Download Microbiology

Pathology, Infection, and Disease
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Pathology: the study of disease
Etiology: the study of the cause of a disease
Pathogenesis: the development of disease
Infection: colonization of the body by pathogens
Disease: an abnormal state in which the body is
not functioning normally
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Normal Microbiota and the Host
 Transient microbiota may be present for days,
weeks, or months
 Normal microbiota permanently colonize the host
 Symbiosis is the relationship between normal
microbiota and the host
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Figure 14.1 Representative normal microbiota for different regions of the body.
Bacteria (orange
spheres) on the surface of
the nasal epithelium
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Bacteria (brown)
on the lining of the stomach
Bacteria (orange)
in the small intestine
Symbiosis
 In commensalism, one organism benefits, and the
other is unaffected
 In mutualism, both organisms benefit
 In parasitism, one organism benefits at the
expense of the other
 Some normal microbiota are opportunistic
pathogens
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Table 14.1 Normal Microbiota on the Human Body
Eyes (conjunctiva)
Nose and throat
(upper respiratory
system)
Mouth
Skin
Large intestine
Urinary and
reproductive
systems (lower
urethra in both
sexes and vagina
in females)
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Normal Microbiota and the Host
 Microbial antagonism is a competition between
microbes
 Normal microbiota protect the host by
 Occupying niches that pathogens might occupy
 Producing acids
 Producing bacteriocins
 Probiotics: live microbes applied to or ingested
into the body, intended to exert a beneficial effect
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Koch’s Postulates
1. The same pathogen must be present in every
case of the disease.
2. The pathogen must be isolated from the diseased
host and grown in pure culture.
3. The pathogen from the pure culture must cause
the disease when it is inoculated into a healthy,
susceptible laboratory animal.
4. The pathogen must be isolated from the
inoculated animal and must be shown to be the
original organism.
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Figure 14.3 Koch’s Postulates: Understanding Disease.
1 Microorganisms are
isolated from a diseased
or dead animal.
2a The microorganisms are
grown in pure culture.
3 The microorganisms
are injected into a healthy
laboratory animal.
Colony
2b The microorganisms
are identified.
4 Disease is reproduced
in a laboratory animal.
5a The microorganisms are
isolated from this animal
and grown in pure culture.
5b Microorganisms
are identified.
The microorganism from the
diseased host caused the same
disease in a laboratory host.
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Koch’s Postulates
 Koch’s postulates are used to prove the cause of
an infectious disease
 Some pathogens can cause several disease conditions
 Some pathogens cause disease only in humans
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Classifying Infectious Diseases
 Symptom: a change in body function that is felt by
a patient as a result of disease
 Sign: a change in a body that can be measured or
observed as a result of disease
 Syndrome: a specific group of signs and
symptoms that accompany a disease
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Classifying Infectious Diseases
 Communicable disease: a disease that is spread
from one host to another
 Contagious disease: a disease that is easily
spread from one host to another
 Noncommunicable disease: a disease that is not
transmitted from one host to another
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Occurrence of a Disease
 Incidence: fraction of a population that contracts a
disease during a specific time
 Prevalence: fraction of a population having a
specific disease at a given time
 Sporadic disease: disease that occurs
occasionally in a population
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Occurrence of a Disease
 Endemic disease: disease constantly present in a
population
 Epidemic disease: disease acquired by many
hosts in a given area in a short time
 Pandemic disease: worldwide epidemic
 Herd immunity: immunity in most of a population
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Figure 14.4 Reported AIDS cases in the United States.
Number of cases
120,000
Second
250,000
cases
First 250,000 cases
Third
250,000
cases
Fourth
250,000
Cases
100,000
80,000
Expansion of
surveillance
case definition
60,000
40,000
20,000
0
1979
1983
1987
1991
1995
Year
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1999
2003
2007
Severity or Duration of a Disease
 Acute disease: symptoms develop rapidly
 Chronic disease: disease develops slowly
 Subacute disease: symptoms between acute
and chronic
 Latent disease: disease with a period of no
symptoms when the causative agent is inactive
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Extent of Host Involvement
 Local infection: pathogens are limited to a small
area of the body
 Systemic infection: an infection throughout the
body
 Focal infection: systemic infection that began as a
local infection
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Extent of Host Involvement
 Sepsis: toxic inflammatory condition arising from
the spread of microbes, especially bacteria or their
toxins, from a focus of infection
 Bacteremia: bacteria in the blood
 Septicemia: growth of bacteria in the blood
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Extent of Host Involvement
 Toxemia: toxins in the blood
 Viremia: viruses in the blood
 Primary infection: acute infection that causes the
initial illness
 Secondary infection: opportunistic infection after a
primary (predisposing) infection
 Subclinical disease: no noticeable signs or
symptoms (inapparent infection)
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Predisposing Factors
 Make the body more susceptible to disease
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Short urethra in females
Inherited traits, such as the sickle cell gene
Climate and weather
Fatigue
Age
Lifestyle
Chemotherapy
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Time
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Period of
illness
Period of
decline
Most severe signs
and symptoms
Signs and
symptoms
Period of convalescence
Prodromal period (mild signs or symptoms)
Incubation period (no signs or symptoms)
Number of microbes
Figure 14.5 The stages of a disease.
Reservoirs of Infection
 Continual sources of infection
 Human: AIDS, gonorrhea
 Carriers may have inapparent infections
or latent diseases
 Animal: rabies, Lyme disease
 Some zoonoses may be transmitted to humans
 Nonliving: botulism, tetanus
 Soil
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Transmission of Disease
 Contact
 Direct: requires close association between infected and
susceptible host
 Indirect: spread by fomites
 Droplet: transmission via airborne droplets
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Figure 14.6ad Contact transmission.
Direct contact transmission
Droplet transmission
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Vehicle Transmission
 Transmission by an inanimate reservoir
(food, water, air)
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Figure 14.7 Vehicle transmission.
Water
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Food
Air
Vectors
 Arthropods, especially fleas, ticks, and mosquitoes
 Transmit disease by two general methods:
 Mechanical transmission: arthropod carries pathogen
on feet
 Biological transmission: pathogen reproduces in vector
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Figure 14.8 Mechanical transmission.
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Figure 12.31 Mosquito.
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Nosocomial Infections
 Are acquired as a result of a hospital stay
 Affect 5–15% of all hospital patients
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Figure 14.6b Contact transmission.
Preventing direct contact transmission through the use of gloves, masks, and face
shields
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Figure 14.9 Nosocomial infections.
Microorganisms
in hospital
environment
Compromised
host
Nosocomial
infection
Chain of transmission
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Common Causes of Nosocomial
Infections
Coagulase-negative
staphylococci
S. aureus
15%
Percentage
Resistant to
Antibiotics
89%
15%
80%
Enterococcus
10%
4–71%
15–25%
3–32%
13%
Not reported
Percentage of
Total Infections
Gram-negative rods
C. difficile
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MRSA
 USA100: 92% of health care strains
 USA300: 89% of community-acquired strains
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Emerging Infectious Diseases
 Diseases that are new, increasing in incidence, or
showing a potential to increase in the near future
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Emerging Infectious Diseases
 Contributing factors
 Genetic recombination
 E. coli O157, avian influenza (H5N1)
 Evolution of new strains
 V. cholerae O139
 Inappropriate use of antibiotics and pesticides
 Antibiotic-resistant strains
 Changes in weather patterns
 Hantavirus
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Emerging Infectious Diseases
 Modern transportation
 West Nile virus
 Ecological disaster, war, and expanding human
settlement
 Coccidioidomycosis
 Animal control measures
 Lyme disease
 Public health failure
 Diphtheria
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Clinical Focus 13.1 Influenza: Crossing the Species Barrier
Avian
gene pool
1918 H1N1
Human H3N2
North American swine
Triple reassortment
H1N2
Eurasian
swine H1N1
2009 H1N1 pandemic
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Epidemiology
 The study of where and when diseases occur
 Centers for Disease Control and Prevention
(CDC)
 Collects and analyzes epidemiological information in the
United States
 Publishes Morbidity and Mortality Weekly Report
(MMWR)
 www.cdc.gov
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Epidemiology
John Snow
1848–1849
Mapped the occurrence of
cholera in London
Ignaz Semmelweis 1846–1848
Showed that handwashing
decreased the incidence of
puerperal fever
Florence
Nightingale
Showed that improved
sanitation decreased the
incidence of epidemic
typhus
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1858
Epidemiology
 Descriptive: collection and analysis of data
 Snow
 Analytical: comparison of a diseased group and a
healthy group
 Nightingale
 Experimental: controlled experiments
 Semmelweis
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Epidemiology
 Case reporting: health care workers report
specified disease to local, state, and national
offices
 Nationally notifiable diseases: physicians are
required to report occurrence
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The CDC
 Morbidity: incidence of a specific notifiable disease
 Mortality: deaths from notifiable diseases
 Morbidity rate: number of people affected in
relation to the total population in a given time period
 Mortality rate: number of deaths from a disease in
relation to the population in a given time
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Figure 14.10 a & b Epidemiological graphs.
40,000
Number of reported cases
35,000
30,000
25,000
20,000
15,000
10,000
5,000
0
1999
2000
2001
2002
2003
2004
2005
Apr
May
Jun
Jul
Month
2006
2007
2008
2009
2010
(a) Lyme disease cases, 1999–2010
600
Reported cases per
100,000 people
500
400
300
200
100
0
Jan
Feb
(b) Lyme disease by month, 2009
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Mar
Aug
Sep
Oct
Nov
Dec
Figure 14.10c Epidemiological graphs.
Reported cases per
100,000 people
120
100
80
60
40
20
0
1948
1958
1968
1978
Year
Reported tuberculosis cases, 1948–2010
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1988
1998
2008
Mechanisms of Pathogenicity
 Pathogenicity: the ability to cause disease
 Virulence: the extent of pathogenicity
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Portals of Entry
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Mucous membranes
Skin
Parenteral route
Preferred portal of entry
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Numbers of Invading Microbes
 ID50: infectious dose for 50% of the test
population
 LD50: lethal dose (of a toxin) for 50% of the test
population
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Bacillus anthracis
Portal of Entry
Skin
ID50
10–50 endospores
Inhalation
10,000–20,000 endospores
Ingestion
250,000–1,000,000
endospores
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Toxins
Portal of Entry
Botulinum
Shiga toxin
Staphylococcal enterotoxin
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ID50
0.03 ng/kg
250 ng/kg
1350 ng/kg
Adherence
 Adhesins/ligands bind to receptors on host cells
 Glycocalyx: Streptococcus mutans
 Fimbriae: Escherichia coli
 M protein: Streptococcus pyogenes
 Form biofilms
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Figure 15.1a Adherence.
Adhesin (ligand)
Pathogen
Host
cell
surface
Receptor
Surface molecules on a pathogen, called adhesins or ligands, bind specifically to complementary surface
receptors on cells of certain host tissues.
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Figure 15.1b-c Adherence.
E. coli bacteria (yellow-green) on
human urinary bladder cells
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Bacteria (purple) adhering to
human skin
Capsules
 Prevent phagocytosis
 Streptococcus pneumoniae
 Haemophilus influenzae
 Bacillus anthracis
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Cell Wall Components
 M protein resists phagocytosis
 Streptococcus pyogenes
 Opa protein inhibits T helper cells
 Neisseria gonorrhoeae
 Mycolic acid (waxy lipid) resists digestion
 Mycobacterium tuberculosis
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Enzymes
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Coagulase: coagulates fibrinogen
Kinases: digest fibrin clots
Hyaluronidase: hydrolyzes hyaluronic acid
Collagenase: hydrolyzes collagen
IgA proteases: destroy IgA antibodies
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Penetration into the Host Cell
Cytoskeleton
 Invasins
 Salmonella alters host actin to enter a host cell
 Use actin to move from one cell to the next
 Listeria
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Figure 21.12 Cold sores, or fever blisters, caused by herpes simplex virus.
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Direct Damage
 Disrupt host cell function
 Produce waste products
 Toxins
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The Production of Toxins
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Toxin: substance that contributes to pathogenicity
Toxigenicity: ability to produce a toxin
Toxemia: presence of toxin in the host’s blood
Toxoid: inactivated toxin used in a vaccine
Antitoxin: antibodies against a specific toxin
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Figure 15.4 Mechanisms of Exotoxins and Endotoxins.
exotoxins
endotoxins
Exotoxins are proteins produced inside
pathogenic bacteria, most commonly grampositive bacteria, as part of their growth and
metabolism. The exotoxins are then
secreted into the surrounding medium
during log phase.
Endotoxins are the lipid portions of
lipopolysaccharides (LPS) that are part of
the outer membrane of the cell wall of gramnegative bacteria (lipid A; see Figure 4.13c).
The endotoxins are liberated when the
bacteria die and the cell wall breaks apart.
Cell wall
Exotoxin: toxic
substances released
outside the cell
Clostridium botulinum,
an example of a grampositive bacterium that
produces exotoxins
Salmonella typhimurium,
an example of a gramnegative bacterium that
produces endotoxins
Endotoxins: toxins
composed of lipids
that are part of the
cell membrane
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Exotoxins
 Specific for a structure or function in host cell
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Figure 15.5 The action of an A-B exotoxin.
DNA
Exotoxin
mRNA
A (active)
A
B (binding) B
1
Bacterium
produces and
releases exotoxin.
2
B (binding)
component of
exotoxin attaches
to host cell
receptor.
3
A-B exotoxin
enters host cell
by receptormediated
endocytosis.
4
A-B exotoxin
enclosed in
pinched-off
portion of plasma
membrane during
pinocytosis.
5
A-B components of
exotoxin separate.
The A component
alters cell function
by inhibiting
protein synthesis.
The B component
is released from
the host cell.
Exotoxin
polypeptides
Bacterium
A
B
Receptor
Plasma
membrane
Nucleus
Cytoplasm
Host cell
A
B
A
B
A
B
B
A
Protein
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Membrane-Disrupting Toxins
 Lyse host’s cells by
 Making protein channels in the plasma
membrane
– Leukocidins
– Hemolysins
– Streptolysins
 Disrupting phospholipid bilayer
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Superantigens
 Cause an intense immune response due to release
of cytokines from host cells
 Symptoms: fever, nausea, vomiting, diarrhea,
shock, and death
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Exotoxin
Source
Relation to microbe
Chemistry
Mostly gram-positive
By-products of growing cell
Protein
Fever?
No
Neutralized by antitoxin?
Yes
LD50
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Small
Exotoxins and Lysogenic Conversion
Exotoxin
Corynebacterium
diphtheriae
A-B toxin
Lysogeny
+
Streptococcus
pyogenes
Membrane-disrupting
erythrogenic toxin
+
Clostridium botulinum
A-B toxin; neurotoxin
+
C. tetani
A-B toxin; neurotoxin
Vibrio cholerae
A-B toxin; enterotoxin
+
Staphylococcus
aureus
Superantigen
+
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Endotoxins
Source
Relation to Microbe
Chemistry
Gram-negative
Outer membrane
Lipid A
Fever?
Yes
Neutralized by Antitoxin?
No
LD50
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Relatively large
Figure 15.6 Endotoxins and the pyrogenic response.
Macrophage
Nucleus
Endotoxin
Endotoxin
Hypothalamus of brain
Prostaglandin
Cytokines
Fever
Blood
vessel
Vacuole
Pituitary
gland
Bacterium
1
A macrophage ingests
a gram-negative
bacterium.
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2
The bacterium is
degraded in a vacuole,
releasing endotoxins
that induce the
macrophage to
produce cytokines IL-1
and TNF-.
3
4
The cytokines are
released into the
bloodstream by the
macrophages,
through which they
travel to the
hypothalamus of the
brain.
The cytokines induce
the hypothalamus to
produce prostaglandins,
which reset the body’s
“thermostat” to a
higher temperature,
producing fever.
Portals of Exit
 Respiratory tract
 Coughing and sneezing
 Gastrointestinal tract
 Feces and saliva
 Genitourinary tract
 Urine and vaginal secretions
 Skin
 Blood
 Arthropods that bite; needles or syringes
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Figure 15.9 Microbial Mechanisms of Pathogenicity.
When the balance between host and microbe is tipped in favor of the
microbe, an infection or disease results. Learning these mechanisms of
microbial pathogenicity is fundamental to understanding how pathogens
are able to overcome the host’s defenses.
H1N1 flu virus
portals of entry
Mucous membranes
• Respiratory tract
• Gastrointestinal tract
• Genitourinary tract
• Conjunctiva
Skin
Parenteral route
Number of
invading
microbes
penetration
or evasion of
host defenses
Capsules
Cell wall components
Enzymes
Antigenic variation
Invasins
Intracellular growth
Adherence
Mycobacterium
intracellulare
Clostridium
tetani
Micrographs
are not shown
to scale.
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damage to
host cells
Siderophores
Direct damage
Toxins
• Exotoxins
• Endotoxins
Lysogenic conversion
Cytopathic effects
portals of exit
Generally the same as
the portals of entry for a
given microbe:
• Mucous membranes
• Skin
• Parenteral route