Related Experiment Videos
The metabolism of platelet-activating factor in severe and cerebral malaria
T M Davis1, T Q Binh, N van Phuong
1University of Western Australia, Department of Medicine, Fremantle Hospital.
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.
Insights
In severe malaria, plasma lyso-platelet-activating factor (PAF) was depressed, suggesting PAF may influence parasite burden and metabolic disturbances. However, its precise role in cerebral malaria remains unclear.
Area of Science:
- Biomedical Science
- Infectious Diseases
- Malariology
Background:
- Platelet-activating factor (PAF) is implicated in inflammatory processes.
- Complicated Plasmodium falciparum infections, or severe malaria, involve complex pathophysiological mechanisms.
Purpose of the Study:
- To investigate the role of platelet-activating factor (PAF) and its metabolite lyso-PAF in severe malaria.
- To measure plasma and cerebrospinal fluid (CSF) concentrations of PAF and lyso-PAF in patients with severe malaria.
Main Methods:
- Plasma lyso-PAF and PAF concentrations were measured in 25 Vietnamese adults with severe malaria.
- CSF PAF concentrations were measured in 23 comatose patients.
- Plasma acetylhydrolase activity and lipoprotein concentrations were also assessed.
Main Results:
- Plasma lyso-PAF concentrations were significantly lower in severe malaria patients compared to controls.
- CSF PAF concentrations were lower in comatose patients on admission than after recovery.
- Plasma lyso-PAF levels correlated with parasitaemia and serum triglyceride levels.
Conclusions:
- Depressed plasma lyso-PAF in severe malaria may indicate altered PAF metabolism.
- PAF might modulate parasite burden and hepatic metabolic disturbances like hypoglycemia and lactic acidosis.
- The specific role of PAF in the pathogenesis of cerebral malaria requires further investigation.