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  Table of Contents    
ORIGINAL ARTICLE
Year : 2020  |  Volume : 37  |  Issue : 2  |  Page : 126-129  

Changes of serum adenosine deaminase level in new cases of pulmonary tuberculosis before and after intensive phase treatment


1 Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
2 Department of Clinical Pathology, Faculty of Medicine, Ciputra University, Surabaya, East Java, Indonesia
3 Department of Clinical Pathology, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia

Date of Submission27-Aug-2019
Date of Decision18-Oct-2019
Date of Acceptance05-Dec-2019
Date of Web Publication27-Feb-2020

Correspondence Address:
Soedarsono Soedarsono
Jl. Mayjen. Prof. Dr. Moestopo No. 47 Surabaya 60131, East Java
Indonesia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/lungindia.lungindia_395_19

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   Abstract 


Background and Objectives: Tuberculosis (TB) continues to be a public health crisis with an estimated 10 million people developing TB disease in 2017. Adenosine deaminase (ADA) level in serum and pleural fluid as a biomarker may be used to diagnose pulmonary TB (PTB), but it is not always easy to obtain those samples at the end of treatment. This study was conducted to analyze the changes of serum ADA level in the new case of PTB patients with acid-fast bacilli (AFB) smear-positive sputum and sputum conversion status as treatment monitoring in PTB patients. Materials and Methods: This was a prospective observational analytic study conducted in Dr. Soetomo General Hospital, Surabaya, from January 2018 to May 2018. Participants were all new cases of PTB patients with AFB smear-positive sputum, and a positive rapid molecular test for Mycobacterium tuberculosis. Blood serums were taken at the same time on the 1st day of TB treatment and also taken at the end of intensive phase treatment to analyze the changes of serum ADA level. Results: There were 26 TB patients and 26 healthy control people. Serum ADA level at the beginning of TB treatment was higher than the level at the end of intensive phase treatment. There was a significant difference between serum ADA level before and after the intensive phase of TB treatment (P < 0.001). Conclusions: The examination of serum ADA levels can be used to evaluate the PTB treatment response.

Keywords: Pulmonary tuberculosis, serum adenosine deaminase, sputum conversion


How to cite this article:
Soedarsono S, Prinasetyo KW, Tanzilia M, Nugraha J. Changes of serum adenosine deaminase level in new cases of pulmonary tuberculosis before and after intensive phase treatment. Lung India 2020;37:126-9

How to cite this URL:
Soedarsono S, Prinasetyo KW, Tanzilia M, Nugraha J. Changes of serum adenosine deaminase level in new cases of pulmonary tuberculosis before and after intensive phase treatment. Lung India [serial online] 2020 [cited 2020 Apr 3];37:126-9. Available from: http://www.lungindia.com/text.asp?2020/37/2/126/279578




   Introduction Top


Tuberculosis (TB) is a major health problem with an estimated 10 million people having developed TB disease causing 1.3 million deaths in 2017. Indonesia was ranked third high TB burden country in 2017 with 842,000 TB cases.[1] Acid-fast bacilli (AFB) and culture of Mycobacterium tuberculosis from sputum samples were commonly used for TB diagnosis and monitoring. The culture of M. tuberculosis has better sensitivity and specificity than smear examination.[2],[3] However, the time needed to obtain culture results is around 8 weeks[4] which cause significant delays in diagnosis and starting treatment, also monitoring treatment response. Sputum conversion can be a strong prediction and an early indication of treatment success. There were different times for sputum conversion in every patient, even though treated with the same standard regimen. According to Rutta et al., sputum conversion occurred in the 2nd month of intensive phase treatment. Sputum conversion in patients is also associated with predictions of antituberculosis drug (ATD) resistance.[5] Meanwhile, some patients have problems from the beginning with the examination of sputum specimens, so that evaluation of therapy response monitoring is only based on clinical and chest X-ray series.

Adenosine deaminase (ADA) is an enzyme which plays a role in purine catabolism which catalyzes the conversion of adenosine to inosine and deoxyadenosine to deoxyinosine. The examination of ADA activity is fast, affordable, and has high sensitivity and specificity to be used as a supporting diagnosis of pulmonary TB (PTB).[4] Elevated serum ADA levels in PTB patients conform to the severity of the disease, high bacterial isolation, and lung tissue damage. This suggests that ADA measurement is an additional criterion in assessing the response of TB treatment and is used as a prognosis in PTB patients.

Studies of serum ADA levels comparison in TB patients during TB treatment in Indonesia are limited. This study was conducted to analyze changes in serum ADA levels in new PTB cases with smear postive tuberculosis who experienced sputum conversion, so as to assess its utility as a possible treatment monitoring method in PTB.


   Material and Methods Top


This was a prospective observational analytic study conducted in TB clinic Dr. Soetomo Hospital, Surabaya, from January 2018 to May 2018. All samples were taken from new PTB cases with sputum-positive smear with positive GeneXpert for M. tuberculosis that were put on treatment with standard WHO regimen at Dr. Soetomo Hospital. Sputum smear examination was done using Ziehl–Neelsen staining according to the WHO recommendation. AFBs identified were graded according to the International Union against Tuberculosis and Lung Disease and the WHO smear grading scale. Serum ADA levels were analyzed using the enzymatic colorimetric method, using Erba XL 600. Results of serum ADA levels of TB patients were analyzed and compared to serum ADA levels of healthy people. Participants of this study were healthy control people and PTB patients who agreed and signed written informed consent form. This study was approved by the Ethics Committee of Dr. Soetomo Hospital with ethical clearance number 0005/KEPK/I/2018 and was approved on January 22, 2018.


   Results Top


There were 26 new cases of TB patients with M. tuberculosis detected results and positive AFB, with mean age 42.85 years and 26 healthy control people with mean age 39.69 years. TB patients were 21/26 (80.8%) men and 5/26 (19.2%) women [Table 1].
Table 1: Profile of study participants

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All TB patients had sputum conversion and showed a decreased in serum ADA levels after the end of the intensive phase of TB treatment. Patients with AFB + 3 have a higher mean value of serum ADA level before and after the end of the intensive phase of TB treatment. After the end of intensive phase of TB treatment, serum ADA levels of TB patients with baseline AFB + 1 had the closer value (15.51 IU/L) to the serum ADA levels of healthy people (10.18 IU/L) [Table 2].
Table 2: Serum adenosine deaminase levels before and after the end of the intensive phase of tuberculosis treatment

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Mann–Whitney test showed that there was a significant difference in serum ADA levels of TB patients before and after the intensive phase of TB treatment, compared to healthy people with P < 0.001 [Table 3].
Table 3: The difference in serum adenosine deaminase test results of tuberculosis patients before and after the intensive phase of tuberculosis treatment compared to healthy people

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All patients experienced sputum conversion after the intensive phase of TB treatment. Examination of serum ADA levels showed that the mean value of serum ADA levels before treatment was higher than after receiving ATDs with (26.40 IU/L vs. 19.67 IU/L). Paired t-test results showed a significant difference in serum ADA levels before and after the intensive phase of TB treatment with P < 0.001 [Table 4].
Table 4: Differences in serum test results in tuberculosis patients before and after the intensive phase of tuberculosis treatment

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[Table 5] shows that serum ADA levels of TB patients decreased after the intensive phase of TB treatment impying that serum ADA levels decreased as patients were on TB treatment and the value of serum ADA levels became closer to the serum ADA levels of healthy people.
Table 5: Differences in serum test results before and after the intensive phase of tuberculosis treatment compared to healthy people

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   Discussion Top


There were 26 TB patients in this study with an average age of 42.85 years from 21/26 (80.8%) men to 5/26 (19.2%) women. PTB is common in men, and this is due to the greater smoking habits in men increased risk of incident TB[6] and the high mobility causes the high transmission.

All study participants before getting TB treatment showed positive AFB sputum and after receiving treatment for 2 months, all the study participants experienced smear sputum conversion. The success of treatment for PTB is directly related to the microbiological status of the sputum specimen of the patient during treatment. Sputum conversion has been widely reported as a predictor of treatment success.[7],[8]

Our study found that the highest mean value of serum ADA levels before TB treatment was among AFB + 3 with 34.04 IU/L, followed by AFB + 2 with 24.44 IU/L, and AFB + 1 with 19.99 IU/L. Previous study reported the same results that the mean value of serum ADA level was higher among 3+graded sputum-positive patients. This is due to the stimulation of cell-mediated immunity.[9]

In this study, serum ADA levels increased in higher AFB load in sputum smears of TB patients. Serum ADA levels in PTB patients decreased by TB treatment and suggest that serum ADA levels can be used as a prognostic marker. Higher AFB sputum smear shows the severity of the disease based on the number of bacterial loads. Saini et al. stated that the average level of serum ADA levels increased significantly in PTB patients, although there was no statistically significant difference in the value of serum ADA levels related to the level of bacterial load on sputum smear.[10] This shows that the measurement of ADA serum does not have a role in determining the bacteriological burden of the disease. A study by Pandey et al. reported that the increase in serum ADA levels along with the increase of the sputum AFB grading, and the increase in serum ADA level was caused by stimulation of cell mediated immunity.[9]

All participants in this study experienced sputum conversion. The results of the examination of ADA serum levels after the end of the intensive phase of TB treatment have decreased. This indicates that examination of ADA serum levels can be used in monitoring TB therapy response. Kartaloglu et al. reported that there was a significant decrease in serum ADA levels in PTB patients who had received ATDs therapy after the intensive phase. There was an increase in serum ADA in the 1st month but decreased during treatment.[11] ADA serum levels were expected to increase twice in PTB patients at the time of diagnosis and subsequently experienced a significant decrease in the mean value of ADA serum levels after treatment in PTB patients.[12] ADA serum levels decreased to normal levels after 1 month of effective treatment in patients with PTB. A decrease in ADA serum levels can be caused by changes in the number of lymphocytes induced by M. tuberculosis.[13] Significant differences were obtained in ADA serum activity before and after treatment, and also from older TB patients and healthy control patients, indicating that ADA serum activity was increased in PTB patients.[14]

Serum ADA levels decreased during TB treatment, although there is a significant difference, compared to serum ADA levels in healthy people with P < 0.001 [Table 3], this is because the TB treatment is not completed yet till the end of continuation phase. It was shown that after the end of intensive phase of TB treatment, serum ADA levels decreased and reached closer to the mean value of serum ADA levels in healthy people (19.67 IU/L after the end of the intensive phase of TB treatment and 10.18 IU/L in healthy people) as presented in [Table 5].

In this study, the mean serum ADA levels in PTB patients before receiving TB treatment was 26.40 IU/L and decreased during PTB treatment with serum ADA levels of 19.67 IU/L. Paired t-test showed a significant difference in serum ADA levels before TB treatment and after the end of the intensive phase of TB treatment with P < 0.001. These data suggests that ADA measurement is an additional marker in assessing therapy response or treatment monitoring in PTB patients. Rao et al. reported the decrease in serum ADA levels during PTB treatment. Serum ADA levels showed a significant difference between serum ADA levels before and after the 2nd month of TB treatment with P < 0.001 (41.48 U/L vs. 29.66 U/L). The measurement of serum ADA could help the evaluation of therapy response.[15] Other study reported the same results that serum ADA levels decreased during TB treatment.[16],[17]

Changes of serum ADA levels can be used as a therapeutic response marker. Serial examination of serum ADA levels can be used to monitor therapy response of TB treatment, especially in patients with negative sputum microscopic examination results. The future study was needed by measuring the serum ADA levels at the baseline before therapy and followed up till the end of TB treatment.


   Conclusions Top


The mean value of serum ADA levels was significantly decreased after the end of the intensive phase of TB treatment. The examination of serum ADA levels can be used to evaluate the response of PTB treatment.

Limitations of the study

The present study had several limitations. TB diagnosis is based on GeneXpert and AFB microscopy examination. The culture of M. tuberculosis as a gold standard for TB diagnosis was not used. Furthermore, sputum conversion in only based on AFB microscopy examination, not with serial culture.

Acknowledgment

The author would like to thank Gleneagles Diagnostic Centre for funding this research and Mrs. Atika, M. Sc., Department of Public Health - Preventive Medicine, Faculty of Medicine, Universitas Airlangga who helped us in data analysis.

Financial support and sponsorship

This study was financially supported by Gleneagles Diagnostic Centre.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
World Health Organization. Global Tuberculosis Report 2015. Geneva: World Health Organization; 2016. p. 1-34.  Back to cited text no. 1
    
2.
Albert H, Heydenrych A, Brookes R, Mole RJ, Harley B, Subotsky E, et al. Performance of a rapid phage-based test, FASTPlaqueTB, to diagnose pulmonary tuberculosis from sputum specimens in South Africa. Int J Tuberc Lung Dis 2002;6:529-37.  Back to cited text no. 2
    
3.
Levinson W. Review of Medical Microbiology and Immunology. United States: The McGraw-Hill Companies Inc.; 2008. p. 164.  Back to cited text no. 3
    
4.
Barua R, Hossain M. Adenosin deaminase in diagnosis of tuberculosis: A review. Anwer Khan Mod Med Coll J 2014;5:43-8.  Back to cited text no. 4
    
5.
Rutta E, Kipingili R, Lukonge H, Assefa S, Mitsilale E, Rwechungura S. Treatment outcome among Rwandan and Burundian refugees with sputum smear-positive tuberculosis in Ngara, Tanzania. Int J Tuberc Lung Dis 2001;5:628-32.  Back to cited text no. 5
    
6.
Jee SH, Golub JE, Jo J, Park IS, Ohrr H, Samet JM. Smoking and risk of tuberculosis incidence, mortality, and recurrence in South Korean men and women. Am J Epidemiol 2009;170:1478-85.  Back to cited text no. 6
    
7.
van der Kuyp F, Mahan CS. Prolonged positivity of sputum smears with negative cultures during treatment for pulmonary tuberculosis. Int J Tuberc Lung Dis 2012;16:1663-7.  Back to cited text no. 7
    
8.
Lv L, Li T, Xu K, Shi P, He B, Kong W, et al. Sputum bacteriology conversion and treatment outcome of patients with multidrug-resistant tuberculosis. Infect Drug Resist 2018;11:147-54.  Back to cited text no. 8
    
9.
Pandey R, Tamrakar D, Jaiswal S, Sharma A, Koju S, Duwal SR, et al. Serum adenosine deaminase: A novel biomarker tool for the diagnosis of tuberculosis. Biosci Biotech Res Asia 2016;13:551-6.  Back to cited text no. 9
    
10.
Saini V, Lokhande B, Jaswal S, Aggarwal D, Garg K, Kaur J. Role of serum adenosine deaminase in pulmonary tuberculosis. Indian J Tuberc 2018;65:30-4.  Back to cited text no. 10
    
11.
Kartaloglu Z, Okutan O, Bozkanat E, Ugan MH, Ilvan A. The course of serum adenosine deaminase levels in patients with pulmonary tuberculosis. Med Sci Monit 2006;12:CR476-80.  Back to cited text no. 11
    
12.
Cimen F, Ciftci TV, Berktaft BM, Sipit T, Hoca NT, Dulkar G. The relationship between serum adenosine deaminase level in lung tuberculosis along with drug resistance and the category of tuberculosis. Turk Respir J 2008;9:20-3.  Back to cited text no. 12
    
13.
Conde MB, Marinho SR, Pereira Mde F, Lapa e Silva JR, Saad MH, Sales CL, et al. The usefulness of serum adenosine deaminase 2 (ADA2) activity in adults for the diagnosis of pulmonary tuberculosis. Respir Med 2002;96:607-10.  Back to cited text no. 13
    
14.
Alataş F, Uslu S, Moral H, Alataş O, Metintaş M, Erginel S, et al. Serum adenosine deaminase activity in pulmonary tuberculosis. Tuberk Toraks 2003;51:277-81.  Back to cited text no. 14
    
15.
Rao KS, Kumar HA, Rudresh BM, Srinivas T, Bhat KH. Evaluation of serum adenosine deaminase activity during the course of pulmonary tuberculosis treatment. Biomed Res 2012;23:109-14.  Back to cited text no. 15
    
16.
Bhandari S, Regmi S, Dhakali N, Gautam G, Karki S, Shrestha S, et al. Evaluation of serum adenosine deaminase lactate dehydrogenase and ceruplasmin during anti-tuberculosis treatment. EC Microbiol 2018;14:694-8.  Back to cited text no. 16
    
17.
Ige O, Edem VF, Arinola OG. Plasma Adenosine Deaminase Enzyme Reduces with Treatment of Pulmonary Tuberculosis in Nigerian Patients: Indication for diagnosis and treatment monitoring. Niger J Physiol Sci 2016;31:49-53.  Back to cited text no. 17
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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