Title

Principles of Disease Chapter 7

X
Why Is This Important?

This chapter introduces you to

etc
the principles of disease, and in
particular how diseases are caused
(the etiology), how they can be
characterized, and the concepts of
sepsis and shock. These concepts are
important for developing an in-depth
understanding of infections.

OVERVIEW

This is an important chapter because here is where we begin to look at the prin-
ciples of infectious disease. Armed with the things we learned in the previous
chapters, we are well prepared for these discussions, and the things we learn
here will become part of the foundation for all of the other topics we examine.
Our discussions will be broken down into three major parts. The first will ex-
amine how infectious disease can get started, which is referred to as etiology.
Part two will examine how disease can develop, including communicability and
contagiousness. The final discussion will be about infections that move into the
systemic circulation.
We will divide our discussions into the following topics:

Principles of Disease

THE ETIOLOGY DEVELOPMENT THE SCOPE

OF DISEASE OF DISEASE OF INFECTIONS

Now that we have looked at the primary requirements for a successful

infection (Chapters 5 and 6), we can examine some of the principles asso-
ciated with disease. Table 7.1 lists several of the terms used when discuss-
ing disease. We can start off by defining disease as any negative change
in a person’s health. This change has a cause, and we refer to the cause of
the disease as its etiology. Thus, for infectious disease, we can say:

s 4HATTHEDECLINEINHEALTHˆINOTHERWORDSTHEDISEASEˆISCAUSED
by microorganisms invading a host’s body What Do I Need to Know?
s 4HAT THESE MICROORGANISMS ARE THE ETIOLOGICAL AGENTS OF THE
To get the most out of this chapter,
disease
please review the following terms
One of the things we need to re-examine is the presence of normal micro- from your previous courses in biology,
bial flora, which we mentioned in Chapter 6. There is no denying that we anatomy, physiology, or chemistry or
exist in an environment of microorganisms and that our bodies contain in previous chapters of this book as
a variety of them that have a useful relationship with us. There are many indicated in parentheses: endocytosis
microorganisms located in many places in the body that make up the (4), exocytosis (4), electrolyte,
normal microbial flora (Table 7.2). For example, the large intestine has lipoprotein (2), phospholipid (2),
the largest population of bacteria (in fact, fecal material is mostly bac- lipopolysaccharide (2), lysis, lamina
teria). These organisms are supposed to be there because they provide propria, Peyer’s patches, cytokine.
118 Chapter 7 Priciples of Disease

Term Defining Characteristic

Acute disease Symptoms develop quickly but infection lasts only a short time
Chronic disease Symptoms develop slowly and disease can last a long time
Subacute disease Symptoms are between those of acute disease and those of chronic disease
Latent disease Symptoms can continue to reappear long after initial infection
Local infection Confined to a small area of the body
Focal infection Initial site of a spreading infection
Systemic infection Pathogens use blood or lymph to move around body
Bacteremia Presence of bacteria in the blood
Septicemia Organisms multiplying in the blood
Viremia Presence but not multiplication of viruses in the blood
Toxemia Presence of toxins in the blood
Primary infection Initial infection
Secondary infection )MMEDIATELYFOLLOWSPRIMARYINFECTIONCANBEMOREDANGEROUSTHANINITIALINFECTION

Table 7.1 Some Common Terms Used
When Describing Infections
necessary functions that are helpful to us. To use another example, the
skin is covered with bacteria of many kinds, including normal resident
bacteria, transient organisms, and even pathogens. As we saw in Chapter
6, however, unless these organisms can find a way through the skin (and
some do), they are essentially harmless because the intact skin is such an
impenetrable barrier. The mouth, nose, and throat are also places where
large numbers of microorganisms are found, and once again many of
these are harmless. Some are pathogenic, though, so it is important to
remember that this area of the body is the most common portal of entry
for bacteria. The respiratory system is readily accessible to potential
pathogens from the nasopharynx and oropharynx.

There are three types of relationship between a host and bacteria living
in that host (Table 7.3). The first is commensalism, in which one partner
is benefited but the other is unaffected. The relationship between humans
and the microbial flora named in Table 7.2 is one form of commensal-
ism. The second type of host–bacteria relationship, mutualism, is one in
which the host offers benefits to the bacteria and the bacteria offer ben-
Table 7.2 Representative Normal efits to the host. Some bacteria provide us with vitamins such as K and
Microflora B, for instance, and we provide them with nutrients and a place to stay.

Region of the Body Representative Microorganisms

Skin Staphylococcus epidermidis, Staphylococcus aureus, Propionibacterium acnes, Candida species,
and Corynebacterium species
Conjunctiva Staphylococcus aureus, Staphylococcus epidermidis, and Corynebacterium species
Nose and throat Staphylococcus aureus and Staphylococcus epidermidisINTHENOSEStaphylococcus aureus,
Streptococcus pneumoniae, Haemophilus, Corynebacterium, and Neisseria species in the throat
Mouth Streptococcus species, Lactobacillus, and Corynebacterium
Large Intestine Lactobacillus, Enterococcus, Escherichia coli, Enterobacter, Proteus, Klebsiella, and
Corynebacterium species
Urogenital tract Staphylococcus epidermidis, Enterococcus, Lactobacillus, Pseudomonas, Klebsiella, and Proteus
INTHEURETHRALactobacillus, Streptococcus, and Staphylococcus in the vagina
 THE ETIOLOGY OF DISEASE 119

Type of Relationship Microorganism Host Example

Commensalism Benefits Neither benefits Saprophytic bacteria that live off sloughed-off cells in
nor is harmed the ear and external genitalia

Mutualism Benefits Benefits Bacteria in colon

Parasitism Benefits Is harmed Tuberculosis in lungs

The third type of relationship is called parasitism, and here one of the Table 7.3 Host–Microorganism
partners benefits at the expense of the other. This is the relationship we Relationships
see with pathogens, which benefit at the expense of our health.

There are two points that are important to remember about host–bac-
teria relationships. First, microbial flora can protect us from disease.
This is accomplished by microbial antagonism. Like a dog that marks
its territory, bacteria that reside in certain areas of the body will fight
to prevent “outsiders” (such as pathogens) from taking up residence.
This prevention is easy for the resident bacteria to accomplish because
they are well established in the host. For instance, our microbial flora
competitively inhibits the growth of pathogenic interlopers by more effi-
ciently using all the available nutrients and all the available oxygen,
leaving none for the pathogens. In addition, the flora can acidify the
region and make it less hospitable to any infringing pathogen. In fact,
many bacteria, such as Streptococcus species and Escherichia coli, can
produce bacteriocins, which are essentially localized bacterial antibiot-
ics. These bacteriocins can kill invading organisms but do not affect the
bacteria that produce them. Bacteriocins are specific for the bacteria
that produce them, and for that reason they are useful as diagnostic
tools for identifying bacteria.

The second important point about host–bacteria relationships is that

many normally harmless resident bacteria are in fact opportunistic path-
ogens. Recall from the previous chapter that this type of pathogen is
defined as one that is harmless in its normal location but can cause dis-
ease if it moves to aºon. One of the most prevalent of these is caused by
Escherichia coli, which moves from the large intestine, where it is part of
the normal microbial flora, to the urethra, where it is a pathogen. Urinary
tract infections can occur repeatedly and become increasingly dangerous
if the infection moves into the bladder or the kidneys. (We discuss this in
more detail in Chapter 23.)

THE ETIOLOGY OF DISEASE

To understand the etiology of disease, it is important to mention one of

the fundamental paradigms of microbiology, Koch’s postulates. Robert
Koch was a physician in the nineteenth century who studied anthrax in
cattle. His studies were the first to close the loop between cause and
effect for infectious disease and became a prerequisite for establishing
the etiology of bacterial diseases. His postulates can be listed as follows:

s 4HESAMEPATHOGENMUSTBEPRESENTINEVERYCASEOFTHEDISEASE

s 4HEPATHOGENMUSTBEISOLATEDFROMTHESICKHOSTANDPURIlED

s 4HE PURE PATHOGEN MUST CAUSE THE SAME DISEASE WHEN GIVEN TO
uninfected hosts.

s 4HEPATHOGENMUSTBERE ISOLATEDFROMTHESENEWLYINFECTEDHOSTS
120 Chapter 7 Priciples of Disease

The procedure for testing the four postulates is illustrated in Figure 7.1.

These postulates allow us to place the responsibility for infection clearly

1 microorganisms are isolated
from a dead mouse
and squarely on the organism that caused it, and they are still required
today for determining the etiology of infections. Unfortunately, there
are several exceptions, in particular the requirement for isolation and
purification of the potential pathogen. There are many organisms that
will not grow on artificial media and therefore cannot be purified. For
example, the spirochete Treponema pallidum and the Gram-positive acid-
fast rod Mycobacterium leprae (which causes leprosy) cannot be used in
conjunction with Koch’s postulates, and neither can Rickettsia organisms
and viruses. In addition, some organisms can cause a variety of diseases,
making the use of Koch’s postulates impossible. Consequently, there are
some diseases in which we can identify the etiological agent by using
Koch’s postulates, such as tuberculosis (etiological agent Mycobacterium
tuberculosis) and Lyme disease (etiological agent Borrelia burgdorferi),
and some in which we cannot use the postulates.

colony Keep in Mind

s 4HECAUSEOFADISEASEISREFERREDTOASTHEETIOLOGY
s 4HEBODYCONTAINSNORMALMICROBIALmORAMADEUPOFBACTERIATHATARE
beneficial to the host.
2 microorganisms microorganisms s 4HEREARETHREETYPESOFRELATIONSHIPBETWEENBACTERIAANDTHEIRHOSTS
are grown in are identified commensalism, mutualism, and parasitism.
pure culture
s +OCHSPOSTULATESAREANIMPORTANTWAYOFEVALUATINGTHEETIOLOGYOFA
disease.

3 microorganisms are injected
into a healthy mouse
4 disease is reproduced in
the second mouse;
microorganisms are isolated
DEVELOPMENT OF DISEASE
The course of a disease can be broken down into five specific periods
(Figure 7.2). The first is called the incubation period and covers the
time between the initial infection and the first symptoms of the dis-
ease. The length of the incubation period depends on the virulence of
the pathogen: the lower the virulence, the longer this period will last
(Figure 7.3). The second period is the prodromal period, during which
the first mild symptoms appear. Once major symptoms are noted the
disease has moved into the period of illness. It is here that the immune
response is highest, and depending on the severity of the illness the
patient may die during this period. The fourth period is called the period
of decline, during which the symptoms subside. Although this period is
an indicator of the end of the illness, it is also a time when the patient
can acquire a secondary infection. This is particularly true of opportun-
istic infections and of nosocomial infections. In many cases, because of
the debilitated condition of the patient, these secondary infections can
be more dangerous than the initial problem. The final period is called
the period of convalescence, during which the patient regains strength
and proceeds to a full recovery.

Communicable and Contagious Disease

Some diseases are communicable, which means that they can spread
pathogenic identical
microorganisms microorganisms from one person to another. Tuberculosis is one example. Others are
are grown in are identified non-communicable, which means they cannot spread from one person
pure culture to another, with tetanus being a common example. In addition, commu-
Figure 7.1 Koch’s postulate test nicable diseases that spread very easily, such as chickenpox or measles,
system. This test is used to determine the are classified as contagious, meaning that they are communicable on
etiology of infectious diseases. contact with an infected individual.
 DEVELOPMENT OF DISEASE 121

Figure 7.2 A graphical representation

severity of symptoms
incubation prodromal illness decline convalescence
period period (most severe (declining signs (no signs or of the five periods of infection. The
(no signs or (vague, signs and symptoms) and symptoms) symptoms) duration of the incubation period varies
symptoms) general
symptoms)
with the virulence of the pathogen, and
secondary infections can occur during the
period of decline. Because the patient is
already debilitated, secondary infections
can be more dangerous than the primary
infection.

time

There are three methods available for full or partial control of communi-
cable and contagious diseases: isolation, quarantine, and vector control.

Isolation means preventing an infected person from having contact with

the general population. There are seven categories of isolation, which
is usually done in a hospital. However, patients with diseases such as
tuberculosis can be difficult to isolate before they have been diagnosed.
As we saw in Chapter 1, in a busy emergency room, preference is given
to individuals who are bleeding or who have chest pain. Someone with
tuberculosis might be asked to be seated in a crowded waiting room for
hours before being examined, diagnosed, and isolated. In a situation like
this, the term contagious becomes easily understandable.

Quarantine involves separating from the general population healthy indi-

viduals (either humans or animals) who may have been exposed to a
communicable disease. Quarantine usually lasts as long as the expected
incubation times for the suspected disease and is lifted if symptoms do
not present during that period. Although quarantine is the oldest method
of dealing with communicable diseases, it is now generally used only for
very severe diseases, such as cholera and yellow fever. In fact, quaran-
tine is rarely used today because of the difficulty in enforcing it.

whooping cough

tetanus

rocky mountain spotted fever

plague

herpes
disease

gonorrhea

E. coli diarrhea

diphtheria

gas gangrene

influenza

cholera

Salmonella (food poisoning)

Figure 7.3 Durations of the period of
0 7 14 21 incubation for selected organisms and
time (days) diseases.
122 Chapter 7 Priciples of Disease

The third method for controlling communicable diseases is vector con-

trol, where vector is defined as any organism that carries disease patho-
gens from one host to another. The principal means of vector control
are the destruction of vector habitats and the inhibition of vector breed-
ing habits and feeding behaviors. In addition, measures such as window
screens, mosquito netting, and insect repellents can be used to protect
against transmission. For instance, malaria control in the United States is
accomplished through control of the mosquito population.

Keep in Mind

s 4HEDEVELOPMENTOFADISEASECANBEBROKENDOWNINTOlVEPERIODS
incubation, prodromal, illness, decline, and convalescence.
s #OMMUNICABLEDISEASESCANBESPREADFROMONEPERSONTOANOTHER
s #ONTAGIOUSDISEASESARECOMMUNICABLEONCONTACTWITHANINFECTED
individual.
s -ETHODSFORTHECONTROLOFCOMMUNICABLEANDCONTAGIOUSDISEASESINCLUDE
isolation, quarantine, and vector control.

Duration of Disease
The duration of a disease can vary depending on several factors, in par-
ticular the overall health of the host. When we look at duration, there
are four basic categories we can use. Acute diseases such as chicken-
pox and measles develop quickly but last for only a short time, whereas
chronic diseases, such as hepatitis, mononucleosis, and tuberculosis,
develop slowly but remain for long periods. Diseases such as sclerosing
panencephalitis fall in the category of subacute. This disease has an
insidious onset that can take 6–12 months to develop and can be fatal.
Latent diseases are those that remain in the host after the initial signs
and symptoms disappear and can be become reactivated after long peri-
ods. Latency is seen in several viral diseases, the most common example
being chickenpox. The patient initially shows the classical signs of this
pox infection (reviewed in Chapter 13), and after a while these disappear.
However, the virus has taken up residence in the patient’s neurons. At
some point it can be reactivated and the patient will present with the rash
identified as shingles. The reasons for reactivation of the virus are not yet
understood, but they may involve stress or emotional anxiety.

Persistent Bacterial Infections

Some pathogenic bacteria are capable of maintaining infections in hosts,
even in the presence of inflammatory and specific antimicrobial mech-
anisms as well as a perfectly good immune response (Table 7.4). Even
though they are infected, some people with persistent infections show
no clinical signs of the disease. Mycobacterium tuberculosis, Salmonella
enterica serovar Typhi, and Helicobacter pylori are good examples of bac-
teria that can cause persistent infections, and there are many questions as
to how a persistent infection can occur in spite of the innate and adaptive
immune responses of the host. In an effort to understand this, let’s look at
two examples of persistent infections: tuberculosis and typhoid fever.

Tuberculosis is one of the oldest known diseases and affects one-third of

the world’s population. The infection starts at a site in a lung and can move
throughout the lung. It is interesting to note that there is some evidence
that this movement is performed by dendritic cells that are part of the host
defense. Most people resolve infections with Mycobacterium tuberculosis
after the onset of the adaptive immune response, but in some individuals
 DEVELOPMENT OF DISEASE 123

Pathogen Disease Site of Persistence

Mycobacterium Tuberculosis Granulomas and in other sites in

tuberculosis macrophages

Salmonella enterica Typhoid fever Macrophages in the bone marrow

serovar Typhi and possibly the gall bladder

Chlamydia species 2ESPIRATORYANDCARDIOVASCULARDISEASETRACHOMAGENITAL Epithelial and endothelial cells

tract infections and Lymphogranuloma venereum

Helicobacter pylori Gastritis, ulcers, and gastric cancer Extracellular and possibly
intracellular in the stomach

Neisseria Genital tract infection, which can lead to pelvic %XTRACELLULARINTRACELLULARAT

gonorrhoeae inflammatory disease and infertility mucosal sites

Streptococcus 0NEUMONIAACUTEOTITISMEDIAMENINGITIS Nasopharynx

pneumoniae

Streptococcus !CUTETONSILLITISPNEUMONIAENDOCARDITISNECROTIZING Nasopharynx

pyogenes fasciitis

Haemophilus 0NEUMONIAMENINGITIS Nasopharynx

influenzae type B

the organisms are never completely cleared. Persistently infected hosts Table 7.4 Selected Persistent
can harbor the pathogens for life, and in some cases the tuberculosis is Infections in Humans
reactivated later in life. This reactivation usually occurs in patients who
have become immunocompromised through the aging process. It is for
this reason that tuberculosis is seen in so many nursing homes.

In persistent tuberculosis infections, pathogens survive inside granulo-

mas, which are bodies made up of host defensive cells, such as macro-
phages, T cells, B cells, dendritic cells, neutrophils, fibroblasts, and matrix
components (Figure 7.4). Granulomas form as activated macrophages
aggregate into gigantic cells similar to the syncytia seen in viral infec-
tions. The question is: How do the pathogens survive initial contact with
cells that are programmed to phagocytose and kill them? This process is
not completely understood, but it seems that the Mycobacterium tuber-
culosis organism gets taken into a phagosome in the normal fashion but
then “remodels” this structure and prevents the development of an acidic,
hydrolytic environment. In addition, the pathogens inhibit the formation
of phagolysosomes by preventing the fusion of the phagosome with cel-
lular lysosomes. Several genes have been identified in M. tuberculosis and
seem to be involved in this process, but the events remain to be com-
pletely worked out.

Figure 7.4 Gross pathology of human

lung tissue granuloma removed during
resection surgery. The arrow indicates a
granuloma.
124 Chapter 7 Priciples of Disease
Figure 7.5 A schematic representation
of persistent Salmonella infection in
humans caused by Salmonella enterica
serovar Typhi. Bacteria enter the intestinal
tract by invading M cells (which are
cells that are specifically localized in the
digestive tract). This invasion is followed
by inflammation, phagocytosis of bacteria
by neutrophils and macrophages, and
recruitment of immune T and B cells. In
typhoid fever, Salmonella may use dendritic
cells to disseminate to lymph nodes and
deep tissues, which can lead to transport of
the pathogens to the spleen, bone marrow,
liver, and gall bladder. Re-infection and
transmission occur by way of pathogens
that are released from the gall bladder and
re-enter the digestive system with bile.
ingestion
Peyer’s
patch
T cell
mesenteric
lymph node
gall
bladder spleen
liver
Typhoid fever is caused by Salmonella enterica serovar Typhi and can
cause a variety of problems in the intestinal tract, such as localized gas-
tritis. However, if this pathogen becomes systemic, it can cause typhoid
fever. This disease starts with a localized infection and inflammatory
response, usually in connection with Peyer’s patches in the intestine. The
Salmonella infect the phagocytic cells in the lamina propria of the intes-
tine and gain access to the blood and lymph. Once in those liquids, they
can spread to the liver and spleen and can become persistent in the gall
bladder and bone marrow (Figure 7.5).
Salmonella infection is a major public health problem and is endemic in
regions of the world in which there are unclean water supplies and a
general lack of sanitation. It is also difficult to treat because the level of
antibiotic resistance is rising. Between one and six per cent of people
infected with Salmonella enterica serovar Typhi will become carriers who
will shed large numbers of pathogens in their stool and urine for the rest
of their lives but will never show symptoms of the infection (remember
Mary from Chapter 1). The process by which Salmonella survives the host
defensive response seems to be similar to the process by which Mycobac-
terium does: the invaders are phagocytosed, but the phagosomes never
join with lysosomes to form phagolysosomes.
It is important to remember that several other mechanisms are used by
pathogenic bacteria to survive a host’s defensive responses and cause
persistent infection. Some pathogens evade the innate response by enzy-
matically destroying the antimicrobial toxin nitric oxide as it is produced.
Others, such as Helicobacter pylori, form megasomes inside a host mac-
rophage by fusing together many phagosomes. Megasomes seem to pro-
tect the pathogens even though they are inside a phagocytic cell, but the
reasons for this protection are still unclear. Some persistent pathogens
subvert the adaptive immune response by blocking the activation of T
bacteria
M cell epithelial cell shedding
neutrophil
B cell
dendritic
cell
mesenteric movement of
lymph node pathogen via bile
gall
bone liver bladder
marrow
B cell T cell infected macrophage
 THE SCOPE OF INFECTIONS 125

cells, whereas others take advantage of genetic diversity (similar to that

seen in influenza virus) to confuse the adaptive immune response. In
fact, some pathogens change the level and type of lipopolysaccharide on
their cells so that it will not bind as well to receptors on defensive cells,
thereby lessening the host response against them.

Herd Immunity
One of the most important aspects of infection and the spread of infec-
tion is herd immunity, illustrated in Figure 7.6. This immunity can be
conferred through vaccination or developed after infection. Let’s look at
smallpox as a way of understanding this concept. In years past, smallpox
was a dangerous killer and had a hand in wiping out thousands. When
a vaccination against the disease was developed and given widely, the
population became immune to this infection. (Many older people carry
the vaccination mark on an arm.) When the population had become
immune, the disease essentially disappeared because there were no more
potential hosts in the “herd”. When smallpox was no longer a problem,
vaccinations stopped. As a result, there are now lots of potential (non-
vaccinated) targets in the herd and the infection can spread once again.

Herd immunity is a major and fundamental parameter for infectious dis-

eases. However, it also presents a socioeconomic problem. Should we
vaccinate against diseases that are no longer present in the population?
What about poliomyelitis, a disease that killed and crippled thousands in
the past but is today essentially nonexistent in the United States? What is
the herd immunity like for this disease? What would happen if we stopped
vaccinating against it? Keep in mind that polio is still prevalent in other
countries in the world and therefore could resurface here at any time.

THE SCOPE OF INFECTIONS

Infections can be local or systemic. In many cases the host defenses

wall off an infection and keep it a local infection, as occurs with boils
or abscesses. From a host defense perspective, these infections are the
easiest to deal with. However, when pathogens find a way to move from
their original location in a host, a point called the focus of infection, they Figure 7.6 Herd immunity. Notice
that the lower the percentage of immune
can become far more dangerous. An infection that has moved away from
individuals in the group, the greater is the
the focus of infection is called a systemic infection and is usually accom- number of potential targets and therefore
plished when pathogens gain access to the blood or lymph. Remember, the greater is the number of cases of
the blood and lymph go everywhere in the body and interact with all the disease.

infected susceptible immune

10% of the population is immune 50% of the population is immune 90% of the population is immune
126 Chapter 7 Priciples of Disease
Fast Fact
Sepsis is the most common cause of
death in hospital intensive care units,
and there are about 225,000 deaths
from sepsis each year in the United
States alone.
organs. Bacteria in the blood are called a bacteremia, and if organisms are
growing in the blood, the condition is referred to as a septicemia. When
bacterial toxins move through the blood, the condition is referred to as
toxemia, whereas viruses moving through the blood are called viremia.
Infections can also be primary, subclinical, or secondary. A primary
infection is the one causing the initial acute onset of symptoms, whereas
a subclinical infection is one in which symptoms do not appear even
though the infection is ongoing (for example, polio and hepatitis A). Even
though individuals with subclinical infections do not show signs of the
disease or feel any symptoms, they are carriers who can infect others.
A secondary infection is one that establishes itself in a host weakened
by some primary infection. Secondary infections, such as Pneumocystis
pneumonia, which is often seen in connection with AIDS, can be more
dangerous than the primary infection because they take advantage of the
weakened state of the host.
Toxic Shock and Sepsis
It is important that we take a minute here to discuss sepsis and toxic
shock. These are two distinctly different clinical situations that arise as
a result of infection. In toxic shock, there is massive leakage of plasma
from the circulation that causes the blood pressure to plummet. This con-
dition is fatal for between 30 and 70% of patients in which it occurs. It has
been shown that toxic shock is caused by the activation of neutrophils,
which occurs when the neutrophils come in contact with such bacte-
rial surface proteins as the M proteins found on streptococcal species.
In fact, when Streptococcus pyogenes begins to reproduce in the blood, it
can cause streptococcal toxic shock syndrome (STSS), a condition that
can rapidly cause death.
The mechanism by which STSS occurs is interesting and may provide
researchers with possible methods to prevent a negative outcome. The M
proteins of S. pyogenes are shed while the pathogens are growing in the
blood. These proteins then bind to the plasma protein fibrinogen, which
normally promotes clotting. The M protein–fibrinogen complexes then
bind to and activate neutrophils that begin to release potent inflamma-
tory molecules called heparin-binding proteins. It is these proteins that
induce dynamic changes in vascular permeability in the host, changes
that cause a rapid loss of fluids from the body, a catastrophic decrease in
blood pressure, and difficulty in ventilating the lungs. In fact, strains of
S. pyogenes that are rich in M proteins have been shown to be far more
virulent than those containing only small amounts of these proteins.
The dynamic changes in the host just described result in a state of shock for
the host. This type of shock is not the same as that seen in infections with
Gram-negative endotoxins, however. Although a similar rapid decrease in
blood pressure is seen with some Gram-negative endotoxins, the cause of
the decrease does not seem to be related to activated neutrophils.
Sepsis syndrome is a general term indicating the presence of either path-
ogenic organisms or their toxins in the blood. There are two categories of
sepsis: severe sepsis and acute septic shock. Severe sepsis is defined by
signs of systemic inflammation and organ dysfunction accompanied by
abnormal temperature, heart rate, respiratory rate, and leukocyte count
as well as elevated levels of liver enzymes and altered cerebral func-
tion. Severe sepsis kills slowly over several weeks, and autopsy shows
minimal tissue inflammation or necrosis. In contrast, acute septic shock
occurs suddenly, and patients can die within 24–48 hours. At autopsy
after acute septic shock, there is widespread indication of tissue inflam-
mation and cell damage.
 THE SCOPE OF INFECTIONS 127

Keep in Mind

s $ISEASECANBEACUTECHRONICORSUBACUTE

s ,ATENTDISEASEREMAINSINTHEHOSTAFTERSIGNSANDSYMPTOMSHAVE
disappeared but can be reactivated after long periods.
s 0ATHOGENSSUCHASMycobacterium tuberculosis can cause persistent
disease in which infections continue even though the host has a working
immune defense.
s (ERDIMMUNITYCANLIMITTHESPREADOFINFECTION
s )NFECTIONCANBELOCALIZEDORSYSTEMICANDCANBECLASSIlEDASPRIMARY
(with acute initial symptoms), subclinical (without symptoms), or secondary
(occurring after a primary infection).
s )NFECTIONCANRESULTINTOXICSHOCKORSEPSIS

SUMMARY

s .ORMALMICROBIALmORAHELPSTOPROTECTAGAINSTOPPORTUNISTICPATHOGENS
s %TIOLOGYISDElNEDASTHECAUSEOFADISEASE
s +OCHSPOSTULATESCANBEUSEDTOEVALUATEANDIDENTIFYTHEETIOLOGYOFADIS-
ease.
s $ISEASECANBEACUTECHRONICSUB ACUTEORLATENT
s )NFECTIONCANBELOCALORSYSTEMIC
s 2ELATIONSHIPSBETWEENBACTERIAANDHOSTSCANBEDESCRIBEDASCOMMENSAL
mutual, or parasitic.
s 4HEREARElVEPERIODSINTHEDEVELOPMENTOFANINFECTIONINCUBATIONPERIOD
prodromal period, period of disease, period of illness, and period of convales-
cence.
s #OMMUNICABLEDISEASESCANBESPREADFROMONEPERSONTOANOTHER
s #ONTAGIOUSDISEASESARESPREADONCONTACTWITHANINFECTEDPERSON
s (ERDIMMUNITYCANLIMITTHESPREADOFINFECTION
s )NFECTIONCANCAUSESEPTICSHOCKORSEPSIS
This chapter has taught us about how different infections get started, how
diseases can develop and be characterized, and how infections can spread
throughout the body. In addition, we learned about the importance of herd im-
munity and also about communicable and contagious diseases. Coupled with
Chapter 5 on the requirements for infection and Chapter 6 on the transmission
of infection, the material presented here completes our discussion of the infec-
tion process.
128 Chapter 7 Priciples of Disease

SELF EVALUATION AND CHAPTER CONFIDENCE

Multiple Choice
Answers are given in the back of the book and help can be found in the student resources at:
www.garlandscience.com/micro
1. Etiology refers to 6. The first mild symptoms of diseases are seen in the
A. Viral infection A. Illness period
B. The results seen after a disease occurs B. Decline period
C. The cause of the disease C. Prodromal period
D. The portal of exit D. Incubation period
E. None of the above E. None of the above

2. Microbial antagonism refers to 7. The period when major disease occurs is called the

A. An increase in bacterial metabolism A. Period of illness

B. A decrease in bacterial metabolism B. Period of decline
C. An increase in infection symptoms C. Prodromal period
D. Protection by normal bacterial flora D. Period of convalescence
E. Enhanced disease due to normal bacterial flora E. Major period

8. Chronic diseases
3. The relationship in which one partner benefits at the
expense of the other is called A. Develop quickly and subside quickly
B. Develop quickly but subside slowly
A. Mutualism
C. Develop slowly and subside quickly
B. Parasitism
D. Develop slowly and remain for a long time
C. Commensalism
E. Develop quickly and remain for a long time
D. Discordance
E. None of the above 9. Latent diseases

4. Koch’s postulates were the first to show the A. Develop quickly and subside quickly
B. Develop quickly and subside slowly
A. Portals of entry for pathogens into the body
C. Remain in the host only when symptoms are
B. Portals of exit for pathogens leaving the body present
C. Existence of exotoxins D. Remain in the host after symptoms have gone but
D. Etiology of viral infections are able to be reactivated
E. Etiology of bacterial infections E. Remain in the host after symptoms have gone but
5. The time between the initial infection and the onset of are never reactivated
symptoms is called the 10. Septicemia refers to pathogens growing in the
A. Disease period A. Focus of infection
B. Illness period B. Tissues
C. Incubation period C. Urinary tract
D. Prodromal period D. Blood
E. Decline period E. None of the above
 CLINICAL CORNER 129

DEPTH OF UNDERSTANDING
Questions listed here require you to bring together the concepts you
have learned in this chapter into a discussion format. This helps you to
increase your depth of understanding of the material you have learned.
Help can be found in the student resources at:
www.garlandscience.com/micro

1. Overuse of antibiotics can lead to antibiotic resistance and opportunistic

infections. Why would these problems occur when antibiotics are our first
choice for the treatment of bacterial infections?

2. There are three methods used to control communicable diseases. In

today’s world, which of them is most effective and why?

3. Tuberculosis has been referred to as both a persistent infection and a

re-emerging infection. Justify this duality of classification.

CLINICAL CORNER

Help can be found in the student resources at:

www.garlandscience.com/micro

1. Your patient is a 78-year-old male who is in the hospital because of a

serious bladder infection. He has been on antibiotic therapy for 4 days
and seems to be getting better. Although he says he feels better, he is
tired and not eating well. On the fifth day, you are surprised to find that
he has been transferred to the intensive care unit. The doctor informs
you that he has developed a severe upper respiratory infection and is in
a grave condition. How will you explain to his wife and family what has
happened?

2. Your neighbor has had frequent bouts of severe gastritis. She has been
to the doctor and was diagnosed with a salmonella infection each time.
After she was given antibiotics, the infection subsided but always seemed
to reoccur. Finally the doctor explained that she needed to have her
gall bladder removed. She is confused by all this and frightened by the
possibility of surgery.
A. How would you explain her condition to her?
B. Why does the doctor want to remove her gall bladder?
C. Why did the infection keep recurring even after antibiotic therapy?
3. Montrose elementary school is located in southern Florida, a region
that sees a seasonal influx of migrant workers who help during the fruit
picking season. Two weeks into the orange-picking season, there was an
outbreak of measles in the second grade. Of the 26 students, only 4 came
down with the infection and one of those was the daughter of a migrant
worker.
A. Explain why only four students got the measles.
B. Why did the daughter of the migrant workers get infected?
C. Why did the three other children who were not from migrant worker
families get sick?