Diagnosis of tuberculous meningitis: clinical and laboratory parameters
Open accessAbstract
BACKGROUND: Confirming the clinical suspicion of tuberculous meningitis (TBM) has always been problematic. Whilst smear and culture positivity are diagnostic, these tests have low sensitivity. The polymerase chain reaction (PCR) assay has given variable results. AIM: This study attempted to improve the diagnostic yield by: (a) increasing the cerebrospinal fluid (CSF) volumes; (b) testing the yield from three specimens of CSF assumed to represent lumbar, cervico-thoracic cord, and base of brain CSF samples; (c) undertaking PCR assays using multiple primer sets; and (d) using real-time PCR. METHOD: Patients suspected of having cranial or spinal meningeal tuberculosis were entered into the study. Three aliquots of CSF were subjected to smear, culture, and conventional and real-time PCR. Three sets of primers - IS6110, MPB64, and PT8/9 - were used. Patients were retrospectively classified into four categories: 'definite TB' (culture positive), 'probable TB' (clinical and other tests suggestive of TB), 'not TB', and 'uncertain diagnosis'. RESULTS: A total of 68 patients were studied. There were 20 patients classified as definite TB, 24 probable TB, 17 not TB, and seven uncertain diagnosis. Forty-eight of 57 (84.2%) patients tested were HIV seropositive. The IS6110 PCR was positive in 27 patients which included 18/20 culture positive cases, six in the probable TB group, and three in the not TB group. The MPB64 and PT8/9 primers did not increase the yield. Real-time PCR was positive in seven additional patients. Combining the definite and probable TB, the sensitivity of all PCR assays was 70.5% (31/44) and specificity 87.5% (21/24). CONCLUSION: Targeting multiple sites of the TB genome using conventional PCR did not increase the number of positive cases. Real-time PCR was more sensitive. However, all the current techniques are still too insensitive to confidently exclude the diagnosis on laboratory grounds.
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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 [73]
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- Authors
- Bhigjee, A. I., Padayachee, R., Paruk, H., Hallwirth-Pillay, K. D., Marais, S., & Connoly, C.
- Affiliations
- University of KwaZulu-Natal (ZA)
- Corresponding author
- Bhigjee, Ahmed Iqbal
- Venue
- International Journal of Infectious Diseases
- Publisher
- Elsevier BV
- Published
- 2007-07
- Volume
- 11
- Issue
- 4
- Pages
- 348-354
- ISSN
- 1201-9712 (ISSN-L)
- OpenAlex
- W1991492906
- Cited by
- 116
- References
- 44
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 10 · 2019: 6 · 2018: 6 · 2017: 10 · 2016: 8 · 2015: 9 · 2014: 9 · 2013: 11 · 2012: 11
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- tuberculous meningitis, cerebrospinal fluid PCR, IS6110, MPB64, real-time PCR, diagnostic sensitivity, HIV coinfection, spinal tuberculosis
- MeSH terms
- Adult, Female, Humans, Male, Mycobacterium tuberculosis, Retrospective Studies, Tuberculosis, Meningeal, HIV Infections, Polymerase Chain Reaction
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