?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%2F8767%2F&rft.title=Hemoglobinopathies+in+Children+within+a+Malaria+Holoendemic+Region+of+Western+Kenya&rft.creator=Remo%2C+Allison+M.&rft.description=Plasmodium+falciparum+malaria+is+one+of+the+predominant+causes+of+morbidity+and+mortality+in+children+under+five+years+of+age+in+sub-Saharan+Africa.+In+malaria+endemic+regions%2C+the+intensity+of+transmission+and+the+age+at+which+malaria+is+first+acquired+are+important+in+conditioning+disease+outcomes.+In+addition%2C+inter-individual+variability+in+disease+severity+among+age-matched+children+(aged+%3C3+yrs)+with+similar+levels+of+parasite+exposure+is+largely+determined+by+genetic+variability.+Historical+exposure+to+malaria+in+endemic+populations+has+exerted+tremendous+selective+pressure+on+the+human+genome%2C+particularly+in+the+host-immune+response+genes+that+mediate+susceptibility+and+clinical+outcomes.+Hemoglobinopathies%2C+such+as+the+alpha+thalassemia+3.7+kb+deletion+and+sickle-cell+trait+(HbAS)+also+confer+protection+against+severe+malaria+through+a+mechanism(s)+that+are+yet+to+be+fully+elucidated.+As+such%2C+this+study+examined+the+role+of+alpha+thalassemia+3.7+kb+deletion+and+HbAS+in+protection+against+severe+malaria+anemia+(SMA)+in+children+(n%3D468%3B+aged+3-36+months)+residing+in+a+holoendemic+P.+falciparum+transmission+region+of+western+Kenya.+These+investigations+demonstrated+that+successful+genotyping+of+the+deletion+required+high-quality+genomic+DNA+from+large+volumes+of+whole+blood+that+was+unavailable+for+most+of+the+small%2C+underweight-for-age%2C+severely+anemic+children+in+which+DNA+was+isolated+from+dried+blood+spots.+Results+presented+here+further+demonstrated+that+the+HbAS+genotype+was+significantly+associated+with+a+reduced+burden+of+both+low+(%3C10%25%3B+P%3D0.03)+and+high+(greater+than+or+equal+to+10%25%3B+P%3C0.001)+pigment-containing+monocytes+(PCM).+In+addition%2C+hemoglobin+(Hb%3B+P%3D0.05)+and+red+blood+cell+(RBC%3B+P%3D0.04)+counts+were+significantly+higher+in+the+HbAS+group+relative+to+children+with+the+HbAA+genotype.+The+HbAS+genotype+was+also+significantly+associated+with+protection+against+SMA+using+both+the+World+Health+Organization+(i.e.%2C+%3C5.0+g%2FdL%3B+P%3D0.04)+and+modified+definitions+of+SMA+(i.e.%2C+%3C6.0+g%2FdL%3B+P%3D0.02).+Taken+together%2C+results+presented+here+suggest+that+the+HbAS+genotype+confers+protection+against+SMA+by+reducing+the+natural+acquisition+of+malarial+pigment+(hemozoin)+in+monocytes.+This+study+has+significant+public+health+importance+by+demonstrating+that+one+of+the+mechanisms+by+which+HbAS+provides+protection+against+SMA+is+through+reducing+the+overall+burden+of+hemozoin+in+monocytes.&rft.date=2007-09-27&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%2F8767%2F1%2FRemothesis.pdf&rft.identifier=++Remo%2C+Allison+M.++(2007)+Hemoglobinopathies+in+Children+within+a+Malaria+Holoendemic+Region+of+Western+Kenya.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++