The concept that disease could be caused by entities
too small to see with the naked eye was first proposed in the sixteenth
century by the Italian scholar Girolamo Fracastoro. Though
he did not know of the existence of microorganisms, he believed that tiny
"seeds" of illness could be passed from one organism to another.
This was not a wholly fantastic idea for his time, since many also believed
in the concept of spontaneous generation, and that diseases were attributable
to such phenomena as bad blood and gasses in the atmosphere.
The term malaria, for example, is derived from the Latin for "bad air".
However, with the advent of the microscope and the work of others, by the
Nineteenth Century it was understood that microorganisms such as bacteria
were indeed the causitive agents of many illnesses.
In the nineteenth century, Robert Koch would
develop a series of steps or postulates, which he used to determine the
etiologic (causitive) agent of the disease anthrax. Koch, like Frederich
Cohn, Jacob Henle, Louis Pasteur, and others, was convinced that bacteria
and other microbes were responsible for illness. This germ theory
of disease was one of the great concepts to become established during the
golden age of microbiology. Koch's Postulates could be used to show
cause and effect relationships between the disease and its agent:
1. The suspected pathogen must be found in all individuals suffering
from the disease, but not in
2. The suspected pathogen must be isolated and grown as a pure culture
outside of its host.
3. If the suspected pathogen is introduced into the body of healthy
test subjects, they should
manifest clinical signs of the same disease as the
original infected population.
4. The suspected pathogen must be re-isolated from the test subject
and shown to be identical
to the original suspected pathogen.
Colonization, Virulence, and Pathogenicity
Colonization vs. Disease
Infection occurs when microorganisms contact
the body of a host. Colonization occurs if, after contact,
the organisms establish themselves in or on the body of the host.
There are two types of colonization: (1) transient colonization,
wherein the organisms only temporarily reside on the body of a host and
are removed by mechanical means such as the sloughing away of dead skin
cells or washing, and (2) resident colonization, wherein organisms
become permanently established in or on the body, as in the case of resident
microflora (often called normal flora) of the skin, oral cavity, and gastrointestinal
Disease refers to any adverse change
away from the normal homeostatic balance. Disease may be triggered
by exposure to damaging physical factors such as radiation, chemical agents
which trigger adverse changes in the structure or function of cells or
tissues, genetic malfunctions or inherited genetic conditions which trigger
damage to the individual, or infection by pathogenic microbes such as viruses,
bacteria, protists, or fungi. Disease only follows infection, however,
if the presence of the microbe causes adverse host reactions which damage
cells and tissues, or if the products of microbial metabolism or reproduction
damage or destroy host tissues. Infection is therefore distinct
The body of any multicellular organism serves
as a host to a multitude of different microbial forms. The microbial
complement inhabiting the body are referred to as normal microflora
or normal flora, terms which date to a time when bacteria were still considered
part of the plant kingdom. The relationships owing to this colonization
can be considered either commensualistic, mutualistic, or parasitic, and
the likelihood of the establishment of disease depends on the type of relationships
which are established. Commensals are organisms which live
in or on the body of a host, do no harm in this association, but conversely
do no good either, such as the Staphylococcus epidermidis and the
diptheroid bacteria which live on the surface of the skin. Mutuals
form beneficial relationships with their hosts, such as many of the bacteria
of the gastrointestinal tract which synthesize vitamin K, riboflavin, and
biotin used by the host in return for nutrients and a warm, moist habitat.
Many of the same bacteria inhibit the growth of opportunistic pathogens
(usually commensals which can trigger disease if allowed to exceed small
population sizes) such as the fungal agent of yeast infections, Candida
albicans, by competitive exclusion or the release of inhibitory chemical
compounds. Parasites, unlike commensals or mutuals, live in
or on the body of the host and do it harm. These organisms are usually
not part of the normal microflora component, but find ways to establish
themselves and either directly or indirectly cause damage to host tissues.
Some pathogenic microorganisms are parasites which have evolved along with
at least one host species, and in so doing have found ways to overcome
many of the host defense mechanisms. These organisms often cause
serious and persistant diseases.
Virulence and Pathogenicity
Pathogenicity refers to the capability
to cause disease. To be considered a pathogen, an organism must be
capable of infection, and once established, triggerring a sequence of events
which result in disease. Virulence is a measurement of the
degree of pathogenicity, composed of infectivity (the ability to
establish and colonize), and severity (the degree of host damage
caused by the presence and activity of the infective agent).
Those attributes an organism has which enables
it to be a pathogen are called virulence factors. These include attachment
factors, spreading factors, growth and survival factors, and toxic factors.
Attachment factors enable a microorganism to adhere to the surface
of cells or tissues and prevent it from becoming dislodged. Examples
of these include hemagluttinin receptor spikes on the envelope of
some of the orthomyxoviruses such as influenza A, fimbriae (attachment
pili), slime layers (glycocalyces) produced by various bacteria,
adhesive discs produced by some protists such as Giardia
lamblia, and hooks and suckers used by large multicellular
parasites such as tapeworms and leeches. Spreading factors
are chemical compounds which enable microorganisms to spread between layers
of cells and tissues, or to elude some nonspecific forms of host resistance.
Examples include exoenzymes such as hyaluronidase, collagenase,
and lecithinase produced by Clostridium perfringens to destabilize
plasma membranes and break down extracellular matrix which holds tissues
together, and fibrolysins produced by clostridia, pathogenic staphylococci
and streptococci to break down fibrin clots in the bloodstream. Growth
and survival factors enable a pathogen to take from the host those
nutrient compounds it needs for reproduction and to prevent destruction
due to host defenses and artificial agents used to limit and stop microbial
growth. These include siderophores, chemical compounds which
sequester elemental iron, which is necessary for the replication of some
microorganisms, capsules, which help cells clump together and form
aggregates too large for phagocytosis by macrophages and other host cell
types, and resistance enzymes such as the b-lactamases
produced by penicillin and cephalosporin-resistant bacterial species.
Toxic factors are chemical compounds which when released from the
pathogen cause host cell and tissue damage. Examples of these include
endotoxins such as the lipopolysaccharide A (lipid A) component
of the outer cell membrane of some Gram negative bacteria, which can trigger
vasodilation leading to shock once released by cell lysis, exotoxins
such as botulin, a neurotoxin produced by Clostridium botulinum,
diptheria toxin produced by Corynebacterium diptheriae, tetanus
toxin produced by Clostridium tetani, hemolysins which
break down red blood cells and release iron from hemoglobin, and fungal
mycotoxins, such as aflatoxin produced by some Aspergillus
species, ergot toxin produced by Claviceps purpurea, and
a-amanitin, produced by Amanita
How Diseases are Spread
Initiation of Disease
As previously stated, virulence is associated
with infectivity. Infectivity is measured in terms of the infectious
dose, i.e. the number of microbes which is necessary to initiate establishment
of a growing colony. In general, the lower the infectious dose,
the more virulent a pathogenic species is. If the potential host
is compromised, meaning that its immune response has been lessened by some
other factor, the normal infectious dose can be reduced and the likelihood
of infection and disease can be greatly increased.
Those outside influences which can compromise
a potential host are called predisposing factors, which are either
behavioral or environmental. Behavioral predisposing factors
include smoking, overeating, poor hygenic practices and food handling techniques,
indiscriminant I.V. drug use, and engaging in sexual activities without
taking proper precautions against direct contact with potential pathogens.
Environmental predisposing factors include air and water pollution,
exposure to radiation emitted either artificially by devices such as microwaves
or naturally via ultraviolet radiation from sunlight, and contact with
the carriers or vectors of infectious disease such as arthropods, mammals,
and contagious humans.
Some pathogenic microbes have the ability to
form pockets of infection which become chronic, leading to development
of carriers who do not exhibit visible signs of disease. Salmonella
cholersesuis var. typhimurium, a pathogen responsible for food
infections, can reside in the liver and gizzard of birds such as chickens
and pass through the shell of the egg while it is still housed in the cloaca.
This is because the shell does not harden until after it leaves the body.
Since the bird shows no visible sign of disease, it can infect any human
who consumes it if the flesh is not properly handled and thoroughly cooked.
Also, if the egg is not properly cooked, it can serve as a source of infection.
In humans, pathogens such as Salmonella typhi and Trichmonas
vaginalis can be passed by carriers as well. Trichomonas
is a sexually transmitted protist which causes vaginitis (inflammation
of the vaginal canal) in women. Infection of this protist in the
male, however, is asymptomatic. This means that even if a women is
given the proper medication for the infection, she can be re-infected unless
both she and her sex partner are treated together.
Expression and Progress of Disease
The way a disease expresses itself may be directly
obvious or may be invisible to the individual attempting to make a diagnosis.
Any outwardly visible aspects like development of lesions, visible pyogenic
activity such as in strep throat infections by Streptococcus pyogenes,
copious diarrhea, sneezing and coughing, and others, which present themselves
as consequences of the disease process are called signs.
Invisible aspects of the disease which are related by the infected individual
to the health care professional such as nausea, headache, and body pains
are called symptoms. The combination of both signs and symptoms
is called the disease syndrome.
Some diseases leave behind cell and tissue
damage as they subside. These residual products of the disease process
are called sequelae, and they may inhibit the proper functioning
of tissues or organs even long after the pathogen has been eliminated from
the body. Sequale can have a direct and sometimes permanent impact
on the health of the individual, and can make the individual more prone
to infection by microbes in the future.
Diseases begin with a period of incubation,
which represents the time from initial infection and subsequent colonization,
to the first appearance of the disease syndrome. This period may
be relatively brief, two to three days as with some food and waterbourne
infections, or as long as several weeks, months, or sometimes years depending
on the type of microbe involved, the site of entry, since some microbes
infect more quickly closer to the area of the body they most readily colonize,
and the level of immune resistance carried by the host. However,
once colonization is established, the host enters the prodromal phase,
which is generally a period of dissimated, general symptoms such as headache,
fever, and nausea. This is soon followed by the acme period,
which is the most acute stage of the disease. During this period,
visible signs of disease appear, such as rashes, skin and mucus membrane
lesion, mucus or fluid discharge, jaundice, and/or high fever. If
the body of the host is sufficiently immunocompetent, the acme period will
eventually begin to subside, and the individual will enter convalescence,
where the body begins to return to its normal level of homeostasis.
Types of Infections
Infections occur as either primary or secondary
forms. A primary infection occurs the first time a previously
healthy host is exposed to a pathogen, if the microbe colonizes and stimulates
disease. Secondary infections are caused by opportunistic
pathogens which are either already part of the normal microflora of the
host, or can only infect once bodily defenses have been compromised.
An example of the secondary type which represents a major concern for the
health care industry is called the nosocomial infection. This
is hospital-aquired, and is usually transmitted by the health care workers
themselves. Opportunistic pathogens such as enterococci, Staphylococcus
aureus, Streptococcus pyogenes, Enterococcus faecalis,
and Pseudomonas aeruginosa are carried from place to place on the
hands of staff who fail to follow proper sanitary procedures when traveling
from one patient to another. The most serious of the secondary infections
is called a superinfection, which can sometimes occur when an opportunistic
pathogen establishes itself so firmly that it overwealms and eliminates
normal commensal and mutual microflora. Superinfections are extremely difficult
ot treat, since they usually are caused by microbes which are resistant
to most forms of antibiotic therapy.
Routes of Transmission
Before infection and disease can occur, a potential
pathogen must find some way to enter the body of the host. Commonly
this is via direct contact, wherein the individual becomes exposed
to the pathogen which is present either in air as aerosol droplets spread
through the coughing and sneezing of infected individuals, or by sexual
intercourse, or indirectly, through food which was handled improperly,
or contact with contaminated fomites. Sexual, contact, and food borne
transmission could also be considered behavioral, in that these routes
could be blocked by simple prevention techniques such as handwashing, abstinence,
and prophylaxis. The parenteral route allows invasion through the
protective outer layers of the skin, such as in bites, cuts, invasive surgical
procedures, burns, and intravenous drug use.
In general, the spread of many infectious diseases
can be attributed to the four Fs of infection: fingers, fomites,
flies, and feces. Improper sanitary measures such as
the washing of hands provides a pathway for microorganisms to be spread
from human to human quickly. Fomites are any nonliving objects an
individual might touch, including books, counter surfaces, appliances,
and surgical implements which have not been properly disinfected or sterilized
prior to contact. Flies, roaches, and other arthropods which commonly
associate themselves with areas inhabited by humans carry diseases either
on the hairy surface of their bodies or in their gastrointestinal tracts.
Human feces contaminated with disease-causing microorganisms can be spread
through the anal-to-oral route or serve as a source of contamination for
improperly sanitized water supplies. Zoonoses are outbreaks of disease
carried by animal reserviors, usually mammals associated with arthropod
vectors including fleas, lice, biting flies, and ticks.
The study of the sources and spread of disease
is called epidemiology. The earliest example of this was in
1849, when a English physician named John Snow was asked to determine
the source of an outbreak of cholera in London. He systematically
traced the spread of the disease by linking the infected individuals to
specific parts of the city, and was suprised to find that almost all of
the patients had at one time or the other taken water from a single well.
After he removed the handle from the pump, the incidence of cholera subsided.
He was thus able to establish a cause-and-effect relationship between the
occurrence of a disease and its reservior.
Today, epidemiologists apply demographic and
statistical techniques to determine the precise point of origin of a disease
and to track its spread. With luck, a specific index (first)
case can be found, which gives the scientist what they need to establish
where a disease first appeared. This can be extremely difficult since
geographic barriers which once existed between populations of individuals
have been removed by modern modes of mass transportation. Data gathered
is divided into two major categories, morbidity, or the rate of incidence,
and mortality, the death rate due to a particular disease. This data
is gathered primarily by the World Health Organization (WHO), and
in the United States by the Centers for Disease Control (CDC).
The CDC issues a constantly updated publication called the Morbitity
and Mortality Weekly Report (MMWR), both as a magazine and electronically
on the World Wide Web to keep epidemiologists, health care workers, and
scientists apprised of any new data concerning any cause of disease and
death on a constant basis.
How Diseases Spread across Populations
Diseases which have established themselves in
a specific area due to environmental factors such as climate, but which
are present with a regular or constant pattern, are said to be endemic.
One example of an endemic disease is African trypanosomaisis, also called
African sleeping sickness. The etiologic (causal) agents of this
disease are protists such as Trypanosoma gambiense and T.
rhodesiense, which are carried by an arthropod vector, the
tse tse fly. These flies are very sensitive to environmental changes,
thus they remain within relatively strict boundaries, keeping the disease
local to the area. Epidemic diseases, however, begin at one
site and quickly spread over larger areas. The black plague, caused
by Yersinia pestis, a gram negative member of the Enterobacteriaceae,
was carried by the Norwegian rat from the Middle East throughout Europe
in the fourteenth century and was responsible for over 25 million deaths.
Pandemic diseases spread worldwide. In the nineteenth century,
the influenza A virus rapidly travelled around the world, killing countless
millions. Currently, the human immunodeficiency virus (HIV) is responsible
for a pandemic of acquired immunodeficiency syndrome (AIDS). With
no currently known effective treatment for this viral disease, it is highly
likely that it will continue to sweep the globe for some time to come.
Control of Disease
One can control disease either through prevention
or containment. It is preferable to prevent the spread of
disease by keeping it from occurring at all. This can be accomplished
by avoiding contact with infected individuals or reservoirs of infection,
proper water and sewage treatment, proper food handling and preparation,
and the control of pathogen vectors. If infection does or has already
occurred, the first step in prevention of spread is isolation and quarantine
of diseased animals or humans. Next, the suspected pathogen must
be isolated and identified, so treatment options can be considered.
Finally, proper aseptic and antiseptic techniques must be maintained to
prevent the nosocomial spread of the agents of infection to others.
Critical Thinking Exercises
1. It has been hypothesized that the best type of parasite is one
which forms a mutualistic
symbiotic relationship with its host.
Yet, many severe pathogens, such as the ebola virus
replicate in tissues so rapidly that they
almost always kill the host. Do agree with the idea
that pathogens eventually must evolve into
symbiotic partners? Defend your answer.
2. During the disease cycle, which of the periods (incubation,
prodromal, acme, convalescence)
are most likely to be associated with the
spread of a contagious pathogen. Why?
3. Why is it that contagious diseases such as influenza and AIDS
are able to spread so rapidly?
Test Yourself- Use this to quiz yourself about