Advances in molecular diagnostic testing for central nervous system infections
Open accessAbstract
Purpose of review: Central nervous system (CNS) infections present an ongoing diagnostic challenge for clinicians, with an aetiological agent remaining unidentified in the majority of cases even in high-income settings. This review summarizes developments in a range of diagnostic methods published in the past 18 months. Recent findings: Several commercial assays exist for the detection of viral, bacterial and fungal pathogens using single multiplex PCR. Multicentre validation of the Biofire FilmArray panel illustrated high sensitivity for bacterial and fungal pathogens, but poor results for Cryptococcus species detection. The development of microarray cards for bacterial CNS pathogens shows promise but requires further validation. Few developments have been made in proteomics and transcriptomics, contrasted with significant increase in the use of metagenomic (or unbiased) sequencing. Novel viruses causing CNS infection have been described using this technique but contamination, cost, expertise and turnaround time requirements remain restrictive. Finally, the development of Gene Xpert and Ultra has revolutionized tuberculosis meningitis diagnostics with newly released recommendations for their use from the WHO. Summary: Progress has been made in the clinical validation and international recommendation of PCR-based tests for CNS infections. Sequencing techniques present the most dynamic field, although significant ongoing challenges persist.
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The normal CSF in these infected patients is not a sign of no infection, but rather a sign of a pathogen that has successfully employed its molecular virulence machinery to enter the CNS undetected by the initial wave of immune response.
“The normal CSF in these infected patients is not a sign of no infection, but rather a sign of a pathogen that has successfully employed its molecular virulence machinery to enter the CNS undetected by the initial wave of immune response (32).”
From Pathogen detection in acellular cerebrospinal fluid: diagnostic insights from a pediatric cohort in Colombia (2026) · cites this paper as [32]
The Introduction says many CNS infections remain undiagnosed, and the Sequencing section describes pathogens found in CSF samples from some patients previously thought to have non-infectious disorders. Neither passage addresses normal CSF findings or attributes them to pathogen virulence and evasion of an initial immune response. Searches for normal CSF and immune evasion found no passage supporting that explanation; page numbers were unavailable. (LLM, conf=0.75)
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- Authors
- Houlihan, C. F., Bharucha, T., & Breuer, J.
- Affiliations
- London School of Hygiene & Tropical Medicine (GB)
- Mahosot Hospital (LA)
- University College London (GB)
- Corresponding author
- Breuer, Judith
- Venue
- Current Opinion in Infectious Diseases
- Published
- 2019-06
- Volume
- 32
- Issue
- 3
- Pages
- 244-250
- ISSN
- 0951-7375 (ISSN-L)
- 1473-6527
- OpenAlex
- W2936830133
- Cited by
- 24
- References
- 40
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 3
- FWCI
- 0.33
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Locations
- Current Opinion in Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute for Health and Care Research (ACF-2015-18-026)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Keywords
- central nervous system infection, molecular diagnosis, multiplex PCR, BioFire FilmArray, metagenomic sequencing, proteomics, transcriptomics, tuberculous meningitis, GeneXpert, CNS viral infection
- MeSH terms
- Bacteria, Central Nervous System Infections, Fungi, Humans, Viruses, Molecular Diagnostic Techniques, Proteomics, Metagenomics
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