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

Abstract

BackgroundTuberculous 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.MethodsFrom 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.ResultsOf 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).ConclusionsuIFNγ offers superior accuracy for the diagnosis of microbiologically confirmed TBP compared to the ADA assay and the Xpert MTB/RIF test.

2015 ESC Guidelines for the diagnosis and management of pericardial diseases

“…Rozpoznanie jest "prawdopodobne", jeżeli w regionie endemicznym u chorego z zapaleniem osierdzia o niewyjaśnionej etiologii potwierdzono zakażenie prątkami w materiale z innej części ciała, w wysięku z osierdzia stwierdzono limfocytozę i zwiększone stężenie interferonu gamma bez stymulacji (uIFNg), aktywność deaminazy adenozyny (ADA) lub lizozymu i/lub kliniczną odpowiedź na zastosowane leczenie przeciwgruźlicze [79]. Oznaczenie uIFNg wzmacnia rozpoznanie gruźlicy ustalone na podstawie badania mikrobiologicznego materiału z osierdzia w większym stopniu niż test ADA lub badanie Xpert MTB/RIF [142]. W tabeli 17 przedstawiono proponowany schemat postępowania diagnostycznego w przypadku podejrzenia gruźliczego zapalenia osierdzia.…”

IP-10 and MIG Are Compartmentalized at the Site of Disease during Pleural and Meningeal Tuberculosis and Are Decreased after Antituberculosis Treatment

“…A recent report indicated a sensitivity of 86.1% for the Xpert MTB/RIF test and 69.4% for nested PCR for detection of M. tuberculosis during routine clinical practice in a geographical area with intermediate TB incidence (5). Notably, the diagnostic value of the Xpert MTB/RIF test was limited when it was used for diagnosis of extrapulmonary TB (patients without sputum samples), such as tuberculous pericarditis, with a sensitivity that was inferior even to that of unstimulated gamma interferon (IFN-␥) (6).…”

Tuberculous pericarditis: Challenges and controversies in the modern era

“…It has been demonstrated to have a low sensitivity in the setting of pleural TB, 46% vs. 99% by culture, and more recently its potential value was evaluated in the setting of pericardial disease on pericardial fluid specimens. (21,22) It achieved a low sensitivity of 63,8% and was found to be inferior to both ADA and uIFN-γ in microbiologically confirmed TBP. (22) Its potential value in the evaluation of pericardial tissue specimens remains unknown.…”

“…(21,22) It achieved a low sensitivity of 63,8% and was found to be inferior to both ADA and uIFN-γ in microbiologically confirmed TBP. (22) Its potential value in the evaluation of pericardial tissue specimens remains unknown. An older PCR assay was evaluated in 20 patients, who underwent open surgical pericardial biopsy, on both fluid and tissue samples.…”