Year : 2014 | Volume : 2 | Issue : 1 | Page : 34 - 36  

Short Communications
Diagnostic Value of the Ratio of Pleural Fluid Adenosine Deaminase Activity to Serum Adenosine Deaminase Activity in Children with Tuberculosis and Non Tuberculosis Pleural Effusion

A Sujatha Rani1, H.Kishan Reddy2, Prabhavati Modi3,

1Associate Professor, Department of Biochemistry, Gandhi Medical College, Secunderabad. 2Assistant Professor, Dept of Biochemistry, Prathima Institute of Medical sciences, Karimnagar.

3Professor and Head of Biochemistry, Malla Reddy Institute of Medical Sciences, Hyderabad


Adenosine deaminase (ADA) activity was assayed in pleural fluid and serum of 78 subjects with pleural effusion. 48 of them had tuberculosis (TB) pleural effusion and the remaining 30 had pleural effusions due to non TB respiratory diseases. It is a retrospective study conducted in the biochemistry department, Niloufer hospital, Hyderabad. Serum and pleural fluid ADA activities were assayed spectrophotometrically by the method of guisti and gallant. The aim is to evaluate the value of (ADA) concentration in the pleural effusions for differentiating TB pleural effusions from non TB pleural effusions. The mean pleural ADA (99.78±75.80), serum ADA (79.19±59.17), and pleural fluid/serum ADA ratio(1.26±0.21) are significantly higher in TB pleural effusion cases as compared to non TB pleural effusion cases (The mean pleural ADA 23.10±11.92, Serum ADA 21.69±8.98, Pleural fluid/serum ADA ratio 1.07±0.47) respectively. Using the cutoff value 1.26 the ratio of pleural fluid/serum ADA was found to have a sensitivity of 40% and specificity of 81.25% for the diagnosis of tuberculosis in children. From this study it is concluded that ratio of pleural fluid ADA to serum ADA is a useful tool to diagnose tuberculous pleural effusion cases in children.      

Key words: Adenosine deaminase, Pleural effusion, Tuberculosis.

Corresponding Author: Dr H Kishan Reddy, Assistant professor, Dept of Biochemistry, Prathima institute of Medical sciences, Karimnagar. Email:


Tuberculosis is a bacterial disease caused by the Mycobacterium tuberculosis. It is estimated that globally, approximately 16 million people are suffering from active TB, with an estimated 8.5 million developing active TB each year, [1] of which an estimated 11% cases were children and the reported percentage of all TB cases occurring in children varied from 3% to more than 25% in different countries. [2] About one third of the world’s population is infected with these bacteria. Not all people infected have the disease, and most of them are adults. Tuberculosis (TB), however, remains an under-diagnosed and neglected entity in children. India is home to over 3.4 million T.B patients, about 1/5th of the global figure making the most prevalent country

The clinical manifestations of tuberculosis are dependent on the cellular immune responses to the tubercule bacilli, characterized by the accumulation of monocyte/macrophages, lymphocytes and polymorphonuclear leucocytes in tuberculosis lesions. These responses are initiated on sensitization of T-lymphocytes by the bacterial antigen with the release of cytokines which regulate macrophage function.

Adenosine deaminase (AD; EC is an enzyme required for converting adenosine to inosine in the purine salvage pathway. Its activity is involved in the differentiation and proliferation of lymphocytes and activation of macrophages. [1, 3]

ADA is found in most cells, but its chief role concerns the proliferation and differentiation of lymphocytes, especially T-lymphocytes. For that reason ADA has been looked on as a marker of cell-mediated immunity, which encompasses the delayed hypersensitivity reaction.

The sensitivity of Ziehl-Neelsen staining is 10-40% and culture is 8-49%. Mycobacterium tuberculosis grows very slowly; it can take up to 6 weeks to isolate it in culture. [1] There is a need of a simple, rapid & reliable test which can be easily carried out in the clinical laboratory.

The present study is undertaken to evaluate the diagnostic utility of ADA activity in pleural fluid and serum of tuberculosis patients compared to non Tuberculous cases.

Material and Methods:

This is a retrospective study. The data was collected from Niloufer Hospital during the period June 2009 to June 2010 from medical records after taking prior consent of the superintendent of Niloufer hospital. 78 cases of pleural effusion of age group (1 to 14 yrs) were selected, out of which 48 were diagnosed as TB pleural effusion and 30 were diagnosed as non -TB (para pneumonic) effusion. Children less than one year and more than 14years were excluded from the study.

The following parameter analyzed was selected.

1) ADA: By Guisti and Galanti (Colorimetric method) in serum and Pleural fluid. Though many molecular diagnostic tests are available which are sensitive and specific, such technology is not available in developing countries like India. The colorimetric method for the measurement of Total ADA described by GUISTI and GALANTI has an advantage over other methods because of its low cost, simplicity of technique and rapid-turnaround time.

The study was approved by ethical committee in Osmania Medical College.

The results were analyzed using graph pad instat 3 version software. Independent sample T-test between means of the parameter in two groups (non-T.B&T.B) was done.


In the present study, it was observed that Pleural Fluid ADA levels are significantly higher (P<0.001) in TB when compared with non-TB group. Serum ADA levels are significantly higher (P<0.001) in TB compared with non-TB group. Pleural fluid ADA levels are higher compared to Serum ADA in TB group and non-TB group. Ratio of Pleural fluid ADA/Serum ADA in TB group are significantly higher (P is 0.0151) compared to ratio of Pleural fluid ADA / Serum ADA in non-TB group.


In the present study, we have found higher ADA activity in serum & pleural fluid of T.B cases. ADA activity is increased in infections, such as tuberculosis and typhoid fever, where cell-mediated immunity (CMI) is stimulated. [1]

The increased ADA activity observed in T.B is due to activation of cell mediated immunity. In Tuberculosis, there are increased number of T-lymphocytes and macrophages [4] in pleural fluid & serum, which may be associated with highly elevated ADA activity, as it is greater in these cells. The present study showed that the levels of pleural fluid ADA were significantly higher than serum ADA levels in both tuberculous and non tuberculous pleural effusions, suggesting a localized intra pleural production of ADA. [4] Serum ADA activity and lysozyme levels have been noted to be significantly elevated in children with different forms tuberculosis in comparison to controls. [1]

Burgess LJ [5] showed ADA activity in tuberculous effusion was higher than in any other diagnostic group. Strakinga WF [6] investigated 10 patients with tuberculosis pleurisy and 76 patients with pleural effusions of other etiology. The ADA activity in the tuberculosis patients was significantly higher than in the other groups.

Shibagaki T [7] concluded that tuberculous pleural effusion had a much higher ADA activity than cancer effusion and total ADA activity in tuberculous pleural effusion decreases after anti tubercular therapy. The determination of a cut of value requires a compromise between sensitivity and specificity. The determination of a cut of value requires a compromise between sensitivity and specificity. ADA in pleural fluid and seum was measured by GUISTY and GALANTI method ,which was compared with, Ziehl-Neelsen stain and culture for Mycobacterium tuberculosis positive cases of tuberculous pleural effusion cases to get sensitivity and specificity of the ratio of pleural fluid ADA to serum ADA to diagnose tuberculous pleural effusion cases in children. From our study we have found that using a cut off value 1.06 the sensitivity and specificity of the ratio in the diagnosis of Tuberculosis was found to be 93.33% (true positives are 28 and false negatives are 2) and 60.41%(true negatives are 29 and false positives are 19) respectively. At the cut off level 1.26 the ratio was found to have a sensitivity of 40%(true positives are 12 and false negatives are 18) and specificity of 81.25%(true negatives are 39 and false positives are 9) for the diagnosis of tuberculosis in children. Therefore, the ratio of pleural fluid ADA / serum ADA has a utility in the diagnosis as well as prognosis of T.B pleural effusion.


Although many sensitive tests like molecular diagnostics are available for rapid diagnosis of tuberculosis, such technology is not available in developing countries like india. The method we have used is a simple colorimetric method for the measurement of ADA in serum and pleural fluid described by GUISTI and GALANTI. It has an advantage over other methods because of its low cost, simplicity of technique. Thus we conclude that ratio of pleural fluid ADA to serum ADA is a useful tool in differentiating tuberculous pleural effusion cases from non tuberculous pleural effusion cases. We further conclude that it had limited sensitivity and specificity for differentiating TB from non TB pleural effusion cases compared to Zeihl-Nelson stain and culture for Mycobacterium tuberculosis. Thus we propose simultaneous use of ratio of pleural fluid ADA to serum ADA with other investigations may be helpful.


  1. Lamsal M, Gautam N, Bhatta N, Majhi S, Baral N, Bhattacharya SK. Diagnostic utility of adenosine deaminase activity in pleural fluid and serum of tuberculous and non tuberculous respiratory disease patients. Southeast Asian J Trop Med Public Health. 2007 Mar;38(2):363-9
  2. Tahmeed Ahmed, Farzana S, Shamsir Ahmed AM, Sayera Banu, Asif Mujtaba M, Khurshid AH et al. Childhood Tuberculosis: a Review of Epidemiology, Diagnosis and Management. Infectious Diseases Journal of Pakistan Apr-Jun 2008;17(2):52-60.
  3. Jadhav AA, Bardapurkar JS. Diagnostic value of Adenosine Deaminase to Differentiate Exudates and Transudates. Indian J Physiol Pharmacol 2007;51(2):170-4.
  4. Sharma SK, Suresh V, Mohan A, Kaur P, Saha P, Kumar A et al. A prospective study of sensitivity and specificity of adenosine deaminase in the diagnosis of tuberculous pleural effusion. Indian J Chest Dis Allied Sci. 2001 Jul-Sep;43(3):149-55.
  5. Burgess LJ, Maritz FJ, Le Roux I, Taljaard JJ. Use of adenosine deaminase as a diagnostic tool for tuberculous pleurisy. Thorax 1995;50(6):672-4.
  6. Strankinga WF, Nauta JJ, Straub JP, Stam J. Adenosine Deaminase activity in tuberculous pleural effusions: a diagnostic test. Tubercle. 1987 Jun;68(2):137-40.
  7. Shibagaki T, Hasegawa Y, Saito H, Yamori S, Shimokata K. Adenosine Deaminase isoenzymes in tuberculous pleural effusion. J Lab Clin Med. 1996 Apr;127(4):348-52.


Table 1: Mean ± S.D & P value of ADA in non T.B and T.B Cases.


ADA type                                          Non TB PF Cases       TB PF Cases               p value

                                                           (N = 30)                      (N = 48)

PF ADA                                             23.10±11.92                99.78±75.80                0.0001

Serum ADA                                       21.69±8.98                  79.19±59.17                0.0001

PF ADA/Serum ADA Ratio                     1.07±0.47                    1.26±0.21                 0.0151

Fig. 1: Distribution of patients: PLEASE REFER FROM PDF FILE

Source of Support: Nil. Conflict of Interest: None.


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