Descriptive epidemiology characterizes health according to person place and time

Epidemiology for Public Health Practice Robert H. Friis, PhD Professor, Emeritus, and Chair Emeritus Health Science Department California State University Long Beach, California

Thomas A. Sellers, PhD, MPH Director Moffitt Cancer Center & Research Institute Tampa, Florida

FIFTH EDITION

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Library of Congress Cataloging-in-Publication Data Friis, Robert H. Epidemiology for public health practice / Robert H. Friis and Thomas Sellers.—5th ed. p. ; cm. Includes bibliographical references and index. ISBN 978-1-4496-5158-9 (pbk.) I. Sellers, Thomas A. II. Title. [DNLM: 1. Epidemiology. 2. Epidemiologic Methods. 3. Public Health. WA 105] 614.4—dc23

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New to This Edition ................................................... ix

Introduction ............................................................... xiii

Preface ........................................................................ xvii

Acknowledgments ...................................................... xix

About the Authors ............................................................ xxiii

Chapter 1 History and Scope of Epidemiology ........................... 1 Introduction ................................................................... 2 Epidemiology Defined .................................................... 8 Foundations of Epidemiology ......................................... 15 Historical Antecedents of Epidemiology ......................... 23 Recent Applications of Epidemiology ............................. 41 Conclusion ..................................................................... 48 Study Questions and Exercises ........................................ 49 References ....................................................................... 51

Chapter 2 Practical Applications of Epidemiology ..................... 55 Introduction ................................................................... 56 Applications for the Assessment of the Health Status of Populations and Delivery of Health Services .............. 59 Applications Relevant to Disease Etiology ....................... 83 Conclusion ..................................................................... 101 Study Questions and Exercises ........................................ 101 References ....................................................................... 104

Contents

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Chapter 3 Measures of Morbidity and Mortality Used in Epidemiology ......................................................... 107

Introduction ................................................................... 108 Definitions of Count, Ratio, Proportion, and Rate ......... 108 Risk Versus Rate; Cumulative Incidence ......................... 121 Interrelationship Between Prevalence and Incidence ....... 124 Applications of Incidence Data ....................................... 126 Crude Rates .................................................................... 126 Specific Rates and Proportional Mortality Ratio ............. 138 Adjusted Rates ................................................................ 144 Conclusion ..................................................................... 151 Study Questions and Exercises ........................................ 152 References ....................................................................... 155

Chapter 4 Descriptive Epidemiology: Person, Place, Time ......... 157 Introduction ................................................................... 158 Characteristics of Persons ................................................ 163 Characteristics of Place ................................................... 203 Characteristics of Time ................................................... 217 Conclusion ..................................................................... 223 Study Questions and Exercises ........................................ 223 References ....................................................................... 225 Appendix 4—Project: Descriptive Epidemiology of a Selected Health Problem ......................................... 233

Chapter 5 Sources of Data for Use in Epidemiology ................... 235 Introduction ................................................................... 236 Criteria for the Quality and Utility of Epidemiologic Data ................................................... 239 Online Sources of Epidemiologic Data ........................... 241 Confidentiality, Sharing of Data, and Record Linkage .... 244 Statistics Derived from the Vital Registration System ..... 247 Reportable Disease Statistics ........................................... 254 Screening Surveys ........................................................... 259 Disease Registries ............................................................ 260 Morbidity Surveys of the General Population ................. 262 Insurance Data................................................................ 267 Clinical Data Sources ...................................................... 267 Absenteeism Data ........................................................... 271 School Health Programs ................................................. 272

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Morbidity in the Armed Forces: Data on Active Personnel and Veterans .............................................. 272 Other Sources: Census Data ........................................... 273 Conclusion ..................................................................... 274 Study Questions and Exercises ........................................ 274 References ....................................................................... 276

Chapter 6 Study Designs: Ecologic, Cross-Sectional, Case-Control .......................................................... 279

Introduction ................................................................... 280 Observational Versus Experimental Approaches in Epidemiology ............................................................. 281 Overview of Study Designs Used in Epidemiology ......... 282 Ecologic Studies .............................................................. 287 Cross-Sectional Studies ................................................... 294 Case-Control Studies ...................................................... 303 Conclusion ..................................................................... 317 Study Questions and Exercises ........................................ 317 References ....................................................................... 319

Chapter 7 Study Designs: Cohort Studies ................................... 323 Introduction ................................................................... 324 Cohort Studies Defined .................................................. 325 Sampling and Cohort Formation Options ...................... 335 Temporal Differences in Cohort Designs ........................ 341 Practical Considerations .................................................. 344 Measures of Effect: Their Interpretation and Examples ... 347 Summary of Cohort Studies ............................................ 358 Conclusion ..................................................................... 359 Study Questions and Exercises ........................................ 362 References ....................................................................... 363

Chapter 8 Experimental Study Designs ...................................... 367 Introduction ................................................................... 368 Hierarchy of Study Designs ............................................ 371 Intervention Studies ........................................................ 373 Clinical Trials ................................................................. 374 Community Trials .......................................................... 392 Conclusion ..................................................................... 404 Study Questions and Exercises ........................................ 405 References ....................................................................... 406

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Chapter 9 Measures of Effect ...................................................... 409 Introduction ................................................................... 410 Absolute Effects .............................................................. 410 Relative Effects ............................................................... 414 Statistical Measures of Effect ........................................... 420 Evaluating Epidemiologic Associations ........................... 423 Models of Causal Relationships ...................................... 425 Conclusion ..................................................................... 430 Study Questions and Exercises ........................................ 431 References ....................................................................... 432 Appendix 9—Cohort Study Data for Coffee Use and Anxiety ................................................................ 433

Chapter 10 Data Interpretation Issues .......................................... 435 Introduction ................................................................... 436 Validity of Study Designs ............................................... 437 Sources of Error in Epidemiologic Research .................... 440 Techniques to Reduce Bias ............................................. 449 Methods to Control Confounding .................................. 450 Bias in Analysis and Publication ...................................... 454 Conclusion ..................................................................... 456 Study Questions and Exercises ........................................ 456 References ....................................................................... 458

Chapter 11 Screening for Disease in the Community ................... 461 Introduction ................................................................... 462 Screening for Disease ...................................................... 464 Appropriate Situations for Screening Tests and Programs .................................................................... 468 Characteristics of a Good Screening Test ........................ 471 Evaluation of Screening Tests ......................................... 471 Sources of Unreliability and Invalidity ............................ 476 Measures of the Validity of Screening Tests .................... 476 Effects of Prevalence of Disease on Screening Test Results........................................................................ 479 Relationship Between Sensitivity and Specificity ............. 482 Evaluation of Screening Programs ................................... 483 Issues in the Classification of Morbidity and Mortality ... 485 Conclusion ..................................................................... 486 Study Questions and Exercises ........................................ 487 References ....................................................................... 488 Appendix 11—Data for Problem 6 ................................. 490

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Chapter 12 Epidemiology of Infectious Diseases .......................... 491 Introduction ................................................................... 492 Agents of Infectious Disease ............................................ 493 Characteristics of Infectious Disease Agents .................... 496 Host ............................................................................... 497 The Environment ........................................................... 499 Means of Transmission: Directly or Indirectly from Reservoir .................................................................... 500 Measures of Disease Outbreaks ....................................... 506 Procedures Used in the Investigation of Infectious Disease Outbreaks ...................................................... 511 Epidemiologically Significant Infectious Diseases in the Community ............................................................... 513 Conclusion ..................................................................... 539 Study Questions and Exercises ........................................ 539 References ....................................................................... 542 Appendix 12—Data from a Foodborne Illness Outbreak in a College Cafeteria ................................. 545

Chapter 13 Epidemiologic Aspects of Work in the Environment .......................................................... 547

Introduction ................................................................... 548 Health Effects Associated with Environmental Hazards .. 550 Study Designs Used in Environmental Epidemiology ..... 550 Toxicologic Concepts Related to Environmental Epidemiology ............................................................. 555 Types of Agents .............................................................. 557 Environmental Hazards Found in the Work Setting ....... 571 Noteworthy Community Environmental Health Hazards ...................................................................... 575 Conclusion ..................................................................... 588 Study Questions and Exercises ........................................ 591 References ....................................................................... 592

Chapter 14 Molecular and Genetic Epidemiology ........................ 599 Introduction ................................................................... 600 Definitions and Distinctions: Molecular Versus Genetic Epidemiology ............................................................. 605 Epidemiologic Evidence for Genetic Factors ................... 609 Causes of Familial Aggregation ....................................... 610 Shared Family Environment and Familial Aggregation ... 612 Gene Mapping: Segregation and Linkage Analysis .......... 616

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Genome-Wide Association Studies (GWAS) .................. 626 Linkage Disequilibrium Revisited: Haplotypes ............... 628 Application of Genes in Epidemiologic Designs .............. 631 Genetics and Public Health ............................................ 638 Conclusion ..................................................................... 642 Study Questions and Exercises ........................................ 642 References ....................................................................... 643

Chapter 15 Social, Behavioral, and Psychosocial Epidemiology ... 649 Introduction ................................................................... 650 Research Designs Used in Psychosocial, Behavioral, and Social Epidemiology ................................................... 655 The Social Context of Health ......................................... 657 Independent Variables .................................................... 660 Moderating Variables ...................................................... 669 Dependent (Outcome) Variables: Physical and Mental Health ........................................................................ 684 Conclusion ..................................................................... 691 Study Questions and Exercises ........................................ 692 References ....................................................................... 694

Chapter 16 Epidemiology as a Profession ..................................... 701 Introduction ................................................................... 702 Specializations within Epidemiology ............................... 703 Career Roles for Epidemiologists .................................... 705 Epidemiology Associations and Journals ......................... 708 Competencies Required of Epidemiologists .................... 711 Resources for Education and Employment ..................... 712 Professional Ethics in Epidemiology ............................... 714 Conclusion ..................................................................... 719 Study Questions and Exercises ........................................ 720 References ....................................................................... 721

Appendix A—Guide to the Critical Appraisal of an Epidemiologic/Public Health Research Article ...... 723

Appendix B—Answers to Selected Study Questions ... 727

Glossary ...................................................................... 737

Index ............................................................................. 759

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New to This Edition

Chapter 1: History and Scope of Epidemiology

●● New and updated images ●● Updated chart: three presentations of epidemiologic data ●● Updated chart: pneumonia and influenza mortality ●● New chart on the interdisciplinary nature of epidemiology ●● Glossary of terms used in the yearly bill of mortality for 1632 ●● Expanded information on cholera and John Snow

Chapter 2: Pract ical Applicat ions of Epidemiology

●● Updated information on leading causes of death from 1900 to 2009 ●● Expanded discussion of population dynamics and predictions about the future ●● More information provided on the health of the community and health

disparities, including the GINI index

Chapter 3: Measures of Morbidity and Mortal i ty Used in Epidemiology

●● Expanded coverage of epidemiologic measures (e.g., sex ratios) ●● More information on prevalence given with figure to show interrelationships

between prevalence and incidence ●● Further clarification of perinatal mortality provided

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Chapter 4: Descript ive Epidemiology: Person, Place, Time

●● Updated coverage of morbidity and mortality data by descriptive epidemiologic variables provided throughout the chapter

●● New examples of case studies and case series ●● New information on age effects associated with morbidity and mortality ●● Many new charts added to this chapter ●● Updates from the 2010 Census, with current definitions of race/ ethnicity

Chapter 5: Sources of Data for Use in Epidemiology

●● Updated information on data sources including notifiable diseases ●● Further clarification of criteria for the quality of epidemiologic data ●● Rationale strengthened for the need for high-quality epidemiologic data

Chapter 6: Study Designs: Ecologic, Cross- Sectional , Case-Control

●● Clarification regarding design and applications of case-control studies ●● More information on matching in case-control studies ●● Clearer definitions of terms provided ●● Further discussion of comparisons between cross-sectional and case-

control studies

Chapter 7: Study Designs: Cohort Studies

●● Introduction updated ●● Additional clarification of terminology used in cohort studies ●● Exhibit on life table methods updated to the most recent information

Chapter 8: Experimental Study Designs

●● Expanded coverage of intervention studies ●● Several new images, including an image of a scurvy victim ●● Discussion of phase 4 clinical trials ●● New table and a glossary of terms used in clinical trials ●● Applications of epidemiology to vaccines and prevention: HPV vaccine

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Chapter 9: Measures of Effect

●● Introduction revised ●● STROBE guidelines and quality of epidemiologic studies ●● Meta-analysis and systematic reviews

Chapter 10: Data Interpretat ion Issues

●● More information on Simpson’s Paradox, including a new figure ●● Information bias and screening mammography

Chapter 11: Screening for Disease in the Community

●● New figure showing participants in a mammogram and a blood pressure screening test

●● New figure showing participation rates in screening for colorectal cancer, breast cancer, and cervical cancer

●● Updated discussion on controversies in screening ●● Difficulties with false positive screening test results

Chapter 12: Epidemiology of Infect ious Diseases

●● Many updated charts showing data on disease incidence and prevalence (e.g., measles, malaria, hepatitis, valley fever, Lyme disease)

●● Information on the cholera epidemic in Haiti ●● Revised exhibit on viral hepatitis

Chapter 13: Epidemiologic Aspects of Work in the Environment

●● New information on methodologic topics (e.g., exposure assessments, clustering, and confounding)

●● Updated data on blood lead levels and mercury advisories ●● New topics include global warming, the BP oil spill, and the Japanese

tsunami and its effects on the Fukushima nuclear reactor ●● Many new images to capture students’ interest in this topic

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Chapter 14: Molecular and Genetic Epidemiology

●● New diagram of Mendelian inheritance ●● Additional discussion of the population genetics concept of linkage

disequilibrium ●● Expanded discussion of the concept of haplotypes ●● A thorough update of this chapter with the latest developments in the field

Chapter 15: Social , Behavioral , and Psychosocial Epidemiology

●● Many new illustrations added to this chapter ●● The concept of community-based participatory research added ●● New information on the social context of health (e.g., poverty, the Glasgow

effect) ●● Healthy People 2020 overarching goals included ●● Update on depression

Chapter 16: Epidemiology as a Profession

●● Updated to show current professional resources and issues

Other

●● Exciting new figures, tables, and exhibits provided throughout ●● Additional exercises and study questions

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Introduction

Epidemiology is an important, exciting, and rewarding field for the public health practitioner! Almost daily, one hears dramatic media reports about flare-ups of diseases, either previously known or seemingly new conditions. These accounts demonstrate how epidemiologists help to uncover the causes of human illnesses in the population and thereby underscore the importance of epidemiology to society. Deadly outbreaks of communicable diseases, the ongoing threat of resur- gent epidemics, and the possible intentional spread of pathogenic microorgan- isms through acts of bioterrorism present challenges to the field. By assisting the reader in understanding why and how diseases occur and how they may be pre- vented, epidemiology is a valuable pursuit. In this text you will learn that many epidemiologic investigations into the causes of mysterious outbreaks are similar to detective work.

One of the challenges for the authors has been to distill with sufficient breadth and depth all of the fascinating components of this discipline. As the Fifth Edition is being finalized, new and resurgent health conditions challenge public health practitioners; some current examples are resurgent whooping cough, outbreaks of foodborne diseases, hantavirus infections (which normally are infrequent) in a national park, fungal meningitis associated with epidural steroid injections, and a West Nile virus epidemic. Thus, the ongoing flow of accounts of disease outbreaks (noted in the First Edition) has not been staunched and, in fact, is con- tinuing unabated during the second decade of the 21st century.

Since the publication of the earlier editions of this book, the wealth of epidemiologic research findings has continued to proliferate and win the atten- tion of the popular media and professional journals. For example, some of these recent discoveries relate to continuing advances in genetics and molecu- lar biology, recognition of emerging infections, and the growing use of the Internet. As a result, the Second Edition introduced several enhancements: a new chapter on molecular and genetic epidemiology, a new chapter on experimental

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epidemiology, material on epidemiology Internet sites, and updated charts and tables throughout the text.

The Third Edition incorporated a new chapter on cohort designs, a glossary, and an expanded coverage of ecologic and case-control study designs. The Third Edition also included new material on the role of epidemiology in policy making, epidemiology and geographic information systems, and the definition of race used in Census 2000. A new Appendix A provided an extended guide to critiqu- ing published research studies in public health and epidemiology. Several new tables summarized unadjusted measures of morbidity and mortality, contrasted different types of observational study designs, and compared observational versus intervention study designs.

The Fourth Edition presented new information on infectious disease threats associated with E. coli foodborne illness and avian influenza as well as expanded coverage of the historical background of epidemiology. Chapter 3, “Measures of Morbidity and Mortality Used in Epidemiology,” was updated to reflect the use of the 2000 standard population in age standardization. A new Chapter 16, titled “Epidemiology as a Profession,” covered methods for accessing the profes- sion and employment opportunities in the field.

The Fifth Edition provides an extensive update of information from the previ- ous editions. Examples are coverage of the 2009 H1N1 influenza epidemic, the 2010 U.S. Census, and numerous additional and updated figures, charts, and photographs throughout the book. Trends in morbidity have been updated to reflect the most recently available information. New information is presented throughout the text: for example, in Chapter 12 (infectious diseases), Chapter 13 (environmental health), and Chapter 14 (molecular and genetic epidemiol- ogy). Definitions used in the text have been aligned with the 2008 Dictionary of Epidemiology, a standard reference in the field.

We intend the audience for the textbook to be beginning public health mas- ter’s degree students, undergraduate and graduate health education and social ecology students, undergraduate medical students, nursing students, residents in primary care medicine, and applicants who are preparing for medical board examinations. These students are similar to those with whom both authors have worked over the years. Students from the social and behavioral sciences also have found epidemiology to be a useful tool in medical sociology and behavioral med- icine. We have included study questions and exercises at the end of each chapter; this material would be helpful to review for board examinations. Appendix B contains an expanded answer set to selected problems.

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Each chapter begins with a list of learning objectives and an outline to help focus the reader’s attention to key points. Some of the major issues and examples are highlighted in text boxes and tables. Chapter 1, which defines epidemiol- ogy and provides a historical background for the discipline, is complemented by Chapter 2, which provides examples of practical applications of epidemiology as well as a discussion of causal inference. Although examples of epidemiologic statistical techniques are interspersed throughout the book, Chapter 3 focuses on the “nuts and bolts” of measures of morbidity and mortality. Chapters 4 through 11 deal with the important topics of descriptive epidemiology: data sources, study designs, measures of effect, data interpretation, and screening. Chapters 12 through 15 focus on four content areas in epidemiology: infec- tious diseases, occupational and environmental health, molecular and genetic epidemiology, and psychosocial epidemiology. Finally, Chapter 16 covers pro- fessional issues in epidemiology. This text provides a thorough grounding in the key areas of methodology, causality, and the complex issues that surround chronic and infectious disease investigations. The authors assume that the reader will have had some familiarity with introductory biostatistics, although the text is intelligible to those who do not have such familiarity. A companion website for students is available for the text. This website provides extensive resources for students, including the student study guide that was included with the last edition. We recommend that students and instructors navigate through the site during class time. For example, the flashcards available may be used as part of an in-class activity to drill students for the class examinations. Dr. Friis uses in-class Internet navigation in order to show students how to locate resources for the project shown in the Appendix at the end of Chapter 4. Completion of the proj- ect can be one of the major assignments in an epidemiology class. In addition to completing a written version of the assignment, students may enjoy delivering a brief PowerPoint presentation of their research to the entire class. Students’ motivation and success in an epidemiology course are enhanced by reviewing the various activities provided.

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Preface

My interest in epidemiology began during the 1960s when, as an undergraduate student at the University of California at Berkeley and a graduate student at Columbia University, I observed the student revolts and activism that occurred during that era. Student unrest was, I believed, a phenomenon that occurred in large groups and could be explained by a theoretical framework, perhaps one that would include such concepts as alienation or anomie. I became interested in studying the distribution of these psychological states in student populations. Unknowingly, I had embarked upon epidemiologic research. I find epidemiol- ogy to be a field that has great personal appeal because it is capable of impacting the health of large groups of people through improvements in social conditions and environmental modifications.

My formal training in epidemiology began at the Institute for Social Research of the University of Michigan, where I spent 2 years as a postdoctoral fellow. My first professional position in epidemiology was as an assistant professor in the Division of Epidemiology at the School of Public Health, Columbia University. As a fledgling professor, I found epidemiology to be a fascinating discipline, and began to develop this textbook from my early teaching experiences. I concluded that there was a need for a textbook that would be oriented toward the begin- ning practitioner in the field, would provide coverage of a wide range of topics, and would emphasize the social and behavioral foundations of epidemiology as well as the medical model. This textbook has evolved from my early teaching experience at Columbia as well as later teaching and research positions at Albert Einstein College of Medicine, Brooklyn College, the University of California at Irvine, and the California State University system. Practical experience in epide- miology, as an epidemiologist in a local health department in Orange County, California, is also reflected in the book.

—Robert H. Friis

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Like many others now reading this book, I had absolutely no idea what epidemiology was before I took my first required class in it at Tulane University School of Public Health and Tropical Medicine. What I discovered was a method to combine my training in nutrition and interest in health with an aptitude for math and analytical reasoning. This led to a change in majors and ultimately a PhD in epidemiology.

My first faculty appointment was at the University of Minnesota School of Public Health. Before I knew it, I was assigned to teach the introduction to epi- demiology course during the winter quarter. This was the time of year when only nonmajors enrolled. I quickly learned, as had my predecessors, that my teaching and learning style was quite different from those of my students. Moreover, most of the textbooks available at that time were geared toward epidemiology majors. For 9 years, I studied learning styles (and even co-developed and co-taught a graduate course on teaching) and experimented to find new ways to present the fundamentals of epidemiology in a nontechnical, nontheoretical, intuitive man- ner. This text reflects these learning experiences.

—Thomas A. Sellers

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Acknowledgments

First, I express my gratitude to my teachers and colleagues at the settings where I have worked during the past 4 decades. Their insights and suggestions have helped me clarify my thinking about epidemiology. Among these individu- als are the late Dr. Sidney Cobb and the late Dr. John R. P. French, Jr., who were my postdoctoral supervisors at the University of Michigan’s Institute for Social Research. Dr. Mervyn Susser offered me my first professional employ- ment in epidemiology at the School of Public Health, Columbia University. He and Dr. Zena Stein helped me to greatly increase my fund of knowledge about research and teaching in the field. The late Professor Anna Gelman pro- vided me with many practical ideas regarding how to teach epidemiology. Dr. Stephen A. Richardson also contributed to my knowledge about epidemiologic research. Finally, Dr. Jeremiah Tilles, former Associate Dean, California College of Medicine, University of California at Irvine, helped to increase my insights regarding the epidemiology of infectious diseases.

I also thank students in my epidemiology classes who contributed their suggestions and read early drafts of the first edition. The comments of anony- mous reviewers were particularly helpful in revising the manuscript. Jonathan Horowitz, former instructor in Health Science at California State University, Long Beach, spent a great deal of time reviewing several chapters of a very early version of the text, and I acknowledge his contributions. Sherry Stock, a former student in medical sociology at Long Beach, typed the first draft and provided much additional valuable assistance in securing bibliographic research materials. Dr. Yee-Lean Lee, Professor, Infectious Disease Division in the Department of Medicine at the University of California at Irvine, reviewed and commented on the chapter dealing with the epidemiology of infectious diseases. Also, Dr. Harold Hunter, Professor Emeritus of Health Care Administration, California State University, Long Beach, reviewed several chapters of the manuscript.

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Finally, my wife, Carol Friis, typed the final version of the manuscript and made helpful comments. Without her support and assistance, completion of the text would not have been possible.

For the second edition of the text, I again thank my epidemiology students, who continued to provide much useful feedback. Graduate students Janelle Yamashita, Cindy Bayliss, and Jocelin Sabado were extremely helpful in con- ducting literature searches and preparing the text. Sharon Jean assisted with typ- ing the manuscript.

With respect to the third edition, I would like to thank students at my home university and at other universities who provided many worthwhile sugges- tions for enhancement of the text. I am also grateful for the informal feedback I received from faculty members (across the United States and in several for- eign countries) who adopted this text in their courses. Former California State University graduate student Ibtisam Khoury, now a lecturer in the Health Science Department, conducted background research, provided ideas for clari- fication of complex concepts, and helped to develop several new tables. Faculty members Dr. Javier Lopez-Zetina and Dr. Dennis Fisher, housed at the same university, reviewed several of the chapters. Critiques from anonymous reviewers also were instrumental in development of the third edition. Once again, I am deeply indebted to my wife, Carol Friis, who assisted with editing and typing the manuscript. Without her keen eye, writing this book would have been a much more difficult task.

Regarding the fourth edition, I once again acknowledge my students’ sugges- tions for continued improvement of this book. Although many students are wor- thy of recognition, I would especially like to thank graduate student Lesley Shen. Claire Garrido-Ortega, a former student and now a lecturer in the Department of Health Science, contributed her ideas to the new edition. I have received many suggestions from the readers of the previous edition of this text; I would like to thank them also—particularly Dr. Lee Caplan at Morehouse University. Once more, I recognize the support of my wife, Carol Friis, who helped with preparation of the text.

The fifth edition benefited from the input of students and faculty members in the Department of Health Science. Particularly noteworthy were the sugges- tions provided by faculty member Dr. Javier Lopez-Zetina and former graduate students (and now faculty members) Ibtisam Khoury, Che Wanke, and Claire Garrido-Ortega. Jaina Pallasigui, MPH graduate, helped with background research for this revision. Roxanne Garza reviewed the manuscript.

—R.H.F.

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I have been most fortunate to receive training and guidance from a significant number of individuals. First and foremost, I thank Dr. Dorothy Clemmer, who taught me my first course in epidemiology at Tulane University School of Public Health and Tropical Medicine. Her enthusiasm and support helped me to “see the light.” The early years of my education included mentorship with Dr. Gerald Berenson and Dr. Robert C. Elston. Both have been extremely influential in my practical and theoretical understanding of this discipline. Dr. J. Michael Sprafka was a great supporter and colleague for those first precarious episodes of teach- ing. I owe many thanks to the numerous bright and challenging public health students at the University of Minnesota for their support, encouragement, and patience while I experimented with methods of presentation to find out what worked best for “nonmajors.” Finally, I acknowledge my father, Gene R. Sellers, who has published many fine textbooks and gave me the courage to attempt this project; my loving wife, Barbara, for her understanding and enduring belief in me; and my two sons, Jamison Thomas and Ryan Austin, who are my inspira- tion and loves of my life.

For the second edition, I acknowledge the encouragement of the students and colleagues who had used the first edition of this text. I also thank our publisher and their staff for their professionalism. Finally, I acknowledge the drive and creativity of Bob Friis, whose energies made this book a reality and a success.

For the fourth edition, I would like to particularly thank my wonderful friends and colleagues at the Moffitt Cancer Center (especially Yifan Huang, Cathy Phelan, Jong Park, and Anna Giuliano) and the Mayo Cancer Center (espe- cially Ellen Goode, Jim Cerhan, Celine Vachon, and Shane Pankratz) for their brilliance and dedication. I’ve learned that the application of the epidemiologic method can be fun if you work with the right team. I have certainly benefited from being around such a wonderful cast of bright and stimulating people. This has translated into exciting research projects, new knowledge, and practical insights added to this edition. Moreover, they share my hope and dream for an end to cancer and the terrible impact of this disease.

For the fifth edition, I want to add a posthumous note of love and apprecia- tion to my mother for always believing in me and for encouraging my pursuit of an academic career dedicated to cancer research. That she lost her life to the disease has reconfirmed my determination to make an impact through applica- tion of the epidemiologic method.

—T.A.S.

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About the Authors

Robert H. Friis, PhD, is a Professor Emeritus of Health Science and Chair Emeritus of the Department of Health Science at California State University, Long Beach, and former Director of the CSULB-VAMC, Long Beach, Joint Studies Institute. He is also a former Clinical Professor of Community and Environmental Medicine at the University of California at Irvine. Previously, he was an Associate Clinical Professor in the Department of Medicine, Department of Neurology, and School of Social Ecology, University of California at Irvine. His entire professional career has been devoted to the field of epidemiology. He has conducted research and taught epidemiology and related subjects for more than 4 decades at universities in New York City and Southern California. In addition to previous employment in a local health department as an epidemi- ologist, he has conducted research and has published and presented numerous papers related to mental health, chronic disease, disability, minority health, and psychosocial epidemiology. His textbook, Essentials of Environmental Health, Second Edition, is also published by Jones & Bartlett Learning. Dr. Friis has been principal investigator or co-investigator on grants and contracts from University of California’s Tobacco-Related Disease Research Program, from the National Institutes of Health, and from other agencies for research on geriatric health, depression in Hispanic populations, nursing home infections, and environmental health issues. His research interests have led him to conduct research in Mexico City and European countries. He has been a visiting professor at the Center for Nutrition and Toxicology, Karolinska Institute, Stockholm, Sweden; the Max Planck Institute, Munich, Germany; and Dresden Technical University, also in Germany. He reviews articles for scientific journals and is a member of the editorial board of Public Health. Dr. Friis is a member of the Society for Epidemiologic Research, the American Public Health Association (epidemiology section), is a past president of the Southern California Public Health Association,

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and is a fellow of the Royal Academy of Public Health. Among his awards are a postdoctoral fellowship (for study at the Institute for Social Research, University of Michigan), and the Achievement Award for Scholarly and Creative Activity from California State University, Long Beach. His biography is listed in Who’s Who in America.

Thomas A. Sellers, PhD, MPH, is Director of the Moffitt Cancer Center & Research Institute and Executive Vice President of the H. Lee Moffitt Cancer Center and Research Institute. Prior to this position in sunny, warm Tampa, Florida, he was Professor of Epidemiology in the Department of Health Sciences Research at the Mayo Clinic and the Deputy Director of the Mayo Clinic Cancer Center. He began his career at the University of Minnesota School of Public Health, where he taught the Introduction to Epidemiology course to nonmajors for 9 years. His primary research interests include understanding the etiology of common adult cancers, particularly breast and ovarian cancer. He has published more than 300 peer-reviewed scientific articles, reviews, and book chapters, and now serves as a Deputy Editor of Cancer Epidemiology, Biomarkers, and Prevention and as Associate Editor of the American Journal of Epidemiology. Dr. Sellers is a long-standing member of the American Association for Cancer Research and the American Society for Preventive Oncology, and is a founding member of the International Genetic Epidemiology Society. Dr. Sellers has been an invited member of Advisory Committees to the National Cancer Institute, has provided invited lectures worldwide, and has served on numerous grant review panels.

xxiv a b o u t t h e a u t h o r s

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1

1Chapte r

History and Scope of Epidemiology

LEARNING OBJECTIVES

By the end of this chapter the reader will be able to:

●● define the term epidemiology ●● def ine the components of epidemiology (determinants,

distribution, morbidity, and mortality) ●● name and describe characteristics of the epidemiologic approach ●● discuss the importance of Hippocrates’ hypothesis and how it dif-

fered from the common beliefs of the time ●● discuss Graunt’s contributions to biostatistics and how they

affected modern epidemiology ●● explain what is meant by the term natural experiments, and give at

least one example

CHAPTER OUTLINE

I. Introduction II. Epidemiology Defined

III. Foundations of Epidemiology IV. Historical Antecedents of Epidemiology V. Recent Applications of Epidemiology

VI. Conclusion VII. Study Questions and Exercises

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2 C h a p t e r 1 h i s t o r y a n d s C o p e o f e p i d e m i o l o g y

Introduction

Controversies and speculations regarding the findings of epidemiologic research are frequent topics of media reports; these findings sometimes arouse public hysteria. Examples of the questions raised by media reports include: “Is it more dangerous to vaccinate an entire population against smallpox (with result- ing complications from the vaccine) or to risk infection with the disease itself through a terrorist attack?” “Is Ebola virus a danger to the general public?” “Should I give up eating fatty foods?” “Is it safe to drink coffee or alcoholic beverages?” “Will chemicals in the environment cause cancer?” “Should one purchase bottled water instead of consuming tap water from public drinking supplies?” “Will medications for chronic diseases (long-standing illnesses that are difficult to eradicate) such as diabetes cause harmful side effects?” “Will the foods that I purchase in the supermarket make me sick?” “When can we expect the next global pandemic influenza and what shall be the response?”

Consider the 2009–2010 episode of influenza first identified in the United States1 and eventually called 2009 H1N1 influenza. Ultimately the 2009 H1N1 outbreak threatened to become an alarming pandemic that public health officials feared could mimic the famous 1918 “killer flu.” In April 2009, 2 cases of 2009 H1N1 came to the attention of the Centers for Disease Control and Prevention (CDC), which investigates outbreaks of infectious diseases such as influenza. Thereafter, the number of cases expanded rapidly in the United States and then worldwide. When the epidemic eventually subsided during summer 2010, an estimated 60 million cases had occurred in the United States. According to the CDC, people in the age range of 18–64 years were most heavily affected by the virus; less affected were those 65 years of age and older. Exhibit 1–1 provides an account of the pandemic.

the 2009 h1N1 pandemic

During spring 2009, a 10-year-old California child was diagnosed with an unusual variety of influenza. Soon afterwards a case of the same flu strain was identified in an 8-year-old who lived approxi- mately 130 miles from the first patient. This was an alarming event e

x h

ib it

1 –1

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i n t r o d u C t i o n 3

Exhibit 1–1 continued

in several respects. The type of influenza virus was usually found among swine. However, the newly identified virus appeared to have been transmit- ted among humans. Secondly, the appearance of these two unusual cases raised public health officials’ suspicions that a deadly flu pandemic similar to the 1918 pandemic might be under way.

Scientists named the new virus 2009 H1N1. The agent was “. . . a unique combination of influenza virus genes never previously identified in either animals or people.”1 The genes of the new virus were closely related to North American swine-lineage H1N1 influenza viruses. Before this outbreak, human-to-human spread of swine-origin influenza viruses was highly unusual. During the previous three years (from December 2005 to January 2009), only 12 U.S. cases of swine influenza had been reported. The vast majority (n = 11) had indicated some contact with pigs. One of the unusual features of infections with the 2009 H1N1 virus were reports of a high prevalence of obesity among influenza-affected patients in inten- sive care units.

Following the identification of the initial cases in California, swine flu spread across the United States and jumped international borders. In response to a potential widespread epidemic, some schools and pub- lic health officials implemented pandemic preparedness plans, which included school closures and social distancing. In June, the World Health Organization (WHO) declared that a global pandemic was under way. Here is a brief chronology of the events that transpired during the

pandemic.

●● April 15, 2009—first case of pandemic influenza (2009 H1N1) identi-

fied in a 10-year-old California patient. ●● April 17—eight-year-old child living 130 miles away from first case devel-

ops influenza. ●● April 21—Centers for Disease Control and Prevention (CDC) began

work on a vaccine against the virus. ●● April 22—three new cases are identified in San Diego County and Impe-

rial County. ●● April 23—two new cases identified in Texas.

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4 C h a p t e r 1 h i s t o r y a n d s C o p e o f e p i d e m i o l o g y

Exhibit 1–1 continued

●● April 23—seven samples from Mexico were positive for 2009 H1N1. ●● April 25—WHO declares a “Public Health Emergency of International

Concern.” ●● April 25—cases diagnosed in New York City, Kansas, and Ohio. ●● April 29—WHO raises the influenza pandemic alert from phase 4 to

phase 5. ●● May 6—CDC recommends prioritized testing and antiviral treatment

for people at high risk of complications from flu. ●● June 11—WHO raises the worldwide pandemic alert level to phase 6

and declares the global pandemic is under way. ●● June 11—more than 70 countries have reported cases of pandemic

influenza. ●● June through July—the number of countries reporting influenza has

nearly doubled; all 50 states in the U.S. have reported cases. ●● Summer and fall—extraordinary influenza-like illness activity reported

in the U.S. ●● September 30—initial supplies of 2009 H1N1 vaccine distributed on a

limited basis. ●● December—vaccine made available to all who wanted it. ●● Summer 2010—flu activity reaches normal summer time levels in the U.S.

According to the CDC approximately 60 million people became infected with 2009 H1N1 between April 2009 and March 13, 2010. The estimated range of the number of cases was between 43 million and 88 million. The process of estimating the number of flu cases is imprecise because many patients who become ill do not seek medical care, and those who do are not tested for the virus. Figure 1–1 reports CDC estimates of 2009 H1N1 cases in the US by age group. n

Source: Data from Centers for Disease Control and Prevention. The 2009 H1N1pandemic: summary highlights, April 2009—April 2010. Available at: http://www.cdc.gov/h1n1flu/ cdcresponse.htm. Accessed July 19, 2012.

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i n t r o d u C t i o n 5

Another example of a disease that elicited public hysteria was the outbreak of Escherichia coli (E. coli) infections during late summer and fall 2006. The outbreak affected multiple states in the United States and captured media head- lines for several months. Known as E. coli O157:H7, this bacterial agent can be ingested in contaminated food. The agent is an enteric pathogen, which can pro- duce bloody diarrhea, and in some instances, the hemolytic-uremic syndrome (HUS), a type of kidney failure. Severe cases of E. coli O157:H7 can be fatal.

The 2006 outbreak was a mysterious event that gradually unfolded over time. The outbreak sickened 199 persons across United States and caused 3 deaths (as of October 6, 2006, when the outbreak appeared to have subsided). Figure 1–2 shows the affected states. The 2006 outbreak caused 102 (51%) of the ill persons to be hospi- talized; in all, 31 patients (16%) were afflicted with HUS. The majority of cases (141, 71%) were female. A total of 22 children 5 years of age and younger were affected.2

FiGURE 1–1 CDC estimates of 2009 H1N1 cases in the United States by age group. Source: Reproduced from Centers for Disease Control and Prevention. The CDC Estimates of 2009 H1N1 Influenza Cases, Hospitalizations and Deaths in the United States, April 2009–March 13, 2010. Available at: http://www.cdc.gov/h1n1flu/estimates/April_March_13. htm. Accessed August 23, 2012.

60,000,000

50,000,000

40,000,000

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20,000,000

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0– 17

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April – Oct 17, 2009

April – Nov 14, 2009

April 2009 – Dec 12, 2010

April 2009 – Jan 16, 2010

April – Feb 13, 2010

April – March 13, 2010

Age Group Data by Date Range

18 –6

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rs

≥6 5

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Y rs

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4 Y

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0

Exhibit 1–1 continued

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6 C h a p t e r 1 h i s t o r y a n d s C o p e o f e p i d e m i o l o g y

Tracking down the mysterious origins of the outbreak required extensive detective work. The outbreak was linked to prepackaged spinach as the most likely vehicle. Investigators traced the spinach back to its source, Natural Selec- tion Foods near Salinas, California. The producer announced a recall of spinach on September 15, 2006.3 The FDA and State of California conducted a trace- back investigation, which implicated four ranches in Monterey and San Benito Counties. Cattle feces from one of the four ranches contained a strain of E. coli O157:H7 that matched the strain that had contaminated the spinach and also matched the strain found in the 199 cases.4 The mechanism for contamination of the spinach with E. coli bacteria was never established definitively.

Noteworthy is the fact that subsequent to this major outbreak, E. coli O157:H7 continues to threaten the food supply of the United States, not only from spinach but also from other foods.5 During November and December 2006, Taco Bell restaurants in the northeastern United States experienced a major outbreak that caused at least 71 persons to fall ill. Contamination of Topp’s brand frozen ground beef patties and Totino’s or Jeno’s brand frozen pizzas with E. coli O157:H7 is believed to have sickened more than 60 residents

FiGURE 1–2 Distribution of Escherichia coli serotype O157:H7 cases across the United States, September 2006. Source: Reproduced from Centers for Disease Control and Prevention. Ongoing multistate outbreak of Escherichia coli serotype O157:H7 infections associated with consumption of fresh spinach— United States, September 2006. MMWR. 2006;55:1045–1046.

WA

OR ID

WY

NV

CA

UT

AZ

CO

NM

IL

MN WI

NE

MI

IN OH

WV

PA

NY

VA KY

ME

CT

MD

TN

1–4 5–9 10–14 15 or higher

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i n t r o d u C t i o n 7

of the eastern half of the United States during summer and early fall 2007. In 2008 and 2009, E. coli outbreaks were associated with ground beef and prepack- aged cookie dough. Ground beef, cheese, romaine lettuce, bologna, and hazel- nuts caused outbreaks during 2010 and 2011. A major outbreak of E. coli O104 occurred in Germany in 2011; 6 travelers from the United States were made ill, with one of the six dying. During summer 2012, a multistate outbreak caused by E. coli O145 sickened 18 persons and caused 9 deaths.

In summary, the 2009 H1N1 flu pandemic (Exhibit 1–1) and the E. coli spinach-associated outbreak illustrate that epidemiologic research methods are a powerful tool for studying the health of populations. In many instances, epidemiology resembles detective work, because the causes of disease occurrence are often unknown. Both examples raise several issues that are typical of many epidemiologic research studies:

●● When there is a linkage or association between a factor (i.e., contaminants in food and water; animal reservoirs for disease agents) and a health out- come, does this observation mean that the factor is a cause of disease?

●● If there is an association, how does the occurrence of disease vary according to the demographic characteristics and geographic locations of the affected persons?

●● Based on the observation of such an association, what practical steps should individuals and public health departments take? What should the individual consumer do?

●● Do the findings from an epidemiologic study merit panic or a measured response?

●● How applicable are the findings to settings other than the one in which the research was conducted? What are the policy implications of the findings?

In this chapter we answer the foregoing questions. We discuss the stages that are necessary to unravel mysteries about diseases, such as those due to environ- mental exposures or those for which the cause is entirely unknown.

Epidemiology is a discipline that describes, quantifies, postulates causal mechanisms for diseases in populations, and develops methods for the control of diseases. Using the results of epidemiologic studies, public health practitioners are aided in their quest to control health problems such as foodborne disease out- breaks and influenza pandemics. The investigation into the spinach-associated E. coli outbreak illustrates some of the classic methods of epidemiology; first, describing all of the cases, enumerating them, and then following up with addi- tional studies. Extensive detective work was involved in identifying the cause of the outbreak. The hypothesized causal mechanism that was ultimately linked to

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contaminated spinach was the bacterium E. coli. All of the features described in the investigation are hallmarks of the epidemiologic approach. In this example, the means by which E. coli contaminated the spinach remains an unresolved issue.

The 2009 H1N1 pandemic demonstrated the use of epidemiologic data to identify the source of the initial outbreaks, describe pandemic spread, and mount a public health response to control a pandemic. Officials created public awareness of the need to be vaccinated against the virus and to prevent spread of the virus by covering up one’s mouth when coughing and washing one’s hands frequently.

Epidemiology Defined

The word epidemiology derives from epidemic, a term that provides an immediate clue to its subject matter. Epidemiology originates from the Greek words epi (upon) + demos (people) + logy (study of). Although some conceptions of epidemiology are quite narrow, we suggest a broadened scope and propose the following definition:

Epidemiology is concerned with the occurrence, distribution, and determinants of “health-related states or events”6 (e.g., health and diseases, morbidity, injuries, disabil- ity, and mortality in populations). Epidemiologic studies are applied to the control of health problems in populations. The key aspects of this definition are determinants, distribution, population, and health phenomena (e.g., morbidity and mortality).

Determinants Determinants are factors or events that are capable of bringing about a change in health. Some examples are specific biologic agents (e.g., bacteria) that are associated with infectious diseases or chemical agents that may act as carcino- gens. Other potential determinants for changes in health may include less spe- cific factors, such as stress or adverse lifestyle patterns (lack of exercise or a diet

Case 1: Intentional Dissemination of Bacteria That Cause Anthrax

After the United States experienced its worst terrorist attack on September 11, 2001, reports appeared in the media about cases of anthrax in Florida beginning in early October. In the United States, anthrax usually affects herbivores (livestock and some wild animals);

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e p i d e m i o l o g y d e f i n e d 9

human cases are unusual. Anthrax is an acute bacterial disease caused by exposure to Bacillus anthracis. Cutaneous anthrax affects the skin, producing lesions that develop into a black scab. Untreated cutaneous anthrax has a case-fatality rate of 5–20%. The much more severe inhala- tional form, which affects the lungs and later becomes disseminated by the bloodstream, has a high case fatality rate.7 Observations of an alert infectious disease specialist along with the support of laboratory staff led to the suspicion that anthrax had been deliberately sent through the postal system.8 The CDC, in collaboration with officials at the state and local levels, identified a total of 21 anthrax cases (16 confirmed and 5 suspected) as of October 31, 2001. The majority of the cases occurred among employees located in four areas: Florida, New York City, New Jersey, and the District of Columbia.9–12 Figure 1–3 portrays the dis- tribution of the 21 cases in 4 geographic areas of the United States. n

As of October 31, 2001, 21 cases were reported

in four states and one isolated case in

Connecticut (not linked to any exposure source)

Florida (2 cases) Workers at America

Media, Inc First case was 63-year-old

worker who dies from inhalational anthrax.

Second case identified in co-worker with positive

nasal sample. Environmental sample from workplace tests positive for anthrax.

New York City (7 cases) 1 inhalational (confirmed), 6 cutaneous (3 confirmed,

3 suspected) cases in 4 media companies

One of six cases involved suspected mail room

contact with letter that contained anthrax.

Case seven: inhalational case (patient worked in

hospital stockroom)

New Jersey (7 cases at 2 postal facilities) 5 cases confirmed 2 cases suspected

5 cases at a New Jersey postal facility

No contaminated letters identified, but contaminated

mail suspected. 2 cases at a second New Jersey postal center (mail sorter and another worker)

District of Columbia (5 cases, all inhalational)

4 cases in DC postal facility 1 case in U.S. State

Department mail facility (This facility receives

mail from the DC facility that had 4 cases.)

FiGURE 1–3 Occurrence of anthrax cases during the 2001 terrorist incident according to the investigation by the Centers for Disease Control and Prevention.

CasE 1 continued

high in saturated fats). The following four vignettes illustrate the concern of epidemiology with disease determinants. For example, consider the steps taken to track down the source of the bacteria that caused anthrax and were sent through the mail; contemplate the position of an epidemiologist once again. Imagine a possible scenario for describing, quantifying, and identifying the determinants for each of the vignettes.

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Case 2: Outbreak of Fear

When a 36-year-old lab technician known as Kinfumu checked into the general hospital in Kikwit, Zaire, complaining of diarrhea and a fever, anyone could have mistaken his illness for the dysentery that was plagu- ing the city. Nurses, doctors, and nuns did what they could to help the young man. They soon saw that his disease wasn’t just dysentery. Blood began oozing from every orifice in his body. Within 4 days he was dead. By then the illness had all but liquefied his internal organs.

That was just the beginning. The day Kinfumu died, a nurse and a nun who had cared for him fell ill. The nun was evacuated to another town 70 miles to the west where she died—but not until the contagion had spread to at least three of her fellow nuns. Two subsequently died. In Kikwit, the disease raged through the ranks of the hospital’s staff. Inhabitants of the city began fleeing to neighboring villages. Some of the fugitives carried the deadly illness with them. Terrified health officials in Kikwit sent an urgent message to the World Health Organization. The Geneva-based group summoned expert help from around the globe: a team of experienced virus hunters composed of tropical-medicine specialists, microbiologists, and other researchers. They grabbed their lab equipment and their bubble suits and clambered aboard transport planes headed for Kikwit.13 n

Case 3: Fear on Seventh Avenue

On normal workdays, the streets of New York City’s garment district are lively canyons bustling with honking trucks, scurrying buyers, and sweat- ing rack boys pushing carts loaded with suits, coats, and dresses. But during September 1978 a tense new atmosphere was evident. Sanitation trucks cruised the side streets off Seventh Avenue flushing pools of stag- nant water from the gutters and spraying out disinfectant. Teams of health officers drained water towers on building roofs. Air condition- ers fell silent for inspection, and several chilling signs appeared on 35th Street: “The New York City Department of Health has been advised of

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Case 4: Red Spots on Airline Flight Attendants

From January 1 to March 10, 1980, Eastern Airlines received 190 reports of episodes of red spots appearing on the skin of flight attendants (FAs) during various flights. Complaints of symptoms accompanying the spots were rare, but some FAs expressed concern that the spots were caused by bleeding through the skin and might indicate a serious health hazard. On March 12, investigators from the CDC traveled to Miami to assist in the investigation. No evidence of damage to underlying skin was noted on these examinations, nor was any noted by consultant dermatologists who examined affected FAs after the spots had disappeared. Chemical tests on clinical specimens for the presence of blood were negative. Airline personnel had investigated the ventilation systems, cleaning materials and procedures, and other environmental factors on affected aircraft. Airflow patterns and cabin temperatures, pressures, and rela- tive humidity were found to be normal. Cleaning materials and routines had been changed, but cases continued to occur. Written reports by FAs of 132 cases occurring in January and February showed that 91 different FAs had been affected, 68 once and 23 several times. Of these cases, 119 (90%) had occurred on a single type of aircraft. Of the 119 cases from implicated aircraft, 96% occurred on north- or southbound flights between the New York City and Miami metropolitan areas, flights that are partially over water. Only rarely was a case reported from the same airplane when flying transcontinental or other east-west routes.15 n

possible cases of Legionnaires’ disease in this building.” By the weekend, there were 6 cases of the mysterious disease, 73 more suspected, and 2 deaths. In the New York City outbreak, three brothers were the first vic- tims. Carlisle, Gilbert, and Joseph Leggette developed the fever, muscle aches, and chest congestion that make the disease resemble pneumo- nia. Joseph and Gilbert recovered; Carlisle did not. “He just got sick and about a week later he was dead,” said John Leggette, a fourth brother who warily returned to his own job in the garment district the next week. “I’m scared,” he said. “But what can you do?”14 n

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Health departments, the CDC in Atlanta, and epidemiologic researchers frequently confront a problem that has no clear determinants or etiologic basis. The methods and findings of epidemiologic studies may direct one to, or suggest, particular causal mechanisms underlying health-related events or conditions, such as the four examples cited in the vignettes: anthrax, the suspected outbreak of Ebola virus, Legionnaires’ disease, and red spots on airline flight attendants. Read the solution to Case 4 to clear up the mystery of Case 4.

Solution to Case 4: Red Spots

The investigation then concentrated on defining the clinical picture more clearly. An Eastern Airlines (EAL) physician, a consultant dermatologist, and a physician from the National Institute for Occupational Safety and Health (NIOSH) rode on implicated flights on March 14 and examined three new cases considered by the EAL physician and other flight atten- dants (FAs) to be typical cases. Although the spots observed consisted of red liquid, they did not resemble blood. To identify potential environmen- tal sources of red-colored material, investigators observed the standard activities of FAs on board implicated flights. At the beginning of each flight FAs routinely demonstrated the use of life vests, required in emer- gency landings over water. Because the vests used for demonstration were not actually functional, they were marked in bright red ink with the words “Demo Only.” When the vests were demonstrated, the red ink areas came into close contact with the face, neck, and hands of the demonstrator. Noting that on some vests the red ink rubbed or flaked off easily, inves- tigators used red material from the vests to elicit the typical clinical pic- ture on themselves. On preliminary chemical analyses, material in clinical specimens of red spots obtained from cases was found to match red-ink specimens from demonstration vests. On March 15 and 16, EAL removed all demonstration model life vests from all its aircraft and instructed FAs to use the standard, functional, passenger-model vests for demonstra- tion purposes. The airline . . . continue[d] to request reports of cases to verify the effectiveness of this action. Although all demonstration vests were obtained from the same manufacturer, the vests removed from spe- cific aircraft were noted to vary somewhat in the color of fabric and in the color and texture of red ink, suggesting that many different production lots may have been in use simultaneously on any given aircraft.15 n

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e p i d e m i o l o g y d e f i n e d 13

Distribution Frequency of disease occurrence and mortality rates vary from one population group to another in the United States. For example, in 2006 death rates from coronary heart disease (CHD) and stroke were higher among African-Americans (blacks) than among American Indians/Alaskan natives, Asian/Pacific islanders, or whites.16 In comparison with other racial/ethnic groups, Hispanics have lower mortality rates for CHD than non-Hispanics.16,17 Such variations in disease fre- quency illustrate how disease may have different distributions depending upon the underlying characteristics of the populations being studied. Population sub- groups that have higher occurrence of adverse health outcomes are defined as having health disparities, which need to be targeted for appropriate interventions.

Population Epidemiology examines disease occurrence among population groups rather than among individuals. Lilienfeld18 noted that this focus is a widely accepted feature of epidemiology. For this reason, epidemiology is often referred to as “population medicine.” As a result, the epidemiologic and clinical descriptions of a disease are quite different. Sometimes, when a new disease is first recognized, clinical descriptions of the condition are the first data available. These initial clinical descriptions can lead to subsequent epidemiologic investigations.

Note the different descriptions of toxic shock syndrome (TSS), a condition that showed sharp increases during 1980 in comparison with the immediately previous years. TSS is a severe illness that in the 1980 outbreak was found to be associated with vaginal tampon use. The clinical description of TSS would include specific signs and symptoms, such as high fever, headache, malaise, and other more dramatic symp- toms, such as vomiting and profuse watery diarrhea. The epidemiologic description would indicate which age groups would be most likely to be affected, time trends, geographic trends, and other variables that affect the distribution of TSS.

A second example is myocardial infarction (MI; heart attack). A clinical description of MI would list specific signs and symptoms, such as chest pain, heart rate, nausea, and other individual characteristics of the patient. The epi- demiologic description of the same condition would indicate which age groups would be most likely to be affected, seasonal trends in heart attack rates, geo- graphic variations in frequency, and other characteristics of persons associated with the frequency of heart attack in populations.

Referring again to the vignettes, one may note that the problem that plagued Kinfumu in Case 2 was recognized as a particularly acute problem for epidemiol- ogy when similar complaints from other patients were discovered and the disease