A Toolbox for Tuberculosis Diagnosis: An Indian Multicentric Study (2006-2008): Microbiological Results

Philippe Lagrange ,Kiran Katoch,Marc Leportier,Balambal Raman,Beenu Joshi,Guy Vernet,Camilla Rodrigues,Rajeshwar Dayal,Alka Despande,Amit Singh,Archana Sodha,Basirudeen Syed Ahamed Kabeer,Enrico Girardi,Satheesh K Thangaraj,Deepthi Nair,Manoj Kumar,Subbalaxmi V S Malladi,Delia Goletti,Christophe Longuet,Deepali Mukerjee,Alamelu Raja,Sarman Singh,Vishwa Mohan Katoch ,Prafull Sharma ,V Lakshmi ,Nirmal Kumar Ganguly

doi:10.1371/journal.pone.0043739

Abstract

BackgroundThe aim of this multicentric prospective study in India was to assess the value of several microbiological tools that contribute to the diagnosis of tuberculosis (TB) according to HIV status.MethodsStandard microbiological tools on individual specimens were analyzed.ResultsAmong the 807 patients with active TB, 131 were HIV-infected, 316 HIV-uninfected and 360 had HIV-unknown status. Among the 980 non-active TB subjects, 559 were at low risk and 421 were at high risk of M. tuberculosis (Mtb) exposure. Sensitivity of smear microscopy (SM) was significantly lower in HIV-infected (42.2%) than HIV-uninfected (75.9%) (p = 0.0001) and HIV-unknown pulmonary TB patients (61.4%) (p = 0.004). Specificity was 94.5% in non-TB patients and 100% in health care workers (HCW) and healthy family contacts. Automated liquid culture has significantly higher diagnostic performances than solid culture, measured by sensitivity (74.7% vs. 55.9%) (p = 0.0001) and shorter median time to detection (TTD) (12.0 vs. 34.0 days) (p = 0.0001). Specificity was 100% in HCW and cured-TB patients, but was lower in non-TB patients (89%) due to isolation of Mycobacteria other than tuberculosis (MOTT). TTD by both methods was related to AFB score. Contamination rate was low (1.4%). AccuProbe hybridization technique detected Mtb in almost all culture-positive specimens, but MOTT were found in 4.7% with a significantly higher frequency in HIV-infected (15%) than HIV-uninfected TB patients (0.5%) (p = 0.0007). Pre-test classification significantly increased the diagnostic value of all microbiological tests in pulmonary TB patients (p<0.0001) but to a lesser degree in extrapulmonary TB patients.ConclusionsConventional microbiological tools led to results similar to those already described in India special features for HIV-infected TB patients included lower detection by SM and culture. New microbiological assays, such as the automated liquid culture system, showed increased accuracy and speed of detection.

Highlights

Tuberculosis (TB) is a major global health problem
The remaining files correspond to 807 patients with active TB: 131 HIV-infected, 316 HIV-uninfected and 360 with unknown HIV-status
Among the 980 adults without active TB, we identified 6 groups according to their characteristics

Summary

Introduction

Tuberculosis (TB) is a major global health problem. In 2010, 8.8 million incident cases of TB and 1.1 million deaths were reported by the World Health Organization (WHO) [1]. In India 2.3 million new TB cases are estimated to have occurred in 2010, accounting for one-quarter of the world’s new TB cases [1] This makes India the country with the highest TB burden in the world. Regarding smearpositive TB, HIV infection was 1.4 times more likely to occur among smear-negative patients and 1.3 times more likely among extrapulmonary patients [3]. The aim of this multicentric prospective study in India was to assess the value of several microbiological tools that contribute to the diagnosis of tuberculosis (TB) according to HIV status

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Results

Discussion

Conclusion