The Tuberculin Skin Test: Within-Subject Variability, Boosting, and Comparison with the QuantiFERON-TB Gold In-Tube Test Público
Ilieva-Hughes, Emilia (Fall 2017)
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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