?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F8630%2F&rft.title=Role+of+HIV-1+and+Bacteremia+Co-infection+in+Promoting+Inflammatory+Mediator+production+in+Kenyan+Children+with+Severe+Malarial+Anemia&rft.creator=Davenport%2C+Gregory+Charles&rft.description=Severe+anemia+is+the+primary+outcome+of+childhood+malaria+in+holoendemic+malaria+transmission+regions+such+as+western+Kenya.+HIV-1+and+bacteremia+are+equally+important+diseases+in+Kenyan+children.+Anemia+is+also+the+hallmark+trait+of+pediatric+HIV-1+infection%2C+and+despite+our+previous+reports+of+exacerbated+anemia+in+malaria%2FHIV-1+co-infected+childrena%2C+we+also+observed+significantly+lower+parasitemias+without+worsening+anemia+in+malaria%2Fbacteremia+co-infected+children.+Abundant+production+of+pro-inflammatory+cytokines+is+known+to+adversely+affect+erythropoiesis+and+is+common+to+malaria%2C+HIV-1%2C+and+bacteremia.+As+such%2C+we+performed+a+comprehensive+bead-based+25-plex+Multiplex+assay+to+identify+cytokines+patterns+and+profiles+associated+with+negative+and+positive+hematolgic+outcomes+in+co-infected+children.+Children+in+Aims+1+and+2+infected+with+P.+falciparum+malaria+(Pf%5B%2B%5D%2C+aged+3-36+mos.%2C+n%3D542)+were+stratified+into+three+groups%3A+HIV-1+negative+(HIV-1%5B-%5D%2FPf%5B%2B%5D)%3B+HIV-1+exposed+(HIV-1%5Bexp%5D%2FPf%5B%2B%5D)%3B+and+HIV-1+infected+(HIV-1%5B%2B%5D%2FPf%5B%2B%5D).+In+Aim+3%2C+malaria+and+bacteremia+co-infected+children+(n%3D192)+were+divided+into+three+categories%3A+malaria+alone%2C+Pf%5B%2B%5D%3B+Gram+negative+bacteremia%2Fmalaria+co-infected%2C+G%5B-%5D%2FPf%5B%2B%5D%3B+and+Gram+positive+bacteremia%2Fmalaria+co-infected%2C+G%5B%2B%5D%2FPf%5B%2B%5D.+Univariate%2C+correlational%2C+and+hierarchical+regression+analyses+were+used+to+determine+differences+among+the+groups+and+to+define+predictors+of+worsening+anemia.+Aim+1+analyses+revealed+HIV-1%5B%2B%5D%2FPf%5B%2B%5D+children+had+significantly+more+malarial+pigment-containing+neutrophils+(PCN)%2C+monocytosis%2C+increased+severe+anemia+(Hb%3C6.0g%2FdL)%2C+and+~10-fold+greater+mortality.+Hierarchical+multiple+regression+revealed+that+worsening+anemia+was+associated+with+elevated+pigment-containing+monocytes%2C+younger+age%2C+and+increasing+HIV-1+status+(HIV-1%5B-%5D%E2%86%92HIV-1%5Bexp%5D%E2%86%92HIV-1%5B%2B%5D).+Aim+2%2C+addressing+the+inflammatory+milieu%2C+demonstrated+that+exacerbated+anemia+was+associated+with+inflammatory+mediator+(IM)+dysregulation%2C+but+not+parasitemic+or+erythropoietic+indices.+A+principal+component+analysis+revealed+that+IL-12+was+the+most+influential+variable+on+Hb+levels+in+HIV-1%5B%2B%5D%2FPf%5B%2B%5D+children%2C+while+the+IL-1%CE%B2%3AIL-10+ratio+was+most+influenced+by+PCN.+In+Aim+3%2C+both+bacteremia+co-infected+groups+had+lower+parasitemia+compared+to+the+Pf%5B%2B%5D+group.+A+multiple+mediation+model+examining+IMs+responsible+for+decreased+parasitemia+in+the+bacteremia+co-infected+groups+identified+IL-4%2C+IL-10%2C+IL-12%2C+and+IFN-%CE%B3+as+the+key+molecules+in+decreasing+parasitemia.+Thus%2C+malaria%2FHIV-1+co-infection+is+defined+by+significantly+enhanced+anemia+that+is+associated+with+unique+IM+profiles+known+to+exacerbate+anemia%2C+while+enhanced+immune+activation+in+malaria%2Fbacteremia+co-infected+children+appears+to+promote+reduced+parasitemia+without+adversely+affecting+anemia+outcomes.+By+defining+the+inflammatory+milieu+associated+with+severe+anemia%2C+therapies+can+be+developed+to+mitigate+detrimental+immune+responses%2C+thereby+lessening+the+pediatric+public+health+burden+in+western+Kenya.&rft.date=2010-09-28&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F8630%2F1%2FDavenport_Gregory_C_09012010.pdf&rft.identifier=++Davenport%2C+Gregory+Charles++(2010)+Role+of+HIV-1+and+Bacteremia+Co-infection+in+Promoting+Inflammatory+Mediator+production+in+Kenyan+Children+with+Severe+Malarial+Anemia.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++