Spread of Artemisinin Resistance in Plasmodium falciparum Malaria

被引：1548

作者：

Ashley, E. A. ^{[1
,7
]}

Dhorda, M. ^{[7
,8
,14
]}

Fairhurst, R. M. ^{[15
]}

Amaratunga, C. ^{[15
]}

Lim, P. ^{[15
,16
]}

Suon, S. ^{[16
]}

Sreng, S. ^{[16
]}

Anderson, J. M. ^{[15
]}

Mao, S. ^{[17
]}

Sam, B. ^{[18
]}

Sopha, C. ^{[19
]}

Chuor, C. M. ^{[16
]}

Nguon, C. ^{[16
]}

Sovannaroth, S. ^{[16
]}

Pukrittayakamee, S. ^{[2
]}

Jittamala, P. ^{[2
]}

Chotivanich, K. ^{[2
]}

Chutasmit, K. ^{[3
]}

Suchatsoonthorn, C. ^{[5
]}

Runcharoen, R. ^{[4
]}

Hien, T. T. ^{[7
,20
]}

Thuy-Nhien, N. T. ^{[20
]}

Thanh, N. V. ^{[20
]}

Phu, N. H. ^{[20
]}

Htut, Y. ^{[21
]}

Han, K-T. ^{[21
]}

Aye, K. H. ^{[21
]}

Mokuolu, O. A. ^{[22
]}

Olaosebikan, R. R. ^{[22
]}

Folaranmi, O. O. ^{[23
]}

Mayxay, M. ^{[7
,24
,25
]}

Khanthavong, M. ^{[26
]}

Hongvanthong, B. ^{[26
]}

Newton, P. N. ^{[7
,24
]}

Onyamboko, M. A. ^{[7
,27
]}

Fanello, C. I. ^{[1
,7
]}

Tshefu, A. K. ^{[27
]}

Mishra, N. ^{[28
]}

Valecha, N. ^{[28
]}

Phyo, A. P. ^{[1
,6
,7
]}

Nosten, F. ^{[1
,6
,7
]}

Yi, P. ^{[16
]}

Tripura, R. ^{[1
]}

Borrmann, S. ^{[29
,30
,31
]}

Bashraheil, M. ^{[29
]}

Peshu, J. ^{[29
]}

Faiz, M. A. ^{[32
,33
]}

Ghose, A. ^{[32
,33
,35
]}

Hossain, M. A. ^{[32
,33
,35
]}

Samad, R. ^{[32
,33
,35
]}

机构：

[1] Mahidol Univ, Mahidol Oxford Trop Med Res Unit, Bangkok 10400, Thailand

[2] Mahidol Univ, Fac Trop Med, Bangkok 10400, Thailand

[3] Phusing Hosp, Srisaket, Thailand

[4] Khunhan Hosp, Srisaket, Thailand

[5] Kraburi Hosp, Ranong, Thailand

[6] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Shoklo Malaria Res Unit, Mae Sot, Thailand

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

[8] Univ Oxford, Ctr Trop Med, Worldwide Antimalarial Resistance Network, Oxford, England

[9] Univ Oxford, Nuffield Dept Med, Med Res Council Ctr Genom & Global Hlth, Oxford, England

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

[11] Wellcome Trust Sanger Inst, Cambridge, England

[12] London Sch Hyg & Trop Med, Fac Publ Hlth & Policy, Dept Global Hlth & Dev, London WC1, England

[13] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Policy & Clin Res Dept, London WC1, England

[14] Univ Maryland, Sch Med, Howard Hughes Med Inst, Malaria Grp,Ctr Vaccine Dev, Baltimore, MD 21201 USA

[15] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA

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

[17] Sampov Meas Referral Hosp, Pursat, Cambodia

[18] Ratanakiri Referral Hosp, Ratanakiri, Cambodia

[19] Makara 16 Referral Hosp, Preah Vihear, Cambodia

[20] Oxford Univ Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam

[21] Dept Med Res, Lower Myanmar, Yangon, Myanmar

[22] Univ Ilorin, Dept Paediat & Child Hlth, Ilorin, Nigeria

[23] Univ Ilorin, Teaching Hosp, Dept Histopathol, Ilorin, Nigeria

[24] Mahosot Hosp, Lao Oxford Mahosot Hosp Wellcome Trust Res Unit, Viangchan, Laos

[25] Univ Hlth Sci, Fac Postgrad Studies, Viangchan, Laos

[26] Ctr Malariol Parasitol & Entomol, Viangchan, Laos

[27] Kinshasa Sch Publ Hlth, Kinshasa, DEM REP CONGO

[28] Indian Council Med Res, Natl Inst Malaria Res, Sect 8, New Delhi, India

[29] Kenya Govt Med Res Ctr, Wellcome Trust Res Programme, Kilifi, Kenya

[30] Univ Tubingen, Inst Trop Med, Tubingen, Germany

[31] German Ctr Infect Res, Tubingen, Germany

[32] Malaria Res Grp, Dhaka, Bangladesh

[33] Dev Care Fdn, Dhaka, Bangladesh

[34] Shaheed Suhrawardy Med Coll, Dhaka, Bangladesh

[35] Chittagong Med Coll, Chittagong, Bangladesh

[36] Ramu Upazila Hlth Complex, Coxs Bazar, Bangladesh

[37] Nanyang Technol Univ, Sch Biol Sci, Singapore 639798, Singapore

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2014年 / 371卷 / 05期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

PARASITE CLEARANCE; ARTESUNATE; CAMBODIA; SUSCEPTIBILITY; EFFICACY; PROVINCE; RATES;

D O I：

10.1056/NEJMoa1314981

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing in-fections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U. K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.)

引用

页码：411 / 423

页数：13

共 36 条

[1] Artemisinin-resistant Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study [J].

Amaratunga, Chanaki ;

Sreng, Sokunthea ;

Suon, Seila ;

Phelps, Erika S. ;

Stepniewska, Kasia ;

Lim, Pharath ;

Zhou, Chongjun ;

Mao, Sivanna ;

Anderson, Jennifer M. ;

Lindegardh, Niklas ;

Jiang, Hongying ;

Song, Jianping ;

Su, Xin-zhuan ;

White, Nicholas J. ;

Dondorp, Arjen M. ;

Anderson, Tim J. C. ;

Fay, Michael P. ;

Mu, Jianbing ;

Duong, Socheat ;

Fairhurst, Rick M. .

LANCET INFECTIOUS DISEASES, 2012, 12 (11) :851-858

[2] A molecular marker of artemisinin-resistant Plasmodium falciparum malaria [J].

Ariey, Frederic ;

Witkowski, Benoit ;

Amaratunga, Chanaki ;

Beghain, Johann ;

Langlois, Anne-Claire ;

Khim, Nimol ;

Kim, Saorin ;

Duru, Valentine ;

Bouchier, Christiane ;

Ma, Laurence ;

Lim, Pharath ;

Leang, Rithea ;

Duong, Socheat ;

Sreng, Sokunthea ;

Suon, Seila ;

Chuor, Char Meng ;

Bout, Denis Mey ;

Menard, Sandie ;

Rogers, William O. ;

Genton, Blaise ;

Fandeur, Thierry ;

Miotto, Olivo ;

Ringwald, Pascal ;

Le Bras, Jacques ;

Berry, Antoine ;

Barale, Jean-Christophe ;

Fairhurst, Rick M. ;

Benoit-Vical, Franoise ;

Mercereau-Puijalon, Odile ;

Menard, Didier .

NATURE, 2014, 505 (7481) :50-+

[3] Increased gametocytemia after treatment: An early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria [J].

Barnes, Karen I. ;

Little, Francesca ;

Mabuza, Aaron ;

Mngomezulu, Nicros ;

Govere, John ;

Durrheim, David ;

Roper, Cally ;

Watkins, Bill ;

White, Nicholas J. .

JOURNAL OF INFECTIOUS DISEASES, 2008, 197 (11) :1605-1613

[4] Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar [J].

Bhattarai, Achuyt ;

Ali, Abdullah S. ;

Kachur, S. Patrick ;

Martensson, Andreas ;

Abbas, Ali K. ;

Khatib, Rashid ;

Al-Mafazy, Abdul-wahiyd ;

Ramsan, Mahdi ;

Rotllant, Guida ;

Gerstenmaier, Jan F. ;

Molteni, Fabrizio ;

Abdulla, Salim ;

Montgomery, Scott M. ;

Kaneko, Akira ;

Bjorkman, Anders .

PLOS MEDICINE, 2007, 4 (11) :1784-1790

[5] Malaria Burden and Artemisinin Resistance in the Mobile and Migrant Population on the Thai-Myanmar Border, 1999-2011: An Observational Study [J].

Carrara, Verena I. ;

Lwin, Khin Maung ;

Phyo, Aung Pyae ;

Ashley, Elizabeth ;

Wiladphaingern, Jacher ;

Sriprawat, Kanlaya ;

Rijken, Marcus ;

Boel, Machteld ;

McGready, Rose ;

Proux, Stephane ;

Chu, Cindy ;

Singhasivanon, Pratap ;

White, Nicholas ;

Nosten, Francois .

PLOS MEDICINE, 2013, 10 (03)

[6] Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous Deployment [J].

Carrara, Verena Ilona ;

Zwang, Julien ;

Ashley, Elizabeth A. ;

Price, Ric N. ;

Stepniewska, Kasia ;

Barends, Marion ;

Brockman, Alan ;

Anderson, Tim ;

McGready, Rose ;

Phaiphun, Lucy ;

Proux, Stephane ;

van Vugt, Michele ;

Hutagalung, Robert ;

Lwin, Khin Maung ;

Phyo, Aung Pyae ;

Preechapornkul, Piyanuch ;

Imwong, Mallika ;

Pukrittayakamee, Sasithon ;

Singhasivanon, Pratap ;

White, Nicholas J. ;

Nosten, Francois .

PLOS ONE, 2009, 4 (02)

[7] A Major Genome Region Underlying Artemisinin Resistance in Malaria [J].

Cheeseman, Ian H. ;

Miller, Becky A. ;

Nair, Shalini ;

Nkhoma, Standwell ;

Tan, Asako ;

Tan, John C. ;

Al Saai, Salma ;

Phyo, Aung Pyae ;

Moo, Carit Ler ;

Lwin, Khin Maung ;

McGready, Rose ;

Ashley, Elizabeth ;

Imwong, Mallika ;

Stepniewska, Kasia ;

Yi, Poravuth ;

Dondorp, Arjen M. ;

Mayxay, Mayfong ;

Newton, Paul N. ;

White, Nicholas J. ;

Nosten, Francois ;

Ferdig, Michael T. ;

Anderson, Timothy J. C. .

SCIENCE, 2012, 336 (6077) :79-82

[8] Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum [J].

Chotivanich, Kesinee ;

Tripura, Rupam ;

Das, Debashish ;

Yi, Poravuth ;

Day, Nicholas P. J. ;

Pukrittayakamee, Sasithon ;

Chuor, Char Meng ;

Socheat, Duong ;

Dondorp, Arjen M. ;

White, Nicholas J. .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2014, 58 (06) :3157-3161

[9] Efficacy of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Cambodia [J].

Denis, Mey Bouth ;

Tsuyuoka, Reiko ;

Lim, Pharath ;

Lindegardh, Niklas ;

Yi, Poravuth ;

Top, Sophoan Narann ;

Socheat, Duong ;

Fandeur, Thierry ;

Annerberg, Anna ;

Christophel, Eva Maria ;

Ringwald, Pascal .

TROPICAL MEDICINE & INTERNATIONAL HEALTH, 2006, 11 (12) :1800-1807

[10]

Dondorp AM, 2009, NEW ENGL J MED, V361, P1714

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