Prevalence and prognostic significance of viral co-infection of the brain in HIV-infected adults with bacterial meningitis in Malawi

Current research

Bacterial meningitis is associated with an unacceptably high rate of death and disability in sub-Saharan Africa. Previous MRF-funded studies have found no benefit from either adjunctive corticosteroids or oral glycerol in these populations. The cause of this high mortality remains uncertain but late presentation and delayed door-to-needle times, marked fluid, acid-base and electrolyte derangement on admission, impaired sterilisation of the cerebrospinal fluid (CSF), brain infection with neurotropic HIV quasi-species and viral co-infection of the central nervous system may all contribute.

A study is currently underway at Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi to look at the operational and clinical factors. The proposed project will focus on the virological contribution to poor outcome with three specific aims: to determine the frequency and aetiology of brain viral co-infection in adults with bacterial meningitis; to examine quasi-species compartmentalization of HIV in the CNS; and to determine whether this viral co-infection is associated with increased mortality.

We will analyse CSF samples taken from adult patients enrolled in two prospective studies of meningitis conducted at QECH. CSF highly suggestive of viral meningitis will be used to establish and validate CSF viral PCR in Blantyre. These assays will then be applied to the analysis of CSF from adult patients with proven or probable bacterial meningitis. This study will enable us to identify new targets for intervention in addition to conventional antibiotics. These may include antiviral agents against cytomegalovirus, herpes zoster virus and herpes simplex virus; and antiretroviral drugs that are highly active in the brain.