于准确预测控制耐药性的干预措施可能很重要。
A major issue in the control of malaria is the evolution of drug resistance. Ecological theory has demonstrated that pathogen superinfection and the resulting within-host competition influences the evolution of specific traits. Individuals infected with Plasmodium falciparum are consistently infected by multiple parasites; however, while this probably alters the dynamics of resistance evolution, there are few robust mathematical models examining this issue. We developed a general theory for modelling the evolution of resistance with host superinfection and examine: (i) the effect of transmission intensity on the rate of resistance evolution; (ii) the importance of different biological costs of resistance; and (iii) the best measure of the frequency of resistance. We find that within-host competition retards the ability and slows the rate at which drug-resistant parasites invade, particularly as the transmission rate increases. We also find that biological costs of resistance that reduce transmission are less important than reductions in the duration of drug-resistant infections. Lastly, we find that random sampling of the population for resistant parasites is likely to significantly underestimate the frequency of resistance. Considering superinfection in mathematical models of antimalarial drug resistance may thus be important for generating accurate predictions of interventions to contain resistance.