Skip to main content
Top
Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

The dubious value of cerebrospinal fluid adenosine deaminase measurement for the diagnosis of tuberculous meningitis

Authors: Pieter Ekermans, Adriano Dusé, Jaya George

Published in: BMC Infectious Diseases | Issue 1/2017

Login to get access

Abstract

Background

The diagnosis of tuberculous meningitis (TBM) can be extremely difficult in the absence of culture confirmation. Cerebrospinal fluid (CSF) adenosine deaminase (ADA) can potentially assist in this regard, although its current value remains unclear. The literature on the usefulness of CSF ADA in TBM diagnosis is inconsistent, especially from an analytical point of view.

Methods

A retrospective analysis of clinical and laboratory data relating to all CSF ADA requests during 2009 and 2010 in a South African quaternary healthcare setting was performed. A CSF ADA cut-off for TBM diagnosis was calculated using receiver operating characteristic curve analysis. The performance of CSF ADA in different infective and non-infective categories was assessed.

Results

In total, 3548 CSF ADA requests were considered over the 2-year period. Of these, 1490 were for patients for whom both a CSF ADA and a mycobacterial culture were requested. The optimal cut-off was calculated at 2.0 U/L (AUC = 0.86; 95% CI = 0.82 – 0.89; p-value < 0.01; sensitivity of 85.9% (95% CI of 77.0 – 92.3) and specificity of 77.7% (95% CI of 75.4 – 79.8%); positive likelihood ratio = 3.85 and negative likelihood ratio = 0.18). At this cut-off 13 TBM cases were missed.

Conclusion

An optimal cut-off for routine use could not be established as too many TBM cases were missed. Specimen integrity, lack of ADA assay standardisation and overlap in performance of the assay in different diagnostic categories affect interpretation.
Literature
1.
go back to reference Mishra OP, Loiwal V, Ali Z, et al. Cerebrospinal fluid adenosine deaminase activity for the diagnosis of tuberculous meningitis in children. J Trop Pediatr. 1996;42:129–32.CrossRefPubMed Mishra OP, Loiwal V, Ali Z, et al. Cerebrospinal fluid adenosine deaminase activity for the diagnosis of tuberculous meningitis in children. J Trop Pediatr. 1996;42:129–32.CrossRefPubMed
2.
go back to reference Rana SV, Singhal RK, Singh K, et al. Adenosine deaminase levels in cerebrospinal fluid as a diagnostic test for tuberculous meningitis in children. Ind J Clin Biochem. 2004;19(2):5–9.CrossRef Rana SV, Singhal RK, Singh K, et al. Adenosine deaminase levels in cerebrospinal fluid as a diagnostic test for tuberculous meningitis in children. Ind J Clin Biochem. 2004;19(2):5–9.CrossRef
3.
go back to reference Pettersson T, Klockars M, Weber TH, et al. Diagnostic value of cerebrospinal fluid adenosine deaminase determination. Scand J Infect Dis. 1991;23:97–100.CrossRefPubMed Pettersson T, Klockars M, Weber TH, et al. Diagnostic value of cerebrospinal fluid adenosine deaminase determination. Scand J Infect Dis. 1991;23:97–100.CrossRefPubMed
4.
go back to reference Schutte C-M, Ungerer JPJ, du Plessis H, et al. Significance of cerebrospinal fluid adenosine deaminase isoenzymes in tuberculous (TB) meningitis. J Clin Lab Anal. 2001;15:236–8.CrossRefPubMed Schutte C-M, Ungerer JPJ, du Plessis H, et al. Significance of cerebrospinal fluid adenosine deaminase isoenzymes in tuberculous (TB) meningitis. J Clin Lab Anal. 2001;15:236–8.CrossRefPubMed
5.
go back to reference Corral I, Quereda C, Navas E, et al. Adenosine deaminase activity in cerebrospinal fluid of HIV-infected patients: limited value for diagnosis of tuberculous meningitis. Eur J Clin Microbiol Infect Dis. 2004;23:471–6.CrossRefPubMed Corral I, Quereda C, Navas E, et al. Adenosine deaminase activity in cerebrospinal fluid of HIV-infected patients: limited value for diagnosis of tuberculous meningitis. Eur J Clin Microbiol Infect Dis. 2004;23:471–6.CrossRefPubMed
6.
go back to reference Blake J, Berman P. The use of adenosine deaminase assays in the diagnosis of tuberculosis. S Afr Med J. 1982;62:19–21.PubMed Blake J, Berman P. The use of adenosine deaminase assays in the diagnosis of tuberculosis. S Afr Med J. 1982;62:19–21.PubMed
7.
go back to reference Ribera E, Martinez-Vasquez JM, Ocaňa I, et al. Activity of adenosine deaminase in cerebrospinal fluid for the diagnosis and follow-up of tuberculous meningitis in adults. J Infect Dis. 1987;155(4):603–7.CrossRefPubMed Ribera E, Martinez-Vasquez JM, Ocaňa I, et al. Activity of adenosine deaminase in cerebrospinal fluid for the diagnosis and follow-up of tuberculous meningitis in adults. J Infect Dis. 1987;155(4):603–7.CrossRefPubMed
8.
go back to reference Choi S-H, Kim YS, Bae I-G, et al. The possible role of cerebrospinal fluid adenosine deaminase activity in the diagnosis of tuberculous meningitis in adults. Clin Neurol Neurosurg. 2002;104:10–5.CrossRefPubMed Choi S-H, Kim YS, Bae I-G, et al. The possible role of cerebrospinal fluid adenosine deaminase activity in the diagnosis of tuberculous meningitis in adults. Clin Neurol Neurosurg. 2002;104:10–5.CrossRefPubMed
9.
go back to reference Kaur A, Basha A, Ranjan M, et al. Poor diagnostic value of adenosine deaminase in pleural, peritoneal & cerebrospinal fluids in tuberculosis. Indian J Med Res. 1992;95:270–7.PubMed Kaur A, Basha A, Ranjan M, et al. Poor diagnostic value of adenosine deaminase in pleural, peritoneal & cerebrospinal fluids in tuberculosis. Indian J Med Res. 1992;95:270–7.PubMed
10.
go back to reference Kashyap RS, Ramteke SP, Deshpande PS, et al. Comparison of an adenosine deaminase assay with ELISA for the diagnosis of tuberculous meningitis infection. Med Sci Monit. 2007;13(9):BR200–204.PubMed Kashyap RS, Ramteke SP, Deshpande PS, et al. Comparison of an adenosine deaminase assay with ELISA for the diagnosis of tuberculous meningitis infection. Med Sci Monit. 2007;13(9):BR200–204.PubMed
11.
go back to reference Lópés-Cortés IF, Cruz-Ruiz M, Gómez-Mateos J, et al. Adenosine deaminase activity in the CSF of patients with aseptic meningitis: utility in the diagnosis of tuberculous meningitis or neurobrucellosis. Clin Infect Dis. 1995;20:525–30.CrossRef Lópés-Cortés IF, Cruz-Ruiz M, Gómez-Mateos J, et al. Adenosine deaminase activity in the CSF of patients with aseptic meningitis: utility in the diagnosis of tuberculous meningitis or neurobrucellosis. Clin Infect Dis. 1995;20:525–30.CrossRef
12.
go back to reference Oosthuizen HM, Ungerer JPJ, Bissbort SH. Kinetic determination of serum adenosine deaminase. Clin Chem. 1993;39(10):2182–5.PubMed Oosthuizen HM, Ungerer JPJ, Bissbort SH. Kinetic determination of serum adenosine deaminase. Clin Chem. 1993;39(10):2182–5.PubMed
13.
go back to reference Maldarelli F. Diagnosis of HIV infection. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and Practice of Infectious Diseases. London: Churchill Livingstone, 2005; pp 1516–20. Maldarelli F. Diagnosis of HIV infection. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and Practice of Infectious Diseases. London: Churchill Livingstone, 2005; pp 1516–20.
15.
go back to reference Dawson-Saunders B, Trapp RG, editors. Estimating and comparing means, Evaluating diagnostic procedures. In: Basic & Clinical Biostatistics. Appleton and Lange, 1994; pp 117–119, 243–245. Dawson-Saunders B, Trapp RG, editors. Estimating and comparing means, Evaluating diagnostic procedures. In: Basic & Clinical Biostatistics. Appleton and Lange, 1994; pp 117–119, 243–245.
16.
go back to reference Akobeng AK. Understanding diagnostic tests 3: receiver operating characteristic curves. Acta Pediatr. 2007;96:644–7.CrossRef Akobeng AK. Understanding diagnostic tests 3: receiver operating characteristic curves. Acta Pediatr. 2007;96:644–7.CrossRef
17.
go back to reference Marais S, Thwaites G, Schoeman JF, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis. 2010;10:803–12.CrossRefPubMed Marais S, Thwaites G, Schoeman JF, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis. 2010;10:803–12.CrossRefPubMed
18.
go back to reference Donald PR, Malan C, Van der Walt A, et al. The simultaneous determination of cerebrospinal fluid and plasma adenosine deaminase activity as a diagnostic aid in tuberculous meningitis. S Afr Med J. 1986;69:505–7.PubMed Donald PR, Malan C, Van der Walt A, et al. The simultaneous determination of cerebrospinal fluid and plasma adenosine deaminase activity as a diagnostic aid in tuberculous meningitis. S Afr Med J. 1986;69:505–7.PubMed
19.
go back to reference Xu H-B, Jiang R-H, Sha W, et al. Diagnostic value of adenosine deaminase in cerebrospinal fluid for tuberculous meningitis: a meta-analysis. Int J Tuberc Lung Dis. 2010;14(11):1382–7.PubMed Xu H-B, Jiang R-H, Sha W, et al. Diagnostic value of adenosine deaminase in cerebrospinal fluid for tuberculous meningitis: a meta-analysis. Int J Tuberc Lung Dis. 2010;14(11):1382–7.PubMed
20.
go back to reference Malan C, Donald PR, Golden M, et al. Adenosine deaminase levels in cerebrospinal fluid in the diagnosis of tuberculous meningitis. J Trop Med Hyg. 1984;87(1):33–40.PubMed Malan C, Donald PR, Golden M, et al. Adenosine deaminase levels in cerebrospinal fluid in the diagnosis of tuberculous meningitis. J Trop Med Hyg. 1984;87(1):33–40.PubMed
21.
go back to reference Coovadia YM, Dawood A, Ellis ME, et al. Evaluation of adenosine deaminase activity and antibody to Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid and the radioactive bromide partition test for the early detection of tuberculosis meningitis. Arc Dis Child. 1986;61:428–35.CrossRef Coovadia YM, Dawood A, Ellis ME, et al. Evaluation of adenosine deaminase activity and antibody to Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid and the radioactive bromide partition test for the early detection of tuberculosis meningitis. Arc Dis Child. 1986;61:428–35.CrossRef
22.
go back to reference Rohani MY, Cheong YM, Rani JM. The use of adenosine deaminase activity as a biochemical marker for the diagnosis of tuberculous meningitis. Malays J Pathol. 1995;17(2):67–71.PubMed Rohani MY, Cheong YM, Rani JM. The use of adenosine deaminase activity as a biochemical marker for the diagnosis of tuberculous meningitis. Malays J Pathol. 1995;17(2):67–71.PubMed
23.
go back to reference Donald PR, Malan C, Schoeman JF. Letter to the editor: Adenosine deaminase activity as a diagnostic aid in tuberculous meningitis. J Infect Dis. 1987;156(6):1040–1.CrossRefPubMed Donald PR, Malan C, Schoeman JF. Letter to the editor: Adenosine deaminase activity as a diagnostic aid in tuberculous meningitis. J Infect Dis. 1987;156(6):1040–1.CrossRefPubMed
24.
go back to reference Feres MC, De Martino MC, Maldijian S, et al. Laboratorial validation of an automated assay for the determination of adenosine deaminase activity in pleural fluid and cerebrospinal fluid. J Bras Pneumol. 2008;34(12):1003–39.CrossRef Feres MC, De Martino MC, Maldijian S, et al. Laboratorial validation of an automated assay for the determination of adenosine deaminase activity in pleural fluid and cerebrospinal fluid. J Bras Pneumol. 2008;34(12):1003–39.CrossRef
25.
go back to reference Ungerer JPJ, Oosthuizen HM, Bissbort SH, et al. Serum adenosine deaminase: isoenzyme and diagnostic application. Clin Chem. 1992;38(7):1322–6.PubMed Ungerer JPJ, Oosthuizen HM, Bissbort SH, et al. Serum adenosine deaminase: isoenzyme and diagnostic application. Clin Chem. 1992;38(7):1322–6.PubMed
26.
go back to reference Tuon FF, Higashino HR, Banks MI, et al. Adenosine deaminase and tuberculous meningitis – a systematic review with meta-analysis. Scand J Infect Dis. 2010;42:198–207.CrossRefPubMed Tuon FF, Higashino HR, Banks MI, et al. Adenosine deaminase and tuberculous meningitis – a systematic review with meta-analysis. Scand J Infect Dis. 2010;42:198–207.CrossRefPubMed
27.
go back to reference Bota A, Gella F-J, Profilis C, et al. Production and certification of an enzyme reference material for adenosine deaminase 1 (BCR 647). Clin Chim Act. 2001;306:79–89. Bota A, Gella F-J, Profilis C, et al. Production and certification of an enzyme reference material for adenosine deaminase 1 (BCR 647). Clin Chim Act. 2001;306:79–89.
28.
go back to reference Delacour H, Sauvanet C, Ceppa F, et al. Analytical performances of the Diazyme ADA assay on the Cobas® 6000 system. Clin Biochem. 2010;43:1468–71.CrossRefPubMed Delacour H, Sauvanet C, Ceppa F, et al. Analytical performances of the Diazyme ADA assay on the Cobas® 6000 system. Clin Biochem. 2010;43:1468–71.CrossRefPubMed
Metadata
Title
The dubious value of cerebrospinal fluid adenosine deaminase measurement for the diagnosis of tuberculous meningitis
Authors
Pieter Ekermans
Adriano Dusé
Jaya George
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-017-2221-3

Other articles of this Issue 1/2017

BMC Infectious Diseases 1/2017 Go to the issue