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MICR 201 Microbiology for Health Related Sciences

Lecture 16: Microbial diseases of the respiratory systemEdith Porter, M.D.

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Lecture outline

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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Structure of the upper respiratory system

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Structure of the lower respiratory system

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Normal microbiota of the respiratory system

Upper respiratory tract

Lower respiratory tract Mucociliary escalator Scarcely populated

Nasooropharynx

Gram+Gram- anaerobes

Neisseria spec.a-hemolytic streptococciHaemophilus spec.

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Upper respiratory tract infections 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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Otitis media

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Otitis media

More common in young children Small auditory tube which connects middle ear and

throat 50% of all office visits to pediatrician

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%

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Streptococcal pharyngitis (Strep throat)

Streptococcus pyogenes Group A streptococci

Resistant to phagocytosis

Streptokinases lyse clots Streptolysins are

cytotoxic Diagnosis

indirect agglutination ELISA

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Scarlet fever

Streptococcus pyogenes Pharyngitis + exanthem

Erythrogenic toxin produced by lysogenized S. pyogenes

Tongue strawberry like

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Diphtheria

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)

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Corynebacterium diphteriae

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Diphtheria

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Common cold

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

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Lower respiratory tract infections

Bacteria, viruses, & fungi cause: Bronchitis Bronchiolitis Pneumonia

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Pertussis (whooping cough)

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Bordetella pertussis

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Pertussis pathogenesis

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

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Pertussis clinical course

Stage 1: Catarrhal stage, like common cold

Stage 2: Paroxysmal stage: Violent coughing sieges

Stage 3: Convalescence stage http://www.vaccineinformation.org/photos/

pert_wi001.jpg

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Complications and prevention of pertussis

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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Tuberculosis

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Causes of tuberculosis

Mycobacteria Acid-fast rods Lipid rich cell wall

M. tuberculosis 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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Tuberculosis symptoms

Bad cough over 3 weeks Sputum production

Thick, viscous Later on blood stained

Weight loss Night sweat Weakness or fatigue Evening lower grade temperature or

chills

Development of disease depends on host resistance

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Airborne Infection

No symptomsNot sick

Cannot spread diseaseChest X Ray and sputum

are normal

AIDS increases susceptibility

Reactivation(secondary) TB

Untreated:Severe illness,

Death

SymptomsCan spread infection

Positive skin testPossible abnormal chest

X rayPositive sputum smear

or cultureDissemination

Latent TB TB Disease

10 %90 %

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Tuberculosis diagnosis

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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Tuberculosis treatment and prophylaxis

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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Pneumomoccal Pneumonia

Streptococcus pneumoniae Gram-positive

encapsulated diplococci Over 90 serotypes

Symptoms High fever Difficulty breathing Chest pain

Diagnosis by culturing bacteria

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Mycoplasmal pneumonia

Mycoplasma pneumoniae 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

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Q Fever

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

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Viral pneumonia

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

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Influenza

Chills, fever, headache, muscle aches (no intestinal symptoms)

1% mortality due to secondary bacterial infections

Vaccine for high-risk individuals

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Influenza virus

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

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High mutation rate of influenza viruses

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

How do we acquire viruses from pigs?

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Diagnosis of influenza

Direct antigen detection with nasal swabs

Cell culture and PCR

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Fungal respiatory tract infections

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

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Important to Remember 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

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Check your understanding1) Which of the following does NOT confirm a diagnosis of strep throat?

A) Hemolytic reactionB) Bacitracin inhibitionC) SymptomsD) Serological testsE) Gram stain

2) Which of the following pairs is mismatched?A) Epiglottitis – HaemophilusB) Q fever – RickettsiaC) Diphteria - CorynebacteriumD) Whooping cough – BordetellaE) All are correct

3) The recurrence of influenza epidemics is due toA) Lack of antiviral drugs.B) The Guillain-Barré syndrome.C) Antigenic shift.D) Lack of naturally acquired active immunity.E) HA spikes.