Methods of rapid diagnosis for the etiology of meningitis in adults

Abstract

Infectious meningitis may be due to bacterial, mycobacterial, fungal or viral agents. Diagnosis of meningitis must take into account numerous items of patient history and symptomatology along with regional epidemiology and basic cerebrospinal fluid testing (protein, etc.) to allow the clinician to stratify the likelihood of etiology possibilities and rationally select additional diagnostic tests. Culture is the mainstay for diagnosis in many cases, but technology is evolving to provide more rapid, reliable diagnosis. The cryptococcal antigen lateral flow assay (Immuno-Mycologics) has revolutionized diagnosis of cryptococcosis and automated nucleic acid amplification assays hold promise for improving diagnosis of bacterial and mycobacterial meningitis. This review will focus on a holistic approach to diagnosis of meningitis as well as recent technological advances.

Keywords: Cryptococcus meningitis; aseptic meningitis; bacterial meningitis; diagnosis; diagnostic tests; tuberculosis meningitis.

Figure 1. Algorithm for diagnosis of meningitis in patients with known immune compromise

^†Most likely bacterial meningitis, institute empiric antibiotics after lumbar puncture (or before if the patient is unstable). If Gram stain and culture are negative may consider 16s rRNA PCR (if available). ^‡Most likely tuberculous meningitis. If acid fast bacilli smear unremarkable and duration of symptoms correlate strongly consider empiric treatment and/or nucleic acid amplification tests, ideally testing a large volume (>5 ml) of centrifuged cerebrospinal fluid. ^§Most likely aseptic meningitis. Consider nucleic acid amplification tests for viral pathogens if serum inflammatory biomarkers (e.g., C-reactive protein, procalcitonin) are minimally elevated or normal. AFB: Acid-fast bacilli; CM: Cryptococcal meningitis; CrAg: Cryptococcal antigen; CSF: Cerebrospinal fluid; LFA: Lateral flow immunochromatographic assay.

Figure 2. Algorithm for diagnosis of meningitis in patients without known immune compromise

*If appropriate consider rapid HIV test, If HIV-infected, refer to Figure 1 algorithm. **If mild immune compromise include cryptococcal antigen lateral flow assay, treat bacterial etiology accordingly if positive. ^†Likely bacterial meningitis, continue empiric antibiotics, await definitive etiology. ^‡Most likely aseptic meningitis, consider stopping empiric antibiotics, consider sending appropriate nucleic acid amplification tests (NAATs). ^§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. ^¶Most likely aseptic meningitis, although may be tuberculosis meningiti as well. If strong clinical suspicion, consider TB NAATs. AFB: Acid-fast bacilli; CrAg: Cryptococcal antigen; CSF: Cerebrospinal fluid.