The Tuberculin Skin Test: Within-Subject Variability, Boosting, and Comparison with the QuantiFERON-TB Gold In-Tube Test Público

Ilieva-Hughes, Emilia (Fall 2017)

Permanent URL: https://etd.library.emory.edu/concern/etds/xd07gs68j?locale=es
Published

Abstract

Introduction/Rationale:

Tuberculin skin test (TST) and interferon-gamma release assays, such as the QuantiFERON®-TB Gold In-Tube Test (QFT-GIT), are used to detect Mycobacterium tuberculosis infection. Information on the relative variability of TST and QFT-GIT, and effect of tuberculin injection on subsequent test results is limited.

 

Methods:

To assess 1) within-subject variability of TST when given simultaneously in the right vs. left arm, 2) agreement between simultaneously performed TST and QFT-GIT, 3) effect of initial TST on subsequent TST when performed a week apart, and 4) effect of initial TST on QFT-GIT when performed a week apart, we enrolled healthy adults with a prior positive TST but no TST in 3 previous years. All testing was performed blindly by healthcare workers with documented proficiency. Paired analyses compared categorical test interpretations using a 10mm TST cutoff and a 0.35 IU/mL QFT-GIT cutoff. Significance in differences of proportions was assessed using McNemar’s test.  

 

Results:

There were 158 total subjects available for the analysis. Of those with analyzable results, 75/154 (49%), 80/155 (52%), and 31/149 (21%) were positive by initial TST on the right arm, initial TST on the left arm, and initial QFT-GIT, respectively.  When repeated 1 week later, 72/124 (58%) TSTs were positive and 71/153 (46%) QFT-GITs were positive.

 

1) TSTs performed simultaneously in the right and left arm were discordant in 14% of subjects, while previous analyses of simultaneously performed QFT-GITs in this population demonstrated 5% discordance (p<0.01).

 

2) As compared to initial TST on the left arm, initial QFT-GIT results were discordant for 66 (45%) subjects. As compared to initial TST on the right arm, initial QFT-GIT results were discordant for 57 (39%) subjects.

 

3) Repeat TST was discordant with initial TST on the left arm for 34 (28%) subjects, with the majority of discordance (22%) due to TST conversion (i.e., negative to positive).  Of 71 subjects with negative initial left arm TST, 27 (38%) converted to positive when TST was administered a week later.  Repeat TST was discordant with initial TST on the right arm for 36 (29%) subjects, again with the majority of discordance (25%) due to TST conversion.  Of 77 subjects with negative initial right arm TST, 31 (40%) converted to positive when TST was administered a week later.

 

4) Repeat QFT-GIT was discordant with initial QFT-GIT for 40 (27%) subjects with the majority of discordance (26.7%, all but one subject) due to conversion. Of 115 subjects with negative initial QFT-GIT prior to TST, 39 (34%) converted to positive when QFT-GIT was performed a week after TST.

 

5) The proportions of subjects with conversion (38% to 40% for TST, and 34% for QFT-GIT) were greater than within-subject variability when the tests were performed simultaneously (14% for TST and 5% for QFT-GIT, p < 0.0001).

 

Conclusions: 

In a population with prior positive TSTs, TST was more variable than QFT-GIT when pairs of each test were performed simultaneously. TSTs may trigger conversion of subsequent TST and QFT-GIT.

Table of Contents

 

 

Table of Contents

CHAPTER I: INTRODUCTION     1

INFECTION AND DISEASE DUE TO MYCOBACTERIUM TUBERCULOSIS    1

Historical Perspective         1

Epidemiology           2

Transmission 4

MYCOBACTERIUM TUBERCULOSIS INFECTION     5

Treatment and Control       6

Targeted Testing     7

IMMUNOLOGIC TESTS FOR MYCOBACTERIUM TUBERCULOSIS INFECTION  9

Tuberculin Skin Test (TST) 9

Interferon-Gamma Release Assay (IGRA)         11

PROBLEMS ADDRESSED BY THIS RESEARCH       14

Within-Subject TST Variability      14

TST – QFT Agreement       15

Boosting of Immunologic Responses as Measured by TST    15

Boosting of Immunologic Responses as Measured by QFT-GIT        17

ANALYSIS GOALS 18

CHAPTER II: LITERATURE REVIEW     19

MEASURES OF VARIABILITY AND BOOSTING REPORTED IN PRIOR STUDIES      19

WITHIN-SUBJECT TST VARIABILITY (WITHIN-SUBJECT COMPARISON OF TST RESULTS)       20

WITHIN-SUBJECT COMPARISON OF TST AND QFT-GIT RESULTS           22

TST BOOSTING     26

CHAPTER III: METHODS  28

STUDY POPULATION       28

ANALYSIS AND STUDY DESIGN          29

TEST METHODS    30

STATISTICAL ANALYSIS METHODS    31

CHAPTER IV: RESULTS   32

SUBJECT CHARACTERISTICS  32

TEST RESULTS     33

OBJECTIVE I: ASSESSMENT OF WITHIN-SUBJECT TST VARIABILITY           33

OBJECTIVE II: ASSESSMENT OF TST - QFT-GIT AGREEMENT   34

OBJECTIVE III: ASSESSMENT OF TST BOOSTING OF A SUBSEQUENT TST           34

OBJECTIVE IV: ASSESSMENT OF TST BOOSTING OF A SUBSEQUENT QFT-GIT   35

CHAPTER V: DISCUSSION         36

INTRODUCTION     36

SUMMARY AND FINDINGS         37

LIMITATIONS          39

IMPLICATIONS       40

RECOMMENDATIONS FOR FUTURE STUDIES        42

CONCLUSIONS      42

FIGURES     43

TABLES        47

REFERENCES       52

 

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