Potential impact of intermittent preventive treatment (IPT) on spread of drug-resistant malaria
Potential impact of intermittent preventive treatment (IPT) on spread of drug-resistant malaria
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DOI：
10.1371/journal.pmed.0030141
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发表时间：
2006-05-01
期刊：
影响因子：
15.8
通讯作者：
McKenzie, F. Ellis
中科院分区：
文献类型：
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作者：
O'Meara, Wendy Prudhomme;Smith, David L.;McKenzie, F. Ellis
研究背景：已提出对无症状的疟疾患者，不论其疟疾感染状况如何，定期间隔治疗剂量的抗疟药物，作为降低疟疾发病率和死亡率的一种方法。这一战略被称为间歇性预防性治疗（OPT），目前用于孕妇，也正在研究用于婴儿OPTO。与任何基于药物的干预策略一样，重要的是要了解实施如何影响耐药寄生虫的传播。这是一个很难通过实验解决的问题，因为IPTi试验的规模和持续时间有限，以及当在两种情况下使用相同的药物时，难以区分由于疟疾发作的常规治疗引起的耐药性传播与由于IPTi引起的耐药性传播。我们评估了定期使用抗疟药物治疗个体的可能影响，无论其感染状况如何。我们将个体治疗策略和药物药代动力学转化为寄生虫种群动态效应，并表明免疫力、治疗率、药物衰减动力学和假定治疗率是耐药寄生虫传播的重要因素。我们的模型预测，部分耐药寄生虫更有可能在低传播地区传播，但完全耐药寄生虫更有可能在高传播条件下传播，这与一些流行病学观察结果一致。我们还能够区分由于治疗症状性感染引起的耐药传播和由于IPTi引起的耐药传播。我们发现，IPTi可以加速耐药寄生虫的传播，但这种效果只可能是显着的低或不稳定的transmission.Conclusions在这里提出的结果表明，考虑药物的半衰期和现有的耐药水平时，选择一种药物IPTi的重要性。对于高传播地区的IPT，不建议使用很少或没有耐药性的药物，但IPTi不太可能显著影响已经建立部分耐药性的地区的高耐药性寄生虫的传播。IPTi比成人中的IPT更有可能加速高传播地区的耐药性传播（即，孕妇）。
Background Treatment of asymptomatic individuals, regardless of their malaria infection status, with regularly spaced therapeutic doses of antimalarial drugs has been proposed as a method for reducing malaria morbidity and mortality. This strategy, called intermittent preventive treatment OPT), is currently employed for pregnant women and is being studied for infants OPTO as well. As with any drug-based intervention strategy, it is important to understand how implementation may affect the spread of drug-resistant parasites. This is a difficult issue to address experimentally because of the limited size and duration of IPTi trials as well as the intractability of distinguishing the spread of resistance due to conventional treatment of malaria episodes versus that due to IPTi when the same drug is used in both contexts.Methods and Findings Using a mathematical model, we evaluated the possible impact of treating individuals with antimalarial drugs at regular intervals regardless of their infection status. We translated individual treatment strategies and drug pharmacokinetics into parasite population dynamic effects and show that immunity, treatment rate, drug decay kinetics, and presumptive treatment rate are important factors in the spread of drug-resistant parasites. Our model predicts that partially resistant parasites are more likely to spread in low-transmission areas, but fully resistant parasites are more likely to spread under conditions of high transmission, which is consistent with some epidemiological observations. We were also able to distinguish between spread of resistance due to treatment of symptomatic infections and that due to IPTi. We showed that IPTi could accelerate the spread of resistant parasites, but this effect was only likely to be significant in areas of low or unstable transmission.Conclusions The results presented here demonstrate the importance of considering both the half-life of a drug and the existing level of resistance when choosing a drug for IPTi. Drugs to which little or no resistance exists are not advisable for IPT in high-transmission areas, but IPTi is not likely to significantly impact the spread of highly resistant parasites in areas where partial resistance is already established. IPTi is more likely to accelerate the spread of resistance in high-transmission areas than is IPT in adults (i.e., pregnant women).