Citation
Adherence to Tuberculosis Infection Control Measures: Addressing the "Knowledge-Action" Gap among Healthcare Workers in the Dominican Republic

Material Information

Title:
Adherence to Tuberculosis Infection Control Measures: Addressing the "Knowledge-Action" Gap among Healthcare Workers in the Dominican Republic
Creator:
Chapman, Helena Jeanne
Publisher:
University of Florida
Publication Date:
Language:
English

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Public Health
Environmental and Global Health
Committee Chair:
LAUZARDO,MICHAEL
Committee Co-Chair:
SABO-ATTWOOD,TARA L
Committee Members:
MORRIS,JOHN GLENN
POMERANZ,JAMIE L
YANG,YANG

Subjects

Subjects / Keywords:
control
dominican
healthcare
infection
latent
powerlessness
republic
tuberculosis
workers

Notes

General Note:
Healthcare workers (HCWs), due to occupational exposure, have an increased risk of infection with Mycobacterium tuberculosis, including drug-resistant strains. They are challenged to remain up-to-date, not only with current clinical standards but also with evidence-based infection control practices, and translate that knowledge into effective infection control measures. This "knowledge-action" gap, which describes observed inconsistencies in the application of clinical knowledge to practice, may reflect barriers at individual- or systems-levels, thus influencing healthcare service delivery. In the Dominican Republic (DR), a country of high tuberculosis (TB) burden and drug resistance levels, one national study documented nosocomial M. tuberculosis transmission in HCWs employed at tertiary-level health institutions, but the rates of nosocomial transmission in HCWs remain unknown. Thus, driven by increased utilization of healthcare services by persons who are evaluated and managed for TB disease, occupational exposure among HCWs is overlooked. This dissertation aims to improve understanding of advanced TB clinical presentation that can influence infectiousness and occupational M. tuberculosis exposure in health institutions as well as examine the "knowledge-action" gap among HCWs in their use of recommended M. tuberculosis infection control measures. First, we examine associations of clinical, demographic and epidemiological characteristics of M. tuberculosis infection and pulmonary cavitation to understand infectiousness and occupational risk. Then, we conduct a two-phase study to explore the use of M. tuberculosis infection control practices among DR HCWs. By identifying HCWs perceived barriers that influence their adherence to M. tuberculosis infection control measures, we then explore the specific intrinsic and extrinsic processes that impact their clinical decision-making process to use these measures, thus adding to the "knowledge-action" gap in clinical practice. We also present recommendations that HCWs propose as potential strategies to enhance TB infection control. This theoretical framework can guide the development of evidence-based recommendations at institutional and national levels. Finally, we describe the public health implications of our findings related to M. tuberculosis infection control measures in tertiary-level health institutions in a high TB burden country, like the DR.

Record Information

Source Institution:
UFRGP
Rights Management:
All applicable rights reserved by the source institution and holding location.
Embargo Date:
12/31/2017

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ADHERENCE TO TUBERCULOSIS INFECTION CONTROL MEASURES: ACTION GAP AMONG HEALTHCARE WORKERS IN THE DOMINICAN REPUBLIC By HELENA J. CHAPMAN A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2016

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2016 H elena J. C hapman

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To my parents To public health professionals who investigate and prevent disease globally

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4 ACKNOWLEDGMENTS First, I am most thankful to my parents, Captain Robert Chapman ( USMC ) and Major General (ret) Marianne Mathewson Chapman PhD, MSN ( ARNG ) for their love and never ending support during my international academic journey in medicine and public health ; I was able to reach for the stars and achiev e my dreams. I am most apprecia tive for the continued support of family, especially my (late) grandmother Ensign Jeanne Mathewson RN ( US N) aunt LtCol (ret) Jud ith Mathewson PhD ( ANG ) and uncle Sven Welin. I am indebted to the academic guidance of my dissertation committee chair, Dr. Mi chael Lauzardo, who has provided this prestigious training in tuberculosis, inspiration and continued support to develop my international research project in the Dominican Republic. I am grateful for the continued academic support, patience and guidance by my dissertation committee, Dr. Jamie Pomeranz, Dr. J. Glenn Morris, Jr., Dr. Richard Rheingans, and Dr. Yang Yang. I also thank my graduate department chair, Dr. Tara Sabo Attwood, Dr. Song Liang, and professors and staff for their academic support. I am truly humbled and appreciative for the strong international support that I have received from my academic mentors and colleagues in the Dominican Republic. First, I am forever grateful to Dr. Eddy Prez Then, Director of O&M Medical School (O&MED) who ha s served as my in country advisor and mentor and provided overall guidance and inspiration along my international career journey. I would like acknowledge Dr. Belkys Marcelino, Director of the National Tuberculosis Program of the Dominican Republic Ministr y of Health, and her staff for their unrelenting support of this project. Finally, I also thank Dr. Bienvenido Veras, epidemiologist at the Hospital Regional Universitario Jos Mara Cabral y Bez, for his special collaboration during the

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5 project developme nt, data collection and analysis phases. Collectively, t his academic support and mentorship provided essential feedback on my research questions, which would allow my dissertation findings to contribute to the medical and public health scientific knowledge base in tuberculosis in the Dominican Republic. I am appreciative for the additional academic training that I received from the Gonzlez Ochoa, Dr. Luis a Arm as Prez and Dr. Alexander Gonz lez Daz. This international training formed a significant part of my repertoire of professional experiences and cultural immersion, learning about the Cuban primary healthcare model that focuses on prevention and providing innovation f or my dissertation research in the Dominican Republic. Finally, I am appreciative for the time and support of all research study participants who shared their personal experiences in adherence to tuberculosis infection control measures in their health institution. Their vocation to medicine and public health in the Dominican Republic is admirable and inspirational. It is hoped that the se research findings will provide further knowledge toward improving tuberculosis control in the Dominican Republic

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6 TA BLE OF CONTENTS page ACKNOWLEDGMENTS ................................ ................................ ................................ .. 4 LIST OF TABLES ................................ ................................ ................................ ............ 8 LIST OF FIGURES ................................ ................................ ................................ .......... 9 LIST OF ABBREVIATIONS ................................ ................................ ........................... 10 ABSTRACT ................................ ................................ ................................ ................... 11 CHAPTER 1 BACKGROUND ................................ ................................ ................................ ...... 13 Introduction ................................ ................................ ................................ ............. 13 Global Epidemiology of Tuberculosis ................................ ................................ ...... 13 Nosocomial Transmission of Tuberculosis ................................ ....................... 14 Occupational Risk to Healthcare Workers ................................ ........................ 15 Epidemiology of Tuberculosis in the Dominican Republic ................................ ...... 17 Nosocomial Transmission of Tuberculosis in the Dominican Republic ............. 18 Occupational Risk to Healthcare Wo rkers in the Dominican Republic ............. 19 ................................ ........................... 20 Overview of the Dissertation ................................ ................................ ................... 20 2 IS THE BEIJING STRAIN OF Mycobacterium tuberculosis ASSOCIATED WITH CAVITARY LUNG DISEASE? ................................ ................................ ................ 24 Introduction ................................ ................................ ................................ ............. 24 Materials and Methods ................................ ................................ ............................ 25 Results ................................ ................................ ................................ .................... 27 Discussion ................................ ................................ ................................ .............. 28 Conclusions ................................ ................................ ................................ ............ 30 3 BARRIERS RELATED TO ADHERENCE TO TUBERCULOSIS INFECTION CONTROL MEASURES AMONG HEALTHCARE WORKERS IN THE DOMINICAN REPUBLIC ................................ ................................ ........................ 36 Introduction ................................ ................................ ................................ ............. 36 Methods ................................ ................................ ................................ .................. 37 Setting and Sample ................................ ................................ .......................... 37 Data Collection ................................ ................................ ................................ 38 Data Analysis ................................ ................................ ................................ ... 39 Ethical Aspects ................................ ................................ ................................ 39 Results ................................ ................................ ................................ .................... 39

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7 Sense of Invincibility of Healthcare Workers ................................ .................... 40 Personal Beliefs of Healthcare Workers Related to Direct Patient Communication ................................ ................................ ............................. 41 Low Provider to Patient Ratio at Health Centers ................................ .............. 42 Absence of Tuberculosis Isolation Units for Patients within Health Centers ..... 43 Limited Availability of Protecti ve Masks for Healthcare Workers ...................... 44 Discussion ................................ ................................ ................................ .............. 45 Conclusions ................................ ................................ ................................ ............ 49 4 UNDERSTANDING WORKERS TO REDUCE OCCUPATIONAL EXPOSURE TO Mycobacterium tuberculosis : A GROUNDED THEORY APPROACH ................................ ............. 53 Introduction ................................ ................................ ................................ ............. 53 Methods ................................ ................................ ................................ .................. 55 Study Design ................................ ................................ ................................ .... 55 Participant Samp le ................................ ................................ ........................... 56 Data Collection ................................ ................................ ................................ 56 Data Analysis ................................ ................................ ................................ ... 57 Ethical Aspects ................................ ................................ ................................ 58 Results ................................ ................................ ................................ .................... 59 The Context of Feeling Powerless ................................ ................................ .... 60 Intrinsic Factors ................................ ................................ ................................ 61 Extrinsic Factors ................................ ................................ ............................... 64 Perceived Recommendations for Empowerment in Infection Control ............... 70 Discussion ................................ ................................ ................................ .............. 71 Conclusions ................................ ................................ ................................ ............ 76 5 CONCLUSIONS, IMPLICATIONS AND FUTURE RESEARCH ............................. 84 Contributions of the Dissertation ................................ ................................ ............. 84 Implications of Nosocomial Tuberculosis Transmission in Healthcare Worke rs ..... 85 Future Directions ................................ ................................ ................................ .... 86 Implementing Surveillance Systems for Tuberculosis Infection Control Measures ................................ ................................ ................................ ...... 87 Addressing Powerlessness and Limits of Education Programs ........................ 87 Applying Intervent ions to Empower Healthcare Workers in Clinical Duties ...... 88 Conclusion ................................ ................................ ................................ .............. 90 APPENDIX A INTERVIEW GUIDE FOR SEMI STRUCTURED INTERVIEWS ............................ 91 B INTERVIEW GUIDE FOR FOCUS GROUP DISCUSSIONS ................................ .. 92 LIST OF REFERENCES ................................ ................................ ............................... 94 BIOGRAPHICAL SKETCH ................................ ................................ .......................... 106

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8 LIST OF TABLES Table page 2 1 Clinical and epidemiologic characteristics of 975 culture confirmed tuberculosis cases in Florida, 2008 2011. ................................ .......................... 31 2 2 Unadjusted and adjusted associations between clinical and epidemiologic characteristics and ca vitation in 975 culture confirmed tuberculosis cases in Florida, 2008 2011. ................................ ................................ ............................ 34 3 1 Demographic and administrative variables of th e two selected tertiary level health institutions in the Dominican Republic, 2014 ................................ ........... 51 3 2 Demographic characteristics of the study participants of the semi structured interviews ................................ ................................ ................................ ........... 52 4 1 Demographic and administrative variables of the two selected tertiary level health institutions in the Dominican Republic, 2015 ................................ ........... 77 4 2 Demographic characteristics of the study participants of the focus group discussions ................................ ................................ ................................ ......... 78 4 3 Mycobacterium tuberculosis infection c ontrol measures at institutional and national levels ........ 81

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9 LIST OF FIGURES Figure page 1 1 Tuberculosis (TB) incidence and prevalence rates (per 100,000 people) in the Dominican Republic, 2002 2014. ................................ ................................ .. 23 1 2 Total numb er of notified tuberculosis (TB) cases in the Dominican Republic, 2003 2015. ................................ ................................ ................................ ......... 23 3 1 Conceptual model about perceived individual and institutional level barriers faced by healthcare workers that impact the risk of occupational Mycobacterium tuberculosis (MTB) exposure in the Dominican Republic .......... 52 4 1 making process in the application of Mycobacterium tuberculosis (MTB) infection control measures in clin .... 80

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10 LIST OF ABBREVIATIONS AIC BCG CDC CI DOTS DR FDOH HCW HIV HMS IGRA LTBI Akaike Information Criterion Bacillus Calmette Gurin Centers for Disease Control and Prevention Confidence Interval Directly Observed Treatment, Short course Dominican Republic Florida Department of Health Healthcare Worker Human Immunodeficiency Virus Health Management System Interferon Gamma Release Assay Latent Tuberculosis Infection MDG MDR TB MTB NTP OR TB TIMS TST WHO Millennium Development Goals Multidrug R esistant Tuberculosis Mycobacterium tuberculosis National Tuberculosis Program Odds Ratios Tuberculosis Tuberculosis Information Management System Tuberculin Skin Test World Health Organization

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11 Abstract of Dissertation Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy ADHERENCE TO TUBERCULOSIS INFECTION CONTROL MEASURES: ACTION GAP AMONG HEALTHCARE WORKERS IN THE DOMINICAN REPUBLIC By H elena J. C hapman December 2016 Chair: Michael Lauzardo Major: Public Health Healthcare workers (HCWs), due to occupational exposure, have an increased risk of infection with Mycobacterium tuberculosis including drug resistant strains. They are challenged to remain up to date not only with current clinical standards but also with evidence based infection control practices and translate that knowledge into effective i nfection control measures nowledge which describes observed inconsistenc i es in the application of clinica l knowledge to practice, may reflect barriers at individual or systems levels thus i nfluenc ing healthcare service delivery. In the Dominican Republic (DR), a country of high tuberculosis (TB) burden and drug resistance levels, one national study document ed nosocomial M. tuberculosis transmission in HCWs employed at tertiary level health institutions but the rate s of nosocomial transmission in HCWs remain unknown. Thus, driven by increased utilization of healthcare services by persons who are evaluated an d managed for TB disease, occupational exposure among HCWs i s overlooked. This dissertation aims to improve understanding of advanced TB clinical presentation that can influence infectiousness and occupational M. tuberculosis exposure in health institution s a s well

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12 as M. tuberculosis infection control measures First, w e examine associations of clinical, demographic and epidemiological characteristics of M. tuberculosis infection and pulmonary cavitation to understand infectiousness and occupational risk. Then, we conduct a two phase study to explore the use of M tuberculosis infection control practice s among DR H CWs perceived barriers that influence their adhere nce to M. tuberculosis infection control measures w e then explore the specific in trinsic and extrinsic processes that i mpact the ir clinical decision making process to use these measures thus adding to the We a lso present recommendations that HCWs p ropose as potential strategies to enhance TB infection control. This theoretical framework can guide the development of evidence based recommendations at institutional and national levels Finally, we describe the public health implications of our findings related to M. tuberculosis infection control measures in tertiary level health institutions in a high TB burden country like the DR

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13 CHAPTER 1 BACKGROUND Introduction Tuberculosis (TB) is historically known as one of the leading infectious causes of global mortality. Transmitted through aerosol droplets from an individual with active pulmonary TB disease, an estimated 10.4 million new TB cases and 1. 4 million TB fatalities were reported in 201 5 (World Health Organization, 2016a) However, one third of the global population is infected with Mycobacterium tuberculosis and at risk of reactivation (Glaziou, Falzon, Floyd, & Raviglione, 2013) where up to 10 percent may progress to active TB disease during the lifetime (Zumla, Raviglione, Hafner, & von Reyn, 2013) Early identification of high risk population groups and initiation of anti TB chemotherapy are key to curtail M tuberculosis transmission and improve global TB control. Global E pidemiology of Tuberculosis D iscovered by Robert Koch in 1882, M tuberculosis has successfully adapted its pathogenicity over time as a leading cause of morbidity and mortality. Over the past two decades, global prevalence and morality rates have continued to fall, but incidence rates have only began to decrease since 2 001 (Glaziou, Fl oyd, & Raviglione, 2009) These trends are attributed to multiple factors, including roll out of the cost effective, directly observed treatment short course (DOTS) strategy in the 1990s for optimal anti TB pharmacological management (Hargreaves et al., 2011) new diagnostic strategies (Dorman, 2010) and interventions that reach communities and target soci al determinants of health (Rasanathan, Sivasankara Kurup, Jaramillo, & Lnnroth, 2011) However, challenges in access to health care services, development of drug resistance,

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14 reactivation of TB infection, and co morbidities, including co infection with human immunodeficiency virus (HIV), remain concerns for global TB con trol (Dye & Floyd, 2006) More specifically, healthcare workers ( HCW s ) have historically been recognized as one vulnerable group with increased risk of nos ocomial M. tuberculosis transmission (Baussano et al., 2011) including multidrug resistant strains (Nathanson et al., 2010) Nosocomial T ransmission of Tuberculosis Evidence of nosocomial M tuberculosis transmission was noted in high income cou ntries during the mid 1980s through epidemiological investigations to describe the emergence of multi drug resistant M. tuberculosis outbreaks in health institutions (Frieden et al., 1996) The emerging HIV epidemic and ineffective infection control measures related to environmental and respiratory protection controls within healt h institutions accounted for increased nosocomial M. tuberculosis transmission (Harries, Maher, & Nunn, 1997) The W orld Health Organization (W HO ) infection control guidelines were revised by the C enters for Disease Control and Prevention (C DC ) WHO and the Int ernational Union Against Tuberculosis and Lung Disease for improved infection control in limited resource settings (World Health Organization, 1999) M. tuberculosis infection control guidelines should consider the disease proces s, such as susceptible, infection and disease, and ideal areas for appropriate interventions. However, with potential limitations in hospital infrastructure, increased patient flow, reduced number of HCW staff for operations, or limited resources for biosa fety measures (Alp, Leblebicioglu, Doganay, & Voss, 2011) limited resource health institutions may be unable to implement some or all of the categories of the M. tuberculosis infection control measures

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15 Previous studies have evaluated the use of M. tuberculosis infection control guidelines in high TB burden settings, concluding that guidelines are not universally implemented across health institutions (Harries, Hargreaves, Gausi, Kwanjana, & Salaniponi, 2002; Malangu & Mngomezulu, 2015) Health institutions with inadequate i nfection control policies, together with inaccurate understanding of T B risk can encounter complicat ions in TB management (Malangu & Mngomezulu, 2015; von Delft et al., 2015) In additi on, studies recommended that direct observation in health institutions is key to complement quantitative approaches to evaluate adherence to infection control guidelines (Harries et al., 2002; Malangu & Mngomezulu, 2015) However, neither study determined which specific component of the administrative, environmental or respiratory protection controls that play s an integral role in the successful implementation of M. tuberculosis infection control guidelines. In comparison to high resource health institutions, which depend primarily on environmental and respiratory protec tion control measures, low resource health institutions may only focus on administrative control measures (Nardell, 2003) Occupational Risk to Healthcare Workers Identification of risk factors that are associated with increased M. tuberculosis transmission is another essential strategy to reduce M. tuberculosis disease or infection in HCWs. First, an individual with a weak or immunocompromised immune system will be more susceptible to M. tuberculosis transmission and disease progression. Second, pulmonary cavitation is a clinical sign of advanced disease, which is linked to increased number of M. tuberculosis bacilli or increased infectiousness (Gadkowski & Stout, 2008) Thus, disease management may require a longer treatment regimen for recovery (Wang et al., 2009) Third, M. tuberculosis strains vary by geographic diversity as well

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16 as virulence. For example, the Beijing strain, which has been linked to the regions of East Asia (46% of cases), Oceania (17% of cases) and Middle East Central Asia (17% of cases), has been associated with increased M. tuberculosis transmission and drug re sistance (Brudey et al., 2006; Sun et al., 2006) Higher virulence of the M. tuberculosis strain can increase transmission, disease progression and mortality (Smith, 2003) Thus, integrating effective M. tuberculosis infection control measures and knowledge about associated risk factors can reduce nosocomial transmission and occupational risk of HCWs. Annual risk of TB disease in HCWs was two to three times higher across low, intermediate and high incidence regions (Baussano et al., 2011) In addition, global prevalence of TB infection in HCWs has been estimated at 63% (range 33 79%) in low and middle income countries, a nd 24% (range 4 46%) in high income countries, with an annual risk of 5.8% (range 0 11%) and 1.1% (0.2 12%), respectively (Menzies, Joshi, & Pai, 2007) Historical studies have reported higher M. tu berculosis transmission risk in nursing and medical students (Baussano et al., 2011) as well as laboratory staff (Harries et al., 2002) One study, in particular, reported a 2% annual incidence rate of TB disease and 17% annual tuberculin skin test (TST) conversion rate in Peruvian medical residents (Bonifacio et al., 2002) Nurses had higher TB infection rates than other HCWs (Joshi, Reingold, Menzies, & Pai, 2006) However, individual studies reported varying prevalence rates of TB infection including 43.4% in laboratory staff, 39.4% in technicians, 34.4% in physicians and 32.2% in nurse s in China (Zhang et al., 2013) ; 21.8% in physicians and 19.6% in nurses in Cuba (Borroto et al., 2011) ; 26.3% in

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17 clinical laboratory or respiratory ward staff in Chile (Hernndez et al., 2014) ; and 10.6% in administrative and clinical ward staff in Malaysia (Rafiza, Rampal, & Tahir, 2011) Epidemiolog y of Tuberculosis in the Dominican Republic The D ominican Republic (D R ) is a middle income country of high TB incidence (60/100,000 in 201 5 ) (World Health Organization, 2016c) and high levels of multidrug resistance identified from two national surveys (Espinal et al., 1998; Prez Then, Bez, Garca Siragusa, & Medina, 2009) Reported TB in cidence has been on the decline over the past 20 years (Prez Then, Acosta, Marcelino, & Espinal, 2007) with successful roll out of DOTS in 1999 and expanded coverage to 85% of the country by 2009 (Dominican Republic Ministry of Health, 2010) and 94% by 2012 (Dominican Republic Ministry of H ealth, 2014) Figure 1 1 shows the declining TB incidence and prevalence rates between 2002 and 2014, and Figure 1 2 presents the total number of TB case notification rates between 2002 and 2015. T he DR Ministry of Health has revised and disseminated guidelines, based on WHO and CDC recommendations, to enhance TB prevention and control across DR communities (Dominican Republic Ministry of Health, 2010) In addition to DOTS coverage, the Bacill us Calmette Gurin (BCG) immunization program aims to prevent advanced TB disease in children, such as tuberculous meningitis and miliary disease They reported an excess of 90% BCG immunization coverage in children who were less than one year of age However, there are two national studies that contrasted this stated achievement for population health. First, one study reported inadequate BCG coverage in school aged children (Prez Then, Shor Posner, Crandall, & Wilkinson, 2007) Second, t he only known study that measured M. tuberculosis infection in the DR reported prevalence of TB infection at 5% of the

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18 participating 672 children between five and 15 years of age who never received the BCG vaccination (Cruz Bournigal et al., 1986) T he DR Nationa l TB Program (NTP) has encountered three significant challenges for optimal TB control and prevention. First, due to treatment relapse or failure, primary drug resistance has ranged from 6.6% (1994 1995), 5.8% (2007 2008), and 6.6% (2012) (Espinal et al., 1998; Prez Then et al., 2009) recognizing the DR as (multidrug resistant TB prevalence of > 5%) (Blower & Chou, 2004) Second, due to decreased immunological protection, some high risk populations such as immunocompromised patients may be more susceptible to developing TB disease from initial contact with an infectious case or experiencing reactivation of previous M. tuberculosis exposure to TB disease. Third, specific drivers of TB transmission including the influence of the social determinants of health related to physical and social environments as well as health seeking behaviors (Lnnroth, Jaramillo, Williams, Dye, & Raviglione, 2009) should b e closely examined since M. tuberculosis t ransmission continues in DR communities Accordingly, g iven the indispensable attention to these three challenges that contribute to the overall national TB burden, occupational M. tuberculosis exposure of HCWs to drug susceptible and drug resistant strain s is minimized or disregarded. Nosocomial T ransmission of Tuberculosis in the Dominican Republic Current DR guidelines for M. tuberculosis control in health institutions have adopted the three recommended infection control strategies administrative contr ols, environmental controls and personal respiratory protection measures (Dominican Republic Ministry of Health, 2014) However, universal implementation in low and

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19 middle income countries has been limited (Jones Lpez & Ellner, 2005; Pai, Kalantri, Aggarwal, Menzies, & Blumberg, 2006) which is suggested to be the case in the DR. As frontline agents in DR health centers w ith increased occupational exposure to drug susceptible or drug resistant M. tuberculosis strains HCWs are susceptible to develop TB infection or disease Their risk of M. tuberculosis exposure, in effect, can influence overall healthcare service delivery for ambulatory or hospitalized patient care, and ultimately, negatively affect patient outcomes With limited efficacy of the BCG vaccine for lifetime immunological protection against M. tuberculosis personal protection for HCWs is essential to prevent M tuberculosis transmission. However, no governing DR agency actively monitors adherence to infection control policies or practices, albeit with reported M. tuberculosis transmission to HCWs in DR health institutions. Occupational Risk to Healthcare Worke rs in the Dominican Republic The estimated risk of M. tuberculosis nosocomial transmission to HCWs and prevalence of TB infection in HCWs are unknown The only national study to address nosocomial M. tuberculosis transmission was conducted at 49 provincial and regional DR hospitals, reporting that of the 116 HCWs who developed TB disease between 2005 and 2012, 27% were nurses, 17% were janitorial s taff and 11% were physicians (Genao & Rodrguez, 2013) Notably, these three HCW professions differ by the duration and scope of the respective clinical training N urses and physicians received academic coursework and supervised clinical rotations, and thus, are knowledgeable and skilled in TB pathology, di agnosis and management as well as M. tuberculosis infection control measure s. As such, it is essential to identify the underlying factors that drive M. tuberculosis transmission in the clinical setting, especially where trained clinicians face

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20 the daily risk of occupational exposure through their daily responsibilities in healthcare service delivery. K nowledge A G ap HCWs face daily challenges in order to remain up to date with evidence based clinical practices and, in turn, transl ate the educational information into changes in healthcare service delivery well documented in low and high income countries (Haines, Kuruvilla, & Borchert, 2004) Multiple barriers may hinder how HCWs can translate their knowledge into practi ce, especially in a time constrained or short staffed health setting (Haines et a l., 2004) Absence of financial resources can influence how HCWs are able to apply their knowledge into healthcare service delivery, thus fostering the development of health disparities in disease control (Farmer, 2013) One such example is the development of drug resistant M. tuberculosis where HCWs were unaware of the complex dynamics surrounding M. tuberculosis pathogen transmission and impor tance for establishing appropriate diagnostic and management measures for optimal infection control (Farmer, 2013) Thus, by increasing attention educated and empowered to apply their knowledge in to their clinical practices, health institutions can strengthen their application of optimal M. tuberculosis infection control measures. Overview of the Diss ertation This dissertation aims to improve understanding of occupational M. tuberculosis exposure among HCWs in health institutions. Since HCWs are historically recognized to have increased risk of occupational M. tuberculosis exposure in their workplace, it is essential to explore pathogen infectiousness related to advanced clinical presentation

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21 as well as application of infection control measures in clinical practice. In chapter two, we investigate the association of clinical demographic and epidemiological characteristics of M. tuberculosis infection and pulmonary cavitation to understand infectiousness and occupational risk We hypothesize that t he M. tuberculosis Beijing strain, which has been linked to increased risk of t ransmission, will be more associated with lung cavitation, when compared to the non Beijing strain. Then, using a qualitative approach and theoretical sampling, we conduct a two phase data collection period to examine how HCWs understand their occupational M. tuberculosis risk and report their application of infection control measures in three tertiary level health institutions in a high TB burden country, the DR. In chapter three, we identify the perceived barriers of HCWs that influence their use of M. tu berculosis infection control measures in clinical practice. In chapter four, we examine the intrinsic and extrinsic processes perceived by HCWs that influence the clinical decision making process to use infection control measures. We develop a theoretical framework that w ill identify reasons for this in adherence to M. tuberculosis infection control measures We also present several recommendations that HCWs suggested as potential strategies to enhance TB infection control within heal th institutions and the country. To our knowledge, this is the first known study to explore gap of HCWs in the application of M. tuberculosis infection control measures in clinical practice. Although TB incidence rates in the general DR population have declined over the past decade, the actual rate of nosocomial M. tuberculosis transmission in HCWs is unknown and overlooked. In our analyses, we identify barriers and comprehensively ex amine the intrinsic and extrinsic processes that hinder their

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22 consistent application of M. tuberculosis infection control measures in clinical practice. Th e s e findings ha ve the potential to propose specific target areas where future evidence based interventions can be implemented in DR health institutions to empower HCWs in the application of M. tuberculosis infection control measures in practice, thus Collectively, these three studi es contribute to improved understanding of the individual and systems M. tuberculosis infection control practices a nd provide a foundation for future studies t o evaluate evidence based interventions to empower HCWs as frontline agents to promote strategies to reduce nosocomial M. tuberculosis control in DR health institutions.

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23 Figure 1 1. T uberculosis (TB) incidence and prevalence rates (per 100,000 people ) in the Dominican Republic, 2002 2014 [ Data obtained from the World Health Organization Global Health Observatory data repository for TB incidence and prevalence data of the Dominican Republic. ] Figure 1 2. Total number of notified tuberculosis (TB) cases in the Dominican Republic, 2003 201 5. [Data obtained from the World Health Organization Global Health Observatory data repository for TB data of the Dominican Republic.] 0 20 40 60 80 100 120 140 160 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Rate (per 100,000) Year TB Incidence Rate (per 100,000) TB Prevalence Rate (per 100,000) 0 1000 2000 3000 4000 5000 6000 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Number of notified TB cases Year Total number of notified TB cases

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24 CHAPTER 2 IS THE BEIJING STRAIN OF M ycobacterium tuberculosis ASSOCIATED WITH CAVITARY LUNG DISEASE? 1 Introduction Th Mycobacterium tuberculosis has been linked to an increased risk of tuberculosis (TB) transmission and drug resistance (Bifani, Mathema, Kurepina, & Kreiswirth, 2002; Drobniewski et al., 2005; European Concerted Action on New Generation Genetic Markers and Techniques for the Epidemiology and Contr ol of Tuberculosis, 2006; Langlois Klassen et al., 2012; Sun et al., 2006) TB caused by the Beijing strain is associated with 45.9% of cases of TB in East Asia, 17.2% in Oceania, and 16.5% in the Middle East Central Asia (Br udey et al., 2006) Although the selective advantage of the Beijing strain has been noted, the specific clinical characteristics that might be associated with and hence promote transmission are unknown and have been for some time (Mathema, Kurepina, Bifani, & Kreiswirth, 2006) Pulmonary cavitation presents in less than 50% of TB patients, more commonly in advanced disease, which corresponds to increased infectiousness or quantity of M. tuber culosis b acilli (Gadkowski & Stout, 2008) Cavitation can increase the risk of TB transmission to susceptible individuals, facilitate the emergence of spontaneous mutations that may lead to drug resistance, and is a n independent risk factor for relapse 1 This chapter is published: Chapma n, H. J., Phillips, S. A., Hosford, J. L., Sraphin, M. N., & Lauzardo, M. (2015). Is the Beijing strain of Mycobacterium tuberculosis associated with cavitary lung disease? Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolution ary Genetics in Infectious Diseases 33, 1 5. https://doi.org/10.1016/j.meegid.2015.04.012

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25 after treatment completion (Yoder, Lamichhane, & Bishai, 2004) With high pathogen presence in cavitation, studies have demonstrated that indiv iduals with cavitation on initial treatment will take a longer period of time for negative sputum conversion (Wang et al., 2009) Further review of risk factors that play a role in the pathogenesis of advanced TB disease will be key to improve clinical management. It remains uncertain, however, whether the Beijing strain promotes the presence study in Russia reported increased risk of cavitation (Drobniewski e t al., 2005) while another study in Singapore found decreased risk of cavitation and presence of constitutional symptoms (Sun et al., 2006) The objective of our study is to determine whether the Beijing strain is associated with evide nce of lung cavitation on radiological imaging. A second objective is to describe key demographic and clinical characteristics of TB disease caused by Beijing strains as compared to non Beijing strains. Materials and M ethods A cross sectional study was con ducted using the Florida Department of Health (FDOH) TB Registry to examine culture confirmed M tuberculosis Beijing and non Beijing strains, reported in Florida, between January 1, 2008 and November 1, 2011. Data were extract Management System (HMS) and the Tuberculosis Information Management System (TIMS) databases. Genotyping is performed routinely for the FDOH through the National Tuberculosis Genotyping and Surveillance Network and retrospective data were used (Crawford, Braden, Schable, & Onorato, 2002) Spoligotyping and MIRU VNTR (12 MIRU) wer e performed utilizing methods previously described (Allix Bguec, Harmsen, Weniger, Supply, & Niemann, 2008; Kamerbeek et al., 1997)

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26 Demographic and epidemiological variables i ncluded age, sex, race/ethnicity, region of birth, homelessness, residency in a long term care facility or correctional institution, substance or illicit drug use, human immunodeficiency virus (HIV) status, previous TB infection, presence of cavitation on chest radiograph, presence of miliary disease, status at diagnosis (alive vs dead), and treatment completion. Due to sparse observations, we collapsed the race/ethnicity categories of Native Hawaiians and American Indians into the Asian/Other category. We dichotomized region of birth as (World Health Organization, 2014) Laboratory variables included sputum and culture smear results drug susceptibility results, and genotyping lineage. Data were analyzed using SAS Version 9.3 (SAS Institute Inc, Cary, NC, USA). Chi categorical variables. In the case of covaria tes missing more than 5.0% observations, we evaluated the influence of missingness on our predictor (Beijing strain) and outcome (cavitation). We used logistic regression to examine the unadjusted and adjusted associations between each covariate and the ou tcome of interest, cavitation. We selected the final model using backward manual selection (Bursac, Gauss, Williams, & Hosmer, 2008) We started with a fully adjusted model which included all the covariates of interest. Covariate influence on the association between the Beijing strain and cavitation was assessed using changes in model estimates as compared to the fully adjusted model. Indicators which when removed only changed parameter estimates for the Beijing strain by less than 10.0% and did not significantly affect model fit were considered to not be a confounder and were dropped from the final model. Final model

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27 fit was tested usi ng change in the Akaike Information Criterion (AIC). Significant odds ratios (ORs) were evaluated at a 0.05 alpha level and 95% confidence intervals (CIs). The study was approved by the Institutional Review Boards of the University of Florida and the FDOH and funding was provided by the University of Florida. Results Between January 1, 2008, and November 1, 2011, a total of 1,582 M. tuberculosis cases were recorded in the FDOH TB registry. A total of 476 (30.1%) cases were of extra pulmonary origin or negat ive confirmed culture results, 45 (2.8%) cases did not have spoligotyping, and 170 (10.8%) cases lacked radiographic imaging, and were excluded from the analyses. Our study analyzed the remaining 975 cases, where 144 (14.8%) isolates were classified as the Beijing strain. Table 2 1 shows descriptive statistics of the selected clinical and epidemiologic variables of TB disease associated with the exposure (Beijing strain) and outcome (cavitation). Our results show that cavitation was not associated with infe ction with the Beijing strain. In the unadjusted analyses, alcohol use (OR=1.7; 95%CI: 1.249 2.313; p=0.0007) was significantly associated with increased risk of cavitation. Older age ( > 65 years) (OR=0.5; 95%CI: 0.294 0.847; p=0.0100), being black (OR=0.7; 95%CI: 0.470 0.914; p=0.0127), Hispanic (OR=0.6; 95%CI: 0.390 0.814; p=0.0022) or foreign born (OR=0.7; 95%CI: 0.568 0.970; p=0.0290), and co infection with HIV (OR=0.2; 95%CI: 0.121 0.371; p<0.0001) were significant protective predictors of pulmonary cav itation. In the adjusted analyses, although alcohol use (OR=1.5; 95%CI: 0.980 2.289) was not statistically significant, we observed an increased risk of cavitation among those who reported alcohol use compared to those who did not. Older age ( > 65 years) (O R=0.5; 95% CI: 0.233 0.871), Hispanic ethnicity (OR=0.6; 95% CI: 0.312 0.962), and co

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28 infection with HIV (OR=0.1; 95%CI: 0.068 0.295) continued to have protective effects for cavitation. Due to sparse observations, status at diagnosis was not included in t he predictive model. Table 2 2 presents unadjusted and adjusted estimates. Discussion There are several potential reasons why the Beijing strain has been successful in establishing itself in populations around the world. A propensity to cause extensive di sease as manifested by cavitation on chest radiograph is one way since patients with extensive disease and cavitation are more infectious (Lohmann et al., 2012; Nava Aguilera et al., 2009) This study found that the presence of cavitation at diagnosis of pulmonary TB was not significantly associated with the Beijing strain. This is consistent with other investigations that have shown a similar lack of association in a similar relatively low incidence area as the United States (Langlois Klassen et al., 2012) Foreign born individuals were more likely to have the Beijing strain, which most likely reflects the ubiquitous presence of the Beijing strains among those who immigrated from the Western Pacific where the Beijing strain is more prevalent. Although HIV status has not been clearly associated with the Beijing strain (Drobniewski et al., 2005; European Concerted Action on New Generation Genetic Markers and Techniques for the Epidemiology and Control of Tuberculosis, 2006; Middelkoop et al., 2009) our study showed that co infection with HIV and older age ( > 65 years) had significant protective effects on cavitation, both of which are likely to result in a weakened immune system making cavitation less likely (Gadkowski & Stout, 2008) Also, we observed that alcohol use may be a significant predictor of cavitation, an association that has been observed in other bacterial infections and is most likely

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29 due to the fact that alcohol use may be associa ted with delayed presentation and hence advanced disease (Gadkowski & Stout, 2008) This is a cross sectional analysis and as such our results should not be interpreted as causal relationships. In addition, our stu dy did not account for many other factors that could explain the association between infection with the Beijing strain and pulmonary cavitation. There are multiple explanations for the wide dissemination of the Beijing strain throughout the world and its a ssociation with drug resistance. Increased virulence, increased transmissibility, characteristics of the population at risk, historically poor TB control in the countries where the Beijing strain is common, or any combination of these factors could account for the near ubiquitous presence of this strain. Furthermore, there is evidence that there is a difference between sub lineages of Beijing strains and the more modern lineages may be associated with factors that increase virulence or transmissibility (Iwamoto, Yoshida, Suzuki, & Wada, 2008; Mokrousov et al., 2005, 2006; Ribeiro et al., 2014) Future studies looking more closely at clinical features among the various sub lineages of Beijing strains may yield important answers. We also evaluated the effect of excluding for all covariates of the final sample, and two covariates, region of birth and co infection with HIV, showed a significant association with the Beijing strain and cavitation, respectively. The association between region of birth and Beijing can be attributed to the robust phylogeographical structure of M. tuberculosis (Gagneux, 2012) Second, although co infection with HIV has been strongly linked to reactivation or progression of TB infection or disease, respectively (Diedrich & Flynn, 2011) it may predispose individuals to infection with other fitter M.

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30 tuberculosis strains, such as the Beijing strain (Bekker & Wood, 2010) Lastly, differentiating the clinical characteristics attributable to the strain from the clinical characteristics attributable to the patient is a vexing problem but can be done with a prospec tive study powered to address issues not effectively dealt with in cross sectional study design. Conclusions Between 2008 and 2011, the Beijing strain was isolated in 144 (14.8%) of the 975 culture confirmed TB cases reported in the state of Florida. In t his cross sectional study, our hypothesis that cavitation would be associated with the Beijing strain in a low incidence area such as the United States was not confirmed. Cavitation was not significantly associated with infection with the Beijing strain. U nderstanding the clinical and epidemiological characteristics of the Beijing strain as well as the characteristics of the ancient and modern Beijing sub lineages will be essential for improved TB management and control.

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31 T able 2 1 Clinical and epid emiologic characteristics of 975 culture confirmed tuberculosis cases in Florida, 2008 2011 Characteristic Sample Beijing non Beijing p value Cavitation No cavitation p value Total (%) n=144 (14.8%) n=831 (85.2%) n=331 (34.0%) n=644 (66.0%) n (%) n (%) n (%) n (%) Age < 24 years 116 (11.9) 20 (17.2) 96 (82.8) 0.4250 47 (40.5) 69 (59.5) 0.0639 25 44 years 321 (32.9) 39 (12.2) 282 (87.8) 114 (35.5) 207 (64.5) 45 64 years 396 (40.6) 62 (15.7) 334 (84.3) 134 (33.8) 262 (66.2) > 65 years 142 (14.6) 23 (16.2) 119 (83.8) 36 (25.4) 106 (74.6) Sex Male 692 (71.0) 105 (15.2) 587 (84.8) 0.5780 238 (34.4) 454 (65.6) 0.6468 Female 283 (29.0) 39 (13.8) 244 (86.2) 93 (32.9) 190 (67.1) Race/ethnicity White 244 (25.0) 36 (14.8) 208 (85.2) <0.0001 103 (42.2) 141 (57.8) 0.0137 Black 383 (39.3) 20 (5.2) 363 (94.8) 124 (32.4) 259 (67.6) Hispanic 264 (27.1) 32 (12.1) 232 (87.9) 77 (29.2) 187 (70.8) Asian/Other 84 (8.6) 56 (66.7) 28 (33.3) 27 (32.1) 57 (67.9) Foreign born Yes 454 (46.6) 90 (19.8) 364 (80.2) <0.0001 138 (30.4) 316 (69.6) 0.0288 No 521 (53.4) 54 (10.4) 467 (89.6) 193 (37.0) 328 (63.0) Region of birth Americas region 800 (82.0) 73 (9.1) 727 (90.9) <0.0001 266 (33.3) 534 (66.7) 0.2733 Other regions 110 (11.3) 67 (60.9) 43 (39.1) 37 (33.6) 73 (66.4) Missing 65 (6.7) 4 (6.2) 61 (93.8) 28 (43.1) 37 (56.9) Homeless Yes 102 (10.5) 14 (13.7) 88 (86.3) 0.8207 34 (33.3) 68 (66.7) 0.7158 No 862 (88.4) 128 (14.8) 734 (85.2) 292 (33.9) 570 (66.1) Missing 11 (1.1) 2 (18.2) 9 (81.8) 5 (45.5) 6 (54.5)

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32 Table 2 1. Continued Characteristic Sample Beijing non Beijing p value Cavitation No cavitation p value Total (%) n=144 (14.8%) n=831 (85.2%) n=331 (34.0%) n=644 (66.0%) Correctional institution Yes 50 (5.1) 3 (6.0) 47 (94.0) 0.0983 14 (28.0) 36 (72.0) 0.3618 No 925 (94.9) 141 (15.2) 784 (84.8) 317 (34.3) 608 (65.7) Long term care facility Yes 11 (1.1) 3 (27.3) 8 (72.7) 0.2134 3 (27.3) 8 (72.7) 0.7582 No 964 (98.9) 141 (14.6) 823 (85.4) 328 (34.0) 636 (66.0) Alcohol use Yes 220 (22.6) 26 (11.8) 194 (88.2) 0.2942 96 (43.6) 124 (56.4) <0.0001 No 751 (77.0) 118 (15.7) 633 (84.3) 235 (31.3) 516 (68.7) Missing 4 (0.4) 0 (0) 4 (100) 0 (0) 4 (100) Non intravenous drug use Yes 122 (12.5) 8 (6.6) 114 (93.4) 0.0109 45 (36.9) 77 (63.1) 0.1751 No 847 (86.9) 136 (16.1) 711 (83.9) 286 (33.8) 561 (66.2) Missing 6 (0.6) 0 (0) 6 (100) 0 (0) 6 (100) Intravenous drug use Yes 20 (2.1) 2 (10.0) 18 (90.0) 0.7143 9 (45.0) 11 (55.0) 0.1129 No 949 (97.3) 142 (15.0) 807 (85.0) 322 (33.9) 627 (66.1) Missing 6 (0.6) 0 (0) 6 (100) 0 (0) 6 (100) HIV status Positive 127 (13.0) 10 (7.9) 117 (92.1) 0.0019 15 (11.8) 112 (88.2) <0.001 Negative 731 (75.0) 107 (14.6) 624 (85.4) 283 (38.7) 448 (61.3) Refused 76 (7.8) 14 (18.4) 62 (81.6) 24 (31.6) 52 (68.4) Missing 41 (4.2) 13 (31.7) 28 (68.3) 9 (22.0) 32 (78.0)

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33 Table 2 1. Continued Characteristic Sample Beijing non Beijing p value Cavitation No cavitation p value Total (%) n=144 (14.8%) n=831 (85.2%) n=331 (34.0%) n=644 (66.0%) Previous TB infection Yes 32 (3.3) 3 (9.4) 29 (90.6) 0.6678 14 (43.7) 18 (56.3) 0.4090 No 942 (96.6) 141 (15.0) 801 (85.0) 317 (33.6) 625 (66.4) Missing 1 (0.1) 0 (0) 1 (100) 0 (0) 1 (100) Any drug resistance Yes 3 (0.3) 2 (66.7) 1 (33.3) 0.0089 1 (33.3) 2 (66.7) 0.5938 No 953 (97.7) 136 (14.3) 817 (85.7) 326 (34.2) 627 (65.8) Missing 19 (2.0) 6 (31.6) 13 (68.4) 4 (21.0) 15 (79.0) Multi drug resistance Yes 13 (1.3) 4 (30.8) 9 (69.2) 0.0162 6 (46.2) 7 (53.9) 0.5218 No 940 (96.4) 133 (14.2) 807 (85.8) 319 (33.9) 621 (66.1) Missing 22 (2.3) 7 (31.8) 15 (68.2) 6 (27.3) 16 (72.7) Miliary TB Yes 51 (5.2) 9 (17.7) 42 (82.3) 0.2531 18 (35.3) 33 (64.7) 0.0023 No 910 (93.3) 135 (14.8) 775 (85.2) 302 (33.2) 608 (66.8) Missing 14 (1.5) 0 (0) 14 (100) 11 (78.6) 3 (21.4) Status at diagnosis Alive 964 (98.9) 141 (14.6) 823 (85.4) 0.2134 330 (34.2) 634 (65.8) 0.1101 Dead 11 (1.1) 3 (27.3) 8 (72.7) 1 (9.1) 10 (90.9) Treatment completion Completed 840 (86.2) 125 (14.9) 715 (85.1) 0.8590 285 (33.9) 555 (66.1) 0.5853 Did not complete 92 (9.4) 12 (13.0) 80 (87.0) 34 (37.0) 58 (63.0) Missing 43 (4.4) 7 (16.3) 36 (83.7) 12 (27.9) 31 (72.1) Abbreviation: TB, tuberculosis. Bold values refer to significant p values for chi square test of comparison between the groups.

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34 Table 2 2. Unadjusted and adjusted associations between clinical and epidemiologic characteristics and cavitation in 975 culture confirmed tuberculosis cases in Florida, 2008 2011. Characteristic Unadjusted Unadjusted Adjusted Adjusted OR (95%CI) p value OR (95%CI) a p value a Beijing strain No 1.0 (referent) 1.0 (referent) Yes 0.87 (0.592, 1.267) 0.4591 1.14 (0.683, 1.884) 0.6253 Age < 24 years 1.0 (referent) 1.0 (referent) 25 44 years 0.81 (0.523, 1.250) 0.3387 1.05 (0.629, 1.749) 0.8537 45 64 years 0.75 (0.491, 1.149) 0.1865 0.74 (0.430, 1.254) 0.2579 > 65 years 0.50 (0.294, 0.847) 0.0100 0.45 (0.233, 0.871) 0.0177 Sex Male 1.0 (referent) 1.0 (referent) Female 0.93 (0.696, 1.252) 0.6469 1.03 (0.717, 1.468) 0.8889 Race/ethnicity White 1.0 (referent) 1.0 (referent) Black 0.66 (0.470, 0.914) 0.0127 0.76 (0.489, 1.195) 0.2389 Hispanic 0.56 (0.390, 0.814) 0.0022 0.55 (0.312, 0.962) 0.0362 Asian/Other 0.65 (0.384, 1.095) 0.1049 0.91 (0.333, 2.474) 0.8498 Foreign born No 1.0 (referent) 1.0 (referent) Yes 0.74 (0.568, 0.970) 0.0290 0.89 (0.559, 1.403) 0.6045 Region of birth Americas region 1.0 (referent) 1.0 (referent) Other regions 1.02 (0.667, 1.552) 0.9356 0.69 (0.273, 1.759) 0.4407 Homeless No 1.0 (referent) 1.0 (referent) Yes 0.98 (0.632, 1.508) 0.9132 0.77 (0.430, 1.385) 0.3852 Correctional institution No 1.0 (referent) 1.0 (referent) Yes 0.75 (0.396, 1.403) 0.3634 0.54 (0.230, 1.271) 0.1585 Long term care facility No 1.0 (referent) 1.0 (referent) Yes 0.73 (0.192, 2.759) 0.6396 0.30 (0.032, 2.852) 0.2959

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35 Table 2 2. Continued Characteristic Unadjusted Unadjusted Adjusted Adjusted OR (95%CI) p value OR (95%CI) a p value a Alcohol use No 1.0 (referent) 1.0 (referent) Yes 1.70 (1.249, 2.313) 0.0007 1.50 (0.980, 2.289) 0.0617 Illicit drug use No 1.0 (referent) 1.0 (referent) Yes 1.19 (0.805, 1.753) 0.3851 0.89 (0.528, 1.501) 0.6618 HIV status Negative 1.0 (referent) 1.0 (referent) Positive 0.21 (0.121, 0.371) <0.0001 0.14 (0.068, 0.295) <0.0001 Refused 0.73 (0.440, 1.212) 0.2242 0.88 (0.490, 1.585) 0.673 0 Previous TB infection No 1.0 (referent) 1.0 (referent) Yes 1.53 (0.753, 3.123) 0.2388 1.38 (0.603, 3.171) 0.4441 Any drug resistance No 1.0 (referent) 1.0 (referent) Yes 1.35 (0.846, 2.138) 0.2109 1.50 (0.877, 2.554) 0.1395 Miliary TB No 1.0 (referent) 1.0 (referent) Yes 1.10 (0.608, 1.982) 0.7561 0.89 (0.417, 1.911) 0.7697 Treatment completion Completed 1.0 (referent) 1.0 (referent) Did not complete 1.14 (0.730, 1.785) 0.5614 1.55 (0.854, 2.793) 0.1502 Abbreviations: OR, odds ratio; CI, confidence interval. Bold values refer to significant associations between cavitation and covariates, evaluated at p < 0.05. a Sample size for the final adjusted model is n = 777.

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36 CHAPTER 3 B ARRIERS RELATED TO ADHERENCE TO TUBERCULOSIS INFECTION CONTROL MEASURES AMONG HEALTHCARE WORKERS IN THE DOMINICAN REPUBLIC 2 Introduction Healthcare workers (HCWs) have an increased ri sk of infection due to occupational Mycobacterium tuberculosis exposure including multidrug resistant strains. HCWs may be exposed and subsequently develop tuberculosis (TB) infection or active disease (Menzies et al., 2007) Annual risk of TB disease in HCWs was two to three times higher across low, int ermediate and high TB incidence regions (Baussano et al., 2011) Compliance with infection control measures, including personal protective equipment, administrative and environmental conditions, is es sential to reduce risk of M tuberculosis transmission between suspected TB patients and HCWs (Jensen, Lambert, Iademarco, Ridzon, & CDC, 2005) However, in limited resource settings, ineffective infection control strategies within health institutions coupled with erroneous understanding or perceptions of TB risk complicate TB management (von Delft et al., 2015) The Dominican Republic (DR) is a middle income c ountry in the Caribbean with high TB incidence (60/100,000 in 2014) (World Health Organization, 2016b) The directly observed treatment, short course (DOTS), which be gan in 1999, has been successful in reaching 94% of the population as of 2012 (Dominican Republic Ministry 2 This chapter has been submitted to a peer reviewed journal: Chapman, H. J., Veras, B. A., Pomeranz, J. L., Prez Then, E. N., Marcelino, B., & Lauzardo, M. (n.d.). Barriers related to adherence to tuberculosis infection control measures among healthcare workers in the Dominican Republic. MEDICC Review

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37 of Health, 2014) DOTS has been demonstrated to reduce TB incidence rate estimates. However, high reported levels of multidrug resist ance still have been reported (Espinal et al., 1998) especially for HCWs who may be in contact with patients susceptible or resistant to M tuberculosis strains. For example, according to one study, 116 HCWs [31(27%) nurses, 20(17%) janitorial services, 13(11%) physicians], who were employed at 49 provincial and regional hospitals, developed active TB disease between 2005 and 2012 (Genao & Rodrguez, 2013) Thus, to reduce occupational r isk of nosocomial M tuberculosis how HCWs understand their occupational risk and reported use of preventive strategies in their clinical practices. This is especially important since there is no established national surveillance program that reports the number of HCWs who become exposed and develop latent TB infection (LTBI) or active TB disease. With advancements in TB diagnostics, treatment and prevention, qualitative research studies are scarce, yet may add value to collaborative methods used for global TB control (Engel & Pai, 2013) Using a qualitative approach, the study purpose was to identify perceived barriers related to adherence to TB infection control measures among HCWs in the DR. M e thods Setting and S ample During August 2014, a qualitative study was conducted in two tertiary level health institutions within two regions of the DR Table 3 1 shows the demographic and administrative variables of the two selected institutions. A purposiv e sample of nine HCWs (seven physicians, two nurses), from emergency and internal medicine specialties, who were involved in TB prevention, control or management within the

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38 health institution w as recruited for this study. Inclusion criteria included: a) p hysicians who had completed at least one year of their medical specialty; and b) nurses who had completed at least one year (technical training) of their nursing education. Exclusion criteria included any physician or nurse with part time employment, or le ss than 25 hours per week. Table 3 2 describes the demographic characteristics of the s tudy participants. Data C ollection The socio ecological framework, adapted for social science and behavioral research in TB, guided the study design, methods and data analysis (Centers for Disease Control and Prevention, 2005) A semi structured interview guide was developed and used to facilitate data collection in Spanish. Topics included a) clinical experi ences related to M tuberculosis infection and disease; b) knowledge about disease transmission and utilized preventive practices; c) clinical management strategies; and d) perceptions related to DOTS effectiveness and disease coping strategies. Questions were written in English and translated into Spanish, and then verified by a bilingual Dominican physician. Each interview was conducted by the principal author, a general physician trained in the DR, and digitally recorded at the main desk of the closest c linical ward or in a private office. The duration of the interview varied based on the length of responses provided by the participant. Field notes were made by hand after the completion of each interview. Data collection was finalized when no new emerging themes were observed, thus reaching data saturation (Charmaz, 2000)

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39 Data A nalysis Data were transcribed and de identified by the principal author and verified by the co (QSR International Inc., Burlington, MA) was used to manage transcripts and facilitate the coding process. Based on knowledge and experiences in TB, both researchers developed initial categories prior to the start of the interviews. They coded the interview transcripts separately and then met to discuss all coded nodes and discrepancies to enhance int er observer reliability. Using thematic analysis, they analyzed these coded notes and developed emerging themes with illustrating quotations (Ryan & Bernard, 2003; Sandelowski & Barroso, 2003) Card sorting and peer debriefing were used to ensure reliability and validity in the analytical process (Lincoln & Guba, 1985; Ryan & Bernard, 2003) A descriptive and illustrative model was developed to represent the emerging themes Ethical Aspects This study was approved by the Institutional Review Boards of the University of Florida (Gainesville, Florida, USA) and O&M Medical School (O&MED) (Santo Domingo, DR). The protocol was evaluated and authorized by the National Tuberculosi s Program (NTP) (Santo Domingo, DR). Finally, the protocol was approved by the Department of Academics of Hospital A (Santo Domingo, DR) and the Institutional Review Board of Hospital B (Santiago de los Caballeros, DR). Written informed consent was obtaine d from all participants. R esults A total of nine HCWs (seven physicians, two nurses) participated in t he study. Of the physicians (five males, two females), five were attending physicians and two were

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40 resident physician s Both nurses were female and had un iversity level training. Interviews ranged from nine to 25 minutes (average of 15 minutes) in duration. Perceived barriers were described as: 1) sense of invincibility of HCWs; 2) personal beliefs of HCWs related to direct patient communication; 3) low pro vider to patient ratio at health centers; 4) absence of TB isolation units for patients within health centers; and 5) limited availability of protective masks for HCWs. Figure 3 1 presents the illustrative model of the emerging themes. S ense of Invincibili ty of H ealthcare Workers Most participants conveyed only a minor concern for nosocomial TB transmission in the health center, alluding to their prior M tuberculosis exposure by the Bacillus Calmette Gurin (BCG) vaccine, clinical exposure due to their short or long term employment at the center or both. One female nurse mentioned that all HCWs most I imagine that all [healthcare workers] who have worked in clinical wards, I believe we all have [TB] sensitivity One male physician re iterated this sentiment that all physicians will most likely have a positive result if given the tuberculin skin test (TST) suggesting that previous M. tuberculosis exposure has resulted in LTBI: Normally, we [physicians] are positive for TB [infection]. In the majority of health centers, physicians who work in these centers will have a positive result to the tuberculin skin test. We do not have prophylaxis for this. Well, we take care of ourselves enough, some of us. In fact, two physicians used humor to express their belief that little could be done if the entire country has been infected with M. tuberculosis One male physician stated, result of the tuberculin skin test. How can we act when the source [ M. tuberculosis ] is

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41 The majority of the population (laughs) of this country, you can classify as latent tuberculosis. What are we going to do with this group? We are not going to do anything because the majority of the population has it [latent tuberculosis], where I even include myself. Three participants mentioned that they did not develop TB disease, even though they had clinical responsibilities caring for TB patients. One fe with TB. I did not even develop the flu (laughs) that they have observed that HCWs had developed TB disease d ue to confirmed occupational exposure and successfully completed prescribed treatment regimens. One center and were confirmed to be cured [of TB disease] Participants me ntioned that one primary preventive measure is placing the protective mask on TB patients. One female nurse commented that aside from the BCG patients in order to protec physician remained optimistic and added that HCWs are knowledgeable and conscious of the TB transmission cycle and do not want to continue transmission to family members at home. Personal B eliefs o f H ealthcare Workers R elated to D irect P atient C ommunication Physicians and nurses emphasized that as HCWs, they genuinely aim to provide the best attention and quality of clinical care services to patients. They expressed, however, that their personal bel iefs about direct patient communication influence how they choose to protect themselves from the risk of possible occupational exposure to M. tuberculosis In one example, effective provider patient dialogue was maximized when

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42 the protective respiratory ma sk, a physical barrier, was removed. When caring for patients in the Emergency Department, one male physician responded that empathy associated with building patient rapport is a greater priority than wearing personal protective equipment such as a mask: I t is more cultural than anything. It looks ugly when you are in the Emergency Room I put on a mask as if I am going to become infected [by a patient]. It looks ugly, so we do not do this. We do, however, keep our distance from patients and avoid speaking closely face to face. In a second example, these provider patient communication strategies during medical appointments or ward rounds appeared to be more effective by relying simply on spiritual faith. Whether considered as an organized religion or a sour ce of hope and peace, this invisible form of defense from M. tuberculosis transmission was one last protective measure. As one female physician described her clinical experiences with direct care of TB patients, she credits her spiritual faith for not havi ng developed TB us (laughs) with the prevention, unfortunately Low P rovider to P atient R atio at H ealth C enters Physicians and nurses were knowledgeable about the high burden of TB cases in the DR as well as the clinical protocol of patients with respiratory symptoms who seek medical services at their health center They noted that the typical flow of patients to be evaluated for TB disease at medical consults is high. In particular, one physician stated that her consult receives new and follow up cases for evaluation and management, respectively, of TB disease: The day to day [flow] I see approximately 20 to 25 patients, just as (name of physician), that we

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43 function here in the department, with new patients ranging from one to five up tuberculo sis cases. Another female physician expanded this view to illustrate the increased patient admissions to clinical wards who are probable or confirmed TB cases, often maximizing hospital capacity for patient admissions: Right now, of patients admitted to the clinical ward of eight [patients], four are probable tuberculosis, two are confirmed tuberculosis. The patient who just arrived is probable tuberculosis. Many times, the entire clinical ward of eight beds for men and eight beds for women is full of tub erculosis. Participants mentioned that many patients who develop respiratory symptoms will self medicate with over the counter antibiotics or home remedies, and thus, remain undetected and untreated, thus continuing to transmit M. tuberculosis They state d that TB patients will commonly present with severe clinical manifestations, which are associated with increased risk of severe consequences or death. One female physician emphasized that TB patients who remain undiagnosed in the communities will succumb to the disease if they are not evaluated and admitted to the hospital with aggressive TB patient comes, and if you do not admit the patient [to the hospital], he or she will die Absence of T uberculosis I solation U nits for P atients within H ealth C enters Participants responded that their health centers do not have appropriate isolation units to separate probable or confirmed TB patients from other patients of other pathologie s. They were aware that the absence of this environmental control placed them at increased risk of M. tuberculosis her h

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44 because what should be done is that there would be an isolation area [for the patient], One male physician expressed that as the frontli ne agents to M. tuberculosis exposure, HCWs lack the necessary protective measures to reduce nosocomial TB with high transmission of pulmonary TB, and in this health center we do not have the appropriate protective resources or specific isolation unit in order to control [TB] transmission TB isolation unit in the health center may place other patient s at risk for nosocomial TB transmission. Limited A vailability of P rotective M asks for H ealthcare Workers Physicians and nurses recognized that health centers have limited budgets to manage daily functions, including administrative, clinical and laboratory responsibilities. Participants mentioned that protective masks are inconsistently available for use by HCWs or patients. One female physician described the protective function of masks s] are ideal, but you know, the costs of masks should be provided by the government. Here, we do not mentioned that she was quite aware of the limited protection of using surgi cal type protect us [as HCWs] but rather them [patients]. We place these masks on them Recognizing that TB is one of multiple diseases that HCWs encounter in their workplace, one nurse admitted that HCWs are unable to fully protect themselves from

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45 nosocomial M. tuberculosis transmission in the health center. She mentioned that her health center has not priorit ized the use of specialized masks as the best preventive approach to reduce possible M. tuberculosis transmission among HCWs and patients: We should use the N95 [mask], but all health personnel, physicians like nurses, use the simple [surgical] mask. Real use because immediately we know that there is a TB patient. We take precaution measures, but in the general sense, what should be done, is using the correct mask, isolation area for patients, really we lack [these measures]. D iscussion This is the first known study to explore perceived barriers of HCWs related to adherence to TB infection control measures in DR health institutions. As a high TB burden country, where TB incidence and prevalence rates have decreased over the last decade (World Health Organization, 2016b) four common challenges in TB control have been reported by the DR NTP. These include reaching marginalized populations living in hi gh TB burden geographical provinces; assessing influence of domestic (rural to urban regions) and international migration from Haiti; understanding social determinants of health associated with impoverished living conditions; and promoting community partic associated stigma and discrimination in vulnerable populations (Dominican Republic Ministry of Health, 2014) Occupational exposure of HCWs, however, remains overlooked, driven by increased utilization of medical services by persons who are undiagnosed and untreated for susceptible or resistant M. tuberculosis strains. Over the past two decades, published international guidelines have focused on a hierarchal strategy administra tive, environmental and personal respiratory protection as effective strategies to reduce nosocomial M. tuberculosis transmission in healthcare

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46 institutions (Jensen et al., 2005; World Health Organization, 1999) The World Health Organization (WHO) in 1999 disseminated recommendations for low resource health institutions (World Health Organization, 1999) In addition, in 2005, the Cent ers for Disease Control and Prevention (CDC) distributed guidelines for preventing M. tuberculosis transmission in healthcare settings (Jensen et al., 2005) However, the elaborate infrastructure required to build, finance, manage and sustain these infection control strategies was a limiting factor in the universal utilizati on within low income countries (Pai et al., 2006) Although these guides are ideal for healthcare settings, they fail to con sider the perceived barriers of those HCWs who serve as the frontline clinical support for their healthcare institutions. In our study, participants expressed individual level barriers that they perceive to hinder their ability to adhere to recommended M. tuberculosis infection control measures. They expressed that exposure to M. tuberculosis is inevitable, whether by prior history of BCG vaccination or their duration of employment in the healthcare environment. This presents a three fold challenge. First, although the BCG vaccine has shown immunological protection for the development of advanced TB disease in children, studies have shown that immunological protection is estimated to be less than 10 years with no protective effect in adult (Abubakar et al., 2013; Brouwer et al., 2014) Second, HCWs expressed self reassurance that they had not developed TB, but rather only the common cold or flu, although employe d in TB endemic settings. Thus, they may erroneously perceive that their habitual occupational exposure to the pathogen has (von Delft et al., 2015)

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47 patient communication, aiming to i mprove patient rapport by avoiding close contact with patients, as a basic, but not necessarily most effective, protective measure. Thus, HCWs may decide to relinquish protective precautions, such as a mask, and maximize perceived communication and deliver y of compassionate care to patients while reducing associated stigma (Brouwer et al., 2014) They also reported perceive d institutional level barriers that reflected the limited availability of institutional funding to provide appropriate and effective protection for HCWs from M. tuberculosis One fundamental risk of nosocomial M. tuberculosis transmission in healthcare institutions is the failure to promptly diagnose and implement appropriate infection control measures for suspected TB patient s (Jensen et al., 20 05) Since nosocomial M. tuberculosis transmission in HCWs has been documented by the DR Ministry of Health (Genao & Rodrguez, 2013) dual challenges will need to be addressed. First, although successful DOTS roll out reached an estimated 94% national coverage by 2012 (Dominican Republic Ministry of Health, 2014) interrelating factors such as personal, health service, social and structural continue to complicate patient adher ence to long term M. tuberculosis pharmaceutical regimen (Munro et al., 2007) Thus, HCWs may be exposed to M. tuberculosis by erroneously assuming that TB patients a re compliant to treatment when seeking healthcare services. Second, pre employment or annual screening of HCWs with TST or interferon gamma release assay (IGRA) for LTBI is not routinely conducted in the DR. Without these regular evaluations, this high ris k group may not receive the LTBI diagnosis and recommended preventive therapy to reduce the estimated five to 10 percent risk of reactivation TB over the lifetime (Zumla et al., 2013) By limiting the logistical assessment of nosocomial M.

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48 tuberculosis transmission in HCWs, health institutions will be unable to pri oritize the physical health of HCWs. Although participants described that occupational exposure to M. tuberculosis is daily, suggesting the clinical need for airborne protection measures within institutions as essential, such as appropriate masks and isola was notably observed This gap can be described as the observed inconsistent application of clinical knowledge in direct clinical practice (Graham et al., 2006; Haines et al., 2004) which can increase risk of occupational exposure to pathogens or negatively affect delivery of healthcare services (Haines et al., 2004) In low and high income countries, well documented facto rs that enable the expansion of this constrained or short staffed health settings, limited knowledge or erroneous perceptions of HCWs, lack of access to clinical research or reports, political ideologies that confl ict with scientific evidence, and absence of financial resources (Farmer, 2013; Haines et al., 2004) Since this study identified five perceived barriers among HCWs that limit their ability to co mply with preventive strategies that reduce risk of TB transmission, additional in depth exploration of these barriers should be studied to build a theoretical framework for dual purposes. First, stakeholders and other leaders of health institutions can ta ilor interventions and develop practical recommendations, in collaboration with HCWs, which aim to promote adherence to infection control measures among HCWs. Second, this framework can serve as a baseline for the preparation of research studies, using qua ntitative or mixed methods approaches, which can test hypotheses and identify causal associations

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49 between selected variables, such as effectiveness in the implementation of the recommended hierarchal strategy within institutional infection control programs Our study inc luded nine HCWs from two health institutions, yet saturation was reached as defined when no new information was added to categories (Charmaz, 2000) This study intended to explore overall clinical knowledge, perspectives and infection control practices among HCWs about TB infection and disease related to transmission, diagnosis, management and prevention. Thus, in dept h exploration and review, rather than generalizability, were essential to examine the cultural processes related to delivery of healthcare services. By understanding these cultural processes, however, hypotheses can be subsequently formed and tested in a f uture studies that incorporate quantitative or mixed methods design. Although two researchers reviewed the data, it should be recognized that there may be additional ways to interpret the data and more variables to explore in future study designs to valida te our results (Miles & Huberman, 1994) C onclusions Using a qualitative approach, this study identified perceived barriers related to adherence to TB infection control measures among HCWs in the DR. Our findings report that ineffective TB infectio n control strategies within health institutions coupled with erroneous understanding or perceptions of TB risk complicate TB management in limited resource settings. These perceived barriers at the individual or institutional level may hinder how HCWs und erstand the actual risk of TB transmission and are able to comply with preventive strategies that reduce their risk of M. tuberculosis exposure. Addressing these barriers by strengthening the infrastructure of infection control

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50 programs and implementing ed ucational interventions within institutions may reduce risk of nosocomial M. tuberculosis transmission to HCWs.

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51 T able 3 1. Demographic and administrative variables of the two selected tertiary level h ealth institutions in the Dominican Republic 2014 Hospital A Hospital B Demographic City Santo Domingo Santiago de los Caballeros Population (2010) 2,374,370 963,422 General Hospital classification National Regional Year opened 1946 1978 Annual number of admissions 11,513 24,822 Annual number of emergency visits 168,485 105,337 Annual number of consultations 117,110 175,759 Number of hospital beds* 214 425 Medical training programs Number of medical specialty programs 6 10 Number of medical subspecialty programs 2 13 Tuberculosis Number of reported cases with respiratory symptoms 1,062 524 Number of reported TB cases diagnosed at center Patients 139 15 Healthcare workers 4 1 Number of reported MDR TB cases diagnosed at center Patients 0 0 Healthcare workers 0 0 Presence of TB isolation area Internal Medicine ward No No Intensive Care Unit No No Abbreviations: MDR = multidrug resistant; TB = tuberc ulosis *Due to hospital renovations by the Dominican Republic Ministry of Health, the number of hospital beds varied per month in 2014. Thus, we calculated the average number of hospital beds in 2014 by adding the number of hospital beds per month and dividing this total number by 12. [Data provided by the Dominican Republic Ministry of Health National Department of Statistics, National Tuberculosis Program, and Hospital B.]

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52 T able 3 2 Demographic characteristics of the study pa rticipants of the semi structured interviews # Hospital Profession Sex Department Role 1 A Physician Male Emergency Chief physician 2 A Physician Male Emergency Attending physician 3 A Physician Male Internal Medicine Attending physician 4 B Physician Male Internal Medicine Chief resident physician (4 th year) 5 A Physician Male Internal Medicine Resident physician (4 th year) 6 A Physician Female Internal Medicine Chief physician 7 A Physician Female Internal Medicine Attending physician 8 A Nurse Female Nursing Nursing Coordinator 9 B Nurse Female Nursing Nursing Director Figure 3 1 Conceptual model about perceived individual and institutional level barriers faced by healthcare workers that impact the risk of occupational Mycobacterium tuberculosis (MTB) exposure in the Dominican Republic

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53 CHAPTER 4 U ACTION GAP IN HEALTHCARE WORKERS TO REDUCE OCCUPATIONAL EXPOSURE TO M ycobacterium tuberculosis : A GROUNDED THEORY APPROACH Introduction Globally, healthcare workers (HCWs) are recognized to have an increased risk of infection with Mycobacterium tuberculosis in the workplace, estimated at two to three times the risk in the general population (Baussano et al., 2011) Occupational categor ies with clinical responsibilities related to direct patient care influence overall risk of M. tuberculosis infection or disease (Institute of Medicine Committee on Regulating Occupational Exposure to Tuberculosis 2001; Menzies et al., 2007) The threat of nosocomial M. tuberculosis transmission has been linked to the number of active tuberculosis ( TB ) patients and the application of infection control measures in the health institution (Menzies et al., 2007) Infection control measures, including administrative, environmental and personal respiratory protection, however, may not be consistently implemented in health institutions of low and middle income countries (Jones Lpez & Ellner, 2005; Pai et al., 2006) As a middle income country in the Caribbean region, the Dominican Republic (DR) has reported a decline in T B incidence from 100 (per 100,000 people) in 2000 to 60 (per 100,0 0 0 people) in 2015 (World Health Organization, 2015, 2016c) High drug resistance levels have been reported, with 3% and 12% in new and previously treated TB cases, respe ctively (World Health Organization, 2016c) Rates of nosocomial M. tuberculosis transmission in HCWs are unknown. Only one national DR study documented that 116 HCWs, who were employed at 49 specialized health institutions between 2005 and 2012, developed TB disease, representing nurses (27%), janitorial

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54 s taff (11%), and physicians (11%) (Genao & Rodrguez, 2013) With the large TB burden in the general population, no current research or active surveillance programs evaluate adherence to M. tuberculosis infection control measures or measure risk of exposure or disease. HCWs encounter daily challenges in order to remain up to date with evidence based clinical practices and translate educational information into actions in clinical practice (Graham et al., 2006) crepancies observed when applying clinical knowledge to practice (Haines et al., 2004; Thamlikitkul, 2006) Observed gaps in practice may reflect barriers at the individual or systems level (Kitson & Straus, 2010) thus influencing healthcare service delivery to patients. Once these b arriers are identified and analyzed, authorities can engage stakeholders or policy makers, leading subsequent action where research findings will influence adherence of clinical practices examining the decision making process by which HCWs understand their occupational risk and use preventive strategies to reduce nosocomial M. tuberculosis transmission in clinical practice. Our purpose is two fold. First, we aim to contribute new findings about how trained DR clinicians, who are familiar with TB disease management and World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) evidence based guidelines, use their knowledge as a foundation when applying scientific co ncepts to the clinical setting. This study will provide the first step to understanding

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55 presented in open dialogue with stakeholders. Second, based on the underlying challen ges faced by HCWs that hinder consistent use of M. tuberculosis infection improved TB control in the health institution and country. For this reason, our research quest ion is as follows: What is the decision making process by which HCWs use preventive strategies to reduce nosocomial M. tuberculosis transmission in their clinical practice? Methods Study D esign Using a grounded theory approach, we aimed to better understa nd how HCWs perceived their ability to use TB infection control strategies in clinical practice. We used the socio ecological framework, modified for social science and behavioral research in TB, to facilitate the research design, methodology and data anal ysis and interpretation (Centers for Disease Control and Prevention, 2005) Then, through grounded theory methods, we were able to explore the processes that influence the perceptions of participa nts regarding their ability to adhere to M. tuberculosis infection control practices (Charmaz, 2006) Focus group discussions were used to facilitate an open dialogue with participants about their perspectives and experiences on the phenomenon, permitting back and forth exch anges of agreement or disagreement (Kru eger, 1988) In particular, what participants think, but they excel at uncovering why (Morgan, 1988, p. 25). Based on the context of the research question, selected participants may share common characteristics, such as demogr aphic variables, but should maintain adequate diversity

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56 to promote conversation (Krueger, 1988) Participants who perceive that they have shared general interests with other group members are more likely to discuss their experiences, opinions and perspectives openly (Kidd & Parshall, 2000) Participant Sample A purposive sample of 40 HCWs, composed of 24 physicians and 16 nurses who had direct clinical patient care responsibilities in the emergency, internal and family medicine specialties at one of two selected tertiary level health institutions, was invited t o participate in focus group discussions. Using theoretical sampling strategies, we were able to expand our data collection from the previous chapter and elaborate on the study findings (Charmaz, 2000) To reduce any potential power imbalance or dynamics in the focus group discussions (Barbour, 2005) we organized focus groups of the same sex and occupation. Of our sample, physicians and nurses must have completed at least one y ear of their medical specialty or one year (technical training) of their nursing education, respectively. Any physician or nurse with part time employment, or less than 25 hours per week, was not recruited for the study. Data Collection Based on the five barriers identified from the semi structured interviews with physicians and nurses and described in the preceding chapter, a semi structured focus group interview guide was developed. Questions were prepared in English, translated into Spanish, and verifie d by a bilingual Dominican physician for accuracy and clarity. Prior to the start of each focus group discussion, each participant completed a demographic survey regarding their age, educational formation, clinical responsibilities and duration of employme nt within the institution, regular work schedules, and frequency of on call schedules. Then, focus group discussions were conducted by the

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57 principal author and digitally recorded in a quiet, conference room in the hospital, lasting approximately 60 minutes Most focus group discussions included a co facilitator, appointed from administration, for note taking during the session. At the end of the focus group discussion, each participant received a small gift bag of various office supplies for personal use. F ield notes from jottings of informal dialogue with HCWs, diary notes about daily activities in the health institution, and daily log of the timetable of events were prepared (Bernard, 2011) Data collection continued until saturation, or no new emerging themes, w as reached (Charmaz, 2000) The focus group discussions followed three steps. First, interview questions facilitated an open dialogue about indivi dual, institutional and socio cultural factors that influenced the ability of HCWs to adhere to recommended M. tuberculosis infection control practices. Each of the previously described five barriers were presented to allow a more in depth discussion of th e specific challenge. Interview probing techniques were after each barrier, participants were asked about their recommendations to improve overall compliance to M. tuber culosis infection control measures in the institution. Finally, at the end of the focus group discussion, participants were asked about their recommendations to improve M. tuberculosis infection control measures and prevention in the DR. Table 2 presents t he sample interview questions of the focus group discussions. Data Analysis Focus group interview data were digitally recorded, transcribed verbatim into Spanish, and verified by a bilingual Dominican physician to confirm accuracy of the data transcriptio n. Co facilitator and field notes, diary notes and daily log of the timetable

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58 were de identified and transcribed to maintain confidentiality of responses. QSR Burlington, MA) was used to manage data transcripts and facilitate the coding process. Grounded theory and dimensional analysis techniques were used to guide the data analysis process (Charmaz, 2006; Schatzman, 1991) Two investigators, familiar with the research subject and study described in the previous chapter, developed initial codes prior to data collection. In order to improve inter observer reliability, they coded each data transcript independently and subsequently discussed all codes and arising discrepancies. Memos were prepared throughout the three steps of analysis: 1) open coding to identify categories and sub categories from the data; 2) axial coding to identify how cat egories are related; 3) selective coding to establish the primary category (Corbin & Strauss, 1990) The use of comparative analyses, or comparing how categories are similar or different, aided the process of theor y development (Corbin & Strauss, 1990) Card sorting was used to examine relationships among emerging constructs of the model development (Ryan & Bernard, 2003) Audit trails documented the data collection, including field notes, diary notes and daily log of the timetable, and interpretat ions during the analytical process (Guba, 1981) Peer debriefing (Lincoln & Guba, 1985) with qualitative experts of the UF Qualitative Data Analysis Group, occurred throughout the preparation of the study design and analysis to ensure rigor, reliability and validity in the analytical process. An explanatory model was developed to represent the th eoretical framework. Ethical Aspects This study had the approval of the Institutional Review Boards of the University of Florida (Gainesville, Florida, USA) and O&M Medical School (O&MED) (Santo

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59 Domingo, DR). The National Tuberculosis Program (NTP) (Santo Domingo, DR) evaluated and authorized the protocol. Finally, the Department of Academics of Hospital A (San Pedro de Macors, DR) and the Institutional Review Board of Hospital B (Santiago de los Caballeros, DR) approved the protocol. All participants pro vided written informed consent for study participation. Results A total of 40 focus group discussions (24 physicians, 16 nurses) were conducted, ranging from 45 to 60 minutes (average of 55 minutes) in duration. Participants had direct clinical responsibil ities in emergency medicine (n=26), family medicine (n=6) and internal medicine (n=8). Physicians were second or third year medical residents, and nurses had certificate associate or bachelor level training. The average age of participants was 34.2 yea rs, divided between physicians (29.0 years) and nurses (42.1 years). Table 2 presents the demographic characteristics of the sample population. describe: a) context of feeling p owerless; and b) intrinsic and extrinsic conditions that influenced the use of M. tuberculosis infection control strategies (knowledge and perceptions, institutional policies, clinical responsibilities, institutional infrastructure). We perceived recommendations, which together with future evidence based interventions, can empower HCWs in improving adherence to M. tuberculosis infection control strategies in clinical practice. The first cycle describes the context of powerlessness, while the second cycle represents how empowerment through evidence based interventions can be applied in the future. Figure 1 represents the M. tuberculosis infection control measures in owledge

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60 The Context of Feeling P owerless Participants expressed that they had numerous limitations in their clinical practice, which did not allow them to consistently adhere to M. tuberculosis infection control measures. One male physician s tated that HCWs are often unable to apply their [TB] patient, we do not have the space [isolation ward] and sometimes neither the resources, although we have the knowledge examples of when this emotional distress was experienced. One female nurse mentioned that applying infection control measures in practice was often outside her ies, but sometimes we feel helpless. We want to do [more], but we cannot physician commented more specifically on the inability to separate patients of highly hat we should not have placed the [TB] patient with other [non TB] patients, but with limited space, we have no In addition, participants described their limited voice as clinicians and observed inaction of health authorities, demonstrating evidence of power dynamics or imbalance in their clinical practice. One male physician stated that medical residents felt that they are unable to influence changes in clinical practice even if they were to repo rt these requests to health authorities: These limitations in clinical practice bother us. We see these things and unfortunately we sometimes feel angered [because] as a resident we cannot complain. We express that we have justification, but they [authorities] do not take our concerns into consideration.

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61 Many participants stated that their clinical responsibilities had minimal supervision for oversight f rom health authorities, expressing that they feel that no authority figure holds their presence or well being at high esteem or priority. Finally, participants described the absence of collaborations among stakeholders in efforts to improve healthcare service delivery to patients. One male nurse questioned how HCWs could be effectively empowered in t to us to want to collaborate if we do not have the [administrative] input and supply of essential role that influenced the overall o utcome of service delivery: mean, if patients do not help themselves, if healthcare workers are not actively playing a role, if the government does not provide the necessary resources, if health promotion activities do not have incentives, it [use of preventive strategies] will be difficult but not impossible. It is a matter of willingness and desire to work. Nothing more. Intrinsic Factors Knowled ge about TB disease and management Participants expressed that TB was a common clinical presentation in the emergency room and hospital ward of their institutions, due to the high TB burden in the DR. They described common socio demographic characteristic s of suspected TB patients, including low socio economic status, overcrowded living conditions, drug or substance abuse, and lack of family support. In particular, participants emphasized that the undocumented immigration of Haitians, who typically reside in overcrowding and impoverished conditions of the bateys (sugarcane plantations), remains a significant challenge in TB prevention and control in the DR. One male physician expressed that this recognized social disease of poverty would be difficult to con

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62 country [of Haiti] come here. This would be another challenge for us to eradicate the pathology because they bring TB here from their country language barriers that exist in their institutions, they also mentioned that many TB patients hide their diagnosis and do not follow recommended treatment or prevention measures, often leading to disease transmission, advanced disease progression or death. One female physician noted how TB patients will often fail to disclose their health to ask them again and again, and then they will respond. Sometimes they abandon treatment and remain quiet, saying no thing to their health provider Participants shared empathy for TB patients, as they must endure the extensive recovery period on directly observed t reatment, short course (DOTS), including facing medication side effects and risk for t reatment abandonmen t, fluctuation in emotional and psychological health, and stigma influencing family dynamics and social support. They expressed that health promotion tools are key to empower TB patients to better understand their disease process, recognize the importance to complete DOTS, and us e prevention measures to protect further disease transmission to family and friends. One female physician stated that health and human rights could be protected through gy can better defend their rights and protect themselves as well as others patients can be spokespersons for [TB] prevention because they have alr eady lived and

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63 Perception about occupational risk Participants expressed that HCWs serve on the frontline to direct patient care in the emergency room and hospital wards, assuming an o ccupational risk of nosocomial transmission of multiple pathogens. One female types of hospital acquired infections of th to do reduce transmission risk, but we still continue our clinical work without consistently using [prevention strategies] to reduce risk they knew at least one other HCW who had developed TB disease while employed at their institution. Moreover, they expressed deep concern about the increased risk of disease transmission in non clinician HCWs, such as employees working in the cafeteria, hum an resources, janitorial services or patient transport, who are not formally trained in clinical disease knowledge. and ethical role in direct patient care. One male nurse expr essed that as HCWs they understand their occupational risk in clinical practice, demonstrating commitment to the risks that you will be exposed to. If I dedicate myself to study nursing, it was physician mentioned that HCWs may knowingly not comply with prevention measures in ase [and] we do not protect ourselves because we want to help another person. It all depends on the vocation of each person

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64 Participants expressed a general sense of invincibility, although conscious of their increased risk of occupational exposure to T B or other pathogen. One female physician stated that their occupational exposure over time has served as a protective evelop the latent infection. W e and do not develop the disea se described this TB exposure in relation to the hypothetical screening measures using the tuberculosis infection, whether due to the vaccine or c ontinued exposure, and we will have a positive [TB] screening test that their direct patient care with TB patients has not resulted in the development of active TB disease. One male physician expressed this erroneous confidence related to and are confident that since they have worked for five or six years [with TB patients], they will not develop TB disease. They fall in this trap. But, in reality, we have a high Extrinsic F actors Institutional policies. Participants described the absence of institutional programs that regularly evaluate the physical health of HCWs, including M. tuberculosis exposure. One female physician believed that economic factors may hinder the comprehensive or other personnel. I think that these programs may exist only on paper and are not claimed that they had never received any health evaluation while employed at their health institution. One female nurse, however, described that health authorities

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65 appea our center do not provide monthly, biannual or annual health evaluations. When there is an outbreak, then they worry about the employees m entioned that the institutional priorities do not include protecting the health of HCWs: health institution is more concerned about training physicians than providing care to country and the Ministry of Health, but they do not invest the necessary resources to protect healthcare workers who care for these [TB] patients so that they can provide high quality healthcare services Participants mentioned that health educational programs for HCWs could serve as the foundation for effective TB control in health institutions. Most participants shared that they were unaware of and had not attended any regular continuing education programs related to TB or other general health threats while employed at their health institution. One male nurse stated that s ome general trainings were provided randomly provide direct medical attention. Last year, there were several trainings only for bachelor level nurses, but certificate an d associate level nurses have not received any type of training for years had appointed a health educator to conduct health seminars and case study presentations and educate nursing personnel about different infectious diseases. At the same time, they mentioned that the DR Ministry of Health conduct ed irregular TB

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66 educational campaigns as well as the annual World TB Day promotion, which aim to educate communities about TB disease. One female nu rse asserted that HCWs were educational outlets. We [healthcare workers] do not actively educate ourselves. We are disobedient to education because these programs constantly inform us about TB and Finally, participants described the challenge in sustainable and consistent communication between the TB program and their clinical department related to TB patient management. One female physician stated the typ ical scenario in the emergency department: We receive patients, we diagnose them by their clinical symptoms, and then after you find the [diagnostic] results, you send them to the [TB] program. There, they record the patient and manage the disease. From t here onward, we do not have further contact with the patient, only with those patients who do not follow treatment and later return to the emergency room [with complications] and we identify them and admit them to the hospital. Participants added that the Ministry of Health appeared to prioritize the maternal infant health indicators, rather than TB incidence rates, although both are critical aspects of the Millennium Development Goals. One male physician said that reducing TB incidence should be an institu administration understands this responsibility, where they are conscious about disease control HCW responsibilities. Whether participants had daily clinical responsibilities in the emergency room or ho spital ward, they described their demanding schedule to manage patient clinical evaluations, admissions, discharges and referrals. In particular, they described that there is a low patient provider ratio, or an inadequate number of

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67 HCWs to provide high qua lity healthcare services to patients. One male nurse emphasized the context of this busy clinical setting with patient overcrowding: her male nurse used one example to describe guidelines and I have 70 patients. In any given time, the protocol will be disrupted because myself alone with 70 patients, how c participants emphasized that the presence of few HCWs in the clinical area negatively impacted the quality of healthcare service delivery to patients. Many participants recognized that suspected TB cases may eve n be missed in their patient evaluations due to this hectic clinical environment. One female physician described the consequence of limited and insufficient time to conduct a comprehensive patient evaluation in the emergency room: The lack of health provi ders influences the rapid patient evaluation and sometimes fails to provide the best diagnosis of the patient. It influences the fact that if we had more health providers, since we have a high patient he process for patient treatment and management. Participants mentioned that the excess workload, where they managed daily work schedules and on call services, increased physical and mental exhaustion and stress. One male physician focused on the impact o f the workplace stress: I believe that the stress does not allow us to think about TB infection, to but rather job stress, that we are unable to think about transmission, but simply do our job. Likewise, another male physician echoed this perspective, emphasizing that

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68 we should [use prevention strategies], we overlook them clinic al responsibilities that greatly impact their own analysis of their occupational risk, the possibilities of [occupational] risk for one second of the day. We simply work w ith despite their rapid actions in the clinical setting, HCWs can lower their guard on risk we lose the equilibrium of this order. We may enter with a mask first, but then trusting that the protective masks or gloves, if not available in the clinical area, wou ld require completion and submission of a hospital form to the supply room outside of the clinical where leaving the clinical area to obtain protective equipment for herself and her patient would result in visible without using prevention strategies because I cannot leave the patient alone [to look for a mask] Institutional infrastructure. All participants expressed that the absence of an isolation ward for TB patients facilitated the spread of M. tuberculosis to HCWs and other patients in the health institution. Two participants referenced that HCWs ser ved as TB patients were placed in the same clinical area in lieu of an isolation ward. One male nurse described the high risk of nosocomial M. tuberculosis transmission in the hospital ward in an environment where [TB] bacilli are in the air, and we have patients with other

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69 pathologies [in the area], when we are beside the [TB] patient, we are exposing the neighboring patient to possible disease transmission of the [TB] patient Participants mentioned that hospital overcrowding is a daily and constant challenge, expressing that patients cannot chose their disease pathology or management, trusting their HCWs. One male physician stated tient who is beside them. They cannot protect themselves. This is what worries me. You can only take precautions for what you know healthcare services in clinical areas without adequate ventilation One m ale physician stated, emergency room, so if patient with active tuberculosis disease arrives, everyone can be exposed not feel healthcare workers Participants mentioned that their health insti tutions only dispersed surgical masks for HCW and patient use. One female nurse stated that HCWs understood that their use masks because at least it is something, but w female physician noted that she often observed an exhausted supply of masks: This is what promotes [disease] transmission also identified that the N95 type respiratory masks were ideal for TB control, and they questioned the relative cost of these masks and why health institutions were unable to purchase them. They

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70 mentioned that although surgical masks were frequently limite d in supply, they would confirm that at least the patient wore the surgical mask. One female physician, however, have a mask or not, the patient receives medical attenti on. This does not affect our Perceived R ecommendations for Empowerment in Infection Control Participants discussed recommendations that they believed could empower HCWs to adhere to M. tuberculosis infection control measures within health institu tions and the country. They reported four common categories between institutional and national recommendations, including: a) education and training to increase awareness to patients, HCWs and community members about TB disease and preventive measures while d ispel ling myths and reduc ing social stigma or discrimination ; b) policy to prioritize HCW health and well being and TB surveillance, diagnosis and prevention strategies; c) infrastructure to reinforce strategies that reduce hospital overcrowding an d risk of nosocomial M. tuberculosis transmission; and d) economic considerations to identify available funding sources to maintain adequate suppl ies of disposable materials and equipment and overall health expenditure for TB control. They also reported tw o additional categories for national recommendations, such as: a) r esearch to assess basic health indicators, identify barriers in service delivery and examine the influence of stigma and social determinants of health ; and f ) p olitical considerations to i d entify any modifications in local or national political leadership that can strengthen TB control and prevention Table 4 presents the se six categories of proposed recommendations by HCWs

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71 Discussion This is the first known study in the DR ability to use preventive strategies for M. tuberculosis control in the workplace, and more specifically, illustrate how the intrinsic and extrinsic factors in fluenced their decision making process to adhere to these inf ection control practices. The observed powerlessness to prevent nosocomial M. tuberculosis transmission in their clinical practice. The DR Ministry of Health has regularly updated an d widely disseminated guidelines to improve hospital and community TB control (Dominican Republic Ministry of Health, 2010, 2014) based on evidence based guidelines by the CDC and WHO (Jensen et al., 2005; World Health Organization, 1999) Supervision of the application of these infection control strategies, however, has not been universally prioritized across the public and private health sectors, thus leaving the existing threat of nosocomial M. tuberculosis transmission for HCWs and pat ients. The feeling of powerlessness in the clinical setting, as evidenced in this study, has been reported as a barrier when physicians or nurses independently coordinate work schedules (Gask, 2004) complete assigned clinical tasks (Kuokkanen & Leino Kilpi, 2001; Norrish & Rundall, 2001) or use evidence based guidelines (Lipman, 2000) The concept of power, defined as a combination of authority and influence over others, has been described historically in nursing practice (Prescott & Dennis, 1985) On e review control over competence, content of practice, and context of practice (Manojlovich, 2007) Thus, although th e academic formation of physicians and nurses differ by philosophical model, length of academic and clinical training, depth of clinical skills, and

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72 projected clinical responsibilities, HCWs collectively were unable to attain full level s of empowerment and consistently adhere to M. tuberculosis infection control measures. Competence or expertise in the scientific discipline is key to provide high quality healthcare service delivery and optimal patient outcomes. Participants were knowledgeable about their in creased occupational risk of nosocomial M. tuberculosis transmission, including the high TB burden that exists in the DR (60/100,000 in 2015) and the neighboring country of Haiti (194/100,000 in 2015 ) (World Health Organization, 2016c, 2016d) Their knowledge and perceptions about TB infection and disease, however, limited their abil ity to protect themselves and their colleagues in three distinct ways. First, HCWs expressed that they had previous M. tuberculosis exposure due to Bacillus Calmette Gurin (BCG) vaccine. These combined discrepancies in the immunological protection of the BCG vaccine and risk associated with continued o ccupational exposure resulted in feelings of invincibility, which may hinder their use of infection control strategies in clinical practice. Second, HCWs expressed their strong sense of vocation to maximize service delivery to patients regardless whether they were able to adhere to infection control measures. Although this altruistic view to provide personalized care to all patients is admirable, their failure to consistently adhere to infection control strategies increase s their risk of nosocomial M. tube rculosis transmission to HCWs and patients. Third, s cien tific and skill based expertise do not equal experience or duration of employment, which is important to recognize in a country like the DR where license re certification and continuing education pr ograms are not currently mandatory (Iglesias et al., 2015)

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73 The c ontent of clinical practice which emphasizes p rofessional autonomy, or appropriate dec ision making and independent action based on professional expertise (Skr, 2010) plays an essential role in practitioner control in clinical practice. In this study, HCWs were limited in full expression of their professional autonomy in two ways. First, physicians and nurses have different academic and clinical training, where nurses, in particular, select one of three spec ialty levels: professional (e.g., bachelor level), technical (e.g., associate level) and auxiliary (e.g., certificate level) (Siantz & Malvrez, 2008) Howev er, with limited continuing education programs offered to physicians and nurses, they may only count on their previously acquired knowledge as they serve as independent practitioners. Second, absence of isolation wards for suspected TB patients coupled wit h excess workload and hospital overcrowding, HCWs were inevitably forced to place patients of different pathologies in one hospital room, ultimately feeling helpless in their clinical decision making. To combat this limitation, the DR government has financ ed the national reconstruction and renovation of more than 50 hospitals since 2013, where many health institutions will be designed with an isolation ward to improve infection control. The context of clinical practice, which can motivate HCWs to maximize their leadership potential and serve as key stakeholders in health decision making can foster a positive workplace environment as well as job satisfaction (Manojlovich, 2007; Weston, 2010) In this study, HCW s expressed dissatisfaction and disillusion that institutional health leaders and stakeholders failed to identify and prioritize clear deficiencies in healthcare service delivery. This presents two challenges. First, HCWs who feel devalued or unimportant t

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74 affected in their completion of daily clinical responsibilities as well as their reflections on their selected vocation, including motivation to adhere to infection control strategies. Second, with weak co mmunication links between the hospital TB program, emergency room and hospital ward for TB management, HCWs may be perceive that they have an insignificant role in strengthening TB diagnosis, management or infection control. Finally, by understanding the limitations that foster feelings of powerlessness, key evidence based interventions can be implemented to empower HCWs to incorporate and implement their knowledge and skills into infection control practice s The concept of individual e mpowerment incorpora tes three main components (Manojlovich, 2007) First, o pportunit ies to pursue professional development within the workplace, combined with adequate institutional support and available resources, can motivate employees to apply their leadership across organizational levels Second, psychological motivation to maximize self confidence and self efficacy is an active process that incorporates workplace environment as well as personality characteristi cs of employees Third, by building relationships to promote compassionate and empathetic care employees can feel confident to apply their leadership skills in practice T hese three components may help to empower HCWs intrinsically in their daily clinical practice ; however, the extrinsic or systems level limitations within health institutions persist and should be promptly addressed. campaign, t he DR Ministry of Health can motivate all health institutions to understand the TB burden and mandate that they become familiarized with reported limitations in physical infrastructure and policies, influencing how HCWs adhere to M. tuberculosis infection control measures in clinical practice. Consequently, health institutions can take

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75 appropriate and prompt action to adapt and repair the presence of these structural limitations In this study, we also examined how HCWs believe that M. tuberculosis infection control measures can be strengthened at institutional and national levels, by em phasizing six main categories. roposed recommendations with evidence based strategies in M. tuberculosis infection control, gap by empowering HCWs in their application of M. tuberculosis infection control measures in practice. Our study was comprised of 40 HCWs who were employed in emergency, family or internal medicine specialties from two health institutions. Two additional focus groups, each with four physicians, were added to the total sample, to compensate for one health institution where family medicine residents were primarily female. Due to the excessive workload, not all focus group discuss ions could obtain a co facilitator for note taking during the session, which would have provided additional field notes to analyze. Using theoretical sampling, participants could elaborate on their experiences and perceptions related to the five barriers i dentified from the previous chapter; however, no new emerging themes were apparent in these discussions (Charmaz, 2000) Although the primary researcher conducted all 10 focus groups, as an external member of the health institution, she gained rapport and trust with participants since she received academic and research support (e.g., ) from hospital administration. Two resear chers conducted in depth analysis of the dat a transcripts and two additional researchers assisted in the development of the model confirming the influence of cultural or social processes evident in various constructs; however, we recognize that

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76 the data may be uniquely analyzed and interpreted in multiple ways (Miles & Huberman, 1994) Conclusions This study identified how the intrinsic and extrinsic factors in fluenced the decision making process among HCWs to adhere to M. tuberculosis infection c ontrol practices in two DR health M. tuberculosis transmission. HCWs proposed six categories of institutional and nationa l recommendations, such as education and training; policy; infrastructure; economic considerations; research; and political considerations. By identifying reasons behind th e future evidence based strategies can be combined with HCWs perceived recommendations to empower HCWs to strengthen M. tuberculosis i nfection control strategies employing interventions to reduce nosocomial M. tuberculosis transmission in DR health institutions.

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77 T able 4 1. Demographic and administrative variables of the two selected tertiary level h ealth institutions in the Dominican Republic 201 5 Hospital A Hospital B Demographic City San Pedro de Macors Santiago de los Caballeros Population (2010) 290,458 963,422 General Hospital classification Regional Regional Year opened 1999 1978 Annual number of admissions 10,422 1 7 648 Annual number of emergency visits 86,145 84 529 Annual number of consultations 96,469 1 28 999 Number of hospital beds 190 418 Medical training programs Number of medical specialty programs 3 10 Number of medical subspecialty programs 0 13 Tuberculosis Number of reported cases with respiratory symptoms 1, 299 389 Number of reported TB cases diagnosed at center Patients 30 15 Healthcare workers 1 2 Number of reported MDR TB cases diagnosed at center Patients 2 0 Healthcare workers 0 0 Presence of TB isolation area Internal Medicine ward No No Intensive Care Unit No No Abbreviations: MDR = multidrug resistant; TB = tuberculosis [ Data provided by the Dominican Republic Ministry of Health National Department of Statistics, National Tuberculosis Program, and Hospital s A and B]

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78 Table 4 2 Demographic characteristics of the study participants of the focus group discussions # Hospital Sex Age Length of Institution al E mployment (yrs) Profession Department Role 1 A F 27 3 Physician Emergency Third year resident 2 A F 26 3 Physician Emergency Third year resident 3 A F 26 2 Physician Emergency Second year resident 4 A F 30 2 Physician Emergency Second year resident 5 A F 28 3 Physician Family Medicine Third year resident 6 A F 29 3 Physician Family Medicine Third year resident 7 A F 28 3 Physician Family Medicine Third year resident 8 A F 26 3 Physician Family Medicine Third year resident 9 A F 24 5 Nurse Emergency Associate level nurse 10 A F 59 30 Nurse Emergency Bachelor level nurse 11 A F 49 16 Nurse Emergency Bachelor level nurse 12 A F 49 22 Nurse Emergency Bachelor level nurse 13 A F 47 8 Nurse Emergency Bachelor level nurse 14 A F 40 16 Nurse Emergency Associate level nurse 15 A M 28 3 Physician Emergency Third year resident 16 A M 28 3 Physician Emergency Third year resident 17 A M 26 3 Physician Family Medicine Third year resident 18 A M 26 3 Physician Family Medicine Third year resident 19 A M 33 3 Nurse Internal Medicine Certificate level nurse 20 A M 25 7 Nurse Emergency Bachelor level nurse 21 B F 29 2 Physician Emergency Second year resident 22 B F 31 2 Physician Emergency Second year resident 23 B F 32 2 Physician Emergency Second year resident 24 B F 29 3 Physician Emergency Third year resident 25 B F 58 28 Nurse Internal Medicine Bachelor level nurse 26 B F 52 27 Nurse Internal Medicine Bachelor level nurse 27 B F 48 6 Nurse Internal Medicine Bachelor level nurse

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79 Table 4 2. Continued # Hospital Sex Age Length of Institutional Employment (yrs) Profession Department Role 28 B F 28 1 Nurse Emergency Bachelor level nurse 29 B M 51 19 Nurse Emergency Certificate level nurse 30 B M 28 10 Nurse Emergency Certificate level nurse 31 B M 47 22 Nurse Emergency Certificate level nurse 32 B M 35 5 Nurse Emergency Bachelor level nurse 33 B M 30 2 Physician Emergency Second year resident 34 B M 30 2 Physician Emergency Second year resident 35 B M 35 3 Physician Emergency Third year resident 36 B M 34 3 Physician Emergency Third year resident 37 B M 27 3 Physician Internal Medicine Third year resident 38 B M 30 2 Physician Internal Medicine Second year resident 39 B M 26 3 Physician Internal Medicine Third year resident 40 B M 35 3 Physician Internal Medicine Third year resident

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80 Figure 4 1. Conceptual model that presents the healthcare workers decision making process in the application of M ycobacterium tuberculosis (MTB) infection control measures in clinical practice, influencing the Abbreviations: TB=tuberculosis ; WHO=World H ealth Organization

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81 Table 4 3 H ealthcare workers roposed recommendations to improve M ycobacterium tuberculosis infection control measures at institutional and national level s Rec ommendation Institutional level National level Education and Training 1. Develop orientation training seminars for new employees and hospitalized patients: a) TB disease, diagnosis and management b) I mportance for treatment adherence c) F actors about TB as social disease and associated stigma 2. Implement daily health campaigns to educate patients and families about TB disease and importance for treatment adherence 3. Initiate regular and active training programs and workshops for non clinical and clinical HCWs to critic ally analyze and reflect on current TB health burden 1. Verify that all HCWs receive regular continuing education programs 2. Promote national TB educational campaigns for the public through daily programming on media sources ( e.g., television, radio, social media) and transportation services ( e.g., bus, public cars, taxi) 3. Develop a health education television or radio channel or require channels to promote one hour of health education topics (e g educational announcements on commer cial breaks) 4. Implement monthly community education campaigns ( e.g., seminars, activities) in primary, secondary and postsecondary institutions 5. Form relationships with community centers (e g Junta de Vecino) and local industries for participation in TB he alth promotion activities 6. Prioritize the role of family physicians at primary health centers to improve TB diagnosis and management in communities

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82 Table 4 3 Continued Recommendation Institutional level National level Policy 1. Continue surveillance program with patients who have respiratory symptoms > 2 weeks 2. Complete appropriate diagnostic work up ( e.g., smears, cultures) for suspected TB patients in an adequate time frame without time lapse 3. Strengthen psychological support for patients and familie s during TB management 4. Require orientation and annual periodic health evaluations for HCWs 5. Assign one HCW to each specific clinical area to supervise HCWs and patients, observe compliance with TB infection control measures, and verify sufficient supply o f disposable materials 6. Designate one HCW to maintain hygiene and disinfection in emergency and hospital wards 7. Increase number of HCWS in clinical areas and reduce cumulative work hours 8. Implement disciplinary acts in the form of sanctions, salary discount, or firing for HCWs who fail to adhere to TB infection control measures 1. Require orientation and annual medical evaluations for HCWs and employees of high risk industries 2. Form national s upervisory teams to observe HCW adherence to TB infection control measures across all health institutions 3. Strengthen links between primary health centers and hospitals in order to improve TB case finding, refer patients as needed, or manage DOTS Infrastr ucture 1. Build TB isolation ward to meet capacity 2. Confirm that clinical areas have adequate ventilation 3. Evaluate the quality of disposable resources ( e.g., type of mask, gloves) for infection control 4. Require monthly reports from each department to identify necessary provisions of disposable materials and equipment for TB management 1. Develop TB isolation wards at select hospitals to manage suspected TB patients 2. Build various regional centers to specifically care for patients with respiratory diseases

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83 Table 4 3 Continued Recommendation Institutional level National level Economic considerations 1. Assign an administrative personnel or team to develop fundraising campaigns for disposable materials and equipment (e g telethons, medical outreach) 2. Request sponsor ship from private companies 1. Request that the Ministry of Health increases the annual health budget for tertiary level health institutions 2. Educate national health authorities about high national TB burden and need to meet MDGs 3. Increase Gross Domestic Product allocated for health expenditure Research 1. Develop epidemiologic studies in private and public sectors to examine TB incidence in health institutions and geographic regions 2. Design baseline studies that can provide a framework for future TB research: a) I dentify barriers in continued healthcare service delivery b) I nfluence of stigma and discrimination c) I mpact of social determinants of health Political considerations 1. Decentralize politics from the health system where no politician ( e.g., physician or non physician) should direct the health system Abbreviations: DOTS=directly observed t reatment, short course; HCW=healthcare worker; MDG=Millennium Development Goals ; T B=tuberculosis

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84 CHAPTER 5 CONCLUSIONS, IMPLICATIONS AND FU TURE RESEARCH Con tributions of the Dissertation Globally, n osocomial M. tuberculosis transmission has been recognized as a major challenge for healthcare workers (HCWs) in health institutions in low and high resource settings. However, since M. tuberculosis infection control measures are not universally implemented in health institutions, the occupational exposure of HCWs continues to be overlooked In the Dominican Republic (DR), health leaders recognize the high national tuberculosis (TB) burde n and have focused public health efforts on TB diagnosis, treatment and prevention in the general community as well as high risk groups such as immunocompromised marginalized and incarcerated populations. However, in o rder to continue TB control efforts t o ward TB elimination, more action is obligatory. This p aradigm shift in TB control will need to prioritize measures that maximize the adherence to M. tuberculosis infection control measures and ultimately reduce nosocomial transmission in health institutio ns. This thesis provides a comprehensive overview of intrinsic and extrinsic factors that limit the application of M. tuberculosis infection control strategies in clinical practice, and thus influencing among HCWs We provide evi dence that HCWs expressed feelings of powerlessness to prevent nosocomial M. tuberculosis transmission in clinical practice. Notably, we identify that intrinsic and extrinsic factors strongly influence how HCWs decide to apply these infection control measures in the clinical setting. Since HCWs represent a high risk group for increased risk of M. tuberculosis infection in their daily workplace TB elimination will not be complete without reducing risk of nosocomial transmission among HCWs and patients in health

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85 institutions. We describe the implications of our results for TB infection control efforts in DR health institutions. We also discuss future directions that implement specific initiatives to inform health authorities and motivate them to take app ropriate and prompt action to reduce risk of nosocomial M. tuberculosis transmission in the DR. Implications of Nosocomial Tuberculosis Transmission in Healthcare Workers N osocomial M. tuberculosis transmission in HCWs has and will continue to challenge health institutions in their implementation and monitoring of infection control practices. Although transmission of the M. tuberculosis Beijing strain has been infrequently r eported in Latin America (Institut Pasteur de la Guadeloupe, 2011; Ritacco et al., 2008) the attention to pathogen infectiousness and drug resistance takes precedence in nosocomial transmission in health institutions. A lthough our first study reported that pulmonary cavitation was not significantly associated with infection with the M. tuberculosis Beijing strain in a low incidence area like t he United States, it is imperative to understand the clinical and epidemiologic characteristics of drug susceptible and drug resistant M. tuberculosis strains. With no active national surveillance system to robustly seek HCWs who have M. tuberculosis infection or di sease in real time measure (Nsubuga et al., 2006) DR health authorities rely on passive surveillance strategies that monitor TB diagno ses, treatment regimens and deaths by institutional reports. As such, by investing in an active national surveillance system with electronic database that links each health institution to the National TB Program (NTP), TB cases can be documented rapidly an d timely, and thus provide insight into institutional health priorities as well as motivate health leaders to take clinical action to ward effective TB control.

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86 Historically, it is recognized that HCWs have had a positive image to serve others in need, prom oting selfless and altruistic actions in clinical practice (Rhodes, Morris, & Lazenby, 2011; White, 2002) In addition, patient advocacy can be an essential element mpower their physical and emotional health during their short or long term recuperation (Gaylord & Grace, 1995; N egarandeh, Oskouie, Ahmadi, Nikravesh, & Hallberg, 2006) This dissertation provides evidence that HCWs identified strongly with their vocation and desire to deliver high quality healthcare services to patients, regardless of their ability to apply M. t uberculosis infection control measures. However, combined with their feelings of powerlessness in clinical practice, whether due to intrinsic factors such as erroneous perceptions about their risk of M. tuberculosis transmission due to their previous histo ry of Bacillus Calmette Gurin (BCG) vaccine or habitual occupational exposure or extrinsic factors such as absence of isolation wards, health authorities will be unable to markedly reduce M. tuberculosis transmission in health institutions. For this reaso n, by addressing the factors employee health programs can educate HCWs about the important links between patient advocacy to care for their physical and emotional health and well being and use of M. tuberculosi s infection control measures in clinical practice. Future Directions This study has the potential to serve as a framework for future studies that focus on implementing surveillance systems for TB infection control measures, addressing powerlessness and limits of education programs for HCWs a nd appl ying interventions that empower HCWs in their clinical duties. Furthermore, it is imperative to note that these three focus areas must accompany and complement the structural modif ications

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87 and repair of the described extrinsic limitations such as physical infrastructure and institutional policies. Implementing S urveillance Systems for Tuberculosis Infection Control Measures In our study, we document ed that no active national survei llance system exist ed for the timely report of HCWs who develop TB infection or disease or who adhere to M. tuberculosis infection control measures The only national evidence that identifie d th e risk of th is occupational health threat reported that 116 HC Ws employed at selected tertiary level health institutions developed TB disease between 2005 and 2012 (Genao & Rodrguez, 2013) However, passive national surveillance systems will not be enough to promptly identify TB cases At the same time, the deficiency of process surveillance systems (Baker, 1997; Friedman, Richter, Skylis, & Brown, 1984) to observe and monitor adherence to infection control measures will not identify inadequate clinical practices that increase occupational risk of M. tuberculosis exposure By investing in an electronic database that connects each local health institution with the NTP, data from active surveillance systems can be reviewed immediately to identify local and national statistics of TB incidence and process surveillance systems can adherence to infection control measures. In effect, HCWs may be empowered in their pr ofessional autonomy and clinical decision making and use of M. tuberculosis infection control practices. Addressing Powerlessness and Limits of Education Programs Although no regular continuing education programs about TB are provided to HCWs in the DR o ur study show ed that the concept of powerlessness was the central theme that hindered how HCWs were able to use available resources and adhere to M. tuberculosis infection control measures. One traditional approach, which can be

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88 inaccurately perceived as all encompassing for long term behavioral changes, includes the sole implementation of continuing education programs. Short term educational interventions kn owledge about inappropriate antibiotic prescribing practices (Iglesias et al., 2015) and dengue fever (Doblecki Lewis et al., 2016) ; however, these short ter m studies did not follow the participants to assess the long lasting effects of the educational intervention on clinical practices. Nonetheless, since the health sciences represent a dynamic field, clinicians who do not remain up to date on revisions in cl inical practice guidelines will be at a disadvantage, placing themselves at risk of nosocomial disease transmission and failing to provide high quality healthcare services to their patients. This is the current scenario in the DR, where clinicians are not required to maintain license re certifications or complete additional education program credits (Iglesias et al., 2015) Nevertheless, regular continui ng education programs in health institutions, where programmed topics are relative to the institutional health priorities in service delivery, such as TB, only influence intrinsic factors (e.g., knowledge) related to adhere to recommended M. tuberculosis infection control measures Inevitably, t hey do not guarantee short or long term behavioral changes and ultimately fail to completely address the overall context of powerlessness expressed by HCWs. Therefore, f uture steps should address th e interplay between intrinsic and extrinsic factors and empower HCWs in their adherence to M. tuberculosis infection control measures Applying Interventions to Empower Healthcare Workers in Clinical Duties Our results describe d that HCWs feel powerless in their ability to use recommended M. tuberculosis infection control measures in their clinical duties. They shared feelings of being devalued as HCWs, noting that health authorities did not

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89 appear to prioritize their physical and mental health by implementing regular medical evaluations for HCWs Previous studies have recognized this concept of powerlessness as a significant barrier in clinical practice (Gask, 2004; Kuokkanen & Leino Kilpi, 2001; Lipman, 2000; Norrish & Rundall, 2001) ; however, to our knowledge, we have not identified studies that examine the concept of powerlessness as a barrier to the application of clinical knowledge to infection control practices. With the antithesis of powerlessness as empowerment, we can devel op interventions that target the three components of empowerment workplace environment, psychological well being and social relationships (Manojlovich, 2007) Even empowering patient provider r elationships as well as individual autonomy can improve communication and overall confidence in the decision making process (Entwistle, Carter, Cribb, & McCaffery, 2010) Since HCWs observed key deficiencies in M. tuberculosis infection control practices in their workplace environment and proposed recommendations for improved TB control at institutional and national levels, it is imperative to consider their real world clinical experiences and observations. Thus, by synthesizing their proposed recommendations with established evidence based practices noted to increase adherence to M. tuberculosis infection control measures, new interventions can target one or more of the specific intrinsic and extrinsic factors that limit adherence. In effect, HCWs can regain the feeling of empowerment to apply M. tuberculosis infection control measures to clinical practice, while playing an active role in reducing nosocomial M. tuberculosis transmission in their health institutions.

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90 Finally, the concept of powerlessness emerg ed during the data collec tion and analysis phases of this study, M. tuberculosis infection control measures in this theoretical framework. Since our study sample included p hysicians and nurses who were employed at thre e tertiary level health institutions in three DR cities, future studies can validate this framework among HCWs who are employed in health institutions in other environments (e.g., rural geographies, low or intermediate TB burden countries primary or seco ndary level health institutions). Further evaluation can confirm if the described intrinsic and extrinsic factors related to the concept of powerlessness are consistent with this study and thus can be generalized across multiple locations. Conclusion This dissertation contributes to the understanding of the impact of M. tuberculosis infectiousness and application of TB infection control measures to occupational M. tuberculosis exposure in health institutions. We provide evidence that eive powerlessness, driven by significant limitations at the individual and institutional levels, which hinder their adherence to M. tuberculosis infection control practices, and thus influenc es

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91 APPENDIX A INTERVIEW GUIDE FOR SEMI STRUCTURED INTERVIEWS 1) Please describe your experiences with TB disease at your health center. 2) Please describe your experiences with TB infection at your health center. 3) How would you describe the communicability of TB? 4) What preventive practices do you use for patients with suspected TB? 5) What clinical management strategies do you use when caring for patients with suspected TB? 6) How would you describe the effectiveness of DOTS? 7) How do believe that patients cope with the TB t reatment via DOTS? 8) If a healthcare worker was diagnosed with TB infection, how would he or she cope during the isoniazid preventive therapy via DOTS? 9) If you were diagnosed with TB infection, how would you cope during the isoniazid preventive therapy v ia DOTS? Abbreviations: DOTS = directly observed treatment short course ; TB = tuberculosis

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92 APPENDIX B INTERVIEW GUIDE FOR FOCUS GROUP DISCUSSIONS Barrier 1: S ense of invincibility of HCWs 1) Why do you think that HCWs perceive that they had a low susceptibility to TB exposure? 2) How does this affect your adherence to use TB infection control measures in clinical practice? a) What is your understanding of how your previous history of BCG vaccination has protected you? b) How has the duration of you r employment at this health center affected your susceptibility to develop TB disease or infection? c) Some HCWs state that they do not want to transmit TB to their families, but report that they do not consistently adhere to TB infection control measures. Why do you believe that this disconnect exists in their adherence to TB infection control measures? 3) Related to these described perceptions of low susceptibility to TB exposure, what do you believe can be done to improve adherence to TB prevention and control measures in this health center? Barrier 2: Personal beliefs of HCWs related to direct patient communication 4) How do you believe that the personal beliefs of HCWs at this health center affect their ability to adhere to TB infection control measu res? a) Probe: Why do you believe that HCWs would express that their spiritual faith may play a role in adherence to TB infection control measures? b) Why do you believe that HCWs preferred to avoid close contact with patients as a protective measure, rath er than using a protective mask? c) Why do you believe that HCWs believed that patient education in disease management is the main strategy for personal protection from TB exposure? 5) Related to these described personal beliefs related to direct patient communication, what do you believe can be done to improve adherence to TB prevention and control measures in this health center? Barrier 3: Low provider to patient ratio at health centers 6) How do you believe that your provider to patient ratio impacts your ability to adhere to TB infection control measures at this health center? a) Do you feel challenged in your ability to follow TB infection control measures? 7) Please describe the characteristics of patients that may influence your adherence to TB i nfection control measures. a) Probe: Which types of patients do you believe may influence your ability to adhere to TB infection control measures? 8) Related to the challenges encountered with a low provider to patient ratio at this health center, what do you believe can be done to improve adherence to TB prevention and control measures in this health center?

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93 Barrier 4: Absence of TB isolation units for patients within health centers 9) Please describe how the absence of patient isolation units impacts y our ability to adhere to TB infection control measures? a) Probe: How do you believe that your limited ability to separate patients with suspected TB from other pathologies impacts your ability to adhere to TB infection control measures? 10) Related to th e absence of TB isolation units for patients at this health center, what do you believe can be done to improve adherence to TB prevention and control measures in this health center? Barrier 5: Limited availability of protective masks for HCWs 11) Please describe how the availability and type of protective mask impact your ability to adhere to TB infection control measures? a) Probe: Do you believe that your perceived level or protection with protective masks impacts your ability to adhere to TB infection control measures? 12) Related to this limited availability of protective masks, what do you believe can be done to improve adherence to TB prevention and control measures in this health center? Conclusions 13) What do you believe can be done to improve adherence to TB prevention and control measures in the Dominican Republic? 14) Is there anything else that you would like to add? Abbreviation s : BCG = Bacillus Calmette Gurin ; HCW = healthcare worker; TB = tuberculosis

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94 LIST OF REFERENCES Rodrigues, L. C. (2013). Systematic review and meta analysis of the current evidence on the duration of protection by bacil lus Calmette Gurin vaccination against tuberculosis. Health Technology Assessment (Winchester, England) 17 (37), 1 372, v vi. https://doi.org/10.3310/hta17370 Allix Bguec, C., Harmsen, D., Weniger, T., Supply, P., & Niemann, S. (2008). Evaluation and St rategy for Use of MIRU VNTRplus, a Multifunctional Database for Online Analysis of Genotyping Data and Phylogenetic Identification of Mycobacterium tuberculosis Complex Isolates. Journal of Clinical Microbiology 46 (8), 2692 2699. https://doi.org/10.1128/J CM.00540 08 Alp, E., Leblebicioglu, H., Doganay, M., & Voss, A. (2011). Infection control practice in countries with limited resources. Annals of Clinical Microbiology and Antimicrobials 10 36. https://doi.org/10.1186/1476 0711 10 36 Baker, O. G. (1997 ). Process surveillance: An epidemiologic challenge for all health care organizations. American Journal of Infection Control 25 (2), 96 101. https://doi.org/10.1016/S0196 6553(97)90034 1 Barbour, R. S. (2005). Making sense of focus groups. Medical Educati on 39 (7), 742 750. https://doi.org/10.1111/j.1365 2929.2005.02200.x Baussano, I., Nunn, P., Williams, B., Pivetta, E., Bugiani, M., & Scano, F. (2011). Tuberculosis among health care workers. Emerging Infectious Diseases 17 (3), 488 494. https://doi.org/ 10.3201/eid1703.100947 Bekker, L. G., & Wood, R. (2010). The Changing Natural History of Tuberculosis and HIV Coinfection in an Urban Area of Hyperendemicity. Clinical Infectious Diseases 50 (Supplement 3), S208 S214. https://doi.org/10.1086/651493 Berna rd, H. R. (2011). Research methods in anthropology: qualitative and quantitative approaches (5th ed.). Lanham, Maryland: AltaMira Press. Bifani, P. J., Mathema, B., Kurepina, N. E., & Kreiswirth, B. N. (2002). Global dissemination of the Mycobacterium tuberculosis W Beijing family strains. Trends in Microbiology 10 (1), 45 52. tuberculosis and the amplificati on dynamics of drug resistance. Nature Medicine 10 (10), 1111 1116. https://doi.org/10.1038/nm1102

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97 Drobniewski, F., Balabanova, Y., Nikolayevsky, V., Ruddy, M., Kuznetzov, S., resistant tuberculosis, clinical virulence, and the dominance of the Beijing strain family in Russi a. JAMA 293 (22), 2726 2731. https://doi.org/10.1001/jama.293.22.2726 Dye, C., & Floyd, K. (2006). Tuberculosis. In D. T. Jamison, J. G. Breman, A. R. Disease Control Priorities in Develo ping Countries (2nd ed.). Washington (DC): World Bank. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK11724/ Engel, N., & Pai, M. (2013). Tuberculosis diagnostics: why we need more qualitative research. Journal of Epidemiology and Global Health 3 (3) 119 121. https://doi.org/10.1016/j.jegh.2013.04.002 Entwistle, V. A., Carter, S. M., Cribb, A., & McCaffery, K. (2010). Supporting Patient Autonomy: The Importance of Clinician patient Relationships. Journal of General Internal Medicine 25 (7), 741 745. https://doi.org/10.1007/s11606 010 1292 2 Espinal, M. A., Bez, J., Soriano, G., Garcia, V., Laszlo, A., Reingold, A. L., & Sanchez, S. (1998). Drug resistant tuberculosis in the Dominican Republic: results of a nationwide survey. The International Journ al of Tuberculosis and Lung Disease 2 (6), 490 498. European Concerted Action on New Generation Genetic Markers and Techniques for the Epidemiology and Control of Tuberculosis. (2006). Beijing/W genotype Mycobacterium tuberculosis and drug resistance. Emerging Infectious Diseases 12 (5), 736 743. https://doi.org/10.3201/eid1205.050400 Farmer, P. E. (2013). Shattuck Lecture. Chronic infectious disease and the future of health care delivery. The New England Journal of Medicine 369 (25), 2424 2436. https://doi.org/10.1056/NEJMsa1310472 Kreisworth, B. N. (1996). A multi institutional outbreak of highly drug resistant tuberculosis: epidemiology and clinical outc omes. JAMA 276 (15), 1229 1235. Friedman, C., Richter, D., Skylis, T., & Brown, D. (1984). Process surveillance: Auditing infection control policies and procedures. American Journal of Infection Control 12 (4), 228 232. https://doi.org/10.1016/0196 6553(8 4)90113 5 Gadkowski, L. B., & Stout, J. E. (2008). Cavitary pulmonary disease. Clinical Microbiology Reviews 21 (2), 305 333, table of contents. https://doi.org/10.1128/CMR.00060 07

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104 Sun, Y. J., Lim, T. K., Ong, A. K. Y., Ho, B. C. H., Seah, G. T., & Pat on, N. I. (2006). Tuberculosis associated with Mycobacterium tuberculosis Beijing and non Beijing genotypes: a clinical and immunological comparison. BMC Infectious Diseases 6 105. https://doi.org/10.1186/1471 2334 6 105 Thamlikitkul, V. (2006). Bridging the gap between knowledge and action for health: Case studies. Bulletin of the World Health Organization 84 (8), 603 607. Immunization summary (p. 226). United nd. Retrieved from http://www.unicef.org/immunization/files/EN ImmSumm 2013.pdf (2015). Why healthcare workers are sick of TB. International Journal of Infectious Dis eases: IJID: Official Publication of the International Society for Infectious Diseases 32 147 151. https://doi.org/10.1016/j.ijid.2014.12.003 Wang, J. Y., Lee, L. N., Yu, C. J., Chien, Y. J., Yang, P. C., & Tami Group. (2009). Factors influencing time t o smear conversion in patients with smear positive pulmonary tuberculosis. Respirology (Carlton, Vic.) 14 (7), 1012 1019. https://doi.org/10.1111/j.1440 1843.2009.01598.x Weston, M. J. (2010). Strategies for Enhancing Autonomy and Control Over Nursing Practice Open Access Library. The Online Journal of Issues in Nursing 15 (1). White, K. (2002). Nursing as vocation. Nursing Ethics 9 (3), 279 290. World Health Organizati on. (1999). Guidelines for the prevention of tuberculosis in health care facilities in resource limited settings Geneva, Switzerland: World Health Organization. World Health Organization. (2014). Global Tuberculosis Report 2014 (p. 171). Geneva, Switzerl and: World Health Organization. Retrieved from http://reliefweb.int/report/world/global tuberculosis report 2014 World Health Organization. (2015). Global Health Observatory data repository: Tuberculosis. Retrieved July 1, 2016, from http://apps.who.int/g ho/data/node.main.1315?lang=en World Health Organization. (2016a). Global Tuberculosis Report 2016 (p. 201). Geneva, Switzerland: World Health Organization. Retrieved from http://www.who.int/tb/publications/global_report/en/

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105 World Health Organization. (2016b). Tuberculosis country profile: Dominican Republic, 2014 World Health Organization. Retrieved from https://extranet.who.int/sree/Reports?op=Replet&name=%2FWHO_HQ_Reports %2FG2%2FPROD%2FEXT%2FTBCountryProfile&ISO2=DO&LAN=EN&outtype =html World Health Organization. (2016c). Tuberculosis country profile: Dominican Republic, 2015 World Health Organization. World Health Organization. (2016d). Tuberculosis country profile: Haiti, 2015 Retrieved from https://extranet.who.int/sree/Reports?op=Replet&name=% 2FWHO_HQ_Reports %2FG2%2FPROD%2FEXT%2FTBCountryProfile&ISO2=HT&LAN=EN&outtype= html Yoder, M. A., Lamichhane, G., & Bishai, W. R. (2004). Cavitary pulmonary tuberculosis: The Holy Grail of disease transmission. Current Science 86 (1), 74 81. and Risk Factors for Latent Tuberculosis Infection among Health Care Workers in China: A Cross Sectional Study. PloS One 8 (6), e66412. https://doi.org/10.1371/journal.p one.0066412 Zumla, A., Raviglione, M., Hafner, R., & von Reyn, C. F. (2013). Tuberculosis. The New England Journal of Medicine 368 (8), 745 755. https://doi.org/10.1056/NEJMra1200894

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106 BIOGRAPHICAL SKETCH Helena Jeanne Chapman graduated from the Department of Environmental and Global Health in the College of Public Health and Health Professions at the University of Florida. She serve d as a graduate research assistant at the Southeastern National Tuberculosis Center in the Division of Infectious Di seases and Global Medicine in the College of Medicine at the University of Florida. Helena earned her Doctor of Medicine from the Iberoamerican University in Santo Domingo Dominican Republic, and Master of Public Health in Epidemiology and Bachelor of Scie nce in Biology from the University of Florida. She also completed a three week cross cultural training in tuberculosis Cuba. Prior to her doctoral studies in public health she completed a one year post graduate internship at the Centers for Diagnosis, Advanced Medicine and Telemedicine (CEDIMAT) in Santo Domingo, Dominican Republic. She also served as adjunct professor at the Iberoamerican University School of Medicine and taught courses in Evidence based Medicine and Preventive Medicine and Public Health. She also was founding member and first President of the first national (non governmental) medical student organization (Organizacin Dominicana de Estudiantes de Medicina ODEM) in the Dominican Republic. Her leadership in medicine and community health has been recognized through awards, presentations, and peer and non peer reviewed publications at the local, national and international levels. include the use of qualitative research methods to evaluate public health practices of clinical and community programs in the prevention and control of infectious diseases.