Malawi has a high incidence of bacterial meningitis among adults. Pilot studies suggest that this is mainly pneumococcal, and that the majority of the patients have HIV co-infection. Currently, mortality for bacterial meningitis in Blantyre is 56%, and 66% for proven pneumococcal meningitis. More effective locally appropriate treatments are an urgent priority.
There is some evidence from clinical trials that steroids reduce morbidity and possibly mortality in children with meningitis, but no trials large enough to address this question have been conducted in adults. Although adjuvant steroid therapy represents a major potential advance in the treatment of bacterial meningitis, its use in adults has been tempered by the fear that possible adverse events will outweigh the possible benefits.
The proposed study is a double blind, placebo controlled, randomised trial of steroids (dexamethasone) in bacterial meningitis in Blantyre, Malawi. The primary endpoint will be mortality, with measures of morbidity as the secondary endpoint.
The sample size to detect a 20% improvement would be around 660 patients, and at current incidence this is likely to be met in around two and a half years from the start of the trial.
By factorial design an additional open-label trial of intramuscular against intravenous ceftriaxone will be incorporated, generating both clinical and pharmacokinetic data. Ceftriaxone is a likely candidate to take over from penicillin and chloramphenicol as the treatment of choice in bacterial meningitis in Malawi, and there would be clear operational advantages if it were equally effective when administered by the intramuscular route.
Clinical and pathophysiological data derived from the trial will be used to try to help identify new therapeutic options.
Read our news release on this project:
Researchers in Liverpool conduct steroid trials to combat meningitis in Africa
Results from this study have been published in a scientific journal as follows:
Scarborough M, Njalale Y,
Bacterial meningitis in a high HIV prevalence setting in sub-Saharan Africa--challenges to a better outcome
Trop Doct 2004 Oct;34(4):203-5.