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Stefanos Bonovas, MD, MSc, PhD Associate Professor of Medical Statistics Department of Biomedical Sciences Humanitas University Course: Biostatistics Lesson 2. March 30, 2023 Introduction to epidemiology: historical evolution News stories… … A recent news story discussed a city’s concerns about...

Stefanos Bonovas, MD, MSc, PhD Associate Professor of Medical Statistics Department of Biomedical Sciences Humanitas University Course: Biostatistics Lesson 2. March 30, 2023 Introduction to epidemiology: historical evolution News stories… … A recent news story discussed a city’s concerns about the rise in the number of children with asthma. … Another story reported the revised recommendations for who should receive the influenza vaccine this year. … A third story described the extensive disease-monitoring strategies implemented in Italy for the Covid-19 epidemic. These stories included interviews with public health officials or researchers who called themselves epidemiologists. Well, who are these epidemiologists, and what they do? What is epidemiology? News stories… … A recent news story discussed a city’s concerns about the rise in the number of children with asthma. … Another story reported the revised recommendations for who should receive the influenza vaccine this year. … A third story described the extensive disease-monitoring strategies implemented in Italy for the Covid-19 epidemic. These stories included interviews with public health officials or researchers who called themselves epidemiologists. Well, who are these epidemiologists, and what they do? What is epidemiology? Definition of Epidemiology The word epidemiology comes from the Greek words: epi, meaning on or upon, demos, meaning people, logos, meaning the study of... So, epidemiology has its roots in the study of what befalls a population… Definition 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 the control of health problems.* * Dictionary of Epidemiology. 4th edition. New York: Oxford University Press; 2001. Definition 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 the control of health problems. Study: Epidemiology is a scientific discipline with sound methods… It relies on the collection, analysis and interpretation of data… It also draws on methods from other scientific fields, including biostatistics, informatics, economics, and social sciences… Definition 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 the control of health problems. Distribution: Epidemiology is concerned with the frequency and pattern of health events in a population… Frequency refers not only to the number of health events (e.g. the number of cases of meningitis or diabetes in a population), but also to the relationship of that number to the size of the population. Pattern refers to the occurrence of health-related events by time, place, and personal characteristics (age, sex, etc). Definition 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 the control of health problems. Determinants: Epidemiology is also used to search for determinants, which are the causes and other factors that influence the occurrence of disease and other health-related events. To search for these determinants, epidemiologists use studies to provide the “why” and “how” of such events. Ideally, the findings provide sufficient evidence to guide prompt and effective public health control and prevention measures. Definition 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 the control of health problems. Health-related states or events: Such as… communicable and non-communicable diseases; injuries; birth defects; maternal-child health; occupational health; environmental health; behaviors related to health and well-being (such as exercise, smoking, diet, condom and seat belt use, etc); genetic markers of disease risk; and many more… Indeed, the term “health-related states or events” may be seen as anything that affects the well-being of a population… Definition 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 the control of health problems. Specified populations: Although epidemiologists and clinicians are both concerned with control of disease, they differ greatly in how they view “the patient”. While the clinician is concerned about the health of an individual; the epidemiologists are concerned about health of the people in a community or population… The epidemiologist focuses on identifying what caused the illness; the number of other individuals who may have been exposed; the potential of further spread; and how to prevent new cases… Definition 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 the control of health problems. Application: Epidemiology uses the knowledge gained by epidemiologic studies to propose and implement appropriate, practical, and acceptable public health interventions to control and prevent disease in the population... Historical evolution of Epidemiology Circa 400 B.C. Epidemiology’s roots are nearly 2500 years old Hippocrates attempted to explain disease occurrence from a rational rather than a supernatural viewpoint... In his essay entitled “On Airs, Waters, and Places”, Hippocrates suggested that environmental and host factors such as behaviors might influence the development of a disease... Hippocrates looked at disease as an imbalance in fluids (or humours): melancholy, phlegm, bile, and blood. Health depended on a proper balance of these fluids… This concept provided some sort of rationale for understanding health and disease. Greek physicians prescribed changes in diet or lifestyle and sometimes prepared drugs or performed surgeries. Historical evolution of Epidemiology 1662 An early contributor to epidemiology was John Graunt. He published a landmark analysis of mortality data (London, 1662). This publication was the first to quantify patterns of birth, death, and disease occurrence, noting disparities between males/females, high infant mortality, urban/rural differences, and seasonal variations... Historical evolution of Epidemiology 1800 William Farr systematically collected and analyzed Britain’s mortality statistics. Farr, the father of modern vital statistics and surveillance, developed many of the basic practices used today in vital statistics and disease classification. He concentrated his efforts on collecting vital statistics, assembling and evaluating those data, and reporting to responsible health authorities and the general public... Historical evolution of Epidemiology 1854 John Snow is considered the father of field epidemiology. Twenty years before the development of the microscope, Snow conducted studies of cholera outbreaks both to discover the cause of disease and to prevent its spread... Because his work illustrates the classic sequence from descriptive epidemiology, to hypothesis generation and hypothesis testing (analytic epidemiology), his investigations will be described in detail... Cholera: an infectious and often fatal bacterial disease of the small intestine, typically contracted from infected water and causing severe vomiting and diarrhoea. Historical evolution of Epidemiology John Snow and the epidemic of cholera Snow conducted one of his now famous studies in 1854, when an epidemic of cholera erupted in the Golden Square of London. He began his investigation by determining where in this area persons with cholera lived and worked. He marked each residence on a map of the area. Today, this type of map, showing the geographic distribution of cases, is called a spot map.... water pump Historical evolution of Epidemiology John Snow and the epidemic of cholera Because he believed that water was a source of infection for cholera, he marked the location of water pumps on his spot map, then looked for a relationship between the distribution of households with cases of cholera and the location of pumps.... He noticed that more case households clustered around Pump A, the Broad Street pump, than around Pump B or C. When he questioned residents who lived in the area, he was told that they avoided Pump B because it was grossly contaminated, and that Pump C was located too inconveniently for most of them. Snow concluded that the Broad Street pump (Pump A) was the primary source of water and the most likely source of infection for most persons with cholera in the Golden Square area. water pump Historical evolution of Epidemiology John Snow and the epidemic of cholera Because he believed that water was a source of infection for cholera, he marked the location of water pumps on his spot map, then looked for a relationship between the distribution of households with cases of cholera and the location of pumps.... He noticed that more case households clustered around Pump A, the Broad Street pump, than around Pump B or C. When he questioned residents who lived in the area, he was told that they avoided Pump B because it was grossly contaminated, and that Pump C was located too inconveniently for most of them. Snow concluded that the Broad Street pump (Pump A) was the primary source of water and the most likely source of infection for most persons with cholera in the Golden Square area. water pump Historical evolution of Epidemiology John Snow and the epidemic of cholera Because he believed that water was a source of infection for cholera, he marked the location of water pumps on his spot map, then looked for a relationship between the distribution of households with cases of cholera and the location of pumps.... He noticed that more case households clustered around Pump A, the Broad Street pump, than around Pump B or C. When he questioned residents who lived in the area, he was told that they avoided Pump B because it was grossly contaminated, and that Pump C was located too inconveniently for most of them. Snow concluded that the Broad Street pump (Pump A) was the primary source of water and the most likely source of infection for most persons with cholera in the Golden Square area. Historical evolution of Epidemiology John Snow and the epidemic of cholera Historical evolution of Epidemiology John Snow and the epidemic of cholera Video: https://youtu.be/753XHXPLrn4 Historical evolution of Epidemiology John Snow’s second investigation Snow reexamined data from the 1854 cholera outbreak in London. He had noted that districts with the highest death rates were serviced by two water companies: the Lambeth Company and the Southwark and Vauxhall Company. Both companies obtained water from the Thames River at intake points that were downstream from London and thus susceptible to contamination from London sewage, which was discharged directly into the Thames. However, to avoid the contamination by London sewage, in 1852 the Lambeth Company had moved its intake water works to a site on the Thames well upstream from London. Historical evolution of Epidemiology John Snow’s second investigation Snow reexamined data from the 1854 cholera outbreak in London. He had noted that districts with the highest death rates were serviced by two water companies: the Lambeth Company and the Southwark and Vauxhall Company. Both companies obtained water from the Thames River at intake points that were downstream from London and thus susceptible to contamination from London sewage, which was discharged directly into the Thames River. However, to avoid the contamination by London sewage, in 1852 the Lambeth Company had moved its intake water works to a site on the Thames well upstream from London. Historical evolution of Epidemiology John Snow’s second investigation For a 7-week period during 1854, Snow compared cholera mortality among districts that received water from one, or the other, or both water companies. The results are shown in the Table below. Historical evolution of Epidemiology John Snow’s second investigation Cholera death rate was more than 5 times higher in districts served only by the Southwark and Vauxhall Company than in those served only by the Lambeth Company… Then, Snow focused on the districts served by both companies, because the households within a district were generally comparable except for the water supply company… Historical evolution of Epidemiology John Snow’s second investigation He identified the water supply company for every house in which a death from cholera had occurred. The table below shows his findings… Historical evolution of Epidemiology John Snow’s investigations: comments With no knowledge of the existence of microorganisms, John Snow demonstrated through epidemiologic studies that water could serve as a vehicle for transmitting cholera and that epidemiologic information could be used to guide prompt and appropriate public health actions.… Based on a characterization of cases and population at risk by time, place, and person, John Snow established the sequence of steps used by current-day epidemiologists to investigate outbreaks of disease… Historical evolution of Epidemiology John Snow’s investigations: comments With no knowledge of the existence of microorganisms, John Snow demonstrated through epidemiologic studies that water could serve as a vehicle for transmitting cholera and that epidemiologic information could be used to guide prompt and appropriate public health actions.… Based on a characterization of cases and population at risk by time, place, and person, John Snow established the sequence of steps used by current-day epidemiologists to investigate outbreaks of disease… A few notes about epidemic disease occurrence… A few notes about epidemic disease occurrence… Level of disease The amount of a disease that is usually present in a community is referred to as “baseline or endemic level of the disease”… This level is not necessarily the desired level (which may be zero) but rather is the observed level… The baseline level is often regarded as the expected level of the disease... A few notes about epidemic disease occurrence… Level of disease While some diseases are so rare in a given population that a single case needs an epidemiologic investigation (e.g., cholera, plague, polio, etc), other diseases occur more often, so that only deviations from the norm need investigation (e.g., gastroenteritis)… Sporadic refers to a disease that occurs infrequently and irregularly. Endemic refers to the constant and/or usual presence of a disease (or infectious agent) in a population within a geographic area. A few notes about epidemic disease occurrence… Occasionally, the amount of disease in a community rises above the expected level… Epidemic refers to an increase, often sudden, in the number of cases of a disease above what is normally expected in that population in that area. Outbreak carries the same definition of epidemic, but is often used for a more limited geographic area. Cluster refers to an aggregation of cases, grouped in place and time, that are suspected to be greater than the number expected, even though the expected number may not be known. Pandemic refers to an epidemic that has spread over continents, usually affecting a large number of people. Historical evolution of Epidemiology Historical evolution of Epidemiology 20th and 21st centuries… In the 1800s, epidemiologists focused on acute infectious diseases... In the 1930s and 1940s, extension to non-infectious diseases (e.g. health-related outcomes, behaviors, knowledge, and attitudes)… In the 1950s and 1960s, Doll and Hill link lung cancer to smoking… In the 1980s, epidemiology was extended to injuries and violence… In the 1990s, extension to molecular and genetic epidemiology… Meanwhile, Ebola, HIV/AIDS, Legionella, SARS, pandemic influenza... From December 2019, Coronavirus disease 2019 (Covid-19)… Historical evolution of Epidemiology 20th and 21st centuries… In the 1800s, epidemiologists focused on acute infectious diseases... In the 1930s and 1940s, extension to non-infectious diseases (e.g. health-related outcomes, behaviors, knowledge, and attitudes)… In the 1950s and 1960s, Doll and Hill link lung cancer to smoking… In the 1980s, epidemiology was extended to injuries and violence… In the 1990s, extension to molecular and genetic epidemiology… Meanwhile, Ebola, HIV/AIDS, Legionella, SARS, pandemic influenza... From December 2019, Coronavirus disease 2019 (Covid-19)… Historical evolution of Epidemiology 20th and 21st centuries… In the 1800s, epidemiologists focused on acute infectious diseases... In the 1930s and 1940s, extension to non-infectious diseases (e.g. health-related outcomes, behaviors, knowledge, and attitudes)… In the 1950s and 1960s, Doll and Hill link lung cancer to smoking… In the 1980s, epidemiology was extended to injuries and violence… In the 1990s, extension to molecular and genetic epidemiology… Meanwhile, Ebola, HIV/AIDS, Legionella, SARS, pandemic influenza... From December 2019, Coronavirus disease 2019 (Covid-19)… Historical evolution of Epidemiology 20th and 21st centuries… In the 1800s, epidemiologists focused on acute infectious diseases... In the 1930s and 1940s, extension to non-infectious diseases (e.g. health-related outcomes, behaviors, knowledge, and attitudes)… In the 1950s and 1960s, Doll and Hill link lung cancer to smoking… In the 1980s, epidemiology was extended to injuries and violence… In the 1990s, extension to molecular and genetic epidemiology… Meanwhile, Ebola, HIV/AIDS, Legionella, SARS, pandemic influenza... From December 2019, Coronavirus disease 2019 (Covid-19)… Historical evolution of Epidemiology 20th and 21st centuries… In the 1800s, epidemiologists focused on acute infectious diseases... In the 1930s and 1940s, extension to non-infectious diseases (e.g. health-related outcomes, behaviors, knowledge, and attitudes)… In the 1950s and 1960s, Doll and Hill link lung cancer to smoking… In the 1980s, epidemiology was extended to injuries and violence… In the 1990s, extension to molecular and genetic epidemiology… Meanwhile, Ebola, HIV/AIDS, Legionella, SARS, pandemic influenza... From December 2019, Coronavirus disease 2019 (Covid-19)… Historical evolution of Epidemiology 20th and 21st centuries… In the 1800s, epidemiologists focused on acute infectious diseases... In the 1930s and 1940s, extension to non-infectious diseases (e.g. health-related outcomes, behaviors, knowledge, and attitudes)… In the 1950s and 1960s, Doll and Hill link lung cancer to smoking… In the 1980s, epidemiology was extended to injuries and violence… In the 1990s, extension to molecular and genetic epidemiology… Meanwhile, Ebola, HIV/AIDS, Legionella, SARS, pandemic influenza... From December 2019, Coronavirus disease 2019 (Covid-19)… Historical evolution of Epidemiology 20th and 21st centuries… In the 1800s, epidemiologists focused on acute infectious diseases... In the 1930s and 1940s, extension to non-infectious diseases (e.g. health-related outcomes, behaviors, knowledge, and attitudes)… In the 1950s and 1960s, Doll and Hill link lung cancer to smoking… In the 1980s, epidemiology was extended to injuries and violence… In the 1990s, extension to molecular and genetic epidemiology… Meanwhile, Ebola, HIV/AIDS, Legionella, SARS, pandemic influenza... From December 2019, Coronavirus disease 2019 (Covid-19)… Historical evolution of Epidemiology The studies by Doll and Hill linking lung cancer to smoking… Historical evolution of Epidemiology The studies by Doll and Hill linking lung cancer to smoking… Historical evolution of Epidemiology The studies by Doll and Hill linking lung cancer to smoking… Historical evolution of Epidemiology The studies by Doll and Hill linking lung cancer to smoking… Historical evolution of Epidemiology The studies by Doll and Hill linking lung cancer to smoking… Historical evolution of Epidemiology The studies by Doll and Hill linking lung cancer to smoking… The public health message: The lung cancer rate among smokers is several times as high as the rate among non-smokers... Smokers who quit can lower their rate considerably, but it never gets back to the low level seen in never-smokers… So the public health message is: “If you smoke, quit. But better yet, don’t start!” Historical evolution of Epidemiology Richard Doll: The man who stopped smoking… Video: https://youtu.be/VBWGM630zG0 Descriptive and analytical epidemiology Taxonomy of epidemiologic studies who where when descriptive population individual ecological crosssectional why hypothesis analytical observational cohort experimental case-control 1. Descriptive epidemiology It describes the cases of a disease • When do they appear? • What ages are they? • Is there any group-defining characteristic that they have in common? • Descriptive epidemiology reveals interesting patterns that we would not have observed if we had not collected the cases and ordered them in a structured manner • And then the question “why” pops up immediately 2. Analytical epidemiology It looks for a certain etiology • We try systematically to compare the group of disease cases with another group of healthy people • We test the clues offered by the descriptive study • Examples: 1. Did the cases of gastroenteritis eat something that the others did not eat? 2. Did the children who contracted measles go to a different school compared to those who did not? Descriptive epidemiology Every newspaper reporter is taught that a story is incomplete, if it does not describe the what, who, where, when, and why of an event (5 W’s), whether it is a bank robbery or a house fire. Epidemiologists strive for similar comprehensiveness in characterizing an epidemiologic event, whether it is a pandemic of Covid-19, or a rise in cancer-related mortality. However, epidemiologists tend to use some synonyms for the 5 W’s listed above: case definition, person, place, time, and causes/risk factors/modes of transmission. Descriptive epidemiology covers time, place, and person. Descriptive epidemiology Describes the disease by Time Time data are usually displayed with a two-dimensional graph. The vertical or y-axis usually shows the number or rate of cases; the horizontal or x-axis shows the time periods such as years, months, or days. The number (or rate) of cases is plotted over time. Graphs of disease occurrence over time are usually plotted as line graphs or histograms. By time 1993 Western States E. coli O157 Outbreak 70 Outbreak detected 1993 Number of Cases 60 50 726 ill, 4 deaths 40 30 39 d 20 10 0 1 8 15 22 29 36 43 50 57 64 71 Day of Outbreak Epidemic curve! By time Cases of salmonellosis (n=65) by date and time of onset of illness. Hospital A, Athens, August 2010 15 cases 14 13 1 case patient 12 1 case staff member 11 10 9 8 7 6 5 Epidemic curve! 4 3 2 1 0 00- 06- 12- 18- 00- 06- 12- 18- 00- 06- 12- 18- 00- 06- 12- 1827 August 28 August 29 August Date and time of onset 30 August By time By time By time Descriptive epidemiology Describes the disease by Place Describing the occurrence of disease by place provides insight into the geographic extent of the problem and its geographic variation. Analyzing data by place can identify communities at increased risk of disease. Even if the data cannot reveal why these people have an increased risk, it can help generate hypotheses to test with additional (analytical) studies. By place By place: Geographic distribution of West Nile Virus cases in Greece with symptoms from the Central Nervous System By place By time and place Εβδ. 41/2003 Εβδ. 44/2003 Εβδ. 42/2003 Εβδ. 45/2003 Εβδ. 43/2003 Εβδ. 46/2003 Sentinel surveillance of influenza in France By time and place Εβδ. 47/2003 Εβδ. 50/2003 Εβδ. 48/2003 Εβδ. 51/2003 Εβδ. 49/2003 Εβδ. 52/2003 Sentinel surveillance of influenza in France Descriptive epidemiology Describes the disease by Person (i.e., personal characteristics) Because personal characteristics may affect illness, organization and analysis of data by “person” may use inherent characteristics of people (e.g. age, sex, race), biologic characteristics (immune status), acquired characteristics (marital status), activities (occupation, use of medications/tobacco/drugs), or the conditions under which they live (socioeconomic status, access to medical care). Age and sex are included in almost all datasets and are the By person By person By person Taxonomy of epidemiologic studies who where when descriptive population individual ecological crosssectional why hypothesis analytical observational cohort experimental case-control Cross-Sectional Studies key features, utility, advantages, limitations Cross-Sectional studies They examine the relationship between diseases (or other health-related characteristics) and variables of interest as they exist in a defined population at one particular time (“snapshot”…) The key features of cross-sectional studies:  They typically take a snapshot of a population at a single point in time…  They usually measure disease prevalence in relation to the exposure prevalence… Cross-Sectional studies Utility of cross-sectional studies: • Public health planning • Etiologic research Advantages: • Generalizability • Low cost Limitations: • They cannot infer the temporal sequence between the exposure and disease • They usually identify a high proportion of prevalent cases of long duration Cross-Sectional studies – an example Cross-Sectional studies – an example Cross-Sectional studies – an example This was a bio-behavioural survey in MSM with a specific focus on HIV prevalence and use of United Nations General Assembly Special Session (UNGASS) indicators in six cities in Southern and Eastern Europe. Questionnaires and oral fluid samples were collected. The data show different socio-demographic patterns across countries regarding age, level of education, living conditions, living area and self-identity. Southern European cities had the highest percentage of people who had tested for HIV and collected the result. More than 50% of respondents in the sample from Barcelona reported having used a condom last time they had anal sex (57.2%), whilst in all other cities this proportion was below 50%. The cities with the highest HIV prevalence in MSM were Barcelona (17.0%) and Verona (11.8%) whilst lower percentages were reported in Bratislava (6.1%), Bucharest (4.6%), Ljubljana (5.1%) and Prague (2.6%). The low prevalence in Eastern Europe is encouraging. However, with the level of high-risk sexual behaviour documented and the lower frequency of HIV test seeking behaviour, there is a clear risk of an increase in HIV transmission. Ecological Studies key features, utility, advantages, limitations Ecological studies They examine the rates of disease in relation to a factor developed on a population level… The two key features of ecological studies:  The population is the unit of analysis…  An exposure status that is the property of the population… Ecological studies The population-level factor may be: • An aggregate measure that summarizes the individual members of the population (e.g. the proportion of individuals above the age of 65 years) • An environmental measure that describes the environment where the population resides/works (e.g. the air pollution level) • A global measure that has no analog on the individual level (e.g., the quality of a health care system) Ecological studies Limitations • Lack of individual level information • An association observed between variables on an aggregate level does not necessarily mirror the association that exists at the individual level (ecological fallacy or bias) • Inability to detect complicated relationships because of the crude nature of data Ecological studies However, they remain popular because:  They can be done quickly and inexpensively since they often rely on pre-existing data  Their analysis and presentation are relatively simple and easy to understand Ecological study – an example Ecological study – an example Ecological study – an example Ecological study – an example Ecological study – an example Ecological Study – Global Health 200 Countries, 200 Years, 4 Minutes Video: https://youtu.be/jbkSRLYSojo Bibliography: Principles of Epidemiology in Public Health Practice. An Introduction to Applied Epidemiology and Biostatistics. U.S. Department of Health and human Services, Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/csels/dsepd/ss1978/SS1978.pdf

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