Rapid diagnosis of TB meningitis is imperative and a biomarker-based test is needed: We need to move beyond detecting the bacilli to combat TBM mortality!

Background

CNS infections are a leading cause of HIV-related deaths in sub-Saharan Africa, but causes and outcomes are poorly defined. We aimed to determine mortality and predictors of mortality in adults evaluated for meningitis in Botswana, which has an estimated 23% HIV prevalence among adults.

Methods

In this prevalent cohort study, patient records from 2004–15 were sampled from the Botswana national meningitis survey, a nationwide audit of all cerebrospinal fluid (CSF) laboratory records from patients receiving a lumbar puncture for evaluation of meningitis. Data from all patients with culture-confirmed pneumococcal and tuberculous meningitis, and all patients with culture-negative meningitis with CSF white cell count (WCC) above 20 cells per μL were included in our analyses, in addition to a random selection of patients with culture-negative CSF and CSF WCC of up to 20 cells per μL. We used patient national identification numbers to link CSF laboratory records from the national meningitis survey to patient vital registry and HIV databases. Univariable and multivariable Cox proportional hazards models were used to evaluate clinical and laboratory predictors of mortality.

Interpretation

Mortality from pneumococcal, tuberculous, and culture-negative meningitis was high in this setting of high HIV prevalence. There is an urgent need for improved access to diagnostics, to better define aetiologies and develop novel diagnostic tools and treatment algorithms.

Funding

National Institutes of Health, President’s Emergency Plan for AIDS Relief, National Institute for Health Research.

Inadequate diagnostics: the case to move beyond the bacilli for detection of meningitis due to Mycobacterium tuberculosis

Tuberculosis (TB) meningitis is extremely difficult to diagnose due to its pauci-bacillary disease nature and new techniques are needed. Improved test sensitivity would allow for greater clinician confidence in diagnostic testing and has the potential to improve patient outcomes. Traditional microbiologic and molecular tests for TB meningitis focus on detection of TB bacilli and are inadequate. Smear microscopy is rapid but only ~10–15  % sensitive. Culture has 50–60  % sensitivity but is slow. Xpert MTB/Rif Ultra is a rapid, automated PCR-based assay with ~70  % sensitivity versus clinical case definition. Thus, even the best current testing may miss up to 30  % of cases. Clinicians are often left to treat empirically with prolonged regimens with significant side effects or risk a missed case that would result in death. Rather than relying strictly on microbiologic or molecular testing to diagnose TB meningitis, we propose that testing of CSF for biomarkers of host response may have an adjunctive role to play in improving the diagnosis of TB meningitis.

Read more: https://jmm.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.000975