Serum Angiopoietin-1 and -2 Levels Discriminate Cerebral Malaria from Uncomplicated Malaria and Predict Clinical Outcome in African Children 英文参考文献.docVIP

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Serum Angiopoietin-1 and -2 Levels Discriminate Cerebral Malaria from Uncomplicated Malaria and Predict Clinical Outcome in African Children 英文参考文献.doc

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Serum Angiopoietin-1 and -2 Levels Discriminate Cerebral Malaria from Uncomplicated Malaria and Predict Clinical Outcome in African Children 英文参考文献

SerumAngiopoietin-1and-2LevelsDiscriminate CerebralMalariafromUncomplicatedMalariaand PredictClinicalOutcomeinAfricanChildren FionaE.Lovegrove1,NoppadonTangpukdee2,RobertO.Opoka3,ErinI.Lafferty1,NimertaRajwans1, MichaelHawkes1,SrivichaKrudsood2,SornchaiLooareesuwan2{,ChandyC.John4,W.ConradLiles1,5., KevinC.Kain1,5. * 1McLaughlin-RotmanCentreforGlobalHealth,McLaughlinCentreforMolecularMedicine,UniversityHealthNetwork,UniversityofToronto,Toronto,Ontario,Canada, 2FacultyofTropicalMedicine,MahidolUniversity,Bangkok,Thailand,3DepartmentofPaediatricsandChildHealth,MakerereUniversity,Kampala,Uganda,4Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America, 5Division of Infectious Diseases, Department of Medicine, UniversityofToronto,Toronto,Ontario,Canada Abstract Background:LimitedtoolsexisttoidentifywhichindividualsinfectedwithPlasmodiumfalciparumareatriskofdeveloping serious complications such as cerebral malaria (CM). The objective of this study was to assess serum biomarkers that differentiatebetweenCMandnon-CM,withthelong-termgoalofdevelopingaclinicallyinformativeprognostictestfor severemalaria. Methodology/PrincipalFindings:Basedonthehypothesisthatendothelialactivationandblood-brain-barrierdysfunction contributetoCMpathogenesis,weexaminedtheendothelialregulators,angiopoietin-1(ANG-1)andangiopoietin-2(ANG- 2), in serum samples from P. falciparum-infected patients with uncomplicated malaria (UM) or CM, from two diverse populations –Thaiadults andUgandanchildren.Angiopoietin levelswerecomparedtotumournecrosis factor (TNF).In bothpopulations,ANG-1levelsweresignificantlydecreasedandANG-2levelsweresignificantlyincreasedinCMversusUM andhealthycontrols(p,0.001).TNFwassignificantlyelevatedinCMintheThaiadultpopulation(p,0.001),butdidnot discriminate well between CM and UM in African children. Receiver operating characteristic curve analysis showed that ANG-1 and the ratio of ANG-2:ANG-1 accurately discriminated C