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Modelling the impact of intermittent preventive treatment for malaria on selection pressure for drug resistance

机译:对间歇性疟疾预防治疗对耐药性选择压力的影响进行建模

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Background Intermittent preventive treatment (IPT) is a promising intervention for malaria control, although there are concerns about its impact on drug resistance. Methods The key model inputs are age-specific values for a) baseline anti-malarial dosing rate, b) parasite prevalence, and c) proportion of those treated with anti-malarials (outside IPT) who are infected. These are used to estimate the immediate effect of IPT on the genetic coefficient of selection (s). The scenarios modelled were year round IPT to infants in rural southern Tanzania, and three doses at monthly intervals of seasonal IPT in Senegal. Results In the simulated Tanzanian setting, the model suggests a high selection pressure for drug resistance, but that IPTi would only increase this by a small amount (4.4%). The percent change in s is larger if parasites are more concentrated in infants, or if baseline drug dosing is less common or less specific. If children aged up to five years are included in the Tanzanian scenario then the predicted increase in s rises to 31%. The Senegalese seasonal IPT scenario, in children up to five years, results in a predicted increase in s of 16%. Conclusion There is a risk that the useful life of drugs will be shortened if IPT is implemented over a wide childhood age range. On the other hand, IPT delivered only to infants is unlikely to appreciably shorten the useful life of the drug used.
机译:背景技术间歇性预防治疗(IPT)是控制疟疾的一种有前途的干预措施,尽管人们担心其对耐药性的影响。方法关键模型输入值是针对以下年龄的特定值:a)基线抗疟疾剂量率,b)寄生虫患病率和c)接受抗疟疾治疗的患者(IPT外)的比例。这些用于估计IPT对选择的遗传系数的直接影响。所模拟的情景是坦桑尼亚南部农村地区的婴儿全年IPT,而塞内加尔则按季节性IPT的每月间隔三剂。结果在模拟的坦桑尼亚环境中,该模型显示出较高的耐药性选择压力,但IPTi仅会增加少量压力(4.4%)。如果寄生虫更多地集中在婴儿中,或者基线药物剂量不常见或特异性较低,则s的变化百分比会更大。如果坦桑尼亚的情景中包括5岁以下的儿童,则s的预计增长将上升到31%。塞内加尔的季节性IPT情景在5岁以下的儿童中,预计s会增加16%。结论如果在广泛的儿童年龄范围内实施IPT,则有可能会缩短药物的使用寿命。另一方面,仅向婴儿提供IPT不太可能明显缩短所用药物的使用寿命。

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