"CHAPTER 1 History and Scope of Epidemiology LEARNING OBJECTIVES By the end of this chapter the reader will be able to:? •• define the term epidemiology ? •• define the components of epidemiology (determinants, distribution, morbidity, andmortality) ? •• name and describe characteristics of the epidemiologic approach ? •• discuss the importance of Hippocrates’ hypothesis and how it differed from the commonbeliefs of the time ? •• discuss Graunt’s contributions to biostatistics and how they affected modernepidemiology ? •• 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 ExercisesIntroduction Controversies and speculations regarding the findings of epidemiologic research are frequenttopics of media reports; these findings sometimes arouse public hysteria. Examples of thequestions raised by media reports include: “Is it more dangerous to vaccinate an entirepopulation against smallpox (with resulting complications from the vaccine) or to risk infectionwith the disease itself through a terrorist attack?” “Is Ebola virus a danger to the generalpublic?” “Should I give up eating fatty foods?” “Is it safe to drink coffee or alcoholicbeverages?” “Will chemicals in the environment cause cancer?” “Should one purchase bottledwater instead of consuming tap water from public drinking supplies?” “Will medications forchronic diseases (long-standing illnesses that are difficult to eradicate) such as diabetes causeharmful 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?”1 Consider the 2009–2010 episode of influenza first identified in the United States andeventually 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 DiseaseControl and Prevention (CDC), which investigates outbreaks of infectious diseases such asinfluenza. Thereafter, the number of cases expanded rapidly in the United States and thenworldwide. When the epidemic eventually subsided during summer 2010, an estimated 60million cases had occurred in the United States. According to the CDC, people in the age rangeof 18–64 years were most heavily affected by the virus; less affected were those 65 years of ageand older. Exhibit 1–1 provides an account of the pandemic.CHAPTER 1 History and Scope of Epidemiology LEARNING OBJECTIVES By the end of this chapter the reader will be able to:? •• define the term epidemiology ? •• define the components of epidemiology (determinants, distribution, morbidity, andmortality) ? •• name and describe characteristics of the epidemiologic approach ? •• discuss the importance of Hippocrates’ hypothesis and how it differed from the commonbeliefs of the time ? •• discuss Graunt’s contributions to biostatistics and how they affected modernepidemiology ? •• 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 ExercisesIntroduction Controversies and speculations regarding the findings of epidemiologic research are frequenttopics of media reports; these findings sometimes arouse public hysteria. Examples of thequestions raised by media reports include: “Is it more dangerous to vaccinate an entirepopulation against smallpox (with resulting complications from the vaccine) or to risk infectionwith 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 alcoholicbeverages?” “Will chemicals in the environment cause cancer?” “Should one purchase bottledwater instead of consuming tap water from public drinking supplies?” “Will medications forchronic diseases (long-standing illnesses that are difficult to eradicate) such as diabetes causeharmful 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?”1 Consider the 2009–2010 episode of influenza first identified in the United States andeventually called 2009 H1N1 influenza. Ultimately the 2009 H1N1 outbreak threatened tobecome 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 DiseaseControl and Prevention (CDC), which investigates outbreaks of infectious diseases such asinfluenza. Thereafter, the number of cases expanded rapidly in the United States and thenworldwide. When the epidemic eventually subsided during summer 2010, an estimated 60million cases had occurred in the United States. According to the CDC, people in the age rangeof 18–64 years were most heavily affected by the virus; less affected were those 65 years of ageand older. Exhibit 1–1 provides an account of the pandemic. EXHIBIT 1–1 The 2009H1N1 Pandemic During spring 2009, a 10-year-old California child was diagnosed with an unusual variety ofinfluenza. Soon afterwards a case of the same flu strain was identified in an 8-year-old wholived approximately 130 miles from the first patient. This was an alarming event in severalrespects. The type of influenza virus was usually found among swine. However, the newlyidentified virus appeared to have been transmitted among humans. Secondly, the appearanceof these two unusual cases raised public health officials’ suspicions that a deadly flu pandemicsimilar to the 1918 pandemic might be under way.Scientists named the new virus 2009 H1N1. The agent was “… a unique combination of1 influenza virus genes never previously identified in either animals or people.” The genes of thenew virus were closely related to North American swine-lineage H1N1 influenza viruses. Beforethis 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 ofswine influenza had been reported. The vast majority (n = 11) had indicated some contact withpigs. One of the unusual features of infections with the 2009 H1N1 virus were reports of a highprevalence of obesity among influenza-affected patients in intensive care units.Following the identification of the initial cases in California, swine flu spread across the UnitedStates and jumped international borders. In response to a potential widespread epidemic, someschools and public health officials implemented pandemic preparedness plans, which includedschool closures and social distancing. In June, the World Health Organization (WHO) declaredthat a global pandemic was under way. Here is a brief chronology of the events that transpiredduring the pandemic. ? •• April 15, 2009—first case of pandemic influenza (2009 H1N1) identified in a 10-year-oldCalifornia patient. ? •• April 17—eight-year-old child living 130 miles away from first case develops influenza. ? •• April 21—Centers for Disease Control and Prevention (CDC) began work on a vaccineagainst the virus. ? •• April 22—three new cases are identified in San Diego County and Imperial County. ? •• April 23—two new cases identified in Texas. ? •• 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 highrisk of complications from flu. ? •• June 11—WHO raises the worldwide pandemic alert level to phase 6 and declares theglobal 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 50states 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 H1N1between April 2009 and March 13, 2010. The estimated range of the number of cases wasbetween 43 million and 88 million. The process of estimating the number of flu cases isimprecise because many patients who become ill do not seek medical care, and those who doare not tested for the virus. Figure 1–1 reports CDC estimates of 2009 H1N1 cases in the US byage group.Source: Data from Centers for Disease Control and Prevention. The 2009 H1N1pandemic: summary highlights, April2009—April 2010. Available at: http://www.cdc.gov/h1n1flu/cdcresponse.htm. Accessed July 19, 2012. 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 inthe United States and captured media headlines 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 produce 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 outbreaksickened 199 persons across United States and caused 3 deaths (as of October 6, 2006, whenthe outbreak appeared to have subsided). Figure 1–2 shows the affected states. The 2006outbreak caused 102 (51%) of the ill persons to be hospitalized; in all, 31 patients (16%) wereafflicted with HUS. The majority of cases (141, 71%) were female. A total of 22 children 5 years2 of age and younger were affected.FIGURE 1–2 Distribution of Escherichia coli serotype O157:H7cases across the United States, September 2006. Source: Reproduced from Centers for Disease Control and Prevention. Ongoing multistate outbreak of Escherichiacoli serotype O157:H7 infections associated with consumption of fresh spinach—United States, September 2006.MMWR. 2006;55:1045–1046.Tracking down the mysterious origins of the outbreak required extensive detective work. Theoutbreak was linked to prepackaged spinach as the most likely vehicle. Investigators traced thespinach back to its source, Natural Selection Foods near Salinas, California. The producer3 announced a recall of spinach on September 15, 2006. The FDA and State of Californiaconducted a trace-back investigation, which implicated four ranches in Monterey and SanBenito Counties. Cattle feces from one of the four ranches contained a strain of E. coli O157:H7that matched the strain that had contaminated the spinach and also matched the strain found4 in the 199 cases. The mechanism for contamination of the spinach with E. coli bacteria wasnever established definitively.Noteworthy is the fact that subsequent to this major outbreak, E. coli O157:H7 continues to5 threaten the food supply of the United States, not only from spinach but also from other foods.During November and December 2006, Taco Bell restaurants in the northeastern United Statesexperienced a major outbreak that caused at least 71 persons to fall ill. Contamination ofTopp’s brand frozen ground beef patties and Totino’s or Jeno’s brand frozen pizzas with E. coliO157:H7 is believed to have sickened more than 60 residents of the eastern half of the United States during summer and early fall 2007. In 2008 and 2009, E. coli outbreaks were associatedwith ground beef and prepackaged cookie dough. Ground beef, cheese, romaine lettuce,bologna, and hazelnuts caused outbreaks during 2010 and 2011. A major outbreak of E. coliO104 occurred in Germany in 2011; 6 travelers from the United States were made ill, with oneof the six dying. During summer 2012, a multistate outbreak caused by E. coli O145 sickened 18persons and caused 9 deaths.In summary, the 2009 H1N1 flu pandemic (Exhibit 1–1) and the E. coli spinach-associatedoutbreak illustrate that epidemiologic research methods are a powerful tool for studying thehealth of populations. In many instances, epidemiology resembles detective work, because thecauses of disease occurrence are often unknown. Both examples raise several issues that aretypical of many epidemiologic research studies:? •• When there is a linkage or association between a factor (i.e., contaminants in food andwater; animal reservoirs for disease agents) and a health outcome, does this observationmean that the factor is a cause of disease? ? •• If there is an association, how does the occurrence of disease vary according to thedemographic characteristics and geographic locations of the affected persons? ? •• Based on the observation of such an association, what practical steps should individualsand 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 wasconducted? What are the policy implications of the findings? In this chapter we answer the foregoing questions. We discuss the stages that are necessary tounravel mysteries about diseases, such as those due to environmental exposures or those forwhich the cause is entirely unknown.Epidemiology is a discipline that describes, quantifies, postulates causal mechanisms fordiseases in populations, and develops methods for the control of diseases. Using the results ofepidemiologic studies, public health practitioners are aided in their quest to control healthproblems such as foodborne disease outbreaks and influenza pandemics. The investigation intothe 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 additionalstudies. Extensive detective work was involved in identifying the cause of the outbreak. Thehypothesized causal mechanism that was ultimately linked to contaminated spinach was thebacterium E. coli. All of the features described in the investigation are hallmarks of theepidemiologic approach. In this example, the means by which E. coli contaminated the spinachremains an unresolved issue.The 2009 H1N1 pandemic demonstrated the use of epidemiologic data to identify the source ofthe initial outbreaks, describe pandemic spread, and mount a public health response to controla 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 washingone’s hands frequently.Epidemiology Defined The word epidemiology derives from epidemic, a term that provides an immediate clue to itssubject matter. Epidemiology originates from the Greek words epi (upon) + demos (people) +logy (study of). Although some conceptions of epidemiology are quite narrow, we suggest abroadened scope and propose the following definition:? Epidemiology is concerned with the occurrence, distribution, and determinants of “health- 6 related states or events” (e.g., health and diseases, morbidity, injuries, disability, andmortality in populations). Epidemiologic studies are applied to the control of healthproblems in populations. The key aspects of this definition are determinants, distribution,population, and health phenomena (e.g., morbidity and mortality). DeterminantsDeterminants are factors or events that are capable of bringing about a change in health. Someexamples are specific biologic agents (e.g., bacteria) that are associated with infectious diseasesor chemical agents that may act as carcinogens. Other potential determinants for changes inhealth may include less specific factors, such as stress or adverse lifestyle patterns (lack ofexercise or a diet high in saturated fats). The following four vignettes illustrate the concern ofepidemiology with disease determinants. For example, consider the steps taken to track downthe source of the bacteria that caused anthrax and were sent through the mail; contemplatethe position of an epidemiologist once again. Imagine a possible scenario for describing,quantifying, and identifying the determinants for each of the vignettes.Case 1: Intentional Dissemination of Bacteria That CauseAnthrax After the United States experienced its worst terrorist attack on September 11, 2001, reportsappeared in the media about cases of anthrax in Florida beginning in early October. In theUnited States, anthrax usually affects herbivores (livestock and some wild animals); humancases are unusual. Anthrax is an acute bacterial disease caused by exposure to Bacillusanthracis. 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 severeinhalational form, which affects the lungs and later becomes disseminated by the bloodstream,7 has a high case fatality rate. Observations of an alert infectious disease specialist along withthe support of laboratory staff led to the suspicion that anthrax had been deliberately sent8 through the postal system. 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 York9 12 City, New Jersey, and the District of Columbia. – Figure 1–3 portrays the distribution of the 21cases in 4 geographic areas of the United States.FIGURE 1–3 Occurrence of anthrax cases during the 2001terrorist incident according to the investigation by the Centersfor Disease Control and Prevention.Case 2: Outbreak of Fear When a 36-year-old lab technician known as Kinfumu checked into the general hospital inKikwit, Zaire, complaining of diarrhea and a fever, anyone could have mistaken his illness forthe dysentery that was plaguing the city. Nurses, doctors, and nuns did what they could to helpthe young man. They soon saw that his disease wasn’t just dysentery. Blood began oozing fromevery orifice in his body. Within 4 days he was dead. By then the illness had all but liquefied hisinternal organs.That was just the beginning. The day Kinfumu died, a nurse and a nun who had cared for himfell ill. The nun was evacuated to another town 70 miles to the west where she died—but notuntil the contagion had spread to at least three of her fellow nuns. Two subsequently died. InKikwit, the disease raged through the ranks of the hospital’s staff. Inhabitants of the city beganfleeing 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. TheGeneva-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 transport13 planes headed for Kikwit.Case 3: Fear on Seventh Avenue On normal workdays, the streets of New York City’s garment district are lively canyons bustlingwith honking trucks, scurrying buyers, and sweating 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 stagnant waterfrom the gutters and spraying out disinfectant. Teams of health officers drained water towerson building roofs. Air conditioners fell silent for inspection, and several chilling signs appearedon 35th Street: “The New York City Department of Health has been advised of possible cases ofLegionnaires’ disease in this building.” By the weekend, there were 6 cases of the mysteriousdisease, 73 more suspected, and 2 deaths. In the New York City outbreak, three brothers werethe first victims. Carlisle, Gilbert, and Joseph Leggette developed the fever, muscle aches, andchest congestion that make the disease resemble pneumonia. Joseph and Gilbert recovered;Carlisle did not. “He just got sick and about a week later he was dead,” said John Leggette, afourth brother who warily returned to his own job in the garment district the next week. “I’m14 scared,” he said. “But what can you do?”Case 4: Red Spots on Airline Flight Attendants From January 1 to March 10, 1980, Eastern Airlines received 190 reports of episodes of redspots appearing on the skin of flight attendants (FAs) during various flights. Complaints ofsymptoms accompanying the spots were rare, but some FAs expressed concern that the spotswere caused by bleeding through the skin and might indicate a serious health hazard. On March12, investigators from the CDC traveled to Miami to assist in the investigation. No evidence ofdamage to underlying skin was noted on these examinations, nor was any noted by consultantdermatologists who examined affected FAs after the spots had disappeared. Chemical tests onclinical specimens for the presence of blood were negative. Airline personnel had investigatedthe ventilation systems, cleaning materials and procedures, and other environmental factors onaffected aircraft. Airflow patterns and cabin temperatures, pressures, and relative humiditywere found to be normal. Cleaning materials and routines had been changed, but casescontinued to occur. Written reports by FAs of 132 cases occurring in January and Februaryshowed 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 Miamimetropolitan areas, flights that are partially over water. Only rarely was a case reported from15 the same airplane when flying transcontinental or other east-west routes.Solution to Case 4: Red Spots"