Limits...
Tuberculin skin testing and treatment modulates interferon-gamma release assay results for latent tuberculosis in migrants.

O'Shea MK, Fletcher TE, Beeching NJ, Dedicoat M, Spence D, McShane H, Cunningham AF, Wilson D - PLoS ONE (2014)

Bottom Line: This resulted in an increase in IGRA concordance to substantial (64.3% agreement; κ = 0.73; 95% CI:0.58-0.88).Thus, in total on day 0 and day 7 after testing, 29 out of 166 participants (17.5%) provided a positive IGRA and of these 13 were TST negative.When the change in the levels of secreted IFN-γ was examined after chemoprophylaxis the median levels were found to have fallen dramatically by 77.3% from a pre-treatment median concentration of IFN-γ 2.73 IU/ml to a post-treatment median concentration IFN-γ 0.62 (p = 0.0002).

View Article: PubMed Central - PubMed

Affiliation: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; School of Immunity and Infection, MRC Centre for Immune Regulation, University of Birmingham Edgbaston, Birmingham, United Kingdom.

ABSTRACT

Background: Identifying latent tuberculosis infection (LTBI) in people migrating from TB endemic regions to low incidence countries is an important control measure. However, no prospective longitudinal comparisons between diagnostic tests used in such migrant populations are available.

Objectives: To compare commercial interferon (IFN)-gamma release assays (IGRAs) and the tuberculin skin test (TST) for diagnosing LTBI in a migrant population, and the influence of antecedent TST and LTBI treatment on IGRA performance.

Materials and methods: This cohort study, performed from February to September 2012, assessed longitudinal IGRA and TST responses in Nepalese military recruits recently arrived in the UK. Concomitant T-SPOT.TB, QFT-GIT and TST were performed on day 0, with IGRAs repeated 7 and 200 days later, following treatment for LTBI if necessary.

Results: 166 Nepalese recruits were prospectively assessed. At entry, 21 individuals were positive by T-SPOT.TB and 8 individuals by QFT-GIT. There was substantial agreement between TST and T-SPOT.TB positives at baseline (71.4% agreement; κ = 0.62; 95% CI:0.44-0.79), but only moderate concordance between positive IGRAs (38.1% agreement; κ = 0.46; 95% CI:0.25-0.67). When reassessed 7 days following TST, numbers of IGRA-positive individuals changed from 8 to 23 for QFT-GIT (p = 0.0074) and from 21 to 23 for T-SPOT.TB (p = 0.87). This resulted in an increase in IGRA concordance to substantial (64.3% agreement; κ = 0.73; 95% CI:0.58-0.88). Thus, in total on day 0 and day 7 after testing, 29 out of 166 participants (17.5%) provided a positive IGRA and of these 13 were TST negative. Two hundred days after the study commenced and three months after treatment for LTBI was completed by those who were given chemoprophylaxis, 23 and 21 participants were positive by T-SPOT.TB or QFT-GIT respectively. When individual responses were examined longitudinally within this population 35% of the day 7 QFT-GIT-positive, and 19% T-SPOT.TB-positive individuals, were negative by IGRA. When the change in the levels of secreted IFN-γ was examined after chemoprophylaxis the median levels were found to have fallen dramatically by 77.3% from a pre-treatment median concentration of IFN-γ 2.73 IU/ml to a post-treatment median concentration IFN-γ 0.62 (p = 0.0002).

Conclusions: This study suggests differences in the capacity of commercially available IGRAs to identify LTBI in the absence of antecedent TST and that IGRAs, in the time periods examined, may not be the optimal tests to determine the success of chemoprophylaxis for LTBI.

Show MeSH

Related in: MedlinePlus

IGRA responses before and after TST administration.(A) IFN-γ responses detected by QFT-GIT in individuals who became positive following TST; (B) SFC numbers in response to ESAT-6 and CFP-10 in individuals who became positive by T-SPOT.TB following TST; (C) SFC numbers in response to ESAT-6 and CFP-10 in individuals who became negative by T-SPOT.TB following TST. Uncertainty zone (grey shaded area); threshold for QFT-GIT positivity (dashed line); upper and lower thresholds for T-SPOT.TB conversion (solid lines). TST =  tuberculin skin test; QFT-GIT =  QuantiFERON Gold in-Tube; IFN-γ =  interferon-gamma; ESAT-6 =  early secretory antigenic target-6; CFP-10 =  culture filtrate protein-10; IU =  international units; SFC =  spot forming cells.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4016319&req=5

pone-0097366-g004: IGRA responses before and after TST administration.(A) IFN-γ responses detected by QFT-GIT in individuals who became positive following TST; (B) SFC numbers in response to ESAT-6 and CFP-10 in individuals who became positive by T-SPOT.TB following TST; (C) SFC numbers in response to ESAT-6 and CFP-10 in individuals who became negative by T-SPOT.TB following TST. Uncertainty zone (grey shaded area); threshold for QFT-GIT positivity (dashed line); upper and lower thresholds for T-SPOT.TB conversion (solid lines). TST =  tuberculin skin test; QFT-GIT =  QuantiFERON Gold in-Tube; IFN-γ =  interferon-gamma; ESAT-6 =  early secretory antigenic target-6; CFP-10 =  culture filtrate protein-10; IU =  international units; SFC =  spot forming cells.

Mentions: Since antecedent TST could alter IGRA positivity we also assessed whether the strength of the IGRA response was also affected. Changes in positive results were observed for both IGRA tests and were often, though not always, associated with increased numbers of results falling into the zones of uncertainty (Table 2). The eight individuals positive by QFT-GIT at both day 0 and day 7 had enhanced IFN-γ levels after the TST (day 0 median IFN-γ 1.43 IU/ml, day 7 median IFN-γ 7.67 IU/ml, p = 0.008). Of the 15 participants initially negative at day 0 by QFT-GIT but subsequently positive after TST, there was a>15 fold increase in IFN-γ levels (Figure 4A; day 0 median IFN-γ 0.09 IU/ml, day 7 median IFN-γ 1.44 IU/ml, p = <0.0001). In contrast, in the 143 individuals QFT-GIT who remained negative at day 7 no change in median IFN-γ levels was observed (−0.01 IU/ml both day 0 and 7, p = 0.85).


Tuberculin skin testing and treatment modulates interferon-gamma release assay results for latent tuberculosis in migrants.

O'Shea MK, Fletcher TE, Beeching NJ, Dedicoat M, Spence D, McShane H, Cunningham AF, Wilson D - PLoS ONE (2014)

IGRA responses before and after TST administration.(A) IFN-γ responses detected by QFT-GIT in individuals who became positive following TST; (B) SFC numbers in response to ESAT-6 and CFP-10 in individuals who became positive by T-SPOT.TB following TST; (C) SFC numbers in response to ESAT-6 and CFP-10 in individuals who became negative by T-SPOT.TB following TST. Uncertainty zone (grey shaded area); threshold for QFT-GIT positivity (dashed line); upper and lower thresholds for T-SPOT.TB conversion (solid lines). TST =  tuberculin skin test; QFT-GIT =  QuantiFERON Gold in-Tube; IFN-γ =  interferon-gamma; ESAT-6 =  early secretory antigenic target-6; CFP-10 =  culture filtrate protein-10; IU =  international units; SFC =  spot forming cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016319&req=5

pone-0097366-g004: IGRA responses before and after TST administration.(A) IFN-γ responses detected by QFT-GIT in individuals who became positive following TST; (B) SFC numbers in response to ESAT-6 and CFP-10 in individuals who became positive by T-SPOT.TB following TST; (C) SFC numbers in response to ESAT-6 and CFP-10 in individuals who became negative by T-SPOT.TB following TST. Uncertainty zone (grey shaded area); threshold for QFT-GIT positivity (dashed line); upper and lower thresholds for T-SPOT.TB conversion (solid lines). TST =  tuberculin skin test; QFT-GIT =  QuantiFERON Gold in-Tube; IFN-γ =  interferon-gamma; ESAT-6 =  early secretory antigenic target-6; CFP-10 =  culture filtrate protein-10; IU =  international units; SFC =  spot forming cells.
Mentions: Since antecedent TST could alter IGRA positivity we also assessed whether the strength of the IGRA response was also affected. Changes in positive results were observed for both IGRA tests and were often, though not always, associated with increased numbers of results falling into the zones of uncertainty (Table 2). The eight individuals positive by QFT-GIT at both day 0 and day 7 had enhanced IFN-γ levels after the TST (day 0 median IFN-γ 1.43 IU/ml, day 7 median IFN-γ 7.67 IU/ml, p = 0.008). Of the 15 participants initially negative at day 0 by QFT-GIT but subsequently positive after TST, there was a>15 fold increase in IFN-γ levels (Figure 4A; day 0 median IFN-γ 0.09 IU/ml, day 7 median IFN-γ 1.44 IU/ml, p = <0.0001). In contrast, in the 143 individuals QFT-GIT who remained negative at day 7 no change in median IFN-γ levels was observed (−0.01 IU/ml both day 0 and 7, p = 0.85).

Bottom Line: This resulted in an increase in IGRA concordance to substantial (64.3% agreement; κ = 0.73; 95% CI:0.58-0.88).Thus, in total on day 0 and day 7 after testing, 29 out of 166 participants (17.5%) provided a positive IGRA and of these 13 were TST negative.When the change in the levels of secreted IFN-γ was examined after chemoprophylaxis the median levels were found to have fallen dramatically by 77.3% from a pre-treatment median concentration of IFN-γ 2.73 IU/ml to a post-treatment median concentration IFN-γ 0.62 (p = 0.0002).

View Article: PubMed Central - PubMed

Affiliation: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; School of Immunity and Infection, MRC Centre for Immune Regulation, University of Birmingham Edgbaston, Birmingham, United Kingdom.

ABSTRACT

Background: Identifying latent tuberculosis infection (LTBI) in people migrating from TB endemic regions to low incidence countries is an important control measure. However, no prospective longitudinal comparisons between diagnostic tests used in such migrant populations are available.

Objectives: To compare commercial interferon (IFN)-gamma release assays (IGRAs) and the tuberculin skin test (TST) for diagnosing LTBI in a migrant population, and the influence of antecedent TST and LTBI treatment on IGRA performance.

Materials and methods: This cohort study, performed from February to September 2012, assessed longitudinal IGRA and TST responses in Nepalese military recruits recently arrived in the UK. Concomitant T-SPOT.TB, QFT-GIT and TST were performed on day 0, with IGRAs repeated 7 and 200 days later, following treatment for LTBI if necessary.

Results: 166 Nepalese recruits were prospectively assessed. At entry, 21 individuals were positive by T-SPOT.TB and 8 individuals by QFT-GIT. There was substantial agreement between TST and T-SPOT.TB positives at baseline (71.4% agreement; κ = 0.62; 95% CI:0.44-0.79), but only moderate concordance between positive IGRAs (38.1% agreement; κ = 0.46; 95% CI:0.25-0.67). When reassessed 7 days following TST, numbers of IGRA-positive individuals changed from 8 to 23 for QFT-GIT (p = 0.0074) and from 21 to 23 for T-SPOT.TB (p = 0.87). This resulted in an increase in IGRA concordance to substantial (64.3% agreement; κ = 0.73; 95% CI:0.58-0.88). Thus, in total on day 0 and day 7 after testing, 29 out of 166 participants (17.5%) provided a positive IGRA and of these 13 were TST negative. Two hundred days after the study commenced and three months after treatment for LTBI was completed by those who were given chemoprophylaxis, 23 and 21 participants were positive by T-SPOT.TB or QFT-GIT respectively. When individual responses were examined longitudinally within this population 35% of the day 7 QFT-GIT-positive, and 19% T-SPOT.TB-positive individuals, were negative by IGRA. When the change in the levels of secreted IFN-γ was examined after chemoprophylaxis the median levels were found to have fallen dramatically by 77.3% from a pre-treatment median concentration of IFN-γ 2.73 IU/ml to a post-treatment median concentration IFN-γ 0.62 (p = 0.0002).

Conclusions: This study suggests differences in the capacity of commercially available IGRAs to identify LTBI in the absence of antecedent TST and that IGRAs, in the time periods examined, may not be the optimal tests to determine the success of chemoprophylaxis for LTBI.

Show MeSH
Related in: MedlinePlus