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Transcript
Lecture 16: Microbial diseases of the respiratory system
Edith Porter, M.D.
1


Respiratory systems: structure and normal microbiota
Upper respiratory tract infections
 General: pharyngitis, tonsillitis, laryngitis, sinusitis, epiglottitis,
otitis media
 Bacterial diseases
 Viral diseases

Lower respiratory tract infections
 General: bronchitis, bronchioliis, pneumonia
 Bacterial diseases
 Viral diseases
 Fungal diseases
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3
4

Upper respiratory tract
Nasooropharynx

Gram+
Gram- anaerobes
Neisseria spec.
a-hemolytic streptococci
Haemophilus spec.
Lower respiratory tract
 Mucociliary escalator
 Scarcely populated
5
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Laryngitis: S. pneumoniae, S. pyogenes, viruses
Tonsillitis: S. pyogenes, S. pneumoniae, viruses
Sinusitis: Bacteria, fungi
Epiglottitis: H. influenzae
Sinusitis in right maxillary sinus in a CT scan (Ilana
Seligman)
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7

More common in young children
 Small auditory tube which connects middle ear and throat
 50% of all office visits to pediatrician



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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 vaccineby 6
– 7%
8

Streptococcus pyogenes
 Group A streptococci




Resistant to phagocytosis
Streptokinases lyse clots
Streptolysins are cytotoxic
Diagnosis
 indirect agglutination
 ELISA
9


Streptococcus pyogenes
Pharyngitis + exanthem
 Erythrogenic toxin produced by lysogenized S. pyogenes

Tongue strawberry like
10

Corynebacterium diphtheriae
 Gram-positive rod, pleomorphic

Diphtheria (Greek: leather) membrane forms in throat
 fibrin, dead tissue, and bacteria

Diphtheria toxin produced by lysogenized C. diphtheriae
 Blocks protein biosynthesis

Infection is local but toxin may spread systemically
 Kidney failure, heart failure

Prevented by DTaP and Td vaccine (Diphtheria toxoid)
11
12
13


Over 200 different viruses capable of causing
common cold
Rhinoviruses (50%, over 100 serotypes)
 A single virus attached to mucosa might be
sufficient to cause a cold


Coronaviruses (15-20%)
Less frequent in older people
 Possibly accumulated immunity

Duration ~1 week
 With remedies ~ 7 days
14

Bacteria, viruses, & fungi cause:
 Bronchitis
 Bronchiolitis
 Pneumonia
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16
17

Bordetella pertussis
 Gram-negative coccobacillus


Capsule
Numerous toxins and pathogenic factors
 Tracheal cytotoxin
▪ Selective damages ciliated respiratory cells
▪ Local action
 Pertussis toxin
▪ Overstimulates cells leading to dysfunction
▪ Locall + systemic action
18


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Stage 1: Catarrhal
stage, like
common cold
Stage 2:
Paroxysmal
stage: Violent
coughing sieges
Stage 3:
Convalescence
http://www.vaccineinformation.org/photos/pert_wi001.jpg
stage
19
Major complications most common among infants
and young children
 Include hypoxia, apnea, pneumonia, seizures,
encephalopathy, and malnutrition
 Young children can die from pertussis
 Most deaths occur among unvaccinated children
or children too young to be vaccinated


Prevented by DTaP vaccine (acellular Pertussis cell
fragments)
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21
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Mycobacteria
 Acid-fast rods
 Lipid rich cell wall

M. tuberculosis

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Primary cause
Transmitted from human to human
20 h generation time: slow growth
M. bovis
 <1% U.S. cases
 not transmitted from human to human
 Attenuated strain used in BCG vaccine

M. avium-intracellulare complex
 infects people with late stage HIV infection
 Faster growing
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Bad cough over 3 weeks
Sputum production
 Thick, viscous
 Later on blood stained
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Weight loss
Night sweat
Weakness or fatigue
Evening lower grade temperature or chills
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Airborne Infection
90 %
10 %
Latent TB
TB Disease
No symptoms
Not sick
Cannot spread disease
Chest X Ray and sputum
are normal
Symptoms
Can spread infection
Positive skin test
Possible abnormal chest X
ray
Positive sputum smear or
culture
Dissemination
AIDS increases
susceptibility
Reactivation
(secondary) TB
Untreated:
Severe illness,
Death
26

Diagnosis: Tuberculin skin test screening
 + = current or previous infection
 Followed by X-ray or CT, acid-fast staining of
sputum, culturing bacteria, PCR
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
Prolonged treatment with multiple drugs
 6 months at least
 Combinantion
 Pronounced side effects

Vaccines
 BCG, live, avirulent M. bovis
 Not widely used in U.S.
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

Streptococcus pneumoniae
 Gram-positive
encapsulated diplococci
 Over 90 serotypes
Symptoms
 High fever
 Difficulty breathing
 Chest pain

Diagnosis by culturing
bacteria
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
Mycoplasma pneumoniae





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
Pleomorphic
Bacteria without a cell wall
Require cholesterol for growth
“Fried egg” appearance on agar
media
Also called primary atypical
pneumonia and walking
pneumonia
Common in children and
young adults
Diagnosis by PCR or by IgM
antibodies
30



Coxiella burnetii
Obligate intracellular bacterium
Flulike pneumonia





High fever
Headache
Muscle ache
Coughing
Long recovery
2% may develop endocarditis
60% of all infections
asymptomatic
 Reservoir: cattle
 Infection via aerosol or ingestion
of unpasteurized milk


31
Viral pneumonia as a complication of influenza,
measles, chickenpox
 Viral etiology suspected if no other cause
determined
 Respiratory Syncytial Virus (RSV)

 Common in infants; 4500 deaths annually
 Causes cell fusion (syncytium) in cell culture
 Symptoms: coughing
 Diagnosis by serologic test for viruses and antibodies
32



Chills, fever, headache, muscle aches (no
intestinal symptoms)
1% mortality due to secondary bacterial
infections
Vaccine for high-risk individuals
33

Segmented RNA virus
 8 separate segments
Enveloped
Hemagglutinin (H)
spikes used for
attachment to host cells
 Neuraminidase (N)
spikes used to release
virus from cell


34

Antigenic drift
 No proof reading of RNA polymerase
 Mutations in genes encoding H or N spikes
 May involve only 1 amino acid
 Allows virus to avoid mucosal IgA antibodies

Antigenic shift
 Changes in H and N spikes
 Probably due to genetic recombination between different
strains infecting the same cell
 Causes pandemic
 1918/1919: over 20,000,000 deaths world wide
35
37


Direct antigen detection with nasal swabs
Cell culture and PCR
38

Histoplasmosis
 Eastern US
 Tb like symptoms but tuberculin negative
 Can spread throughout the body

Coccidioidomycosis:
 Southwestern US
 Increased incidences after natural disasters,
e.g. earthquakes

Pneumocystis
 Associated with immunodificiency e.g. AIDS
 Pneumonia with dry strong and prolonged
cough
39


Respiratory systems: structure and normal microbiota
Upper respiratory tract infections
 General: pharyngitis, tonsillitis, laryngitis, sinusitis, epiglottitis, otitis
media
 Bacterial diseases: strep throat, scarlet fever, dipheteria,
 Viral diseases: Common cold

Lower respiratory tract infections
 General: bronchitis, bronchiolitis, pneumonia
 Bacterial diseases: pneumonia (lobar, atypical), tuberculosis
 Viral diseases: influenza, RSV
 Fungal diseases: histoplasmosis, coccidiomycosis, pneumocystis
40
1) Which of the following does NOT confirm a diagnosis of strep throat?
A) Hemolytic reaction
B) Bacitracin inhibition
C) Symptoms
D) Serological tests
E) Gram stain
2) Which of the following pairs is mismatched?
A) Epiglottitis – Haemophilus
B) Q fever – Rickettsia
C) Diphteria - Corynebacterium
D) Whooping cough – Bordetella
E) All are correct
3) The recurrence of influenza epidemics is due to
A) Lack of antiviral drugs.
B) The Guillain-Barré syndrome.
C) Antigenic shift.
D) Lack of naturally acquired active immunity.
E) HA spikes.
41