Interferon-gamma assay in combination with tuberculin skin test are insufficient for the diagnosis of culture-negative pulmonary tuberculosis

Marcin Wlodarczyk; Wieslawa Rudnicka; Beata Janiszewska-Drobinska; Grzegorz Kielnierowski; Magdalena Kowalewicz-Kulbat; Marek Fol; Magdalena Druszczynska

doi:10.1371/journal.pone.0107208

Interferon-gamma assay in combination with tuberculin skin test are insufficient for the diagnosis of culture-negative pulmonary tuberculosis

PLoS One. 2014 Sep 15;9(9):e107208. doi: 10.1371/journal.pone.0107208. eCollection 2014.

Authors

Marcin Wlodarczyk¹, Wieslawa Rudnicka¹, Beata Janiszewska-Drobinska², Grzegorz Kielnierowski², Magdalena Kowalewicz-Kulbat¹, Marek Fol¹, Magdalena Druszczynska¹

Affiliations

¹ Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
² Regional Specialised Hospital of Tuberculosis, Lung Diseases and Rehabilitation, Tuszyn, Poland.

Abstract

Objective: Early diagnosis of infectious cases and treatment of tuberculosis (TB) are important strategies for reducing the incidence of this disease. Unfortunately, traditional TB diagnostic methods are time-consuming and often unreliable. This study compared the accuracy and reliability of the tuberculin skin test (TST) and interferon (IFN)-γ-based assay (IGRA) for the diagnosis of active pulmonary TB Polish cases that could or could not be confirmed by M. tuberculosis (M.tb) culture.

Methods: In total, 126 adult patients with clinically active TB or non-mycobacterial, community-acquired lung diseases (NMLD) hospitalised at the Regional Specialised Hospital of Tuberculosis, Lung Diseases and Rehabilitation in Tuszyn, Poland were enrolled in the present study. Sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV), and analytic accuracy (Acc) of TST and IGRA testing for the diagnosis of culture-positive and culture-negative TB patients were calculated. The quantities of IFN-γ produced in the response to M.tb specific antigens (TB Ag - Nil) in the cultures of blood from patients with active TB and NMLD patients were also analysed.

Results: The IGRA sensitivity in culture-positive and culture-negative TB patients was similar, measuring 65.1% and 55.6%, respectively. The sensitivity of TST did not differ from the parameters designated for IGRA, measuring 55.8% in culture-positive and 64.9% in culture-negative TB. The sensitivity of TST and IGRA was age-dependent and decreased significantly with the age of the patients. No differences in the frequency or intensity of M.tb-stimulated IFN-γ production, as assessed by IGRA testing between culture-positive and culture-negative TB were noticed. Significantly lower concentrations of IFN-γ were observed in patients with advanced TB forms compared with those with mild or moderate TB pathologies.

Conclusions: Our results do not show that a combination of IGRA and TST might be a step forward in the diagnosis of culture-negative TB cases. However, M. tuberculosis-stimulated IFN-γ levels might help to assess the extent of pulmonary TB lesions.

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Community-Acquired Infections / diagnosis
Community-Acquired Infections / immunology
Female
Humans
Interferon-gamma / blood*
Male
Middle Aged
Tuberculin Test*
Tuberculosis / diagnosis*
Tuberculosis / immunology

Substances

Interferon-gamma

Grants and funding

This work was supported by a grant from the Polish Ministry of Science and Higher Education (N N402 098539) and co-financed by the European Union through the European Social Fund under the Human Resources Operational Programme, Priority VIII, Sub-action 8.2.1. from the project “PhD students – Regional Investment in Young Scientists – Acronym D-RIM.” The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.