Philip S. Brachman, M.D.
Rollins
Reprinted
with permission of the Author
General Concepts
Definitions
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.
Chain of Infection
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 Methods
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.
INTRODUCTION
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).
Chain of Infection
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.
Epidemiologic Methods
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
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.
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
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
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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Disclaimer: This material is for training purposes only. Its purpose is to inform employers of best practices in occupational safety and health and general OSHA compliance requirements. This material is not, in any way, a substitute for any provision of the Occupational Safety and Health Act of 1970 or any standards issued by OSHA.