Latent Tuberculosis Infection in United States Military: Concordance, Conversion, and Adverse ...

113 Pages·2014·0.62 MB·English

UC San Diego
UC San Diego Electronic Theses and Dissertations
Title
Latent Tuberculosis Infection in United States Military : Concordance, Conversion, and
Adverse Events Associated with Treatment
Permalink
https://escholarship.org/uc/item/1bv1h9tn
Author
Tang, Janet June
Publication Date
2014

Peer reviewed|Thesis/dissertation
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University of California
UNIVERSITY OF CALIFORNIA, SAN DIEGO
Latent Tuberculosis Infection in United States Military: Concordance,
Conversion, and Adverse Events Associated with Treatment
A dissertation submitted in partial satisfaction of the
requirements for the degree
Doctor of Philosophy
in
Public Health (Epidemiology)
by
Janet June Tang
Committee in charge:
San Diego State University
Caroline A. Macera, Chair
Andrew J. MacGregor
Susan I. Woodruff
University of California, San Diego
Edward D. Gorham
Sonia Jain
Tabitha Woolpert
2014
Copyright
Janet June Tang, 2014
All rights reserved.
The dissertation of Janet June Tang is approved, and it is acceptable
in quality and form for publication on microfilm and electronically:
Chair
University of California, San Diego
San Diego State University
2014
iii
DEDICATION
To my family, friends, and co-workers who supported me
throughout the process.
iv
TABLE OF CONTENTS
Signature Page . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii
Dedication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iv
Table of Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
List of Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
List of Figures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viii
List of Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x
Vita . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Abstract of the Dissertation . . . . . . . . . . . . . . . . . . . . . . . . . . . xii
Chapter 1 Background and Significance/Research Objectives . . . . . . . 1
1.1 Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Tuberculosis and the Military . . . . . . . . . . . . . . . 7
1.3 Adverse Events Related to Treatment of latent tubercu-
losis infection . . . . . . . . . . . . . . . . . . . . . . . . 10
1.4 Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Chapter 2 Concordance of Pharmacy and Medical Records for Surveil-
lance of Latent Tuberculosis Infection in the United States
Military . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.1 Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.2 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.3 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
2.4 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
2.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.7 Acknowledgements . . . . . . . . . . . . . . . . . . . . . 29
Chapter 3 Latent Tuberculosis Infection in Health Care Workers in the
United States Navy . . . . . . . . . . . . . . . . . . . . . . . . 39
3.1 Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3.2 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 40
3.3 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
3.4 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
v
3.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . 46
3.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . 51
3.7 Acknowledgements . . . . . . . . . . . . . . . . . . . . . 51
Chapter 4 AdverseEventsRelatedtoLatentTuberculosisInfectionTreat-
ment in the United States Military . . . . . . . . . . . . . . . 62
4.1 Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
4.2 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 63
4.3 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
4.4 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
4.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . 69
4.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . 74
4.7 Acknowledgements . . . . . . . . . . . . . . . . . . . . . 74
Chapter 5 Overall Conclusions and Discussion . . . . . . . . . . . . . . . 89
5.1 Research Contributions . . . . . . . . . . . . . . . . . . . 89
5.2 Summary of Findings . . . . . . . . . . . . . . . . . . . . 90
5.3 Limitations and Strengths . . . . . . . . . . . . . . . . . 94
5.4 Future Directions . . . . . . . . . . . . . . . . . . . . . . 95
vi
LIST OF ABBREVIATIONS
BCG, bacille Calmette-Guerin
CDC, Centers for Disease and Control and Prevention
CHAMPS, Career History Archival Medical Personnel System
CI, confidence interval
EMB, ethambutol
HMO, health maintenance organization
HR, hazard ratio
HCW, health care worker
ICD-9-CM, International Classification of Diseases, 9th Revision, Clinical Modifi-
cation
IFN-g, Interferon-gamma
IGRA, interferon-gamma release assay
INH, isoniazid
LTBI, latent tuberculosis infection
MDR, Military Health System Data Repository
MTF, military treatment facilities
NPV, negative predictive value
OR, odds ratio
PDTS, Pharmacy Data Transaction Service
PPV, positive predicted value
PZA, pyrazinamide
RIF, rifampin
SD, standard deviation
TST, tuberculin skin test
TB, tuberculosis
US, United States of America
WHO, World Health Organization
vii
LIST OF FIGURES
Figure 3.1: Study Sample Flowchart . . . . . . . . . . . . . . . . . . . . . . 52
Figure 3.2: Latent Tuberculosis Infection Incidence Rates in Navy Health
Care Workers (2003-2008) . . . . . . . . . . . . . . . . . . . . . 56
Figure 4.1: Count of Service Members that Started Latent Tuberculosis In-
fection Treatment and Percentage of those that Experienced
Any Adverse Event (2002-2010). . . . . . . . . . . . . . . . . . 77
viii
LIST OF TABLES
Table 2.1: Definitions for Latent Tuberculosis Infection Classifications . . . 30
Table 2.2: ConcordanceBetweenLatentTuberculosisInfection(LTBI)Phar-
macy and Medical Records in Active Duty Military Personnel (N
= 3,089,436) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Table 2.3: Performance Characteristics of Pharmacy Records to Identify
Latent Tuberculosis Infection (LTBI) Using Medical Record Di-
agnoses as a Reference in Active Duty Military Service Members
(N=3,089,436) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Table 2.4: Characteristics of Latent Tuberculosis Infection Match Cases
Identified in Pharmacy and Medical Records in Active Duty Mil-
itary Personnel . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Table 3.1: Select Characteristics of Active Duty Navy Health Care Workers
(October 1, 2001-February 12, 2009) . . . . . . . . . . . . . . . . 53
Table 3.2: Risk Factors of Latent Tuberculosis Infection in Navy Health
Care Workers. Adjusted Cox Proportional Hazard Model. Haz-
ard Ratio, 95% Confidence Interval (October 1, 2001-February
12, 2009) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Table 4.1: ICD-9-CM Codes for Adverse Events . . . . . . . . . . . . . . . 75
Table 4.2: ICD-9-CM Codes for Pre-existing Medical Conditions . . . . . . 76
Table 4.3: Select Characteristics of Active Duty Military Service Members
Treated for Latent Tuberculosis Infection (2001-2011). . . . . . . 78
Table 4.4: AdverseEventsbyLatentTuberculosisInfectionTreatment(2001-
2011). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Table 4.5: Characteristics Associated with any Adverse Event Among Mil-
itary Service Members that Received Treatment for Latent Tu-
berculosis Infection 2001-2011 (n=74,537). Adjusted Logistic
Regression Model. . . . . . . . . . . . . . . . . . . . . . . . . . . 82
ix