Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, W2 1PG, UK.
Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Nat Commun. 2017 Nov 9;8(1):1373. doi: 10.1038/s41467-017-01352-3.
Artemether-lumefantrine (AL) is the most widely-recommended treatment for uncomplicated Plasmodium falciparum malaria worldwide. Its safety and efficacy have been extensively demonstrated in clinical trials; however, its performance in routine health care settings, where adherence to drug treatment is unsupervised and therefore may be suboptimal, is less well characterised. Here we develop a within-host modelling framework for estimating the effects of sub-optimal adherence to AL treatment on clinical outcomes in malaria patients. Our model incorporates the data on the human immune response to the parasite, and AL's pharmacokinetic and pharmacodynamic properties. Utilising individual-level data of adherence to AL in 482 Tanzanian patients as input for our model predicted higher rates of treatment failure than were obtained when adherence was optimal (9% compared to 4%). Our model estimates that the impact of imperfect adherence was worst in children, highlighting the importance of advice to caregivers.
青蒿琥酯- 咯萘啶（AL）是目前全球范围内推荐用于治疗无并发症恶性疟原虫疟疾的首选药物。临床试验已经广泛证明了它的安全性和疗效；然而，在常规医疗保健环境中，药物治疗的依从性是无人监督的，因此可能并不理想，其疗效的特征描述则较少。在此，我们开发了一种基于个体水平的模型框架，用于估计青蒿琥酯治疗依从性欠佳对疟疾患者临床结局的影响。我们的模型纳入了人体对寄生虫免疫反应的数据，以及青蒿琥酯的药代动力学和药效动力学特性。利用 482 名坦桑尼亚患者的青蒿琥酯治疗依从性的个体水平数据作为模型的输入，预测治疗失败率高于依从性最佳时的情况（9% 对比 4%）。我们的模型估计，不完全依从的影响在儿童中最为严重，这凸显了向看护人提供建议的重要性。
