As the inadequacies of germ theory became increasingly evident, epidemiologists began to rethink the causation of disease.
This new and broader formulation was perhaps most clearly stated by Theobald Smith in his 1934 book, Parasitism and Disease.
Concerning himself only with the infectious diseases, Smith explained disease as an instance of parasitism, in which the infectious
agent lives in or on the human host. He saw disease as the result of forces within a dynamic system consisting of the agent
of infection, the host, and the environment. This model has come to be known as the epidemiologic triad.
In terms of this model, patterns of disease depend on factors that determine the probability of contact between an infectious
agent and a susceptible host. The route by which the agent is shed by an ill host, the length of time over which it is shed,
the climatic conditions surrounding the host, and the presence of alternate nonhuman hosts that may serve as a continuing
reservoir of infection all play a part in determining whether a host will be exposed to infection. The availability of sus¬ceptible
hosts depends on population density and mobility, community vaccination status, and extent and degree of immunity from previous
infections with the same or related agents.
Eventually, the concept of agent was generalized beyond infectious agents. Many epidemiologists found that this model was
applicable to noninfectious diseases as well as those with infectious agents. The term agent had to be reconceptualized beyond
infectious organisms. In terms of this broader conceptualization, the agent is the one factor that must be present for the
disease to occur (as the smallpox virus, for example, must be present for a case of smallpox to occur). In the terms of formal
logic, an agent is a necessary but not sufficient cause of a diseased is, a particular disease cannot occur without the agent
even though presence of the agent does not, by itself, guarantee that the disease occur.
We can define an agent as an organism, substance, or force the relative presence or relative absence of which is necessary
for a particular disease process to occur. In this definition you will see that one further element has entered the concept
of agent. In some diseases it is the absence of some organism, substance, or force that makes the disease process possible.
In the following descriptions of the types of agents it can seen that there are those of each type that make disease possible
through their presence or excess, and those that make disease possible through their absence or deficiency.
The many varieties of infectious agents -- of viruses, bacteria, and so on -- are the agents first identified by the germ
theorists. To this may be added a variety of external parasites, such as lice (for pediculosis), mites (for scabies), or fungi
(for athlete's foot). There is also a form of diarrhea that results in persons whose "intestinal flora" (the bacteria normally
found in plentiful quantities in the bowel) have been killed off by antibiotics or radiation.
We are most familiar with nutrients as agents in instances where it is their relative absence that is necessary for the
disease process occur. Lind's (1753) demonstration that citrus fruits are a preventive of scurvy was one of the first discoveries
of a disease with a nutritive element as its agent. Scurvy was finally found to be due to a lack of vitamin C (ascorbic acid).
Since that time there have been a whole range of vitamin deficiency diseases identified. More recently, a dietary deficiency
of protein has been identified as the agent of kwashiorkor.
On the other hand, saturated fats may be the agent of arteriosclerosis (hardening of the arteries). Some epidemiologists
have speculated that sodium (especially in the form of salt) might be the agent of hyperten¬sion (high blood pressure), but
this hypothesis is increasingly in doubt. If obesity can be regarded as a disease, then calories in general might be regarded
as its agent.
The term exogenous chemicals refers to those chemicals (other than nutrients) affecting the body that originate outside
the body. Techni¬cally, this term is identical to the definition of a drug (Duncan & Gold, 1982) but it is used here to convey
a broader sense than that in which the term drug is ordinarily used. Alcohol is the agent of alcoholism as nicotine is the
agent of tobacco addiction. The range of other exogenous chemical agents extends over the entire scope of irritants, poisons,
and allergens arising outside the host—from arsenic to ragweed pollen. Fox, Hall, and Elveback (1970) muse on whether
the agent of drowning is water (too much) or air (too little) in the lungs of the host.
The human body itself gives rise to chemicals that may act as agents. These may be abnormal products, such as those that
arise from the breakdown of tissue in extensive burns. More often they are normal bodily products that are in relative excess
or deficiency. Excesses or deficiencies in the production of various hormones serve as the agents for a number of diseases.
For example, if pituitary growth hormone is oversecreted during childhood it is the agent of gigantism, and when undersecreted
it is the agent of dwarfism; in adulthood oversecretion of growth hormone is the agent of acromegaly, a disfiguring disorder
in which the bones and cartilage of the face, hands, and feet resume growth, becoming greatly enlarged. An excess of uric
acid is the agent of gout, a form of arthritis in which crystals of uric acid are deposited in joints, especially of the hands
A number of diseases have been identified as having a gene or combination of genes as their agent. These range from the
very common, such as alopecia (pattern baldness), through the less than rare such as diabetes, to the rare, such as Tay-Sachs
disease or hemophilia. Some others, such as Down's syndrome (mongolism), have as agent some structural abnormality of the
Psychosocial Factors and Stress
These are undoubtedly the most speculated on but least understood of the agents. In the past, it was widely believed that
stress was the agent of stomach ulcers, but we now know that the true agent is an infection. There is great uncertainty about
other possible psychic agents.
Most of us have experienced sunburn for which the agent is ultraviolet light. Likewise, the agent of radiation sickness
is ionizing radiation. The agent for fractures is mechanical force (including that resulting from gravity) against a bone.
The agent of caisson disease (or "the bends") is excessive atmospheric pressure—nitrogen becomes soluble in the blood
of divers operating under high air pressure for deep dives and forms bubbles in their blood if they return to normal pressure
too quickly. Low atmospheric pressure, on the other hand, is the agent for altitude sickness.
Characteristics of Infectious Agents
Infectious agents vary in their inherent ability to infect and disease in a host. The ability of an infectious organism
to invade and multiply in a host is known as infectivity. This is usually means. the secondary attack rate, which is:
For a given infectious agent, of course, the secondary attack rate may vary greatly from one species of host to another or,
within one host species, with the manner of transmission or differing host characteristics.
Pathogenicity refers to the ability of an agent to produce disease in an infected host. This may be measured by
This varies from highly pathogenic agents, such as those of rabies, smallpox, measles, and chickenpox, which produce illness
in virtually every infected host to, for instance, poliovirus, which produces illness only once in every 300-1,000 infections.
Although the term virulence is commonly used by physicians as a synonym for pathogenicity, it really means the ability
of an infectious agent to produce severe illness in diseased hosts. Severe illness is a difficult concept to define in a way
that can be concretely applied to all diseases. For this reason, it has become accepted practice to use the case fatality
rate as a proxy measure for virulence. A proxy measure does not actually measure the hard-to-measure concept you wish
to measure, but instead measures a second more easily measured concept that parallels the one you wish to measure. This gives
an estimate of the first concept but not a true measure of it. The case fatality rate is:
Virulence varies from diseases such as chickenpox, rubella, or the common cold, which almost never produce any form of
severe illness to such extremely virulent diseases as rabies or ebola, both of which are essentially universally fatal illnesses.
HIV disease (or AIDS) was fatal in about 80% of all cases when it was first discovered but death rates have declined as improved
treatments have become available and perhaps also due in some small degree to host adaptation as the most resistant hosts
survived and reproduced. Smallpox, which is fatal in 20-40 percent of all cases, may seem minor in com¬parison to rabies and
AIDS but is highly virulent compared to most human diseases.
Although these concepts developed specifically with reference to infectious agents, they have some applicability to other
types of agents. They help to emphasize the point that while the agent is necessary for the disease to occur it is not sufficient.
As Rene Dubos (1965), said "Throughout nature, infection without disease is the rule rather than the exception" (p. 190).
Many agents are transmitted from host to host by blood-insects. Malaria, yellow fever, and encephalitis are conveyed from
to host by mosquitoes. Plague and murine typhus are both conveyed by rat fleas. Rocky Mountain spotted fever is carried by
ticks. The term vector was coined for such blood-sucking insects as carriers of ir
Other animals also convey agents from host-to-host. Epidemic typhus, for instance, is carried by the human body louse.
Rabies is carried by the bite of an infected animal. These were sometimes referred to as vectors, although they are not blood-sucking
insects. Many agents may be carried on the feet of flies whose taste buds are located on the soles of their feet, and who
therefore taste possible food by walking on it.
Agents may also be conveyed from one host to another via non-living items. These non-living carriers have been called vehicles
or mechanical vectors. Included would be hypodermic needles shared by drug addicts, which can convey serum hepatitis
or AIDS. Intimate personal items, such as handkerchiefs, toothbrushes, or smoker’s pipes, that are not normally shared
between people can carry agents from person to person when they are shared. Such personal items are called fomites
The distinctions between vectors, vehicles, and fomites seem to have been regarded as less important in recent years. The
term vector is increasingly used for all means by which agents may be conveyed from one host to another. It has been broadened
by some theorists far beyond any of these original concepts and has even been applied by some epidemiologists (c.f. Justice
& Duncan, 1975; Justice & Justice, 1976) to abstract concepts that may bring psychic agents to bear on hosts.
Hosts differ in their exposure to agents and in the likelihood developing a disease in response to the agent. They vary
in the state of their natural defenses against disease as well as in the behaviors that may expose them to agents.
Immunity and Immunologic Responses
Specific immunity to infectious disease is usually the result of the body's production of substances known as antibodies.
These antibodies are present in the blood, tissue fluids, and often the mucous secretions of the immune host. The immunity
possessed by a host is classified on the one hand as being active or passive and on the other hand as being natural or artificial.
Active immunity means that the host is producing its own antibodies. Natural active immunity (or naturally acquired
active immunity) is the result of having previously had and recovered from a case of the disease. Artificial (or artificially
acquired) active immunity is the result of vaccination.
Passive immunity means that the host possesses antibodies but is not capable of producing its own new antibodies
when the old ones "wear out" with age. Newborn infants possess natural passive immunity to the diseases that their mothers
are immune to, due to the passage through the placenta of antibodies from the mother's blood to the fetus' blood. In breast-fed
infants the mother continues to replenish the infants' natural passive immunity by transmitting antibodies through her milk.
Passive immunity may also be artificially induced by injecting antibody material acquired from an actively immune host. Gamma
globulin, the antibody-containing fraction of pooled adult human blood plasma, is used for short-term protection against infectious
hepatitis and measles. Likewise, antibodies from horses (or sometimes other animals) are used to provide temporary immunity
to tetanus or rabies.
The behavior of a potential host determines in large part the likelihood of exposure to agents or the degree of susceptibility
to disease. The best known systematic examination of this broad area is the well-known work of Belloc and Breslow (1972).
They identified five health habits that were highly associated with lower death rates and better health status. These five
health habits were: sleeping 7-8 hours per night, exercising moderately several times per week, maintaining normal weight,
not smoking, and drinking either in moderation or not at all.
Environmental factors affect the exposure of potential hosts to vectors and agents as well as the ability of the hosts
to maintain high levels of resistance. The environment may be thought of as being comprised of three broad aspects: the physical,
which includes the geographic, geologic, and climatic features of the environment; the biological, which includes all the
living creatures in the environment; and the social, which includes social institutions, cultural norms, and economic features
of the environment.
Geographic features may influence the occurrence of disease in a variety of ways. Geographic features such as mountain ranges,
rivers, or deserts constitute natural boundaries limiting the spread of disease agents or their vectors. On the other hand,
trade routes provided by roads, rivers or mountain passes may also constitute the routes along which diseases spread from
place to place. Geographic features may also provide ideal circumstances for a concentration of disease agents or vectors.
For instance, malaria, yellow fever, and encephalitis are all more common in low-lying, swampy areas that provide an ideal
home for the mosquitoes that carry the agent.
Climate and geography are often related in their effects a distribution of disease. Epidemic typhus, for example, is found
only in temperate zones and high altitude areas of the subtropics, whereas murine typhus is common in the lowlands of the
tropics and subtropics. The cooler climate in which epidemic typhus is found encourages the wearing of many clothes, which
along with infrequent laundering favors the human body louse that spreads the infection of epidemic typhus. The warm climate
of the tropical and subtropical lowlands discourages wearing many clothes and lice infestation but favors an abundance of
rats, the fleas of which carry the agent of murine typhus.
Geologic formations determine the ability of soil to hold and purify water, the availability and types of fuel and mineral
deposits, and the ability of soils to support crops. These features may have a great impact on disease patterns in the population.
The distribution of disease is often affected by the plentifulness of vectors or of alternate hosts in the environment.
The role of such vectors as rat fleas and mosquitoes has already been noted above. Rabies is conveyed to humans by contact
with rabid animals. Because rabies is common among skunks, nearness to a large skunk population increases the risk of rabies.
Encephalitis infection is common among birds and is carried from bird to bird by mosquitoes. When the bird population is reduced
by a bad winter, for instance, the mosquitoes that normally prey on birds seek nourishment elsewhere, biting people and conveying
the infection to them.
Population density relates to the adequacy of food, water, and other resources. The age distribution within a population
has major impact on the disease experiences of that population. A youthful population will suffer higher rates of infectious
diseases and traumatic injuries, while an older population will suffer more from degenerative and other chronic diseases.
Many of the host behaviors that affect exposure and susceptibility to disease are culturally patterned. For instance, the
dietary pattern and food-handling practices within a society influence not only the exposure to nutritive elements as agents
but also exogenous chemicals and living agents with which foods may become contaminated. Patterns of personal hygiene and
of waste disposal have major effects on the exposure of the population to many agents.
The same is true of norms for personal contact. For instance, in our society epidemics of the parasitic disease scabies,
which is readily transmitted through hand-holding, is seen mostly in preschool and elementary school children who often hold
hands. In Arab societies it is not uncommon for men to hold hands while walking together—as a result, scabies epidemics
often extend to the adult population. The relevance to venereal diseases is even more obvious.