Brown Tyler S, Jacob Christopher G, Silva Joana C, Takala-Harrison Shannon, Djimdé Abdoulaye, Dondorp Arjen M, Fukuda Mark, Noedl Harald, Nyunt Myaing Myaing, Kyaw Myat Phone, Mayxay Mayfong, Hien Tran Tinh, Plowe Christopher V, Cummings Michael P
Johns Hopkins University School of Medicine, Baltimore, MD, USA; Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
Infect Genet Evol. 2015 Mar;30:318-322. doi: 10.1016/j.meegid.2014.12.010. Epub 2014 Dec 13.
Multiple transcontinental waves of drug resistance in Plasmodium falciparum have originated in Southeast Asia before spreading westward, first into the rest of Asia and then to sub-Saharan Africa. In vitro studies have suggested that hypermutator P. falciparum parasites may exist in Southeast Asia and that an increased rate of acquisition of new mutations in these parasites may explain the repeated emergence of drug resistance in Southeast Asia. This study is the first to test the hypermutator hypothesis using field isolates. Using genome-wide SNP data from human P. falciparum infections in Southeast Asia and West Africa and a test for relative rate differences we found no evidence of increased relative substitution rates in P. falciparum isolates from Southeast Asia. Instead, we found significantly increased substitution rates in Mali and Bangladesh populations relative to those in populations from Southeast Asia. Additionally we found no association between increased relative substitution rates and parasite clearance following treatment with artemisinin derivatives.
恶性疟原虫的多次跨大陆耐药性浪潮起源于东南亚，然后向西传播，首先传播到亚洲其他地区，接着传播到撒哈拉以南非洲。体外研究表明，东南亚可能存在高突变恶性疟原虫，这些寄生虫新突变获得率的增加可能解释了东南亚耐药性的反复出现。本研究首次使用现场分离株检验高突变假说。利用来自东南亚和西非人类恶性疟原虫感染的全基因组SNP数据以及相对速率差异检验，我们没有发现东南亚恶性疟原虫分离株相对替代率增加的证据。相反，我们发现马里和孟加拉国人群的替代率相对于东南亚人群显著增加。此外，我们没有发现相对替代率增加与青蒿素衍生物治疗后寄生虫清除之间的关联。
