Epidemiology
Epidemiology
History and Scientific Foundations
Introduction
Epidemiology is the study of the causes and distribution of illness and injury. It constitutes the scientific underpinning of public health practice. According to noted British epidemiologist Sir Richard Doll (1912–2005), “Epidemiology is the simplest and most direct method of studying the causes of disease in humans, and many major contributions have been made by studies that have demanded nothing more than an ability to count, to think logically and to have an imaginative idea.” In practice, epidemiology is applied in the three main areas of public health: safety and injuries, chronic disease, and infectious disease. This article will emphasize examples and applications in infectious disease epidemiology.
History and Scientific Foundations
The first physician known to consider the fundamental concepts of disease causation was the ancient Greek Hippocrates (c.460—c.377 BC), when he wrote that medical thinkers should consider the climate and seasons, the air, the water that people use, the soil and people's eating, drinking and exercise habits in a region. Subsequently and until recent times, these causes of diseases were often considered, but not quantitatively measured. In 1662, John Graunt (1620–1674), a London haberdasher, published an analysis of the weekly reports of births and deaths in London, the first statistical description of population disease patterns. Among his findings, he noted a higher death rate for men than women, a high infant mortality rate, and seasonal variations in mortality. Graunt's study, with its meticulous counting and disease pattern description, set the foundation for modern public health practice.
Graunt's data collection and analytical methodology was furthered by the physician William Farr, who assumed responsibility for medical statistics for England and Wales in 1839 and set up a system for the routine collection of the numbers and causes of deaths. In analyzing statistical relationships between disease and such circumstances as marital status, occupations such as mining and working with earthenware, elevation above sea level and imprisonment, he addressed many of the basic methodological issues that contemporary epidemiologists deal with. These issues include defining populations at risk for disease and the relative disease risk between population groups, and considering whether associations between disease and the factors mentioned above might be caused by other factors, such as age, length of exposure to a condition, or overall health.
A generation later public health research came into its own as a practical tool when another British physician, John Snow (1813–1858), tested the hypothesis that a cholera epidemic in London was being transmitted by contaminated water. By examining death rates from cholera, he realized that they were significantly higher in areas supplied with water by the Lambeth and the Southwark and Vauxhall companies, which drew their water from a part of the Thames River that was grossly polluted with sewage. When the Lambeth Company changed the location of its water source to another part of the river that was relatively less polluted, rates of cholera in the areas served by that company declined, while no change occurred among the areas served by the Southwark and Vauxhall. Areas of London served by both companies experienced a cholera death rate that was intermediate between the death rates in the areas supplied by just one of the companies. The geographic pattern of infections was carefully recorded and plotted on a map of London. In recognizing the grand but simple natural experiment posed by the change in the Lambeth Company water source, Snow was able to make a uniquely valuable contribution to epidemiology and public health practice.
After Snow's seminal work, investigations by epidemiologists have come to include many chronic diseases with complex and often still unknown causal agents, and the methods of epidemiology have become similarly complex. Today researchers use genetics, molecular biology, and microbiology as investigative tools, and the methods used to establish relative disease risk make use of the most advanced statistical techniques available. Yet, reliance on meticulous counting and categorizing of cases and the imperative to think logically and avoid the pitfalls in mathematical relationships in medical data remain at the heart of all of the research used to show elevated disease risk in population subgroups and to prove that medical treatments are safe and effective.
Basic Epidemiological Concepts and Terms
The most basic concepts in epidemiology are the measures used to discover whether a statistical association exists between various factors and disease. These measures include various kinds of rates, proportions, and ratios. Mortality (death) and morbidity (disease) rates are the raw material that researchers use in establishing disease causation. Morbidity rates are most usefully expressed in terms of disease incidence (the rate with which members of a population or research sample contract a disease) and prevalence (the proportion of the group that has a disease over a given period of time).
WORDS TO KNOW
INCIDENCE: The number of new cases of a disease or injury that occur in a population during a specified period of time.
MORBIDITY: The term “morbidity” comes from the Latin word morbus, which means sick. In medicine it refers not just to the state of being ill, but also to the severity of the illness. A serious disease is said to have a high morbidity.
MORTALITY: Mortality is the condition of being susceptible to death. The term “mortality” comes from the Latin word mors, which means “death.” Mortality can also refer to the rate of deaths caused by an illness or injury, i.e., “Rabies has a high mortality.”
NOTIFIABLE DISEASES: Diseases that the law requires must be reported to health officials when diagnosed, including active tuberculosis and several sexually transmitted diseases; also called reportable diseases.
PREVALENCE: The actual number of cases of disease (or injury) that exist in a population.
SURVEILLANCE: The systematic analysis, collection, evaluation, interpretation, and dissemination of data. In public health, it assists in the identification of health threats and the planning, implementation, and evaluation of responses to those threats.
The most important task in epidemiology is the assessment or measurement of disease risk. The population at risk is the group of people that could potentially contract a disease, which can range from the entire world population (e.g., at risk for the flu) to a small group of people within a remote and isolated community (e.g., at risk for contracting a particular, ecologically restricted parasite). The most basic measure of a population group's risk for a disease is relative risk—the ratio of the prevalence of a disease in one group with particular biological, demographic, or behavioral characteristics to the prevalence in another group with different characteristics.
The simplest measure of relative risk is the odds ratio, which is the ratio of the odds that a person in one group has a disease to the odds that a person in a second, comparator group has the disease. The odds for contracting a disease are the ratio between the proportion of people in a population group that share particular characteristics that put them at risk for a disease to the proportion of people in a reference or control population (often the general population in a certain region or jurisdiction). For example, patients with chronic obstructive pulmonary disease (COPD), an inflammatory condition of the lungs associated with smoking and long exposure to air pollution, are at significantly greater risk of contracting community-acquired pneumonia (CAP) compared to a general population group matched on age and gender. Thus in a sample of subjects that includes both COPD patients and subjects who do not have COPD, epidemiologists expect that the odds ratio for the COPD patients contracting CAP would be significantly greater than 1.0.
The mortality rate is the ratio of the number of deaths in a population, either in total or disease-specific, to the total number of members of that population, and is usually given in terms of a large population denominator, so that the numerator can be expressed as a whole number. Thus, in 1982, the number of deaths from all causes was 1,973,000 and number of people in the United States was 231,534,000, yielding a death rate from all causes of 852.1 per 100,000 per year. That same year there were 1,807 deaths from tuberculosis yielding a disease-specific mortality rate of 7.8 per million per year.
Assessing disease frequency is more complex because of the factors of time and disease duration. For example, disease prevalence can be assessed at a point in time (point prevalence) or over a period of time, usually a year (period prevalence, annual prevalence). This is the prevalence that is usually measured in illness surveys that are reported to the public in the news. Researchers can also measure prevalence over an indefinite time period, as in the case of lifetime prevalence, which is the prevalence of a disease over the course of the entire lives of the people in the population under study up to the point in time when the researchers make the assessment. Researchers calculate this by determining for every person in the study sample whether or not he or she has ever had the disease, or by checking lifetime health records for everybody in the population for the occurrence of the disease, counting the occurrences, and then dividing by the number of people in the population.
The other basic measure of disease frequency is incidence, the number of cases of a disease that occur in a given period of time. Incidence is a critical statistic in describing the course of a fast-moving epidemic, in which medical decision-makers must know how quickly a disease is spreading. The incidence rate is the key to public health planning because it enables officials to understand what the prevalence of a disease is likely to be in the future. Prevalence is mathematically related to the cumulative incidence of a disease over a period of time as well as the expected duration of a disease, which can be a week in the case of the flu or a lifetime in the case of juvenile onset diabetes. Therefore, incidence not only indicates the rate of new disease cases, but is the basis of the rate of change of disease prevalence.
Epidemiologists use statistical analysis to discover associations between death and disease in populations and various factors—including environmental (e.g., pollution), demographic (age and gender), biological (e.g., body mass index or “BMI” and genetics), social (e.g., educational level), and behavioral (e.g., tobacco smoking, diet or type of medical treatment)—that could be implicated in causing disease.
Familiarity with basic concepts of probability and statistics is essential in understanding health care and epidemiological research. Statistical associations take into account the role of chance in contracting disease. Researchers compare disease rates for two or more population groups that vary in their environmental, genetic, pathogen exposure, or behavioral characteristics and observe whether a particular group characteristic is associated with a difference in rates that is unlikely to have occurred by chance alone.
Applications and Research
Applications in Public Health Practice
Certain concepts are basic to infectious disease epidemiology. These include the infectious agent, which is the organism that can develop within a human host and be passed along to other people via a particular mode of transmission, for example by air, food, or sexual intercourse. Infectious diseases have geographic scope or occurrence, and take a certain length of time to result in disease symptoms called the incubation period. After this incubation period, there is a period during which the individual can pass the infection along to others, called the period of communicability of the disease. The infectivity of a disease is the probability that an infected individual can pass the infection to an uninfected person, and the virulence of an infectious agent is the relative power and pathogenicity possessed by the organism. Populations of animals or human groups that harbor the infectious agent constitute a reservoir of the disease, and an organism such as a tick or insect that carries the infectious agent from such a reservoir to vulnerable individuals is called a vector.
Once the epidemic is underway, public health officials must begin attempts to control it even as they continue to gather epidemiological information about its cause and distribution. These control efforts consist of preventive measures for individuals and groups, which are measures designed to prevent further spread of the disease, and treatment in order to minimize the period of communicability of the infection, as well as reduce morbidity and mortality. Control of patient contacts and the immediate environment are foremost among such preventive measures, which can extend to patient isolation and observance of universal precautions, including handwashing, wearing of gloves and masks, and sterilization in dangerous instances. Epidemic measures, including the necessary abrogation of civil rights as in quarantines, are sometimes necessary to contain a communicable disease that has spread within an area, state, or nation. The epidemic may have disaster implications if effective preventive actions are not initiated, and the scope of actions can be international, requiring the coordination of disparate public health capabilities across national boundaries.
Screening Programs
Screening a community using relatively simple diagnostic tests is one of the most powerful tools that healthcare professionals and public health authorities have in preventing or combating disease. Familiar examples of screening include HIV testing to help prevent AIDS, tuberculin testing to screen for tuberculosis, and hepatitis C testing by insurers to detect subclinical infection that could result in liver cirrhosis over the long term. In undertaking a screening program, authorities must always judge whether the benefits of preventing the illness in question outweigh the costs and the number of cases that have been mistakenly identified, called false positives.
The ability of the test to identify true positives (sensitivity) and true negatives (specificity) makes screening a valuable prevention tool. However, the usefulness of the screening test is proportional to the disease prevalence in the population at risk. If the disease prevalence is very low, there are likely to be more false positives than true positives, which would cast doubt on the usefulness and the cost-effectiveness of the test. For example, if the prevalence of a disease in the population is only 2% and a test with a false positive rate of 4% is given to everyone (normally a good rate for a screening test), then individuals falsely identified as having the disease would be twice as frequent as individuals accurately identified with the disease. This would render the test results virtually useless. Public health officials deal with this situation by screening only population subgroups that have a high risk of contracting the disease. In infectious disease, screening tests are valuable for infections with a long latency period, which is the period of time during which an infected individual does not show disease symptoms, or which have a lengthy and ambiguous symptomatic period.
Clinical Trials
Clinical trials are the experimental branch of epidemiology in which scientific sampling with randomized selection of research subjects is combined with prospective study design and experimental controls involving a placebo or comparator active treatment control group. The statistical analysis used in clinical trials is similar to what is used in other types of epidemiological studies, usually simple counting of cases that improve or deteriorate and comparisons of morbidity and mortality rates between the trial treatment groups.
Clinical trials in infectious disease are most common when a significant follow-up period is available. One such trial was a rigorous test of the effectiveness of condoms in HIV/AIDS prevention. This experiment was reported in 1994 in the New England Journal of Medicine. Although in the United States and Western Europe the transmission of AIDS has been largely within certain high-risk groups, including drug users and homosexual males, worldwide the predominant mode of HIV transmission is heterosexual intercourse. The effectiveness of condoms to prevent HIV transmission is generally acknowledged, but even after more than 25 years of the growth of the epidemic, many people remain ignorant of the scientific support for their preventive value.
A group of European scientists conducted a prospective study of HIV negative subjects that had no risk factor for AIDS other than having a stable heterosexual relationship with an HIV infected partner. A sample of 304 HIV negative subjects (196 women and 108 men) was followed for an average of 20 months. During the trial 130 couples (42.8%) ended sexual relations, usually due to the illness or death of the HIV-infected partner. Of the remaining 256 couples that continued having exclusive sexual relationships, 124 couples (48.4%) consistently used condoms. None of the seronegative partners among these couples became infected with HIV. On the other hand, among the 121 couples that inconsistently used condoms, the seroconversion rate was 4.8 per 100 person-years.
Because none of the seronegative partners among the consistent condom-using couples became infected, this trial presents extremely powerful evidence of the effectiveness of condom use in preventing AIDS. On the other hand, there appear to be several main reasons why some of the couples did not use condoms consistently. Therefore, the main issue in the journal article shifts from the question of whether or not condoms prevent HIV infection—they clearly do—to the issue of why so many couples do not use condoms in view of the obvious risk. Couples with infected partners that got their infection through drug use were much less likely to use condoms than when the seropositive partner got infected through sexual relations. Couples with more seriously ill partners at the beginning of the study were significantly more likely to use condoms consistently. Finally, the longer the couple had been together before the start of the trial was positively associated with condom use.
Impacts and Issues
The control of infectious disease is an urgent mission for epidemiologists employed in various state and federal public health agencies and their partners in private industry and research foundations. The American Public Health Association (APHA) provides guidance for the epidemiology and control of more than 100 communicable diseases that confront public health practitioners at present.
Infectious disease epidemiology requires accurate and timely incidence and prevalence data such as is provided with comprehensive disease surveillance of usual and emerging diseases. Although the development of an organized surveillance system is critical to the provision of these data, the system's effectiveness depends on the willingness and ability of health care providers to detect, diagnose, and report the incidence of cases that the system is supposed to track. A reporting system functions at four levels: 1) the basic data is collected in the local community where the disease occurs; 2) the data are assembled at the district, state, or provincial levels; 3) information is aggregated under national auspices (e.g., the Centers for Disease Control and Prevention (CDC) in the United States); and 4) for certain prescribed diseases, the national health authority reports the disease information to the World Health Organization (WHO).
The reporting of cases at the local level is mandated for notifiable illnesses that come to the attention of healthcare providers. Case reports provide patient information, suspect organisms, and dates of onset with basis for diagnosis, consistent with patient privacy rights. Collective case reports are compiled at the district level by diagnosis stipulating the number of cases occurring within a prescribed time. Any unusual or group expression of illness that may be of public concern should be reported as an epidemic, whether the illness is included in the list of notifiable diseases and whether it is a well-known identified disease or an unknown clinical entity.
Because of the emergence or re-emergence of HIV/AIDS and resistant strains of tuberculosis, malaria, gonorrhea, and E. coli among others, infectious disease epidemiology, once thought to be waning in importance due to significant advances in public sanitation and immunization programs, has re-emerged as an urgent challenge. Infectious diseases currently threaten to destroy social order in some developing nations and pose extremely difficult public health problems even in the wealthiest societies. Hantavirus infections, thought to be a serious problem primarily in Asia, have emerged as an epidemic in the southwestern United States. Lyme disease continues to afflict ever larger populations in the Northeast United States; Ebola virus has jumped from monkeys to humans in Africa and pneumococci are becoming resistant to the antibiotics used to treat infections.
Air travel has created the situation in which travelers can return home from areas where particular pathogens are endemic within the incubation period of every infectious disease, which can potentially precipitate an epidemic.
Primary Source Connection
John Snow (1813–1858) was an English physician who made great advances in the understanding of both anesthetics and the spread of disease, especially cholera.
The first pandemic, which reached Great Britain in 1831, caused as much fear and panic as tuberculosis did in the early twentieth century and HIV/AIDS does today. The death rate from cholera was over 50 percent and medical opinion was sharply divided as to the cause. At the time, John Snow was a doctor's apprentice gaining his first experience with the disease, noting its symptoms of diarrhea and extreme dehydration.
The germ theory of disease, which holds that viruses and bacteria are the causative infectious agents of diseases such as yellow fever, smallpox, typhoid, cholera, and others, was in its infancy at this time. Some doctors accepted the hypothesis of contagion in which disease spreads from one person to another. Others assumed that “miasmata” or toxins in the air, spread disease.
Snow first began a serious scientific investigation of cholera transmission during the 1848 London epidemic. In his classic essay, On the Mode of Communication of Cholera, published on August 29, 1849, he postulated that polluted water was a source of cholera—especially water contaminated by the waste of an infected person, a not-uncommon occurrence at the time. When an outbreak erupted a few years later in central London at the end of August 1854, close to where Snow himself lived, he resumed his research.
The historical claim that Snow removed the pump handle himself—which would, of course, have stopped exposure to the contaminated water—has little evidence and may be a myth. Snow recommended its removal, but the actual removal was probably done by the local curate, Henry Whitehead, several days after the outbreak began.
It is partially thanks to John Snow's work in the Broad Street area that Britain suffered fewer major outbreaks of cholera after this time. An influential figure in medical circles, he had been elected president of the Medical Society of London in 1855. Fortunately for British public health, the successful proof of his theory on the transmission of cholera—from person to person via contaminated water— took hold, and the “environmental” theory eventually died away. Although the actual causative agent, the bacterium Vibrio cholerae, would not be identified until 1883, Snow's preventive methods worked. Indeed, they are still effective today, for despite the advent of vaccination and antibiotics, handwashing and the avoidance of contaminated food and water are still fundamental ways of preventing infection.
Because Snow based his investigation on the idea of germ theory, which French microbiologist Louis Pasteur (1822–1895) would later prove, he used a scientific approach and epidemiological study of cholera victims to validate his hypothesis. As his case notes amply demonstrate, much of his research was driven by his patients’ visible suffering.
See AlsoDemographics and Infectious Disease; Public Health and Infectious Disease; Notifiable Diseases.
BIBLIOGRAPHY
Books
Bennenson, A.S., ed. Control of Communicable Diseases Manual. 16th ed. Washington, DC: American Public Health Association, 1995.
Centers for Disease Control. Tuberculosis Statistics: States and Cities, 1984. Atlanta: Centers for Disease Control, 1985.
Graunt, J. Natural and Political Observations Made upon the Bills of Mortality. London, 1662. Reprinted by Johns Hopkins Press, 1939.
Hennekens, C.H., and J.E. Buring. Epidemiology in Medicine. Boston: Little, Brown, 1987.
Hippocrates. On Airs, Waters and Places. Shephard, David A.E. John Snow: Anaesthetist to a Queen and Epidemiologist to a Nation. Cornwall, Prince Edward Island, Canada: York Point, 1995.
Periodicals
De Vincenzi, I. “A Longitudinal Study of Human Immunodeficiency Virus Transmission by Heterosexual Partners.” New England Journal of Medicine 331 (August 11, 1994): 341–346.
UCLA. Department of Epidemiology. School of Public Health. “John Snow.” <http://www.ph.ucla.edu/epi/snow.html> (accessed March 30, 2007).
Kenneth LaPensee