1. Microbial Diseases of the Respiratory System
Chapter 24
Microbial Diseases of the Respiratory System
Lectures prepared by Christine L. Case
© 2013 Pearson Education, Inc. 1

3. Figure 24.1 Structures of the upper respiratory system.
Sinus
Middle ear
Sinus
Nasal cavity
Auditory (eustachian) tube
Opening of auditory tube
Oral cavity
Tongue
Tonsils
Epiglottis
Pharynx (throat)
Layrnx (voice box)
Spine (backbone)
Esophagus
Trachea (windpipe)

4. Figure 24.2 Structures of the lower respiratory system.
Branch from the pulmonary artery
Bronchiole
Blood capillaries
Branch from the pulmonary vein
Pharynx (throat)
Larynx (voice box)
Left lung
Trachea (windpipe)
Right lung
Alveoli
Bronchus
Bronchiole
Pleura
Heart
Diaphragm (breathing muscle)

5. Normal Microbiota of the Respiratory System
Suppress pathogens by competitive inhibition in upper respiratory system
Lower respiratory system is sterile

6. Upper Respiratory System Diseases
Pharyngitis
Laryngitis
Tonsillitis
Sinusitis
Epiglottitis: H. influenzae type b

7. Streptococcal Pharyngitis
Also called strep throat
Streptococcus pyogenes
Resistant to phagocytosis
Streptokinases lyse clots
Streptolysins are cytotoxic
Diagnosis by enzyme immunoassay (EIA) tests
Scarlet fever
Erythrogenic toxin produced by lysogenized S. pyogenes

8. Figure 24.3 Streptococcal pharyngitis.

9. Clubbed cells Palisade arrangement
Figure 24.4 Corynebacterium diphtheriae, the cause of diphtheria.
Clubbed cells
Palisade arrangement

10. Figure 24.5 A diphtheria membrane.
Membrane on tonsils

11. Diphtheria Corynebacterium diphtheriae: gram-positive rod
Diphtheria toxin produced by lysogenized C. diphtheriae
Prevented by DTaP vaccine
Diphtheria toxoid
Cutaneous diphtheria
Infected skin wound leads to slow-healing ulcer

12. Otitis Media 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 vaccine

13. Figure 24.6 Acute otitis media, with bulging eardrum.

14. The Common Cold
Rhinoviruses (30–50%)
Coronaviruses (10–15%)

15. Diseases in Focus: Diseases of the Upper Respiratory System
A patient presents with fever and a red, sore throat. Later, a grayish membrane appears in the throat. Gram-positive rods are cultured from the membrane.
Can you identify infections that could cause these symptoms?

16. Characteristic swollen lymph nodes of this disease.
Diseases in Focus: Microbial Diseases of the Upper Respiratory System
Characteristic swollen lymph nodes of this disease.

17. Lower Respiratory System Diseases
Bacteria, viruses, and fungi cause
Bronchitis
Bronchiolitis
Pneumonia

18. Pertussis (Whooping Cough)
Bordetella pertussis
Gram-negative coccobacillus
Capsule
Tracheal cytotoxin of cell wall damages ciliated cells
Pertussis toxin
Prevented by DTaP vaccine (acellular Pertussis cell fragments)

19. Figure 24.7 Ciliated cells of the respiratory system infected with Bordetella pertussis.
B. pertussis
Cilia
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20. Pertussis (Whooping Cough)
Stage 1: catarrhal stage, like common cold
Stage 2: paroxysmal stage—violent coughing sieges
Stage 3: convalescence stage

21. Figure 24.8 Mycobacterium tuberculosis.
Corded growth

22. Tuberculosis Mycobacterium tuberculosis
Acid-fast rod; transmitted human-to-human
M. bovis: <1% of U.S. cases; not transmitted from human to human
M. avium-intracellulare complex infects people with late-stage HIV infection

23. Reported tuberculosis cases, 1948–2010
Figure 14.10c Epidemiological graphs.
120
100 80 60 40 20
Reported cases per
100,000 people
Year
Reported tuberculosis cases, 1948–2010

24. Estimated tuberculosis incidence worldwide, per 100,000 population
Figure 24.11a Distribution of tuberculosis.
0 – 24
100 – 299
25 – 49 _
> 300
50 – 99
Estimated tuberculosis incidence worldwide, per 100,000 population

25. Reported cases per 100,000 population
Figure 24.11b Distribution of tuberculosis.
Reported tuberculosis cases per 100,000 population among American ethnic groups in 2009
Asian and Pacific Islanders
Black, non-Hispanic
Hispanic
American Indian/ Alaskan native
White, non-Hispanic
Reported cases per 100,000 population

26. Interior of alveolus Blood capillary Alveolar walls
Figure The pathogenesis of tuberculosis.
Interior of alveolus
Blood capillary
Alveolar walls
Interior of alveolus
Ingested tubercle
bacillus
Alveolar macrophage
Bronchiole
Tubercle bacilli that reach the alveoli of the lung (see Figure 24.2) are ingested by macrophages, but often some survive. Infection is present, but no symptoms of disease. 1

27. Infiltrating macrophage (not activated)
Figure The pathogenesis of tuberculosis.
Infiltrating macrophage (not activated)
Early tubercle
Tubercle bacilli multiplying in macrophages cause a chemotactic response that brings additional macrophages and other defensive cells to the area. These form a surrounding layer and, in turn, an early tubercle. Most of the surrounding macrophages are not successful in destroying bacteria but release enzymes and cytokines that cause a lung-damaging inflammation. 2

28. Activated macrophages
Figure The pathogenesis of tuberculosis.
Tubercle bacillus
Caseous center
Activated macrophages
Lymphocyte
After a few weeks, disease symptoms appear as many of the macrophages die, releasing tubercle bacilli and forming a caseous center in the tubercle. The aerobic tubercle bacilli do not grow well in this location. However, many remain dormant (latent TB) and serve as a basis for later reactivation of the disease. The disease may be arrested at this stage, and the lesions become calcified. 3

29. Outer layer of mature tubercle
Figure The pathogenesis of tuberculosis.
Outer layer of mature tubercle
Tuberculous cavity
Tubercle bacillus 4
In some individuals, disease symptoms appear as a mature tubercle is formed. The disease progresses as the caseous center enlarges in the process called liquefaction. The caseous center now enlarges and forms an air-filled tuberculous cavity in which the aerobic bacilli multiply outside the macrophages.

30. Rupture of alveolar wall
Figure The pathogenesis of tuberculosis.
Rupture of alveolar wall 5
Liquefaction continues until the tubercle ruptures, allowing bacilli to spill into a bronchiole (see Figure 24.2) and thus be disseminated throughout the lungs and then to the circulatory and lymphatic systems.

31. Treatment of Tuberculosis
Treatment: prolonged treatment with multiple antibiotics
Vaccines: BCG vaccine, live culture of avirulent M. bovis; not widely used in United States

32. Figure 24.10 A positive tuberculin skin test on an arm.

33. Diagnosis of Tuberculosis
Tuberculin skin test screening
Positive reaction means current or previous infection
Followed by X-ray or CT exam, acid-fast staining of sputum, culturing of bacteria

34. Figure 24.12 Streptococcus pneumoniae, the cause of pneumococcal pneumonia.
Paired cocci
Capsule
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35. Pneumococcal Pneumonia
Streptococcus pneumoniae: encapsulated diplococci
Symptoms: infected alveoli of lung fill with fluids; interferes with oxygen uptake
Diagnosis: optochin-inhibition test or bile solubility test; serological typing of bacteria
Treatment: macrolides, fluoroquinolones
Prevention: pneumococcal vaccine

36. Haemophilus influenzae Pneumonia
Gram-negative coccobacillus
Predisposing factors: alcoholism, poor nutrition, cancer, or diabetes
Symptoms: resemble those of pneumococcal pneumonia
Diagnosis: isolation; special media for nutritional requirements
Treatment: cephalosporins

37. Mycoplasmal Pneumonia
Primary atypical pneumonia; walking pneumonia
Mycoplasma pneumoniae
Pleomorphic, wall-less bacteria
Common in children and young adults

38. Figure 24.13 Colonies of Mycoplasma pneumoniae, the cause of mycoplasmal pneumonia.

39. Figure 11.18b Mycloplasma pneumoniae.
This micrograph shows the filamentous growth of M. pneumoniae. Some individual cells can also be seen (arrow). The organism reproduces by fragmentation of the filament at the bulges.

40. Mycoplasmal Pneumonia
Symptoms: mild but persistent respiratory symptoms; low fever, cough, headache
Diagnosis: PCR and serological testing
Treatment: tetracyclines

41. Legionellosis Legionella pneumophila Found in water
Gram-negative rod
Found in water
Transmitted by inhaling aerosols; not transmitted from human to human

42. Legionellosis
Symptoms: potentially fatal pneumonia that tends to affect older men who drink or smoke heavily
Diagnosis: culture on selective media, DNA probe
Treatment: erythromycin

43. Psittacosis (Ornithosis)
Chlamydophila psittaci
Gram-negative intracellular bacterium
Transmitted to humans by elementary bodies from bird droppings
Reorganizes into reticulate body after being phagocytized

44. Psittacosis (Ornithosis)
Symptoms: symptoms, if any, are fever, headache, chills
Diagnosis: growth of bacteria in eggs or cell culture
Treatment: tetracyclines

45. Elementary body Reticulate body Intermediate body
Figure 11.22b Chlamydias
Elementary body
Reticulate body
Intermediate body
Micrograph of Chlamydophila psittaci in the cytoplasm of a host cell. The elementary bodies are the infectious stage; they are dense, dark, and relatively small. Reticulate bodies, the form in which chlamydias reproduce within the host cell, are larger with a speckled appearance. Intermediate bodies, a stage between the two, have a dark center.

46. Chlamydial Pneumonia Chlamydophila pneumoniae
Transmitted from human to human
Symptoms: mild respiratory illness common in young people; resembles mycoplasmal pneumonia
Diagnosis: serological tests
Treatment: tetracyclines

47. Q Fever Causative agent: Coxiella burnetii Reservoir: large mammals
Tick vector
Can be transmitted via unpasteurized milk

48. E Figure 24.14 Coxiella burnetii, the cause of Q fever.
Masses of Coxiella burnetii growing in a placental cell.
This cell has just divided; notice the endospore-like body (E), which is probably responsible for the relative resistance of the organism.

49. Q Fever
Symptoms: mild respiratory disease lasting 1–2 weeks; occasional complications such as endocarditis occur
Diagnosis: growth in cell culture
Treatment: doxycycline and chloroquine

50. Melioidosis Causative agent: Burkholderia pseudomallei Reservoir: soil
Mainly in southeast Asia and northern Australia
Symptoms: pneumonia, or tissue abscesses and severe sepsis
Diagnosis: bacterial culture
Treatment: ceftazidime

51. Diseases in Focus: Common Bacterial Pneumonias
A 27-year-old man with a history of asthma is hospitalized with a 4-day history of progressive cough and 2 days of spiking fevers. Gram-positive cocci in pairs are cultured from a blood sample.
Can you identify infections that could cause these symptoms?

52. An optochin-inhibition test of the cultured bacteria, on blood agar.
Diseases in Focus: Common Bacterial Pneumonias
An optochin-inhibition test of the cultured bacteria, on blood agar.

53. Viral Pneumonia
Viral pneumonia occurs as a complication of influenza, measles, or chickenpox
Viral etiology suspected if no other cause is determined

54. Respiratory Syncytial Virus (RSV)
Common in infants; 4500 deaths annually
Causes cell fusion (syncytium) in cell culture
Symptoms: pneumonia in infants
Diagnosis: serological test for viruses and antibodies
Treatment: ribavirin, palivizumab

55. Influenza (Flu) Symptoms: chills, fever, headache, and muscle aches
No intestinal symptoms
1% mortality, very young and very old
Treatment: zanamivir and oseltamivir inhibit neuraminidase
Prophylaxis: multivalent vaccine

56. 2 of 8 RNA segments in genome
Figure Detailed structure of the influenza virus.
2 of 8 RNA segments in genome
NA spike
Capsid layer
HA spike
Envelope
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57. The Influenza Virus
Hemagglutinin (HA) spikes used for attachment to host cells
Neuraminidase (NA) spikes used to release virus from cell
Antigenic shift
Changes in HA and NA spikes
Probably due to genetic recombination between different strains infecting the same cell
Antigenic drift
Point mutations in genes encoding HA or NA spikes
May involve only one amino acid
Allows virus to avoid mucosal IgA antibodies

58. Influenza Serotypes Type Antigenic Subtype Year Severity A H3N2 H1N1
1889
1918
1957
1968
1977
Moderate
Severe
Low B
None
1940 C
1947
Very mild

59. Figure 24.16 Histoplasma capsulatum, a dimorphic fungus that causes histoplasmosis.
Yeastlike H. capsulatum
Microconidia
Macroconidia
Yeastlike form typical of growth in tissue at 37°C. Notice that one yeastlike cell to the left of center is budding.
The macroconidia are especially useful for diagnostic purposes. Microconidia bud off from hyphae and are the infectious form. At 37°C in tissues, the organism converts to a yeast phase composed of oval, budding yeasts.

60. Figure 24.17 Histoplasmosis distribution.

61. Coccidioidomycosis Causative agent: Coccidioides immitis
Reservoir: desert soils of American Southwest
Symptoms: fever, coughing, weight loss
Diagnosis: serological tests
Treatment: amphotericin B

62. Figure 24.18 The life cycle of Coccidioides immitis, the cause of coccidioidomycosis.
Human
Soil
Arthroconidium (about 5 mm long) germinates into tubular hypha.
Spherule releases endospores.
Tubular hypha
Endospores develop within spherule.
Hypha begins to segment into arthroconidia.
Released endospores spread in tissue—each developing into new spherule
Arthroconidia separate from hypha
Some arthroconidia return to soil
Spherule in tissue (about 30 mm in diameter)
Some arthroconidia become airborne
Inhaled arthroconidium enlarges and begins to develop into a spherule.
Airborne arthroconidium is inhaled.

63. Figure 24.19 The U.S. endemic area for coccidioidomycosis.
2001 outbreak
San Joaquin Valley
Areas where disease is known to be endemic

64. Pneumocystis Pneumonia
Causative agent: Pneumocystis jirovecii
Reservoir: unknown; possibly humans or soil
Symptoms: pneumonia
Diagnosis: microscopy
Treatment: trimethoprim

65. Figure 24.20 The life cycle of Pneumocystis jirovecii, the cause of Pneumocystis pneumonia.
Mature cyst
Cyst
Intracystic bodies
The mature cyst contains 8 intra-cystic bodies.
Each trophozoite develops into a mature cyst.
The cyst ruptures, releasing the bodies.
Trophozoite
The bodies develop into trophozoites.
Trophozoite, note extensions for feeding on tissue.
The trophozoites divide.

66. Blastomycosis Causative agent: Blastomyces dermatitidis
Reservoir: soil in Mississippi valley area
Symptoms: abscesses; extensive tissue damage
Diagnosis: isolation of pathogen
Treatment: amphotericin B

67. Other Fungi Involved in Respiratory Disease
Systemic
Predisposing factors:
Immunocompromised state
Cancer
Diabetes
Aspergillus fumigatus
Mucor
Rhizopus

68. Diseases in Focus: Diseases of the Lower Respiratory System
A worker is hospitalized for acute respiratory illness. He had been near a colony of bats. The mass is surgically removed. Microscopic examination of the mass reveals ovoid yeast cells.
Can you identify infections that could cause these symptoms?

69. Mycelial culture grown from the patient’s lung mass.
Diseases in Focus: Microbial Diseases of the Lower Respiratory System
Mycelial culture grown from the patient’s lung mass.