CHAPTER 7

PRINCIPLES OF DISEASE

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WHY IS THIS IMPORTANT?

¿ How diseases are caused (etiology), how they

can be characterized, and the concepts of
sepsis and shock are important for developing
an in-depth understanding of infections
¿ It is important to understand the differences
between normal microbial flora and abnormal
or infectious microbial organisms

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WHY IS THIS IMPORTANT?

¿ Understanding how diseases develop will help

you to understand the communicability and
contagiousness of microorganisms
¿ Understanding the etiology of a disease is
critical to understanding the progression of
disease into systemic circulation

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 OVERVIEW

Principles of Disease

THE RELATIONSHIP BETWEEN THE ETIOLOGY DEVELOPMENT THE SCOPE OF

THE HUMAN HOST AND OF DISEASE OF DISEASE INFECTIONS
MICROORGANIMS

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USEFUL DEFINITIONS

¿ A disease is any damage to the host (patient)

¿ Etiology is the cause of a disease
¿ Normal microbial flora (the microbiota of
humans) are the useful microorganisms found
in the body

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COMMON TERMS FOR

DESCRIBING INFECTION

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 THE HUMAN MICROBIOME
¿ Humans are ecosystems, called a superorganism
¿ In a healthy adult microbial cells can make up as
much as five pounds of adult body weight
¿ The human microbiome:

¿ Includes the microbes inhabiting us, their genetic

information (called metagenome), and the
environment in which they interact
¿ Affects our development, physiology, immunity,
and nutrition

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NORMAL MICROBIAL FLORA

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HOST-MICROORGANISM
RELATIONSHIPS

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 HOST RELATIONSHIPS

¿ Microbial flora can protect us through

microbial antagonism
¿ Many bacteria produce bacteriocins which are
localized bacterial antibiotics
¿ Bacteriocins can kill invading organisms but do
not affect the bacteria that produce them

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HOST RELATIONSHIPS

¿ Opportunistic pathogenicity occurs when

normal flora become pathogenic
¿ E. coli is part of the normal flora of the digestive
tract but can cause infection if it enters the urinary
tract

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HOST RELATIONSHIPS
¿ The microbiome composition
¿ Varies from person to person
¿ Naturally depends on the site of the body
¿ Fluctuates due to dietary change, seasonal change, hormonal
change, and exposure to antibiotics
¿ Possibly imparts susceptibility to certain infectious diseases
¿ Could contribute to obesity, diabetes, atherosclerosis, autism,
allergies, and asthma, chronic gastrointestinal diseases, can
affect response to drug treatment, and even choice of partner
¿ The delivery mode and the mother’s microbiome may
affect the child’s microbiota and health
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 MICROBIOME OF VARIOUS
ANATOMICAL SITES

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MICROBIOME IN
NEWBORNS

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THE ETIOLOGY OF DISEASE

¿ Etiology is the cause of disease

¿ Proof of etiology can be found using Koch’s
postulates
¿ Allow us to identify the cause of a disease

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 THE ETIOLOGY OF DISEASE

¿ In some cases, we need to adapt the tests

when using Koch’s postulates in our
modern times, because some organisms
cannot be grown in pure culture:
¿ Treponema pallidum (syphilis)
¿ Mycobacterium leprae (leprosy)
¿ Viruses and rickettsial organisms

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THE ETIOLOGY OF DISEASE

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THE ETIOLOGY OF DISEASE

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 FIVE PERIODS OF DISEASE

¿ Incubation period – the time between the initial

infection and the first symptoms. The more
virulent the pathogen, the shorter the
incubation time
¿ Prodromal period – first mild symptoms
appear

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FIVE PERIODS OF DISEASE

¿ Period of illness – the majority of symptoms
manifest and when the immune response is at
its highest level
¿ Period of decline – symptoms subside. During
the period, secondary nosocomial infections
can occur of a nature more serious than the
original infection
¿ Period of convalescence – the patient actively
regains strength and returns to health
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DEVELOPMENT OF DISEASE

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 COMMUNICABLE AND
CONTAGIOUS DISEASES
¿ Some diseases are communicable
¿ They can spread from one person to another
¿ Some diseases are not communicable
¿ They cannot spread from one person to another
and simply remain within the infected host
¿ Some communicable diseases are easily spread
from person to person and these are referred to
as being contagious
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COMMUNICABLE & CONTAGIOUS

DISEASES: Three Methods of Control

¿ First method – Isolation:

¿ It prevents an infected individual from having
contact with the general population
¿ There are seven categories of isolation
¿ Patients are usually isolated in hospital
¿ Can be difficult to achieve as it cannot be imposed
until firm diagnosis

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COMMUNICABLE & CONTAGIOUS

DISEASES: Three Methods of Control

¿ Second method – Quarantine:

¿ Exposed humans or animals are separated from the
general population
¿ Lasts as long as the incubation period for the
disease in question
¿ If there are no longer any symptoms, the
quarantine is lifted
¿ Rarely used today because it is difficult to enforce

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 COMMUNICABLE & CONTAGIOUS
DISEASES: Three Methods of Control

¿ Third method – Vector Control:

¿ It is used to control the population of vectors, such
as mosquitoes, that carry pathogens

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DURATION OF DISEASE
¿ Disease duration can vary depending on the overall
health of the host
¿ There are four categories of disease duration:
¿ Acute diseases develop quickly and last only a short time
e.g. measles
¿ Chronic diseases develop slowly but last for a long time
e.g. tuberculosis
¿ Sub-acute diseases have an insidious onset (usually 6–12
months) and are almost always fatal e.g. sclerosing pan-
encephalitis
¿ Latent diseases remain in the host after the symptoms
disappear and can become reactivated years later e.g.
chicken pox/shingles
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PERSISTENT BACTERIAL
INFECTIONS

¿ Some pathogenic bacteria are capable of

maintaining infections in hosts, even in the
presence of inflammatory and specific
antimicrobial mechanisms as well as a
perfectly good immune response
¿ Persistent bacterial infections are treated with
specific antimicrobial therapy

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 PERSISTENT BACTERIAL
INFECTIONS
¿ Examples of persistent bacterial infections
include:
¿ Mycobacterium tuberculosis (causes tuberculosis)
¿ Salmonella enterica serovar Typhi (causes typhoid
fever)
¿ Helicobacter pylori (causes stomach and duodenal
ulcers)
¿ Neisseria gonorrhoeae (causes gonorrhea)

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TUBERCULOSIS (TB)

¿ TB 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, possibly via host
defense cells
¿ Most people resolve the infection after the
onset of the adaptive immune response

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TUBERCULOSIS (TB)

¿ Some hosts become persistently infected and

harbor the pathogen for life
¿ It can then be reactivated later in life, with
reactivation usually associated with a diminished
immune response
¿ In persistent TB, the pathogen is found inside
granulomas

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 TUBERCULOSIS (TB)

¿ Granulomas are composed of host defensive

cells including:
¿ Macrophages, T cells, B cells, dendritic cells,
neutrophils, and fibroblasts
¿ Granulomas form as activated macrophages
and aggregate into gigantic cells similar to the
syncytia seen in viral infections

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TUBERCULOSIS (TB)

Macmillan Publishers, Ltd. Nature Review of Microbiology 3:71, © (2005)

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TYPHOID FEVER

¿ Typhoid fever is caused by Salmonella

enterica serovar Typhi and can cause a variety
of problems in the intestinal tract
¿ It begins as a localized infection that
eventually becomes systemic
¿ The localized infection elicits an inflammatory
reaction

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 TYPHOID FEVER
¿ The pathogen infects macrophages in the
lamina propria of the intestine and can then
gain access to the blood and the lymph
¿ Once the infection is the blood and lymph, it
can spread to the liver and spleen and can
become persistent in the gall bladder and bone
marrow
¿ Typhoid fever is difficult to treat because the
level of antibiotic resistance is rising

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TYPHOID FEVER

¿ One in six people who contract typhoid fever

will become carriers and shed off large
numbers of the pathogens in their stool and
urine
¿ Salmonella organisms are phagocytozed by the
host cell defenses but are not destroyed

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TYPHOID FEVER

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 PATHOGENS USE SPECIFIC MECHANISMS
TO SURVIVE HOST DEFENSES

¿ Mycobacterium and Salmonella prevent

formation of the phagolysosome
¿ Some pathogens:
¿ Produce enzymes that destroy nitric oxide as it is
produced by the host
¿ Form megasomes inside host cells which prevent
the host enzymes from reaching the pathogens
¿ Block the adaptive immune response of the host
¿ Use genetic diversity to confuse the host defenses
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THE SCOPE OF INFECTIONS

¿ Infections can be localized

¿ A local infection is contained (walled off) such as
a boil or an abscess
¿ Local infections are the easiest to deal with
medically

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THE SCOPE OF INFECTIONS

¿ Infections can be systemic

¿ Systemic infections occur when pathogens move
away from the initial infection location (also
known as the focus of infection)
¿ This movement is usually associated with the
blood or the lymphatic system

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 TERMS RELATED TO
SYSTEMIC INFECTIONS

¿ Bacteremia – bacteria in the blood

¿ Septicemia – bacteria growing in the blood
¿ Toxemia – toxins in the blood
¿ Viremia – viruses in the blood

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THREE TYPES OF INFECTION

¿ Primary – the initial infection which has acute

onset of symptoms
¿ Subclinical – no symptoms are visible even
though the person is infected
¿ These people are carriers of the disease and can
infect others
¿ Secondary – seen in people that are already
weakened from a primary infection and can be
more dangerous
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TOXIC SHOCK AND SEPSIS

¿ Toxic shock and sepsis are two different clinical
situations that can result from infection
¿ Toxic shock is a massive leakage of plasma from
the circulatory system
¿ This causes a dramatic drop in blood pressure
(hypotension)
¿ It is fatal for 30–70% of patients
¿ It is caused when neutrophils come in contact with
bacterial surface proteins such M proteins
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 TOXIC SHOCK AND SEPSIS

¿ Sepsis is a general term referring to the

presence of the pathogen or toxin in the blood
¿ There are two forms of sepsis:
¿ Severe sepsis
¿ Acute septic shock

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TOXIC SHOCK AND SEPSIS

¿ Severe sepsis is characterized by systemic

inflammation and organ dysfunction
¿ It is accompanied by abnormal temperature, heart
rate, respiratory rate, and white blood cell count
¿ It induces elevated numbers of liver enzymes and
altered cerebral function
¿ Severe sepsis kills slowly over a period of weeks
with minimal tissue inflammation or damage

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TOXIC SHOCK AND SEPSIS

¿ Acute septic shock has a sudden onset and

death occurs in 24–48 hours
¿ It causes widespread tissue inflammation and cell
damage

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