Skip to main content

Advertisement

Log in

Rational application of adenosine deaminase activity in cerebrospinal fluid for the diagnosis of tuberculous meningitis

  • Original Paper
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Purpose

Tuberculous meningitis (TBM) is one of the most serious and difficult to diagnose manifestations of TB. An ADA value >9.5 IU/L has great sensitivity and specificity. However, all available studies have been conducted in areas of high endemicity, so we sought to determine the accuracy of ADA in a low endemicity area.

Methods

This retrospective study included 190 patients (105 men) who had ADA tested in CSF for some reason. Patients were classified as probable/certain TBM or non-TBM based on clinical and Thwaite’s criteria. Optimal ADA cutoff was established by ROC curves and a predictive algorithm based on ADA and other CSF biochemical parameters was generated.

Results

Eleven patients were classified as probable/certain TBM. In a low endemicity area, the best ADA cutoff was 11.5 IU/L with 91 % sensitivity and 77.7 % specificity. We also developed a predictive algorithm based on the combination of ADA (>11.5 IU/L), glucose (<65 mg/dL) and leukocytes (≥13.5 cell/mm3) with increased accuracy (Se: 91 % Sp: 88 %).

Conclusions

Optimal ADA cutoff value in areas of low TB endemicity is higher than previously reported. Our algorithm is more accurate than ADA activity alone with better sensitivity and specificity than previously reported algorithms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Eurosurveillance editorial t. WHO publishes Global tuberculosis report 2013. Euro Surveill. 2013;18(43).

  2. Global Tuberculosis Report 2014, Geneva WHO, 2014. Available at: http://apps.who.int/iris/bitstream/10665/137094/1/9789241564809_eng.pdf?ua=1.

  3. Xu HB, Jiang RH, Li L, Sha W, Xiao HP. Diagnostic value of adenosine deaminase in cerebrospinal fluid for tuberculous meningitis: a meta-analysis. Int J Tuberc Lung Dis Off J Int Union Against Tuberc Lung Dis. 2010;14:1382–7.

    Google Scholar 

  4. Gupta BK, Bharat A, Debapriya B, Baruah H. Adenosine deaminase levels in CSF of tuberculous meningitis patients. J Clin Med Res. 2010;2:220–4. doi:10.4021/jocmr429w.

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Chin JH, Mateen FJ. Central nervous system tuberculosis: challenges and advances in diagnosis and treatment. Curr Infect Dis Rep. 2013;. doi:10.1007/s11908-013-0385-6.

    PubMed  Google Scholar 

  6. Marais S, Thwaites G, Schoeman JF, Torok ME, Misra UK, Prasad K, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis. 2010;10:803–12. doi:10.1016/S1473-3099(10)70138-9.

    Article  PubMed  Google Scholar 

  7. Youssef FG, Afifi SA, Azab AM, Wasfy MM, Abdel-Aziz KM, Parker TM, et al. Differentiation of tuberculous meningitis from acute bacterial meningitis using simple clinical and laboratory parameters. Diagn Microbiol Infect Dis. 2006;55:275–8. doi:10.1016/j.diagmicrobio.2006.01.027.

    Article  CAS  PubMed  Google Scholar 

  8. Thwaites GE, Chau TT, Stepniewska K, Phu NH, Chuong LV, Sinh DX, et al. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features. Lancet. 2002;360:1287–92.

    Article  CAS  PubMed  Google Scholar 

  9. Sun Q, Sha W, Xiao HP, Tian Q, Zhu H. Evaluation of cerebrospinal fluid adenosine deaminase activity for the differential diagnosis of tuberculous and nontuberculous meningitis. Am J Med Sci. 2012;344:116–21. doi:10.1097/MAJ.0b013e318238fee3.

    Article  PubMed  Google Scholar 

  10. Solari L, Soto A, Agapito JC, Acurio V, Vargas D, Battaglioli T, et al. The validity of cerebrospinal fluid parameters for the diagnosis of tuberculous meningitis. Int J Infect Dis. 2013;17:e1111–5. doi:10.1016/j.ijid.2013.06.003.

    Article  CAS  PubMed  Google Scholar 

  11. Rana SV, Chacko F, Lal V, Arora SK, Parbhakar S, Sharma SK, et al. To compare CSF adenosine deaminase levels and CSF-PCR for tuberculous meningitis. Clin Neurol Neurosurg. 2010;112:424–30. doi:10.1016/j.clineuro.2010.02.012.

    Article  CAS  PubMed  Google Scholar 

  12. Thwaites GE, Chau TT, Farrar JJ. Improving the bacteriological diagnosis of tuberculous meningitis. J Clin Microbiol. 2004;42:378–9.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Erdem H, Ozturk-Engin D, Elaldi N, Gulsun S, Sengoz G, Crisan A, et al. The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study. Clin Microbiol Infect. 2013. doi:10.1111/1469-0691.12478.

    Google Scholar 

  14. Chen P, Shi M, Feng GD, Liu JY, Wang BJ, Shi XD, et al. A highly efficient Ziehl-Neelsen stain: identifying de novo intracellular Mycobacterium tuberculosis and improving detection of extracellular M. tuberculosis in cerebrospinal fluid. J Clin Microbiol. 2012;50:1166–70. doi:10.1128/JCM.05756-11.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Thwaites GE. Advances in the diagnosis and treatment of tuberculous meningitis. Curr Opin Neurol. 2013;26:295–300. doi:10.1097/WCO.0b013e3283602814.

    Article  CAS  PubMed  Google Scholar 

  16. Riantawan P, Chaowalit P, Wongsangiem M, Rojanaraweewong P. Diagnostic value of pleural fluid adenosine deaminase in tuberculous pleuritis with reference to HIV coinfection and a Bayesian analysis. Chest. 1999;116:97–103.

    Article  CAS  PubMed  Google Scholar 

  17. Riquelme A, Calvo M, Salech F, Valderrama S, Pattillo A, Arellano M, et al. Value of adenosine deaminase (ADA) in ascitic fluid for the diagnosis of tuberculous peritonitis: a meta-analysis. J Clin Gastroenterol. 2006;40:705–10.

    Article  CAS  PubMed  Google Scholar 

  18. Burgess LJ, Reuter H, Carstens ME, Taljaard JJ, Doubell AF. The use of adenosine deaminase and interferon-gamma as diagnostic tools for tuberculous pericarditis. Chest. 2002;122:900–5.

    Article  CAS  PubMed  Google Scholar 

  19. Fortun J, Martin-Davila P, Gomez-Mampaso E, Vallejo A, Cuartero C, Gonzalez-Garcia A, et al. Extra-pulmonary tuberculosis: a biomarker analysis. Infection. 2014;42:649–54. doi:10.1007/s15010-014-0602-8.

    Article  CAS  PubMed  Google Scholar 

  20. Cho BH, Kim BC, Yoon GJ, Choi SM, Chang J, Lee SH, et al. Adenosine deaminase activity in cerebrospinal fluid and serum for the diagnosis of tuberculous meningitis. Clin Neurol Neurosurg. 2013;115:1831–6. doi:10.1016/j.clineuro.2013.05.017.

    Article  PubMed  Google Scholar 

  21. Jakka S, Veena S, Rao AR, Eisenhut M. Cerebrospinal fluid adenosine deaminase levels and adverse neurological outcome in pediatric tuberculous meningitis. Infection. 2005;33:264–6. doi:10.1007/s15010-005-5005-4.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None to declare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jorge Parra-Ruiz.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Parra-Ruiz, J., Ramos, V., Dueñas, C. et al. Rational application of adenosine deaminase activity in cerebrospinal fluid for the diagnosis of tuberculous meningitis. Infection 43, 531–535 (2015). https://doi.org/10.1007/s15010-015-0777-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-015-0777-7

Keywords

Navigation