Molecular tests for encephalitis

Etiology	Availability^*	When inclusion of NAT is indicated	Preferred testing method(s)^¶
Bacteria
Coxiella burnetti (Q fever)	Yes	When clinically suspected	NAT, serology
Listeria spp	Yes^Δ	Rarely	Culture, +/– NAT and serology
Mycobacterium tuberculosis^◊	Yes	Potentially	AFB stain, culture, histologic exam, and NAT
Fastidious organisms (Mycoplasma spp, Bartonella spp)	Yes	When clinically suspected, especially in children	Serology, NAT including alternative sites where appropriate (eg, respiratory)
Viruses
Adenoviruses	Yes	Rarely	Testing of alternative sites (eg, respiratory) +/– CSF
Arboviruses	Limited	When clinically suspected	Serology (+/- NAT in selected cases)^§
Epstein-Barr virus	Yes	When clinically suspected	Serology and NAT, preferably quantitative
Enteroviruses	Widespread^Δ	When clinically suspected	NAT
Human herpesvirus 6	Yes^Δ	When clinically suspected	NAT, preferably quantitative
Herpes simplex virus	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	History, culture, serology, and NAT
Parechoviruses^¥	Yes^Δ	Primarily in young children (<5 years old)	NAT
Rabies^‡	Limited (CDC)	When clinically suspected	Combination of serology, biopsy, NAT
Varicella-zoster virus	Yes^Δ	When clinically suspected	NAT (plus CSF serology in selected cases)^†
West Nile virus**	Yes	Rarely (unless immunodeficient)	Serology
Fungal
Cryptococcus	Yes^Δ	No	Antigen detection, culture
Other fungi	Limited	No	Culture, serology, histologic exam
Rickettsia^¶¶	Limited	Occasionally	Serology
Spirochetes
Borrelia burgdorferi (the agent of Lyme disease)	Yes	Rarely	Serology
Treponema pallidum (syphilis)	Limited	When clinically suspected	Serology, CSF VDRL
Parasites
Microsporidia	Limited	Rarely	Serology, stains, histologic exam
Free-living amebae (eg, Naegleria fowleri)	Limited	When clinically suspected	CSF wet mount and NAT
Other parasites (Baylisascaris spp, Balamuthia mandrillaris)	Limited	Rarely (eg, CSF eosinophilia)	Histologic exam, serology +/– NAT

PPV: positive predictive value; CDC: Centers for Disease Control and Prevention; HHV-6: human herpesvirus 6; 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.
◊ Limited experience, presumably variable sensitivity, high PPV.
§ NAT may be useful for diagnosis in immunocompromised patients.
¥ Not detected by most enterovirus assays.
‡ In conjunction with other modalities.
† 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 encephalitis