MICR 201 Microbiology for Health Related Sciences

1. Lecture 16: Microbial diseases of the respiratory system Edith Porter, M.D. MICR 201 Microbiology for Health Related Sciences

2. 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

3. Structure of the upper respiratory system

4. Structure of the lower respiratory system

5. Normal microbiota of the respiratory system • Upper respiratory tract • Lower respiratory tract • Mucociliary escalator • Scarcely populated

6. 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 (IlanaSeligman)

7. Otitis media

8. Otitismedia • 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%

9. Streptococcal pharyngitis (Strep throat) • Streptococcus pyogenes • Group A streptococci • Resistant to phagocytosis • Streptokinaseslyse clots • Streptolysins are cytotoxic • Diagnosis • indirect agglutination • ELISA

10. Scarlet fever • Streptococcus pyogenes • Pharyngitis + exanthem • Erythrogenic toxin produced by lysogenizedS. pyogenes • Tongue strawberry like

11. Diphtheria • Corynebacteriumdiphtheriae • Gram-positive rod, pleomorphic • Diphtheria (Greek: leather) membrane forms in throat • fibrin, dead tissue, and bacteria • Diphtheria toxin produced by lysogenizedC. diphtheriae • Blocks protein biosynthesis • Infection is local but toxin may spread systemically • Kidney failure, heart failure • Prevented by DTaP and Td vaccine (Diphtheria toxoid)

12. Corynebacteriumdiphteriae

13. Diphtheria

14. 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

15. Lower respiratory tract infections • Bacteria, viruses, & fungi cause: • Bronchitis • Bronchiolitis • Pneumonia

16. Pertussis(whooping cough)

17. Bordetellapertussis

18. Pertussispathogenesis • Bordetellapertussis • 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

19. Pertussisclinical course • Stage 1: Catarrhal stage, like common cold • Stage 2: Paroxysmal stage: Violent coughing sieges • Stage 3: Convalescencestage http://www.vaccineinformation.org/photos/pert_wi001.jpg

20. 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 (acellularPertussis cell fragments)

21. Tuberculosis

23. 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-intracellularecomplex • infects people with late stage HIV infection • Faster growing

25. 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

26. Development of disease depends on host resistance 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 Untreated: Severe illness, Death Reactivation (secondary) TB

27. 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

28. Tuberculosis treatment and prophylaxis • Prolonged treatment with multiple drugs • 6 months at least • Combinantion • Pronounced side effects • Vaccines • BCG, live, avirulentM. bovis • Not widely used in U.S.

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

30. Mycoplasmalpneumonia • Mycoplasmapneumoniae • 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

31. Q Fever • Coxiellaburnetii • 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

32. 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

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

34. 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

35. 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

36. How do we acquire viruses from pigs?

38. Diagnosis of influenza • Direct antigen detection with nasal swabs • Cell culture and PCR

39. 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

40. 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

41. Check your understanding 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.