An Analytical Method for Assessing Stage-Specific Drug Activity in Plasmodium vivax Malaria Implications for Ex Vivo Drug Susceptibility Testing 英文参考文献.docVIP

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An Analytical Method for Assessing Stage-Specific Drug Activity in Plasmodium vivax Malaria Implications for Ex Vivo Drug Susceptibility Testing 英文参考文献.doc

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An Analytical Method for Assessing Stage-Specific Drug Activity in Plasmodium vivax Malaria Implications for Ex Vivo Drug Susceptibility Testing 英文参考文献

AnAnalyticalMethodforAssessingStage-SpecificDrug ActivityinPlasmodiumvivaxMalaria:ImplicationsforEx VivoDrugSusceptibilityTesting DouglasH.Kerlin1,KaneBoyce1,JuttaMarfurt2,JulieA.Simpson3,EnnyKenangalem4,5,6,QinCheng7, RicN.Price2,8,MichelleL.Gatton1* 1MalariaDrugResistanceandChemotherapyLaboratory,QueenslandInstituteofMedicalResearch,Brisbane,Australia,2MenziesSchoolofHealthResearchandCharles DarwinUniversity,Darwin,Australia,3CentreforMolecular,Environmental,GeneticandAnalyticEpidemiology,UniversityofMelbourne,Melbourne,Australia,4Papuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia, 5District Health Authority and the Menzies School of Health Research-National Institute ofHealthResearchandDevelopment,Timika,Papua,Indonesia, 6DistrictMinistryofHealth,Timika,Papua,Indonesia,7DepartmentofDrugResistanceand Diagnostics,AustralianArmyMalariaInstitute,Brisbane,Australia,8CentreforTropicalMedicine,NuffieldDepartmentofClinicalMedicine,UniversityofOxford,Oxford, UnitedKingdom Abstract Theemergenceofhighlychloroquine(CQ)resistantP.vivaxinSoutheastAsiahascreatedanurgentneedforanimproved understandingofthemechanismsofdrugresistanceintheseparasites,thedevelopmentofrobusttoolsfordefiningthe spreadofresistance,andthediscoveryofnewantimalarialagents.TheexvivoSchizontMaturationTest(SMT),originally developedforthestudyofP.falciparum,hasbeenmodifiedforP.vivax.Weretrospectivelyanalysedtheresultsfrom760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasitesusceptibilitytoantimalarialdrugs.Previousobservationsofthestage-specificactivityofCQagainstP.vivaxwere confirmed,andshowntohaveprofoundconsequencesforinterpretationoftheassay.Usinganonlinearmodelweshow increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreasedeffectiveconcentration(EC50)valuesofCQ,andidentifyathresholdwheretheseassociations nolongerho