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What Lurks in the 42% of Cases of Meningitis Without an Identified Cause?

Amesh A. Adalja, MD, FACP, FACEP, FIDSA, July 24, 2018

Some infectious disease syndromes are more consequential than others in terms of severity of illness and significance for the emergence of a novel organism with pandemic potential. One such syndrome is meningitis, which can have viral, bacterial, fungal, protozoal, and parasitic causes. Because the identification of a traditional bacterial cause such as meningococcus or pneumococcus constitutes a medical emergency, most diagnostic efforts are limited to including or excluding these possibilities. However, the etiologies of nonbacterial infectious meningitis may include potential high-consequence microorganisms, which may offer an opportunity for antibiotic and antiviral stewardship. A new study, published in Lancet Infectious Diseases, provides insight into the causes of meningitis and how they are pursued.


42% Without Etiology

In this multicenter observational study conducted in 42 English hospitals over a 3-year period, patients older than 16 years of age who were clinically suspected of having meningitis were recruited. Attempts to catalog the causes of meningitis were made for 638 patients using routine culture and PCR testing for herpes simplex virus (HSV) types 1 and 2, varicella zoster virus (VZV), enteroviruses, pneumococcus, and meningococcus.

Important findings included meningitis being attributed to viral etiologies in 36% of cases, bacterial etiologies in 16%, and having no identified cause in 42%. The most common viruses identified were enteroviruses (55%) and herpesviruses (mostly HSV-2 and VZV). Over half of bacterial causes were due to pneumococcus. No patients with viral meningitis required ICU admission or died.

Of the meningitis cases without an etiology, most exhibited a lymphocytic CSF pleocytosis. Interestingly, most patients underwent neuroimaging prior to lumbar puncture—a major departure from guidelines that strictly delimit the need for such imaging pre-procedure. Consequently, the median time to lumbar puncture was 18 hours in those who underwent imaging. Additionally, in those with viral meningitis, each hour delay in lumbar puncture reduced diagnostic yield by 1%.


Race to Diagnosis Needed

This study makes several important points. First, even using relatively sophisticated diagnostic testing, 42% of patients had no etiology identified for their condition. This might have reflected delayed lumbar puncture and overuse of neuroimaging—itself a major finding. While some CSF PCR testing for culprit viruses was employed, it is important to develop a method, using more broadly targeted molecular diagnostic testing, to drive the 42% rate of unknowns as close to zero as possible because important causes may lurk within that group. Second, specific diagnosis enables clinicians to discontinue empiric antibacterial agents more rapidly if the cause is not bacterial. Third, the high proportion of viral meningitis cases due to VZV suggests that the United Kingdom may see benefit from moving to routine vaccination against this virus.



McGill F, Griffiths MJ, Bonett LJ, et al. Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study. Lancet Infect Dis 2018; Accessed July 23, 2018.