Assessing specificity and discordance between the tuberculin skin test and a whole-blood interferon-γ release assay for the detection of Mycobacterium tuberculosis infection among United States Navy recruits. Open Access

Lempp, Jason Matthew (2011)

Permanent URL: https://etd.library.emory.edu/concern/etds/f7623c87g?locale=en%5D
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Abstract

Purpose
Military application of tests for the detection of M ycobacterium tuberculosis
infection requires accuracy to limit unnecessary treatment and prevent the
development and spread of active tuberculosis. This study sought to estimate
specificity of the tuberculin skin test (TST) and the whole-blood interferon-
gamma release assay QuantiFERON -TB Gold In-Tube (QFT-GIT) and identify
factors associated with test discordance.


Methods
Cross-sectional data on US Navy recruits tested with TST and QFT-GIT is
assessed through secondary analyses using univariate and multivariate methods.


Results
Among 787 recruits with determinate TST and QFT -GIT results, 5.3% of TST
indurations were > 10mm, 2.9% of TSTs were > 15mm, and 1.7% of QFT-GITs
were positive. Assuming recruits at low risk for tuberculosis exposure were not
infected, estimates of TST specificity were 99.0% (95% confidence interval [CI]:
98.2-99.9%) using a 15mm cutoff, and 98.2% (95% CI: 97.1-99.4%) using a
10mm cutoff. Estimated QFT-GIT specificity was 98.8% (95% CI: 97.9-99.8%).
Recruits born in countries with a high prevalence of tuberculosis were 18 to 34
times more likely to have TST-positive but QFT-GIT-negative discordance than
recruits born in low-prevalence countries. Half (18/37) of the recruits with this
discordance type had TST > 15mm.


Conclusions
The specificity of QFT-GIT was high and similar to TST at either cutoff.
Test discordance observed in recruits with increased risk may be due to lower
TST specificity, lower QFT-GIT sensitivity, or both. Negative QFT-GIT results
for recruits born in countries with high-TB prevalence and whose TST is > 15mm
suggest that QFT-GIT may be less sensitive than TST. Additional studies are
needed to determine the risk of developing TB when TST and QFT -GIT results
are discordant.

Table of Contents

CHAPTER I: BACKGROUND 4
EPIDEMIOLOGY OF TUBERCULOSIS 4
PATHOGENESIS OF MYCOBACTERIUM TUBERCULOSIS INFECTION 6
DIAGNOSTICS FOR MYCOBACTERIUM TUBERCULOSIS INFECTION 11
THE TUBERCULIN SKIN TEST 14
INTERFERON-GAMMA RELEASE ASSAYS 19
WHOLE-BLOOD INTERFERON-GAMMA RELEASE ASSAYS 22
DISCORDANCE IN RESULTS FOR THE DETECTION OF M. TUBERCULOSIS
INFECTION 29
LIMITATIONS TO INTERFERON-GAMMA RELEASE ASSAYS 36
TUBERCULOSIS AND THE UNITED STATES NAVY 40
LATENT TUBERCULOSIS INFECTION IN MILITARY RECRUITS 45
CHAPTER II: MANUSCRIPT 52
TITLE PAGE 52
INTRODUCTION 53
MATERIALS AND METHODS 58
RESULTS 64
DISCUSSION 70
LIMITATIONS AND STRENGTHS 83
CONCLUSION 87
REFERENCE LIST 89
TABLES 115
FIGURES 122

CHAPTER III: PUBLIC HEALTH IMPLICATIONS 124
SUMMARY 124
APPLICATIONS OF THE QUANTIFERON-TB GOLD IN-TUBE ASSAY 126
FUTURE DIRECTIONS 128
REFERENCES 131
APPENDICES 173
MILITARY HISTORY FORM FROM STUDY PROTOCOL 173
LINK TO MAZUREK ET AL. - M. TUBERCULOSIS INFECTION IN NAVY RECRUITS,
2007 175

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