Highly Accurate Diagnosis of Pleural Tuberculosis by Immunological Analysis of the Pleural Effusion

Jayne S Sutherland,Danlani Garba,Martin O C Ota,Awa Mendy-Gomez,Martin Antonio,Augustin E Fombah,Readon C Ideh,John Townend,Francis S Mendy,Tumani Corrah,T Mark Doherty

doi:10.1371/journal.pone.0030324

Abstract

Pleural TB is notoriously difficult to diagnose due to its paucibacillary nature yet it is the most common cause of pleural effusions in TB endemic countries such as The Gambia. We identified both cellular and soluble biomarkers in the pleural fluid that allowed highly accurate diagnosis of pleural TB compared to peripheral blood markers. Multi-plex cytokine analysis on unstimulated pleural fluid showed that IP-10 resulted in a positive likelihood ratio (LR) of 9.6 versus 2.8 for IFN-γ; a combination of IP-10, IL-6 and IL-10 resulted in an AUC of 0.96 and positive LR of 10. A striking finding was the significantly higher proportion of PPD-specific IFN-γ+TNF-α+ cell population (PPD-IGTA) in the pleural fluid compared to peripheral blood of TB subjects. Presence of this pleural PPD-IGTA population resulted in 95% correct classification of pleural TB disease with a sensitivity of 95% and specificity of 100%. These data suggest that analysis of the site of infection provides superior diagnostic accuracy compared to peripheral blood for pleural TB, likely due to the sequestration of effector cells at this acute stage of disease.

Highlights

Tuberculosis (TB) still remains one of the top three deadly diseases in developing countries with 1.7 million deaths recorded in 2009 [1]
In this study we show that the immune profile in the pleural fluid is distinct from the peripheral blood in subjects with pleural TB illustrating the sequestration of effector cells to the site of infection at this acute stage of disease
We have determined both cellular and soluble biomarkers in the pleural fluid that can discriminate between pleural effusions caused by TB and those caused by other diseases such as pneumonia or malignancy

Summary

Introduction

Tuberculosis (TB) still remains one of the top three deadly diseases in developing countries with 1.7 million deaths recorded in 2009 [1]. Sputum smear (which is unreliable, in HIV-positive and extrapulmonary TB) and sputum culture (which is time-consuming and expensive) remain the ‘goldstandard’ techniques for diagnosis of TB. Host immune factors provide greater diagnostic accuracy, including levels of IFN-c and Adenosine Deaminase (ADA) [3], both of which have .95% specificity and sensitivity, appear to be unaffected by HIV co-infection and do not require any sample preparation [3–7]. These markers are less definitive in TB-endemic countries and have not been evaluated in a West African cohort

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