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Effective Strategies Used to Describe and Address the Burden of Sickle Cell Disease in The

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Effective Strategies Used to Describe and Address the Burden of Sickle Cell Disease in The Effective strategies used to describe and address the burden of sickle cell disease in the Republic of Uganda: The Uganda Sickle Surveillance Study A thesis submitted to the Graduate School of the University of Cincinnati in partial fulfillment of the requirements for the degree of MASTER OF PUBLIC HEALTH (M.P.H.) in Epidemiology in the Division of Public Health Sciences of the Department of Environmental Health of the College of Medicine by Arielle G. Hernandez Bachelor of Arts (B.A.), University of Kansas, 2011 Committee: Ranjan Deka, Ph.D. Aimin Chen, M.D. Ph.D. Russell E. Ware, M.D. Ph.D. Patrick T. McGann, M.D. M.S. Effective strategies used to describe and address the burden of sickle cell disease in the Republic of Uganda: The Uganda Sickle Surveillance Study ABSTRACT Background Sickle cell disease (SCD) contributes substantially to childhood mortality in sub-Saharan Africa. In the Republic of Uganda, the number of annual SCD births and the geographical distribution of the disease burden are unknown. A partnership between the Uganda Ministry of Health, Makerere University College of Health Sciences, and Cincinnati Children’s Hospital Medical Center was established to design and conduct the Uganda Sickle Surveillance Study. Objective To describe the current prevalence and distribution of SCT and SCD in Uganda. The goals were to establish a partnership between academia and government, build local sickle cell laboratory capacity and determine the feasibility of testing a high-volume of samples for SCD, and create an accurate geospatial map of the SCD burden across Uganda. Methods A Sickle Cell Laboratory was constructed and outfitted, and local personnel were recruited and trained. Hemoglobin electrophoresis was performed by isoelectric focusing on dried blood spots already collected in the Ministry of Health’s Early Infant Diagnosis Program from HIV-exposed children over a one-year period, to identify and quantify the presence of sickle cell trait (SCT), SCD, and other hemoglobin variants. ii Effective strategies used to describe and address the burden of sickle cell disease in the Republic of Uganda: The Uganda Sickle Surveillance Study Results A total of 99,243 dried blood spots were tested between February 2014 and March 2015, with 97,631 results successfully obtained. The national prevalence of SCT was 13.3%, ranging from 4.6% in the South Western region to 19.8% in the East Central region, and the SCD prevalence was 0.7%, ranging from 0.2% in the South Western region to 1.5% in the East Central region. SCT was detected in all districts, with the highest prevalence being 23.9% in Alebtong district. Analysis by region revealed that the observed SCT prevalence positively correlated with published malaria prevalence. SCD was less common in children older than 12 months and those who were HIV-positive, consistent with early mortality and co-morbidity. Conclusions A successful North-South partnership joined academia and government to design and conduct an integrated national surveillance study, and to build local sickle cell laboratory capacity through training and program monitoring and evaluation. These successful strategies have positioned the Ministry of Health to begin to address the country’s high disease burden, and will motivate and prioritize efforts for improving the management of SCD in Uganda. iii Effective strategies used to describe and address the burden of sickle cell disease in the Republic of Uganda: The Uganda Sickle Surveillance Study iv Effective strategies used to describe and address the burden of sickle cell disease in the Republic of Uganda: The Uganda Sickle Surveillance Study ACKNOWLEDGMENTS There are many people who contributed to the story of the Uganda Sickle Surveillance Study and the completion of this thesis. First and foremost, I want to thank my mentor, Dr. Russell Ware. From day one, he has given me his time, support, and trust. Dr. Ware’s belief in me has been the ultimate motivator, and I am so grateful for the autonomy that demands creativity, cultivates profound learning, and pushes personal thresholds. I thank him for being a devoted teacher and for encouraging me to develop and invest in my own sickle cell education. I have come to deeply appreciate the complexities and far-reaching implications of this cause and research that I will dedicate my career to. The past four years have been a steep and rapid learning curve, and I am looking forward to many more years of working with and learning from Dr. Ware. I also want to thank my other committee members. I am very thankful to Dr. Patrick McGann, who is such a great teacher and friend who I look up to. Thank you to my Academic Advisor, Dr. Ranjan Deka, who has shared his expertise to foster my interest in population genetics and has always shown me great support and kindness. I also want to thank Dr. Aimin Chen, for his support throughout the MPH program. I am very grateful to my Ugandan colleagues for a wonderful research partnership and friendships that make the thousands of miles between Uganda and Ohio feel so much closer. Their dedication to their work and country is incredibly inspiring to witness. Finally, I want to thank my family for being a constant source of love and inspiration all my life. v Effective strategies used to describe and address the burden of sickle cell disease in the Republic of Uganda: The Uganda Sickle Surveillance Study TABLE OF CONTENTS Abstract ..................................................................................................................................ii Acknowledgments..................................................................................................................v List of Tables, Images, and Figures .......................................................................................viii I. Introduction ......................................................................................................................1 i. Background ..........................................................................................................1 ii. Problem Statement ...............................................................................................3 iii. Approach ..............................................................................................................5 II. Methods............................................................................................................................6 i. Partnership. ..........................................................................................................6 ii. Study Design ........................................................................................................7 iii. Sickle Cell Laboratory .........................................................................................8 iv. Data Management and Analysis ..........................................................................17 v. Monitoring and Evaluation ..................................................................................18 III. Results ..............................................................................................................................19 i. Partnership ...........................................................................................................19 ii. Sickle Cell Laboratory .........................................................................................21 iii. Program Assessment ............................................................................................23 iv. Surveillance Study ...............................................................................................25 v. Dissemination of Results .....................................................................................40 IV. Discussion ........................................................................................................................41 vi Effective strategies used to describe and address the burden of sickle cell disease in the Republic of Uganda: The Uganda Sickle Surveillance Study i. Goals ....................................................................................................................42 ii. Strengths, Limitations, and Challenges ...............................................................44 iii. Significance to Public Health ...............................................................................50 iv. Direction for Future Planning and Research ........................................................52 V. Institutional Review Board/Ethics Committee Approval ................................................55 VI. References ........................................................................................................................56 VII. Vita ...................................................................................................................................60 Appendix A: Isoelectric Focusing (IEF) Hemoglobin Electrophoresis Procedure ................61 Appendix B: Uganda Sickle Surveillance Study Program Assessment Plan ........................76 Appendix C: Uganda Sickle Surveillance Study Program On-Site Assessment Report .......83 Appendix D: Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study ...............................................................................................96 Appendix E: Is integrating sickle cell disease and HIV screening logical? ..........................103 Appendix F: Prevalence
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