Methods for rapid diagnosis of meningitis etiology in adults

Abstract

Infectious meningitis can be caused by viral, bacterial or fungal pathogens. Despite widely available treatments, many types of infectious meningitis are still associated with significant morbidity and mortality. Delay in diagnosis contributes to poor outcomes. Cerebrospinal fluid cultures have been used traditionally but are time intensive and sensitivity is decreased by empiric treatment prior to culture. More rapid techniques such as the cryptococcal lateral flow assay (IMMY), GeneXpert MTB/Rif Ultra (Cepheid) and FilmArray multiplex-PCR (Biofire) are three examples that have drastically changed meningitis diagnostics. This review will discuss a holistic approach to diagnosing bacterial, mycobacterial, viral and fungal meningitis.

Keywords: aseptic meningitis; bacterial meningitis; cryptococcal meningitis; diagnosis; diagnostic testing; tuberculous meningitis.

Figure 1.. Simplified diagnostic algorithm for diagnosis of subacute meningitis in advanced HIV.

^†Most likely bacterial meningitis, particularly L. monocytogenes. Institute empiric antibiotics after lumbar puncture (or before if the patient is unstable). ^‡Most likely tuberculous meningitis. If acid-fast bacilli smear unremarkable and duration of symptoms correlate strongly consider empiric treatment and/or nucleic acid amplification testing, ideally utilizing a large volume (>5 ml) of centrifuged cerebrospinal fluid. Also consider work up for other fungal meningitis, such as Aspergillus, Blastomyces, Coccidioides and Histoplasma in the proper setting. The Delphi method of consensus was used to construct this figure. CM: Cryptococcal meningitis; CrAg: Cryptococcal antigen; CSF: Cerebrospinal fluid; LFA: Lateral flow immunochromatographic assay.

Figure 2.. Algorithm for diagnosis of subacute meningitis in patients with presumed normal immune system.

^†If appropriate consider rapid HIV test, if HIV-infected, refer to Figure 1 algorithm. ^‡Most likely tuberculosis meningitis. If duration of symptoms are compatible, strongly consider empiric treatment and/or NAATs, ideally testing a large volume (>5 ml) of centrifuged cerebrospinal fluid. Consider fungal etiologies as well such as Aspergillus, Blastomyces, Coccidioides and Histoplasma. ^§Most likely aseptic meningitis, particularly non-infectious etiologies. Although may be tuberculosis meningitis as well. If strong clinical suspicion, consider TB NAATs. The Delphi method of consensus used to construct this figure. CrAg: Cryptococcal antigen; CSF: Cerebrospinal fluid; TBM: Tuberculosis meningitis.