Validity of serum adenosine deaminase in diagnosis of tuberculosis

Introduction Tuberculosis is one of the most important infectious causes of death worldwide. Ziehl-Neelsen staining of sputum has high specificity in tuberculosis endemic countries, but modest sensitivity which varies among laboratories. This study was set up to investigate the diagnostic value of serum Adenosine deaminase in diagnosis of tuberculosis. Methods In a cross sectional and prospective study Serums of 200 patients of positive sputum smear, negative sputum smear, extra-pulmonary tuberculosis and bacterial community acquired pneumonia collected from March 2011 to May 2012 were evaluated. The data were analyzed using SPSS software and P-value of <0.05 was considered significant. Results A total of 200 subjects were included in the study designed in four groups. In cut-off value of ≥24 U/l for ADA in smear positive patients defined the sensitivity, specificity and positive predictive value 12%, 98% and 86% respectively. In smear negative patients defined the 6%, 98% and 75%, and in extra-pulmonary tuberculosis patients defined the sensitivity 14%, 98% and 88% respectively. Conclusion This study indicated that measurement of serum ADA level do not have enough sensitivity to assist in the diagnoses of tuberculosis patients from other respiratory diseases and not evaluated perform well enough to replace sputum smear microscopy. Thus, this tests have little role in the diagnosis of pulmonary tuberculosis.


Introduction
Tuberculosis is a major cause of morbidity and mortality throughout the world. One-third of the world's population is infected with the TB bacillus [1]. The global tuberculosis epidemic results in nearly two million deaths and nine million new cases of the disease per year,95% in developing countries [2]. Once infected active disease develops in about 10% of cases usually within 1-2 years after exposure from TB [3]. The remainder stay in a state of latent tuberculosis infection (LTBI), which can reactivate at a later stage, particularly if the individual is elderly or becomes immune compromised. The simplest rapid method is the detection of acidfast bacilli by microscopy. However, 40 to 60% of patients with pulmonary disease and about 75% of patients with extra-pulmonary disease are smear negative, and in this situation even contemporary culture methods take several weeks to become positive where the diagnosis of tuberculosis relies on the identification of acid-fast bacilli on unprocessed sputum smears using conventional Ziehl-Neelsen staining [4][5][6]. Acid-fast staining has high specificity in tuberculosis endemic countries, but modest sensitivity which varies among laboratories (range 20% to 80%) [7,8]. Moreover, the sensitivity is poor for paucibacillary disease (e.g., pediatric and HIV associated tuberculosis) [9]. Thus, the development of rapid and accurate new diagnostic tools is imperative. There are contradictory reports about the diagnostic value of serum adenosine deaminase in tuberculosis. Adenosine deaminase is involved in the propagation and differentiation of various lymphocytes, particularly Tlymphocytes, so that estimation of its level of activity in various body fluids has been used in the diagnosis of tuberculous effusions especially pleural forms [10]. This study was set up to investigate the diagnostic value of serum Adenosin deaminase in diagnosis of tuberculosis because rapid and accurate diagnosis is an important element of TB treatment and control.
In One-way Analysis of Variance (ANOVA) of mean differences of four groups the differences between group III (Ex-pul.) and group IV (CAP) was significant. (P-value =0.0115) (

Discussion
In our study, no significant differences in age, sex, place of residence and compared the serum levels of ADA in four groups were not found significant differences. Several studies were carried out, have suggested the use of serum ADA levels for the diagnosis of pulmonary tuberculosis. Thora et al. [11] studied ADA levels of whereas there were no changes in those patients with normal initial levels (p=0.27). Similar results were obtained by Ishii et al. [14] in Japan together with a direct association between serum ADA level and erythrocyte sedimentation rate. Joshaghani et al. [15] showed that the assessment of these enzymes in serum to some extend can be a useful method for differentiation of healthy subjects from respiratory disease, but these tests do not have enough sensitivity to assist in the diagnoses of tuberculosis patients from other respiratory diseases. Conde et al. [16] evaluated serum ADA in active pulmonary tuberculosis and other pulmonary infections and showed no significant difference between them. Their results were in disagreement with the report by Yasuhara et al. [17] in which serum ADA activity of children with active pulmonary tuberculosis was found to be significantly greater than those with bacterial or

Acknowledgments
This study is part of a medical student´s thesis, the authors thankfully acknowledge Deputy of Research of Arak University of

Medical Sciences and Tuberculosis and Pediatrics Infectious
Diseases Research Center for their support. The authors also would like to thank and are grateful to all the health care workers as well as the patients who took part in the study. Table 1: One-way Analysis of Variance (ANOVA) of four groups