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The impact of HIV infection and CD4 cell count on the performance of an interferon gamma release assay in patients with pulmonary tuberculosis.

Aabye MG, Ravn P, PrayGod G, Jeremiah K, Mugomela A, Jepsen M, Faurholt D, Range N, Friis H, Changalucha J, Andersen AB - PLoS ONE (2009)

Bottom Line: The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%).Sensitivity when excluding indeterminate results was 86% (95% CI: 81-92%) and did not differ between HIV-negative and HIV-positive patients (88 vs. 83%, p = 0.39).However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark. martine@aabye.com

ABSTRACT

Background: The performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance.

Methodology/principal findings: 161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03). 23 patients (14%) had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p = 0.03). Low CD4 cell count (<300 cells/microl) did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81-92%) and did not differ between HIV-negative and HIV-positive patients (88 vs. 83%, p = 0.39).

Conclusions/significance: Sensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent.

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Antigen dependent and mitogen induced absolute IFN-γ levels by HIV-status and CD4 cell count group.Horisontal lines represent medians with interquartile range. Dotted lines represent the applied cut-off values as recommended by the manufacturer: 0.35 IU/ml for antigen (ESAT-6, CFP-10, TB7.7) dependent IFN-γ production and 0.50 IU/ml for mitogen (PHA) induced IFN-γ production respectively. The assay is not able to quantify values above 10 IU/ml why values above this limit were assigned the value 10 IU/ml.
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pone-0004220-g002: Antigen dependent and mitogen induced absolute IFN-γ levels by HIV-status and CD4 cell count group.Horisontal lines represent medians with interquartile range. Dotted lines represent the applied cut-off values as recommended by the manufacturer: 0.35 IU/ml for antigen (ESAT-6, CFP-10, TB7.7) dependent IFN-γ production and 0.50 IU/ml for mitogen (PHA) induced IFN-γ production respectively. The assay is not able to quantify values above 10 IU/ml why values above this limit were assigned the value 10 IU/ml.

Mentions: Median antigen dependent and mitogen induced IFN-γ production for QFT-IT positive, negative and indeterminate results for HIV-negative and HIV-positive patients respectively are depicted in figure 1. No significant differences were found in levels of IFN-γ between HIV-positive and HIV-negative patients when looking at each group of test results (p>0.05). However, as shown in figure 2, overall median values of antigen dependent IFN-γ production were lower in HIV-positive than in HIV-negative patients (p = 0.02). This was not the case for the mitogen induced IFN-γ production. No significant differences in IFN-γ were found between patients with a CD4 cell count above compared to below 300 cells/µl.


The impact of HIV infection and CD4 cell count on the performance of an interferon gamma release assay in patients with pulmonary tuberculosis.

Aabye MG, Ravn P, PrayGod G, Jeremiah K, Mugomela A, Jepsen M, Faurholt D, Range N, Friis H, Changalucha J, Andersen AB - PLoS ONE (2009)

Antigen dependent and mitogen induced absolute IFN-γ levels by HIV-status and CD4 cell count group.Horisontal lines represent medians with interquartile range. Dotted lines represent the applied cut-off values as recommended by the manufacturer: 0.35 IU/ml for antigen (ESAT-6, CFP-10, TB7.7) dependent IFN-γ production and 0.50 IU/ml for mitogen (PHA) induced IFN-γ production respectively. The assay is not able to quantify values above 10 IU/ml why values above this limit were assigned the value 10 IU/ml.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2626632&req=5

pone-0004220-g002: Antigen dependent and mitogen induced absolute IFN-γ levels by HIV-status and CD4 cell count group.Horisontal lines represent medians with interquartile range. Dotted lines represent the applied cut-off values as recommended by the manufacturer: 0.35 IU/ml for antigen (ESAT-6, CFP-10, TB7.7) dependent IFN-γ production and 0.50 IU/ml for mitogen (PHA) induced IFN-γ production respectively. The assay is not able to quantify values above 10 IU/ml why values above this limit were assigned the value 10 IU/ml.
Mentions: Median antigen dependent and mitogen induced IFN-γ production for QFT-IT positive, negative and indeterminate results for HIV-negative and HIV-positive patients respectively are depicted in figure 1. No significant differences were found in levels of IFN-γ between HIV-positive and HIV-negative patients when looking at each group of test results (p>0.05). However, as shown in figure 2, overall median values of antigen dependent IFN-γ production were lower in HIV-positive than in HIV-negative patients (p = 0.02). This was not the case for the mitogen induced IFN-γ production. No significant differences in IFN-γ were found between patients with a CD4 cell count above compared to below 300 cells/µl.

Bottom Line: The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%).Sensitivity when excluding indeterminate results was 86% (95% CI: 81-92%) and did not differ between HIV-negative and HIV-positive patients (88 vs. 83%, p = 0.39).However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark. martine@aabye.com

ABSTRACT

Background: The performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance.

Methodology/principal findings: 161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03). 23 patients (14%) had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p = 0.03). Low CD4 cell count (<300 cells/microl) did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81-92%) and did not differ between HIV-negative and HIV-positive patients (88 vs. 83%, p = 0.39).

Conclusions/significance: Sensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent.

Show MeSH
Related in: MedlinePlus