Genomic pneumococcal load and CSF cytokines are not related to outcome in Malawian adults with meningitis

Emma C Wall,Jenna F Gritzfeld,Matthew Scarborough,Katherine M.B Ajdukiewicz,Mavuto Mukaka,Caroline Corless,David G Lalloo,Stephen B Gordon

doi:10.1016/j.jinf.2014.06.011

Abstract

SummaryObjectiveBacterial meningitis in sub-Saharan Africa is predominantly caused by Streptococcus pneumoniae, is often associated with HIV co-infection and mortality rates are double those seen in better resourced settings.MethodsTo investigate the cause of this excessive mortality we quantified the pneumococcal DNA load and six common pro-inflammatory cytokines in the cerebrospinal fluid (CSF) of Malawian adults with culture proven pneumococcal meningitis and correlated the results to clinical parameters and outcome. There are currently no published data relating bacterial load to outcome in adults with pneumococcal meningitis.ResultsThe mean age of patients was 32 years, 82% were HIV infected and 49% had died by day 40. CSF bacterial loads were high (median 6.5 × 105 copies/ml CSF) and there was no significant variation in bacterial load between survivors and non-survivors. All pro-inflammatory CSF cytokines were elevated in the CSF, with no clinically important differences between survivors and non-survivors. HIV status did not affect the CSF bacterial load or cytokine response.ConclusionMortality from pneumococcal meningitis in adults in sub-Saharan Africa is not related to pneumococcal bacterial load. More research is needed to understand the very high mortality from meningitis in this region.

Highlights

The incidence of pneumococcal meningitis in adults is estimated to be 0.1e1/100,000 in well-resourced countries[1,2]; in sub-Saharan Africa where there are few surveillance data, the incidence is estimated to be 12/100,000 adult population[3]
High Streptococcus pneumoniae bacterial load in the cerebrospinal fluid (CSF) has been associated with increased mortality in children with meningitis in Malawi and Finland, higher bacterial loads in the blood of adults with pneumococcal sepsis in Europe are associated with poor outcome.6e8 Pro-inflammatory cytokines are elevated in the CSF of adults with bacterial meningitis compared to viral meningitis[9,10] but little data are available to determine if elevated CSF cytokines are associated with outcome from meningitis in adults
We examined the association between pneumococcal load and host cytokine response and mortality from pneumococcal meningitis in Malawian adults

Summary

Introduction

The incidence of pneumococcal meningitis in adults is estimated to be 0.1e1/100,000 in well-resourced countries[1,2]; in sub-Saharan Africa where there are few surveillance data, the incidence is estimated to be 12/100,000 adult population[3]. In addition to the increased burden of disease in this region, the adult mortality rate from pneumococcal meningitis is 54%, compared to 30% in Europe.[4,5] High Streptococcus pneumoniae bacterial load in the cerebrospinal fluid (CSF) has been associated with increased mortality in children with meningitis in Malawi and Finland, higher bacterial loads in the blood of adults with pneumococcal sepsis in Europe are associated with poor outcome.6e8 Pro-inflammatory cytokines are elevated in the CSF of adults with bacterial meningitis compared to viral meningitis[9,10] but little data are available to determine if elevated CSF cytokines are associated with outcome from meningitis in adults. We examined the association between pneumococcal load and host cytokine response and mortality from pneumococcal meningitis in Malawian adults

Methods

Results

Discussion

Conclusion