CEREBROSPINAL-FLUID LEVELS OF BIOPTERIN, NITRIC-OXIDE METABOLITES, AND IMMUNE ACTIVATION MARKERS AND THE CLINICAL COURSE OF HUMAN CEREBRAL MALARIA

Cerebrospinal fluid samples from 130 children who presented with cereb ral malaria were investigated to elucidate the impact of biopterin pro duction, NO formation, and local immune activation on the clinical cou rse of this disease. Biopterin levels were significantly lower in pati ents who were in a deeper coma (P = .02). Cerebrospinal fluid concentr ations of NO were significantly higher in children who died than in su rvivors (P = .037); however, this was not the case for macrophage acti vation markers, neopterin, and soluble tumor necrosis factor receptor p75 (sTNFR-75). Biopterin, neopterin, and sTNFR-75 but not NO concentr ations were significantly related to each other. Low biopterin levels in deep coma are compatible with an impaired local Th1 response, but t he low levels could also be due to the scavenging of radicals or to de creased neurotransmitter synthesis. Local production of NO, most likel y by nonimmune mechanisms, may be detrimental in cerebral malaria; how ever, this appears not to be the case for local Th1-mediated immune pa thways.