title: The metabolism of platelet-activating factor in severe and cerebral malaria.
abstract: In order to examine the effects of platelet-activating factor (PAF) in complicated Plasmodium falciparum infections, plasma concentrations of lyso-PAF, stable metabolite and principal precursor of PAF, were measured in 25 Vietnamese adults with severe malaria. The concentration of PAF in the cerebrospinal fluid (CSF) was determined in a sub-group of 23 comatose patients and, together with that of lyso-PAF, in the plasma of 20 patients on recovery of consciousness. The concentration of lyso-PAF in the plasma was depressed on admission to hospital (median [range]; 21 [8-143] vs. 293 [215-410] ng/ml in 10 controls; P < 0.001). There was, however, no change in plasma activity of acetylhydrolase which converts PAF to lyso-PAF (P > 0.01 vs. controls) while simultaneous reduction in the concentration of lipoproteins associated with lyso-PAF were less than those of lyso-PAF per se in the plasma. The plasma concentration of lyso-PAF on admission was associated with parasitaemia and the concentration of serum triglycerides (rs = -0.42, P = 0.04 in each case), the latter being consistent with hepatic effects of PAF reported in previous studies. CSF concentrations of PAF on admission were low (2.3 [0.5-7.7] vs. 0.9 [0-2.5] ng/ml after recovery, P < 0.01) compared with values reported previously in bacterial meningitis. Plasma concentrations of lyso-PAF after recovery lay between admission and control values. While increased availability of PAF may reflect parasite burden and may modulate liver-mediated metabolic disturbances such as hypoglycaemia and lactic acidosis, the role of PAF in cerebral malaria is uncertain.
authors.affiliation: University of Western Australia, Department of Medicine, Fremantle Hospital.
authors.forename: T M
authors.initials: TM
authors.lastname: Davis
authors.forename: T Q
authors.initials: TQ
authors.lastname: Binh
authors.forename: N
authors.initials: N
authors.lastname: van Phuong
authors.forename: M
authors.initials: M
authors.lastname: Sturm
authors.forename: A
authors.initials: A
authors.lastname: St John
authors.forename: J R
authors.initials: JR
authors.lastname: Dyer
authors.forename: T K
authors.initials: TK
authors.lastname: Anh
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003128:Coma / Q000378:metabolism; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D050356:Lipid Metabolism; D016779:Malaria, Cerebral / Q000188:drug therapy / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000378:metabolism*; D014744:Vietnam / Q000208:ethnology; D014904:Western Australia
chemical_list: D000962:Antimalarials; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D002784:Cholesterol