Prevalence and prognostic significance of viral co-infection of the brain in HIV-infected adults with bacterial meningitis in Malawi
Dr David Lalloo, Dr Katharine Cartwright, Dr Matthew Kelly, Prof Rob Heyderman, Prof Tom Solomon
- Start Date:
01 June 2009
Queen Elizabeth Central Hospital, Malawi-Liverpool-Wellcome Research Laboratories, College of Medicine, Blantyre, Malawi, Liverpool School of Tropical Medicine, Liverpool, UK
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.
Brain fluid samples from 149 Malawian adults with meningitis (115 HIV-positive) and 39 adults without meningitis (24 HIV-positive) were studied. Over half the patients with meningitis died. We found an unexpectedly high rate of EBV virus (the cause of glandular fever and some cancers called lymphomas). EBV was detected in 70/115 HIV-positive and 9/34 HIV-negative patients with meningitis, and in 6/24 HIV-positive patients without meningitis. Death was more likely in those with EBV as well as bacterial meningitis. When there was also CMV virus (causes brain, eye, lung and gut problems in AIDS patients) as well as EBV in the brain, only 2/10 patients survived.
In work undertaken in Dr Paul Clapham’s laboratory in Massachusetts using the same samples but not funded directly by MRF, we are beginning to understand how special types of the HIV virus may lead to a higher likelihood of death.
The results will enable us to identify new targets for treatment in addition to the usual antibiotics. These treatments may include anti-virus drugs and drugs against HIV that are highly active in the brain.
This group have published their results in the Journal of Infectious Diseases 2012 Jan;205(1):106-10. Epub 2011 Nov 9.