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Chapter 9 Epidemiology
Philip S. Brachman.
In this Page
General Concepts Go to: General Concepts

Introduction
Definitions
Chain of Infection
Epidemiology is the study of the determinants, occurrence, and distribution of health and disease in a defined
Epidemiologic Methods
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 Epidemic Investigation
environment. References

Chain of Infection
There are three major links in disease occurrence: the etiologic agent, the method of transmission (by contact, by a Related information
common vehicle, or via air or a vector), and the host. PMC

PubMed
Epidemiologic Methods
Epidemiologic studies may be (1) descriptive, organizing data by time, place, and person; (2) analytic, incorporating a
Similar articles in PubMed
case-control or cohort study; or (3) experimental. Epidemiology utilizes an organized approach to problem solving by:
Malaria Surveillance - United States, 2016.
(1) confirming the existence of an epidemic and verifying the diagnosis; (2) developing a case definition and collating [MMWR Surveill Summ. 2019]
data on cases; (3) analyzing data by time, place, and person; (4) developing a hypothesis; (5) conducting further
Malaria Surveillance - United States, 2015.
studies if necessary; (6) developing and implementing control and prevention measures; (7) preparing and distributing [MMWR Surveill Summ. 2018]
a public report; and (8) evaluating control and preventive measures.
Malaria Surveillance - United States, 2017.
[MMWR Surveill Summ. 2021]
Introduction Go to:
Review Diagnosis and Treatment of the Febrile Child.
This chapter reviews the general concepts of epidemiology, which is the study of the determinants, occurrence, [Reproductive, Maternal, Newbor...]
distribution, and control of health and disease in a defined population. Epidemiology is a descriptive science and Review Epidemiology.
includes the determination of rates, that is, the quantification of disease occurrence within a specific population. The [Translational Research in Trau...]
most commonly studied rate is the attack rate: the number of cases of the disease divided by the population among See reviews...
whom the cases have occurred. Epidemiology can accurately describe a disease and many factors concerning its
See all...
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 Recent Activity
streptococcal agent was fully described. One goal of epidemiologic studies is to define the parameters of a disease, Turn Off Clear

including risk factors, in order to develop the most effective measures for control. This chapter includes a discussion Epidemiology - Medical Microbiology
of the chain of infection, the three main epidemiologic methods, and how to investigate an epidemic (Table 9-1).
See more...
Table 9-1

Epidemiologic Methods and Investigation.

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 diseases—cholera, plague,
and yellow fever—will be reported to the World Health Organization in Geneva, Switzerland. In the United States,
the Centers for Disease Control and Prevention (CDC), U.S. Public Health Service, and the state health officers of all
50 states have agreed to report the occurrence of 51 diseases weekly and of another 10 diseases annually from the
states to the CDC. Many states have regulations or laws that mandate reporting of these diseases and often of other
diseases of specific interest to the state health department.

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).

Chain of Infection Go to:

The chain of infection includes the three factors that lead to infection: the etiologic agent, the method of transmission,
and the host (Fig. 9-1). These links should be characterized before control and prevention measures are proposed.
Environmental factors that may influence disease occurrence must be evaluated.

Figure 9-1

Summary of important aspects involved in the chain of any infection.

Etiologic Agent
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. Styphi,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.

Method of Transmission
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.

Host
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 (Table 9-2). Some of these factors are outlined here.

Table 9-2

General Factors That Influence the Occurence of Infectious Disease.

Epidemiologic Methods Go to:

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.

Descriptive Epidemiology
In descriptive 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 United
States since 1920 shows a gradual and steady decline.

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 (Fig. 9-2).

Figure 9-2

An example of a disease showing a seasonal trend. Reported human

Salmonella isolations, by 4-week average, in the United States from 1968 to
1980.

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 undercooked 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.

Analytic Epidemiology
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.

Experimental Epidemiology
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.

Epidemic Investigation Go to:

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.

In the United States, the CDC assists state health departments by providing epidemiologic and laboratory support
services on request. Its assistance supports disease investigations and diagnostic laboratory activities and includes
various training programs conducted in the states and at the CDC. A close working relationship exists between the
CDC and state health departments. Additionally, physicians frequently consult with CDC personnel on a variety of
health-related problems and attend public health training programs.

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 New York City, 12 percent from San Francisco, 8 percent from Los Angeles, and the
remainder from 32 other states. Cases were reported from at least 16 other countries. Among the 90 percent of
patients who were categorized according to possible risk factors, those at highest risk were homosexuals or bisexuals
(70 percent), intravenous drug abusers ( 17 percent), Haitian entrants into the United States (9.5 percent), and persons
with hemophilia (1 percent).

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.

References Go to:

1. Beaglehole R, Bonita R, Kjellstrom T: Basic Epidemiology. World Health Organization, Geneva, Switzerland,
1993 .
2. Benenson A: Control of Communicable Disease Manual 16th Ed., American Public Health Association,
Washington, DC, 1995 .
3. Bennett JV, Brachman PS: Hospital Infections. 3rd Ed., Little, Brown, Boston, 1992 .
4. Evans AS, Brachman PS: Bacterial Infections of Humans. Epidemiology and Control.2nd Ed. Plenum New
York, 1991 .
5. Fox JP, Hall CE, Elveback LR: Epidemiology, Man and Disease. Macmillan, New York, 1970 .
6. Hennekens CH, Buring JE: Epidemiology in Medicine. Little, Brown, Boston, 1987 .
7. Langmuir AD. The surveillance of communicable diseases of national importance. N Engl J Med.
1963;268:182. [PubMed]
8. Lilienfeld DE, Stolley PD: Foundations of Epidemiology. 3rd Ed. Oxford University Press, New York, 1994 .
9. MacMahon B, Pugh TF: Epidemiology Principles and Methods. Little, Brown, Boston, 1970 .
10. Mandell GL, Douglas RG, Jr, Bennett JE: Principles and Practice of Infectious Diseases, 3rd Ed. Churchill
Livingstone, New York, 1990 .
11. Smith DM, Haupt BJ. Hospital discharge data used as feedback in planning research and education for primary
care. Public Health Rep. 1983;98:457. [PMC free article] [PubMed]
12. World Health Organization: The surveillance of communicable diseases. WHO Chron. 1968;22:439. [PubMed]

Copyright © 1996, The University of Texas Medical Branch at Galveston.

Bookshelf ID: NBK7993 PMID: 21413284

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