Abstract
BackgroundDiagnosis of tuberculous (TB) pleuritis is difficult and better diagnostic tools are needed. New blood based interferon-gamma (IFN-γ) tests are promising, but sensitivity could be low in HIV positive patients. The IFN-γ tests have not yet been validated for use in pleural fluid, a compartment with higher level of immune activation than in blood.MethodsThe QuantiFERON TB®-Gold (QFT-TB) test was analysed in blood and pleural fluid from 34 patients presenting with clinically suspected pleural TB. Clinical data, HIV status and CD4 cell counts were recorded. Adenosine deaminase activity (ADA) analysis and TB culture were performed on pleural fluid.ResultsThe patients were categorised as 'confirmed TB' (n = 12), 'probable TB' (n = 16) and 'non-TB' pleuritis (n = 6) based on TB culture results and clinical and biochemical criteria. The majority of the TB patients were HIV infected (82%). The QFT-TB in pleural fluid was positive in 27% and 56% of the 'confirmed TB' and 'probable TB' cases, respectively, whereas the corresponding sensitivities in blood were 58% and 83%. Indeterminate results in blood (25%) were caused by low phytohemagglutinin (PHA = positive control) IFN-γ responses, significantly lower in the TB patients as compared to the 'non-TB' cases (p = 0.02). Blood PHA responses correlated with CD4 cell count (r = 0.600, p = 0.028). In contrast, in pleural fluid indeterminate results (52%) were caused by high Nil (negative control) IFN-γ responses in both TB groups. Still, the Nil IFN-γ responses were lower than the TB antigen responses (p < 0.01), offering a conclusive test for half of the patients. We did not find any correlation between blood CD4 cell count and IFN-γ responses in pleural fluid.ConclusionThe QFT-TB test in blood could contribute to the diagnosis of TB pleuritis in the HIV positive population. Still, the number of inconclusive results is too high to recommend the commercial QFT-TB test for routine use in pleural fluid in a TB/HIV endemic resource-limited setting.
Highlights
Diagnosis of tuberculous (TB) pleuritis is difficult and better diagnostic tools are needed
Study participants Patients presenting with pleural effusion and clinical symptoms of TB pleuritis admitted to the Dr George Mukhari Hospital (DGM), Ga-Rankuwa, Pretoria, South Africa in the period 2004–2005 were recruited into the study
The Adenosine deaminase activity (ADA) levels in pleural fluid were similar in the human immunodefiency virus (HIV) positive and HIV negative patients, and we found no significant correlation between ADA values and CD4 cell counts
Summary
Diagnosis of tuberculous (TB) pleuritis is difficult and better diagnostic tools are needed. New blood based interferon-gamma (IFN-γ) tests are promising, but sensitivity could be low in HIV positive patients. The IFN-γ tests have not yet been validated for use in pleural fluid, a compartment with higher level of immune activation than in blood. TB pleuritis occurs in about 30% of TB patients, the majority of cases in the HIV positive population [2]. The diagnosis of TB pleuritis is generally difficult and the acid fast bacilli [AFB] microscopy method rarely detects the tubercle bacilli, whereas culture is positive in about 40% of cases [3]. Adenosine deaminase activity (ADA) in pleural fluid is used as a marker of TB pleuritis and a meta-analysis conclude that it has variable performance, it is still a useful test [6]. A sensitivity as low as 17% in pleural fluid has been reported for the polymerase chain reaction (PCR) method [9]
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