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Metabolic Acidosis and Other Determinants of Hemoglobin-Oxygen Dissociation in Severe Childhood Plasmodium falciparum Malaria

Metabolic acidosis is a common complication of severe malaria caused by Plasmodium falciparum. The factors contributing to the acidosis were assessed in 62 children with severe falciparum malaria (cases) and in 29 control children who had recently recovered from mild or moderate malaria. The acidosis was largely caused by the accumulation of both lactic and 3-hydroxybutyric acids. The determinants of oxygen release to the tissues were also examined; although there was no difference between cases and controls in respect of 2,3-bisphosphoglycerate and mean corpuscular hemoglobin concentration, there was a marked increase in P₅₀ in the cases, caused by pyrexia, low pH, and base deficit. There was substantial relative or actual hypoglycemia in many cases. The relationship of these observations to therapeutic strategy is discussed.

Received February 26, 2007. Accepted for publication April 27, 2007.

Acknowledgments: This study was published with the permission of the Director of the Kenya Medical Research Institute (KEMRI). The authors thank the parents/guardians of children enrolled in the study for accepting the invitation to participate; the staff of Kilifi District Hospital and the KEMRI Centre for Geographic Medicine Research–Coast for valuable support and assistance during data collection; and Jacktone Obeiro for collaboration in the early stages of the project. The American Society of Tropical Medicine and Hygiene (ASTMH) assisted with publication expenses.

Financial support: This study was funded through the KEMRI/ Wellcome Trust Research Programme. P. Sasi was supported by a Research Capacity Strengthening Grant from WHO (TDR/MIM Grant 980074) to Professor Gilbert Kokwaro.

^* Address correspondence to Robert D. Cohen, Longmeadow, East, Chichester, West Sussex PO18 0JB, UK. E-mail: rcohen{at}doctors.org.uk

Authors’ addresses: Philip Sasi and Moses Mosobo, KEMRI/ Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, PO Box 230-80108, Kilifi, Kenya, E-mail: Psasi{at}kilifi.mimcom.net. Shamus P. Burns, Claire L. Hobson, and Christopher G. King, School of Applied Sciences (Biological Sciences), University of Huddersfield, Huddersfield, UK, E-mail: S.P.Burns{at}hud.ac.uk. Catherine M. Waruiru, Department of Immunology, Royal Victoria Infirmary, Queen Victoria Road. Newcastle-upon-Tyne NE1 4LP, UK, E-mail: cmwaruiru{at}doctors.org.uk. Michael English, Child and Newborn Health Group, Centre for Geographic Medicine Research-Coast, PO Box 43640, 00100 GPO, Nairobi, Telephone: 254-2027-15160; E-mail: Menglish{at}nairobi.kemri-wellcome.org. John S. Beech, Department of Anaesthesia, University of Cambridge, Cambridge, UK, E-mail: jsb36{at}cam.ac.uk. Richard A. Iles, Department of Radiology and Physics, Institute of Child Health, 30 Guilford Street, London WC1N 3JH, UK, E-mail: R.A.Iles{at}qmul.ac.uk. Barbara J. Boucher and Robert D. Cohen, Longmeadow, East Dean, Chichester, West Sussex PO18 0JB, UK, Telephone: 440-1243-811230, Fax: 440-1243-811924, E-mails: rcohen{at}doctors.org.uk and bboucher{at}doctors.org.uk.

Reprints requests: R. D. Cohen, Longmeadow, East, Chichester, West Sussex PO18 0JB, UK. E-mail: rcohen{at}doctors.org.uk.