Wellems T E, Plowe C V
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Infect Dis. 2001 Sep 15;184(6):770-6. doi: 10.1086/322858. Epub 2001 Aug 7.
The development of chloroquine as an antimalarial drug and the subsequent evolution of drug-resistant Plasmodium strains had major impacts on global public health in the 20th century. In P. falciparum, the cause of the most lethal human malaria, chloroquine resistance is linked to multiple mutations in PfCRT, a protein that likely functions as a transporter in the parasite's digestive vacuole membrane. Rapid diagnostic assays for PfCRT mutations are already employed as surveillance tools for drug resistance. Here, we review recent field studies that support the central role of PfCRT mutations in chloroquine resistance. These studies suggest chloroquine resistance arose in > or = 4 distinct geographic foci and substantiate an important role of immunity in the outcomes of resistant infections after chloroquine treatment. P. vivax, which also causes human malaria, appears to differ from P. falciparum in its mechanism of chloroquine resistance. Investigation of the resistance mechanisms and of the role of immunity in therapeutic outcomes will support new approaches to drugs that can take the place of chloroquine or augment its efficiency.
氯喹作为一种抗疟药物的研发以及随后耐药疟原虫菌株的演变，在20世纪对全球公共卫生产生了重大影响。在导致最致命人类疟疾的恶性疟原虫中，氯喹耐药性与PfCRT的多个突变有关，PfCRT是一种可能在寄生虫消化液泡膜中起转运蛋白作用的蛋白质。针对PfCRT突变的快速诊断检测已被用作耐药性监测工具。在此，我们综述了支持PfCRT突变在氯喹耐药性中核心作用的近期实地研究。这些研究表明，氯喹耐药性出现在≥4个不同的地理区域，并证实了免疫在氯喹治疗后耐药感染结果中的重要作用。间日疟原虫也会导致人类疟疾，其氯喹耐药机制似乎与恶性疟原虫不同。对耐药机制以及免疫在治疗结果中的作用进行研究，将有助于开发能够替代氯喹或提高其疗效的新型药物。
