Evaluation of polymerase chain reaction, adenosine deaminase, and interferon-gamma in pleural fluid for the differential diagnosis of pleural tuberculosis.

STUDY OBJECTIVES Pleural tuberculosis (TB) is a diagnostic challenge because of its nonspecific clinical presentation and paucibacillary nature. The inefficiency of conventional laboratory methods and the reliance on pleural biopsy have motivated the evaluation of alternative diagnostic strategies. We have evaluated polymerase chain reaction (PCR) directed to the IS6110 sequence of Mycobacterium tuberculosis, the determination of adenosine deaminase (ADA) activity, and measurement of interferon (IFN)-gamma levels in pleural fluid in the diagnosis of pleural TB. PATIENTS ADA activity, IFN-gamma levels, and PCR were evaluated in 140 cases of pleural effusion, 42 with confirmed pleural TB, 19 with probable pleural TB, 70 with a nontuberculous etiology, and 9 having an undetermined etiology. RESULTS ADA activity, IFN-gamma levels, and PCR were 88%, 85.7%, and 73.8% sensitive, respectively, and 85.7%, 97.1%, and 90% specific, respectively, for pleural TB that had been confirmed by either culture or pleural biopsy specimens. The combination of PCR, IFN-gamma measurement, and ADA activity determination allowed the selective increase of sensitivity and specificity for probable and confirmed cases compared to individual methods. Positive and negative predictive values for these individual or combined methods were maintained over a wide range of prevalence of pleural TB in the patient population presenting with pleural effusions. Fever and younger age were associated with tuberculous pleural effusion (p < 0. 0001), while blood in sputum and older age were associated with malignant etiology (p < 0.008). CONCLUSIONS These clinical variables together with the use of ADA activity determination, PCR, and measurement of IFN-gamma levels provide the basis for the rapid and efficient diagnosis of pleural TB in different clinical settings.

[1]  K. Shimokata,et al.  Adenosine deaminase isozymes in tuberculous pleural effusion. , 1996, The Journal of laboratory and clinical medicine.

[2]  G. Maartens,et al.  Tuberculous pleural effusions: increased culture yield with bedside inoculation of pleural fluid and poor diagnostic value of adenosine deaminase. , 1991, Thorax.

[3]  S. Kohno,et al.  Differential diagnosis of tuberculous pleurisy by measurement of cytokine concentrations in pleural effusion. , 1997, Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[4]  P. Pineda,et al.  Adenosine deaminase in the diagnosis of tuberculous pleural effusions. A report of 218 patients and review of the literature. , 1991, Chest.

[5]  L. Valdés,et al.  Tuberculous pleurisy: a study of 254 patients. , 1998, Archives of internal medicine.

[6]  S. Kuijper,et al.  Mycobacterium smegmatis strain for detection of Mycobacterium tuberculosis by PCR used as internal control for inhibition of amplification and for quantification of bacteria , 1994, Journal of clinical microbiology.

[7]  M. Sanaka,et al.  [Pleural adenosine deaminase levels in tuberculous pleurisy--its diagnostic performance under the different prevalences in the different age of population]. , 1998, The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyobu Geka Gakkai zasshi.

[8]  B. Plikaytis,et al.  Large-scale use of polymerase chain reaction for detection of Mycobacterium tuberculosis in a routine mycobacteriology laboratory , 1993, Journal of clinical microbiology.

[9]  B. Ross,et al.  Characterization of Mycobacterium tuberculosis strains from Vietnamese patients by Southern blot hybridization , 1993, Journal of clinical microbiology.

[10]  C. Chan,et al.  Diagnosis of tuberculous pleural effusion by the detection of tuberculostearic acid in pleural aspirates. , 1991, Chest.

[11]  K. Ruxrungtham,et al.  Interferon gamma for diagnosing tuberculous pleural effusions , 1999, Thorax.

[12]  D. Persing,et al.  Clinical Evaluation of the Gen-Probe Amplified Direct Test for Detection of Mycobacterium tuberculosisComplex Organisms in Cerebrospinal Fluid , 1998, Journal of Clinical Microbiology.

[13]  M. Gaga,et al.  Tumour necrosis factor, interleukin-1 and adenosine deaminase in tuberculous pleural effusion. , 1996, Respiratory medicine.

[14]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[15]  Youngchul Kim,et al.  Combining ADA, Protein and IFN- γ Best Allows Discrimination Between Tuberculous and Malignant Pleural Effusion , 1997, The Korean journal of internal medicine.

[16]  K. M. Mathews,et al.  Epidemiology of extrapulmonary tuberculosis. A comparative analysis with pre-AIDS era. , 1991, Chest.

[17]  G. Maartens,et al.  A comparative study of the polymerase chain reaction and conventional procedures for the diagnosis of tuberculous pleural effusion. , 1992, Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[18]  A. Kolk,et al.  Detection of Mycobacterium tuberculosis in clinical samples by using polymerase chain reaction and a nonradioactive detection system , 1992, Journal of clinical microbiology.

[19]  G. Pfyffer,et al.  Diagnostic performance of amplified Mycobacterium tuberculosis direct test with cerebrospinal fluid, other nonrespiratory, and respiratory specimens , 1996, Journal of clinical microbiology.

[20]  E. Palenque,et al.  Polymerase chain reaction for the diagnosis of pleural tuberculosis in immunocompromised and immunocompetent patients. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  J. García-de-Lomas,et al.  Rapid diagnosis of pleural tuberculosis by polymerase chain reaction. , 1995, American journal of respiratory and critical care medicine.

[22]  N. Hara,et al.  Evaluation of nested polymerase chain reaction for detecting mycobacterial DNA in pleural fluid. , 1995, Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases.

[23]  R. Báez-Saldaña,et al.  Diagnostic methods of primary tuberculous pleural effusion in a region with high prevalence of tuberculosis. A study in Mexican population. , 1997, Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion.

[24]  L. Valdés,et al.  Diagnosis of tuberculous pleurisy using the biologic parameters adenosine deaminase, lysozyme, and interferon gamma. , 1993, Chest.

[25]  A. Cukier,et al.  The relationship between pleural fluid findings and the development of pleural thickening in patients with pleural tuberculosis. , 1991, Chest.

[26]  I. Ocaña,et al.  Adenosine deaminase activity in the diagnosis of lymphocytic pleural effusions of tuberculous, neoplastic and lymphomatous origin. , 1986, Tubercle.

[27]  L. Valdés,et al.  Adenosine deaminase (ADA) isoenzyme analysis in pleural effusions: diagnostic role, and relevance to the origin of increased ADA in tuberculous pleurisy. , 1996, The European respiratory journal.

[28]  Á. Ruibal,et al.  High level of interferon gamma in tuberculous pleural effusion. , 1988, Chest.

[29]  J. Hartley,et al.  Use of uracil DNA glycosylase to control carry-over contamination in polymerase chain reactions. , 1990, Gene.

[30]  D van Soolingen,et al.  Comparison of various repetitive DNA elements as genetic markers for strain differentiation and epidemiology of Mycobacterium tuberculosis , 1993, Journal of clinical microbiology.

[31]  Y. Aoki,et al.  A comparison study of IFN-γ, ADA, and CA125 as the diagnostic parameters in tuberculous pleuritis , 1994 .

[32]  J. Echave,et al.  Rapid automated determination of adenosine deaminase and lysozyme for differentiating tuberculous and nontuberculous pleural effusions. , 1996, Clinical chemistry.

[33]  A H Kolk,et al.  Clinical utility of the polymerase chain reaction in the diagnosis of extrapulmonary tuberculosis. , 1998, The European respiratory journal.

[34]  H. Satoh,et al.  [Clinical significance of cytokine measurement in pleural effusion]. , 1997, Kekkaku : [Tuberculosis].

[35]  F. Maritz,et al.  Use of adenosine deaminase as a diagnostic tool for tuberculous pleurisy. , 1995, Thorax.