RIFAMYCIN-RESISTANT TUBERCULOSIS IN THE UNITED STATES, 1998-2008; an Analysis of the National Tuberculosis Surveillance System Open Access

Sharling, Lisa (2011)

Permanent URL: https://etd.library.emory.edu/concern/etds/wh246s56b?locale=en
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Abstract


RIFAMYCIN-RESISTANT TUBERCULOSIS IN THE UNITED STATES,
1998-2008;

an Analysis of the National Tuberculosis Surveillance System
By Lisa Sharling
Background: Tuberculosis (TB) incidence rates in the United States have declined since
1993; however drug resistance and HIV co-infection have slowed this decline over the
past decade. Mycobacterium tuberculosis bacteria resistant to the first line rifamycin
(RIF) drugs pose significant challenges to TB control. RIF resistance results in fewer and
more expensive treatment options, prolonged duration of treatment and poor treatment
outcomes. Through analysis of the National TB Surveillance System (NTSS) this study
examines the demographic and clinical characteristics associated with RIF-resistant TB.

Methods:
Two definitions of RIF resistance were considered; (1) cases reported at the
initial drug susceptibility test to be infected with rifampin (RMP)-monoresistant (RMR)
M. tuberculosis and (2) possible acquired RIF resistance. Polytomomous logistic
regression was used to examine the associations between RIF resistance and a number of
social, clinical and treatment outcome variables with particular focus on the two main
exposures of interest - HIV co-infection and prior TB diagnosis. Confounding and
interactions were assessed using multiple logistic regression. The proportions of drug-
resistant cases before and after the year 2002 were compared using a two-sample t-test.
The time until culture conversion from a positive to a negative culture was compared for
RIF-resistant TB cases and drug-susceptible controls using a Wilcoxon test.
Results: All forms of RIF resistance examined were positively associated with HIV co-
infection and this association was strongest for possible acquired RIF-monoresistance
(prevalence odds ratio [POR], 31.82; 95% confidence interval [CI], 14.76-68.69). RMR
cases were more likely to have HIV infection (POR, 3.46; CI, 2.65-4.52) or a prior
diagnosis of TB (POR, 3.50; CI, 2.61-4.71). Among RMR-TB cases with a previous TB
diagnosis the magnitude of the association with HIV co-infection was larger (POR, 6.88;
CI, 3.50, 13.52). Patients with RIF resistance took longer to culture convert and were
more likely to die during TB treatment.
Conclusions: This is the first report of the epidemiology of RIF-resistant TB on the
national level for the United States. Our findings should aid in supporting
recommendations for the case management of HIV co-infected patients. This study
highlights the significant burden of RIF resistance on the patient and on local TB control
programs.

RIFAMYCIN-RESISTANT TUBERCULOSIS IN THE UNITED STATES,
1998-2008;

an Analysis of the National Tuberculosis Surveillance System
By
Lisa Sharling
MBiochem, Bath University, 2000
PhD, Edinburgh University, 2005
Thesis Committee Chair: Michael Goodman, MD, MPH
A thesis submitted to the Faculty of the
Rollins School of Public Health of Emory University
in partial fulfillment of the requirements for the degree of
Master of Public Health
in Global Epidemiology
2011

Table of Contents

CONTENTS
INTRODUCTION................................................................................................................... 1
METHODS ............................................................................................................................... 5
Study population ................................................................................................................... 5
Univariate Analysis of RIF-monoresistance at Initial Drug Susceptibility Testing ......... 5
Multivariate Analysis for RMR-TB .................................................................................... 7
Univariate Analysis of Cases with Possible Acquired RIF-Resistant TB......................... 9
RESULTS ................................................................................................................................ 5
RIF-monoresistant TB at Initial Drug Susceptibility Testing .......................................... 10
Possible Acquired RIF-Resistant TB................................................................................. 13
DISCUSSION........................................................................................................................ 16
REFERENCES ....................................................................................................................... 21
TABLES AND FIGURES ..................................................................................................... 25
Figure 1. Defining Possible Cases of Acquired RIF-resistant TB with Consideration for Initial and Acquired INH Resistance ................................................................................. 25
Figure 2. Selection of RIF-monoresistant Cases at Initial DST (1998-2008) ................ 26
Figure 3. Selection of Possible Cases of Acquired RIF-resistant TB (1998-2008) ....... 27
Figure 4. RIF-Monoresistant Tuberculosis Reported at Initial Drug Susceptibility Test in the United States, 1998 to 2008 ..................................................................................... 28
Figure 5. INH-Monoresistant Tuberculosis Reported at Initial Drug Susceptibility Test in the United States, 1998 to 2008 ..................................................................................... 29
Figure 6. Multidrug-Resistant Tuberculosis Reported at Initial Drug Susceptibility Test in the United States, 1998 to 2008 ..................................................................................... 30
Table 1. Predictive Factors for Acquired RIF Resistance and Relapse or Treatment Failure. ................................................................................................................................ 31
Table 2. RIF-Monoresistant Tuberculosis Reported at Initial Drug Susceptibility Test before and after 2003. ......................................................................................................... 32
Table 3. Sociodemographic Characteristics of RIF-Monoresistant Tuberculosis (RMR-TB), INH-Monoresistant Tuberculosis (IMR-TB), Mutidrug-Resistant Tuberculosis (MDR-TB) and Drug Susceptible TB Cases at Initial Drug Susceptibility Test, United States, 1998-2008 ............................................................................................................... 33
Table 4. Clinical Characteristics of RIF-Monoresistant Tuberculosis (RMR-TB), INH-Monoresistant Tuberculosis (IMR-TB), Mutidrug-Resistant Tuberculosis (MDR-TB) and Drug Susceptible TB Cases at Initial Drug Susceptibility Test, United States, 1998-2008 .................................................................................................................................... 35
Table 5. Directly Observed Therapy (DOT) Use and Treatment Outcomes of RIF-Monoresistant Tuberculosis (RMR-TB), INH-Monoresistant Tuberculosis (IMR-TB), Mutidrug-Resistant Tuberculosis (MDR-TB) and Drug Susceptible TB Cases at Initial Drug Susceptibility Test, United States, 1998-2008 ........................................................ 37
Table 6. Model Fit Statistics for the final logistic model ................................................. 39
Table 7. Summary Prevalence Ratio Estimates for Exposure variables. ....................... 40
Table 8. Summary Prevalence Ratio Estimates for Control Variables. ......................... 41
Table 9. Sociodemographic Characteristics of All Forms of Possible Acquired RIF-resistant (ARR) TB and 3 Sub-categories of Acquired RIF-resistant TB with consideration for INH susceptibility, and RIF and INH Susceptible TB Cases, United States, 1998-2008 ............................................................................................................... 43
Table 10. Clinical Characteristics of All Forms of Possible Acquired RIF-resistant (ARR) TB and 3 Sub-categories of Acquired RIF-resistant TB with consideration for INH susceptibility, and RIF and INH Susceptible TB Cases, United States, 1998-2008............................................................................................................................................. 45
Table 11. Directly Observed Therapy (DOT) Use and Treatment Outcomes of All Forms of Possible Acquired RIF-resistant (ARR) TB and 3 Sub-categories of Acquired RIF-resistant TB with consideration for INH susceptibility, and RIF and INH Susceptible TB Cases, United States, 1998-2008 ............................................................. 47
APPENDICES ........................................................................................................................ 49
Appendix A. CDC Report of a Verified Case of Tuberculosis Form in Use 1993 through 2008 ....................................................................................................................... 49
Appendix B. Emory University IRB Exemption Letter ................................................... 53
Appendix C. Signed Assurance of Confidentiality for Non CDC/NCHHSTP Employees With Access to the National Tuberculosis Surveillance System ................. 54

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