Abstract:
Malaria caused by Plasmodium falciparum is one of the deadliest and most common tropical infectious diseases. However, the emergence of artemisinin drug resistance associated with the parasite\'s Pfk13 gene, threatens the public health of individual countries as well as current efforts to reduce malaria burdens globally. It is of concern that artemisinin-resistant parasites may be selected or have already emerged in Africa. This narrative review aims to evaluate the published evidence concerning validated, candidate, and novel Pfk13 polymorphisms in ten Central African countries. Results show that four validated non-synonymous polymorphisms (M476I, R539T, P553L, and P574L), directly associated with a delayed therapy response, have been reported in the region. Also, two Pfk13 polymorphisms associated to artemisinin resistance but not validated (C469F and P527H) have been reported. Furthermore, several non-validated mutations have been observed in Central Africa, and one allele A578S, is commonly found in different countries, although additional molecular and biochemical studies are needed to investigate whether those mutations alter artemisinin effects. This information is discussed in the context of biochemical and genetic aspects of Pfk13, and related to the regional malaria epidemiology of Central African countries.
摘要:
由恶性疟原虫引起的疟疾是最致命和最常见的热带传染病之一。然而,与寄生虫Pfk13基因相关的青蒿素耐药性的出现,威胁到各个国家的公共健康以及目前在全球范围内减轻疟疾负担的努力。令人关切的是,抗青蒿素的寄生虫可能被选择或已经在非洲出现。这篇叙述性综述旨在评估已发表的关于验证的证据,候选人,和十个中非国家的新Pfk13多态性。结果表明,四个验证的非同义多态性(M476I,R539T,P553L,和P574L),与延迟治疗反应直接相关,据报道,该地区。此外,已经报道了两个与青蒿素耐药相关但未经验证的Pfk13多态性(C469F和P527H)。此外,在中非观察到了一些未经验证的突变,和一个等位基因A578S,常见于不同的国家,尽管需要更多的分子和生化研究来研究这些突变是否会改变青蒿素的作用。这些信息是在Pfk13的生化和遗传方面进行讨论的,与中非国家的区域疟疾流行病学有关。