Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom.
Sci Rep. 2016 Sep 8;6:32762. doi: 10.1038/srep32762.
Most current antimalarial drugs are combinations of an artemisinin plus a 'partner' drug from another class, and are known as artemisinin-based combination therapies (ACTs). They are the frontline drugs in treating human malaria infections. They also have a public-health role as an essential component of recent, comprehensive scale-ups of malaria interventions and containment efforts conceived as part of longer term malaria elimination efforts. Recent reports that resistance has arisen to artemisinins has caused considerable concern. We investigate the likely impact of artemisinin resistance by quantifying the contribution artemisinins make to the overall therapeutic capacity of ACTs. We achieve this using a simple, easily understood, algebraic approach and by more sophisticated pharmacokinetic/pharmacodynamic analyses of drug action; the two approaches gave consistent results. Surprisingly, the artemisinin component typically makes a negligible contribution (≪0.0001%) to the therapeutic capacity of the most widely used ACTs and only starts to make a significant contribution to therapeutic outcome once resistance has started to evolve to the partner drugs. The main threat to antimalarial drug effectiveness and control comes from resistance evolving to the partner drugs. We therefore argue that public health policies be re-focussed to maximise the likely long-term effectiveness of the partner drugs.
大多数当前的抗疟药物都是青蒿素与另一种类别药物的“组合”，被称为青蒿素为基础的联合疗法（ACT）。它们是治疗人类疟疾感染的一线药物。作为最近疟疾干预和遏制工作全面扩大的重要组成部分，这些药物也具有公共卫生作用，旨在作为长期消除疟疾努力的一部分。最近有报道称，青蒿素已经出现耐药性，这引起了相当大的关注。我们通过量化青蒿素对 ACT 整体治疗能力的贡献来研究青蒿素耐药性的可能影响。我们使用一种简单、易于理解的代数方法和更复杂的药物作用药代动力学/药效学分析来实现这一点；这两种方法给出了一致的结果。令人惊讶的是，青蒿素成分通常对最广泛使用的 ACT 的治疗能力的贡献微不足道（≪0.0001%），并且只有在对伙伴药物的耐药性开始演变时，它才开始对治疗结果产生重大贡献。抗疟药物有效性和控制的主要威胁来自对伙伴药物的耐药性演变。因此，我们认为公共卫生政策应重新聚焦，以最大限度地提高伙伴药物的长期有效性。
