Genomic Analysis Reveals a Common Breakpoint in Amplifications of the Plasmodium vivax Multidrug Resistance 1 Locus in Thailand.
Genomic Analysis Reveals a Common Breakpoint in Amplifications of the Plasmodium vivax Multidrug Resistance 1 Locus in Thailand.
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DOI：
10.1093/infdis/jiw323
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发表时间：
2016-10-15
期刊：
影响因子：
--
通讯作者：
Price RN
中科院分区：
文献类型：
--
作者：
Auburn S;Serre D;Pearson RD;Amato R;Sriprawat K;To S;Handayuni I;Suwanarusk R;Russell B;Drury E;Stalker J;Miotto O;Kwiatkowski DP;Nosten F;Price RN
在恶性疟原虫和间日疟原虫同流行的地区，使用甲氟喹治疗恶性疟原虫感染，多药耐药 1 基因 (pvmdr1) 拷贝数增加介导的药物压力可能会选择耐甲氟喹的间日疟原虫。监测并未常规进行，部分原因是基因扩增检测的方法学挑战。利用来自泰国西部的 88 个间日疟原虫样本的基因组数据，我们在 17 个分离株中发现了 pvmdr1 扩增，所有分离株都表现出具有相同断点的 37.6 千碱基对区域的串联拷贝。设计了一种新颖的断点特异性聚合酶链反应测定来检测扩增。该检测显示出高灵敏度，可识别另外 13 种多克隆感染的扩增。对 132 个进一步样本的应用确定了所有测试年份（2003-2015）的共同断点，2012 年之后患病率下降，对应于甲氟喹治疗方案的局部终止。对其他地理区域 pvmdr1 扩增结构的评估将产生有关断点的群体特异性和潜在扩增机制的信息。
In regions of coendemicity for Plasmodium falciparum and Plasmodium vivax where mefloquine is used to treat P. falciparum infection, drug pressure mediated by increased copy numbers of the multidrug resistance 1 gene (pvmdr1) may select for mefloquine-resistant P. vivax. Surveillance is not undertaken routinely owing in part to methodological challenges in detection of gene amplification. Using genomic data on 88 P. vivax samples from western Thailand, we identified pvmdr1 amplification in 17 isolates, all exhibiting tandem copies of a 37.6–kilobase pair region with identical breakpoints. A novel breakpoint-specific polymerase chain reaction assay was designed to detect the amplification. The assay demonstrated high sensitivity, identifying amplifications in 13 additional, polyclonal infections. Application to 132 further samples identified the common breakpoint in all years tested (2003–2015), with a decline in prevalence after 2012 corresponding to local discontinuation of mefloquine regimens. Assessment of the structure of pvmdr1 amplification in other geographic regions will yield information about the population-specificity of the breakpoints and underlying amplification mechanisms.
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影响因子：
3.7
作者：
Abdullah NR;Barber BE;William T;Norahmad NA;Satsu UR;Muniandy PK;Ismail Z;Grigg MJ;Jelip J;Piera K;von Seidlein L;Yeo TW;Anstey NM;Price RN;Auburn S
通讯作者：
Auburn S
DOI：
10.1093/cid/ciq249
发表时间：
2011-03-01
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Douglas NM;Nosten F;Ashley EA;Phaiphun L;van Vugt M;Singhasivanon P;White NJ;Price RN
通讯作者：
Price RN
影响因子：
64.8
作者：
Carlton, Jane M.;Adams, John H.;Silva, Joana C.;Bidwell, Shelby L.;Lorenzi, Hernan;Caler, Elisabet;Crabtree, Jonathan;Angiuoli, Samuel V.;Merino, Emilio F.;Amedeo, Paolo;Cheng, Qin;Coulson, Richard M. R.;Crabb, Brendan S.;del Portillo, Hernando A.;Essien, Kobby;Feldblyum, Tamara V.;Fernandez-Becerra, Carmen;Gilson, Paul R.;Gueye, Amy H.;Guo, Xiang;Kang'a, Simon;Kooij, Taco W. A.;Korsinczky, Michael;Meyer, Esmeralda V. -S.;Nene, Vish;Paulsen, Ian;White, Owen;Ralph, Stuart A.;Ren, Qinghu;Sargeant, Tobias J.;Salzberg, Steven L.;Stoeckert, Christian J.;Sullivan, Steven A.;Yamamoto, Marcio M.;Hoffman, Stephen L.;Wortman, Jennifer R.;Gardner, Malcolm J.;Galinski, Mary R.;Barnwell, John W.;Fraser-Liggett, Claire M.
通讯作者：
Fraser-Liggett, Claire M.
影响因子：
15.8
作者：
Carrara VI;Lwin KM;Phyo AP;Ashley E;Wiladphaingern J;Sriprawat K;Rijken M;Boel M;McGready R;Proux S;Chu C;Singhasivanon P;White N;Nosten F
通讯作者：
Nosten F
影响因子：
3
作者：
Gray KA;Dowd S;Bain L;Bobogare A;Wini L;Shanks GD;Cheng Q
通讯作者：
Cheng Q