BMSC 5260_M1_Introduction to Epidemiology.pdf

Module 1: Introduction to Epidemiology I. Module Learning Objectives MLO 1.1: Define the objectives and approaches of epidemiology and how they integrate with clinical practice. MLO 1.2: Define and explain the natural history of disease. MLO 1.3: Describe the levels of prevention and apply t...

Module 1: Introduction to Epidemiology I. Module Learning Objectives MLO 1.1: Define the objectives and approaches of epidemiology and how they integrate with clinical practice. MLO 1.2: Define and explain the natural history of disease. MLO 1.3: Describe the levels of prevention and apply them to the natural history of disease. MLO 1.4: Define and explain major terms related to disease transmission and epidemic patterns. MLO 1.5: Summarize and apply the steps of an outbreak investigation. II. Chapter 1- Introduction A. Objectives of Epidemiology Epidemiology is the study of the ___________ distribution and ____________ determinants of health-related states or events in specified ___________ populations and the ___________ application of this study to control of ______ problems. health There are 5 specific objectives of epidemiology: 1. Identify the ________, etiology or cause, of a disease and its relevant ___________ risk factors (factors that increase a person's risk for a disease). a. We want to know how the disease is transmitted. b. Intervene to reduce _________ morbidity (presence of disease) and _________ mortality (death) c. Develop a rational basis for prevention programs. d. Develop appropriate vaccines and treatments to prevent the transmission of the disease to others. 2. Determine the ______ extent of disease found in the community a. What is the burden of disease in the community? 3. Study the natural _______ history and prognosis of disease a. Not all diseases are equal. Some diseases are more severe than others; some may be rapidly lethal, whereas others may have extended durations of survival. b. We need to define the baseline natural history of a disease in quantitative terms so we can compare the results of new _____________ interventions (treatments or preventative methods) with the baseline data to determine whether our new approaches have truly been effective. 4. Evaluate both existing and newly developed interventions and modes of health care delivery. a. Examples i. Does screening men for prostate cancer using the prostate-specific antigen (PSA) test improve survival in people found to have prostate cancer?  ii. Has the growth of managed care and other new systems of health care delivery and health care insurance had an impact on the health outcomes of the patients involved and on their quality of life? 5. Provide the foundation for developing ___________ public policy relating to environmental problems, genetic issues, and other social and behavioral considerations regarding disease prevention and health promotion a. Examples: i. Is the electromagnetic radiation that is emitted by cell phones, electric blankets and heating pads, and other household appliances a hazard to human health? ii. Are high levels of atmospheric ozone or particulate matter a cause of adverse acute or chronic health effects in human populations? iii. Is radon in homes a significant risk to human beings? iv. Which occupations are associated with increased risks of disease in workers, and what types of regulation are required to reduce these risks? B. Epidemiology and Prevention Major use of epidemiologic evidence is to ________ identify subgroups in the population who are at high ____ for disease. risk If we can identify these high-risk groups, we can direct preventive efforts to populations that are most likely to benefit from any interventions that are developed for the disease. We may be able to identify the specific factors or characteristics that put them at high risk and then try to modify those factors There are 3 types of prevention: _______, primary _________, secondary and ________ tertiary (Table 1.2) Table 1.2 Three Types of Prevention Examples of each type of prevention: a. Primary. We know that most lung cancers are ___________. preventable If we can help to stop people from ever smoking, we can eliminate 80% to 90% of lung cancer in human beings.  b. Secondary. Most cases of ______ breast cancer in older women can be detected through mammography. c. Tertiary. Prompt and appropriate _________ treatment of the illness to prevent complications. _______ Primary prevention is our ultimate goal. However, for many diseases, such as prostate cancer and Alzheimer disease, we do not yet have the biologic, clinical, or epidemiologic data on which to base effective primary prevention programs. The rationale for secondary prevention is that if we can identify disease earlier in its natural history than would ordinarily occur, intervention measures may be more effective and life prolonged. C. Epidemiology and Clinical Practice The practice of medicine, diagnosis, treatment, and prognosis is dependent on ______________. population data If a physician hears an apical systolic murmur, a heart sound produced when blood flows across the heart valves, how does he or she know whether it represents mitral regurgitation? The diagnosis is based on correlation of the clinical findings with the findings of surgical pathology or autopsy and with the results of echocardiography, magnetic resonance, or catheterization studies in a large group of patients. Randomized clinical trials that study the effects of a treatment in large groups of patients are the ideal means (the so-called gold standard) for identifying appropriate therapy. We will cover randomized trials in Module 5. A patient asks his physician, “How long do I have to live, doctor?” and the doctor replies, “Six months to a year.” He or she does so based on experience with large groups of patients who have had the same disease, were observed at the same stage of disease, and received the same treatment. The practice of clinical medicine relies heavily on population concepts. The data available about illness in the community can be very helpful in suggesting a _________, diagnosis even if they are not conclusive. For example, the data regarding the etiology of sore throats according to a child's age are particularly relevant (Fig. 1.5). If the infection occurs early in life, it is likely to be viral in origin. If it occurs at ages 4 to 7 years, it is likely to be streptococcal in origin. In an older child, Mycoplasma becomes more typical. Although these data do not make the diagnosis, they do provide the health care provider with a good clue as to what agent(s) to suspect. Fig. 1.5 Frequency of agents by age of children with pharyngitis, 1964-1965. D. Epidemiologic Approach Epidemiologic reasoning is a multistep process and often begins with ___________ descriptive data. 1. Determine whether an ___________ association exists between exposure to a factor (e.g., an environmental agent) or a characteristic of a person (e.g., an increased serum cholesterol level) and the presence of the disease in question. a. We do this by studying the characteristics of groups and the characteristics of individuals. b. Caveat: remember, not all associations are ______. casual 2. If there is an association, we need to try to derive _____________________ appropriate inferences about a possible causal relationship from the patterns of the associations that have been previously found. a. How we do this will be discussed in Module 7. Let’s look at an example of beginning the epidemiologic approach. Fig. 1.6 shows the rates of gonorrhea in the United States in 2015. There are clearly _________ regional variations in reported cases of gonorrhea. As we begin the epidemiologic approach, we start to ask these questions: 1. Are the differences seen between regions real? 2. Are the data from each area of comparable quality? a. Before we try to interpret the data, we should be satisfied that the data are valid. 3. If the differences are real, then we ask, “Why have these differences occurred?”  exposures 4. Are there differences in potential _________ between high-risk and low-risk areas, or are there differences in the people who live in those areas? Fig. 1.6 Gonorrhea: reported cases per 100,000 population, United States and territories, 2015. E. From Observations to Preventive Actions (historical prevention cases) Edward Jenner and Smallpox In the late 18th century, 400,000 people died from smallpox each year and one-third of survivors were blinded because of corneal infections. It was known that those who survived smallpox were subsequently immune to the disease, and consequently it became a common preventive practice to infect healthy individuals with smallpox by administering material taken from smallpox patients, a procedure called variolation. However, this was not the optimal method: some variolated individuals died from the resulting smallpox, infected others with smallpox, or developed other infections. Jenner was interested in finding a better, safer approach to preventing smallpox. He observed, as had other people before him, that dairy maids, the young women whose occupation was milking cows, developed a mild disease called cowpox. In 1768 Jenner heard a claim from a dairy maid, “I can't take the smallpox for I have already had the cowpox.” These data were observations and were not based on any rigorous study, but Jenner became convinced that cowpox could protect against smallpox and decided to test his hypothesis.  In 1796, Jenner removed cowpox material from a dairy maid and administered it to an 8-year-old “volunteer”. Jenner was so convinced that cowpox would be protective that 6 weeks later, to test his conviction, he inoculated the child with material that had just been taken from a smallpox pustule. The child did not contract the disease. We won’t explore the ethical issues in this course, but this was unethical and would not be approved today. The results of the first vaccination and of what followed eventually saved literally millions of human beings throughout the world from disability and death caused by smallpox. The important point is that Jenner knew nothing about viruses and nothing about the biology of the disease. He operated purely on _________________ observational data that provided him with the basis for a __________ preventive intervention. John Snow and Cholera In September 1854, approximately 600 people living within a few blocks of the Broad Street pump in London died of cholera. The Registrar General adhered to what was called the miasmatic theory of disease. According to this theory, which was commonly held at the time, disease was transmitted by a miasm, or cloud, that clung low on the surface of the earth. Snow did not agree; he believed that cholera was transmitted through contaminated water In London at that time, water was obtained by signing up with one of the water supply companies. The intakes for the water companies were in a very polluted part of the Thames River. At one point in time, one of the companies, the Lambeth Company, shifted its water intake upstream in the Thames to a less polluted part of the river; the other companies did not move the locations of their water intakes. Snow reasoned therefore that based on his hypothesis that contaminated water caused cholera, the mortality rate from cholera would be lower in people getting their water from the Lambeth Company than in those obtaining their water from the other companies. He carried out what we currently call “shoe-leather epidemiology”, going from house to house, counting all deaths from cholera in each house, and determining which company supplied water to each house. Snow’s findings are shown in Table 1.5. Table 1.5 Deaths from Cholera per 10,000 houses, by Source of Water Supply, London, 1854 Snow’s data were so convincing that they led the Registrar General to require the registrar of each district in south London to record which water company supplied  each house in which a person died of cholera. Snow's conclusion that contaminated water was associated with cholera was based entirely on observational data. III. Chapter 2- The Dynamics of Disease Transmission Human disease results from an interaction of the ____ host (a person), the _____ agent (e.g., a bacterium), and the __________ (e.g., polluted air). Although some diseases are largely enviornment genetic in origin, virtually all disease results from an interaction of genetic, behavioral, and environmental factors, with the proportions differing for different diseases. Many of the underlying principles governing the transmission of disease are most clearly demonstrated using communicable diseases as a model. We will primarily use such diseases as examples in reviewing these principles. However, the concepts discussed are also applicable to diseases that are not infectious in origin (e.g., second-hand smoke causing cancer). Disease has been classically described as the result of the epidemiologic triad shown in Fig. 2.1. Disease is the product of an interaction of the human host, an infectious pathogen or other type of agent, and the environment that promotes the exposure. A ______, vector such as the mosquito or the tick, may be involved. For such an interaction to take place, the host must be ___________, susceptible capable of or at risk of developing disease. Human susceptibility is determined by a variety of factors including genetic background and behavioral, nutritional, and immunologic characteristics. The immune status of an individual is determined by many factors including prior experience both with natural infection and with immunization. Fig. 2.1 Epidemiologic triad of a disease. A. Modes of Transmission Diseases can be transmitted directly or indirectly. For example, a disease can be transmitted from person to person (__________________) direct transmission by means of direct physical contact, such as in the case of sexually transmitted infections, or by droplet contact. ____________________ indirect transmission can occur through a common vehicle such as a contaminated air, food, or water supply or by a vector such as mosquitos or cockroaches. Jara (2021). J. Nucl. Med. Technol., 49(2). 10.2967/jnmt.121.262281 Fig. 2.2 is a classic photograph showing droplet dispersal after a sneeze. It vividly demonstrates the potential for an individual to infect many people in a brief period. Fig. 2.2. Droplet dispersal following a violent sneeze. Different organisms ______ spread in different ways, and the potential of a given organism for spreading and producing outbreaks depends on the characteristics of the organism, such as its rate of growth, the route by which it is transmitted from one person to another, and the number of susceptible persons in the community. The figures below portrait the main _______________, portals of entry how a pathogen enters a host, and the _____________, portals of exit how pathogens leave a host. Notice that most of the portals of entry, or their natural secretions or excretions, also serve as portals of exit. Portals of entry Portals of exit Images © 2018 Pearson Education, Inc. B. Clinical and Subclinical Disease Disease severity has a broad spectrum which is best illustrated by the iceberg concept of disease (see figure below). Just as most of an iceberg is under water and hidden from view with only its tip visible, so it is with disease: only ____________ clinical illness is readily apparent. Image modified from University of Michigan School of Public Health (2020). The iceberg concept is important because it is not sufficient to count only the clinical cases, those with _________________ signs and symptoms of disease. For example, most cases of polio in prevaccine days were ___________, subclinical inapparent due to mild or asymptomatic infections. Nevertheless, they were still capable of spreading the virus to others. As a result, we cannot understand and explain the spread of polio unless the pool of subclinical cases is recognized. This is the same for many noncommunicable diseases, even though these diseases are not spread from person to person. For example, many individuals can live a long time with subclinical chronic kidney disease, and it is only when they experience a clinical complication that a diagnosis of chronic kidney disease is made. C. Endemic, Epidemic, and Pandemic Endemic is defined as the __________ consistent presence of a disease within a given geographic area. It may also refer to the usual occurrence of a given disease within such an area (sometimes referred to as the “background rate of disease”). Epidemic is defined as the occurrence in a community or region of a group of illnesses of similar nature, clearly _______________ more than normal expectancy and derived from a common or a propagated source. Pandemic refers to a _________ worldwide epidemic. Refer to the figure below for a visual representation. Image © 2018 Pearson Education, Inc. How do we know when we have an excess over what is expected? How do we even know how much to expect? There is no precise answer to either question. Through ongoing ____________, surveillance we may determine what the usual or expected level may be. Refer to Gordis Epidemiology for two examples that demonstrate how pandemics and fear of pandemics relate to the development of public policy. D. Disease Outbreaks Let us assume that a food becomes contaminated with a microorganism. If an outbreak occurs in the group of people who have eaten the food, it is called a _______________ common-vehicle __________, because all the cases that occurred were in persons exposed to the exposure suspected contaminated food. The food may be served only once—for example, at a catered luncheon—resulting in a ______________ single exposure to the people who eat it, or the food may be served more than once, resulting in _________________ multiple exposures to people who eat it more than once. When a water supply is contaminated with sewage because of leaky pipes, the contamination can be either ________, periodic causing multiple exposures because of changing pressures in the water supply system, which may cause intermittent contamination, or __________, continous in which case a constant leak leads to persistent contamination. The epidemiologic picture that is manifested depends on whether the exposure is single, multiple, or continuous. Let’s focus on a single-exposure, common-vehicle outbreak. What are the characteristics of such an outbreak? 1. These outbreaks are generally explosive, there is a sudden and rapid increase in the number of cases of the disease or condition in a population. 2. The cases are limited to people who share the common exposure. 3. In a food-borne outbreak, cases rarely occur in persons who did not eat the food. E. Immunity and Susceptibility The amount of disease in a population depends on a _______ balance between the number of people in that population who are susceptible and therefore at risk for the disease and the number of people who are ______ immune or not susceptible and therefore not at risk. They may be immune because they have had the disease previously (and have antibodies) or because they have been _________ immunized (received a vaccine). They also may not be susceptible on a genetic basis. For example, the CCR5 delta 32 mutation confers resistance to HIV infection. If the entire population is immune, no ________ epidemic can develop. But the balance is usually somewhere in between immunity and susceptibility, and when it moves toward susceptibility, the likelihood of an outbreak increases. This has been observed particularly in formerly isolated populations who were later exposed to disease. Below are two examples: In the 19th century, measles occurred in the Faroe Islands in epidemic form when infected individuals entered the isolated and susceptible population. Outbreaks of streptococcal sore throats developed when new susceptible recruits arrived at the Great Lakes Naval Station. Smallpox, measles, and flu epidemics killed 90% of the indigenous people of the Americans due to contact with Europeans. F. Herd Immunity Herd immunity is defined as the __________ resistance of a group of people to an attack by a disease to which a _____ proportion of the members of the group are ______. large immune If a large percentage of the population is immune, the ______ entire population is likely to be protected, not just those who are immune. Because disease spreads from one person to another in any community, once a certain proportion of people in the community are immune, the __________ likelihood is small that an infected person will encounter a susceptible person to whom they can transmit the infection; more of their encounters will be with people who are immune. The presence of a large proportion of immune persons in the population lessens the likelihood that a person with the disease will encounter a susceptible individual. Herd immunity operates optimally if the probability of an infected person encountering every other individual in the population (“random mixing”) is the same. This is a theoretical concept because, obviously, populations are never completely randomly mixed. What percentage of a population must be immune for herd immunity to operate? This percentage varies from disease to disease. For example, in the case of measles, which is highly communicable, it has been estimated that 94% of the population must be immune before the chain of transmission is interrupted. Let’s look at a specific example of how herd immunity works. Fig. 2.9 shows the expected number of cases of polio in the United States from 1958-1961 (red line). However, far fewer cases were actually observed (blue line) due to the effect of herd immunity (gray shaded area). Fig. 2.9 Effect of herd immunity, United States, 1958–61. G. Incubation Period The incubation period is defined as the interval from _________________ receipt of infection to the time of onset of clinical illness. If you become infected today, the disease with which you are infected may not develop for several days or weeks. During this time, the incubation period, you feel completely well and show no signs of the disease. During at least part of the incubation period, the individual can transmit the disease to others. The incubation period: May reflect time needed for the organism to replicate sufficiently until it reaches the critical mass needed for clinical disease to result. Relates to the site in the body at which the organism replicates, whether it replicates superficially, near the skin surface, or deeper in the body (e.g., in the gut). May be influenced by the dose of the infectious agent received at the time of infection. With a large dose, the incubation period may be shorter. Different diseases have different incubation periods. A _______ precise incubation period does not exist for a given disease; rather, a _____ range of incubation periods is characteristic of that disease. Fig. 2.11 shows the range of incubation periods for viral diseases. Fig. 2.11 Incubation periods of viral diseases. Based on the incubation period, we can create guidelines for isolation and quarantine to prevent further cases. _________ Isolation separates sick people with a contagious disease from people who are not sick. __________ separates and restricts the movement of people Quarantine who were exposed to a contagious disease to see if they become sick. There are three critical variables in investigating an outbreak or epidemic: 1. When did the exposure take place? 2. When did the disease begin? 3. What was the incubation period for the disease? If we know any two of these, we can calculate the third. H. Attack Rate An attack rate is defined as: The attack rate is useful for comparing the ____ risk of disease in groups with different _________. exposures The attack rate can be specific for a given exposure. For example, the attack rate in people who ate a certain food is called a food-specific attack rate. It is calculated by: In general, ____ time is not explicitly specified in an attack rate because the exposure is common and the illness is acute; given what is usually known about how long after an exposure most cases develop, the time is implicit in the attack rate. A person who acquires the disease from direct exposure to the outbreak source (e.g., from a contaminated food) is called a __________. primary case A person who acquires the disease from exposure to a primary case is called a secondary case. The secondary attack rate is therefore defined as the attack rate in susceptible people who were ___ not exposed to the suspected agent who have been exposed to a primary case. Caveat: A common mistake is to use the terms primary case and __________ index case interchangeably. The index case (also called patient 0) is the patient in an outbreak who is first noticed by the health authorities, and who makes them aware that an outbreak might be emerging. In many instances, the index case is also a primary case. I. Exploring Occurrence of Disease When a disease appears to have occurred at more than an endemic level and we wish to investigate its occurrence, we ask: 1. ___ Who was attacked by the disease? 2. ____ When did the disease occur? 3. _____ Where did the cases arise? Who The characteristics of the human host are clearly related to disease risk. Factors such as sex, age, and race as well as behavioral risk factors (e.g., smoking) may have major effects. A simple example is pertussis (“whooping cough”). Pertussis occurrence is clearly related to age. Infants aged less than 1 year, who are at the greatest risk for death, continue to have the highest reported rate of pertussis (Fig. 2.17). Fig. 2.17 Pertussis incidence per 100,000 population by year and age group, U.S., 1990-2021. Although the highest rate of pertussis was in infants less than 6 months of age (99 per 100,000) the number of reported cases was highest in children ages 11 to 19 (Fig. 2.18). Approximately half of reported pertussis cases in 2014 and 2015 occurred in 10- to 19-year-olds and in adults over the age of 20 years. Although the specific cause of this phenomenon is unknown, it could result from a waning of protection 5 to 10 years after pertussis immunization. case-fatality rate The _________________ is the proportion of people who develop the disease (cases) who then die of the disease. Fig. 2.18 Pertussis reported numbers of cases by age group, U.S., 2009. When: periodicity Certain diseases occur with a certain ___________. For example, aseptic meningitis peaks at consistent yearly rates (Fig. 2.19). Often, there is a seasonal pattern to the  temporal variation. For example, diarrheal disease is most common during the summer months, and respiratory disease is most common during the winter months. incidence The question of when is also addressed by examining trends in disease _________ over time. In the United States, both the incidence of and deaths from AIDS increased for many years, but it began to decline in 1996, largely due to new therapy and education. Fig. 2.19. Aseptic meningitis, reported cases per 100,000 population by month, U.S., 1986-93. Where: time or _____. Disease is not randomly distributed in ____ place For example, Fig. 2.20 shows the geographic distribution of Lyme disease in the United States. There is a clear clustering of cases along the Northeast coast, in the north-central part of the country, and in the Pacific Coast region. The distribution of the disease closely parallels that of the deer tick vector. Fig. 2.20 Reported cases of Lyme disease in United States, 2015 J. Outbreak Investigation The characteristics just discussed are the central issues in virtually all outbreak investigations. The steps for investigating an outbreak generally follow this pattern: Caveats: Outbreak investigations are not ______. linear Multiple steps can occur ______________. simultaneously Steps often need to be ________ repeated several times. Some steps may not always be __________. applicable Goal of investigation is to ____ stop the outbreak. Outbreaks are not _______ orderly in the way that they unfold.