Epidemiology for public health practice 5th edition answer key

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

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rs

≥6 5

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Y rs

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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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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

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began to spread. If more than one person complains about a health problem, the health provider may develop the suspicion that some widespread exposure rather than something unique to an individual is occurring. The clinical observation might suggest further epidemiologic investigation of the problem.

Health Phenomena As indicated in the definition, epidemiology is used to investigate many differ- ent kinds of health outcomes. These range from infectious diseases to chronic diseases and various states of health, such as disability, injury, limitation of activ- ity, and mortality.19 Other health outcomes have included individuals’ positive functioning and active life expectancy as well as adverse health-related events, including mental disorders, suicide, substance abuse, and injury. Epidemiol- ogy’s concern with positive states of health is illustrated by research into active life expectancy among geriatric populations. This research seeks to determine the factors associated with optimal mental and physical functioning as well as enhanced quality of life and ultimately aims to limit disability in later life.

Morbidity and Mortality Two other terms central to epidemiology are morbidity and mortality. The for- mer, morbidity, designates illness, whereas the latter, mortality, refers to death. Note that most measures of morbidity and mortality are defined for specific types of morbidity or causes of death.

Aims and Levels The preceding sections hinted at the complete scope of epidemiology. As the basic method of public health, epidemiology is concerned with efforts to describe, explain, predict, and control. The term levels denotes the hierarchy of tasks that epidemiologic studies seek to accomplish (e.g., description of the occurrence of diseases is a less-demanding task and therefore ranks lower on the hierarchy of levels than explaining the causes of a disease and predicting and controlling them). More information will be provided later in the chapter.

●● To describe the health status of populations means to enumerate the cases of disease, to obtain relative frequencies of the disease within subgroups, and to discover important trends in the occurrence of disease.

●● To explain the etiology of disease means to discover causal factors as well as to determine modes of transmission.

●● To predict the occurrence of disease is to estimate the actual number of cases that will develop as well as to identify the distribution within populations.

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Such information is crucial to planning interventions and allocation of healthcare resources.

●● To control the distribution of disease, the epidemiologic approach is used to prevent the occurrence of new cases of disease, to eradicate existing cases, and to prolong the lives of those with the disease.

The implication of these aims is that epidemiology has two different goals: one related to the distribution of health outcomes and the second to controlling diseases. The first goal is to achieve an improved understanding of the natural history of disease and the factors that influence its distribution. With the knowl- edge that is obtained from such efforts, one can then proceed to accomplish the second goal, which is control of disease via carefully designed interventions.

Foundations of Epidemiology

Epidemiology Is Interdisciplinary Refer to Figure 1–4, which characterizes the interdisciplinary foundations of epidemiology. As an interdisciplinary field, epidemiology draws from biostatistics and the social and behavioral sciences as well as from the medically related fields such as toxicology, pathology, virology, genetics, microbiology, and clinical medi- cine. Terris20 pointed out that epidemiology is an extraordinarily rich and complex science that derives techniques and methodologies from many disciplines. He wrote that epidemiology “must draw upon and synthesize knowledge from the biological sciences of man and of his parasites, from the numerous sciences of the physical environment, and from the sciences concerned with human society.”20(p 203)

FiGURE 1–4 The interdisciplinary foundations of epidemiology.

Microbiology Virology

BiostatisticsToxicology

Epidemiology is Interdisciplinary

Social and Behavioral Sciences, Demography

Clinical Medicine/ Pathology

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Here are some illustrations of the contributions of other disciplines to epidemiology. Microbiology, the science of microorganisms, yields information about specific disease agents, including their morphology and modes of transmission. Related fields are bacteriology and virology. The previously discussed investigations of anthrax, Legionnaires’ disease, and TSS utilized microbiologic techniques to identify possible infectious agents. Another example is epidemiologic studies of foodborne illnesses (e.g., E. coli); these studies apply microbiologic procedures to reveal the commonalities of bacteria involved in an outbreak in order to define whether it was caused by a common source.

Clinical medicine is involved in the diagnosis of the patient’s state of health, particularly when defining whether the patient has a specific disease or condition. A pathologist’s expertise may help differentiate between normal and diseased tis- sue. From our previous examples, clinical medicine diagnosed the individuals’ symptoms or signs of ill health. Astute physicians and nurses may suggest epide- miologic research on the basis of clinical observations.

Toxicology, the science of poisons, is concerned with the presence and health effects of chemical agents, particularly those found in the environment and the workplace. A crucial issue for the United States is the fate of hazardous chemicals once they have performed their function. In the past, numerous toxic chemicals (e.g., pesticides) were deposited in an unsafe manner into waste sites that were later designated as hazardous. Toxicologic knowledge helps determine the pres- ence of noxious chemical agents in hazardous waste sites and whether any health effects observed are consistent with the known effects of exposure to toxic agents. When responses to exogenous agents vary from person to person, geneticists may become part of the research team via the disciplines of molecular and genetic epidemiology. Frequently, toxicologists and epidemiologists collaborate in envi- ronmental and occupational investigations.

Social and behavioral sciences elucidate the role of race, social class, edu- cation, cultural group membership, and behavioral practices in health-related phenomena. Social and behavioral science disciplines, that is, sociology and psychology, are devoted respectively to the development of social theory and the study of behavior. The special concern of social epidemiologic approaches is the study of social conditions and disease processes.21 Furthermore, the social sciences provide a great deal of the methodology on sampling; measurement; questionnaire development, design, and delivery; and group comparisons. Increasingly, community interventions have drawn upon the fund of knowledge from the social sciences. Demography is the study of data related to the structure of human populations.

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Finally, the field of biostatistics is critical to the evaluation of epidemiologic data, especially when one is trying to separate chance from meaningful obser- vations. Epidemiology profits from the interdisciplinary approach because the causality of a particular disease in a population may involve the interaction of multiple factors. The contributions of many disciplines help unravel the factors associated with a particular disease.

Methods and Procedures The empirical dimensions of epidemiologic studies require quantification of rele- vant factors. Quantification refers to the translation of qualitative impressions into numbers. Qualitative sources of information about disease may be, for example, a physician’s observations derived through medical practice about the types of people among whom a disease seems to be common. Epidemiologists enumerate cases of disease to objectify subjective impressions; the standard epidemiologic measures often require counting the number of cases of disease and examining their distri- bution according to demographic variables, such as age, sex, race, and other vari- ables as well as exposure category and clinical features. The following quotation

As of March 26, [2003] CDC has received 51 reports of suspected SARS cases from 21 states . . . identified using the CDC updated interim case definition . . . The first suspected case was identified on March 15, in a man aged 53 years who traveled to Singapore and became ill on March 10. Four clusters of suspected cases have been identified, three of which involved a traveler who had visited Southeast Asia (including Guangdong province, Hong Kong, or Vietnam) and a single family contact. One of these clusters involved suspected cases in patients L and M . . . who had stayed together at hotel M during March 1–6, when other hotel guests were symptomatic. Patient L became sick on March 13 after returning to the United States. His wife, patient M, became ill several days after the onset of her husband’s symptoms, suggesting secondary transmission.

The Language of Quantification: Severe Acute Respiratory Syndrome (SARS) in the United States

continues

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illustrates a summary of the characteristics of 51 suspected cases of severe acute respiratory syndrome (SARS) that were reported to the CDC as of early 2003.

Sometimes epidemiologists present quantified information as tables, maps, charts, and graphs. Both charts and graphs are pictorial illustrations of the fre- quency of disease. (Refer to the later section on John Snow for an example of a map.) Quantification facilitates the epidemiologic investigation of the sources of variation of a disease by the characteristics of time, place, and person: When did the case occur? Where was it located? Who was affected?

Key methods for the graphic presentation of data are the use of pie charts, bar graphs, and line graphs. Figure 1–5 shows an example of each type: a pie chart (A, admission diagnoses of discharged hospice care patients); a bar graph (B, diabetes prevalence among adults); and a line graph (C, obesity among children). Epidemiologists use these types of graphs to describe characteristics of data, such as subgroup differences and time trends.23

Use of Special Vocabulary Epidemiology employs a unique vocabulary of terms to describe the frequency of occurrence of disease. Examples from this vocabulary are the words epidemic and pandemic.

Dorland’s Illustrated Medical Dictionary defines the word epidemic as “attack- ing many people at the same time, widely diffused and rapidly spreading.” More precisely, an epidemic refers to an excessive occurrence of a disease: “Most current definitions [of epidemic] stress the concept of excessive prevalence as its basic implication in both lay and professional usage.”24(p 2) The following pas- sage illustrates this notion by defining an epidemic as:

The occurrence, in a defined community or region, of cases of an illness (or an outbreak) with a frequency clearly in excess of normal expectancy. The number of cases indicating presence of an epidemic varies according to the infectious agent, size and type of population exposed, previous experience or lack of exposure to the disease, and time and place of occurrence; epidemicity is thus relative to usual frequency of the disease . . .25(p 705)

Three patients in the United States with suspected SARS (patients I, L, and M) reported staying at hotel M when other persons staying in the hotel were symptomatic. The fourth cluster began with a suspected case in a person who traveled in Guangdong province and Hong Kong. Two [healthcare workers] subsequently became ill at the U.S. hospital where this patient was admitted.22(p 244) n

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FiGURE 1–5 Examples of three different presentations of epidemiologic data. (A) Pie chart. Primary admission diagnoses of discharged hospice care patients: United States, 2007 (B) Bar graph. Diabetes prevalence among adults 20 years of age and over, by age: United States, 1988–1994 and 2005–2008. (C) Line graph. Obesity among children, by age: United States, 1988–1994 through 2007–2008. Source: Adapted and Reprinted from National Center for Health Statistics. Health, United States, 2010: with Special Feature on Death and Dying. Hyattsville, MD, 2011.

*Chronic lower respiratory disease.

All other 26%

Stroke 5%

CLRD* 5%

Heart disease

11%

Cancer 43%

Alzheimer’s and other dementia

11%

20–44 years 3 1988–1994

2005–2008 4

14

14

20

20 30 Percent

100

27

45–64 years

65 years and over

20

15

10

5

6–11 years

12–19 years

2–5 years

0

P er

ce n

t

1988– 1994

1999– 2000 Year

2001– 2002

2003– 2004

2005– 2006

2007– 2008

A

B

C

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The “usual frequency” means the disease’s typical occurrence at the same time, within the same population, and in the same geographic area. Further, when a communicable disease has disappeared and a single case reappears, that event represents an epidemic. Also, the occurrence of two cases of a new disease (“first invasion”) linked in time and place may be considered to be an epidemic, as this happening suggests disease transmission.

Communicable disease—An illness caused by an infectious agent that can be transmitted from one person to another. Infectious disease—A synonym for a communicable disease. Outbreak—A localized disease epidemic (e.g., in a town or healthcare facility). n

Explanation of Key Terms Used in the Definition of “Epidemic”

In current thinking, an epidemic is not confined to infectious diseases. Take, for example, the Love Canal incident that generated spirited public debate and media attention during the late 1970s. Love Canal was a toxic waste disposal site located in Niagara Falls, New York. It was the destina- tion for burial of thousands of chemical-filled drums deposited by the Hooker Chemicals & Plastics Corporation. Eventually, the waste disposal site was covered and converted into a housing tract. Subsequently, residents of the area reported several different types of health effects, including miscarriages, birth defects, and impaired cognitive functioning. The Love Canal site was the focus of extensive health effects studies and epidemiologic research. The threat posed by Love Canal and other hazardous waste sites led to the creation of the Superfund in 1980. Its purpose was to promote the cleanup of hazard- ous wastes.

By referring to the case studies reported in this text, you have seen additional examples—red spots among airline FAs and TSS—that illustrate two instances in which epidemiologic methodology was employed to study noninfectious condi- tions. TSS and red spots among airline FAs both represented apparent epidemics because the usual or expected rate was nil. Epidemiologic methods also are used to investigate occupationally associated illness (e.g., brown lung disease among

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textile workers and asbestosis among shipyard workers), environmental health hazards (e.g., toxic chemicals and air pollution), and conditions associated with lifestyle (e.g., unintentional injuries, ischemic heart disease, and certain forms of cancer).

Related to the term epidemic is the term pandemic, which refers to an epidemic on a worldwide scale; during a pandemic, large numbers of persons may be affected and a disease may cross international borders. Examples are flu pandemics, such as the pandemic of 1918 and more recent flu pandemics that occur periodically. The term endemic is used to characterize a disease that is habitually present in a particular geographical region. To illustrate, malaria is endemic to some tropical areas of Asia, and cholera is endemic to less developed countries where sanitation is lacking. Previously, during the 19th century, cholera was endemic to Western countries, such as England and the United States. However, cholera is no longer endemic to these two countries because of the introduction of sanitation and other public health measures.

Methods for Ascertainment of Epidemic Frequency of Disease The CDC and vital statistics departments of state and local governments gather surveillance data on a continuing basis to determine whether an epidemic is taking place. The word surveillance denotes the systematic collection of data per- taining to the occurrence of specific diseases, the analysis and interpretation of these data, and the dissemination of consolidated and processed information to contributors to the surveillance program and other interested persons. Com- mon surveillance activities include monitoring foodborne disease outbreaks, collecting information on communicable and infectious diseases, and tracking influenza.

As noted previously, an epidemic refers to the occurrence of disease in excess of normal expectancy. In order to ascertain epidemic trends, one must have data about the usual occurrence of a disease. Providing such information is the function of surveillance. For example, suppose a health practitioner states that 500 CHD deaths were reported in an upstate New York community during a particular year and that an epidemic is taking place. This information by itself would be insufficient to justify the assertion that an epidemic of CHD deaths has occurred. The usual frequency of CHD deaths would need to be determined via ongoing surveillance programs in the same community at some prior time. In addition, the size, age, and sex distribution of the population would need to be

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22 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

known. With this information at hand, one could determine whether or not an epidemic of CHD deaths has occurred.

A second example of determining epidemic frequency is shown in Figure 1–6 for influenza and pneumonia deaths. The figure displays weekly pneumonia and influenza deaths in the United States from winter 2007 to spring 2012. The chart demonstrates that influenza (flu) has an underlying sea- sonal baseline, reflected in cyclic seasonal increases and declines in mortality. In the United States and other countries in the Northern hemisphere, flu occurs most frequently during the winter months (i.e., from October through April).26 Therefore, the flu season spans the latter part of one calendar year and the early part of the following year (e.g., the 2011–2012 flu season). In the figure, the lower line denotes the usual number of total deaths to be expected from pneumonia and influenza during each week of the year. An upper paral- lel line indicates the frequency of disease at the epidemic threshold, that is, the minimum number of deaths that would support the conclusion that an epidemic was under way. The epidemic threshold is based on statistical projec- tions. Figure 1–6 demonstrates that the combined pneumonia and influenza deaths peaked substantially above the epidemic threshold during early 2008, late 2009, and early 2011.

FiGURE 1–6 Percentage of all deaths attributable to pneumonia and influenza (P&I), by surveillance week and year—122 Cities Mortality Reporting System, United States, 2007–May 19, 2012. Source: Reproduced Centers for Disease Control and Prevention. Update Influenza Activity—United States, 2011–12 Season and Composition of the 2012–13 Influenza Vaccine. MMWR. 2012;61:418.

Epidemic threshold

% o

f al

l d ea

th s

at tr

ib u

te d

t o

P &

I

Seasonal baseline

105040 4

5

6

7

8

9

10

20 30

20082007

40 50 10 20 30

2009

40 50 10 20 30

2010

40 50 10 20 30

2011

10 20

2012

40 50

Surveillance week and year

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Historical Antecedents of Epidemiology

Epidemiology is often thought of as a relatively new discipline. However, this viewpoint is not entirely correct. The history of epidemiology began with the classical period of the Greeks and Romans and included major developments that occurred during later eras: the medieval period, the Renaissance, the late 1800s and early 1900s, and more recently the mid- to late 20th century, when the pace of epidemiologic activities exploded.

It may be said that epidemiology began with the Greeks, who in their concern for the ancient epidemics and deadly toll of diseases, attributed disease causality to environmental factors. Early causal explanations for epidemics included the wrath of the gods, the breakdown of religious beliefs and morality, the influence of weather, and “bad air.” During the medieval period, the Black Death caused by plague killed more than 25% of the European population. Another terrible scourge was smallpox: Edward Jenner’s work led to the development of an effec- tive vaccination against smallpox. During the late Renaissance, pioneering bio- statisticians quantified morbidity and mortality trends.

When the 19th century arrived, deadly cholera epidemics impacted Europe and the United States The disease is thought to have been spread along trade routes from India to Asia, the Middle East, and Russia. Cholera is a life- threatening condition caused by a bacterium; victims retch from severe (but painless) vomiting and diarrhea and eventually die from dehydration and elec- trolyte disturbances. An example that memorializes the assault of cholera on Europe is the Cholera Fountain (Cholera Brunnen) in Dresden, Germany. Resi- dents constructed the fountain in the mid-1800s to express their gratitude for having escaped a cholera epidemic that threatened the city. (See Figure 1–7.) Often cited as a major historical development is John Snow’s investigations of London cholera outbreaks, reported in Snow on Cholera.27

A contemporary of Snow, William Farr, promoted innovative uses of vital sta- tistics data. During the 19th century, early microbiologists formalized the germ theory of disease, which attributed diseases to specific organisms. At the begin- ning of the 20th century, a flu pandemic killed more than 50 million people worldwide. Each of these historical developments that contributed to the genesis of epidemiology is discussed in turn below.

Environment as a Factor in Disease Causation The following account by Thucydides records, in detail, the ravages produced by a deadly disease, “Thucydides’ plague”28; such graphic descriptions of major

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FiGURE 1–7 The Cholera Fountain in Dresden, Germany.

epidemics in history indicate this early author’s concern with the causality of these remarkable phenomena:

Others, who were in perfect health, were taken suddenly, without any apparent cause, with violent heats in their heads, and with redness and inflammations in their eyes. Their tongues and throats within became immediately bloody; their breath in great disorder and offensive. A sneezing and a hoarseness ensued; and, in a short time, the pain descended into the breast, attended with a violent cough. When it was once settled about the mouth of the stomach, a retching, and vomit- ing of bilious stuff, in as great a variety as ever was known among physicians, suc- ceeded, but not without the greatest anxiety imaginable. Many were seized with a hiccup, that brought up nothing, but occasioned a violent convulsion, which in some went off presently, but in others continued much longer. The body out- wardly was neither very hot to the touch, nor pale, but reddish, livid, and flow- ered (as it were) all over with little pimply eruptions, and ulcers; but inwardly the heat was so exceedingly great, that they could not endure the slightest covering, or the finest linen, or any thing short of absolute nakedness. It was also an infinite pleasure to them to plunge into cold water; and many of those who were not well attended did so, running to the wells, to quench their insatiable thirst: not that it signified whether they drank much or little; a great uneasiness and restless- ness attending them, together with a continual watching. While the distemper was

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advancing to the height, the body did not fall away, but resisted the vehemence of it beyond expectation; so that many of them died the ninth and the seventh day of the inward burning, some strength yet remaining; or, if they held out longer, many of them afterwards died of weakness; the distemper descending into the belly, and there producing violent ulcerations, and fluxes of the simple or unmixed kind.28

Hippocrates, in On Airs, Waters, and Places,29 gave birth in about 400 bc to the idea that disease might be associated with the physical environment; his thinking represented a movement away from supernatural explanations of dis- ease causation to a rational account of the origin of humankind’s illnesses. Note in the following passage his reference to climate and physical environment:

Whoever wishes to investigate medicine properly should proceed thus: in the first place to consider the seasons of the year, and what effects each of them produces (for they are not at all alike, but differ much from themselves in regard to their changes). Then the winds, the hot and the cold, especially such as are common to all countries, and then such as are peculiar to each locality. We must also consider the qualities of the waters, for as they differ from one another in taste and weight, so also do they differ much in their qualities. In the same manner, when one comes into a city to which he is a stranger, he ought to consider its situation, how it lies as to the winds and the rising of the sun; for its influence is not the same whether it lies to the north or the south, to the rising or to the setting sun. These things one ought to consider most attentively, and concerning the waters which the inhabit- ants use, whether they be marshy and soft, or hard, and running from elevated and rocky situations, and then if saltish and unfit for cooking; and the ground, whether it be naked and deficient in water, or wooded and well watered, and whether it lies in a hollow, confined situation, or is elevated and cold; and the mode in which the inhabitants live, and what are their pursuits, whether they are fond of drinking and eating to excess, and given to indolence, or are fond of exercise and labor, and not given to excess in eating and drinking.29(pp 156–157)

The Black Death Occurring between 1346 and 1352, the Black Death is a dramatic example of a pandemic of great historical significance to epidemiology.30 The Black Death is noteworthy because of the scope of human mortality that it produced as well as for its impact upon medieval civilization. Estimates suggest that the Black Death claimed about one-quarter to one-third of the population of Europe. Northern Africa and the near Middle East also were affected severely; at the inception of the outbreak, the population of this region including Europe numbered about 100 million people; 20–30 million people are believed to have died in Europe.

Historians attribute the Black Death to bubonic plague, which is the most common of the three forms of plague.30,31 The bacterium Yersinia pestis pro- duces swelling of the lymph nodes in the groin and other sites of the body.

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These painful swellings, called buboes, are followed in several days by high fever and the appearance of black splotches on the skin. The reservoir for Y. pestis is vari- ous types of rodents, including rats. Plague can be transmitted when fleas that feed on rodents bite a human host. At the time of the Black Death, no method for treat- ment of plague existed. Most victims died within a few days after the occurrence of buboes. Currently, plague is treatable with antibiotics. In addition, improvement in sanitary conditions has led to the decline in plague cases; 2,118 cases were reported worldwide in 2003.31 From 1,000 to 2,000 plague cases are reported annually to the World Health Organization (according to data available in 2012).32

Use of Mortality Counts In 1662, John Graunt published Natural and Political Observations Mentioned in a Following Index, and Made Upon the Bills of Mortality.33 This work recorded descriptive characteristics of birth and death data, including seasonal variations, infant mortality, and excess male over female differences in mortality. Graunt’s work made a fundamental contribution by discovering regularities in medical and social phenomena. He is said to be the first to employ quantitative meth- ods in describing population vital statistics by organizing mortality data in a mortality table and has been referred to as the Columbus of statistics. Graunt’s procedures allowed the discovery of trends in births and deaths due to specific causes. Although his conclusions were sometimes erroneous, his development of statistical methods was highly important.34

Concerning sex differences in death rates, Graunt wrote:

Of the difference between the numbers of Males and Females. The next Observation is, That there be more Males than Females . . . There have been Buried from the year 1628, to the year 1662, exclusive, 209436 Males, and but 190474 Females: but it will be objected, That in London it may be indeed so, though otherwise elsewhere; because London is the great Stage and Shop of business, wherein the Masculine Sex bears the greatest part. But we Answer, That there have been also Christened within the same time 139782 Males, and but 130866 Females, and that the Country- Accounts are consonant enough to those of London upon this matter.33(p 44)

Figure 1–8 shows the 10 leading causes of mortality from the Yearly Mortality Bill for 1632. A legend at bottom of the figure defines the archaic terms used in Graunt’s time.

Edward Jenner and Smallpox Vaccination The term vaccination derives from the Latin word for cow (vacca), the source of the cowpox virus that was used to create a vaccine against smallpox. A precursor

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of smallpox vaccination was variolation, which referred to an early Asian method of conferring immunity to smallpox by introducing dried scabs from smallpox patients into the noses of potential victims who wished to be protected from this disease.35 Variolation often produced a milder case of disease with a much lower fatality rate than that caused by community-acquired smallpox. The method gained popularity in Europe during the early 1700s, when the procedure was modified by injecting infectious material under the skin; variolation was first tested among abandoned children and prisoners. When it was declared safe, members of the English royal family were inoculated.

Edward Jenner (Figure 1–9) is credited with the development of the smallpox vaccination, a lower-risk method for conferring immunity against smallpox than

FiGURE 1–8 Yearly Mortality Bill for 1632: The 10 leading causes of mortality in Graunt’s Time. Source: Data from Graunt J. Natural and Political Observations, Mentioned in a Following Index, and Made upon the Bills of Mortality, 2nd ed. London: Tho. Roycroft; 1662: p. 8.

Chrisom

Consumption

Fever

Collick, Stone, and Strangury

Flux and Small Pox

Bloody Flux, Scowring, and Flux

Dropsie and Swelling

Glossary of Terms Used in Chart

Bloody flux

Chrisom

Consumption

Dropsie

Flox

Flux

Liver grown

Scowring

Small pox

Stone

Strangury

Dysentery

Death of a child within one month of baptism

Tuberculosis

Dropsy—edema

Hemorrhagic smallpox

Excessive flow or discharge from the boby

Having an enlarged liver

Scouring—purging of the bowels; probably referring to diarrhea

Smallpox

Calculus, e.g., gallstone

Slow and painful discharge of urine

Convulsion

Childbed

Liver grown

Number of deaths

0 500 1000 1500 2000 2500

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variolation.36 He was fascinated by folk wisdom, which suggested that dairy- maids who had contracted cowpox seemed to be immune to smallpox. Infec- tion with the cowpox virus produced a much less severe form of disease than smallpox. Jenner conducted an experiment in which he used scabs from the cow- pox lesions on the arm of a dairymaid, Sarah Nelmes (Figure 1–10), to create a smallpox vaccine. He then used the material to vaccinate an 8-year-old boy, James Phipps. Following the vaccination, Phipps appeared to develop immu- nity to the smallpox virus to which he was reexposed several times subsequently.

FiGURE 1–9 Edward Jenner vaccinating a child. Source: Images from the History of Medicine, National Library of Medicine.

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Later, Jenner vaccinated his own son and several other children, obtaining similar positive findings, which were published in 1798. (In 1978 smallpox was finally eliminated worldwide. Since 1972, routine vaccination of the nonmilitary popu- lation of the United States has been discontinued.)37

Use of Natural Experiments A natural experiment refers to “[n]aturally occurring circumstances in which sub- sets of the population have different levels of exposure to a supposed causal factor in a situation resembling an actual experiment, where human subjects would be randomly allocated to groups. The presence of persons in a particular group is typically nonrandom;”6 the following section is an account of John Snow’s natu- ral experiment.

FiGURE 1–10 Arm of Sarah Nelmes with lesions of cowpox. Source: Reproduced from the National Library of Medicine. Smallpox: A great and terrible scourge: Vaccination. Available at: http://www.nlm.nih.gov/exhibition/smallpox/ sp_vaccination.html. Accessed July 19, 2012.

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During the 19th century, water from the highly polluted Thames River was London’s primary source of drinking water. Figure 1–11 expresses concerns about the cleanliness of Thames River water during this time period. In this context John Snow conducted a famous natural experiment.

Snow investigated a cholera epidemic that occurred during the mid-19th century in Broad Street, Golden Square, London. Snow’s work, a classic study that linked the cholera epidemic to contaminated water supplies, is noteworthy because it utilized many of the features of epidemiologic inquiry: a spot map of cases and tabulation of fatal attacks and deaths. Through the application of his keen powers of observation and inference, he developed the hypothesis that contaminated water might be associated with outbreaks of cholera. He made several observations that others had not previously made. One observation was that cholera was associated with water from one of two water supplies that served the Golden Square district of London.38 Broad Street was served by two sepa- rate water companies, the Lambeth Company and the Southwark and Vauxhall Company. Lilienfeld and Lilienfeld39 wrote:

In London, several water companies were responsible for supplying water to differ- ent parts of the city. In 1849, Snow noted that the cholera rates were particularly

FiGURE 1–11 George Cruickshank, 1792–1878, artist. Salus Populi Suprema Lex Source of the South Warwick Water Works. Source: Images from the History of Medicine, National Library of Medicine.

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high in those areas of London that were supplied by the Lambeth Company and the Southwark and Vauxhall Company, both of whom obtained their water from the Thames River at a point heavily polluted with sewage.39(p 36)

Snow’s account of the outbreak of 1849 is found in Exhibit 1–2. Between 1849 and 1854 the Lambeth Company had its source of water relo-

cated to a less contaminated part of the Thames. In 1854, another epidemic of

Snow on Cholera

The most terrible outbreak of cholera which ever occurred in this kingdom, is probably that which took place in Broad Street, Golden Square, and the adjoining streets, a few weeks ago. Within two hun- dred and fifty yards of the spot where Cambridge Street joins Broad Street, there were upwards of five hundred fatal attacks of cholera in ten days. The mortality in this limited area probably equals any

that was ever caused in this country, even by the plague; and it was much more sudden, as the greater number of cases terminated in a few hours. The mortality would undoubtedly have been much greater had it not been for the flight of the population. Persons in furnished lodgings left first, then other lodgers went away, leaving their furniture to be sent for when they could meet with a place to put it in. Many houses were closed alto- gether, owing to the death of the proprietors; and, in a great number of instances, the tradesmen who remained had sent away their families: so that in less than six days from the commencement of the outbreak, the most afflicted streets were deserted by more than three-quarters of their inhabitants.

There were a few cases of cholera in the neighbourhood of Broad Street, Golden Square, in the latter part of August; and the so-called outbreak, which commenced in the night between the 31st August and the 1st September, was, as in all similar instances, only a violent increase of the malady. As soon as I became acquainted with the situation and extent of this irruption of cholera, I suspected some contamination of the water of the much-frequented street-pump in Broad Street, near the end of Cambridge Street; but on examining the water, on the evening of the 3rd September, I found so little impurity in it of an organic nature, that I hesi- tated to come to a conclusion. Further inquiry, however, showed me that

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32 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

there was no other circumstance or agent common to the circumscribed locality in which this sudden increase of cholera occurred, and not extend- ing beyond it, except the water of the above mentioned pump. I found, moreover, that the water varied, during the next two days, in the amount of organic impurity, visible to the naked eye, on close inspection, in the form of small white, flocculent particles; and I concluded that, at the com- mencement of the outbreak, it might possibly have been still more impure.

The deaths which occurred during this fatal outbreak of cholera are indicated in the accompanying map (Figure 1–12), as far as I could ascer- tain them . . . The dotted line on the map surrounds the sub-districts of Golden Square, St. James’s, and Berwick Street, St. James’s, together with the adjoining portion of the sub-district of St. Anne, Soho, extending from Wardour Street to Dean Street, and a small part of the sub-district of St. James’s Square enclosed by Marylebone Street, Titchfield Street, Great Windmill Street, and Brewer Street. All the deaths from cholera which were registered in the six weeks from 19th August to 30th September within this locality, as well as those of persons removed into Middlesex Hospital, are shown in the map by a black line in the situation of the house in which it occurred, or in which the fatal attack was contracted . . . The pump in Broad Street is indicated on the map, as well as all the surrounding pumps to which the public had access at the time. It requires to be stated that the water of the pump in Marlborough Street, at the end of Carnaby Street, was so impure that many people avoided using it. And I found that the persons who died near this pump in the beginning of September, had water from the Broad Street pump. With regard to the pump in Rupert Street, it will be noticed that some streets which are near to it on the map, are in fact a good way removed, on account of the circuitous road to it. These circumstances being taken into account, it will be observed that the deaths either very much diminished, or ceased altogether at every point where it becomes decidedly nearer to send to another pump than to the one in Broad Street. It may also be noticed that the deaths are most numer- ous near to the pump where the water could be more readily obtained . . . The greatest number of attacks in any one day occurred on the 1st of September, immediately after the outbreak commenced. The following

Exhibit 1–2 continued

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Exhibit 1–2 continued

FiGURE 1–12 Cholera deaths in the neighborhood of Broad Street, August 19 to September 30, 1849. Source: Reproduced from John Snow’s dot map of the Broad Street and Golden Square area of London, in Snow on Cholera by John Snow, Commonwealth Fund: New York, 1936.

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Exhibit 1–2 continued

FiGURE 1–13 The 1849 cholera outbreak in Golden Square district, London. Fatal attacks and deaths, August 31– September 8. Source: Data from Table I, Snow J. Snow on Cholera, p. 49, Harvard University Press, © 1965.

Aug. 31 Sept. 1 Sept. 2 Sept. 3 Sept. 4 Sept. 5 Sept. 6 Sept. 7 Sept. 8

160

140

120

100

80

60

40

20

0

N u

m b

er

Date

Legend

Fatal Attacks

Deaths

day the attacks fell from one hundred and forty-three to one hundred and sixteen, and the day afterwards to fifty-four . . . The fresh attacks contin- ued to become less numerous every day. On September the 8th—the day when the handle of the pump was removed—there were twelve attacks; on the 9th, eleven; on the 10th, five; on the 11th, five; on the 12th, only one; and after this time, there were never more than four attacks on one day. During the decline of the epidemic the deaths were more numerous than the attacks, owing to the decrease of many persons who had lingered for

several days in consecutive fever (Figure 1–13). n

Source: Reprinted from Snow J. Snow on Cholera. Cambridge, MA: Harvard University Press: 1965:38–51.

cholera occurred. This epidemic was in an area that consisted of two-thirds of London’s resident population south of the Thames and was being served by both companies. In this area, the two companies had their water mains laid out in an interpenetrating manner, so that houses on the same street were receiving their water from different sources.39

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This was a naturally occurring situation, a “natural experiment,” if you will, because in 1849 all residents received contaminated water from the two water companies. After 1849, the Lambeth Company used less contaminated water by relocating its water supply. Snow demonstrated that a disproportionate number of residents who contracted cholera in the 1854 outbreak used water from one water company, which used polluted water, in comparison with the other com- pany, which used relatively unpolluted water.

Snow’s methodology maintains contemporary relevance. His methods utilized logical organization of observations, a natural experiment, and a quantitative approach.39 All these methods are hallmarks of present-day epi- demiologic inquiry. Note that it is possible to visit the site of the pump that figured so prominently in Snow’s investigation of cholera; a London public house on the original site of the pump has been named in Snow’s honor. A replica of the pump is located nearby. Refer to Exhibit 1–3 for pictures of the site and the pump with a reproduction of the text on the base of the replica.

Another study, occurring during the mid-19th century, also used nascent epidemiologic methods. Ignaz Semmelweis,40 in his position as a clinical assis- tant in obstetrics and gynecology at a Vienna hospital, observed that women in the maternity wards were dying at high rates from puerperal fever. In 1840, when the medical education system changed, he found a much higher mortality rate among the women on the teaching wards for medical students