Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study

Summary Background Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international effort is underway to contain artemisinin-resistant Plasmodium falciparum , but containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establis...

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Veröffentlicht in:The Lancet (British edition) 2012-05, Vol.379 (9830), p.1960-1966
Hauptverfasser: Phyo, Aung Pyae, MD, Nkhoma, Standwell, PhD, Stepniewska, Kasia, PhD, Ashley, Elizabeth A, MD, Nair, Shalini, MSc, McGready, Rose, MD, ler Moo, Carit, Al-Saai, Salma, MSc, Dondorp, Arjen M, MD, Lwin, Khin Maung, MD, Singhasivanon, Pratap, MD, Day, Nicholas PJ, FRCP, White, Nicholas J, FRS, Anderson, Tim JC, PhD, Nosten, François, Prof
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container_end_page 1966
container_issue 9830
container_start_page 1960
container_title The Lancet (British edition)
container_volume 379
creator Phyo, Aung Pyae, MD
Nkhoma, Standwell, PhD
Stepniewska, Kasia, PhD
Ashley, Elizabeth A, MD
Nair, Shalini, MSc
McGready, Rose, MD
ler Moo, Carit
Al-Saai, Salma, MSc
Dondorp, Arjen M, MD
Lwin, Khin Maung, MD
Singhasivanon, Pratap, MD
Day, Nicholas PJ, FRCP
White, Nicholas J, FRS
Anderson, Tim JC, PhD
Nosten, François, Prof
description Summary Background Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international effort is underway to contain artemisinin-resistant Plasmodium falciparum , but containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand–Myanmar (Burma) border. Methods In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≥4% infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms. Findings 3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95% CI 2·5–2·7) in 2001, to 3·7 h (3·6–3·8) in 2010, compared with a mean of 5·5 h (5·2–5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≥6·2 h) increased from 0·6% in 2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identified, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30% between 2001 and 2004, to 66% between 2007 and 2010. Interpretation Genetically determined artemisinin resistance in P falciparum emerged along the Thailand–Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2–6 years. Funding The Wellcome Trust and National Institutes of Health.
doi_str_mv 10.1016/S0140-6736(12)60484-X
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A concerted international effort is underway to contain artemisinin-resistant Plasmodium falciparum , but containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand–Myanmar (Burma) border. Methods In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≥4% infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms. Findings 3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95% CI 2·5–2·7) in 2001, to 3·7 h (3·6–3·8) in 2010, compared with a mean of 5·5 h (5·2–5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≥6·2 h) increased from 0·6% in 2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identified, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30% between 2001 and 2004, to 66% between 2007 and 2010. Interpretation Genetically determined artemisinin resistance in P falciparum emerged along the Thailand–Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2–6 years. Funding The Wellcome Trust and National Institutes of Health.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(12)60484-X</identifier><identifier>PMID: 22484134</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Antimalarials - administration &amp; dosage ; artemisinin ; Artemisinins - administration &amp; dosage ; Biological and medical sciences ; Deoxyribonucleic acid ; DNA ; Drug Resistance - genetics ; Epidemiology ; erythrocytes ; Female ; General aspects ; Genetics ; genotype ; Genotypes ; half life ; Human protozoal diseases ; Humans ; Infectious diseases ; Internal Medicine ; Longitudinal Studies ; Malaria ; Malaria, Falciparum - drug therapy ; Malaria, Falciparum - epidemiology ; Malaria, Falciparum - prevention &amp; control ; Male ; Medical sciences ; Mortality ; National Institutes of Health ; Parasite Egg Count ; Parasites ; Parasitic diseases ; patients ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - genetics ; Polymorphism, Single Nucleotide - genetics ; Protozoal diseases ; Public health. Hygiene ; Public health. Hygiene-occupational medicine ; single nucleotide polymorphism ; Thailand - epidemiology ; Vector-borne diseases</subject><ispartof>The Lancet (British edition), 2012-05, Vol.379 (9830), p.1960-1966</ispartof><rights>Elsevier Ltd</rights><rights>2012 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited May 26-Jun 1, 2012</rights><rights>2012 Elsevier Ltd. All rights reserved. 2012 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c755t-f4841d2e449e688fd016a436967efe4eb7b2abee120a9395ed6a8f2c7011b8f23</citedby><cites>FETCH-LOGICAL-c755t-f4841d2e449e688fd016a436967efe4eb7b2abee120a9395ed6a8f2c7011b8f23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S014067361260484X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=25928379$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22484134$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Phyo, Aung Pyae, MD</creatorcontrib><creatorcontrib>Nkhoma, Standwell, PhD</creatorcontrib><creatorcontrib>Stepniewska, Kasia, PhD</creatorcontrib><creatorcontrib>Ashley, Elizabeth A, MD</creatorcontrib><creatorcontrib>Nair, Shalini, MSc</creatorcontrib><creatorcontrib>McGready, Rose, MD</creatorcontrib><creatorcontrib>ler Moo, Carit</creatorcontrib><creatorcontrib>Al-Saai, Salma, MSc</creatorcontrib><creatorcontrib>Dondorp, Arjen M, MD</creatorcontrib><creatorcontrib>Lwin, Khin Maung, MD</creatorcontrib><creatorcontrib>Singhasivanon, Pratap, MD</creatorcontrib><creatorcontrib>Day, Nicholas PJ, FRCP</creatorcontrib><creatorcontrib>White, Nicholas J, FRS</creatorcontrib><creatorcontrib>Anderson, Tim JC, PhD</creatorcontrib><creatorcontrib>Nosten, François, Prof</creatorcontrib><title>Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Summary Background Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international effort is underway to contain artemisinin-resistant Plasmodium falciparum , but containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand–Myanmar (Burma) border. Methods In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≥4% infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms. Findings 3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95% CI 2·5–2·7) in 2001, to 3·7 h (3·6–3·8) in 2010, compared with a mean of 5·5 h (5·2–5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≥6·2 h) increased from 0·6% in 2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identified, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30% between 2001 and 2004, to 66% between 2007 and 2010. Interpretation Genetically determined artemisinin resistance in P falciparum emerged along the Thailand–Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2–6 years. Funding The Wellcome Trust and National Institutes of Health.</description><subject>Antimalarials - administration &amp; dosage</subject><subject>artemisinin</subject><subject>Artemisinins - administration &amp; dosage</subject><subject>Biological and medical sciences</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Drug Resistance - genetics</subject><subject>Epidemiology</subject><subject>erythrocytes</subject><subject>Female</subject><subject>General aspects</subject><subject>Genetics</subject><subject>genotype</subject><subject>Genotypes</subject><subject>half life</subject><subject>Human protozoal diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Internal Medicine</subject><subject>Longitudinal Studies</subject><subject>Malaria</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Malaria, Falciparum - epidemiology</subject><subject>Malaria, Falciparum - prevention &amp; control</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mortality</subject><subject>National Institutes of Health</subject><subject>Parasite Egg Count</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>patients</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - genetics</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Protozoal diseases</subject><subject>Public health. Hygiene</subject><subject>Public health. Hygiene-occupational medicine</subject><subject>single nucleotide polymorphism</subject><subject>Thailand - epidemiology</subject><subject>Vector-borne diseases</subject><issn>0140-6736</issn><issn>1474-547X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkk9v1DAQxSMEotvCRwAioUrlELAdx0k4FKGq_JEqcWgr7c2aOJNdl6xd7GzRfnsmm2ULvcDFtuTfPM2bN0nygrO3nHH17pJxyTJV5uqEizeKyUpm80fJjMtSZoUs54-T2R45SA5jvGGMScWKp8mBEITzXM6S5nyFYYHOYOq7FMKAKxutsy4LGG0cwA3pCnoIFlLv0mGJ6U-MAwaXNj60GMayqyXYHlz7PoW0925hh3VrHfRppMfmWfKkgz7i8919lFx_Or86-5JdfPv89ezjRWbKohiybmypFShljaqqupZcgsxVrUrsUGJTNgIaRC4Y1HldYKug6oQpGecNPfKj5HTSvV03K2wNuiFAr2-DXUHYaA9W__3j7FIv_J3OC1HUFSOBk51A8D_W5FLTLAz2ZA39OmrO8kpxrlj5HygvlRB0Evr6AXrj14Gms6VqJmrOJFHFRJngYwzY7fvmbOSU3gauxzQ1F3obuJ5T3cs_Te-rfidMwPEOgGig7wI4Y-M9V9SiysuauFcT14HXsAjEXF-SgYIxLmrFFREfJgIpxDuLQUdjx81pbUAz6NbbfzZ7-kDB9LRr1NZ33GC8n4uOQrNJZNTgYqswz38B9xHmrw</recordid><startdate>20120526</startdate><enddate>20120526</enddate><creator>Phyo, Aung Pyae, MD</creator><creator>Nkhoma, Standwell, PhD</creator><creator>Stepniewska, Kasia, PhD</creator><creator>Ashley, Elizabeth A, MD</creator><creator>Nair, Shalini, MSc</creator><creator>McGready, Rose, MD</creator><creator>ler Moo, Carit</creator><creator>Al-Saai, Salma, MSc</creator><creator>Dondorp, Arjen M, MD</creator><creator>Lwin, Khin Maung, MD</creator><creator>Singhasivanon, Pratap, MD</creator><creator>Day, Nicholas PJ, FRCP</creator><creator>White, Nicholas J, FRS</creator><creator>Anderson, Tim JC, PhD</creator><creator>Nosten, François, Prof</creator><general>Elsevier Ltd</general><general>Elsevier</general><general>Elsevier Limited</general><general>Lancet Publishing Group</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TT</scope><scope>0TZ</scope><scope>0U~</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88C</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>KB~</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>5PM</scope></search><sort><creationdate>20120526</creationdate><title>Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study</title><author>Phyo, Aung Pyae, MD ; 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Fisheries Abstracts (ASFA) 1: Biological Sciences &amp; Living Resources</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) 3: Aquatic Pollution &amp; Environmental Quality</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) Professional</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Phyo, Aung Pyae, MD</au><au>Nkhoma, Standwell, PhD</au><au>Stepniewska, Kasia, PhD</au><au>Ashley, Elizabeth A, MD</au><au>Nair, Shalini, MSc</au><au>McGready, Rose, MD</au><au>ler Moo, Carit</au><au>Al-Saai, Salma, MSc</au><au>Dondorp, Arjen M, MD</au><au>Lwin, Khin Maung, MD</au><au>Singhasivanon, Pratap, MD</au><au>Day, Nicholas PJ, FRCP</au><au>White, Nicholas J, FRS</au><au>Anderson, Tim JC, PhD</au><au>Nosten, François, Prof</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2012-05-26</date><risdate>2012</risdate><volume>379</volume><issue>9830</issue><spage>1960</spage><epage>1966</epage><pages>1960-1966</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>Summary Background Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international effort is underway to contain artemisinin-resistant Plasmodium falciparum , but containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand–Myanmar (Burma) border. Methods In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≥4% infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms. Findings 3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95% CI 2·5–2·7) in 2001, to 3·7 h (3·6–3·8) in 2010, compared with a mean of 5·5 h (5·2–5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≥6·2 h) increased from 0·6% in 2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identified, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30% between 2001 and 2004, to 66% between 2007 and 2010. Interpretation Genetically determined artemisinin resistance in P falciparum emerged along the Thailand–Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2–6 years. Funding The Wellcome Trust and National Institutes of Health.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>22484134</pmid><doi>10.1016/S0140-6736(12)60484-X</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0140-6736
ispartof The Lancet (British edition), 2012-05, Vol.379 (9830), p.1960-1966
issn 0140-6736
1474-547X
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3525980
source MEDLINE; Elsevier ScienceDirect Journals
subjects Antimalarials - administration & dosage
artemisinin
Artemisinins - administration & dosage
Biological and medical sciences
Deoxyribonucleic acid
DNA
Drug Resistance - genetics
Epidemiology
erythrocytes
Female
General aspects
Genetics
genotype
Genotypes
half life
Human protozoal diseases
Humans
Infectious diseases
Internal Medicine
Longitudinal Studies
Malaria
Malaria, Falciparum - drug therapy
Malaria, Falciparum - epidemiology
Malaria, Falciparum - prevention & control
Male
Medical sciences
Mortality
National Institutes of Health
Parasite Egg Count
Parasites
Parasitic diseases
patients
Plasmodium falciparum
Plasmodium falciparum - drug effects
Plasmodium falciparum - genetics
Polymorphism, Single Nucleotide - genetics
Protozoal diseases
Public health. Hygiene
Public health. Hygiene-occupational medicine
single nucleotide polymorphism
Thailand - epidemiology
Vector-borne diseases
title Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study
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