1. Lecture 16: Microbial diseases of the respiratory system Edith Porter, M.D. 1

2. 2  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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5.  Upper respiratory tract  Lower respiratory tract  Mucociliary escalator  Scarcely populated 5

6.  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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8.  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

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

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

11.  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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14.  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

15.  Bacteria, viruses, & fungi cause:  Bronchitis  Bronchiolitis  Pneumonia 15

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18.  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

19.  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 19

20.  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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23.  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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25.  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

26. 26 Airborne Infection No symptoms Not sick Cannot spread disease Chest X Ray and sputum are normal AIDS increases susceptibility Reactivation (secondary) TB Untreated: Severe illness, Death Symptoms Can spread infection Positive skin test Possible abnormal chest X ray Positive sputum smear or culture Dissemination Latent TBTB Disease 10 %90 %

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

28.  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. 28

29.  Streptococcus pneumoniae  Gram-positive encapsulated diplococci  Over 90 serotypes  Symptoms  High fever  Difficulty breathing  Chest pain  Diagnosis by culturing bacteria 29

30.  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

31.  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

32.  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

33.  Chills, fever, headache, muscle aches (no intestinal symptoms)  1% mortality due to secondary bacterial infections  Vaccine for high-risk individuals 33

34.  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

35. 35  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

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38.  Direct antigen detection with nasal swabs  Cell culture and PCR 38

39.  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

40. 40  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

41. 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