Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous pericarditis compared to adenosine deaminase and unstimulated interferon-γ in a high burden setting: a prospective study.

BACKGROUND: Tuberculous pericarditis (TBP) is associated with high morbidity and mortality, and is an important treatable cause of heart failure in developing countries. Tuberculous aetiology of pericarditis is difficult to diagnose promptly. The utility of the new quantitative PCR test (Xpert MTB/RIF) for the diagnosis of TBP is unknown. This study sought to evaluate the diagnostic accuracy of the Xpert MTB/RIF test compared to pericardial adenosine deaminase (ADA) and unstimulated interferon-gamma (uIFNγ) in suspected TBP. METHODS: From October 2009 through September 2012, 151 consecutive patients with suspected TBP were enrolled at a single centre in Cape Town, South Africa. Mycobacterium tuberculosis culture and/or pericardial histology served as the reference standard for definite TBP. Receiver-operating-characteristic curve analysis was used for selection of ADA and uIFNγ cut-points. RESULTS: Of the participants, 49% (74/151) were classified as definite TBP, 33% (50/151) as probable TBP and 18% (27/151) as non TBP. A total of 105 (74%) participants were human immunodeficiency virus (HIV) positive. Xpert-MTB/RIF had a sensitivity and specificity (95% confidence interval (CI)) of 63.8% (52.4% to 75.1%) and 100% (85.6% to 100%), respectively. Concentration of pericardial fluid by centrifugation and using standard sample processing did not improve Xpert MTB/RIF accuracy. ADA (≥35 IU/L) and uIFNγ (≥44 pg/ml) both had a sensitivity of 95.7% (88.1% to 98.5%) and a negative likelihood ratio of 0.05 (0.02 to 0.10). However, the specificity and positive likelihood ratio of uIFNγ was higher than ADA (96.3% (81.7% to 99.3%) and 25.8 (3.6 to 183.4) versus 84% (65.4% to 93.6%) and 6.0 (3.7 to 9.8); P = 0.03) at an estimated background prevalence of TB of 30%. The sensitivity and negative predictive value of both uIFNγ and ADA were higher than Xpert-MT/RIF (P < 0.001). CONCLUSIONS: uIFNγ offers superior accuracy for the diagnosis of microbiologically confirmed TBP compared to the ADA assay and the Xpert MTB/RIF test.

Adenosine deaminase in the diagnosis of tuberculous pericardial effusion.

Not long ago, primary tuberculosis was considered a rare disease; now with an increasing incidence worldwide, physicians should relearn many of its basic aspects and manifestations. Pericarditis is a rare finding seen with tuberculosis, but its prognosis is excellent with treatment, so early diagnosis is crucial. Pathogenesis is particularly important, and it must be taken in consideration when interpreting diagnostic tools. Herein we report on a healthy 32-year-old woman who presents with a 1-month history of febrile illness, malaise, and weakness; more recently, she also had resting dyspnea, which was progressively worsening. A positive PPD and an abnormal chest radiograph prompted hospitalization, where she was found to have pulsus paradoxus of 20 mm Hg. The echocardiogram showed diastolic right chamber collapse along with respiratory variation of the mitral inflow, consistent with pericardial tamponade. A pericardiocentesis was performed with resolution of her resting dyspnea; more than 1000 mL of serous fluid drained from the pericardial space over the following 24 hours. Although sputum and pericardial fluid cultures and smear for AFB and other organisms were negative, as well as a negative pericardial fluid PCR for Mycobacterium tuberculosis DNA; an elevated (44.4 U/L [normal, 0 to 18]) adenosine deaminase level in the pericardial fluid was consistent with the probable diagnosis of tuberculous pericardial effusion. The patient was treated with resolution of the clinical syndrome and no recurrence of the effusion thereafter. Adenosine deaminase, an enzyme marker of cell-mediated immune response activity to M tuberculosis that includes activated T-lymphocytes and macrophages, appears in pericardial fluid. The diagnosis of probable tuberculous effusion can be made without demonstration of mycobacterium.

The usefulness of adenosine deaminase in the diagnosis of tuberculous pericarditis.

The objective of this study was to evaluate the adenosine deaminase (ADA) activity usefulness in the diagnosis of tuberculous pericarditis (TP), comparing its value with pericardial effusions (PE) caused by other pericardial diseases. A retrospective case-control study was conducted with nine cases of TP and 39 other than TP diseases (12 neoplastic, 11 septic and 16 unknown origin). Every patient included in this study had PE samples submitted to ADA activity measures and microbiological analysis, and then had pericardial tissue samples submitted to microbiological and histopathological examination. Considering the value of 40 U/L as the cut-off for the diagnosis of TP, the specificity and sensitivity were respectively of 72% and 89%. The specificity of ADA activity for the TP was best applied in the differential diagnosis from PE of unknown origin. The present study demonstrates the clinical value of the measurement of ADA activity in PE in the diagnosis of TP.

The usefulness of adenosine deaminase in the diagnosis of tuberculous pericarditis

The objective of this study was to evaluate the adenosine deaminase (ADA) activity usefulness in the diagnosis of tuberculous pericarditis (TP), comparing its value with pericardial effusions (PE) caused by other pericardial diseases. A retrospective case-control study was conducted with nine cases of TP and 39 other than TP diseases (12 neoplastic, 11 septic and 16 unknown origin). Every patient included in this study had PE samples submitted to ADA activity measures and microbiological analysis, and then had pericardial tissue samples submitted to microbiological and histopathological examination. Considering the value of 40 U/L as the cut-off for the diagnosis of TP, the specificity and sensitivity were respectively of 72 percent and 89 percent. The specificity of ADA activity for the TP was best applied in the differential diagnosis from PE of unknown origin. The present study demonstrates the clinical value of the measurement of ADA activity in PE in the diagnosis of TP.

O objetivo deste estudo foi avaliar a atividade da adenosina deaminase (ADA) como auxiliar no diagnóstico da tuberculose pericárdica (TP), comparando o seu valor no derrame pericárdico com outras doenças pericárdicas. Um estudo retrospectivo tipo caso-controle foi conduzido com nove casos de TP e 39 pacientes com outras doenças pericárdicas (12 neoplasias, 11 pericardites bacterianas e 16 pericardites de etiologia indeterminada). Cada paciente incluído no estudo teve sua amostra de tecido pericárdico encaminhada para estudo microbiológico e histopatológico. Considerando o valor de 40 U/L como corte para o diagnóstico de TP, a especificidade e sensibilidade foram respectivamente 72 e 89 por cento. A especificidade da atividade de ADA para a TP foi melhor aplicada no diagnóstico diferencial entre derrame pericárdico de origem indeterminada. O presente estudo demonstrou o valor clínico da mensuração da atividade de ADA no diagnóstico de TP.

Adenosine deaminase and tuberculous pericarditis--a systematic review with meta-analysis.

BACKGROUND: Adenosine deaminase (ADA) activity in pericardial fluid is a valuable aid in the diagnosis of tuberculous pericarditis (TP), but there is no systematic review performed to evaluate the benefits of ADA activity as an adjunctive test for TP diagnosis. The objective of this systematic review was to evaluate the utility of ADA activity as a diagnostic marker of TP on patients presenting with pericardial effusion. METHODS: MEDLINE, LILACS and Cochrane Library databases (1980-2005) searches to identify articles related to adenosine deaminase activity on TP diagnosis. Articles with patients with at least one TP diagnostic criteria were included. The controls were patients with other pericardial diseases with moderate or large pericardial effusion. To calculate the sensitivity, specificity, as well as positive and negative likelihood ratios we extracted the total number of confirmed TP cases over all patients with pericardial effusion as well as the number of cases with ADA activity values of 40 U/L and over. RESULTS: Thirty one studies met our initial inclusion criteria and five articles were selected. The heterogeneity limited the specificity analysis (p=0.004). The method yielded a sensitivity and specificity of 88% and 83%, respectively. The SROC curve presented an area with a tendency towards 1 (value of 0.9539) and corroborates the diagnostic value of ADA activity. CONCLUSIONS: The present study confirms the clinical value of ADA activity as adjunctive diagnostic marker of TP among other causes of pericardial effusion.

Adenosine deaminase activity--more than a diagnostic tool in tuberculous pericarditis.

AIM: To improve the understanding of factors that influence adenosine deaminase ( ADA) activity in large pericardial effusions. METHODS: A prospective study was carried out at Tygerberg Academic Hospital, South Africa. Patients underwent echocardiographically guided pericardiocentesis. ADA activity, as well as biochemistry, haematology, cytology, and in some cases, histology, were determined. Human immunodeficiency virus (HIV) status was assessed in all patients. RESULTS: Two hundred and thirty-three patients presented to Tygerberg Hospital with large pericardial effusions requiring pericardiocentesis. Tuberculous pericarditis accounted for 162 effusions (69.5%). An ADA cut-off level of 40 U/l resulted in a test sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic efficiency of 84.0%, 80.0%, 91.0%, 66.0% and 83.0%, respectively. Pericardial exudates with an ADA activity > or = 40 U/l were associated with increased total leukocyte and neutrophil counts. Patients with tuberculous pericarditis and ADA > or = 40 U/l also had increased lymphocyte counts. Pericardial ADA activity < 30 U/l was associated with severe depletion of CD4 cell counts in HIV-positive patients. ADA levels were higher in cases with histological evidence of granulomatous inflammation than in cases with serofibrinous pericarditis. CONCLUSIONS: An ADA cut-off level of 40 U/l results in best diagnostic test results. ADA production appears to be influenced by factors associated with the antituberculous immune response.

The use of adenosine deaminase and interferon-gamma as diagnostic tools for tuberculous pericarditis.

BACKGROUND: Traditional diagnostic tests for pericardial tuberculosis (TB) are insensitive and often require long culture periods, and this has led to more emphasis being placed on biochemical tests such as the pericardial adenosine deaminase (ADA) test. However, controversy exists as to its diagnostic utility. In addition, the use of interferon (IFN)-gamma, which is a reliable indicator of pleural and peritoneal TB, has not been explored in pericardial effusions. We investigated ADA and IFN-gamma levels in pericardial effusions of different etiologies. METHODS AND RESULTS: A prospective study was carried out from February 1995 to February 1998 at Tygerberg Hospital (South Africa), with pericardial taps being performed under echocardiographic guidance. During this period, 110 consecutive patients presenting with large pericardial effusions were included in the study. Diagnoses were made according to predetermined criteria, and they included TB (n = 64), malignancy (n = 12), nontuberculous infections (n = 5), other effusions (n = 19), and effusions of uncertain origin (n = 10). The median ADA level in the tuberculous group was 71.7 U/L (range, 10.3 to 303.6 U/L), which was significantly higher than that in any other group (p < 0.05). With a cutoff level for ADA activity of 30 U/L, sensitivity was 94%, specificity was 68%, and positive predictive value was 80%. IFN-gamma levels were determined in 30 subjects. The median IFN-gamma concentration in the tuberculous group was > 1,000 pg/L, which was significantly higher than in any other diagnostic group (p < 0.0005). A cutoff value of 200 pg/L for IFN-gamma resulted in a sensitivity and specificity of 100% for the diagnosis of pericardial TB. CONCLUSION: Pericardial fluid levels of ADA and IFN-gamma are useful in the diagnosis of tuberculous pericarditis.

Diagnostic value of adenosine deaminase activity in pericardial fluids.

BACKGROUND: The activity of adenosine deaminase (ADA) was determined in serum and pericardial fluid of 70 patients (ages 21 to 71 years) with pericardial effusions of various etiologies and in 15 control subjects. METHODS: The patients were subdivided into five groups on the basis of definite diagnosis: 1) 24 patients with tuberculosis; 2) 22 with malignancies; 3) 12 with uremic pericarditis; 4) 12 with purulent pericarditis; 5) 15 control individuals without pericardial disease. The activity of ADA was determined at the same time in serum and cell-free pericardial fluid according to the method of Karker with minor modification. RESULTS: Mean (+/-SD) ADA activity in pericardial fluid was 66.92+/-4.12 IU/L in group 1; 27.50+/-6.02 in group 2; 28.65+/-4.73 in group 3; 53.05+/-11.14 in group 4; and 5.67+/-1.99 in group 5. Comparing the level achieved in group 1 with all others, the difference is significant at the p<0.001 level. When the cut-off value of 50 IU/L is used the sensitivity of the test for diagnosis of tuberculous effusion is 1, and the specificity is 0.83. Statistical analysis showed that there was no correlation between serum ADA activity and ADA activity in pericardial fluid. CONCLUSIONS: We recommend that determinations of ADA activity in pathologic pericardial fluids seem to be of great value in the early diagnosis of tuberculous pericardial effusions. Levels above 50 IU/L in effusions indicate probable tuberculosis.

[The value of measuring adenosine deaminase activity in pericardial effusion fluid for diagnosing the etiology of pericardial effusion]. / Wartosc oznaczania aktywnosci deaminazy adenozyny w plynie osierdziowym w diagnostyce etiologii wysieku osierdziowego.

The diagnosis of tuberculous pericarditis is difficult. The cultures of the pericardial fluid for M.tuberculosis are often negative. The determination of ADA activity in pleural fluid in TB patients /PTS/ is very useful. It seemed reasonable to measure ADA activity in pericardial effusion. ADA activity in pericardial fluid of 40PTS/19 women and 21 men/with large pericardial effusion of different etiologies who were treated in our institute in years 1988-1995 was investigated. The median age was 44 years. In each case the pericardiocentesis was performed. PTS were grouped as follows: group I-4 PTS with strongly suspected TB pericarditis, group II-32 PTS with malignancy and group III-4 PTS with miscellaneous diseases. In group I the mean ADA activity was 24U/I(3-60), in group II 18U/I (3-60) and in group III 18U/I (0-37) (with a cutoff value for ADA activity of 40U/I). It was definitive bacteriologic diagnosis of TB pericarditis in PTS of group I. Our observation does not confirm the earlier data about the high ADA activity in clinically suspected TB pericarditis without bacteriologic diagnosis. The value of ADA determination in pericardial fluid is its high specificity (97%) in excluding of TB etiology of pericardial effusion.

The diagnostic and prognostic value of adenosine deaminase in tuberculous pericarditis.

Because of the difficulty in isolating the causative organism, pericardial tuberculosis is rarely diagnosed. Adenosine deaminase activity measured in the pericardial fluid of 108 patients was initially of undetermined origin. Subsequently, we classified five sources: (1) tuberculosis (20 cases); (2) idiopathy (82 cases); (3) neoplasia (three cases); (4) purulent bacterial infection (two cases); and (5) radiotherapy (one case). The highest mean adenosine deaminase value (126 +/- 16.68 U.l(-1) was found in group 1; other values were 29.4 +/- 8.9, 27 +/- 7.21, 29.5 +/- 13.4, 26 U.l(-1) in the idiopathy, neoplasia, purulent bacterial infection and radiotherapy groups, respectively. there was a statistically significant difference between group 1 and the other groups (P less than 0.001), indicating that the adenosine deaminase value has 100% sensitivity and 91% specificity. In addition, there was a positive correlation between high adenosine deaminase values and the development of constrictive pericarditis. In this study, two patients required pericardectomy. Therefore, the adenosine deaminase value is a significant prognostic indicator for the development of constrictive pericarditis in tuberculous pericarditis.

Tuberculous pericarditis: importance of adenosine deaminase activity in pericardial fluid.

We present a case of tuberculous pericarditis that was diagnosed early by a high titer of adenosine deaminase activity in the pericardial fluid and by a strongly positive tuberculin test. Within 2 weeks of initiation of treatment, pericardial effusion gradually decreased while clinical symptoms improved markedly. Culture from sputum, gastric juice, urine, and pericardial fluid were negative for tubercle bacillus. Measurement of adenosine deaminase activity in the pericardial fluid is a supplementary diagnostic test which is as important as for tuberculous pericarditis as it is for tuberculous pleuritis, because negative Ziehl Neelsen staining and culture for tubercle bacillus are common in tuberculous pericarditis.