Authors’ addresses: Aubrey J. Cunnington, Department of Paediatrics, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom, E-mail: firstname.lastname@example.org. Stuart F.W. Kendrick, Department of Medicine, University Hospital of North Durham, North Road, Durham, DH1 5TW, United Kingdom, E-mail: email@example.com. Betty Wamola, Department of Paediatrics, Whittington Hospital, Highgate Hill, London, N19 5NF, United Kingdom and Kenya Medical Research Institute, Centre for Geographic Medicine Research (Coast)/Wellcome Trust Research Unit, PO Box 230, Kilifi, Kenya, E-mail: firstname.lastname@example.org. Brett Lowe, Kenya Medical Research Institute, Centre for Geographic Medicine Research (Coast)/Wellcome Trust Research Unit, PO Box 230, Kilifi, Kenya, E-mail: email@example.com. Charles R. J. C. Newton, Kenya Medical Research Institute, Centre for Geographic Medicine Research (Coast)/Wellcome Trust Research Unit, PO Box 230, Kilifi, Kenya and Neurosciences Unit, The Wolfson Centre, Mecklenburgh Square, London,WC1N 2AP, United Kingdom, E-mail: firstname.lastname@example.org.
Acknowledgments: We thank the Medical Officer of Health, the Medical Superintendent, the staff of Kilifi District Hospital, and N. Peshu (Director of the centre) for their support. This paper is published with the permission of the director of the Kenya Medical Research Institute.
Financial support: This study was supported by the Kenya Medical Research Institute and the Wellcome Trust. C. R. J. C. Newton is a Wellcome Trust Senior clinical fellow (050533).
Schluesener HJ, Kremsner PG, Meyerman R, 2001. Heme oxygenase-1 in lesions of human cerebral malaria. Acta Neuropathol (Berl) 101 :65–68.
Medana IM, Mai NT, Day NP, Hein TT, Bethell D, Phu NH, Farrar J, White NJ, Turner GD, 2001. Cellular stress and injury responses in the brains of adult Vietnamese patients with fatal Plasmodium falciparum malaria. Neuropathol Appl Neurobiol 27 :421–433.
Clark IA, Awburn MM, Harper CG, Liomba NG, Molyneux ME, 2003. Induction of HO-1 in tissue macrophages and monocytes in fatal falciparum malaria and sepsis. Malaria J 2 :41.
Landaw SA, Callahan EW, Schmid R, 1970. Catabolism of heme in vivo: comparison of the simultaneous production of bilirubin and carbon monoxide. J Clin Invest 49 :914–925.
Coburn RF, Williams WJ, Forster RE, 1964. Effect of erythrocyte destruction on carbon monoxide production in man. J Clin Invest 43 :1098–1103.
Craft JA, Alessandrini E, Kenney LB, Klein B, Bray G, Luban NLC, Meek R, Nadkarni VM, 1994. Comparison of oxygenation measurements in pediatric patients during sickle cell crises. J Pediatr 124 :93–95.
Wagener FA, Eggert A, Boerman OC, Oyen WJ, Verhofstad A, Abraham NG, Adema G, van Kooyk Y, de Witte T, Figdor CG, 2001. Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase. Blood 98 :1802–1811.
Otterbein L, Sylvester SL, Choi AMK, 1995. Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase-1. Am J Respir Cell Mol Biol 13 :595–601.
Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, Davis RJ, Flavell RA, Choi AM, 2000. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6 :422–428.
Fujita T, Toda K, Karimova A, Yan S-F, Naka Y, Yet S-F, Pinsky DJ, 2001. Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis. Nat Med 7 :598–604.
Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S, 1999. Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest 103 :129–135.
Kremsner PG, Greve B, Lell B, Luckner D, Schmid D, 2000. Malarial anaemia in African children associated with high oxygen-radical production. Lancet 355 :40–41.
Griffiths MJ, Ndungu F, Baird KL, Muller DPR, Marsh K, Newton CRJC, 2001. Oxidative stress and erythrocyte damage in Kenyan children with severe Plasmodium falciparum malaria. Br J Haematol 113 :486–491.
Schwarzer E, De Matteis F, Giribaldi G, Ulliers D, Valente E, Arese P, 1999. Hemozoin stability and dormant induction of heme oxygenase in hemozoin-fed human monocytes. Mol Biochem Parasitol 100 :61–72.
Berkley JA, Ross A, Mwangi I, Osier FHA, Mohammed M, Shebbe M, Lowe BS, Marsh K, Newton CRJC, 2003. Prognostic indicators of early and late death in children admitted to district hospital in Kenya: cohort study. BMJ 326 :361–364.
Wald NJ, Idle M, Boreham J, Bailey A, 1981. Carbon monoxide in breath in relation to smoking and carboxyhaemoglobin levels. Thorax 36 :366–369.
Coburn RF, Forster RE, Kane PB, 1965. Considerations of the physiological variables that determine the blood carboxyhemoglobin concentration in man. J Clin Invest 44 :1899–1910.
Uko GP, Gbadebo JA, Banjoko SO, 1998. Carboxyhaemoglobin levels in some Lagos dwellers - a pilot study. West Afr J Med 17 :202–205.
Newton CRJC, Warn PA, Winstanley PA, Peshu N, Snow RW, Pasvol G, Marsh K, 1997. Severe anaemia in children living in a malaria endemic area of Kenya. Trop Med Int Health 2 :165–178.
Shi Y, Pan F, Li H, Pan J, Qin S, Jiang D, Shen C, 2003. Carbon monoxide concentrations in paediatric sepsis syndrome. Arch Dis Child 88 :889–890.
Sears DA, Udden MM, Thomas LJ, 2001. Carboxyhemoglobin levels in patients with sickle-cell anemia: relationship to hemolytic and vasoocclusive severity. Am J Med Sci 322 :345–348.
Looareesuwan S, Davis TM, Pukrittayakamee S, Supanaranond W, Desakorn V, Silamut K, Krishna S, Boonamrung S, White NJ, 1991. Erythrocyte survival in severe falciparum malaria. Acta Trop 48 :263–270.
Chen YH, Wang SC, 1985. A simple method for estimating the hemolytic rate in patients with sickle cell anemia. J Lab Clin Med 105 :201–208.
Eckman JR, Modler S, Eaton JW, Berger E, Engel RR, 1977. Host heme catabolism in drug-sensitive and drug-resistant malaria. J Lab Clin Med 90 :767–770.