title: Decreased endothelial nitric oxide bioavailability, impaired microvascular function, and increased tissue oxygen consumption in children with falciparum malaria.
abstract: Endothelial nitric oxide (NO) bioavailability, microvascular function, and host oxygen consumption have not been assessed in pediatric malaria. We measured NO-dependent endothelial function by using peripheral artery tonometry to determine the reactive hyperemia index (RHI), and microvascular function and oxygen consumption (VO2) using near infrared resonance spectroscopy in 13 Indonesian children with severe falciparum malaria and 15 with moderately severe falciparum malaria. Compared with 19 controls, children with severe malaria and those with moderately severe malaria had lower RHIs (P = .03); 12% and 8% lower microvascular function, respectively (P = .03); and 29% and 25% higher VO2, respectively. RHIs correlated with microvascular function in all children with malaria (P < .001) and all with severe malaria (P < .001). Children with malaria have decreased endothelial and microvascular function and increased oxygen consumption, likely contributing to the pathogenesis of the disease.
authors.affiliation: Global Health Division, Menzies School of Health Research and Charles Darwin University Lee Kong Chian School of Medicine, Nanyang Technological University Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore.
authors.forename: Tsin W
authors.initials: TW
authors.lastname: Yeo
authors.affiliation: District Ministry of Health, Menzies School of Health Research-National Institute of Health Research and Development Research Program, Timika.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lampah
authors.affiliation: District Ministry of Health, Menzies School of Health Research-National Institute of Health Research and Development Research Program, Timika.
authors.forename: Enny
authors.initials: E
authors.lastname: Kenangalem
authors.affiliation: National Institute of Health Research and Development, Jakarta, Indonesia.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Tjitra
authors.affiliation: Division of Hematology, Department of Medicine, School of Medicine, Duke University Division of Hematology-Oncology, Durham VA Medical Center, North Carolina.
authors.forename: J Brice
authors.initials: JB
authors.lastname: Weinberg
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Utah School of Medicine, Division of Infectious Diseases, Department of Internal Medicine, VA Salt Lake Health Care System, Salt Lake City, Utah.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Granger
authors.affiliation: Global Health Division, Menzies School of Health Research and Charles Darwin University Division of Medicine, Royal Darwin Hospital, Australia Centre for Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.affiliation: Global Health Division, Menzies School of Health Research and Charles Darwin University Division of Medicine, Royal Darwin Hospital, Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
mesh_terms: D000818:Animals; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000737:chemistry* / Q000502:physiology*; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000503:physiopathology*; D008297:Male; D055806:Microvessels / Q000502:physiology*; D009569:Nitric Oxide / Q000032:analysis*; D010101:Oxygen Consumption; D019265:Spectroscopy, Near-Infrared
chemical_list: D009569:Nitric Oxide
keywords: Plasmodium falciparum; cerebral malaria; endothelial function; microvascular function; oxygen consumption; severe malaria; tissue hypoxia