University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2009 The epidemiology of La Crosse virus in Tennessee and West Virginia Andrew Douglas Haddow University of Tennessee Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Recommended Citation Haddow, Andrew Douglas, "The epidemiology of La Crosse virus in Tennessee and West Virginia. " PhD diss., University of Tennessee, 2009. https://trace.tennessee.edu/utk_graddiss/6044 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Andrew Douglas Haddow entitled "The epidemiology of La Crosse virus in Tennessee and West Virginia." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Doctor of Philosophy, with a major in Plants, Soils, and Insects. Reid R. Gerhardt, Major Professor We have read this dissertation and recommend its acceptance: Accepted for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduate School (Original signatures are on file with official studentecor r ds.) To the Graduate Council: I am submitting herewith a dissertation written by Andrew Douglas Haddow entitled “The Epidemiology of La Crosse Virus in the Tennessee and West Virginia.” I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Plants, Soils, and Insects. Reid R. Gerhardt, Major Professor We have read this dissertation and recommend its acceptance: Carl J. Jones John K. Moulton Agricola Odoi Daniel G. Mead Uriel Kitron Accepted for the Council: Carolyn R. Hodges, Vice Provost and Dean of the Graduate School The Epidemiology of La Crosse Virus in Tennessee and West Virginia A Dissertation Presented for the Degree of Doctor of Philosophy The University of Tennessee, Knoxville Andrew Douglas Haddow May 2009 Copyright © 2009 by Andrew Haddow All rights reserved. ii For My Parents iii ACKNOWLEDGEMENTS I wish to express my sincere gratitude for the continued support and guidance of my committee members: Reid R. Gerhardt, Department of Entomology and Plant Pathology, University of Tennessee; Carl J. Jones, Department of Entomology and Plant Pathology, University of Tennessee; Agricola Odoi, Department of Comparative Medicine, University of Tennessee; John K. Moulton, Department of Entomology and Plant Pathology, University of Tennessee; Daniel G. Mead, Department of Population Health, University of Georgia; and Uriel Kitron, Department of Environmental Studies, Emory University. This work would not have been possible without the love and support of my parents and sisters. I am indebted to Sabrina, Shannon, and my many friends who have offered their support and encouragement during this project. The author wishes to thank the Centers for Disease Control and Prevention, The Tennessee Department of Heath, and the West Virginia Department of Health and Human Resources for releasing La Crosse virus case data for this project. This research was funded in part by the Tennessee Department of Health, The University of Tennessee Agricultural Experiment Station, The Scholarly Activity and Research Incentive Fund from the University of Tennessee, Discover Life in America, and the Samuel Wendell Williston Diptera Research Fund, Smithsonian Institution. iv ABSTRACT La Crosse virus (LACV) was first recognized as a cause of pediatric viral encephalitis in the upper-Midwestern United States following its isolation from a fatal case of pediatric encephalitis in 1964. From that time, LACV infections have been reported in 24 states, with the number of reported cases increasing in recent years in the Appalachian region of the United States. Two states in Appalachia, West Virginia and Tennessee have both seen a large rise in the number of reported cases in recent years. To investigate the epidemiology of the LACV infections in the eastern United States, Tennessee, and West Virginia a combination of field and laboratory studies were initiated. These studies investigated the spatial and temporal patterns of disease risk and the biology and ecosystem dynamics of both indigenous and invasive disease vectors. Four distinct regional clusters of LACV infections were detected at the national level, as well as a higher incidence risk and case-fatality rate than previously reported. The exploration into the variations of risk using different at-risk populations and geographic scales revealed the possibility of missing disease clusters resulting from performing incidence risk investigations of focal diseases using inappropriate at-risk populations and/or large geographic scales. South-central West Virginia was found to be a focus of LACV transmission and in addition to having the highest incidence risk and case-fatality rate reported in the United States. In eastern Tennessee, Aedes albopictus was found to be the most abundant mosquito collected at all sites and vegetation types, by both CO2-baited CDC trapping and human landing catches. Results from the use of variable pressure scanning electron v microscopy to describe the egg of Aedes japonicus have provided more detailed information on characters of Aedini eggs, while bringing the number of more complete descriptions and micrographs of the micropyle and associated structures of the subgenus Finlaya to three. The results of these studies have provided a more complete understanding of the epidemiology of LACV and its associated vector species at both the national and state levels. These findings will help guide future research and intervention efforts to understand and prevent virus transmission. vi TABLE OF CONTENTS PREFACE ..................................................................................................................................................... 1 SECTION I: BACKGROUND AND LITERATURE REVIEW .............................................................. 3 CHAPTER I ............................................................................................................................................... 4 Background ........................................................................................................................................... 4 Introduction ....................................................................................................................................................... 4 Risk Factors ...................................................................................................................................................... 5 Vector Surveillance ........................................................................................................................................... 6 Prevalence ....................................................................................................................................................... 10 Clinical Studies ............................................................................................................................................... 12 Summary ......................................................................................................................................................... 13 CHAPTER II.............................................................................................................................................14 Literature Review .................................................................................................................................14 Virus ............................................................................................................................................................... 14 Genotypes ....................................................................................................................................................... 15 Virus Evolution ............................................................................................................................................... 15 Virus/Vector Relationship ............................................................................................................................... 17 Virus Isolations from Invertebrates ................................................................................................................. 17 Prototype Vector ............................................................................................................................................. 18 Accessory Vectors ........................................................................................................................................... 18 Virus/Host Relationship .................................................................................................................................. 19 Hosts ............................................................................................................................................................... 20 Geographic Distribution, Incidence, and Environmental Risk