Abstract
Mortality from bacterial meningitis in African adults is significantly higher than those in better resourced settings and adjunctive therapeutic interventions such as dexamethasone and glycerol have been shown to be ineffective. We conducted a study analysing data from clinical trials of bacterial meningitis in Blantyre, Malawi to investigate the clinical parameters associated with this high mortality.MethodsWe searched for all clinical trials undertaken in Blantyre investigating bacterial meningitis from 1990 to the current time and combined the data from all included trial datasets into one database. We used logistic regression to relate individual clinical parameters to mortality. Adults with community acquired bacterial meningitis were included if the CSF culture isolate was consistent with meningitis or if the CSF white cell count was >100 cells/mm3 (>50% neutrophils) in HIV negative participants and >5 cells/mm3 in HIV positive participants. Outcome was measured by mortality at discharge from hospital (after 10 days of antibiotic therapy) and community follow up (day 40).ResultsSeven hundred and fifteen episodes of bacterial meningitis were evaluated. The mortality rate was 45% at day 10 and 54% at day 40. The most common pathogens were S.pneumoniae (84% of positive CSF isolates) and N.meningitidis (4%). 607/694 (87%) participants tested were HIV antibody positive. Treatment delays within the hospital system were marked. The median presenting GCS was 12/15, 17% had GCS<8 and 44.9% had a seizure during the illness. Coma, seizures, tachycardia and anaemia were all significantly associated with mortality on multivariate analysis. HIV status and pneumococcal culture positivity in the CSF were not associated with mortality. Adults with community acquired bacterial meningitis in Malawi present with a severe clinical phenotype. Predictors of high mortality are different to those seen in Western settings. Optimising in-hospital care and minimising treatment delays presents an opportunity to improve outcomes considerably.
Highlights
Since the beginning of the HIV epidemic, many high prevalence Sub-Saharan African countries have reported an increase in patients presenting to health care facilities with acute bacterial meningitis (ABM) [1,2]
Adults and adolescents presenting to hospital in Malawi with bacterial meningitis are young, largely HIV positive and have a very high mortality rate, contrasting significantly with published data from high income countries [3,24]
Eighty seven percent of participants in our study were HIV antibody positive compared to the Queen Elizabeth Central Hospital (QECH) medical inpatient rate of 76% and a current adult national population prevalence of 12% [25]
Summary
Since the beginning of the HIV epidemic, many high prevalence Sub-Saharan African countries have reported an increase in patients presenting to health care facilities with acute bacterial meningitis (ABM) [1,2]. Adult ABM mortality rates in sub-Saharan Africa have been reported to vary between 54–70% without any change over time [9,10,11,12] and survivors experience significantly higher rates of disabling neurological sequelae compared to European patients [13]. Interventions such as adjunctive dexamethasone and glycerol have failed to impact on this high mortality in large randomised controlled trials in Malawi and ABM remains a considerable clinical challenge [14,15]. We took advantage of the large body of prospective clinical trial and observational data collected in Blantyre, Malawi to investigate these dramatically high adult ABM mortality rates and identify risk factors for a poor prognosis
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