Genetic diversity of next generation antimalarial targets: A baseline for drug resistance surveillance programmes.
Genetic diversity of next generation antimalarial targets: A baseline for drug resistance surveillance programmes.
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DOI：
10.1016/j.ijpddr.2017.03.001
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Campino S
中科院分区：
文献类型：
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作者：
Gomes AR;Ravenhall M;Benavente ED;Talman A;Sutherland C;Roper C;Clark TG;Campino S
在防治疟疾的斗争中，耐药性是一个反复出现的问题。抗疟寄生虫等位基因的遗传和流行病学监测对指导药物治疗和临床管理至关重要。新的抗疟化合物目前正处于临床试验和监管评估的不同阶段。利用~ 2000个恶性疟原虫基因组序列，研究了11个有希望的抗疟化合物的基因靶点的遗传多样性，并评估了它们在疟疾流行地区的潜在效率。我们在引入新药之前确定了这些基因座是否处于选择状态，并为未来的监测规划建立了遗传变异基线，包括潜在的耐药等位基因。研究了抗疟新药11个基因靶点的遗传多样性。对18个疟疾流行国家的遗传数据进行了分析。没有观察到选择压力的信号。在非洲寄生虫中发现了一种与对一种新的抗疟药产生耐药性有关的突变。检测到与报道的抗疟耐药突变接近的氨基酸变化。
Drug resistance is a recurrent problem in the fight against malaria. Genetic and epidemiological surveillance of antimalarial resistant parasite alleles is crucial to guide drug therapies and clinical management. New antimalarial compounds are currently at various stages of clinical trials and regulatory evaluation. Using ∼2000 Plasmodium falciparum genome sequences, we investigated the genetic diversity of eleven gene-targets of promising antimalarial compounds and assessed their potential efficiency across malaria endemic regions. We determined if the loci are under selection prior to the introduction of new drugs and established a baseline of genetic variance, including potential resistant alleles, for future surveillance programmes. Genetic diversity of 11gene-targets of new antimalarial compounds was investigated. Genetic data was analysed for 18 malaria endemic countries. No signals of selective pressure was observed. A mutation linked to resistance to a new antimalarial was found in African parasites. Amino-acid changes close to reported antimalarial resistant mutations were detected.