Adenosine Deaminase Activity Is a Sensitive Marker for the Diagnosis of Tuberculous Pleuritis in Patients with Very Low CD4 Counts Kamaldeen Baba1,2,3*, Anwar A. Hoosen 3 , Nina Langeland1,4, Anne M. Dyrhol-Riise1,4 1 Institute of Medicine, University of Bergen, Bergen, Norway, 2 Center for International Health, University of Bergen, Bergen, Norway, 3 Department of Microbiological Pathology, University of Limpopo, Limpopo, South Africa, 4 Department of Medicine, Haukeland University Hospital, Bergen, Norway Abstract Background: Adenosine Deaminase Activity (ADA) is a commonly used marker for the diagnosis of tuberculous pleural effusion. There has been concern about its usefulness in immunocompromised patients, especially HIV positive patients with very low CD4 counts. The objective of this study was to evaluate the sensitivity of ADA in pleural fluid in patients with low CD4 counts. Materials and Methods: This was a retrospective case control study. Medical files of patients with tuberculous pleuritis and non-tuberculous pleuritis were reviewed. Clinical characteristics, CD4 cell counts in blood and biochemical markers in pleural fluid, including ADA were recorded. Results: One ninety seven tuberculous pleuritis and 40 non- tuberculous pleuritis patients were evaluated. Using the cut-off value of 30 U/L, the overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of ADA was 94%, 95%, 19, and 0.06 respectively. The mean CD4 cell counts among TB pleuritis patients was 29 and 153 cells/microL in patients with CD4 ,50 cells/microL and .50 cells/microL, (p,0.05) respectively. The corresponding mean ADA values for these patients were 76 U/L and 72 U/L respectively (p.0.5). There was no correlation between ADA values and CD4 cell counts (r = 20.120, p = 0.369). Conclusion: ADA analysis is a sensitive marker of tuberculous pleuritis even in HIV patients with very low CD4 counts in a high TB endemic region. The ADA assay is inexpensive, rapid, and simple to perform and is of great value for the immediate diagnosis of tuberculous pleuritis while waiting for culture result and this has a positive impact on patient outcome. Citation: Baba K, Hoosen AA, Langeland N, Dyrhol-Riise AM (2008) Adenosine Deaminase Activity Is a Sensitive Marker for the Diagnosis of Tuberculous Pleuritis in Patients with Very Low CD4 Counts. PLoS ONE 3(7): e2788. doi:10.1371/journal.pone.0002788 Editor: Aimee K. Zaas, Duke University, United States of America Received February 20, 2008; Accepted June 30, 2008; Published July 30, 2008 Copyright: 2008 Baba et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was funded by QUOTA fellowship programme at the University of Bergen, Norway and thanks to the Regional Health Authorities of Western Norway who funded the running costs. The funders did not play any role in the study design, data analysis and preparation of manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: adeola12@yahoo.co.uk Introduction Tuberculous pleuritis occurs in about 25% of total tuberculosis (TB) cases in South Africa [1,2]. Rapid diagnosis and prompt treatment is needed to reverse the morbidity and mortality due to TB. The diagnosis of tuberculous pleuritis remains a challenge because of the small numbers of bacilli in the pleural fluid [3,4,5]. Pleural fluid staining for acid fast bacilli (AFB) and culture has low sensitivity [4] and culture takes more than a week even when using automated systems. Pleural biopsy culture and typical histology of necrotizing granuloma is more sensitive than pleural fluid culture [4]. However, the invasiveness of the procedure, inability to get representative pleural tissue and the risk of complications are limitations in obtaining pleural biopsies. We have recently demonstrated that immunohistochemistry with the anti- MPT64 antibody as diagnostic tool offers a reasonable high sensitivity for the diagnosis of TB pleuritis [6]. A well established biological marker for diagnosis of tuberculous pleuritis is Adenosine Deaminase Activity (ADA) [4,7,8,9,10]. The ADA assay principle is based on the detection of either hydrogen peroxide or ammonia after enzymatic deamination of adenosine to inosine by ADA. The unit cost of different commercial assays in South Africa is about South African rands nine (equivalent to U.S dollars 1.2). Production of the enzyme Adenosine Deaminase in pleural fluid reflects the presence of activated T lymphocytes and monocytes [11]. Therefore, it is expected that ADA will be lower in HIV co-infected patients and/or other immunocompromised patients with low blood CD4 counts. It has been shown that ADA values correlate with CD4 counts in the pleural fluid of TB patients [12]. Hsu et al [13] has shown lower sensitivity of ADA for the diagnosis of TB pleural effusion in 10 immunocompromised patients with chronic illness such as diabetes, cirrhosis, renal failure and leukaemia. In contrast, Riantawan et al [14] did not find any difference in the performance of ADA in 37 HIV positive patients with mean CD4 counts above 100 cells/microL. A recent study by Reuter et al [15] reported low sensitivity of ADA in tuberculous pericarditis patients with advanced HIV disease and median CD4 count of 59 (6–115) cells/microL. CD4 counts below PLoS ONE | www.plosone.org 1 July 2008 | Volume 3 | Issue 7 | e2788