使用抗疟药物的群众运动：蒿甲醚-苯芴醇和DHA-哌喹加伯氨喹和不加伯氨喹作为控制和消除疟疾工具的模拟比较
Mass campaigns with antimalarial drugs: a modelling comparison of artemether-lumefantrine and DHA-piperaquine with and without primaquine as tools for malaria control and elimination
摘要：
抗疟药物是控制和消除疟疾的有力工具。青蒿素类复方疗法在运动环境中广泛分发可减少传播。对大规模抗疟运动进行建模可以阐明如何最有效地部署以药物为基础的干预措施，并定量比较治疗、预防和传播阻断在抑制寄生虫流行方面的效果。先前建立的基于代理的模型，包括先天和适应性免疫被用来模拟疟疾感染和传播。蒿甲醚，本芴醇，双氢青蒿素，哌喹，伯氨喹的药代动力学建模与双指数分布消除模型，包括体重依赖性参数和年龄依赖性剂量。根据临床数据校准药物对无性寄生虫和配子体的杀灭。以青蒿素为基础的联合疗法和伯氨喹的质量分布与季节性蚊子动态在传播强度的范围内进行了模拟。在传播率高的情况下，单靠一次大规模的抗疟药物运动不足以永久降低疟疾流行率。目前的诊断方法不够灵敏，无法准确识别无症状感染，大规模筛查和治疗活动的有效性远远低于大规模药物管理。提高运动覆盖率会导致运动结束后一个月的流行率下降，而提高依从性则会延长预防再感染的持续时间。在高传播和适度高覆盖率的条件下，使用长效预防药物作为大规模药物管理方案的一部分可带来最大的益处。添加伯氨喹可以降低患病率，但当与长效预防剂结合时，效果最大。
英文摘要：
Antimalarial drugs are a powerful tool for malaria control and elimination. Artemisinin-based combination therapies (ACTs) can reduce transmission when widely distributed in a campaign setting. Modelling mass antimalarial campaigns can elucidate how to most effectively deploy drug-based interventions and quantitatively compare the effects of cure, prophylaxis, and transmission-blocking in suppressing parasite prevalence. A previously established agent-based model that includes innate and adaptive immunity was used to simulate malaria infections and transmission. Pharmacokinetics of artemether, lumefantrine, dihydroartemisinin, piperaquine, and primaquine were modelled with a double-exponential distribution-elimination model including weight-dependent parameters and age-dependent dosing. Drug killing of asexual parasites and gametocytes was calibrated to clinical data. Mass distribution of ACTs and primaquine was simulated with seasonal mosquito dynamics at a range of transmission intensities. A single mass campaign with antimalarial drugs is insufficient to permanently reduce malaria prevalence when transmission is high. Current diagnostics are insufficiently sensitive to accurately identify asymptomatic infections, and mass-screen-and-treat campaigns are much less efficacious than mass drug administrations. Improving campaign coverage leads to decreased prevalence one month after the end of the campaign, while increasing compliance lengthens the duration of protection against reinfection. Use of a long-lasting prophylactic as part of a mass drug administration regimen confers the most benefit under conditions of high transmission and moderately high coverage. Addition of primaquine can reduce prevalence but exerts its largest effect when coupled with a long-lasting prophylactic.
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