Persistently elevated T cell interferon-γ responses after treatment for latent tuberculosis infection among health care workers in India: a preliminary report

<p>Abstract</p> <p>Background</p> <p>T cell-based interferon-γ (IFN-γ) release assays (IGRAs) are novel tests for latent tuberculosis infection (LTBI). It has been suggested that T cell responses may be correlated with bacterial burden and, therefore, IGRAs may have a r...

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Main Authors: Mendiratta Deepak K, Dogra Sandeep, Joshi Rajnish, Pai Madhukar, Narang Pratibha, Dheda Keertan, Kalantri Shriprakash
Format: Article
Language:English
Published: BMC 2006-05-01
Series:Journal of Occupational Medicine and Toxicology
Online Access:http://www.occup-med.com/content/1/1/7
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author Mendiratta Deepak K
Dogra Sandeep
Joshi Rajnish
Pai Madhukar
Narang Pratibha
Dheda Keertan
Kalantri Shriprakash
author_facet Mendiratta Deepak K
Dogra Sandeep
Joshi Rajnish
Pai Madhukar
Narang Pratibha
Dheda Keertan
Kalantri Shriprakash
author_sort Mendiratta Deepak K
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>T cell-based interferon-γ (IFN-γ) release assays (IGRAs) are novel tests for latent tuberculosis infection (LTBI). It has been suggested that T cell responses may be correlated with bacterial burden and, therefore, IGRAs may have a role in monitoring treatment response. We investigated IFN-γ responses to specific TB antigens among Indian health care workers (HCWs) before, and after LTBI preventive therapy.</p> <p>Methods</p> <p>In 2004, we established a cohort of HCWs who underwent tuberculin skin testing (TST) and a whole-blood IGRA (QuantiFERON-TB-Gold <it>In-Tube </it>[QFT-G], Cellestis Ltd, Victoria, Australia) at a rural hospital in India. HCWs positive by either test were offered 6 months of isoniazid (INH) preventive therapy. Among the HCWs who underwent therapy, we prospectively followed-up 10 nursing students who were positive by both tests at baseline. The QFT-G assay was repeated 4 and 10 months after INH treatment completion (i.e. approximately 12 months and 18 months after the initial testing). IFN-γ responses to ESAT-6, CFP-10 and TB7.7 peptides were measured using ELISA, and IFN-γ ≥0.35 IU/mL was used to define a positive QFT-G test result.</p> <p>Results</p> <p>All participants (N = 10) reported direct contact with smear-positive TB patients at baseline, during and after LTBI treatment. All participants except one started treatment with high baseline IFN-γ responses (median 10.0 IU/mL). The second QFT-G was positive in 9 of 10 participants, but IFN-γ responses had declined (median 5.0 IU/mL); however, this difference was not significant (<it>P </it>= 0.10). The third QFT-G assay continued to be positive in 9 of 10 participants, with persistently elevated IFN-γ responses (median 7.9 IU/mL; <it>P </it>= 0.32 for difference against baseline average).</p> <p>Conclusion</p> <p>In an environment with ongoing, intensive nosocomial exposure, HCWs had strong IFN-γ responses at baseline, and continued to have persistently elevated responses, despite LTBI treatment. It is plausible that persistence of infection and/or re-infection might account for this phenomenon. Our preliminary findings need confirmation in larger studies in high transmission settings. Specifically, research is needed to study T cell kinetics during LTBI treatment, and determine the effect of recurrent exposures on host cellular immune responses.</p>
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spelling doaj.art-e7e80db9b3ed4e90aaeda2e4a7226bf22022-12-22T03:18:41ZengBMCJournal of Occupational Medicine and Toxicology1745-66732006-05-0111710.1186/1745-6673-1-7Persistently elevated T cell interferon-γ responses after treatment for latent tuberculosis infection among health care workers in India: a preliminary reportMendiratta Deepak KDogra SandeepJoshi RajnishPai MadhukarNarang PratibhaDheda KeertanKalantri Shriprakash<p>Abstract</p> <p>Background</p> <p>T cell-based interferon-γ (IFN-γ) release assays (IGRAs) are novel tests for latent tuberculosis infection (LTBI). It has been suggested that T cell responses may be correlated with bacterial burden and, therefore, IGRAs may have a role in monitoring treatment response. We investigated IFN-γ responses to specific TB antigens among Indian health care workers (HCWs) before, and after LTBI preventive therapy.</p> <p>Methods</p> <p>In 2004, we established a cohort of HCWs who underwent tuberculin skin testing (TST) and a whole-blood IGRA (QuantiFERON-TB-Gold <it>In-Tube </it>[QFT-G], Cellestis Ltd, Victoria, Australia) at a rural hospital in India. HCWs positive by either test were offered 6 months of isoniazid (INH) preventive therapy. Among the HCWs who underwent therapy, we prospectively followed-up 10 nursing students who were positive by both tests at baseline. The QFT-G assay was repeated 4 and 10 months after INH treatment completion (i.e. approximately 12 months and 18 months after the initial testing). IFN-γ responses to ESAT-6, CFP-10 and TB7.7 peptides were measured using ELISA, and IFN-γ ≥0.35 IU/mL was used to define a positive QFT-G test result.</p> <p>Results</p> <p>All participants (N = 10) reported direct contact with smear-positive TB patients at baseline, during and after LTBI treatment. All participants except one started treatment with high baseline IFN-γ responses (median 10.0 IU/mL). The second QFT-G was positive in 9 of 10 participants, but IFN-γ responses had declined (median 5.0 IU/mL); however, this difference was not significant (<it>P </it>= 0.10). The third QFT-G assay continued to be positive in 9 of 10 participants, with persistently elevated IFN-γ responses (median 7.9 IU/mL; <it>P </it>= 0.32 for difference against baseline average).</p> <p>Conclusion</p> <p>In an environment with ongoing, intensive nosocomial exposure, HCWs had strong IFN-γ responses at baseline, and continued to have persistently elevated responses, despite LTBI treatment. It is plausible that persistence of infection and/or re-infection might account for this phenomenon. Our preliminary findings need confirmation in larger studies in high transmission settings. Specifically, research is needed to study T cell kinetics during LTBI treatment, and determine the effect of recurrent exposures on host cellular immune responses.</p>http://www.occup-med.com/content/1/1/7
spellingShingle Mendiratta Deepak K
Dogra Sandeep
Joshi Rajnish
Pai Madhukar
Narang Pratibha
Dheda Keertan
Kalantri Shriprakash
Persistently elevated T cell interferon-γ responses after treatment for latent tuberculosis infection among health care workers in India: a preliminary report
Journal of Occupational Medicine and Toxicology
title Persistently elevated T cell interferon-γ responses after treatment for latent tuberculosis infection among health care workers in India: a preliminary report
title_full Persistently elevated T cell interferon-γ responses after treatment for latent tuberculosis infection among health care workers in India: a preliminary report
title_fullStr Persistently elevated T cell interferon-γ responses after treatment for latent tuberculosis infection among health care workers in India: a preliminary report
title_full_unstemmed Persistently elevated T cell interferon-γ responses after treatment for latent tuberculosis infection among health care workers in India: a preliminary report
title_short Persistently elevated T cell interferon-γ responses after treatment for latent tuberculosis infection among health care workers in India: a preliminary report
title_sort persistently elevated t cell interferon γ responses after treatment for latent tuberculosis infection among health care workers in india a preliminary report
url http://www.occup-med.com/content/1/1/7
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