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Chapter 24
Microbial
Diseases of the
Respiratory
System
© 2013 Pearson Education, Inc.
Copyright © 2013 Pearson Education, Inc.
Lectures prepared by Christine L. Case
Lectures prepared by Christine L. Case
© 2013 Pearson Education, Inc.
Figure 24.1 Structures of the upper respiratory system.
Sinus
Sinus
Nasal cavity
Oral cavity
Tongue
Epiglottis
Layrnx
(voice box)
Trachea (windpipe)
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Middle ear
Auditory
(eustachian)
tube
Opening of
auditory tube
Tonsils
Pharynx (throat)
Spine
(backbone)
Esophagus
Figure 24.2 Structures of the lower respiratory system.
Bronchiole
Branch from
the pulmonary
vein
Pharynx
(throat)
Larynx (voice
box)
Branch
from the
pulmonary
artery
Blood
capillaries
Left lung
Trachea
(windpipe)
Right lung
Alveoli
Bronchus
Bronchiole
Pleura
Diaphragm
(breathing
muscle)
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Heart
Normal Microbiota of the Respiratory
System
 Suppress pathogens by competitive inhibition in
upper respiratory system
 Lower respiratory system is sterile
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Upper Respiratory System Diseases


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

Pharyngitis
Laryngitis
Tonsillitis
Sinusitis
Epiglottitis: H. influenzae type b
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Streptococcal Pharyngitis



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


Also called strep throat
Streptococcus pyogenes
Resistant to phagocytosis
Streptokinases lyse clots
Streptolysins are cytotoxic
Diagnosis by enzyme immunoassay (EIA) tests
Scarlet fever
 Erythrogenic toxin produced by lysogenized S. pyogenes
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Figure 24.3 Streptococcal pharyngitis.
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Figure 24.4 Corynebacterium diphtheriae, the cause of diphtheria.
Clubbed cells
Palisade
arrangement
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Figure 24.5 A diphtheria membrane.
Membrane
on tonsils
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Diphtheria
 Corynebacterium diphtheriae: gram-positive rod
 Diphtheria toxin produced by lysogenized
C. diphtheriae
 Prevented by DTaP vaccine
 Diphtheria toxoid
 Cutaneous diphtheria
 Infected skin wound leads to slow-healing ulcer
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Otitis Media



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

S. pneumoniae (35%)
H. influenzae (20–30%)
M. catarrhalis (10–15%)
S. pyogenes (8–10%)
S. aureus (1–2%)
Incidence of S. pneumoniae reduced by vaccine
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Figure 24.6 Acute otitis media, with bulging eardrum.
Bulging
eardrum
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The Common Cold
 Rhinoviruses (30–50%)
 Coronaviruses (10–15%)
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Diseases in Focus: Diseases of the
Upper Respiratory System
 A patient presents with fever and a red, sore throat.
Later, a grayish membrane appears in the throat.
Gram-positive rods are cultured from the membrane.
 Can you identify infections that could cause these
symptoms?
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Diseases in Focus: Microbial Diseases of the Upper Respiratory System
Characteristic swollen lymph nodes of this disease.
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Lower Respiratory System Diseases
 Bacteria, viruses, and fungi cause
 Bronchitis
 Bronchiolitis
 Pneumonia
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Pertussis (Whooping Cough)
 Bordetella pertussis
 Gram-negative coccobacillus
 Capsule
 Tracheal cytotoxin of cell wall damages ciliated
cells
 Pertussis toxin
 Prevented by DTaP vaccine (acellular Pertussis cell
fragments)
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Figure 24.7 Ciliated cells of the respiratory system infected with Bordetella pertussis.
B. pertussis
Cilia
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Pertussis (Whooping Cough)
 Stage 1: catarrhal stage, like common cold
 Stage 2: paroxysmal stage—violent coughing
sieges
 Stage 3: convalescence stage
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Figure 24.8 Mycobacterium tuberculosis.
Corded
growth
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Tuberculosis
 Mycobacterium tuberculosis
 Acid-fast rod; transmitted human-to-human
 M. bovis: <1% of U.S. cases; not transmitted from
human to human
 M. avium-intracellulare complex infects people with
late-stage HIV infection
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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
Figure 24.11a Distribution of tuberculosis.
0 – 24
25 – 49
100 – 299
_> 300
50 – 99
Estimated tuberculosis incidence worldwide, per 100,000 population
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Figure 24.11b Distribution of tuberculosis.
Reported tuberculosis
cases per 100,000
population among
American ethnic groups
in 2009
Asian and Pacific
Islanders
Black, non-Hispanic
Hispanic
American Indian/
Alaskan native
White, non-Hispanic
0
5
10
15
20
25
30
Reported cases per 100,000 population
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Figure 24.9.1 The pathogenesis of tuberculosis.
Interior of
alveolus
Blood capillary
Alveolar walls
Interior of alveolus
Ingested tubercle
bacillus
Alveolar macrophage
Bronchiole
1 Tubercle bacilli that reach the alveoli of the lung (see
Figure 24.2) are ingested by macrophages, but often some
survive. Infection is present, but no symptoms of disease.
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Figure 24.9.2 The pathogenesis of tuberculosis.
Infiltrating macrophage
(not activated)
Early tubercle
2 Tubercle bacilli multiplying in macrophages cause a
chemotactic response that brings additional macrophages
and other defensive cells to the area. These form a
surrounding layer and, in turn, an early tubercle. Most of
the surrounding macrophages are not successful in
destroying bacteria but release enzymes and cytokines that
cause a lung-damaging inflammation.
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Figure 24.9.3 The pathogenesis of tuberculosis.
Tubercle bacillus
Caseous center
Activated macrophages
Lymphocyte
3 After a few weeks, disease symptoms appear as many of
the macrophages die, releasing tubercle bacilli and
forming a caseous center in the tubercle. The aerobic
tubercle bacilli do not grow well in this location.
However, many remain dormant (latent TB) and serve as
a basis for later reactivation of the disease. The disease
may be arrested at this stage, and the lesions become
calcified.
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Figure 24.9.4 The pathogenesis of tuberculosis.
Outer layer of
mature tubercle
Tuberculous
cavity
Tubercle
bacillus
4 In some individuals, disease symptoms appear as a mature
tubercle is formed. The disease progresses as the caseous center
enlarges in the process called liquefaction. The caseous center
now enlarges and forms an air-filled tuberculous cavity in which
the aerobic bacilli multiply outside the macrophages.
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Figure 24.9.5 The pathogenesis of tuberculosis.
Rupture of
alveolar wall
5 Liquefaction continues until the tubercle ruptures, allowing
bacilli to spill into a bronchiole (see Figure 24.2) and thus be
disseminated throughout the lungs and then to the circulatory
and lymphatic systems.
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Treatment of Tuberculosis
 Treatment: prolonged treatment with multiple
antibiotics
 Vaccines: BCG vaccine, live culture of avirulent
M. bovis; not widely used in United States
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Figure 24.10 A positive tuberculin skin test on an arm.
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Diagnosis of Tuberculosis
 Tuberculin skin test screening
 Positive reaction means current or previous infection
 Followed by X-ray or CT exam, acid-fast staining of
sputum, culturing of bacteria
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Figure 24.12 Streptococcus pneumoniae, the cause of pneumococcal pneumonia.
Paired cocci
Capsule
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Pneumococcal Pneumonia
 Streptococcus pneumoniae: encapsulated
diplococci
 Symptoms: infected alveoli of lung fill with
fluids; interferes with oxygen uptake
 Diagnosis: optochin-inhibition test or bile
solubility test; serological typing of bacteria
 Treatment: macrolides, fluoroquinolones
 Prevention: pneumococcal vaccine
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Haemophilus influenzae Pneumonia
 Gram-negative coccobacillus
 Predisposing factors: alcoholism, poor nutrition,
cancer, or diabetes
 Symptoms: resemble those of pneumococcal
pneumonia
 Diagnosis: isolation; special media for nutritional
requirements
 Treatment: cephalosporins
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Mycoplasmal Pneumonia
 Primary atypical pneumonia; walking pneumonia
 Mycoplasma pneumoniae
 Pleomorphic, wall-less bacteria
 Common in children and young adults
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Figure 24.13 Colonies of Mycoplasma pneumoniae, the cause of mycoplasmal pneumonia.
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Figure 11.18b Mycloplasma pneumoniae.
This micrograph shows the filamentous growth of M. pneumoniae.
Some individual cells can also be seen (arrow). The organism
reproduces by fragmentation of the filament at the bulges.
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Mycoplasmal Pneumonia
 Symptoms: mild but persistent respiratory
symptoms; low fever, cough, headache
 Diagnosis: PCR and serological testing
 Treatment: tetracyclines
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Legionellosis
 Legionella pneumophila
 Gram-negative rod
 Found in water
 Transmitted by inhaling aerosols; not transmitted
from human to human
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Legionellosis
 Symptoms: potentially fatal pneumonia that tends
to affect older men who drink or smoke heavily
 Diagnosis: culture on selective media, DNA probe
 Treatment: erythromycin
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Psittacosis (Ornithosis)
 Chlamydophila psittaci
 Gram-negative intracellular bacterium
 Transmitted to humans by elementary bodies from
bird droppings
 Reorganizes into reticulate body after being
phagocytized
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Psittacosis (Ornithosis)
 Symptoms: symptoms, if any, are fever, headache,
chills
 Diagnosis: growth of bacteria in eggs or cell
culture
 Treatment: tetracyclines
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Figure 11.22b Chlamydias
Elementary body
Reticulate body
Intermediate body
Micrograph of Chlamydophila psittaci in the cytoplasm of a host cell. The
elementary bodies are the infectious stage; they are dense, dark, and relatively
small. Reticulate bodies, the form in which chlamydias reproduce within the host
cell, are larger with a speckled appearance. Intermediate bodies, a stage
between the two, have a dark center.
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Chlamydial Pneumonia
 Chlamydophila pneumoniae
 Transmitted from human to human
 Symptoms: mild respiratory illness common
in young people; resembles mycoplasmal
pneumonia
 Diagnosis: serological tests
 Treatment: tetracyclines
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Q Fever




Causative agent: Coxiella burnetii
Reservoir: large mammals
Tick vector
Can be transmitted via unpasteurized milk
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Figure 24.14 Coxiella burnetii, the cause of Q fever.
E
Masses of Coxiella burnetii growing in a
placental cell.
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This cell has just divided; notice the
endospore-like body (E), which is
probably responsible for the relative
resistance of the organism.
Q Fever
 Symptoms: mild respiratory disease lasting
1–2 weeks; occasional complications such as
endocarditis occur
 Diagnosis: growth in cell culture
 Treatment: doxycycline and chloroquine
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Melioidosis

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Causative agent: Burkholderia pseudomallei
Reservoir: soil
Mainly in southeast Asia and northern Australia
Symptoms: pneumonia, or tissue abscesses and
severe sepsis
 Diagnosis: bacterial culture
 Treatment: ceftazidime
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Diseases in Focus:
Common Bacterial Pneumonias
 A 27-year-old man with a history of asthma is
hospitalized with a 4-day history of progressive
cough and 2 days of spiking fevers. Gram-positive
cocci in pairs are cultured from a blood sample.
 Can you identify infections that could cause these
symptoms?
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Diseases in Focus: Common Bacterial Pneumonias
An optochin-inhibition test of the cultured bacteria, on blood agar.
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Viral Pneumonia
 Viral pneumonia occurs as a complication of
influenza, measles, or chickenpox
 Viral etiology suspected if no other cause is
determined
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Respiratory Syncytial Virus (RSV)




Common in infants; 4500 deaths annually
Causes cell fusion (syncytium) in cell culture
Symptoms: pneumonia in infants
Diagnosis: serological test for viruses and
antibodies
 Treatment: ribavirin, palivizumab
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Influenza (Flu)
 Symptoms: chills, fever, headache, and muscle
aches
 No intestinal symptoms
 1% mortality, very young and very old
 Treatment: zanamivir and oseltamivir inhibit
neuraminidase
 Prophylaxis: multivalent vaccine
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Figure 24.15 Detailed structure of the influenza virus.
NA spike
Capsid layer
HA spike
Envelope
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2 of 8 RNA
segments in
genome
The Influenza Virus
 Hemagglutinin (HA) spikes used for attachment to
host cells
 Neuraminidase (NA) spikes used to release virus
from cell
 Antigenic shift
 Changes in HA and NA spikes
 Probably due to genetic recombination between different
strains infecting the same cell
 Antigenic drift
 Point mutations in genes encoding HA or NA spikes
 May involve only one amino acid
 Allows virus to avoid mucosal IgA antibodies
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Influenza Serotypes
Type
Antigenic
Subtype
Year
Severity
A
H3N2
H1N1
H2N2
H3N2
H1N1
1889
1918
1957
1968
1977
Moderate
Severe
Severe
Moderate
Low
B
None
1940
Moderate
C
None
1947
Very mild
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Figure 24.16 Histoplasma capsulatum, a dimorphic fungus that causes histoplasmosis.
Yeastlike H.
capsulatum
Microconidia
Macroconidia
Yeastlike form typical of growth in
tissue at 37°C. Notice that one
yeastlike cell to the left of center is
budding.
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The macroconidia are especially
useful for diagnostic purposes.
Microconidia bud off from hyphae
and are the infectious form. At 37°C
in tissues, the organism converts to
a yeast phase composed of oval,
budding yeasts.
Figure 24.17 Histoplasmosis distribution.
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Coccidioidomycosis

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Causative agent: Coccidioides immitis
Reservoir: desert soils of American Southwest
Symptoms: fever, coughing, weight loss
Diagnosis: serological tests
Treatment: amphotericin B
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Figure 24.18 The life cycle of Coccidioides immitis, the cause of coccidioidomycosis.
Spherule
releases
endospores.
Human
Soil
Arthroconidium
(about 5 mm long)
germinates into
tubular hypha.
Tubular
hypha
Endospores
develop
within
spherule.
Spherule in tissue
(about 30 mm in
diameter)
Inhaled arthroconidium
enlarges and begins to
develop into a spherule.
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Hypha begins to
segment into
arthroconidia.
Released
endospores
spread in
tissue—each
developing
into new
spherule
Some
arthroconidia
return to soil
Arthroconidia
separate from
hypha
Some arthroconidia
become airborne
Airborne arthroconidium
is inhaled.
Figure 24.19 The U.S. endemic area for coccidioidomycosis.
2001
outbreak
San
Joaquin
Valley
Areas where
disease is known
to be endemic
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Pneumocystis Pneumonia

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
Causative agent: Pneumocystis jirovecii
Reservoir: unknown; possibly humans or soil
Symptoms: pneumonia
Diagnosis: microscopy
Treatment: trimethoprim
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Figure 24.20 The life cycle of Pneumocystis jirovecii, the cause of Pneumocystis pneumonia.
Mature
cyst
Cyst
Intracystic
bodies
Each trophozoite
develops into a
mature cyst.
The mature cyst
contains 8 intracystic bodies.
The cyst ruptures,
releasing the
bodies.
Trophozoite
The trophozoites divide.
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The bodies
develop into
trophozoites.
Trophozoite,
note
extensions
for feeding on
tissue.
Blastomycosis





Causative agent: Blastomyces dermatitidis
Reservoir: soil in Mississippi valley area
Symptoms: abscesses; extensive tissue damage
Diagnosis: isolation of pathogen
Treatment: amphotericin B
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Other Fungi Involved in Respiratory
Disease
 Systemic
 Predisposing factors:
 Immunocompromised state
 Cancer
 Diabetes
 Aspergillus fumigatus
 Mucor
 Rhizopus
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Diseases in Focus: Diseases of the
Lower Respiratory System
 A worker is hospitalized for acute respiratory illness.
He had been near a colony of bats. The mass is
surgically removed. Microscopic examination of the
mass reveals ovoid yeast cells.
 Can you identify infections that could cause these
symptoms?
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Diseases in Focus: Microbial Diseases of the Lower Respiratory System
Mycelial culture grown from the patient’s lung mass.
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