Mannitol and inflammatory markers in the cerebral spinal fluid of HIV-infected patients with cryptococcal meningitis

Abstract

Mannitol is a polyol produced by Cryptococcus neoformans and other fungi, including Aspergillus and Saccharomyces species [1]. A by-product of fungal metabolism, mannitol acts as a scavenger for extracellular free radicals protecting the organism from the environment and assists in the evasion of host phagocytic destruction [2–4]. Mannitol has been detected at higher concentrations in the cerebrospinal fluid (CSF) of animals with cryptococcal meningitis (CM) than in uninfected controls [4]. The accumulation of mannitol in the CSF may exert a significant osmotic effect in the central nervous system of patients with C. neoformans meningitis, due to its inability to cross the blood–brain barrier and its resistance to host metabolism [5]. The concentration of mannitol in the CSF has been correlated with both cryptococcal antigen titre and with quantitative cryptococcal culture in animal models of CM [4]. Megson et al. [5] were able to detect mannitol in 19 of 20 CSF samples from HIV-infected patients with CM; however, no comparisons were made to the levels in uninfected controls or to disease severity. CSF was collected with informed consent from HIVinfected patients for whom the diagnosis of CM was being considered. Mannitol may play a role in the development of cerebral oedema and increased intracranial pressure (ICP) seen in patients with CM, and its presence during infection may impact the host local inflammatory response. We hypothesised that an elevated ICP, as measured by the opening pressure (OP), and local central nervous system (CNS) inflammatory parameters from confirmed cases of CM would correlate to the CSF concentration of mannitol and that these levels would be higher than in HIV-infected patients without CM. CM diagnosis was made based on the clinical signs and symptoms of meningitis and either confirmed growth of C. neoformans from CSF or blood and/or a detectable CSF cryptococcal antigen titre of 1:2 or higher. Control patients presented with a clinical suspicion for meningitis, but their CSF and blood cultures did not yield C. neoformans and their CSF cryptococcal antigen tests were negative. Patients with a prior history of CM were excluded. CSF samples were stored at −80°C until batched analysis could be performed. The concentration (μg/ml) of mannitol was determined by the gas–liquid chromatography method previously described by Wong et al. [4]. Undiluted CSF samples were assayed in duplicate for selected inflammatory parameters Eur J Clin Microbiol Infect Dis (2008) 27:477–479 DOI 10.1007/s10096-008-0462-1