Philip S. Brachman, M.D.Rollins School of Public Health,
Epidemiology is the study of the determinants, occurrence, and distribution of health and disease in a defined population. Infection is the replication of organisms in host tissue, which may cause disease. A carrier is an individual with no overt disease who harbors infectious organisms. Dissemination is the spread of the organism in the environment.
There are three major links in disease occurrence: the etiologic agent, the method of transmission (by contact, by a common vehicle, or via air or a vector), and the host.
Epidemiologic studies may be (1) descriptive, organizing data by time, place, and person; (2) analytic, incorporating a case-control or cohort study; or (3) experimental. Epidemiology utilizes an organized approach to problem solving by: (1) confirming the existence of an epidemic and verifying the diagnosis; (2) developing a case definition and collating data on cases; (3) analyzing data by time, place, and person; (4) developing a hypothesis; (5) conducting further studies if necessary; (6) developing and implementing control and prevention measures; (7) preparing and distributing a public report; and (8) evaluating control and preventive measures.
This chapter reviews the general concepts of epidemiology, which is the study of the determinants, occurrence, distribution, and control of health and disease in a defined population.Epidemiology is a descriptive science and includes the determination of rates, that is, the quantification of disease occurrence within a specific population. The most commonly studied rate is the attack rate: the number of cases of the disease divided by the population among whom the cases have occurred. Epidemiology can accurately describe a disease and many factors concerning its occurrence before its cause is identified. For example, Snow described many aspects of the epidemiology of cholera in the late 1840s, fully 30 years before Koch described the bacillus and Semmelweis described puerperal fever in detail in 1861 and recommended appropriate control and prevention measures a number of years before the streptococcal agent was fully described. One goal of epidemiologic studies is to define the parameters of a disease, including risk factors, in order to develop the most effective measures for control. This chapter includes a discussion of the chain of infection, the three main epidemiologic methods, and how to investigate an epidemic.
Proper interpretation of disease-specific epidemiologic data requires information concerning past as well as present occurrence of the disease. An increase in the number of reported cases of a disease that is normal and expected, representing a seasonal pattern of change in host susceptibility, does not constitute an epidemic. Therefore, the regular collection, collation, analysis, and reporting of data concerning the occurrence of a disease is important to properly interpret short-term changes in occurrence.
A sensitive and specific
surveillance program is important for the proper interpretation of disease
occurrence data. Almost every country has a national disease surveillance
program that regularly collects data on selected diseases. The quality of these
programs varies, but, generally, useful data are collected that are important
in developing control and prevention measures. There is an international
agreement that the occurrence of three diseasescholera, plague, and yellow
feverwill be reported to the World Health Organization in
The methods of case reporting vary within each state. Passive reporting is one of the main methods. In such a case, physicians or personnel in clinics or hospitals report occurrences of relevant diseases by telephone, postcard, or a reporting form, usually at weekly intervals. In some instances, the report may be initiated by the public health or clinical laboratory where the etiologic agent is identified. Some diseases, such as human rabies, must be reported by telephone as soon as diagnosed. In an active surveillance program, the health authority regularly initiates the request for reporting. The local health department may call all or some health care providers at regular intervals to inquire about the occurrence of a disease or diseases. The active system may be used during an epidemic or if accurate data concerning all cases of a disease are desired.
The health care provider usually makes the initial passive report to a local authority, such as a city or county health department. This unit collates its data and sends a report to the next highest health department level, usually the state health department.
The number of cases of each reportable disease are presented weekly, via computer linkage, by the state health department to the CDC. Data are analyzed at each level to develop needed information to assist public health authorities in disease control and prevention. For some diseases, such as hepatitis, the CDC requests preparation of a separate case reporting form containing more specific details.
In addition, the CDC prepares and distributes routine reports summarizing and interpreting the analyses and providing information on epidemics and other appropriate public health matters. Most states and some county health departments also prepare and distribute their own surveillance reports. The CDC publishes Morbidity and Mortality Weekly Report, which is available for a small fee from the Massachusetts Medical Society. The CDC also prepares more detailed surveillance reports for specific diseases, as well as an annual summary report, all of which can also be obtained through the Massachusetts Medical Society.
Infection is the replication of organisms in the tissue of a host; when defined in terms of infection, disease is overt clinical manifestation. In an inapparent (subclinical) infection, an immune response can occur without overt clinical disease. A carrier (colonized individual) is a person in whom organisms are present and may be multiplying, but who shows no clinical response to their presence. The carrier state may be permanent, with the organism always present; intermittent, with the organism present for various periods; or temporary, with carriage for only a brief period. Dissemination is the movement of an infectious agent from a source directly into the environment; when infection results from dissemination, the source, if an individual, is referred to as a dangerous disseminator.
Infectiousness is the transmission of organisms from a source, or reservoir (see below), to a susceptible individual. A human may be infective during the preclinical, clinical, postclinical, or recovery phase of an illness. The incubation period is the interval in the preclinical period between the time at which the causative agent first infects the host and the onset of clinical symptoms; during this time the agent is replicating. Transmission is most likely during the incubation period for some diseases such as measles; in other diseases such as shigellosis, transmission occurs during the clinical period. The individual may be infective during the convalescent phase, as in diphtheria, or may become an asymptomatic carrier and remain infective for a prolonged period, as do approximately 5% of persons with typhoid fever.
The spectrum of occurrence of disease in a defined population includes sporadic (occasional occurrence); endemic (regular, continuing occurrence); epidemic (significantly increased occurrence); and pandemic (epidemic occurrence in multiple countries).
The chain of infection includes the three factors that lead to infection: the etiologic agent, the method of transmission, and the host. These links should be characterized before control and prevention measures are proposed. Environmental factors that may influence disease occurrence must be evaluated.
The etiologic agent may be any microorganism that can cause infection. The pathogenicity of an agent is its ability to cause disease; pathogenicity is further characterized by describing the organism's virulence and invasiveness. Virulence refers to the severity of infection, which can be expressed by describing the morbidity (incidence of disease) and mortality (death rate) of the infection. An example of a highly virulent organism is Yersinia pestis, the agent of plague, which almost always causes severe disease in the susceptible host.
The invasiveness of an organism refers to its ability to invade tissue. Vibrio cholerae organisms are noninvasive, causing symptoms by releasing into the intestinal canal an exotoxin that acts on the tissues. In contrast, Shigella organisms in the intestinal canal are invasive and migrate into the tissue.
No microorganism is assuredly avirulent. An organism may have very low virulence, but if the host is highly susceptible, as when therapeutically immunosuppressed, infection with that organism may cause disease. For example, the poliomyelitis virus used in oral polio vaccine is highly attenuated and thus has low virulence, but in some highly susceptible individuals it may cause paralytic disease.
Other factors should be considered in describing the agent. The infecting dose (the number of organisms necessary to cause disease) varies according to the organism, method of transmission, site of entrance of the organism into the host, host defenses, and host species. Another agent factor is specificity; some agents (for example, Salmonella typhimurium) can infect a broad range of hosts; others have a narrow range of hosts. S typhi, for example, infects only humans. Other agent factors include antigenic composition, which can vary within a species (as in influenza virus or Streptococcus species); antibiotic sensitivity; resistance transfer plasmids (see Ch. 5); and enzyme production.
The reservoir of an organism is the site where it resides, metabolizes, and multiplies. The source of the organism is the site from which it is transmitted to a susceptible host, either directly or indirectly through an intermediary object. The reservoir and source can be different; for example, the reservoir for S typhi could be the gallbladder of an infected individual, but the source for transmission might be food contaminated by the carrier. The reservoir and source can also be the same, as in an individual who is a permanent nasal carrier of S aureus and who disseminates organisms from this site. The distinction can be important when considering where to apply control measures.
The method of transmission is the means by which the agent goes from the source to the host. The four major methods of transmission are by contact, by common vehicle, by air or via a vector.
In contact transmission the agent is spread directly, indirectly, or by airborne droplets. Direct contact transmission takes place when organisms are transmitted directly from the source to the susceptible host without involving an intermediate object; this is also referred to as person-to-person transmission. An example is the transmission of hepatitis A virus from one individual to another by hand contact. Indirect transmission occurs when the organisms are transmitted from a source, either animate or inanimate, to a host by means of an inanimate object. An example is transmission of Pseudomonas organisms from one individual to another by means of a shaving brush. Droplet spread refers to organisms that travel through the air very short distances, that is, less than 3 feet from a source to a host. Therefore, the organisms are not airborne in the true sense. An example of a disease that may be spread by droplets is measles.
Common-vehicle transmission refers to agents transmitted by a common inanimate vehicle, with multiple cases resulting from such exposure. This category includes diseases in which food or water as well as drugs and parenteral fluids are the vehicles of infection. Examples include food-borne salmonellosis, waterborne shigellosis, and bacteremia resulting from use of intravenous fluids contaminated with a gram-negative organism.
The third method of transmission, airborne transmission, refers to infection spread by droplet nuclei or dust. To be truly airborne, the particles should travel more than 3 feet through the air from the source to the host. Droplet nuclei are the residue from the evaporation of fluid from droplets, are light enough to be transmitted more than 3 feet from the source, and may remain airborne for prolonged periods. Tuberculosis is primarily an airborne disease; the source may be a coughing patient who creates aerosols of droplet nuclei that contain tubercle bacilli. Infectious agents may be contained in dust particles, which may become resuspended and transmitted to hosts. An example occurred in an outbreak of salmonellosis in a newborn nursery in which Salmonella-contaminated dust in a vacuum cleaner bag was resuspended when the equipment was used repeatedly, resulting in infections among the newborns.
The fourth method of transmission is vector borne transmission, in which arthropods are the vectors. Vector transmission may be external or internal. External, or mechanical, transmission occurs when organisms are carried mechanically on the vector (for example, Salmonella organisms that contaminate the legs of flies). Internal transmission occurs when the organisms are carried within the vector. If the pathogen is not changed by its carriage within the vector, the carriage is called harborage (as when a flea ingests plague bacilli from an infected individual or animal and contaminates a susceptible host when it feeds again; the organism is not changed while in the flea). The other form of internal transmission is called biologic. In this form, the organism is changed biologically during its passage through the vector (for example, malaria parasites in the mosquito vector).
An infectious agent may be transmitted by more than one route. For example, Salmonella may be transmitted by a common vehicle (food) or by contact spread (human carrier). Francisella tularensis may be transmitted by any of the four routes.
The third link in the chain of infection is the host. The organism may enter the host through the skin, mucous membranes, lungs, gastrointestinal tract, or genitourinary tract, and it may enter fetuses through the placenta. The resulting disease often reflects the point of entrance, but not always: meningococci that enter the host through the mucous membranes may nonetheless cause meningitis. Development of disease in a host reflects agent characteristics (see above) and is influenced by host defense mechanisms, which may be nonspecific or specific.
Nonspecific defense mechanisms include the skin, mucous membranes, secretions, excretions, enzymes, the inflammatory response, genetic factors, hormones, nutrition, behavioral patterns, and the presence of other diseases. Specific defense mechanisms or immunity may be natural, resulting from exposure to the infectious agent, or artificial, resulting from active or passive immunization (see Ch. 8).
The environment can affect any link in the chain of infection. Temperature can assist or inhibit multiplication of organisms at their reservoir; air velocity can assist the airborne movement of droplet nuclei; low humidity can damage mucous membranes; and ultraviolet radiation can kill the microorganisms. In any investigation of disease, it is important to evaluate the effect of environmental factors. At times, environmental control measures are instituted more on emotional grounds than on the basis of epidemiologic fact. It should be apparent that the occurrence of disease results from the interaction of many factors. Some of these factors are outlined here.
The three major epidemiologic techniques are descriptive, analytic, and experimental. Although all three can be used in investigating the occurrence of disease, the method used most is descriptive epidemiology. Once the basic epidemiology of a disease has been described, specific analytic methods can be used to study the disease further, and a specific experimental approach can be developed to test a hypothesis.
epidemiology, data that describe the occurrence of the disease are collected by
various methods from all relevant sources. The data are then collated by time,
place, and person. Four time trends are considered in describing the
epidemiologic data. The secular trend describes the occurrence of disease over
a prolonged period, usually years; it is influenced by the degree of immunity
in the population and possibly nonspecific measures such as improved
socioeconomic and nutritional levels among the population. For example, the
secular trend of tetanus in the
The second time trend is the periodic trend. A temporary modification in the overall secular trend, the periodic trend may indicate a change in the antigenic characteristics of the disease agent. For example, the change in antigenic structure of the prevalent influenza A virus every 2 to 3 years results in periodic increases in the occurrence of clinical influenza caused by lack of natural immunity among the population. Additionally, a lowering of the overall immunity of a population or a segment thereof (known as herd immunity) can result in an increase in the occurrence of the disease. This can be seen with some immunizable diseases when periodic decreases occur in the level of immunization in a defined population. This may then result in an increase in the number of cases, with a subsequent rise in the overall level of herd immunity. The number of new cases then decreases until the herd's immunity is low enough to allow transmission to occur again and new cases then appear.
The third time trend is the seasonal trend. This trend reflects seasonal changes in disease occurrence following changes in environmental conditions that enhance the ability of the agent to replicate or be transmitted. For example, food-borne disease outbreaks occur more frequently in the summer, when temperatures favor multiplication of bacteria. This trend becomes evident when the occurrence of salmonellosis is examined on a monthly basis.
The fourth time trend is the epidemic occurrence of disease. An epidemic is a sudden increase in occurrence due to prevalent factors that support transmission.
A description of epidemiologic data by place must consider three different sites: where the individual was when disease occurred; where the individual was when he or she became infected from the source; and where the source became infected with the etiologic agent. Therefore, in an outbreak of food poisoning, the host may become clinically ill at home from food eaten in a restaurant. The vehicle may have been under-cooked chicken, which became infected on a poultry farm. These differences are important to consider in attempting to prevent additional cases.
The third focus of descriptive epidemiology is the infected person. All pertinent characteristics should be noted: age, sex, occupation, personal habits, socioeconomic status, immunization history, presence of underlying disease, and other data.
Once the descriptive epidemiologic data have been analyzed, the features of the epidemic should be clear enough that additional areas for investigation are apparent.
The second epidemiologic method is analytic epidemiology, which analyzes disease determinants for possible causal relations. The two main analytic methods are the case-control (or case-comparison) method and the cohort method. The case-control method starts with the effect (disease) and retrospectively investigates the cause that led to the effect. The case group consists of individuals with the disease; a comparison group has members similar to those of the case group except for absence of the disease. These two groups are then compared to determine differences that would explain the occurrence of the disease. An example of a case-control study is selecting individuals with meningococcal meningitis and a comparison group matched for age, sex, socioeconomic status, and residence, but without the disease, to see what factors may have influenced the occurrence in the group that developed disease.
The second analytic approach is the cohort method, which prospectively studies two populations: one that has had contact with the suspected causal factor under study and a similar group that has had no contact with the factor. When both groups are observed, the effect of the factor should become apparent. An example of a cohort approach is to observe two similar groups of people, one composed of individuals who received blood transfusions and the other of persons who did not. The occurrence of hepatitis prospectively in both groups permits one to make an association between blood transfusions and hepatitis; that is, if the transfused blood was contaminated with hepatitis B virus, the recipient cohort should have a higher incidence of hepatitis than the nontransfused cohort.
The case-control approach is relatively easy to conduct, can be completed in a shorter period than the cohort approach, and is inexpensive and reproducible; however, bias may be introduced in selecting the two groups, it may be difficult to exclude subclinical cases from the comparison group, and a patient's recall of past events may be faulty. The advantages of a cohort study are the accuracy of collected data and the ability to make a direct estimate of the disease risk resulting from factor contact; however, cohort studies take longer and are more expensive to conduct.
Another analytic method is the cross-sectional study, in which a population is surveyed over a limited period to determine the relationship between a disease and variables present at the same time that may influence its occurrence.
The third epidemiologic method is the experimental approach. A hypothesis is developed and an experimental model is constructed in which one or more selected factors are manipulated. The effect of the manipulation will either confirm or disprove the hypothesis. An example is the evaluation of the effect of a new drug on a disease. A group of people with the disease is identified, and some members are randomly selected to receive the drug. If the only difference between the two is use of the drug, the clinical differences between the groups should reflect the effectiveness of the drug.
An epidemic investigation describes the factors relevant to an outbreak of disease; once the circumstances related to the occurrence of disease are defined, appropriate control and prevention measures can be identified. In an epidemic investigation, data are collected, collated according to time, place, and person, and analyzed and inferences are drawn.
In the investigation, the first action should be to confirm the existence of the epidemic by noting from past surveillance data the number of cases suspected and comparing this with the number of cases initially reported. Additionally, the investigator should discuss the occurrence of the disease with physicians or others who have seen or reported cases after examining patients and reviewing laboratory and hospital records. These diagnoses should then be verified. A case definition should be developed to differentiate patients who represent actual cases, those who represent suspected or presumptive cases, and those who should be omitted from further study. Additional cases may be sought or additional patient data obtained, and a rough case count made.
This initial phase consists basically of collecting data, which then must be organized according to time, place, and person. The population at risk should be identified and a hypothesis developed concerning the occurrence of the disease. If appropriate, specimens should be collected and transported to the laboratory. More specific studies may be indicated. Additional data from these studies should be analyzed and the hypothesis confirmed or altered. After analysis, control and prevention measures should be developed and, as far as possible, implemented. A report containing this information should be prepared and distributed to those involved in investigating the outbreak and in implementing control and/or prevention measures. Continued surveillance activities may be appropriate to evaluate the effectiveness of the control and prevention measures.
The use of epidemiology to characterize a disease before its etiology has been identified is exemplified by the initial studies of acquired immune deficiency syndrome (AIDS). The first cases came to the attention of the CDC late in 1981 when an increase was observed in requests for pentamidine for treatment of Pneumocystis carinii pneumonia. This initiated specific surveillance activities and epidemiologic studies that provided important information about this newly diagnosed disease.
Initial symptoms include
fever, loss of appetite, weight loss, extreme fatigue, and enlargement of lymph
nodes. A severe immune deficiency then develops, which appears to be associated
with opportunistic infections. These infections include P carinii pneumonia,
diagnosed in 52 percent of cases; Kaposi sarcoma in 26 percent of cases; and
both P carinii pneumonia and Kaposi sarcoma in 7 percent of
cases. The remaining 15 percent of AIDS patients have other parasitic, fungal,
bacterial, or viral infections associated with immunodeficiencies. Among the
first 2,640 cases reported to the CDC, there were 1,092 deaths, a case-fatality
rate of 41 percent. Approximately 95 percent of the cases were male; 70 percent
were 20 to 49 years of age at the time of diagnosis. Approximately 40 percent
of the cases were reported from
Analysis of these initial data, collected before the etiologic agent of AIDS was identified, supported the hypothesis that transmission occurred primarily by sexual contact, receipt of contaminated blood or blood products, or contact with contaminated intravenous needles. Spread through casual contact did not seem likely. The epidemiologic data indicated that AIDS was an infectious disease. It has now been determined that AIDS results from infection with a retrovirus of the human T cell leukemia/lymphoma virus family, which has been designated human immunodeficiency virus type I (HIV-l). The initial hypotheses have been proven as shown by analysis of data subsequently collected.
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