CoChat
Sign Up
Cited by 69Infectious Encephalopathies and EncephalitisBacterial Infections and VaccinesBacterial Identification and Susceptibility Testing

Diagnostic challenges of central nervous system infection: Extensive multiplex panels versus stepwise guided approach

Open access
Vetter, P., Schibler, M., Herrmann, J.L., Boutolleau, D.·2020·Clinical Microbiology and Infection
DOI 10.1016/j.cmi.2019.12.013
Open this paper in CoChat — free accountOpen PDF

Abstract

Background Cerebrospinal fluid (CSF) testing is a key component for the diagnosis of central nervous system (CNS) infections. Current meningitis and encephalitis management guidelines agree on the need for CSF molecular testing in combination with other direct and indirect biological testing, both in CSF and blood. Multiplex molecular tests have been developed to reduce turnaround times and facilitate the diagnostic approach.Objectives We aim to discuss the role of multiplex molecular panels in the management of CNS infections.Sources The MEDLINE database and the grey literature have been searched for relevant articles.Content New molecular multiplex panels are being developed to simultaneously detect a large array of neuropathogens in CSF. Although one of these assays has been US Food and Drug Administration-approved, extensive analytical and clinical validation is still missing, and suboptimal performance related issues have been raised. Its use has been associated with decreased costs, reduced length of hospital stay and reduced antiviral therapy administration in retrospective, industry-sponsored studies. The pros and cons of this multiplex syndromic approach are discussed in this narrative review.Implications Molecular multiplex CNS infection diagnosis panels have been developed and present several attractive features, including ease of use and low turnaround time. However, suboptimal analytical performances render these tests difficult to use without additional confirmatory tests. Such panels are not comprehensive nor adapted to all situations, depending on the epidemiological or clinical context. Overall, available data in the literature currently do not support the use of a multiplex PCR panel in clinical routine as a 'stand-alone' molecular assay. Except in restricted laboratory capacity settings where such easy-to-use multiplex panels offer the diagnostic means that would otherwise not be available, the stepwise testing approach remains a more rational option. Serological testing both in blood and CSF should not be neglected, but it represents essential complementary tools regarding some neuropathogens.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cmi.2019.12.013

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Epstein-Barr virus positivity in cerebrospinal fluid may indicate latent infection without central nervous system involvement.

    “Similarly, Epstein-Barr virus (EBV) positivity in CSF may indicate latent infection without CNS involvement.1,5,6”

    From Utility and clinical relevance of multiplex PCR panels for diagnosis of central nervous system infections (2026) · cites this paper as [5]

    The Additional considerations section says Epstein–Barr virus is more likely to cause lymphoma than CNS infection, supporting caution about interpreting EBV as a cause of CNS infection. It does not say that EBV positivity in CSF indicates latent infection or discuss that specific interpretation; the nearby example of an incidental positive result concerns HHV-6, not EBV. No page number is available in our copy. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Diagnostic stewardship and development of a diagnostic decision rule with a stepwise approach may improve appropriate use of the ME panel.

    “Several studies showed that diagnostic stewardship and the development of a diagnostic decision rule with a stepwise approach may improve the appropriate use of the ME Panel (12–14).”

    From Utilization of a Meningitis/Encephalitis PCR panel at the University Hospital Basel – a retrospective study to develop a diagnostic decision rule (2024) · cites this paper as [12]

    In Additional considerations (page unavailable), the paper proposes a stepwise testing algorithm guided by clinical findings and local epidemiology, which supports the idea of more selective testing. It does not report a study showing that a diagnostic decision rule improves appropriate use of the ME panel; instead, it calls for trials comparing multiplex panels with a stepwise approach. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Mycobacterium tuberculosis is a major cause of childhood CNS infection in tuberculosis endemic areas such as Uganda.

    “Another microorganism not targeted by FA-ME is Mycobacterium tuberculosis, despite it being a major cause of childhood CNS infection in tuberculosis endemic areas such as Uganda [6, 20].”

    From Clinical utility of the FilmArray® meningitis/encephalitis panel in children with suspected central nervous system infection in a low-resource setting – a prospective study in Southwestern Uganda (2025) · cites this paper as [20]

    The “Multiplex PCR panels: analytical and clinical performances” section lists the FilmArray ME targets without M. tuberculosis, and “Qualitative versus quantitative assays” says its burden is highest in low- and middle-income countries. The paper does not establish that it is a major cause of childhood CNS infection in Uganda or other tuberculosis-endemic areas (page numbers unavailable). (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Frequent HHV-6 and Cytomegalovirus detection by FA-ME is reported by several authors, who in most cases considered them non-pathogenic due to latency capacity and chromosomal integration (HHV-6), and non-significance in immunocompetent patients (Cytomegalovirus).

    “Frequent HHV-6 and Cytomegalovirus detection by FA-ME is reported by several authors, who in most cases considered them non-pathogenic due to their latency capacity and chromosomal integration (HHV-6), and non-significance in immunocompetent patients (Cytomegalovirus) [17, 20, 31, 34–36].”

    From Clinical utility of the FilmArray® meningitis/encephalitis panel in children with suspected central nervous system infection in a low-resource setting – a prospective study in Southwestern Uganda (2025) · cites this paper as [20]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Detection of human herpesvirus-6 may reflect chromosomally integrated viral DNA rather than active infection, particularly in immunocompetent individuals.

    “For example, the detection of human herpesvirus-6 (HHV-6) may reflect chromosomally integrated viral DNA rather than active infection, particularly in immunocompetent individuals.”

    From Utility and clinical relevance of multiplex PCR panels for diagnosis of central nervous system infections (2026) · cites this paper as [5]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Vetter, P., Schibler, M., Herrmann, J. L., & Boutolleau, D.
Affiliations
  • University Hospital of Geneva (CH)
  • Inserm (FR)
Corresponding author
Vetter, P.
ORCID
Venue
Clinical Microbiology and Infection
Publisher
Elsevier BV
Published
2020-06
Volume
26
Issue
6
Pages
706-712
ISSN
1198-743X (ISSN-L)
DOI
10.1016/j.cmi.2019.12.013
OpenAlex
W2998147738
Cited by
64
References
58
Citations by year
2026: 12 · 2025: 9 · 2024: 13 · 2023: 9 · 2022: 12 · 2021: 8 · 2020: 1
FWCI
0.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Microbiology and Infection (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
  • Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
Keywords
central nervous system infection, meningitis, encephalitis, multiplex PCR panels, syndromic testing, stepwise diagnostic approach, serological testing, diagnostic test validation
MeSH terms
Central Nervous System Infections, Diagnostic Tests, Routine, Encephalitis, Humans, Meningitis, Retrospective Studies, Molecular Diagnostic Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review