Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia

被引：354

作者：

Miotto, Olivo ^{[1
,2
,3
]}

Almagro-Garcia, Jacob ^{[1
,3
,4
]}

Manske, Magnus ^{[3
]}

MacInnis, Bronwyn ^{[3
]}

Campino, Susana ^{[3
]}

Rockett, Kirk A. ^{[1
,3
,4
]}

Amaratunga, Chanaki ^{[5
]}

Lim, Pharath ^{[5
,6
]}

Suon, Seila ^{[6
]}

Sreng, Sokunthea ^{[6
]}

Anderson, Jennifer M. ^{[5
]}

Duong, Socheat ^{[6
]}

Nguon, Chea ^{[6
]}

Chuor, Char Meng ^{[6
]}

Saunders, David ^{[7
]}

Se, Youry ^{[8
]}

Lon, Chantap ^{[8
]}

Fukuda, Mark M. ^{[7
,9
]}

Amenga-Etego, Lucas ^{[1
,10
]}

Hodgson, Abraham V. O. ^{[10
]}

Asoala, Victor ^{[10
]}

Imwong, Mallika ^{[2
,11
]}

Takala-Harrison, Shannon ^{[12
]}

Nosten, Francois ^{[2
,13
,14
]}

Su, Xin-zhuan ^{[5
]}

Ringwald, Pascal ^{[15
]}

Ariey, Frederic ^{[16
]}

Dolecek, Christiane ^{[14
,17
]}

Tran Tinh Hien ^{[14
,17
]}

Boni, Maciej F. ^{[14
,17
]}

Cao Quang Thai ^{[17
]}

Amambua-Ngwa, Alfred ^{[18
]}

Conway, David J. ^{[18
,19
]}

Djimde, Abdoulaye A. ^{[20
]}

Doumbo, Ogobara K. ^{[20
]}

Zongo, Issaka ^{[21
]}

Ouedraogo, Jean-Bosco ^{[21
]}

Alcock, Daniel ^{[3
]}

Drury, Eleanor ^{[3
]}

Auburn, Sarah ^{[22
]}

Koch, Oliver ^{[1
]}

Sanders, Mandy ^{[3
]}

Hubbart, Christina ^{[4
]}

Maslen, Gareth ^{[3
]}

Ruano-Rubio, Valentin ^{[3
,4
]}

Jyothi, Dushyanth ^{[3
]}

Miles, Alistair ^{[1
,4
]}

O'Brien, John ^{[4
]}

Gamble, Chris ^{[23
]}

Oyola, Samuel O. ^{[3
]}

机构：

[1] Univ Oxford, MRC, Ctr Genom & Global Hlth, Oxford, England

[2] Mahidol Univ, Mahidol Oxford Trop Med Res Unit, Bangkok 10700, Thailand

[3] Wellcome Trust Sanger Inst, Cambridge, England

[4] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[5] NIAID, US Natl Inst Hlth, Bethesda, MD 20892 USA

[6] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia

[7] US Army Med Component, Armed Forces Res Inst Med Sci USAMC AFRIMS, Dept Immunol & Med, Bangkok, Thailand

[8] USAMC AFRIMS, Phnom Penh, Cambodia

[9] Armed Forces Hlth Surveillance Ctr, Silver Spring, MD USA

[10] Navrongo Hlth Res Ctr, Navrongo, Ghana

[11] Mahidol Univ, Fac Trop Med, Dept Mol Trop Med & Genet, Bangkok, Thailand

[12] Univ Maryland, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21201 USA

[13] Shoklo Malaria Res Unit, Mae Sot, Tak, Thailand

[14] Univ Oxford, Ctr Trop Med, Oxford, England

[15] WHO, Global Malaria Programme, CH-1211 Geneva, Switzerland

[16] Inst Pasteur, Unite Immunol Mol Parasites, Paris, France

[17] Oxford Univ Clin Res Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam

[18] MRC Labs, Fajara, Gambia

[19] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England

[20] Univ Sci Tech & Technol Bamako, Fac Pharm, Malaria Res & Training Ctr, Bamako, Mali

[21] Direct Reg Ouest, Inst Rech Sci Sante, Bobo Dioulasso, Burkina Faso

[22] Charles Darwin Univ, Menzies Sch Hlth Res, Darwin, NT 0909, Australia

[23] Univ Oxford, Dept Stat, Oxford OX1 3TG, England

[24] Univ Oxford, Weatherall Inst Mol Med, Oxford, England

来源：

NATURE GENETICS | 2013年 / 45卷 / 06期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

CHLOROQUINE RESISTANCE; PARASITE CLEARANCE; DIHYDROPTEROATE SYNTHASE; DIHYDROFOLATE-REDUCTASE; DRUG-RESISTANCE; MALARIA; SPREAD; PYRIMETHAMINE; PFCRT; GENE;

D O I：

10.1038/ng.2624

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist in its elimination.

引用

页码：648 / +

页数：10

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