Skip to main content
Erschienen in: Journal of Neurology 10/2006

01.10.2006 | ORIGINAL COMMUNICATION

Interferon γ quantification in cerebrospinal fluid compared with PCR for the diagnosis of tuberculous meningitis

verfasst von: Rafael San Juan, Carmen Sánchez-Suárez, María J. Rebollo, Dolores Folgueira, Elia Palenque, Blanca Ortuño, Carlos Lumbreras, José M. Aguado

Erschienen in: Journal of Neurology | Ausgabe 10/2006

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To assess the utility of interferon γ (INF-γ) levels in cerebrospinal fluid (CSF), for the diagnosis of tuberculous meningitis (TBM), and compare these results with aPCR technique.

Methods

We studied CSF samples from patients with proven or probable TBM and a control group, composed by patients with other causes of meningitis and without meningitis. INFγ levels were measured by radioimmunoassay. A PCR technique was performed using IS6110 primers.

Results

Of the 127 patients studied, 20 (15.6%) had TBM, 59 (46%) had meningitis of another aetiology and 49 (38.4%) had were HIV and non-HIV patients with normal CSF. The area below the ROC curve for interferon γ levels in the diagnosis of TBM was 0.94. A cut-off of 6.4 IU/mL yielded a sensitivity of 70% and a specificity of 94%. False positive results were observed in 7 of the 59 patients (11.8%) with non-TB meningitis, (patients with herpetic meningoencephalitis and meningitis due to intracellular microorganisms). INF-γ sensitivity was higher than PCR (70% vs. 65%). Both tests performed together showed higher sensitivity (80%) and specificity (92.6%).

Conclusion

CSF INF-γ levels (> 6.4 IU/mL) are very valuable in TBM diagnosis. PCR and INF-γ could be simultaneously used to increase the diagnostic yield.
Literatur
1.
Zurück zum Zitat Ishiguro A, Suzuki Y, Inaba Y, Komiyama A, Koeffler HP, Shimbo T (1996) Production of interleukin-10 in the cerebrospinal fluid in aseptic meningitis of children. Pediatr Res 40:610–4PubMed Ishiguro A, Suzuki Y, Inaba Y, Komiyama A, Koeffler HP, Shimbo T (1996) Production of interleukin-10 in the cerebrospinal fluid in aseptic meningitis of children. Pediatr Res 40:610–4PubMed
2.
Zurück zum Zitat Donald PR, Victor TC, Jordaan AM, Schoeman JF, van Helden PD (1993) Polymerase chain reaction in the diagnosis of tuberculous meningitis. Scand J Infect Dis 25:613–7PubMed Donald PR, Victor TC, Jordaan AM, Schoeman JF, van Helden PD (1993) Polymerase chain reaction in the diagnosis of tuberculous meningitis. Scand J Infect Dis 25:613–7PubMed
3.
Zurück zum Zitat Kaneko K, Onodera O, Miyatake T, Tsuji S (1990) Rapid diagnosis of tuberculous meningitis by polymerase chain reaction (PCR). Neurology 40:1617–8PubMed Kaneko K, Onodera O, Miyatake T, Tsuji S (1990) Rapid diagnosis of tuberculous meningitis by polymerase chain reaction (PCR). Neurology 40:1617–8PubMed
4.
Zurück zum Zitat Shankar P, Manjunath N, Mohan KK, et al. (1991) Rapid diagnosis of tuberculous meningitis by polymerase chain reaction. Lancet 337:5–7PubMedCrossRef Shankar P, Manjunath N, Mohan KK, et al. (1991) Rapid diagnosis of tuberculous meningitis by polymerase chain reaction. Lancet 337:5–7PubMedCrossRef
5.
Zurück zum Zitat Lin JJ, Harn HJ, Hsu YD, Tsao WL, Lee HS, Lee WH (1995) Rapid diagnosis of tuberculous meningitis by polymerase chain reaction assay of cerebrospinal fluid. J Neurol 242:147–52PubMedCrossRef Lin JJ, Harn HJ, Hsu YD, Tsao WL, Lee HS, Lee WH (1995) Rapid diagnosis of tuberculous meningitis by polymerase chain reaction assay of cerebrospinal fluid. J Neurol 242:147–52PubMedCrossRef
6.
Zurück zum Zitat Liu PY, Shi ZY, Lau YJ, Hu BS (1994) Rapid diagnosis of tuberculous meningitis by a simplified nested amplification protocol. Neurology 44:1161–4PubMed Liu PY, Shi ZY, Lau YJ, Hu BS (1994) Rapid diagnosis of tuberculous meningitis by a simplified nested amplification protocol. Neurology 44:1161–4PubMed
7.
Zurück zum Zitat Seth P, Ahuja GK, Bhanu NV, et al. (1996) Evaluation of polymerase chain reaction for rapid diagnosis of clinically suspected tuberculous meningitis. Tuber Lung Dis 77:353–7PubMedCrossRef Seth P, Ahuja GK, Bhanu NV, et al. (1996) Evaluation of polymerase chain reaction for rapid diagnosis of clinically suspected tuberculous meningitis. Tuber Lung Dis 77:353–7PubMedCrossRef
8.
Zurück zum Zitat Lee BW, Tan JA, Wong SC, et al. (1994) DNA amplification by the polymerase chain reaction for the rapid diagnosis of tuberculous meningitis. Comparison of protocols involving three mycobacterial DNA sequences, IS6110, 65 kDa antigen, and MPB64. J Neurol Sci 123:173–9PubMedCrossRef Lee BW, Tan JA, Wong SC, et al. (1994) DNA amplification by the polymerase chain reaction for the rapid diagnosis of tuberculous meningitis. Comparison of protocols involving three mycobacterial DNA sequences, IS6110, 65 kDa antigen, and MPB64. J Neurol Sci 123:173–9PubMedCrossRef
9.
Zurück zum Zitat Folgueira L, Delgado R, Palenque E, Noriega AR (1994) Polymerase chain reaction for rapid diagnosis of tuberculous meningitis in AIDS patients. Neurology 44:1336–8PubMed Folgueira L, Delgado R, Palenque E, Noriega AR (1994) Polymerase chain reaction for rapid diagnosis of tuberculous meningitis in AIDS patients. Neurology 44:1336–8PubMed
10.
Zurück zum Zitat Scarpellini P, Racca S, Cinque P, et al. (1995) Nested polymerase chain reaction for diagnosis and monitoring treatment response in AIDS patients with tuberculous meningitis. Aids 9:895–900PubMedCrossRef Scarpellini P, Racca S, Cinque P, et al. (1995) Nested polymerase chain reaction for diagnosis and monitoring treatment response in AIDS patients with tuberculous meningitis. Aids 9:895–900PubMedCrossRef
11.
Zurück zum Zitat Nguyen LN, Kox LF, Pham LD, Kuijper S, Kolk AH (1996) The potential contribution of the polymerase chain reaction to the diagnosis of tuberculous meningitis. Arch Neurol 53:771–6PubMed Nguyen LN, Kox LF, Pham LD, Kuijper S, Kolk AH (1996) The potential contribution of the polymerase chain reaction to the diagnosis of tuberculous meningitis. Arch Neurol 53:771–6PubMed
12.
Zurück zum Zitat Caws M, Wilson SM, Clough C, Drobniewski F (2000) Role of IS6110-targeted PCR, culture, biochemical, clinical, and immunological criteria for diagnosis of tuberculous meningitis. J Clin Microbiol 38:3150–5PubMed Caws M, Wilson SM, Clough C, Drobniewski F (2000) Role of IS6110-targeted PCR, culture, biochemical, clinical, and immunological criteria for diagnosis of tuberculous meningitis. J Clin Microbiol 38:3150–5PubMed
13.
Zurück zum Zitat Aoe K, Hiraki A, Murakami T, et al. (2003) Diagnostic significance of interferon-gamma in tuberculous pleural effusions. Chest 123:740–4PubMedCrossRef Aoe K, Hiraki A, Murakami T, et al. (2003) Diagnostic significance of interferon-gamma in tuberculous pleural effusions. Chest 123:740–4PubMedCrossRef
14.
Zurück zum Zitat Villena V, Lopez-Encuentra A, Pozo F, et al. (2003) Interferon gamma levels in pleural fluid for the diagnosis of tuberculosis. Am J Med 115:365–70PubMedCrossRef Villena V, Lopez-Encuentra A, Pozo F, et al. (2003) Interferon gamma levels in pleural fluid for the diagnosis of tuberculosis. Am J Med 115:365–70PubMedCrossRef
15.
Zurück zum Zitat Truant JP, Brett WA, Thomas W, Jr. (1962) Fluorescence microscopy of tubercle bacilli stained with auramine and rhodamine. Henry Ford Hosp Med Bull 10:287–96PubMed Truant JP, Brett WA, Thomas W, Jr. (1962) Fluorescence microscopy of tubercle bacilli stained with auramine and rhodamine. Henry Ford Hosp Med Bull 10:287–96PubMed
16.
Zurück zum Zitat Bauer HM, Ting Y, Greer CE, et al. (1991) Genital human papillomavirus infection in female university students as determined by a PCR-based method. JAMA 265:472–7PubMedCrossRef Bauer HM, Ting Y, Greer CE, et al. (1991) Genital human papillomavirus infection in female university students as determined by a PCR-based method. JAMA 265:472–7PubMedCrossRef
17.
Zurück zum Zitat Folgueira L, Delgado R, Palenque E, Noriega AR (1993) Detection of Mycobacterium tuberculosis DNA in clinical samples by using a simple lysis method and polymerase chain reaction. J Clin Microbiol 31:1019–21PubMed Folgueira L, Delgado R, Palenque E, Noriega AR (1993) Detection of Mycobacterium tuberculosis DNA in clinical samples by using a simple lysis method and polymerase chain reaction. J Clin Microbiol 31:1019–21PubMed
18.
Zurück zum Zitat Erlich HA, Gelfand D, Sninsky JJ (1991) Recent advances in the polymerase chain reaction. Science 252:1643–51PubMedCrossRef Erlich HA, Gelfand D, Sninsky JJ (1991) Recent advances in the polymerase chain reaction. Science 252:1643–51PubMedCrossRef
19.
Zurück zum Zitat Eisenach KD, Cave MD, Bates JH, Crawford JT (1990) Polymerase chain reaction amplification of a repetitive DNA sequence specific for Mycobacterium tuberculosis. J Infect Dis 161:977–81PubMed Eisenach KD, Cave MD, Bates JH, Crawford JT (1990) Polymerase chain reaction amplification of a repetitive DNA sequence specific for Mycobacterium tuberculosis. J Infect Dis 161:977–81PubMed
20.
Zurück zum Zitat Kwok S, Higuchi R (1989) Avoiding false positives with PCR. Nature 237–238 Kwok S, Higuchi R (1989) Avoiding false positives with PCR. Nature 237–238
21.
Zurück zum Zitat Rodriguez MD (2000) U.D 6: Diseños para el estudio de pruebas diagnósticas y factores pronósticos. In: Domenech JM (eds) Diseño de Estudios Sanitarios. Signo, Barcelona, pp 43–72 Rodriguez MD (2000) U.D 6: Diseños para el estudio de pruebas diagnósticas y factores pronósticos. In: Domenech JM (eds) Diseño de Estudios Sanitarios. Signo, Barcelona, pp 43–72
22.
Zurück zum Zitat Farrar MA, Schreiber RD (1993) The molecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol 11:571–611PubMedCrossRef Farrar MA, Schreiber RD (1993) The molecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol 11:571–611PubMedCrossRef
23.
Zurück zum Zitat Mastroianni CM, Paoletti F, Lichtner M, D’Agostino C, Vullo V, Delia S (1997) Cerebrospinal fluid cytokines in patients with tuberculous meningitis. Clin Immunol Immunopathol 84:171–6PubMedCrossRef Mastroianni CM, Paoletti F, Lichtner M, D’Agostino C, Vullo V, Delia S (1997) Cerebrospinal fluid cytokines in patients with tuberculous meningitis. Clin Immunol Immunopathol 84:171–6PubMedCrossRef
24.
Zurück zum Zitat Donald PR, Schoeman JF, Beyers N, et al. (1995) Concentrations of interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta in the cerebrospinal fluid of children treated for tuberculous meningitis. Clin Infect Dis 21:924–9PubMed Donald PR, Schoeman JF, Beyers N, et al. (1995) Concentrations of interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta in the cerebrospinal fluid of children treated for tuberculous meningitis. Clin Infect Dis 21:924–9PubMed
25.
Zurück zum Zitat Glimaker M, Olcen P, Andersson B (1994) Interferon-gamma in cerebrospinal fluid from patients with viral and bacterial meningitis. Scand J Infect Dis 26:141–7PubMed Glimaker M, Olcen P, Andersson B (1994) Interferon-gamma in cerebrospinal fluid from patients with viral and bacterial meningitis. Scand J Infect Dis 26:141–7PubMed
26.
Zurück zum Zitat De Wit D, Steyn L, Shoemaker S, Sogin M (1990) Direct detection of Mycobacterium tuberculosis in clinical specimens by DNA amplification. J Clin Microbiol 28:2437–41PubMed De Wit D, Steyn L, Shoemaker S, Sogin M (1990) Direct detection of Mycobacterium tuberculosis in clinical specimens by DNA amplification. J Clin Microbiol 28:2437–41PubMed
27.
Zurück zum Zitat Baran J, Jr., Riederer KM, Khatib R (2000) Limits of detection of Mycobacterium tuberculosis in spiked cerebrospinal fluid using the polymerase chain reaction in tuberculous meningitis. Eur J Clin Microbiol Infect Dis 19:47–50PubMedCrossRef Baran J, Jr., Riederer KM, Khatib R (2000) Limits of detection of Mycobacterium tuberculosis in spiked cerebrospinal fluid using the polymerase chain reaction in tuberculous meningitis. Eur J Clin Microbiol Infect Dis 19:47–50PubMedCrossRef
28.
Zurück zum Zitat Hiraki A, Aoe K, Eda R, et al. (2004) Comparison of six biological markers for the diagnosis of tuberculous pleuritis. Chest 125:987–9PubMedCrossRef Hiraki A, Aoe K, Eda R, et al. (2004) Comparison of six biological markers for the diagnosis of tuberculous pleuritis. Chest 125:987–9PubMedCrossRef
Metadaten
Titel
Interferon γ quantification in cerebrospinal fluid compared with PCR for the diagnosis of tuberculous meningitis
verfasst von
Rafael San Juan
Carmen Sánchez-Suárez
María J. Rebollo
Dolores Folgueira
Elia Palenque
Blanca Ortuño
Carlos Lumbreras
José M. Aguado
Publikationsdatum
01.10.2006
Erschienen in
Journal of Neurology / Ausgabe 10/2006
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-006-0215-y

Weitere Artikel der Ausgabe 10/2006

Journal of Neurology 10/2006 Zur Ausgabe

OriginalPaper

ENS COMMUNICATIONS

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.