title: A toolbox for tuberculosis (TB) diagnosis: an Indian multi-centric study (2006-2008); evaluation of serological assays based on PGL-Tb1 and ESAT-6/CFP10 antigens for TB diagnosis.
abstract: BACKGROUND
  The aim of this multi-centric prospective study in India was to assess the accuracy of a serological test as an additional tool for diagnosing active tuberculosis (ATB). In particular, an assay based on ELISA using a phenolic glycolipid (PGL-Tb1) or a fusion protein (ESAT-6/CFP10) was compared to the tuberculin skin test (TST) and the microbiological results according to HIV status.
  
  
  METHODS
  Individuals with and without ATB and HIV infection were enrolled. Serology and TST results were analyzed per se and in combination with the microbiological data.
  
  
  RESULTS
  Among the 778 ATB patients, 102 were HIV-infected, 316 HIV-uninfected and 360 had an HIV-unknown status. Of the 945 non-ATB subjects, 559 were at low risk (community adults) and 386 at high risk of M. tuberculosis exposure. Among those with ATB, the sensitivity of ELISA-PGL-Tb1 for ATB was higher than that of ELISA-ESAT-6/CFP10, both in HIV-infected (72.3% versus 63.7%, p = 0.29) and HIV-uninfected/HIV-unknown groups (40.5% versus 28.6%; p<0.0001), whereas the specificity was around 91% for both tests. Sensitivity for ATB increased when the results of the two ELISA were combined, reaching 75.5% in the HIV-infected and 50.9% in the group of HIV-uninfected/HIV-unknown ATB, with a significant decrease of the global specificity (83.9%). Analyzing the ELISA results with the microbiological results, we observed that the sensitivity of both serology tests was independent of the ATB patients' smear microscopy (SM) status and grade. Combining the results of SM with both ELISA, the detection of ATB patients significantly increased (p<0.0001), particularly in those with extrapulmonary TB (up to 45.1%) or HIV infection (up to 83.3%). No significant association was observed between TST and serology results.
  
  
  CONCLUSIONS
  In this prospective multi-centric study, the combination of two rapid tests, such as SM and serology, might be useful in detecting ATB, especially in HIV-infected patients.
authors.affiliation: Service de Microbiologie, Hôpital Saint Louis, Paris, France.
authors.forename: Philippe H
authors.initials: PH
authors.lastname: Lagrange
authors.affiliation: BioMérieux, Marcy-l'Etoile, France and New Delhi, India.
authors.forename: Satheesh K
authors.initials: SK
authors.lastname: Thangaraj
authors.affiliation: SN Medical College, Agra, India.
authors.forename: Rajeshwar
authors.initials: R
authors.lastname: Dayal
authors.affiliation: Sir J.J. Group of Govt Hosp. & Grant Medical College, Mumbai, India.
authors.forename: Alaka
authors.initials: A
authors.lastname: Deshpande
authors.affiliation: Indian Council of Medical Research, New Delhi, India.
authors.forename: Nirmal K
authors.initials: NK
authors.lastname: Ganguly
authors.affiliation: Department of Epidemiology and Preclinical Research, L. Spallanzani National Institute for Infectious Diseases, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.affiliation: National JALMA Institute of Leprosy & Other Mycrobacterial Diseases, Agra, India.
authors.forename: Beenu
authors.initials: B
authors.lastname: Joshi
authors.affiliation: National JALMA Institute of Leprosy & Other Mycrobacterial Diseases, Agra, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Katoch
authors.affiliation: National JALMA Institute of Leprosy & Other Mycrobacterial Diseases, Agra, India.
authors.forename: Vishwa M
authors.initials: VM
authors.lastname: Katoch
authors.affiliation: All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: Vemu
authors.initials: V
authors.lastname: Lakshmi
authors.affiliation: BioMérieux, Marcy-l'Etoile, France and New Delhi, India.
authors.forename: Marc
authors.initials: M
authors.lastname: Leportier
authors.affiliation: Fondation Mérieux, Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Longuet
authors.affiliation: Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: Subbalaxmi V S
authors.initials: SV
authors.lastname: Malladi
authors.affiliation: Indian Council of Medical Research, New Delhi, India.
authors.forename: Deepali
authors.initials: D
authors.lastname: Mukerjee
authors.affiliation: Safdarjung Hospital, New Delhi, India.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Nair
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Center), Chetput, Chennai, India.
authors.forename: Alamelu
authors.initials: A
authors.lastname: Raja
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Center), Chetput, Chennai, India.
authors.forename: Balambal
authors.initials: B
authors.lastname: Raman
authors.affiliation: Microbiology Section, P D Hinduja Hospital & Medical Research Centre, Veer Savarkar Marg Mahim, Mumbai, India.
authors.forename: Camilla
authors.initials: C
authors.lastname: Rodrigues
authors.affiliation: Safdarjung Hospital, New Delhi, India.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Sharma
authors.affiliation: SN Medical College, Agra, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.affiliation: All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Sarman
authors.initials: S
authors.lastname: Singh
authors.affiliation: Microbiology Section, P D Hinduja Hospital & Medical Research Centre, Veer Savarkar Marg Mahim, Mumbai, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Sodha
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Center), Chetput, Chennai, India.
authors.forename: Basirudeen Syed Ahamed
authors.initials: BS
authors.lastname: Kabeer
authors.affiliation: Fondation Mérieux, Lyon, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Vernet
authors.affiliation: Department of Epidemiology and Preclinical Research, L. Spallanzani National Institute for Infectious Diseases, Rome, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000032:analysis / Q000276:immunology; D058491:Bacterial Load; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007194:India; D008297:Male; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000379:methods; D014374:Tuberculin Test / Q000379:methods; D014376:Tuberculosis / Q000175:diagnosis*
chemical_list: D000942:Antigens, Bacterial