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

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   Respiratory systems: structure and normal microbiota Upper respiratory tract infections  General: pharyngitis, tonsillitis, laryngitis, sinusitis, epiglottitis, otitis media   Viral diseases Lower respiratory tract infections  Bacterial diseases General: bronchitis, bronchioliis, pneumonia  Bacterial diseases  Viral diseases  Fungal diseases 2

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 Upper respiratory tract

Nasooropharynx Gram+ Gram- anaerobes

 Lower respiratory tract  Mucociliary escalator  Scarcely populated

Neisseria spec.

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-hemolytic streptococci

Haemophilus spec.

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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) 6

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       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% 8

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Streptococcus pyogenes

 Group A streptococci Resistant to phagocytosis Streptokinases lyse clots Streptolysins are cytotoxic Diagnosis  indirect agglutination  ELISA 9

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Streptococcus pyogenes

Pharyngitis + exanthem  Erythrogenic toxin produced by lysogenized S. pyogenes Tongue strawberry like 10

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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

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     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 15

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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

   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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    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) 20

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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 23

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  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 25

Airborne Infection

90 %

Latent TB No symptoms Not sick Cannot spread disease Chest X Ray and sputum are normal AIDS increases susceptibility Reactivation (secondary) TB

10 %

TB Disease Symptoms Can spread infection Positive skin test Possible abnormal chest X ray Positive sputum smear or culture Dissemination Untreated: Severe illness, Death

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 Diagnosis: Tuberculin skin test screening  + = current or previous infection  Followed by X-ray or CT, acid-fast staining of sputum, culturing bacteria, PCR 27

 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 29

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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 30

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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

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  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.

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