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A Case-Study Approach to Investigate Transmission, Co-Infection, And Louisiana State University LSU Digital Commons LSU Doctoral Dissertations Graduate School 5-20-2019 A Case-study Approach to Investigate Transmission, Co-infection, and Clinical Sequelae During Epidemics of Dengue and Ebola Virus Disease Jennifer Elizabeth Giovanni [email protected] Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_dissertations Part of the Clinical Epidemiology Commons, Epidemiology Commons, Immunology of Infectious Disease Commons, International Public Health Commons, and the Virology Commons Recommended Citation Giovanni, Jennifer Elizabeth, "A Case-study Approach to Investigate Transmission, Co-infection, and Clinical Sequelae During Epidemics of Dengue and Ebola Virus Disease" (2019). LSU Doctoral Dissertations. 4931. https://digitalcommons.lsu.edu/gradschool_dissertations/4931 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Doctoral Dissertations by an authorized graduate school editor of LSU Digital Commons. For more information, please [email protected]. A CASE-STUDY APPROACH TO INVESTIGATE TRANSMISSION, CO-INFECTION, AND CLINICAL SEQUELAE DURING EPIDEMICS OF DENGUE AND EBOLA VIRUS DISEASE A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy in The Department of Pathobiological Sciences by Jennifer Elizabeth Giovanni B.S., Missouri State University, 1994 M.P.H., Emory University, 2001 M.S.N., University of California, Los Angeles, 2011 August 2019 TABLE OF CONTENTS LIST OF TABLES ................................................................................................................................ iv LIST OF FIGURES .............................................................................................................................. vi LIST OF ACRONYMS AND ABBREVIATIONS ...................................................................................... vii ABSTRACT ........................................................................................................................................ ix CHAPTER I. INTRODUCTION TO THE RESEARCH AND REVIEW OF THE LITERATURE .......................1 CHAPTER II. CLINICAL SEVERITY AND IDENTIFICATION OF DIAGNOSTIC DISCRIMINATORS IN PATIENTS WITH DENGUE VIRUS MULTI-SEROTYPE INFECTIONS AND DENGUE VIRUS- LEPTOSPIRA CO-INFECTION, NORTE DE SANTANDER, COLOMBIA ..................25 CHAPTER III. INDIVIDUAL BEHAVIORS, SOCIAL PRESSURES, AND FAILURES OF EPIDEMIC CONTROL MEASURES THAT CONTRIBUTED TO TRANSMISSION OF ZAIRE EBOLAVIRUS AMONG GEOGRAPHICALLY-DISPERSED FAMILY MEMBERS, LIBERIA ........52 CHAPTER IV. CLINICAL SEQUELAE AND FUNCTIONAL DECLINE AMONG SURVIVORS OF EBOLA VIRUS DISEASE, BOMI COUNTY, LIBERIA ...................................................................73 CHAPTER V. SUMMARY OF RESULTS AND CONTRIBUTIONS TO PUBLIC HEALTH PRACTICE ..........88 APPENDIX A. HISTORY OF HUMAN EBOLAVIRUS OUTBREAKS, 1976-2014.....................................93 APPENDIX B. PUBLISHED REPORTS OF DENGUE VIRUS MULTI-SEROTYPE INFECTIONS, BY COUNTRY AND AUTHOR ..........................................................................................94 APPENDIX C. PATIENT-SPECIFIC FUNCTIONAL SCALE ..................................................................102 APPENDIX D. LSU IRB APPROVAL—DETERMINANT FACTORS OF VIRAL DIVERSITY AND TRANSMISSION ECOLOGY OF DENGUE VIRUS IN COLOMBIA ..................................103 APPENDIX E. COLOMBIA SEROPREVALENCE STUDY ADULT CONSENT AND PEDIATRIC ASSENT FORMS, ENGLISH AND SPANISH ...............................................................................104 APPENDIX F. CENTERS FOR DISEASE CONTROL AND PREVENTION DENGUE CASE REPORT FORM ......................................................................................................................112 APPENDIX G. ADULT AND PEDIATRIC CLINICAL LABORATORY REFERENCE RANGES .....................113 ii APPENDIX H. COLOMBIA SEROPREVALENCE SURVEY SAS CODE ...................................................115 APPENDIX I. COLOMBIA SEROPREVALENCE SURVEY RAW DATA ..................................................148 APPENDIX J. EBOLA VIRUS DISEASE STUDY IRB APPROVAL .........................................................151 APPENDIX K. POST-EBOLA VIRUS DISEASE STUDY CONSENT FORM .............................................152 APPENDIX L. FIELD INVESTIGATION NOTES, LIBERIA, JUNE 2015 ................................................154 APPENDIX M. HISTORY AND PHYSICAL EXAMINATION, HUSBAND, LIBERIA, 2015 ........................155 VITA ..............................................................................................................................................157 iii LIST OF TABLES TABLE 1. SEROPREVALENCE SURVEY DESCRIPTIVE DATA FOR DENGUE-POSITIVE AND NEGATIVE PATIENTS ....................................................................................................................... 33 TABLE 2. COMPARATIVE FREQUENCIES OF PRESENTING SYMPTOMS, FOR ALL ENROLLEES AND BY DENGUE VIRUS INFECTION STATUS .......................................................................... 34 TABLE 3. COMPARATIVE FREQUENCIES OF PRESENTING SYMPTOMS, DENGUE VIRUS SSIS AND MSIS .............................................................................................................................. 35 TABLE 4. MEAN HEMATOLOGIC INDICES, BY DENGUE VIRUS INFECTION STATUS ........................ 36 TABLE 5. BETWEEN-GROUP DIFFERENCES IN MEAN HEMOGLOBIN .............................................. 37 TABLE 6. PREDICTIVE MODELS OF LEUKOPENIA AND DENGUE VIRUS SEROTYPE 1 ....................... 38 TABLE 7. BETWEEN-GROUP DIFFERENCES IN MEAN PLATELET COUNTS ...................................... 38 TABLE 8. ASSOCIATION OF THROMBOCYTOPENIA WITH SEROTYPE-SPECIFIC INFECTION AND MULTI-SEROTYPE INFECTION ........................................................................................ 43 TABLE 9. ADULT MULTI-SEROTYPE INFECTIONS .......................................................................... 44 TABLE 10. PEDIATRIC DENGUE VIRUS MULTI-SEROTYPE INFECTIONS ........................................... 45 TABLE 11. PEDIATRIC MULTI-SEROTYPE INFECTIONS WITH DENGUE VIRUS SEROTYPES 2 AND 4.. 46 TABLE 12. DENGUE VIRUS TRIPLE-SEROTYPE INFECTION .............................................................. 47 TABLE 13. DENGUE VIRUS-LEPTOSPIRA SPP. CO-INFECTIONS ........................................................ 48 TABLE 14. DEMOGRAPHICS AND FREQUENCY OF CLINICAL SYMPTOMS, BY DRY AND WET PHASES OF ILLNESS ....................................................................................................... 60 TABLE 15. EPIDEMIC TRANSMISSION PARAMETER ESTIMATES, EBOLA VIRUS DISEASE FAMILIAL CLUSTER........................................................................................................................ 61 TABLE 16. DEMOGRAPHIC CHARACTERISTICS, TRANSMISSION EVENTS, SYMPTOMS, AND OUTCOMES, EVD CLUSTER .......................................................................................... 67 TABLE 17. ESTIMATIONS OF CASE-SPECIFIC INCUBATION AND INFECTIOUS PERIODS .................... 68 4 TABLE 18. HISTORY AND PHYSICAL EXAMINATION SUMMARIES, EVD SURVIVORS ........................ 75 TABLE 19. FUNCTIONAL ASSESSMENTS USING THE PATIENT-SPECIFIC FUNCTIONAL SCALE ......... 78 5 LIST OF FIGURES FIGURE 1. DENGUE VIRUS GENOME ............................................................................................... 4 FIGURE 2. NUMBER OF PUBLISHED REPORTS OF DENGUE VIRUS MULTI-SEROTYPE INFECTIONS, BY COUNTRY, 1985-2018................................................................................................................ 6 FIGURE 3. PHASES OF CLINICAL DENGUE, WITH CLINICAL SYMPTOMS AND LABORATORY CHANGES ....................................................................................................................... 7 FIGURE 4. FILOVIRUS GENOME STRUCTURE ................................................................................... 9 FIGURE 5. GEODISTRIBUTION OF HUMAN EBOLAVIRUS OUTBREAKS AND PUTATIVE BAT- RESERVOIR SPECIES, SUB-SAHARAN AFRICA .................................................................. 10 FIGURE 6. VIRAL LOAD KINETICS, DISTRIBUTION OF VIRUS IN BODY FLUIDS, AND ANTIBODY RESPONSE ..................................................................................................................... 13 FIGURE 7. REGIONAL MAP OF MEXICO, THE CARIBBEAN, AND NORTHERN LATIN AMERICA ........ 26 FIGURE 8. SEROPREVALENCE STUDY ENROLLMENT FLOWCHART, NORTE DE SANTANDER, COLOMBIA ................................................................................................................... 27 FIGURE 9. PATIENTS WITH DENGUE AND LEPTOSPIROSIS, BY MUNICIPALITY OF RESIDENCE ........ 32 FIGURE 10. MAP OF GUINEA, LIBERIA, AND SIERRA LEONE INTERNATIONAL BORDERS.................. 53 FIGURE 11. LOCATION OF ROADSIDE DRUGGIST, BOMI COUNTY, LIBERIA.................................... 56 FIGURE 12. EVOLUTION OF THE FAMILIAL CLUSTER OF EBOLA VIRUS DISEASE: DISEASE PROGRESSION AND EVENTS ........................................................................................ 58 FIGURE 13. COUNTY AMBULANCE AND CHLORINE SPRAYER, LIBERIA ............................................ 63 FIGURE 14. EBOLA VIRUS DISEASE FAMILIAL CLUSTER: TRANSMISSION EVENTS, SYMPTOM
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