EARLY DETECTION OF DISEASE Identification of a specific disease at an early stage in the natural history of the disease. Detection before the usual clinical diagnosis does not guarantee diagnosis at an early stage, nor does it assure a more effective treatment. Often an ambiguous and misleading expression because of the term detection, which implies that the disease would otherwise be diagnosed “late,” and because sometimes no disease is diagnosed, just a putatively precursor lesion (perhaps, naturally reversible) or a genetic or biochemical alteration (the actual risk of disease conferred by the latter may not have been demonstrated by longitudinal studies).62,63,134 Since detection is not a synonym of diagnosis, confirmation of the suspected diagnosis will require additional tests, properly diagnostic. By definition, early detection of disease does not prevent dis- ease occurrence. It may do so only if early detection of a precursor lesion leads to complete and definitive removal of all such lesions; otherwise long-term medical surveillance of precursor lesions or other alterations (and, as usual, of overt disease) will be required, and no gain will exist over diagnosis of disease through customary clinical paths.

Early detection may be accomplished both by early clinical detection and by population- based screening programs. It includes both symptomatic and asymptomatic individuals. It may be a form of secondary prevention; in certain diseases it may contribute to tertiary prevention. Early detection of disease will usually appear to improve survival, even when it is ineffective (e.g., because treatment is not administered earlier, treatment is not more effective when administered earlier, or no effective treatment is available). Early detection (of disease, of precursor lesions, of genetic factors putatively conferring disease susceptibility, and even of classic risk factors) is not an aim in itself: it is justified only if it improves outcomes meaningful to individuals or communities. See also case-finding; lead time bias; screening.

EARLY CLINICAL DETECTION Early detection of disease in a clinical setting among persons presenting to a clinician or using medical services (by contrast with early detec- tion of disease through a population-based screening program). In principle the term includes both symptomatic and asymptomatic individuals, but in practice most indi- viduals who undergo early clinical etection show signs and symptoms of the diease to be detected or have precursor lesions (i.e., alterations that have conclusively been demonstrated to increase risk of the target disease). See also case finding.

EARLY-WARNING SYSTEM In disease surveillance, a specific procedure to detect as early as possible any departure from usual or normally observed frequency of phenom- ena. For example, the routine monitoring of numbers of deaths from pneumonia and influenza in large American cities has been used as an early warning system for the iden- tification of influenza epidemics. In developing countries, a change in children’s average weights is an early warning signal of nutritional deficiency. See also case report.

EBM See evidence-based medicine.

E-BOOK A method of recording encounters in primary medical care: encounters are arranged by problem or diagnostic category, thus making it possible to count the number of persons seen (and the number of times each was seen) according to problem or diagnostic category in a given period of time.135 It was used in epidemiological studies of primary medical care. See also age-sex register; diagnostic index.

EBPH See evidence-based public health.

EC European Community or European Commission.

ECDC European Centre for Disease Prevention and Control (

ECLOSION Emergence of imago (adult) from pupal case, hatching of larva from egg; a term descriptive of life stages of insect vectors.

ECOEPIDEMIOLOGY In the early 1980s this term was applied to the study of ecological influences on human health, whether related to environmental chemical agents or bio- logical interactions such as life cycles of parasites. Mervyn Susser136 (b. 1921) used the term within a conceptual approach that unifies molecular, clinical, and social epidemi- ology in a multilevel application of methods aimed at identifying causes, categorizing risks, and controlling public health problems. A perspective that balances traditional biomedical concepts of risk with the broader social and environmental context.18

ECOLOGICAL CASE-REFERENT DESIGN A study design suitable for use in the evaluation of communitywide interventions and characterized by measurement of the exposure on a ecological scale and of the outcome on a individual scale.

ECOLOGICAL ANALYSIS Analysis based on aggregated or grouped data; errors in inference may result because associations may be artifactually created or masked by the aggregation process.107 See aggregative fallacy; ecological fallacy; atomistic fallacy.

ECOLOGICAL BIAS See aggregative fallacy; atomistic fallacy; cross-level bias; ecological fallacy.

ECOLOGICAL CORRELATION A correlation in which the units studied are populations or groups rather than individuals. Correlations found in this manner may not hold true for the individual members of the same populations. See also ecological fallacy.

ECOLOGICAL DEPTH A criterion used for assessing the impact or penetration of an intervention into the local system; it includes the intervention scope (number of levels) and the duration of effect. An epidemiological program with high ecological depth yields an effect at multiple levels (individual, environmental) that endures over time.18

ECOLOGICAL FALLACY (Syn: aggregation bias, ecological bias)

  1. An erronous inference that may occur because an association observed between
    variables on an aggregate level does not necessarily represent or reflect the association that exists at an individual level; a causal relationship that exists on a group level or among groups may not exist among the group individuals.18,31,107
  2. An error in inference due to failure to distinguish between different levels of organization. A correlation between variables based on group (ecological) characteristics is not necessarily reproduced between variables based on individual characteristics; an association at one level may disappear at another or even be reversed. Example: At the ecological level, a correlation has been found in several studies between the quality of drinking water and mortality rates from heart disease; it would be an ecological fallacy to infer from this alone that exposure to water of a particular level of hardness necessarily influences the individual’s chances of dying from heart disease. Policies, decisions, and actions at a given level (individual, municipal, regional, etc.) must be based on evidence—on causal relationships at that level. See also aggregative fallacy, atomistic fallacy, cross-level bias.

ECOLOGICAL FOOTPRINT The dimensions and composition of the ecosystem required to sustain the actions or goods of a population, such as a hospital, a factory, a holiday resort, an aircraft. An estimate of the impact of an individual, group, or organization on the environment based on consumption and pollution. The term is applied mainly to the required input of resources and output of waste products. Ecological footprint analysis compares human demand and consumption of natural resources with the system’s ecological capacity to regenerate them.

ECOLOGICAL STUDY In epidemiology, a study in which the units of analysis are populations or groups of people rather than individuals. An example is the study of the relationship between the distribution of income and mortality rates in states or provinces. Conclusions of ecological studies may not apply to individuals; thus caution is needed to avoid the ecological fallacy. Ecological studies can reach valid causal inferences on causal relationships at the ecological level—i.e., on causal processes that occur at the group level or among groups.107 Ecological studies are necessary for decisions that affect entire groups (e.g., for public and private policies that are developed across an entire state, country, or region). See also aggregative fallacy, atomistic fallacy, cross-level bias.

ECOLOGICAL TRANSITION Within a framework of human development, ecological transitions are shifts in roles or settings that occur across the life course (e.g., arrival of a new sibling, entering school, finding a job, getting married, moving one’s household, retiring). These transitions usually entail a change in a person’s role or behavioral expectations.18

ECOLOGY The study of the relationships among living organisms and their environment. The comprehensive science of the relation of the organism to the environment. See also human ecology.

ECOSOCIAL THEORY OF DISEASE DISTRIBUTION One of the multilevel epidemiological frameworks that seek to integrate social and biological reasoning and a historical and ecological perspective so as to develop new insights into determinants of population distributions of disease and social inequalities in health. The central ques- tion for the theory is: “Who and what is responsible for population patterns of health, disease, and well-being as manifested in social inequalities in health?”137

ECOSYSTEM Plant and animal life systems considered in relation to the environmental factors and processes that influence them. The fundamental unit in ecology, comprising the living organisms and the nonliving elements that interact in a defined region. This region may be any size, from a drop of pond water to the entire biosphere. A comparatively stable and enduring arrangement of a population with mutual dependencies, including all living and nonliving (e.g., water, climate) elements within an area. The population operates collectively as a unit in ways that maintain a viable relationship with the environment. Edges of ecosystems are seldom clearly defined.18,138

EFFECT The result of a cause. In epidemiology, frequently a synonym for effect measure.

EFFECTIVENESS In the usage made common among epidemiologists by Archibald L. Cochrane (1909–1988)139 and others, it is a measure of the extent to which a specific intervention, procedure, regimen, or service, when deployed in the field in the usual circumstances, does what it is intended to do for a specified population.140 A measure of the extent to which a health care intervention fulfills its objectives in practice. To be distinguished from efficacy and efficiency. See also intention-to-treat analysis; pragmatic study.

EFFECTIVE POPULATION SIZE The average number of individuals in a population that contribute genes to the next generation.

EFFECTIVE SAMPLE SIZE Sample size after dropouts, deaths, and other specified exclusions from an original sample.

EFFECT MEASURE A quantity that measures the effect of a factor on the frequency or risk of a health outcome. Three such measures are attributable fractions, which measure the fraction of cases due to a factor; risk and rate differences, which measure the amount a factor adds to the risk or rate of a disease; and risk and rate ratios, which measure the amount by which a factor multiplies the risk or rate of disease.

EFFECT MODIFICATION (Syn: effect-measure modification) Variation in the selected effect measure for the factor under study across levels of another factor.12,24 See also interaction.

EFFECT MODIFIER (Syn: modifying factor)

  1. A factor that modifies the measure of effect of a putative causal factor under study.
    There is effect modification when the selected effect measure for the factor under study varies across levels of another factor. An effect modifier may modify different measures in different directions and may modify one measure but not another.
  2. A factor that biologically, clinically, socially, or otherwise alters the effects of a causal factor under study. For example, age-related decline in liver function can lead to stronger effects of toxins in the elderly; immunization reduces or eliminates the adverse consequences of exposure to pathogenic organisms. As another example, age is an effect modifier for many conditions, and immunization status is an effect modifier for the consequences of exposure to pathogenic organisms. See also causality; interaction.

EFFICACY The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions; the benefit or utility to the indi- vidual or the population of the service, treatment regimen, or intervention. Ideally, the determination of efficacy is based on the results of a randomized controlled trial.


  1. The effects or end results achieved in relation to the effort expended in terms of money, resources, and time. The extent to which the resources used to provide a specific intervention, procedure, regimen, or service of known efficacy and effectiveness are minimized. A measure of the economy (or cost in resources) with which a procedure of known efficacy and effectiveness is carried out. The process of making the best use of scare resources.
  1. In statistics, the relative precision with which a particular study design or estimator
    will estimate a parameter of interest.
  2. Health economists identify several types of efficiency:141 technical efficiency refers to the relationship between resources (capital and labor) and health outcomes. productive efficiency refers to maximizing health outcomes for a given cost or minimizing cost for a given outcome.  allocative efficiency is maximizing community health at given levels of technical and productive efficiency.
  3. Other types of efficiency include:
    statistical efficiency is the extent to which a study design maximizes the precision of effect estimates obtained from a given number of subjects or given amount of person-time. study efficiency is the value of information obtained from a study in relation to the number of subjects (or person-time) and/or to the monetary and other costs of the study.
  4. EGG COUNT See worm count.
  5. EIS See Epidemic Intelligence Service.
  6. ELECTROPHILIC Having an affinity for negative charge. Molecules that behave as electron acceptors are electrophilic. Only sufficiently reactive, electrophilic compounds are capable of directly interacting with cellular proteins and DNA. See also nucleophilic; carcinogen; procarcinogen.

ELIGIBILITY CRITERIA An explicit statement of the conditions under which persons are admitted to an epidemiological study, such as a case-control study or a randomized controlled trial.

ELIMINATION Reduction of case transmission to a predetermined very low level; e.g., elimination of tuberculosis as a public health problem was defined by the WHO (1991) as reduction of prevalence to a level below one case per million population. Compare eradication (of disease).

ELISA Enzyme-linked immunosorbent assay.


  1. Processes through which extrinsic factors experienced at different lifestages are inscribed into an individual’s body functions or structures, and the result of such processes.16 How humans biologically incorporate the world in which we live, including aspects of the societal and ecological context. Recognizing that humans are simultaneously social beings and biological organisms, the concept aims to highlight that (1) bodies tell stories about—and cannot be studied divorced from—the conditions of human existence; (2) bodies tell stories that often match people’s stated accounts; and (3) bodies tell stories that people cannot or will not tell. A multilevel phenomenon, integrating soma, psyche, and society within historical and ecological context; hence an antonym to disembodied genes, minds, and behaviors. Pathophysiological responses and clinical expressions of social inequalities result from and reflect how people literally embody and express their experiences of inequality.125–128,137,142–144
  2. A tangible or visible form of an idea, quality, or feeling. The representation or expression of something in such a form.76 A key concept for some schools of phenomenology. The subjective experience of one’s own body is different from the objective or scientific picture of a body in physiological terms. The specific ways in which we experience ourselves as embodied thus become prime data for analyses about knowledge and experience.77,127 See also disease.
  3. EMBRYO Biologically, in the human, the stage of the conceptus from uterine implantation (about 7 days after fertilization) to completion of organ development (about 54–60 days); conventionally, 8 weeks after conception, 10 weeks after the last menstrual period. The distinction between an embryo and a fetus can be important in law and in perinatal epidemiology.

EMERGING INFECTIONS (Syn: emerging pathogens) Infectious diseases that have recently been identified and taxonomically classified. Many of them are capable of caus- ing dangerous epidemics. They include human immunodeficiency virus (HIV) infec- tion, Ebola virus disease, hantavirus pulmonary syndrome and other viral hemorrhagic fevers, Campylobacter infection, transmissable spongiform encephalopathies, Legion- naires’ disease, and Lyme disease. Some appear to be new diseases of humans (e.g., HIV infection). Others, such as the viral hemorrhagic fevers, may have existed for many centuries and have been recognized only recently, because ecological or other environ- mental and demographic changes have increased the risk of human infection. Reemerg- ing infections are certain “old” diseases, such as tuberculosis and syphilis, that have experienced a resurgence because of changed host-agent-environment conditions.

EMPIRICAL Based directly on experience (e.g., observation or experiment) rather than on reasoning or theory alone.

EMPIRICAL-BAYES METHODS Statistical methods that have the mathematical form of Bayesian statistics but that estimate the prior distributions from the data being ana- lyzed instead of deriving them from external data or expert judgment. Such methods are especially useful for addressing multiple comparisons problems, as they arise, for example, in genomewide “scans.” See also shrinkage estimation.

EMPORIATRICS The specialty of travel medicine.145 From the Greek emporion (trade).

ENABLING FACTORS See causation of disease, factors in.

ENCOUNTER A face-to-face transaction between a personal health worker and a patient or client. Not limited to health care settings.

ENDEMIC DISEASE The constant presence of a disease or infectious agent within a given geographic area or population group; may also refer to the usual prevalence of a given disease within such an area or group. See also holoendemic disease; hyperendemic disease; prevalence.

ENDOBIOTIC An endogenous substance that produces a toxic metabolite when it is metabolized. A substance or organisms that grows within a living organism. Contrast xenobiotic.

END RESULTS See outcomes.

ENEE European Network for Education in Epidemiology.

ENTROPY In thermodynamics, entropy is a measure of the disorder in a system. In statistics, entropy means the same; it is a measure of disorder, uncertainty, or chaos or, more loosely, randomness.146

ENVIRONMENT All that which is external to the individual human host. Can be divided into physical, biological, social, cultural, etc., any or all of which can influence the health status of populations.9,72,130,138 “The environment provides the food people eat, the water they drink, the air they breathe, the energy they command, the plagues and pests they combat and the mountains, seas, lakes, streams, plants and animals that they enjoy and depend upon.”147

ENVIRONMENTAL EPIDEMIOLOGY A branch or subspecialty of epidemiology that uses epidemiological principles, reasoning, and methods to study the health effects on populations of exposure to physical, chemical, and biological agents external to the human body and of immediate and remote social, economic, and cultural factors (e.g., urbanization, agricultural development, energy production/combustion) related to these physical, chemical, and biological agents. By studying populations in different exposure circumstances, environmental epidemiologists aim to clarify relationships between exogenous agents and/or factors and health. Recognition of health hazards posed by large-scale environmental changes and by ecological disruption, often via indirect pathways, has added an extra dimension to this field of inquiry.

ENVIRONMENTAL HEALTH CRITERIA DOCUMENT Official publication containing a review of existing knowledge about chemicals, radiation, etc., and their identifiable immediate and long-term effects on health. Environmental health criteria documents are produced by the WHO, the International Agency for Research on Cancer (IARC), and many national agencies, such as the National Institute for Occupational Safety and Health (NIOSH) in the United States.

ENVIRONMENTAL HEALTH IMPACT ASSESSMENT A statement of the beneficial or adverse health effects or risks due to an environmental exposure or likely to follow an environmental change. Such statements may contain or refer to results of epidemiologi- cal and/or toxicological studies of environmental health hazards.

ENVIRONMENTAL HYPERSENSITIVITY An ill-defined concept that refers to a set of poorly understood conditions and syndromes that some authors deem potentially related to exposure to low concentrations of chemical, physical, or other environmen- tal agents. Related conditions might include the sick building syndrome, the chronic fatigue syndrome, and multiple chemical sensitivity.

ENVIRONMENTAL TOBACCO SMOKE (ETS) A specific form of air pollution due to burning tobacco, especially sidestream smoke. ETS is carcinogenic to humans; e.g., it is classified in group 1 by the International Agency for Research on Cancer (IARC). Closely related terms are involuntary smoking or passive smoking and secondhand smoke.

EPA Environmental Protection Agency (United States).

EPI Expanded Programme on Immunization (WHO/UNICEF).

EPIDEMIC [from the Greek epi (upon), demos (people)] The occurrence in a community or region of cases of an illness, specific health-related behavior, or other health-related events clearly in excess of normal expectancy.
The community or region and the period in which the cases occur must be specified precisely.

The number of cases indicating the presence of an epidemic varies according to the agent, size, and type of population exposed; previous experience or lack of exposure to the disease; and time and place of occurrence. Epidemicity is thus relative to usual frequency of the disease in the same area, among the specified population, at the same season of the year.

A single case of a communicable disease long absent from a population or first invasion by a disease not previously recognized in that area requires immediate reporting and full field investigation; two cases of such a disease associated in time and place may be sufficient evidence to be considered an epidemic. Classic epidemics initially identified following the occurrence of small numbers of cases include the epidemic of vaginal cancer in daughters of women who took diethylstilbestrol during pregnancy148 and the pandemic of AIDS, which was heralded by a report149 of cases of Pneumocystis carinii pneumonia among gay men in Los Angeles in 1981.

The purpose of surveillance systems such as the Epidemic Intelligence Service is to identify epidemics as early as possible so that effective control measures can be put in place. This remains a most important use of epidemiology.

The word may be used also to describe outbreaks of disease in animal or plant populations. See also epizootic; epornithic.

EPIDEMIC, COMMON SOURCE (Syn: common vehicle epidemic, holomiantic disease) Outbreak due to exposure of a group of persons to a noxious influence that is common to the individuals in the group. When the exposure is brief and essentially simultaneous, the resultant cases all develop within one incubation period of the disease (a “point” or “point source” epidemic). The term holomiantic disease was used by Stallybrass (1931) to describe outbreaks of this type, but as with several other terms created from Greek or Latin roots, transmission to epidemiologists who lacked a classical education did not take place.


EPIDEMIC, POINT SOURCE See epidemic, common source.

EPIDEMIC CURVE A graphic plotting of the distribution of cases by time of onset.

EPIDEMIC INTELLIGENCE (Syn: epidemiological intelligence) The process of detecting, verifying, analyzing, assessing, and investigating signals that may represent a threat to public health.150 Activities aimed at managing epidemiological crises, biochemical threats, radiological risks, natural disasters, or the public health impact of terrorist attacks and wars. A government body engaged in collecting secret or sensitive information related to epidemic outbreaks. The Global Public Health Intelligence Network (GPHIN) of the World Health Organization is an Internet-based multilingual early-warning tool that continuously searches news wires and websites to identify information about disease outbreaks and other events of potential international public health concern. To ensure a comprehensive picture of the epidemic threat to global health security, WHO also gathers epidemic intelligence from informal sources. With the advent of modern com- munication technologies, many initial outbreak reports now originate in the electronic media and electronic discussion groups.151

EPIDEMIC INTELLIGENCE SERVICE (EIS) A postgraduate training program in epide- miology of the U.S. Centers for Disease Control and Prevention (CDC). Established in 1951 owing to biological warfare concerns arising from the Korean War. EIS officers have been decisive in the investigation of many epidemics, including AIDS, anthrax, hantavirus, and West Nile virus in the United States and Ebola in Uganda and Zaire.

EPIDEMICS, HISTORY OF The effect of diseases on the course of history fascinates epidemiologists and historians alike.10,152 It has preoccupied scholars since the bibli- cal plagues, Hippocrates, and the epidemic, described by Thucydides, that struck the Athenians at the end of the first year of the Peloponnesian War (429 b.c.). Measles and smallpox brought by Europeans defeated the Aztecs and Incas, who, in return, gave tobacco and perhaps syphilis to Europeans. There are innumerable scholarly and popu- lar works on the subject. Early treatises include those of Hecker153 and Creighton154; a modern work by a historian is Plagues and Peoples.155 Perhaps the nearest to a compre- hensive monograph by an epidemiologist is Thomas McKeown’s The Origins of Human Disease.156 Partial accounts include histories of the impact on societies and civilizations of syphilis,157 tuberculosis,158 poliomyelitis,159 typhus,160 and many other conditions.125,161

EPIDEMIC THRESHOLD The number or density of susceptibles required for an epi- demic to occur. According to the mass action principle, the epidemic threshold is the reciprocal of the infection transmission parameter.


EPIDEMIOLOGICAL METHODS, HISTORY OF A domain of history that deals specifically with the evolution of epidemiological methods and concepts.5–11,81

EPIDEMIOLOGICAL RESEARCH Occurrence research—i.e., research among people into the frequency of occurrence of phenomena of public health, clinical, social, or bio- logical relevance, with measures of frequency and causal assessments related to the determinants of such phenomena.5 See also creativity; integrative research.

“EPIDEMIOLOGICAL TRANSITION” THEORY Traditionally,162 the mortality component of the demographic transition was considered to have three phases: (1) The “age of pestilence and famine”; (2) the “age of receding pandemics”; (3) the “age of degenerative and man-made diseases.” According to Omran,162 the shift from the first to third phases took about 100 years in the Western industrial nations, but it occurred more rap- idly in Japan and eastern Europe; many developing countries have yet to undergo the shift. Mackenbach163 shows that the transition from first to third phase took consider- ably longer in Western industrial nations and asserts that “degenerative and man-made diseases” is a misleading term for conditions such as cancer and cardiovascular disease, which have complex etiologies.

EPIDEMIOLOGIST A professional who strives to study and control the factors that influence the occurrence of disease or other health-related conditions and events in defined populations and societies, has an expertise in population thinking and epidemiological methods, and is knowledgeable about public health and causal inferences in health. The control of disease in populations is often considered to be a core task for the epidemiologist involved in the provision of public health services. Epidemiologists may study disease in populations of animals and plants as well as among human populations.

EPIDEMIOLOGY The study of the occurrence and distribution of health-related states or events in specified populations, including the study of the determinants influencing such states, and the application of this knowledge to control the health problems.

Study includes surveillance, observation, hypothesis testing, analytic research, and experiments. Distribution refers to analysis by time, place, and classes or subgroups of persons affected in a population or in a society. Determinants are all the physical, biological, social, cultural, economic and behavioral factors that influence health. Health-related states and events include diseases, causes of death, behaviors, reactions to preventive programs, and provision and use of health services. Specified populations are those with common identifiable characteristics. Application to control… makes explicit the aim of epidemiology—to promote, protect, and restore health.

The primary “knowledge object” of epidemiology as a scientific discipline are causes of health-related events in populations. In the past 70 years, the definition has broadened from concern with communicable disease epidemics to take in all processes and phenomena related to health in populations.4,5,9,11,152,164 Therefore epidemiology is much more than a branch of medicine treating of epidemics. There was a London Epidemiological Society in the 1850s. Epidemiología appears in the title of a Spanish history of epidemics, Epidemiología española (Madrid, 1802). The term epidemic is much older; for instance, it appears in Johnson’s Dictionary (1775), and the Oxford English Dictionary gives a citation dated 1603. The word was, of course, used by Hippocrates. See also population thinking; group comparison.

EPIDEMIOLOGY, DEMARCATION OF Marking or fixing the boundaries or limits of epidemiology as a scientific discipline; assessing epidemiology’s methodologies, objects of research, legitimate uses and applications (e.g., in public health policy, in clinical practice, in basic research); examining its distinctiveness, similarities, or relationships with other scientific disciplines. Defense of scientific identity and solidarity, disciplinary autonomy, and epistemic authority of epidemiology are additional important elements of boundary work. These forms of scientific discourse are important components of the process by which various sciences establish their scientific and intellectual nature, moral order, social status, and mission.4 Epidemiology benefits from a rich plural- ity of scientific cultures and practices; consequently, it enjoys diverse demarcation discourses.4–12,111,136,164–170 Demarcation of many scientific disciplines evolved historically as their intellectual, institutional, and professional environments evolved.4

EPIDEMIOLOGY, ANALYTIC See analytic study.

EPIDEMIOLOGY, APPLIED See applied epidemiology.

EPIDEMIOLOGY, BLACK-BOX See “black-box epidemiology.”

EPIDEMIOLOGY, CANCER See cancer epidemiology.

EPIDEMIOLOGY, CARDIOVASCULAR See cardiovascular epidemiology.

EPIDEMIOLOGY, DESCRIPTIVE See descriptive epidemiology. EPIDEMIOLOGY,DEVELOPMENTAL Seedevelopmentalandlife-courseepidemiology.

EPIDEMIOLOGY, DISASTER See disaster epidemiology.

EPIDEMIOLOGY, ENVIRONMENTAL See environmental epidemiology.

EPIDEMIOLOGY, EXPERIMENTAL See experimental epidemiology.

EPIDEMIOLOGY, FIELD See field epidemiology.

EPIDEMIOLOGY, FORENSIC See forensic epidemiology.

EPIDEMIOLOGY, HEALTHCARE See hospital epidemiology.

EPIDEMIOLOGY, HOSPITAL See hospital epidemiology.

EPIDEMIOLOGY, LIFE COURSE See developmental and life-course epidemiology.

EPIDEMIOLOGY, MECHANISTIC See mechanistic epidemiology.

EPIDEMIOLOGY, OBSERVATIONAL See observational epidemiology.

EPIDEMIOLOGY, OCCUPATIONAL See occupational epidemiology.

EPIDEMIOLOGY, PRIMARY CARE See primary care epidemiology.

EPIDEMIOLOGY, PSYCHOSOCIAL See social epidemiology.

EPIDEMIOLOGY, SOCIAL See social epidemiology.

EPIDEMIOLOGY, SOCIOLOGY OF. See sociology of epidemiology.

EPIDEMIOLOGY, THEORETICAL See theoretical epidemiology.

EPIGENETIC INHERITANCE A set of reversible heritable changes in gene function or other cell phenotype that occur without a change in the genotype. Such changes may be spontaneous, in response to environmental factors, or in response to other genetic events. Several types of epigenetic inheritance systems exist.171 Epigenetic processes include paramutation, bookmarking, imprinting, gene silencing, X chromosome inac- tivation, position effect, reprogramming, or transvection.

EPIGENETICS The study of heritable changes that are not the result of changes in the DNA sequence. Information heritable during cell division other than the DNA sequence itself. Changes in gene expression that are not regulated by the DNA nucleo- tide sequence (e.g., gene silencing by promoter hypermethylation or histone modifi- cation). Amazingly, given that they are not coded in the DNA, some epigenetic changes are heritable across several generations. Changes in gene-expression patterns caused by epigenetic alterations have been observed in biological systems exposed to nickel, cad- mium, or arsenic. Complex diseases like cancer arise from the stepwise accumulation of genetic and epigenetic alterations that confer upon an incipient neoplastic cell (a “clone”) the properties of unlimited, self-sufficient growth and resistance to normal homeostatic regulatory mechanisms.116,172–176

EPIGENOME The overall epigenetic state of a cell. At the intersection between environ- ment and genetic variation, the epigenome is an important target of environmental fac- tors. According to the common disease genetic and epigenetic (CDGE) hypothesis, the epigenome may modulate the effect of genetic variation either by affecting the gene’s expression through the action of chromatin proteins or DNA methylation or by modu- lating protein folding of the gene product. The epigenome may, in turn, be affected by sequence variation in the genes encoding chromatin or chaperone proteins. Envi- ronmental factors (e.g., toxins, growth factors, dietary methyl donors, and hormones) can affect the genome and the epigenome. Although the epigenome is particularly susceptible to dysregulation during gestation, neonatal development, puberty, and old age, it is most vulnerable to environmental exposures during embryogenesis, because the elaborate DNA methylation and chromatin patterning required for normal tissue development is programmed during early development. Many xenobiotics have the potential to modify the epigenome.118 One key component of the cancer epigenome, for example, is an altered DNA methylation pattern composed of global demethylation and promoter localized hypermethylation; these changes fundamentally participate in an altered structure and function of DNA (e.g., unwanted transcription of repeat elements, abnormal activation of oncogenes, genomic instability, aberrant silencing of genes important to the initiation and progression of tumors).177 See also developmental origins hypothesis.

EPI INFO Free software developed by the CDC for epidemiologists and other health professionals. Supports development of a questionnaire or form, the data entry pro- cess, and data analysis, inluding epidemiological measures, tables, graphs, and maps (

EPISODE Period in which a health problem or illness exists, from its on set to its resolution. See also encounter.

EPISTASIS Gene interaction; particularly interaction between different alleles at differ- ent genes (e.g., the suppression by a gene of the effect of another gene).

EPISTEMIC Relating to knowledge or to the degree of its validation.


  1. Transnational networks of scientists and of other knowledge-based professionals. Scientific associations have features of epistemic communities; subgroups within them may act as epistemic communities.7
  2. Networks of experts who define for policy makers what the problems they face are and what they should do about them.
  3. A group of people who do not have any specific history together but share ideas. Those who accept one version of a story that is particularly meaningful for their communities.

EPISTEMIC CULTURES Sets of practices, arrangements, and mechanisms bound together by necessity, affinity, interest, and historical coincidence that, in a given scientific field or area of professional expertise, make up how we know what we know.178 Cultures of pursuing and warranting knowledge; they are pursued by specialists separated off from other specialists by long training periods, stringent division of labor, distinctive techno- logical tools and methodologies, financing sources, scientific associations, journals, and dictionaries … Interiorized processes of knowledge creation. They build the epistemic subject and referents, the meaning of empirical, methods of consensus formation, or forms of engagement with the social world.4 They draw on different background knowl- edges, which become merged in knowledge work. They are forms of life and agree on acceptable forms of life (e.g., what it is to be a “postdoc” in epidemiology). See also knowledge construction; sociology of scientific knowledge.


  1. The theory of knowledge. Epistemological questions include the origin of knowledge; the place of experience and reason in generating knowledge; the relationship between knowledge and certainty and between knowledge and the impossibility of error; the changing forms of knowledge as societies change. These issues are linked with others, such as the nature of truth and the nature of experience and meaning.77
  2. The study of the relation between the knower (or would-be knower) and what can be known. Answers to these questions are constrained by answers to ontological questions.179

In epidemiology and other health sciences, debates have benefited from clarifying the methodological, epistemological, and ontological nature of the issues under analysis4,5,10,180–182 For instance, the proposition that methods used in an epidemiological study must be coherent with the “knowledge object”181 of the study does not primarily address a methodological issue but an epistemological one; also of an essentially epistemological nature are criticisms of studies that suffer from a hypertrophy or a dissonance of the methodological apparatus vis-à-vis the study hypotheses, of studies based on a poor conception of the hypotheses, or of statistical analyses unguided by knowledge available on the study subject.5,68,93 See also ontology.

EPIZOOTIC An outbreak (epidemic) of disease in an animal population; often with the implication that it may also affect human populations.

EPORNITHIC An outbreak (epidemic) of disease in a bird population.

EPR Epidemic and Pandemic (Alert and) Response. See also epidemiological intelligence.

EQUIPOISE A state of genuine uncertainty about the benefits or harms that may result from different exposures or interventions. A state of equipoise is an indication for a randomized controlled trial, because there are no ethical concerns about one regimen being better for a particular patient.

EQUITY Fairness, impartiality. An important concept in bioethics, especially in relation to human rights. See also health equity.

EQUIVALENCE TESTS Significance tests in which the null hypothesis is that samples differ to a prescribed degree. A significant result of an equivalence test comparing the effects of two treatments would support the alternative hypothesis, i.e., that the effects are equivalent. The size of the differences tested is generally the upper limit of dissimi- larity that is considered trivial or not clinically significant.

ERADICATION (OF DISEASE) Termination of all transmission of infection by extermi- nation of the infectious agent through surveillance and containment. Eradication, as in the instance of smallpox, is based on the joint activities of control and surveillance. Regional eradication has been successful with poliomyelitis and in some countries appears close to succeeding for measles. The term elimination is sometimes used to describe eradication of diseases such as measles from a large geographic region or political juris- diction. In 1992, the WHO put it this way: “Eradication is defined as achievement of a status whereby no further cases of a disease occur anywhere, and continued control measures are unnecessary.” Smallpox was eradicated in 1977, based on joint control and surveillance activities.

ERROR A false or mistaken result of a measurement. Any other false or mistaken result obtained in a study or experiment. Two broad kinds of error can occur in studies in the health, life, and social sciences:

  1. Random error: the portion of variation in a measurement that has no apparent
    connection to any other measurement or variable, generally regarded as due to
  2. Systematic error: error that is consistently wrong in a particular direction; it often
    has a recognizable source (e.g., a faulty measuring instrument). See bias.

ERROR, TYPE I (Syn: alpha error) The error of wrongly rejecting a null hypothesis, i.e., declaring that a difference exists when it does not. See also multiple comparison problem; P value; significance, statistical; statistical test.

ERROR, TYPE II (Syn: beta error) The error of failing to reject a false null hypothesis, i.e., declaring that a difference does not exist when in fact it does. See also power; statistical test.

ERROR,TYPE III Wrongly assessing the causes of interindividual variation within a population when the research question requires an analysis of causes of differences between populations or time periods. When the objects of the study are risk differences between groups or periods, the study must examine multiple groups or periods; otherwise a type III error can result. Risk differences between individuals within a particular popu- lation may not have the same causes as differences in the average risk between two different populations.183 See also atomistic fallacy; epistemology; ontology; strategy, “population.”

ERROR BAR A graphical display of the statistical uncertainty of an estimate, displayed as lines having the length of one or more standard deviations, standard errors, or confi- dence intervals for the estimate that extend out from the plotted estimated value.

ESTIMATE A measurement or a statement about the value of some quantity is said to be an estimate if it is known, believed, or suspected to incorporate some degree of error.

ESTIMATOR In statistics, a function (formula) for computing estimates of a parameter from observed data (e.g., the mantel-haenszel odds ratio).

ETHICS The branch of philosophy that deals with distinctions between right and wrong— with the moral consequences of human actions. Ethical principles govern the conduct of epidemiology, as they do all human activities.36,85–87 The ethical issues that arise in epi- demiological practice and research include informed consent, confidentiality, respect for human rights, and scientific integrity. Epidemiologists and others have developed guide- lines for the ethical conduct of epidemiological studies.184–187 See also informed consent.

ETHICS (ETHICAL) REVIEW COMMITTEE See institutional review board.


  1. A social group characterized by a distinctive social and cultural tradition maintained within the group from generation to generation, a common history and origin, and a sense of identification with the group. Members of the group have distinctive features in their way of life, shared experiences, and often a common genetic heritage. These features may be reflected in their health and disease experience.
  2. The social group a person belongs to and either identifies with or is identified with by others as a result of a mix of cultural and other factors, including language,
    diet, religion, ancestry, and physical features traditionally associated with race. Increasingly, the concept is being used synonymously with race, but the trend is pragmatic rather than scientific.108,188

ETHNOEPIDEMIOLOGY Epidemiological study of causal factors for health and disease among different ethnic groups, with development of intervention strategies that take culture into account.189


  1. A synonym for the attributable fraction (exposed).
  2. The fraction of exposed cases for which exposure played a role in the development
    of their disease. See probability of causation.


  1. A synonym for the attributable fraction (population).
  2. The fraction of all cases for which exposure played a role in the development of their
    disease. See probability of causation.

ETIOLOGICAL STUDY A study that aims to unveil causal relationships. Although most analytical studies may be considered to have such an aim, the term may be useful to the extent that it emphasizes that the purpose is not just to analyze relationships but to interpret relationships in causal terms. The etiological study is paradigmal to the intervention study, not vice versa.5 See also causal inference.

ETIOLOGY Literally, the science of causes, causality; in common usage, cause. See also causality; pathogenesis.

EU European Union.

EUPHA European Public Health Association.

EVALUATION A process that attempts to determine as systematically and objectively as possible the relevance, effectiveness, and impact of activities in the light of their objectives. Several varieties of evaluation can be distinguished (e.g., evaluation of structure, process, and outcome). See also clinical trial; effectiveness; efficacy; efficiency; health services research; program evaluation and review techniques; quality of care.

EVANS’S POSTULATES Expanding biomedical knowledge has led to revision of the Henle-Koch postulates.10 Alfred Evans190 developed those that follow, partly based on the Henle-Koch model:

  1. Prevalence of the disease should be significantly higher in those exposed to the
    hypothesized cause than in controls not so exposed.
  2. Exposure to the hypothesized cause should be more frequent among those with the
    disease than in controls without the disease—when all other risk factors are held
  3. Incidence of the disease should be significantly higher in those exposed to the
    hypothesized cause than in those not so exposed, as shown by prospective studies.
  4. The disease should follow exposure to the hypothesized causative agent with a
    normal or log-normal distribution of incubation periods.
  5. A spectrum of host responses should follow exposure to the hypothesized agent
    along a logical biological gradient from mild to severe.
  6. A measurable host response following exposure to the hypothesized cause should
    have a high probability of appearing in those lacking this before exposure (e.g., antibody, cancer cells) or should increase in magnitude if present before exposure. This response pattern should occur infrequently in persons not so exposed.
  1. Experimental reproduction of the disease should occur more frequently in animals or humans appropriately exposed to the hypothesized cause than in those not so exposed; this exposure may be deliberate in volunteers, experimentally induced in the laboratory, or may represent a regulation of natural exposure.
  2. Elimination or modification of the hypothesized cause should decrease the incidence of the disease (e.g., attenuation of a virus, removal of tar from cigarettes).
  3. Prevention or modification of the host’s response on exposure to the hypothesized cause should decrease or eliminate the disease (e.g., immunization, drugs to lower cholesterol, specific lymphocyte transfer factor in cancer).
  4. All of the relationships and findings should make biological and epidemiological sense.

See also causality; Hill’s criteria of causation; Mill’s Canons.

EVENT RATE The number of people experiencing an event as a proportion of the number of people in the population or relative to the person-time experience of the population.

EVIDENCE Scientific knowledge. Results of research used to support decision making.

EVIDENCE-BASED MEDICINE (EBM) The consistent use of knowledge derived from biological, clinical, and epidemiological research in the management of patients, with particular attention to the balance of benefits, risks, and costs of diagnostic tests, screen- ing programs, and treatment regimens, taking account of each patient’s circumstances, including baseline risk, comorbid conditions, culture, and personal preferences.14,62,63,191 There are no major intellectual reasons either against evidence-based (EB) nursing, EB health care planning, EB proteomics,192,193 or, for that matter, EB justice and EB economics.

EVIDENCE-BASED PUBLIC HEALTH (EBPH) Application of the best available evi- dence (i.e., the most valid, precise, and relevant scientific knowledge) in setting public health policies and practices. The evidence may be derived from epidemiological, sta- tistical, medical, economic, demographic, sociological, and several other scientific disci- plines. Sources of evidence should preferably be published, peer-reviewed, and critically appraised articles and reports. Implementation of public health policies, programs, and practices requires good evidence on feasibility, efficacy, effectiveness, efficiency, cost, acceptability to the target population, and careful analysis of ethical and political implications.194–197 Evidence on acceptability and ethical and cultural implications may also be obtained from focus groups. Another definition is: The development, imple- mentation, and evaluation of effective programs and policies in public health through application of the principles of scientific reasoning, including systematic uses of data and information systems and appropriate use of behavioral and social science theory and program planning models. In EBPH, public health activities are explicitly linked with the underlying scientific evidence that suggests relevance and purpose and which demonstrates effectiveness.70,104,194

EXACT METHOD A statistical method based on the actual (i.e., “exact”) probability distribution of the study data rather than on an approximation, such as a normal or a chi- square distribution (e.g., Fisher’s exact test).

EXACT TEST A statistical test based on the actual null probability distribution of the study data rather than, say, a normal approximation. The most used exact test is the Fisher-Irwin test for fourfold tables (or Fisher’s exact test).

EXCEPTION FLAGGING (REPORTING) SYSTEM An automated system of data analysis that calculates thresholds for unusual events. Used in surveillance.

EXCESS RATE AMONG EXPOSED See rate difference.

EXCESS RISK A term sometimes used to refer to the population excess risk and some- times to the risk difference or absolute risk reduction.

EXPANDED PROGRAMME ON IMMUNIZATION (EPI) A program of immunizing against diphtheria, tetanus, measles, pertussis, poliomyelitis, and tuberculosis conducted especially in developing countries. Part of the effort to achieve “Health for All by the Year 2000” under the auspices of WHO, UNICEF, and other agencies.

EXPANSION OF MORBIDITY As life expectancy increases, the prevalence of long-term disease, especially among older persons, increases. Mental disorders such as dementia may be an example.198 Thus this is the opposite of compression of morbidity. Both phe- nomena may coexist in the same population, some disorders becoming less prevalent, others more so.

EXPECTATION OF LIFE (Syn: life expectancy or expectation) The average number of years an individual of a given age is expected to live if current mortality rates continue to apply. A statistical abstraction based on existing age-specific death rates.
Life expectancy at birth (°e0): Average number of years a newborn baby can be expected to live if current mortality trends continue. Corresponds to the total number of years a given birth cohort can be expected to live divided by the number of children in the cohort. Life expectancy at birth is partly dependent on mortality in the first year of life; therefore it is lower in poor than in rich countries because of the higher infant and child mortality rates in the former.

Life expectancy at a given age, age x (°ex): The average number of additional years a person of age x will live, based on the age-specific death rates for a given year, if current mortality trends continue to apply.

Life expectancy is a hypothetical measure and indicator of current health and mortality conditions. It is not a rate.

EXPECTED YEARS OF LIFE LOST A measure of the impact of a disease on society as a result of early death. The expected years of life lost due to a particular cause is the sum, over all persons dying from that cause, of the years these persons would have lived had they experienced normal life expectancy. Life expectancies are usually taken from the population concerned, but another population can be used (e.g., the one with the highest life expectancy), which yields the standard expected years of life lost.199 See also burden of disease; potential years of life lost.

EXPERIMENT The core of an experimental study. Manipulation of one or more independent variables and control of potential confounders by the investigator in order to test a specific hypothesis involving the causal effect of the independent variables on an outcome.

EXPERIMENT, NATURAL See natural experiment.

EXPERIMENTAL STUDY A study in which the investigator intentionally alters one or more factors and controls the other study conditions in order to analyze the effects of so doing. A study in which conditions are under the direct control of the investigator.

EXPERIMENTAL EPIDEMIOLOGICAL STUDY An epidemiological study with a clear experimental component; usually, a large phase III or a phase IV randomized con- trolled trial or a community trial. In community trials (e.g., of fluoridation of drink- ing water), whole communities are (nonrandomly) allocated to experimental and control groups. See also observational study; random allocation.


  1. The application of epidemiological reasoning, knowledge, and methods to experi- ments, particularly to phase III and phase IV randomized controlled trials and to community trials. If the word experiment is qualified by the adjective epidemiological, it usually refers to a randomized controlled trial or to a community trial. Clinical or community-based studies merit the term experiment or quasi-experiment only if it is possible to modify conditions during the period of study. See also natural experiment.
  2. To epidemiologists in the 1920s, it meant the study of epidemics among colonies of experimental animals such as rats and mice. See also animal model; mechanistic epidemiology; observational study.

EXPLANATORY STUDY, EXPLANATORY TRIAL A study (including randomized clini- cal trials) whose main objective is to explain, rather than merely describe, a situation by isolating the effects of specific variables and understanding the mechanisms of action.14 Contrast with pragmatic study.


  1. A variable that causally explains the association or outcome under study.
  2. In statistics, a synonym for independent variable.

EXPLORATORY STUDY A study whose main objective is to examine or ascertain some preliminary facts or to familiarize researchers with a problem or technology, often with- out clear or precise hypotheses; or, sometimes, to screen several hypotheses at once in a preliminary fashion. It may be even more preliminary than a pilot investigation. See also data dredging; data mining; fishing expedition.

EXPOSED In epidemiology, the exposed group (or simply, the exposed) is often used to connote a group whose members have been exposed to a supposed cause of a disease or health state of interest or possess a characteristic that is a determinant of the health outcome of interest.



  1. The variable whose causal effect is to be estimated. Examples of exposures assessed by epidemiological studies are environmental and lifestyle factors, socioeconomic and working conditions, medical treatments, and genetic traits. Exposures may be harmful or beneficial—or even both (e.g., if an immunizable disease is circulating, exposure to immunizing agents helps most recipients but may harm those with adverse reactions to the vaccine).
  2. Proximity and/or contact with a source of a disease agent in such a manner that effective transmission of the agent or harmful effects of the agent may occur.
  3. The amount of a factor to which a group or individual was exposed; sometimes contrasted with dose, the amount that enters or interacts with the organism.
  4. The process by which an agent comes into contact with a person or animal in such a way that the person or animal may develop the relevant outcome, such as a disease.

EXPOSURE ASSESSMENT Process of estimating concentration or intensity, duration, and frequency of exposure to an agent that can affect health.200

EXPOSURE CONTROL See risk management.

EXPOSURE IMPACT NUMBER See impact numbers.

EXPOSURE LIMIT General term defining the regulated level of exposure that should not be exceeded.200


EXPOSURE RATIO The ratio of rates at which persons in the case and control groups of a case-control study are exposed to the risk factor (or to the protective factor) of interest.

EXPRESSION, GENE See gene expression.

EXPRESSIVITY In genetics, the extent to which a gene is expressed, i.e., demonstrated in the phenotype.

EXTENDED TRIAL A study using additional data collected from the same patients after completion of a formal phase III randomized controlled trial. Analysis of such data allows researchers to collect additional information on toleration and efficacy. See also clinical trial.

EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS (XDR) See drug-resistant tuberculosis, extensively.

EXTERNAL VALIDITY See validity, study.

EXTERNALITIES Social benefits and costs that are not included in the market price of an economic good. Examples include benefits to others of treating a case of infectious disease, adverse health effects of industrial air pollution not included in the price of the industrial product, and impact on national economy of natural resource depletion not included in calculation of national income.

EXTRAPOLATE, EXTRAPOLATION To predict the value of a variate outside the range of observations; the resulting prediction. See also interpolate.

EXTREMAL QUOTIENT The ratio of the rate in the geographic region with the highest rate of interventions, such as surgical procedures, to the rate in the region with the lowest rate.201

EXTRINSIC INCUBATION PERIOD Time required for development of a disease agent in a vector from the time of uptake of the agent to the time when the vector is infective. See also incubation period; vector-borne infection.