Diagnostic accuracy of droplet digital PCR analysis of cerebrospinal fluid for tuberculous meningitis in adult patients
Open accessAbstract
Objectives Tuberculous meningitis (TBM) is difficult to diagnose. Digital PCR (dPCR) is a novel method which can quantify trace nucleic acids. This study sought to evaluate the diagnostic accuracy of dPCR analysis of cerebrospinal fluid (CSF) for TBM.Methods We collected CSF specimens from hospitalized TBM and non-TBM patients. Total CSF DNA was purified and the concentrations of Mycobacterium tuberculosis insert sequence 6110 (IS6110) and gyrase subunit B (gyrB) were quantified using droplet dPCR. The receiver operating characteristic curves of dPCR were established and the diagnostic performances were obtained. We also compared the sensitivity of dPCR with routine diagnostic tests.Results A total of 101 patients were recruited, 68 of whom suffered from TBM (26 definite, 34 probable and eight possible TBM) and 33 from non-TBM. The sensitivity of IS6110-dPCR assay for total TBM was higher than that of gyrB-dPCR assay (57.4% (44.8-69.3%) vs. 22.1% (12.9-33.8%)), and there was no significant difference for specificity between them (97.0% (84.2-99.9%) vs. 100% (89.4-100.0%)). The sensitivity of IS6110-dPCR in definite TBM was higher than that in probable and possible TBM (73.1% vs. 52.9% and 25.0%, respectively). IS6110-dPCR assay showed a higher sensitivity than smear microscopy (53.3% vs. 6.7%), mycobacterial culture (50.0% vs. 12.5%), IS6110-quantitative PCR (53.1% vs. 21.9%) and Xpert MTB/RIF (70.4% vs. 29.6%). Long anti-tuberculosis treatment time was found to be significantly associated with negative dPCR results.Conclusion CSF IS6110-dPCR assay is a rapid and sensitive molecular test, which has the potential to be used to enhance the diagnosis of TBM.
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Studies of IS6110 PCR for tuberculous meningitis reported sensitivity between 72% and 100% (median 91%) and specificity between 82% and 100% (median 99%).
“Several studies, with sample sizes ranging from 13 to 102 definite tuberculous meningitis patients and 17 to 127 controls, studied the performance of IS6110 PCR and reported a sensitivity between 72% and 100% (median 91%) with a specificity between 82% and 100% (median 99%) (73–78).”
From Molecular diagnostics in cerebrospinal fluid for the diagnosis of central nervous system infections (2024) · cites this paper as [77]
The Evaluation of the diagnostic performance section reports results for this paper’s own IS6110-dPCR study, not a range across several studies. Searches for the claimed sensitivity and specificity ranges and medians found no passage reporting them; the Discussion also does not give those figures. No page numbers are available in our copy. (LLM, conf=0.76)
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Molecular diagnostics in cerebrospinal fluid for the diagnosis of central nervous system infections
Olie, S. E., Andersen, C. Ø., van de Beek, D., & Brouwer, M. C. (2024) · Clinical Microbiology Reviews · doi:10.1128/cmr.00021-24 · Cited by 38 · see citing works
- Authors
- Li, Z., Pan, L., Lyu, L., Li, J., Jia, H., Du, B., Sun, Q., & Zhang, Z.
- Affiliations
- Capital Medical University (CN)
- Chinese People's Liberation Army (CN)
- Corresponding author
- Zhang, Z.
- Venue
- Clinical Microbiology and Infection
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 26
- Issue
- 2
- Pages
- 213-219
- ISSN
- 1198-743X (ISSN-L)
- OpenAlex
- W2962715452
- Cited by
- 32
- References
- 32
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 1 · 2020: 6 · 2019: 2
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Clinical Microbiology and Infection (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Beijing Municipal Administration of Hospitals Incubating Program (PX2018055)
- National Natural Science Foundation of China (81702097)
- National Science and Technology Major Project of China (2015ZX10004801-003, 2017ZX10201301-004, 2018ZX10731301-003-003)
- Beijing Municipal Administration of Hospitals Ascent Plan (DFL20181601)
- Beijing Natural Science Foundation (7192038)
- Topics
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- tuberculous meningitis, cerebrospinal fluid, droplet digital PCR, IS6110, gyrB, Mycobacterium tuberculosis, diagnostic accuracy, sensitivity and specificity, smear microscopy, mycobacterial culture, Xpert MTB/RIF, molecular diagnosis
- MeSH terms
- Adolescent, Adult, Aged, Bacterial Proteins, Cerebrospinal Fluid, DNA, Bacterial, Female, Hospitalization, Humans, Male, Middle Aged, Mycobacterium tuberculosis, Sensitivity and Specificity, Tuberculosis, Meningeal, Reproducibility of Results, DNA Gyrase, Young Adult, Real-Time Polymerase Chain Reaction
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