SHANNON-DISSERTATION-2016.Pdf

DETERMINANTS OF MALARIA IN THE CHITTAGONG HILL DISTRICTS OF BANGLADESH By Kerry Lee Shannon, MPH A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Public Health Baltimore, Maryland December, 2015 © 2015 Kerry Lee Shannon All Rights Reserved Abstract Objective: This dissertation focuses on understanding the epidemiology of malaria in the Chittagong Hill Districts of Bangladesh, with particular focus on the genetic, seasonal, geographic, demographic and behavioral factors that influence symptomatic and asymptomatic malaria. Methods: The data for this analysis comes from a longitudinal cohort study of approximately 24,000 people that began in October 2009 in an area of Bandarban District of Bangladesh covering an area of 179 km2. A series of detailed surveys were conducted encompassing symptomatic, uncomplicated or asymptomatic malaria; demographics of the population; knowledge and practices related to malaria, hemoglobin E, geographic locations and environmental factors. Results: This dissertation demonstrates a number of risk factors for malaria. Homozygous, but not heterozygous, Hemoglobin E was shown to be associated with an increase in mild clinical malaria infection. A detailed exploration of the epidemiology of sub-clinical P. falciparum infections demonstrated that they occur year-round, and account for the overwhelming majority of infections at any given time. An adjusted prevalence of sub-clinical infection based on active case finding and diagnosis by RDT and or microscopy was found to be 1.0% in the overall population and 3.2% in pregnant woman. The adjusted incidence was 32.9 (19.7-54.9) per 1,000 person-years. When examining incidence during pregnancy we found 19.4 (4.9-76.6) and 19.5 (8.8-43.11) per 1,000 person-years incidence among 15- to 39-year-old pregnant and recently pregnant women respectively compared to zero cases among non-pregnant 15- to 39-year-old women. Risk factors for asymptomatic malaria include pregnant women, males, jhum cultivators, those living closer to forests and at higher elevations, and marginally ii among 5- to 14-year-olds and day laborers. When comparing sub-clinical and symptomatic clinical P. falciparum infections we found that hotspots overlapped, but there were substantial differences. Conclusions: This study demonstrates a number of risk factors for both clinical and sub- clinical P. falciparum infections and describes when and where these infections are most likely to occur. This information can help to inform prevention and control programs, and to focus resources in areas and populations that are of high risk. iii Committee of Thesis Readers Thesis Readers: David Sack, MD; Advisor Professor, Department of International Health David Sullivan, MD; Professor, Department of Molecular Microbiology and Immunology Frank Curriero, PhD; Associate Professor, Department of Epidemiology Clive Shiff, PhD; Associate Professor, Department of Molecular Microbiology and Immunology Henry Perry, MD; Senior Scientist, Department of International Health Alternate Readers: Henry Mosley, MD; Professor – Emeritus, Department of Population, Family and Reproductive Health Steven Harvey, MD Assistant Professor, International Health iv Acknowledgements I would first like to thank my advisor, David Sack, for the immense support and guidance he provided over the last several years. He has always provided a depth of knowledge, kindness and humor combined with a deep understanding of communities, justice and health that that has come from years of research and public health practice. I consider myself fortunate to have had the opportunity to work with him. Secondly, multiple advisors to this project guided the analysis. In particular, the faculty lead investigator for the malaria cohort study, David Sullivan, provided an abundance of support and suggestions. I would also like to thank Frank Curriero for his extensive support in the spatial statistics for the third and fourth chapter of this thesis. I would like to thank Tim Shields for his support with collection of environmental and spatial data. Further, I would like to thank all members of my thesis and defense committees including David Sack, David Sullivan, William Moss, Frank Curriero, Clive Shiff and Henry Perry for taking the time to review, and provide feedback for this project. I would also like to thank Henry Mosley and Steven Harvey for their willingness to step in at a moment’s notice as alternate readers for this project. This research could not have happened without the support of the founding JHSPH faculty members for the JHMI malaria cohort study in Bangladesh, including David Sullivan, David Sack, Malathi Ram, Gregory Glass, Douglas Norris, Myaing Myaing Nyunt, Tim Shields and Malathi Ram as well as the collaborating faculty at icddr,b: Wasif Ali Khan, Md Zahirul Haq, Rashidul Haque, Alejandro Cravioto, and Md Shafiul Alam. There were also numerous collaborating scientists who were essential to the success of the study, including Sabeena Ahmed, Chai Shawi Prue, Jacob Khyang, Jasmin Akter and numerous field staff that did most of v the collection of data and management of cases in the community. I would like to thank all of them for their attention to detail and focus on collecting high-quality data for research while providing meaningful support to the community they serve. I would further like to thank the approximately 24,000 people who participated in this study, taking time to answer numerous surveys, provide blood for analysis, allowing for mosquito catching devises in their homes, among other things, in order for this research to be possible. I would also like to thank numerous other faculty who have served as mentors and advisors to me during graduate and medical school, including Shannon Doocy, Robert Lawrence, Justin Lessler, Rebecca Aslakson, David Cooke, John Flynn, William Checkley, David Dowdy and Henry Mosley. I would further like to thank my family and friends for their immense love and friendship during my training. I would like to thank both my fellow medical school classmates and fellow doctoral students for their friendship and invaluable advice over the years. I would like to thank my parents who have always encouraged me to work hard and push my limits, while exploring the world and developing skills to serve me in my career and life in general. They have also set examples of what it means to live a life in service to others, particularly communities struggling with poverty and other injustices. They have always been there at a moment’s notice, sacrificing much so that I could have the opportunities that have brought me to where I am today. I would like to thank my brother and sister-in-law for their friendship and love. Finally, I would like to thank my husband for his support and sacrifices, so that I could complete this challenging academic path. vi Support This project was carried out at a field area of the International Centre for Diarrhoeal Disease Research, Bangladesh, which receives unrestricted support from the governments of Bangladesh, Canada, the United Kingdom, Sweden, and Australia. This project was funded through a grant from the Johns Hopkins Malaria Research Institute. Additional funding to the icddr,b for this malaria research study was provided by United Kingdom’s Department for International Development (DFID) and the World Bank. Individual graduate support for Kerry Lee Shannon was provided by the Johns Hopkins Medical Scientist Training Program (MSTP) and the Johns Hopkins Bloomberg School of Public Health, Department of International Health. Travel to Bangladesh for fieldwork for Kerry Shannon was supported by a generous grant from the Johns Hopkins Center for Global Health. vii Table of Contents Abstract ......................................................................................................................................... ii Committee of Thesis Readers ...................................................................................................... iv Acknowledgements ........................................................................................................................ v Support ........................................................................................................................................ vii Table of Contents ....................................................................................................................... viii List of Tables ................................................................................................................................. xi List of Figures ............................................................................................................................. xii List of Acronyms ........................................................................................................................ xiii Chapter One: Introduction and Literature Review ................................................................... 1 1.1 Overview of Malaria ......................................................................................................................... 1 1.1.1 Global Disease Burden ................................................................................................................ 1 1.1.2 Clinical Presentation .................................................................................................................... 1 1.1.3 The Life Cycle of Malaria ..........................................................................................................

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