Metabolites of the kynurenine pathway of tryptophan metabolism in the cerebrospinal fluid of Malawian children with malaria.
A retrospective study of 100 Malawian children (87 with malaria and 13 with a diagnosis other than malaria) was conducted to determine the relationship between levels of metabolites of the kynurenine pathway in cerebrospinal fluid (CSF) and disease outcome. Three metabolites were measured: quinolinic acid (QA), an excitotoxin; kynurenic acid (KA), a neuroprotective receptor antagonist; and picolinic acid (PA), a proinflammatory mediator. Elevated levels of QA and PA in CSF were associated with a fatal outcome in Malawian children with cerebral malaria (CM). QA was associated with a history of convulsions. An increase in the QArcolon;KA ratio, which favors neurotoxicity, was observed only in the 3 patients with tuberculosis meningitis. Compared with Vietnamese adults with malaria, Malawian children with malaria had higher concentrations of KA. Elevated levels of KA in children with CM may serve to contain injury in the developing brain, which is more susceptible to excitotoxic damage than is the adult brain.
Medana
Isabelle M
IM
Nuffield Department of Clinical Laboratory Sciences, Oxford-Wellcome Centre for Tropical Medicine, John Radcliffe Hospital, Oxford, UK. isabelle.medana@ndcls.ox.ac.uk
Day
Nicholas P J
NP
Salahifar-Sabet
Houta
H
Stocker
Roland
R
Smythe
George
G
Bwanaisa
Lloyd
L
Njobvu
Alfred
A
Kayira
Kondwani
K
Turner
Gareth D H
GD
Taylor
Terrie E
TE
Hunt
Nicholas H
NH
D000328:Adult; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D006801:Humans; D007737:Kynurenine / Q000134:cerebrospinal fluid* / Q000378:metabolism; D016779:Malaria, Cerebral / Q000134:cerebrospinal fluid* / Q000401:mortality / Q000503:physiopathology*; D008295:Malawi; D010848:Picolinic Acids / Q000134:cerebrospinal fluid; D017378:Quinolinic Acid / Q000134:cerebrospinal fluid; D012189:Retrospective Studies; D014364:Tryptophan / Q000378:metabolism*; D014744:Vietnam
D010848:Picolinic Acids; D007737:Kynurenine; D014364:Tryptophan; D017378:Quinolinic Acid; C030614:picolinic acid