The diminishing returns of atovaquone-proguanil for elimination of Plasmodium falciparum malaria: modelling mass drug administration and treatment
The diminishing returns of atovaquone-proguanil for elimination of Plasmodium falciparum malaria: modelling mass drug administration and treatment
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DOI：
10.1186/1475-2875-13-380
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发表时间：
2014-09-24
期刊：
影响因子：
3
通讯作者：
White, Nicholas J.
中科院分区：
文献类型：
--
作者：
Maude, Richard J.;Nguon, Chea;White, Nicholas J.
背景资料：青蒿素耐药性是目前消灭恶性疟原虫疟疾努力的一个主要威胁，目前的努力严重依赖青蒿素综合疗法的持续疗效。有人建议，在青蒿素耐药性恶性疟原虫流行的地区，不应在大规模给药中使用青蒿素综合疗法，阿托伐醌-氯胍（A-P）可能是一种更可取的替代办法。然而，细胞色素B基因中的单点突变赋予对阿托伐醌的高水平抗性，并且这种突变寄生虫在治疗期间频繁出现，使得A-P成为易受攻击的消除工具。一个决定性的，人口水平，基于柬埔寨的数据开发了数学模型，以探索大规模使用A-P与双氢青蒿素-哌喹ACT相比对大规模药物给药的可能影响，和/或或治疗恶性疟原虫疟疾，使用或不使用抗疟伯氨喹（PQ）和长效驱虫蚊帐（LLIN）。结果：模型显示ACT和A-P对MDA的初始效应相似。然而，每一轮A-P MDA导致阿托伐醌抗性的快速获得和传播。即使是单轮MDA也可能损害疗效，足以排除其用于治疗或预防。转换为A-P治疗症状性发作导致患者在引入后4 - 5年内完全丧失疗效。MDA的影响是暂时的，保持高覆盖率与ACT治疗症状的个人和LLIN相结合是必要的elimination.Conclusion：对于疟疾消除，应避免A-P MDA或治疗症状的情况。高覆盖率与ACT治疗症状发作、LLIN和ACT + P MDA的联合策略将是首选。
Background: Artemisinin resistance is a major threat to current efforts to eliminate Plasmodium falciparum malaria which rely heavily on the continuing efficacy of artemisinin combination therapy (ACT). It has been suggested that ACT should not be used in mass drug administration (MDA) in areas where artemisinin-resistant P. falciparum is prevalent, and that atovaquone-proguanil (A-P) might be a preferable alternative. However, a single point mutation in the cytochrome b gene confers high level resistance to atovaquone, and such mutant parasites arise frequently during treatment making A-P a vulnerable tool for elimination.Methods: A deterministic, population level, mathematical model was developed based on data from Cambodia to explore the possible effects of large-scale use of A-P compared to dihydroartemisinin-piperaquine ACT for mass drug administration and/or treatment of P. falciparum malaria, with and without adjunctive primaquine (PQ) and long-lasting insecticide-treated bed nets (LLIN). The aim was local elimination.Results: The model showed the initial efficacy of ACT and A-P for MDA to be similar. However, each round of A-P MDA resulted in rapid acquisition and spread of atovaquone resistance. Even a single round of MDA could compromise efficacy sufficient to preclude its use for treatment or prophylaxis. A switch to A-P for treatment of symptomatic episodes resulted in a complete loss of efficacy in the population within four to five years of its introduction. The impact of MDA was temporary and a combination of maintained high coverage with ACT treatment for symptomatic individuals and LLIN was necessary for elimination.Conclusion: For malaria elimination, A-P for MDA or treatment of symptomatic cases should be avoided. A combined strategy of high coverage with ACT for treatment of symptomatic episodes, LLIN and ACT + P MDA would be preferable.