Malaria, which is caused by infection of red blood cells with Plasmodium parasites, can be fatal in non-immune individuals if left untreated. The recent approval of the pre-erythrocytic vaccines RTS, S/AS01 and R21/Matrix-M has ushered in hope of substantial reductions in mortality rates, especially when combined with other existing interventions. However, the efficacy of these vaccines is partial, and chemotherapy remains central to malaria treatment and control. For many antimalarial drugs, clinical efficacy has been compromised by the emergence of drug-resistant Plasmodium falciparum strains. Therefore, there is an urgent need for new antimalarial medicines to complement the existing first-line artemisinin-based combination therapies. In this Review, we discuss various opportunities to expand the present malaria treatment space, appraise the current antimalarial drug development pipeline and highlight examples of promising targets. We also discuss other approaches to circumvent antimalarial resistance and how potency against drug-resistant parasites could be retained.

疟疾是由疟原虫寄生虫感染红细胞引起的，如果不及时治疗，对没有免疫力的个体可能是致命的。最近批准的红细胞前疫苗 RTS、S/AS01 和 R21/Matrix-M 带来了大幅降低死亡率的希望，尤其是在与其他现有干预措施结合使用时。然而，这些疫苗的疗效是部分的，化疗仍然是疟疾治疗和控制的核心。对于许多抗疟药，耐药性恶性疟原虫菌株的出现损害了临床疗效。因此，迫切需要新的抗疟药物来补充现有的基于青蒿素的一线联合疗法。在这篇综述中，我们讨论了扩大当前疟疾治疗空间的各种机会，评估了当前的抗疟药物开发管道，并强调了有前途的靶点的例子。我们还讨论了规避抗疟药耐药性的其他方法，以及如何保持对耐药寄生虫的效力。