title: Suppressed circulating bicyclo-PGE2 levels and leukocyte COX-2 transcripts in children co-infected with P. falciparum malaria and HIV-1 or bacteremia.
abstract: In holoendemic Plasmodium falciparum transmission regions, malarial anemia is a leading cause of childhood morbidity and mortality. Identifying biomarkers of malaria disease severity is important for identifying at-risk groups and for improved understanding of the molecular pathways that influence clinical outcomes. We have previously shown that decreased cyclooxygenase (COX)-2-derived prostaglandin E2 (PGE2) levels are associated with enhanced clinical severity in cerebral malaria, malarial anemia, and malaria during pregnancy. Since children with malaria often have increased incidence of additional infections, such as bacteremia and HIV-1, we extend our previous findings by investigating COX-2 and PGE2 in children with falciparum malaria and co-infection with either bacteremia or HIV-1. Plasma bicyclo-PGE2/creatinine levels and peripheral blood COX-2 transcripts were significantly reduced in co-infected children relative to those with malaria mono-infection. Furthermore, suppression of circulating bicyclo-PGE2 was significantly associated with reduced hemoglobin levels in both mono- and co-infected children with malaria, suggesting that bicyclo-PGE2 may represent both a marker and mediator of malaria pathogenesis.
authors.affiliation: University of New Mexico, Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Anyona
authors.forename: Prakasha
authors.initials: P
authors.lastname: Kempaiah
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Davenport
authors.forename: John M
authors.initials: JM
authors.lastname: Vulule
authors.forename: James B
authors.initials: JB
authors.lastname: Hittner
authors.forename: John M
authors.initials: JM
authors.lastname: Ong'echa
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Perkins
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000097:blood* / Q000150:complications; D001643:Bridged Bicyclo Compounds / Q000097:blood; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015232:Dinoprostone / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000201:enzymology*; D016778:Malaria, Falciparum / Q000097:blood* / Q000150:complications; D008297:Male; D010963:Plasmodium falciparum / Q000302:isolation & purification; D012333:RNA, Messenger / Q000097:blood*
chemical_list: D001643:Bridged Bicyclo Compounds; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: Anemia; Bacteremia; COX-2; HIV-1; PGE(2); SMA