Laboratory Diagnosis of Central Nervous System Infection

Abstract

Central nervous system (CNS) infections are potentially life threatening if not diagnosed and treated early. The initial clinical presentations of many CNS infections are non-specific, making a definitive etiologic diagnosis challenging. Nucleic acid in vitro amplification-based molecular methods are increasingly being applied for routine microbial detection. These methods are a vast improvement over conventional techniques with the advantage of rapid turnaround and higher sensitivity and specificity. Additionally, molecular methods performed on cerebrospinal fluid samples are considered the new gold standard for diagnosis of CNS infection caused by pathogens, which are otherwise difficult to detect. Commercial diagnostic platforms offer various monoplex and multiplex PCR assays for convenient testing of targets that cause similar clinical illness. Pan-omic molecular platforms possess potential for use in this area. Although molecular methods are predicted to be widely used in diagnosing and monitoring CNS infections, results generated by these methods need to be carefully interpreted in combination with clinical findings. This review summarizes the currently available armamentarium of molecular assays for diagnosis of central nervous system infections, their application, and future approaches.

Keywords: Central nervous system infections; Culture; Encephalitis; Laboratory diagnosis; Meningitis; Microscopic morphology; Molecular methods; Pan-omic techniques; Rapid antigen testing; Serology.

Figure 1

A diagram of nervous system anatomy and the specific pathogens associated with each structure. Modified with permission from Swanson and McGavern . Abbreviations: AV, alphaviruses; BV, bunyaviruses; CMV, cytomegalovirus; HEV, human enteroviruses; HIV, human immunodeficiency virus; HSV, herpes simplex virus; JCV, John Cunningham virus; JEV, Japanese encephalitis virus; LCMV, lymphocytic choriomeningitis virus; Mev, measles virus; Mum, Mumps virus; Nip, Nipah virus; P V, poliovirus; RV, rabies virus; SLEV, St. Louis encephalitis virus; TBEV, tick-borne encephalitis virus; WNV, West Nile virus. Lm, Listeria monocytogenes; Nm, Neisseria meningitidis; Ec, Escherichia coli; Cn, Cryptococcus neoformans; Hc, Histoplasma capsulatum; Bh, Blastocystis hominis; Ci, Coccidioides immitis; Td, Toxoplasma gondii; GBS, Guillain-Barré syndrome; HIB, Haemophilus influenzae type b; MTB, Mycobacterium tuberculosis; Sp, Streptococcus pneumoniae; Tp, Treponema pallidum