No Seasonal Accumulation of Resistant P. falciparum when High-Dose Chloroquine Is Used 英文参考文献.docVIP

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No Seasonal Accumulation of Resistant P. falciparum when High-Dose Chloroquine Is Used 英文参考文献.doc

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No Seasonal Accumulation of Resistant P. falciparum when High-Dose Chloroquine Is Used 英文参考文献

NoSeasonalAccumulationofResistantP.falciparum whenHigh-DoseChloroquineIsUsed JohanUrsing1,2*,Poul-ErikKofoed2,3,4,AmabeliaRodrigues2,LarsRombo1,5,6 1MalariaResearch,DepartmentofInfectiousDiseases,KarolinskaHospital,KarolinskaInstitutet,Stockholm,Sweden,2ProjectodeSau′dedeBandim,IndepthNetwork, Bissau, Guinea-Bissau, 3Department of Paediatrics, Kolding Hospital, Kolding, Denmark, 4Research Initiative of Health Services, Kolding Hospital, Kolding, Denmark, 5DepartmentofInfectiousDiseases,Ma¨larsjukhuset, Eskilstuna,Sweden,6CenterforClinicalResearch,SormlandCountyCouncil,Eskilstuna,Sweden Abstract Background:PotentiallychloroquineresistantP.falciparum,identifiedbythe76Thaplotypeinthechloroquineresistance transporter(pfcrt76T),arehighlyprevalentthroughoutAfrica.InGuinea-Bissau,normalanddoubledosechloroquinehave respectiveefficaciesof34%and78%againstP.falciparumwithpfcrt76Tandapproximatelythreetimesthenormaldoseof chloroquineisroutinelytaken.Proportionsofpfcrt76Tgenerallyincreaseduringhightransmissionseasons,asP.falciparum withpfcrt76Tcommonlysurvivetreatmentwithnormaldosechloroquine.InGuinea-Bissau,thereshouldbenoseasonal increaseofpfcrt76TifthehighdosesofCQcommonlyusedareeffective. Methods and Findings: P. falciparum parasite density, age, sex, the proportion of chloroquine resistance associated haplotypespfcrt76TandP.falciparummultidrugresistancegene186Ywereassessedin988samplescollectedfromchildren between2002and2007.Therewasnoseasonalaccumulationofanyallele.Duringthehighandlowtransmissionperiods thepfcrt76Tproportionswere24%(95%CI,21–27%)and26%(95%CI,20–33%).Therewasnosignificantchangeofpfcrt 76T(OR1.05,95%CI;0.94–1.16p=0.39)orpfmdr186Y(OR0.92,95%CI;0.83–1.01p=0.08)proportionsbetween2003and 2007.Lowermedianparasitedensity(P.falciparum/ml)wasassociatedwithpfcrt76T(15254[95%CI,12737–17772];n=164) comparedtopfcrt76K(18664[95%CI,16676–20653];p=0.003;n=591).Similarly,pfmdr186Ywasassociatedwithalower medianparasitedensity(16320[95%CI,13696–18944];n=224)comparedtopfmdr1