Molecular tests for meningitis

Etiology	Availability^*	When inclusion of NAT is indicated	Preferred testing method(s)^¶
Bacteria
Common pathogens (eg, Streptococcus pneumoniae, Haemophilus influenzae)	Yes^Δ	Gram stain positive, culture negative; prior antibacterial therapy	Gram stain and culture
Fastidious organisms (Mycoplasma spp, Tropheryma spp, Brucella spp)	Yes	When clinically suspected	Serology, NAT +/– culture
Mycobacterium tuberculosis^◊	Yes	When clinically suspected	AFB stain, culture, and NAT
Prior antibiotic therapy^§	Yes^Δ	Rarely	Culture prior to antibacterial therapy
Viruses
Adenoviruses	Yes	Rarely	Testing of alternative sites (eg, respiratory) +/– CSF
Arboviruses	Limited	When clinically suspected	Serology and NAT
Cytomegalovirus (CMV)	Yes^Δ	When clinically suspected	NAT, preferably quantitative
Epstein Barr Virus (EBV)	Yes	When clinically suspected	Serology and NAT, preferably quantitative
Enteroviruses	Widespread^Δ	When clinically suspected	NAT
Human herpesvirus 6 (HHV-6)	Yes^Δ	When clinically suspected	NAT, preferably quantitative^¥
Herpes simplex virus (HSV)	Widespread^Δ	When clinically suspected	NAT
Influenza	Yes	Rarely	Testing of alternative sites (eg, respiratory) +/– CSF
Lymphocytic choriomeningitis virus	Limited	Rarely	Serology
Mumps	Limited	Rarely	Viral culture, serology, and NAT
Parechoviruses^‡	Yes^Δ	Primarily in young children (<5 years old)	NAT
Varicella-zoster virus	Yes^Δ	When clinically suspected	NAT (plus CSF serology in select cases)^†
West Nile virus**	Yes	Rarely (unless immunodeficient)	Serology
Rickettsia^¶¶	Limited	Occasionally	Serology
Spirochetes
Leptospira	Limited	Rarely	Serology
Borrelia burgdorferi (the agent of Lyme disease)	Yes	Yes	Serology
Treponema pallidum (syphilis)	Limited	No	Serology, CSF VDRL
Fungal
Cryptococcus spp	Yes^Δ	No	Antigen detection, culture
Other fungi (eg, Coccidioides spp)	Limited	Rarely	Culture, serology
Parasites	Limited	Rarely	Serology, histologic exam, NAT for select pathogens

PPV: positive predictive value; PCR: polymerase chain reaction; CDC: Centers for Disease Control and Prevention; NAT: nucleic acid amplification testing; CSF: cerebrospinal fluid; AFB: acid-fast bacilli; VDRL: Venereal Disease Research Laboratories; FDA: US Food and Drug Administration.
* Widespread: readily available; Yes: consistently available, but not yet common; Limited: one or two specialized laboratories (eg, CDC or research groups).
¶ Test on CSF except where noted.
Δ Also available as part of FDA-cleared multiplex NAT at some centers and referral laboratories.
◊ Variable sensitivity, high PPV, rapid.
§ 16s rDNA "universal" PCR.
¥ HHV-6 NAT has a low PPV.
‡ Not detected by most enterovirus assays.
† CSF serology should be performed when clinical suspicion for herpes zoster is high and the presentation is subacute (eg, VZV vasculopathy or onset of CNS symptoms following recent episode of zoster).
** Virus is usually cleared from blood and CSF prior to symptom onset.
¶¶ Limited experience from CSF.

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Molecular tests for meningitis