Achieng Angela O, Rawat Manmeet, Ogutu Bernhards, Guyah Bernard, Michael Ong'echa John, J Perkins Douglas, Kempaiah Prakasha
Department of Internal Medicine, Center for Global Health, University of New Mexico Health Sciences Center, Albuquerque, NM. United States.
Department of Internal Medicine, University of New Mexico School of Medicine and Albuquerque Veterans Affairs Medical Center, Albuquerque. Mexico.
Curr Top Med Chem. 2017;17(19):2114-2128. doi: 10.2174/1568026617666170130115323.
Despite a reduction in the global burden of malaria, the disease remains responsible for 214 million cases and 438,000 deaths annually with 88% of the mortality occurring in sub-Saharan Africa. Malaria control largely depends on effective chemotherapy. However, the historic and current emergence and spread of multi-drug resistant parasite strains provides significant challenges to malaria control and consequently, reduction of malaria-associated morbidity and mortality. Combating parasite drug resistance requires pharmacological compounds that target both known and novel metabolic pathways that are crucial for parasite survival. In addition, the identification of novel therapeutic agents that target distinct molecular pathways, apart from those of the conventional antimalarials, offers an approach for minimizing drug resistance.
This review summarizes current anti-malarial approaches and strategies, therapeutic efficacy for conventional and non-conventional antimalarials, parasitic targets, and the mechanisms responsible for the development of drug resistance.
尽管全球疟疾负担有所减轻,但该疾病每年仍导致2.14亿例病例和43.8万人死亡,其中88%的死亡发生在撒哈拉以南非洲地区。疟疾控制在很大程度上依赖于有效的化疗。然而,历史上和当前出现并传播的多重耐药寄生虫菌株给疟疾控制带来了重大挑战,从而也给降低疟疾相关的发病率和死亡率带来了挑战。对抗寄生虫耐药性需要针对对寄生虫生存至关重要的已知和新型代谢途径的药理化合物。此外,除了传统抗疟药之外,鉴定针对不同分子途径的新型治疗剂为最小化耐药性提供了一种方法。
本综述总结了当前的抗疟方法和策略、传统和非传统抗疟药的治疗效果、寄生虫靶点以及耐药性产生的机制。