Okombo John, Fidock David A
Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.
Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Nat Rev Microbiol. 2025 Mar;23(3):178-191. doi: 10.1038/s41579-024-01099-x. Epub 2024 Oct 4.
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.
疟疾由疟原虫感染红细胞引起，在未免疫个体中若不治疗可能致命。近期红细胞前期疫苗RTS,S/AS01和R21/Matrix-M的获批带来了大幅降低死亡率的希望，尤其是与其他现有干预措施联合使用时。然而，这些疫苗的疗效是部分性的，化疗仍然是疟疾治疗和控制的核心。对于许多抗疟药物，恶性疟原虫耐药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一线青蒿素联合疗法。在本综述中，我们讨论了扩大当前疟疾治疗范围的各种机会，评估了当前抗疟药物的研发进程，并突出了有前景的靶点实例。我们还讨论了规避抗疟耐药性的其他方法以及如何保持对耐药寄生虫的效力。
