Molecular diagnosis of central nervous system infections
- Cathy A Petti, MD
Cathy A Petti, MD
- Adjunct Professor of Medicine
- University of South Florida
- Christopher R Polage, MD
Christopher R Polage, MD
- Associate Professor of Pathology and Infectious Diseases
- University of California, Davis School of Medicine
Molecular diagnostic tests and nucleic acid amplification tests (NATs) are used synonymously in reference to test methods that detect deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) specific to infectious organisms (eg, bacteria, viruses) as a means of diagnosis. Such tests have dramatically impacted both the diagnosis and management of infectious diseases . This is particularly true for central nervous system (CNS) infections where rapid, accurate identification of a pathogen and prompt initiation of antimicrobial therapy are potentially lifesaving.
The increasing availability and use of molecular tests for the detection of microorganisms from cerebrospinal fluid (CSF) has redefined our approach to common CNS infections, such as meningitis, encephalitis, and brain mass lesions (particularly in HIV-infected individuals or other immunocompromised hosts), and improved our ability to identify the etiologic agent responsible for other CNS syndromes, such as transverse myelitis.
The unique aspects of molecular testing as applied to CNS infections and guidance in the use and interpretation of molecular testing for pathogens commonly encountered in the management of patients with CNS infections will be reviewed here. Management of specific CNS infections is discussed in the appropriate topics. (See "Aseptic meningitis in adults" and "Viral meningitis: Clinical features and diagnosis in children" and "Viral encephalitis in adults" and "Acute viral encephalitis in children: Clinical manifestations and diagnosis" and "Herpes simplex virus type 1 encephalitis" and "PCR testing for the diagnosis of herpes simplex virus in patients with encephalitis or meningitis" and "Japanese encephalitis: Epidemiology, diagnosis, treatment, and prevention" and "Arthropod-borne encephalitides" and "Clinical features and diagnosis of acute bacterial meningitis in adults".)
Molecular methods are particularly well suited for the diagnosis of central nervous system (CNS) infections because cerebrospinal fluid (CSF) and spinal and brain tissue are normally sterile body sites, where any evidence of a microorganism is likely to represent infection, and infections, when present, are typically monomicrobial. Furthermore, CSF typically lacks common inhibitors of nucleic acid amplification methods (eg, polymerase chain reaction [PCR]) such as heme, endonucleases, and exonucleases that can lead to false-negative results . As a result, direct detection of nucleic acids from CNS samples may be less prone to common causes of false-positive (eg, contamination or presence of nonpathogenic colonization) or false-negative (eg, inhibition) results compared with other body sites.
Targeted nucleic acid detection methods are often more sensitive than conventional culture-based or antigen detection methods and may detect organisms that are nonviable or uncultivable. However, except for herpes simplex virus (HSV) and JC virus, the true clinical sensitivity of most molecular tests for CNS infections is not known because there are few studies utilizing a reference standard (eg, brain biopsy) for comparison.
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- GENERAL CHARACTERISTICS
- Commercial versus noncommercial assays
- False-positive and -negative results
- Importance of clinical correlation
- ROLE OF MOLECULAR TESTING BY CNS SYNDROME
- - Bacteria
- - Mycobacteria
- - Rickettsia and spirochetes
- - Viruses
- - Fungi and parasites
- - Bacteria
- - Spirochetes, Rickettsia, and Ehrlichiae
- - Viruses
- - Fungi and parasites
- Transverse myelitis
- Brain abscess