Pulmonary Microbiology Flashcards Preview

Pulmonary > Pulmonary Microbiology > Flashcards

Flashcards in Pulmonary Microbiology Deck (259):
1

Tularemia:Francisella Tularensis
Microbiology:

Gram-, aerobic, non-motile, non-spore
coccobacillus

2

Tularemia: Francisella Tularensis
Mechanism of disease/Virulence Factors:

Survives host’s innate immune response:
i. ↓LPS immunostimulation
ii.Capsule = complement resistance
iii.↑Survival in macrophages from iglABCD
transposon mutagenesis

3

Tularemia: Francisella Tularensis
Epidemiology

Not spread person-person
- Yet, occurs in rural areas b/c infected animals
- Incubation from hours --> weeks

4

Tularemia: Francisella Tularensis
Transmission: Modes of Infection:

i. Insect bites (ticks + deerflies) = ulcerogland.
ii.Exposure to sick animals (rabbits) = “””
iii.Rubbing eyes post infection = oculogland.
iv.Airborne = pneumonic
v.Contaminated Food/Water = oropharyngeal

5

Tularemia: Francisella Tularensis
- Normal outbreak vs. Bioterrorism Use

i. Bioterrorism outbreak has point-source outbreak
(urban, non-agricultural city)
ii.Respiratory illness in healthy persons

6

Tularemia: Francisella Tularensis
Disease Types:


1. Ulceroglandular Tularemia (most common):
2. Glandular Tularemia
3. Oculoglandular Tularemia
4. Oropharyngeal Tularemia
5. Pneumonic Tularemia
6. Typhoidal Tularemia (rare)

7

Ulceroglandular Tularemia
Presentation

(most common):
- Skin ulcer at infection site (bug bit) - (“ulcero-”)
- Swollen glands (“glandular)
- Fever, chills, headaches, exhaustion

8

Glandular Tularemia
Presentation

- Swollen glands (“glandular)
- Fever, chills, headaches, exhaustion

9

Oculoglandular Tularemia
Presentation

- Swollen glands + eye pain, redness, discharge, eyelid ulcer.

10

Oropharyngeal Tularemia
Presentation

(eating poorly cooked infected meat)
- Fever + GI symptoms (sore throat, vomit, diarrhea)

11

Pneumonic Tularemia
Presentation

(in elderly and also with typhoidal tularemia)
- Pneumonia symptoms = cough, chest pain, difficulty breathing

12

Typhoidal Tularemia (rare)
Presentation

- Fever, exhaustion, vomit, diarrhea, pneumonia
- Enlarged liver + spleen

13

Tularemia: Francisella Tularensis
Diagnosis:

1. Blood Culture for F. Tularensis
2. Serology for Tularemia (blood test measuring immune response)
3. CXR (patchy infiltrates)
4. PCR sampling ulcer

14

Tularemia: Francisella Tularensis
Treatment:

Tularemia cured w/antibiotics Streptomycin and Tetracycine

15

Comparing Tularemia w/
Anthrax + Plaque CXR:

1. Anthrax: dry, nonproductive cough w/
widened mediastinum on CXR
2. Plague: watery/bloody productive cough w/acute
bacterial pneumonia signs on CXR
3. Tularemia: non-productive cough w/patchy infiltrates.

16

Anthrax: Bacillus Anthrax (Ba)
Microbiology:

-spore forming rod
- Gram+, facultative anaerobe, non-motile
- Spore (infectious form) viable 100yrs in soil
- Spore (1-5 um) reaches lungs

17

Anthrax: Bacillus Anthrax (Ba)
Mechanism of disease/Virulence Factors:

1. Ingested by pulmonary/cutan/GI macrophage
2. Surviving spores released to hilar lymph node
3. Spores vegetate --> acq. virulence factors:
- Anti-phagocytic non-antigenic capsule (poly-dglutamic acid)***

18

Anthrax: Bacillus Anthrax (Ba)
- AB Toxin (Anthrax Exotoxin)?

i. B = Protective Antigen (binds receptor/endo)
ii.A1= Edema Factor (calmodulin activated AC)
↑cAMP --> swelling, medast. edema + ↓PMN
iii. A2= Lethal Factor (metalloprotease) xMAPKs --> no signaling --> cell death

19

Anthrax: Bacillus Anthrax (Ba)
Epidemiology/Transmission:

:1. Reservoir=cows; farmers safe (spores on soil)
2. Imported wools/hides “Woolsorer’s Disease”
3. Misdiagnosed: plague, tularemia (Category A)

20

Anthrax: Bacillus Anthrax (Ba)
Disease Types/Symptoms

Toxins --> SWELLING, SEPSIS, NECROSIS
1. Cutaneous Anthrax (natural + bioterrorism)
- Eschar (black = “Anthracis”), swelling (Edema Factor)
2. Inhalation Anthrax: Spores (natural + bioterrorism) - TWO PHASES

21

Anthrax: Bacillus Anthrax (Ba)
Inhalation Anthrax: Spores (natural + bioterrorism) - TWO PHASES

- Phase 1: Flu-like Symptoms
i. Fever, aches etc --> SOB, chest pain
ii.+/- non-productive cough
- Phase 2: Hemorrhagic Mediastinitis w/Pleural Effusions
i. NOT pneumonia b/c infection of hilar/mediastinal lymph nodes
ii. MEDIASTINAL WIDENING

22

Anthrax: Bacillus Anthrax (Ba)
Diagnosis:

Culture rarely shows +Ba
1. Differentiate from flu (phase 1 symptoms)
- Flu won’t have SOB, nausea, vomit; Anthrax won’t have rhinorrhea
2. Gram stain, immunofl. Ab stain CSF, blood smears for G+ boxcars
- NO SPORES WILL BE SEEN

23

Anthrax: Bacillus Anthrax (Ba)
Treatment:

Incubation can be 6 weeks, leading to:
1. 40 days ciprofloxacin/doxy IV prophylaxis + 1 other (ampicillin)
2. Vaccine

24

Yersinia Pestis (Plaque)
Microbiology:

- Chubby Gram- rods w/bipolar inclusion bodies

25

Yersinia Pestis (Plaque)
Mechanism of disease/Virulence Factors:

- Fraction 1 (F1) paralyzes phagocytes upon
ingestion; ↓innate + adaptive immunity
- Yp --> skin --> macrophages --> lymph nodes
(inguinal > axillary; “boubon”=groin) -->
bloodstream (septicemia) --> ↑organ failure
- Ex: subcutaneous hemorrhage (“Black death”)

26

Yersinia Pestis (Plaque)
Epidemiology:

- Bubonic plague is most common form
- 1° Plague Pneumonia + 2° Plague Pneumonia
(following bubonic)

27

Yersinia Pestis (Plaque)
/Transmission:

- Bubonic Transmission: flea + ground rodent
**New Mexico + SW USA
- 1° Plague Pneumonia: infected person/cat
**Expected bioterrorism
**Plague pneumo (1°+2°) = contagious

28

Yersinia Pestis (Plaque)
Disease Types:

1. Bubonic: “Boubo” = swelling of lymph nodes
2. Septicemic: severe toxemia +/- buboes
3. Pneumonic:

29

Yersinia Pestis (Plaque)
Symptoms Bubonic: :

Bubonic: “Boubo” = swelling of lymph nodes (inguinal) ~60% fatal
- Flea (vector) bite --> 1-8 day incubation
- Swollen, painful lymph nodes
- +/- macular/ulcerative lesions at flea bite site

30

Yersinia Pestis (Plaque)
Symptoms Septicemic:

Septicemic: severe toxemia +/- buboes
- Rapid progression
- Petechiae ---> extreme DIC
- Vomit + diarrhea

31

Yersinia Pestis (Plaque)
Symptoms Pneumonic: :

Pneumonic: ~100% fatal if untreated
- 2°=spreading from primary infection (bubonic flea bite)
i. Contagious; requires isolation + prophylaxis for all exposed
ii.Sputum production = bloody/watery > purelent
- 1°=same symptoms as 2°, but precede septicemia

32

Yersinia Pestis (Plaque)
Differential Bulbo presentation:

- Tularemia: inoculation lesion more prominent; no septicemia
- Strep/staph adenitis: less septic and lymph node is more plaible, less painful; purulent lesions

33

Yersinia Pestis (Plaque)
Differential Septicemic:

meningococcemia, rickettsioses

34

Yersinia Pestis (Plaque)
Differential Pneumonic presentation:

broad; G- rods confirm plague

35

Yersinia Pestis (Plaque)
Diagnosis:

1. +Ab for F1 antigen (Rapid Antigen Detection) OR Immunofl. for Yp
2. history of exposure (flea/rodent) + symptoms
3. Gram stain for Yp safety pin from bubo, SCF, blood, sputum
4. Culture Yp on BAP/enteric media (b/c Yp = enerobacteriacae)
5. Failure to respond to B-lactams/macrolines

36

Yersinia Pestis (Plaque)
Staining appearance?

Safety pin appearance of Yp
b/c ends of rod take up more
than center (“bipolar staining)

37

Yersinia Pestis (Plaque)
Exam Prompt?:

Pt recently camping in new Mexico suddenly develops fever...

38

Yersinia Pestis (Plaque)
Treatment:

IMMEDIATE
1. Gentamicin (streptomycin)
2. Doxy/Cipro
3. Pneumonic post exposure:
doxy for 7 days
4. No vaccine

39

Brucella spp.(Brucellosis) “Brucella”:
Microbiology:

Brucella abortus (cows), suis (pigs)
melitensis (sheep/goats)
- Small Gram- coccobacillus

40

Brucella spp.(Brucellosis) “Brucella”:
Mechanism of disease/Virulence Factors:

1. Brucella penetrates skin, lung, eye, etc.
2. Lymph spread --> facultative intracellular
growth of RES (liver/spleen, bone)

41

Brucella spp.(Brucellosis) “Brucella”:
Epidemiology/Transmission:

- USA: wild animal (cow, sheep, pig) reservoir
- Transmission: contact + unpasteur cheeze
i. vet, farmer, slaughterhouse (animal handling)
ii.Recent Mediterranean/Mexican immigrant (bad
cheese)
- NO Human-human transmission

42

Brucella spp.(Brucellosis) “Brucella”:
Disease/Symptoms:

Brucellus (UNDULANT FEVER)
1. Slow-moving, chronic infection w/relapse fever/nightsweats (undulant)
2. Can be acute onset w/↑fever + flu sypmtoms
3. Infects bone (lower vertebrae), heart, liver
4. Typical lesion = granuloma (bone/liver)

43

Brucella spp.(Brucellosis) “Brucella”:
Diagnosis:

In DDx with TB
1. Serology (↑anti-Brucella)
2. Cultured on rich medium (1 week): bone marrow > blood.

44

Brucella spp.(Brucellosis) “Brucella”:
Treatment:

1. Prolonged course of antibiotics (doxycycline + aminoglycosides)
2. Control in USA: vaccinate cattle + pasteurize milk for cheese

45

Coxiella Burnetii (Q Fever):
Microbiology:

Coxiella Burnetii (Cb)
- Gram- bacillus w/ Endospore form
(imp for inhalation mode of entry, possible
terrorism, and cause of pneumonia)

46

Coxiella Burnetii (Q Fever):
Mechanism of disease/Virulence Factors:

- Obligate intracellular parasite (requires host ATP for growth)
- Replicates w/in phagolysosome

47

Coxiella Burnetii (Q Fever):
Epidemiology/Transmission:

- Mode of entry: inhalation of animal aerosol
- Also, handling of animal viscera, aminotic fluid,
placenta, drinking raw milk, ticks.

48

Coxiella Burnetii (Q Fever):
Disease/Symptoms:

Q Fever Gram- bacillus
1. 1/3 - 1/2 asymptomatic
2. Acute febrile illness
3. Atypical pneumonia (spore like form)
4. Can lead to liver (granulmoatis hep) or heart (endocarditis) damage

49

Coxiella Burnetii (Q Fever):
DDx:

1. Atypical pneumonias / Pneumonic Tularemia
3. Ehrlichioses/RMSF
4. Mycobacterial infections

50

Coxiella Burnetii (Q Fever):
Diagnosis:

1. Serological - ↑Ab titer for Coxiella Burnetti

51

Coxiella Burnetii (Q Fever):
Treatment:

Most spontaneously resolve, but doxycycline ↓chronic infn.

52

Mycobacterium Tuberculosis (MBT):
Buzz Words:

HIV (↓Tcells)

53

Mycobacterium Tuberculosis (MBT):
Additional Forms:

-bovis = cows
-avium = HIV pts
-leprae = leprosy

54

Mycobacterium Tuberculosis (MBT):
Microbiology:

- Large, non-motile rod-shaped bacterium
- Not gram+/-; no characteristics of either
- Gram stain = ghost cells (weakly gram+)
- Serpentine cord colonies (from cord factor)

55

Mycobacterium Tuberculosis (MBT):
Mechanism of disease/Virulence Factors:

- Obligate aerobe (find in apex of lung)
- Facultative intracellular parasite (macrophage)
- Cell Wall: peptidoglycan + 3 ↑lipid proteins:
- MBT bind to macros mann. receptors (LAM) or
via complement receptors/Fc receptors (bypass
oxidative burst w/compl binding)
- Inhibits phago-lyso fusion of macros
- ↓Oxidative toxicity mechanism of macros
- Antigen 85 - MTB secreted protein; may wall off
immune system, protecting MTB
- Slow generation can allow growth under the radar
of the immune system.

56

Mycobacterium Tuberculosis (MBT):
Epidemiology/Transmission:

Rate on the decline
- Coughing is most common
- 25% of exposed become infected
- 10% of infected --> disease in lifetime (1°)
- 10% risk for HIV+ --> disease each year (1°)
- Most common: Reactivation TB
- Not contagious until disease (vs. infection)

57

Mycobacterium Tuberculosis (MBT):
*Mis-used or mis-prescribed Rx =

resistance*

58

Mycobacterium Tuberculosis (MBT):
Two Types of Resistance?

- Multi-Drug-Resistant TB (MDR TB)
i. Resistant to isoniazid + rifampicin
- Extensively-Drug-Resistant TB (XDR TB)
i. Resistant to isoniazid + rifampicin +
fluoroquinolone + amikacin/kanamycin/
capreomycin

59

Mycobacterium Tuberculosis (MBT):
***Both MDR/XDR TB common in pts who?

Don’t take meds as described

60

Mycobacterium Tuberculosis (MBT):
Preventative Treatment:

(isoniazid 2/wk 9mos)
- Preventative therapy = secondary prevention
(stop infected --> disease)
- Screen persons at ↑risk infection--> disease

61

Mycobacterium Tuberculosis (MBT):
Disease: Latent (exposed≠contagious) vs Disease (active=contagious)

- MBT contained by lymphocytes + macrophages
- TB stages of disease (most won’t get to stage 5)

62

Mycobacterium Tuberculosis (MBT):
Disease Stages:

Stage 1
Stage 2 ~ 7-21 days post-infection
Stage 3 ~ “Cell Mediated Response” ~ 6-10 weeks
Stage 4
Stage 5 ~ The Damage We See!

63

Mycobacterium Tuberculosis (MBT):
Disease Stage 1:

Stage1
1. Aerosolized droplet nuclei (3-5 bacilli, infective ~5um each) inhaled
2. Ingested by alveolar macrophages (TB begins when droplet arrives)
- Large droplets remain in nose/pharynx (URT) = no infection

64

Mycobacterium Tuberculosis (MBT):
Disease Stage 2:

Stage 2 ~ 7-21 days post-infection
3. MTB multiplies in macrophages --> other macrophages are recruited
4. New macrophages phagocytose MTB, but cannot destroy them
5. Some MTB spread to lymph nodes in macrophages

65

Mycobacterium Tuberculosis (MBT):
Disease Stage 3:

Stage 3 ~ “Cell Mediated Response” ~ 6-10 weeks
6. Lymphocytes (T-cells) release gamma-IFN --> activate macrophages
7. Activated macrophages destroy MTB (this is when pt is tuberculin+)
8. Activated macros release inflammatory/lytic molecules against MTB, leading to tissue damage and tubercles surrounded by macros
- Tubercle = caseating granulomas
- MBT imprisoned by macrophages (guards), instructed by T-cell (warden)

66

Mycobacterium Tuberculosis (MBT):
Disease Stage 4:

Stage 4
9. Unactivated macrophages targeted by MTB --> tubercle grows
10.Growing tubercle invades bronchus --> pulmonary blood --> milliary TB
***Milliary TB = Disseminated TB = Systemic TB
i. Exudative Lesions = ↑PMN, replication without resistance
ii.Productive/Granulomatous Lesions = host becomes hypersensitivty.

67

Mycobacterium Tuberculosis (MBT):
Disease Stage 5:

Stage 5 ~ The Damage We See!
11. Caseous centers of tubercle/granuloma liquefy --> ↑MTB growth extracellularly
12. Extracellular growth --> necrosis of nearby bronchi --> cavity formed
13. Cavity (allows for spread) --> healing --> calcified fibrosis --> Gohn complex or Simon foci (metastatic foci, usually reactivated because contain viable organism)

68

Mycobacterium Tuberculosis (MBT):
Diagnosis: non-specific, systemic + pulmonary signs/symptoms

1. Symptoms: cough, fever, night sweats, weight loss, hemoptysis
2. Signs: cachexia (↓Tcell function), consolidation signs, pyurea, mening.
3. PPD (Purified Protein Derivative): infection (latent), not disease
- MTB component injected, if macrophages have been activated
- Also “Quantiferon Gold” for IFN-ɣ
4. Radiograph
- Primary TB = lymphadenopathy + pleural effusion any area of lung
- Reactivation TB = upper lobe only, cavitation
- Miliary + caseating granuloma w/multinucleated giant cells
5. Acid Fast+ via Ziehl-Neelson Stain (cell wall lipids don’t dissolve w/ addition of red acid EtoH, holding fast to the red acid) + NAA test

69

Mycobacterium Tuberculosis (MBT):
MTB's cell wall consists of three major components a major determinant of virulence for the bacterium?

i. Mycolic Acid: H2Ophobic lipid shell; ↓permeability of MBT cell = protective from
macrophage ROS defense
ii.Cord Factor: 2xmycolic acid + dissacharide. Allows parallel growth of bacterium, inhibits PMN migration,
found only in virulent stains.
iii.Wax-D: Freund’s adjuvant envelope

70

Mycobacterium Tuberculosis (MBT):
↑Lipid in MBT Cell Wall does five things:

1. Impermeable to stains
2. Antibiotic resistance
3. Acid/base-resistant (fast)
4. Resistant to compl-lysis
5. Intra-macrophage growth

71

Mycobacterium Tuberculosis (MBT)
Treatment:

Take combination therapy exactly as prescribed!
1. 6-9 months of standard:
- RIPE
=Rifambin, Isoniazide, Pyrazinamide, Ethambutol
- At least two drugs needed
- Never add a single new drug
- Directly observe therapy
- Monitor toxicity

72

Mycobacterium Tuberculosis (MBT)
**Patients are no longer infective if they:

1. Adequate multi-therapy
2. Respond well to Rxs
3. 3 negative cultures

73

Pertussis (Whooping Cough): Bordetella Pertussis
Microbiology:

1. Gram-, aerobic, coccobacillus

74

Pertussis (Whooping Cough): Bordetella Pertussis
Mechanism of disease/Virulence Factors:

1. Pertussis toxin: A-B toxin alters intracellular
protective pathways
2. ↑Adenylate Cyclase: taken up by PMNs, monos,
lymphos --> ↓ROS synthesis
3. Filamentous Hemagglutinin (FHA): pili rod that
binds cilia (target with mAb)
4. Tracheal Cytotoxin: paralyzes ciliated cells

75

Pertussis (Whooping Cough): Bordetella Pertussis
Epidemiology/Transmission:

- 200K cases each year before vaccine
- Nowdays, untreated “merely annoyed” patients
become reservoirs for disease
- Transmission: human-human
- Infants get it from seemingly healthy carers
- Adolescents (waining vaccination) can get it

76

Pertussis (Whooping Cough): Bordetella Pertussis
Disease/Symptoms:

Whooping Cough
- Can last as annoyance for 7 weeks
- Clinical Illness Stages: (1-6 weeks post exposure)

77

Pertussis (Whooping Cough): Bordetella Pertussis
Three Stages:

Catarrhal Stage ~ “Common Cold”
Paroxysmal Stage ~ “The Whooping Cough”
Convalescent Stage ~ “Cough Subsides”

78

Pertussis (Whooping Cough): Bordetella Pertussis
Catarrhal Stage ~ “Common Cold”

- Common cold findings for 1-2 weeks
- Unlike most URIs, cough increases
- Most contagious in this stage

79

Pertussis (Whooping Cough): Bordetella Pertussis
Paroxysmal Stage ~ “The Whooping Cough”

- Paroxysmal attacks w/inspiratory gasp through narrowed glottis
- Patients become hypoxemic, cyanotic
- Most complications arise in this stage

80

Pertussis (Whooping Cough): Bordetella Pertussis
Convalescent Stage ~ “Cough Subsides”

- Cough goes away gradually; may come back with another URI

81

Pertussis (Whooping Cough): Bordetella Pertussis
Diagnosis:

Requires special growth medium for culture swab of throat
- PCR based tests
- CXR: looking for pneumonia/URI

82

Pertussis (Whooping Cough): Bordetella Pertussis
Treatment:

Acellular Pertussis (aP) replaced whole-cell pertussis

83

Diphtheria: Corynebacterium diphtheriae
Corynebacterium?

“Koryne”: club
“Bacterion”: little rod

84

Diphtheria: Corynebacterium diphtheriae
Microbiology:

Non-spore forming rod
- Corynebacteria = gram+, aerobic, non-motile, rod shaped bacteria
- Form irregular, club shape (Chinese symbol)

85

Diphtheria: Corynebacterium diphtheriae
Mechanism of Disease/Virulence Factors:

- Avirulent --> toxic by lysogenic conversion
- Diphtheria toxin (Dt) is required for virulence
- Dt coded by tox gene on lysogenic beta-prophage
(no phage = avirulent)
- Follows A (toxic enzyme) + B (adhesin) model
- B binds to heparin-binding EGF (hbEGF)
- A (endocytosed) ADP-ribosylates EF-2 and halts
protein synthesis.
One molecule enough to kill one cell.

86

Diphtheria: Corynebacterium diphtheriae
Epidemiology/Transmission:

No cases in US; endemic if no DPT vaccine (prophylaxis)

87

Diphtheria: Corynebacterium diphtheriae
Diseases:

1. Organism (A+B) colonizes in pharynx forming pseudomembrane
2. Toxin (A) gets in blood --> organ damage (HEART + Cranial Nerves).

88

Diphtheria: Corynebacterium diphtheriae
Presentation:

1. Sore throat + pseudomembrane on tonsils, throat, pharynx
2. Neck swelling (severe disease)
3. Skin lesions (cutaneous diphtheriae)

89

Diphtheria: Corynebacterium diphtheriae
Diagnosis:

If + immediately report to CDC!
1. REQUIRED culture of Corynebacteria Diphtheriae (nose/throat swab)
2. Any confirmation of actual exotoxin (Dt)
3. Additional tests for affected organs (CT of neck, EKG etc)

90

Diphtheria: Corynebacterium diphtheriae
Treatment:

1. Antitoxin - for symptomatic, diffuse cases
- Neutralizes circulating Dt (not effective against bound toxin)
2. Antibiotics (erythromycin/penicillin) - asymptomatic, localized/cutaneous cases
- Eradicate/halt production of toxin; good for preventing transmission

91

Nocardiosis: Nocardia asteroides Complex
Microbiology:

- Gram+ bacilli with branching beaded (coccobacillary) filaments (hyphae)
- Saprophytic (soil normal flora, H2O)
- Aerobic actinomycetes

92

Nocardiosis: Nocardia asteroides Complex
Mechanism of disease/Virulence Factors:

1. Have short (40-60 C) mycolic acid chains (stain
weakly acid-fast)
2. Catalase + superoxide dismutase protect against
PMN/macrophage damage
3. Cord factor (dimycolic acid) prevents phaglysosome fusion

93

Nocardiosis: Nocardia asteroides Complex
Epidemiology/Transmission:

- Inhaled
- Cutaneous skin wound in infected soil
- No person-person / nosocomial infections

94

Nocardiosis: Nocardia asteroides Complex
***Common in pts w/underlying debilitations:

- Immunocompromised + steroid use
- Underlying chronic lung disease
- Diabetes, heme maligancies, AIDS

95

Nocardiosis: Nocardia asteroides Complex
Diseases:

(Nocardiosis) opportunistic pathogen --> pulmonary disease
General: acute inflammation --> necrosis + abscesses
1. Nocardia asteroides inhaled --> grows in lung (infected = pneumonia)
2. Leads to lung abscesses
3. Can become systemic --> infection/abscess in brain, blood, heart

96

Nocardiosis: Nocardia asteroides Complex
Presentation:

Immunocompromised patients
- Pulmonary nocardiosis: hemoptysis, fever/night-sweats, chest pain
- Cerebral nocardiosis: headache, confusion, seizures
- Cutaneous nocardiosis: ulcers

97

Nocardiosis: Nocardia asteroides Complex
Diagnosis:

1. Smear/culture on BCYE (yeast extract + activated charcoal)
2. Gram stain
3. Acid Fast stain to confirm

98

Nocardiosis: Nocardia asteroides Complex
Treatment:

Sulfas!
- Immunocompetent: at least 6 months
- Immunocompromised: at least 12 months
- Sulfa, ceftriaxone, and amikacin in difficult cases

99

Streptococcus Pneumoniae "Pneumococcus"
Microbiology:

Lancet shaped diplococcus

100

Streptococcus Pneumoniae "Pneumococcus"
Mechanism of Disease/Virulence Factors: 10

1. Polysaccharide capsule
2. Pneumolysin
3. Hyaluronidase
4. Neuraminidase
5. Pili:
6. Wall Teichoic Acid (WTA) and LipoTeichoic Acid (LTA)
7. Choline Binding Protein (CBP)
8. Competence Protein
9. Autolysin (LytA)
10.Lipoproteins

101

Streptococcus Pneumoniae "Pneumococcus"
Mechanism of Disease/Virulence Factors:
Polysaccharide capsule

Anti-phagocytic

102

Streptococcus Pneumoniae "Pneumococcus"
Mechanism of Disease/Virulence Factors:
Pneumolysin

Pore-forming toxin binds to
cholesterol in cell membranes --> cell lysis + T/B
cell + TLR4 mediated inflammation

103

Streptococcus Pneumoniae "Pneumococcus"
Mechanism of Disease/Virulence Factors:
Hyaluronidase:

↑spread in hyal. acid tissues

104

Streptococcus Pneumoniae "Pneumococcus"
Mechanism of Disease/Virulence Factors:
Neuraminidase:

xN-acetylneruaminic acid from surface GPs = damage + ↑binding sites

105

Streptococcus Pneumoniae "Pneumococcus"
Mechanism of Disease/Virulence Factors:
Pili:

↑adhesion to epithelium.

106

Streptococcus Pneumoniae "Pneumococcus"
Mechanism of Disease/Virulence Factors:
Petpidoglycan + Teichoic Acid: Wall Teichoic
Acid (WTA) and LipoTeichoic Acid (LTA)

Have (-) phosph groups neutralized by choline (vs. Dalanine normally)
- TA + peptidoglycan = C Polysaccharide (CP)
- CRP (liver inflammatory mol) binds CP
- CRP + CP --> complement activation
- CP + PRR --> cytokine secretion

107

Streptococcus Pneumoniae "Pneumococcus"
Mechanism of Disease/Virulence Factors:
Choline Binding Protein (CBP):

Wall hydrolytic enzymes that bind choline on WTA/LTA and release inflammatory wall components (LytA)
- Others bind respiratory epithelium (PsaA)
- Others bind complement factor H (↓phago)

108

Streptococcus Pneumoniae "Pneumococcus"
Mechanism of Disease/Virulence Factors:
Competence Protein:

Get DNA from environment for drug resistance, capsule, etc.

109

Streptococcus Pneumoniae "Pneumococcus"
Mechanism of Disease/Virulence Factors:
Autolysin (LytA):

Disrupt cell wall --> release inflammatory contents

110

Streptococcus Pneumoniae "Pneumococcus"
Mechanism of Disease/Virulence Factors:
Lipoproteins:

↑↑functions (ex iron uptake)

111

Streptococcus Pneumoniae "Pneumococcus"
Epidemiology/Transmission:

↑ in midwinter
1. S. Pneumoniae = commensal microbiota
2. Colonizes 60% healthy children, 30% adults
i. Can be cleared OR progress to disease
ii.Asymptomatically carried (carriage state)
3. Primary vector = children, then = 65+
4. Transmitted by close contact

112

Streptococcus Pneumoniae "Pneumococcus"
Diseases:

Colonizes nasal cavity --> disease via direct/heme spread

113

Streptococcus Pneumoniae "Pneumococcus"
Community Acquired Pneumonia (Direct)
Disease:

1. Bacteria avoid structural/chemical respiratory defense --> airway
2. Replicate in alveoli --> spread of infection --> inflammation
3. Alveolar damage --> Capillary leakage --> ↑PMNs + complement +
RBC (iron source for bacteria)
4. PMNs/complement can’t do anything to bacteria (capsule), but ↑inflam
===alveolar filling with inflammatory fluid --> suffocation

114

Streptococcus Pneumoniae "Pneumococcus"
Community Acquired Pneumonia (Direct)
Symptoms:

Cough, fever, shaking chills/sweat, SOB, pleuritic pain
- Crackling sounds; ↑TF
- Rust colored sputum
- CXR: multiple/segmental infiltrates in one lobe

115

Streptococcus Pneumoniae "Pneumococcus"
Community Acquired Pneumonia (Direct)
Diagnosis:

Sputum Sample
1. Little saliva (should have ↓squamous epithelium)
2. Gram stain = gram+, lancet shaped diplococci with ↑PMNs

116

Streptococcus Pneumoniae "Pneumococcus"
Community Acquired Pneumonia (Direct)
Treatment:

1. Outpatient:
- Abx 1 (no order): macrolide, doxycyclilne, amoxicillin (+/-clav), quinolone
2. Inpatient - if in doubt hospitalize for initiation therapy
- Abx 1: penicillin, ampicillin, ceftrixone
- If no improvement in 48 hrs --> resistance determined
- ↓Mortality if given B-lactam AND macrolide

117

Streptococcus Pneumoniae "Pneumococcus"
Meningitis (Heme)
Disease:

Most common non-endemic cause of meningitis
1. Most commonly occurs via bacteremia
2. Evasion of phagocytosis + production of inflammation as described

118

Streptococcus Pneumoniae "Pneumococcus"
Meningitis (Heme)
Symptoms:

Headache, stiff neck, photophobia, seizures, coma
(↑Pressure on brain), frontal bulge in infants above fontanel.

119

Streptococcus Pneumoniae "Pneumococcus"
Meningitis (Heme)
Diagnosis:

Blood +/- CSF ar tested

120

Streptococcus Pneumoniae "Pneumococcus"
Meningitis (Heme)
Treatment:

Abx 1: pencillin/vancomycin or ceftriaxone

121

Streptococcus Pneumoniae "Pneumococcus"
Otitis Media/Sinusitis (Direct)
Disease:

Most common middle ear infection
1. Nasal colonization --> Eustachian tube --> middle ear (neuroaminidase)
2. Predisposing factors: viral mucosal congestion, pollutants/allergens

122

Streptococcus Pneumoniae "Pneumococcus"
Otitis Media/Sinusitis (Direct)
Diagnosis:

Observe tympanic membrane

123

Streptococcus Pneumoniae "Pneumococcus"
Otitis Media/Sinusitis (Direct)
Treatment:

1. Antibiotic 1: Amoxicillin + clavulanic acid
2. Abx 2 (if amox fails): ceftriaxone

124

Streptococcus Pneumoniae "Pneumococcus"
Sepsis (Heme)
Disease:

1. Secondary from primary pneumonia/meningitis
2. Primary cases in immunocompromised pts (asplenia) / recent surgery.

125

Streptococcus Pneumoniae "Pneumococcus"
Quellung Reaction shows?

Ab to the polysaccharide capsule

126

Streptococcus Pneumoniae "Pneumococcus"
Predisposing Risk Factors:

1. Asplenia (↓clearance)
2. Defects in complement/Ab
3. Diabetes, Chronic Lung disease, CHF, Alcohol
abuse (bad PMNs)
4. Prior URI (influenza)

127

Streptococcus Pneumoniae "Pneumococcus"
BAP Culture for S. Pneumococcus

1. α-hemolytic - (partial) destroys hemoglobin (pneumolysin)
2. Catalase negative
3. Inhibited by optochin/ehtyl hydrocupreine (used to diff btw S. pneumo vs. S. viridans)
4. Inhibited by bile salts (deoxycholate)

128

Streptococcus Pneumoniae "Pneumococcus"
Prevention:

1. Pneumovax: vaccine w/23 capsular polysaccharides from 23 common serotypes
2. Prevnar 13: w/13 common serotypes + diptheria toxin.

129

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Microbiology:

Chlamydia ~ gram- and inhibited by ampicillin, but
no peptidoglycan wall
- Biphasic lifecycle with 2 distinct forms

130

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Biphasic lifecycle with 2 distinct forms

1. Elementary Body (EB) endocytosed into cell -->
inhibits phagolysosome fusion but metabolically
inert
2. EB --> RB (more metabotically active)
3. RB = obligate intracellular parasite
4. RB divides --> transforms back to mature EB
5. Mature EB Released to infect more cells

131

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Mechanism of Disease/Virulence Factors

1. Secretes Type Three Secretions (TTS) proteins in
cell cytosol --> inhibit pathways

132

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Epidemiology/Transmission:

1. Psittacosis reservoir = birds; spread by
aerosolization
2. Pneumoniae reservoir = humans
3. Trachomatis reservoir = humans; spread by
contact w/eye secretions
- Trachoma = leading/preventable cause of blind
- C. Trachomatis is mostly silent; ↑transmission
because infected people still have sex

133

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Diseases: Pneumoniae

Diseases: most have mild disease; some have severe disease
Pneumoniae (6-10% of community acquired pneumonia)
1. Caused by chlamydia pneumoniae (7-21 day incubation)
2. Spread via respiratory route
3. C. pneumoniae + serum lipoprotein --> immune complex --> atherosclerosis --> CAD

134

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Disease: Psittacosis (parrot fever)

1. Caused by chlamydia psittaci found in birds
2. Inhaled from dead bird feces --> mild/severe respiratory tract infection

135

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Disease: Ocular, Respiratory and Gential Tract Infections

1. Caused by Chlamydia trachomatis (most common STI in industrialized countries) that infect squamocolumnar cells of mucosa

136

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Trachoma (Immunotypes A-C)

Chronic conjunctivitis --> inflammation + scarring --> inward folding of eyelid --> eyelash scratches conjunctiva + cornea --> blindness.

137

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Trachoma Genital Tract Infections (Immunotpes D-K)

- Associated with cervical squamous cell carcinoma
- Neonatal pneumonia/conjunctivitis can occur when child passes through birth canal; give erythromycin and eyedrops

138

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Presentation:

Incubation 3-4 weeks, gradual onsest
1. Most infected are asymptomatic/mild respiratory illness
2. Scant sputum
3. Prominent cough even with antibiotics
4. Ronchi, rales, Hoarseness

139

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Diagnosis:

1. IgM titer > 1:16
2. 4-fold IgG↑
3. PCR testing for C.
Pneumoniae specific DNA

140

Atypical Pneumonia:
Chlamydia Pneumoniae: C. Pneumoniae
Treatment:

60% of cases have mixed infections with other bugs
1. Doxycycline except in <9 y/o and pregnant women
2. Alternate: erythromycin or new macrolides

141

Atypical Pneumonia:
Legionellas pneumophilia: Legionnaires
Microbiology:

1. Aerobic, gram- rods, nonencapsulated, facultative
intracellular parasite.

142

Atypical Pneumonia:
Legionellas pneumophilia: Legionnaires
Mechanism of Disease/Virulence Factors:

1. Inhalation --> ingested by alveolar macros
2. Replicate and avoid phago-lysosome fusion in
macrophages
3. Injects bacterial proteins into host cell that alter
host’s vesicular system --> form specialized
vesicular system = bacterial ER
4. Bacterial ER supports replication>

143

Atypical Pneumonia:
Legionellas pneumophilia: Legionnaires
Epidemiology/Transmission:

1. Legionella bacteria in water sources left in heat -
hot water tanks, air conditioners, etc
2. Transmission: contaminated mist/vapor
3. No human-human spread

144

Atypical Pneumonia:
Legionellas pneumophilia: Legionnaires
Diseases:

Legionnaires’ Disease = atypical pneumonia
1. At risk: elderly, immunocompromised, smokers, alcoholics
2. Males > females
3. Incubation 2-10 days

145

Atypical Pneumonia:
Legionellas pneumophilia: Legionnaires
Presentation:

Legionnaire’s Disease: 2-14 day incubation
1. High fever, chills, cough, aches (flu-like sypmtoms)
2. CXR for pneumonia
3. Milder form: Pontiac Fever
- Creates flu-like symptoms very acutely (2 days); clears quickly (5 days) without pneumonia

146

Atypical Pneumonia:
Legionellas pneumophilia: Legionnaires
Diagnosis:

1. Most will have diagnosable pneumonia (CXR) b/c replication in macros
2. Urinary Antigen Test: finds Legionella in urine sample
3. UAT + pneumonia = Legionnaires’ Disease
4. Serology

147

Atypical Pneumonia:
Legionellas pneumophilia: Legionnaires
Treatment:

Delayed treatment = ↑mortality
1. Levofloxacin/azithromycin
2. Newer macrolides
3. Tracyclines < 12 years; quinolones > 18 years

148

Atypical Pneumonia:
Mycoplasma pneumoniae: M. pneumoniae
Microbiology:

1. Smallest free-living organisms; no cell wall
2. Nutritionally requires cholesterol

149

Atypical Pneumonia:
Mycoplasma pneumoniae: M. pneumoniae
Mechanism of Disease/Virulence Factors:

1. Produces polarized adhesin complex to attach
lung epithelium
2. Attaches to surface of respiratory epithelium
3. Does not enter/penetrate epithelium
4. Mycoplasma’s diacyl-lipoprotein interacts with
TLR2 + TLR6 --> inflammation
5. ↑Macrophage activation clears infection, but also
causes disease symptoms.

150

Atypical Pneumonia:
Mycoplasma pneumoniae: M. pneumoniae
Epidemiology/Transmission:

1. Frequently found in temperate climates
2. Late summer/early fall
3. Frequent in closed populations

151

Atypical Pneumonia:
Mycoplasma pneumoniae: M. pneumoniae
Diseases: Primary Atypical Pneumonia

1. Highest rate of pneumonia 5-20 years old
2. 3 week incubation, compared to influenza (3 days)

152

Atypical Pneumonia:
Mycoplasma pneumoniae: M. pneumoniae
Diseases: Nonspeecific (nongonococcal) urethritis

1. Caused by Ureaplasma urealyticum

153

Atypical Pneumonia:
Mycoplasma pneumoniae: M. pneumoniae
Diseases: Postpartum Fever/Pelvic Inflammatory Disease

1. Caused by M. Hominis

154

Atypical Pneumonia:
Mycoplasma pneumoniae: M. pneumoniae
Presentation:

Gradual onset; days --> weeks
1. Persistent slowly worsening dry cough causing chest tenderness
2. Fever, malaise, headache, chills, sore throat

155

Atypical Pneumonia:
Mycoplasma pneumoniae: M. pneumoniae
Diagnosis:

All non-specific

156

Atypical Pneumonia:
Mycoplasma pneumoniae: M. pneumoniae
Treatment:

Antibiotic prophylaxis for immunocompromised patients

157

Atypical Pneumonia:
Mycoplasma pneumoniae: M. pneumoniae
Buzz Words:

***Persistent slowly worsening dry cough!

158

Opportunistic Pneumonia:
Acinetobacter baumannii: A baumannii
Microbiology:

Opportunistic pathogen
- A. baumannii = gram-, aerobic, pleomorphic bacillus found in hospital environments
- Cultured from respiratory secretions, wounds, urine
(colonizations, not infections)
- Nosocomial b/c baumannii = water organism
colonizes in H2O (IV/irrigating solutions)

159

Opportunistic Pneumonia:
Acinetobacter baumannii: A baumannii
Mechanism of disease/Virulence Factors:

- A. baumannii causes apoptosis/cell death in
laryngeal epithelium via OMP38
- OMP38: outer membrane protein that releases
cytochrome C + apoptosis inducing factor
- Additional virulence factors:
i. Acquired antibiotic resistant genes
ii.Efflux pumps preventing antibiotics
iii.Integrons with multiple resistant determinants

160

Opportunistic Pneumonia:
Acinetobacter baumannii: A baumannii
Epidemiology/Transmission:

Hospital acq > Community acq
1. A baumannii in soil and water
2. Community acquired A baumannii pneumonia in
southeast Asia + Australia

161

Opportunistic Pneumonia:
Acinetobacter baumannii: A baumannii
Diseases:

Commonly in susceptible patients (“opportunistic”); in hospital setting think “4 Ws”
1. Pneumonia (Wind = ventilators)
2. Blood Infection/meningitis (Wire = blood/IV)
3. Urinary Tract Infection (Water = urinary catheter)
4. Skin wounds (Wounds = skin infection)

162

Opportunistic Pneumonia:
Acinetobacter baumannii: A baumannii
Presentation:

1. Fever (bacterial infection)
2. Inflamed (red, swollen, warm, painful) skin wounds
3. Orange, bumpy skin lesions
4. Cough, chest pain, dyspnea (pneumonia)
5. Burning urination (UTI)
6. Sleepiness, headache, stiff neck

163

Opportunistic Pneumonia:
Acinetobacter baumannii: A baumannii
Diagnosis:

Culture blood, urine, tissue for A. Baumannii
1. CXR - pneumonia
2. Lumbar puncture - meningitis

164

Opportunistic Pneumonia:
Acinetobacter baumannii: A baumannii
Treatment:

A. baumannii inherently resistant to multiple antibiotics; colonization is not treated; infection is!

165

Opportunistic Pneumonia:
Acinetobacter baumannii: A baumannii
Rx that +/- work:

1. Meropenem (ultra broad)
2. Polymyxin B + E(Colistin)
3. Amikacin (xprot translation)
4. Rifampin (xDNA synth)
5. Minocycline/tigecycline

166

Actinomycosis: Actinomyces israelii Complex
Buzz Words

*Sinus Tract
*Painless abscess
*Sulfur Granules
*Dental Procedures

167

Actinomycosis: Actinomyces israelii Complex
Microbiology:

1. Gram+ bacilli with branching beaded (coccobacilary) filaments (hyphae)
2. Non-spore, non acid-fast, anaerobic
3. Normal flora of mouth + GI tract

168

Actinomycosis: Actinomyces israelii Complex
Mechanism of Disease/Virulence Factors:

1. Opportunistic pathogen --> chronic disease
2. Endogenous bacterium that attacks when mucosa is disrupted (dental plaque, tonsillar crypts, infection, trauma surgery)
3. Post-injury environment has ↓O2 = ↑growth

169

Actinomycosis: Actinomyces israelii Complex
Epidemiology/Transmission:

Endogenous source (normal flora)

170

Actinomycosis: Actinomyces israelii Complex
Diseases:

- Post-injury, endogenous bacteria burrow sinus tract to skin/mucosa
- Eroding abscesses formed after mucous membrane damage (mouth/GI)
- Abscess = sulfur granules of solidified yellow mycelial masses

171

Actinomycosis: Actinomyces israelii Complex
Types based on structural location:

i. Pulmonary Actinomycosis
ii. Cervico-facial (Jaw/Face) Actinomycosis (lumpy jaw)

172

Actinomycosis: Actinomyces israelii Complex
Presentation:

Slow-infection (chronic disease)
1. Chest pain with deep breath + SOB
2. Sputum producing cough
3. Lethargy, night sweats, weight loss

173

Actinomycosis: Actinomyces israelii Complex
Diagnosis:

Aspiration material w/ sulfur granules
- Grow granules for gram stain, IF stain histopathology

174

Actinomycosis: Actinomyces israelii Complex
Treatment:

IV penicillin (4-6 wks) --> oral penicillin (several months).

175

Fungal Respiratory Infections
Systemic Mycosees (DIMORPHIC)

1. Histoplasma capsulatum:
2. Blastomyces Dermatidis:
3. Coccidiodes immitis:

176

Fungal Respiratory Infections
Systemic Mycosees (DIMORPHIC)
Histoplasma capsulatum:
Microbiology:

Dimorphic w/distinct tuberculate (bumpy) conida
- Mold in soil w/bird or bat excrement in Ohio River
Valley + Central America
- Yeast targets RES system

177

Fungal Respiratory Infections
Systemic Mycosees (DIMORPHIC)
Blastomyces Dermatidis:
Microbiology:

Like histo but does not survive in macros
- Mid-South endemic > south east > mid-west
- Middle age older men.

178

Fungal Respiratory Infections
Systemic Mycosees (DIMORPHIC)
Coccidiodes immitis:
Microbiology:

Tissue form: spherule
- Very contagious; considered bioweapon
- Endemic to semi-erid Southwest USA

179

Fungal Respiratory Infections
Opportunistic Mycosees:

1. Aspergillus spp.:
2. Zygomycetes (Mucormycosis):
3. Pneumocystis Jerovici(Carnii):

180

Fungal Respiratory Infections
Opportunistic Mycosees:
Aspergillus spp.:
Microbiology:

Aspergillus spp.: 45° branch septate hyphae
- Nosocomial infections (hospital air ducts) in
immunocompromised patients

181

Fungal Respiratory Infections
Opportunistic Mycosees:
Zygomycetes (Mucormycosis):
Microbiology:

90° broad septate; ↑ post-soil disturbance (tornado)

182

Fungal Respiratory Infections
Opportunistic Mycosees:
Pneumocystis Jerovici(Carnii):
Microbiology:

Not cultured
- fungal + protozoan traits --> thin cysts with sporozoites (no hyphae, cholesterol in membrane >
ergesterol)

183

Fungal Respiratory Infections
Systemic Mycosees (DIMORPHIC)
Diseases: Damage

Our immune response to phago-resistant fungi

184

Fungal Respiratory Infections
Systemic Mycosees (DIMORPHIC)
H. Capsulatum disease

Histoplasmosis
i. No symptoms > mild flu > pneumo
ii. Immunocompromised/infants have ↑Risk

185

Fungal Respiratory Infections
Systemic Mycosees (DIMORPHIC)
B. Dermatitidis disease

Blastomycosis
iii.Acute pneumo (Brown, purulent / bloody sputum) + wart-like skin lesions > meningitis
iv.Looks like TB / Cancer b/c lung masses develop

186

Fungal Respiratory Infections
Systemic Mycosees (DIMORPHIC)
C. Immitis disease

Coccidiodomycosis (Valley fever - San Joaquin, CA)
i. None > Flu > skin lesions > meningitis
ii.Men, dark skinned, immunocompromised ↑risk for dissemination.

187

Fungal Respiratory Infections
Systemic Mycosees (DIMORPHIC)
H. Capsulatum, B. Dermatitidis, C. Immitis:
Treatment:

None > azole > amphotercin B

188

Fungal Respiratory Infections
Opportunistic Mycosees:
Diseases: Damage

Our immune response to phago-resistant fungi

189

Fungal Respiratory Infections
Opportunistic Mycosees:
A. spp. disease

Aspergillosis
i. pervious respiratory disorders; aspergilloma @ pre-existing lesion.

190

Fungal Respiratory Infections
Opportunistic Mycosees:
Zygomycetes spp. diseases

Mucormycosis/Zygomycosis
i. Acidosis (diabetes) pts or corticosteroids pts
ii.Presents as pneumonia or rhinocerebral form (causes rapid death).

191

Fungal Respiratory Infections
Opportunistic Mycosees:
P. Jerovici (Carinii) disease

Pneumocystis pneumonia (PcP)
i. Looks like diffuse interstitial pneumonia; death from asphyxia

192

Fungal Respiratory Infections
Opportunistic Mycosees:
A. spp., Zygomycetes spp., P. Jerovici (Carinii):
Treatment:

1. Asp./Zyg. = amphotercin B + excision
2. Pneumocystosis = O2 + trimethorpim-sulfa-methoxazole

193

Influenza Viruses
Microbiology:

1. Enveloped, segmented ss-negative RNA
2. Three types (A, B, C); A based on hemagglutinin
(HA) and nueraminidase (NA)

194

Influenza Viruses
Mechanism of Disease/Virulence Factors:
Surface proteins:

- HA: virion attachment/entry; antigenic domain +
receptor binding sites; ↑AA substitution
- NA: virion release; inhibit NA to prevent spread
- M2 (influenza A only): ion channel involved in
uncoating virus; target of aman-/rimantadine
- NS1: IFN antagonist; ↓host mRNA processing

195

Influenza Viruses
Mechanism of Disease/Virulence Factors:
Genome:

- A/B have 8 segments (C=7, no NA gene)
- Ressortment of genes btw co-infected human and
animal influenza --> new strain

196

Influenza Viruses
Epidemiology/Transmission:

1. Transmission: human airborne droplets
(coughing, sneezing, talking + on surfaces)
2. Influenza A Reservoir = avian, human, swine
- Avian: virus grows in resp/GI; found in feces
- Avian reservoir important b/c allows ressortment
and extra-human reservoir
3. B/C reservoir = mainly human
4. ↑Antigenic Drift: minor point mutations in HA +
NA during viral replication from ↑immunity
5. ↑Antigenic Shift: major changes in HA/NA during
ressortment --> pandemic b/c new strain from
ressortment = ZERO IMMUNITY
6. Seasonality (Influenza A + B): winter/spring

197

Influenza Viruses
Diseases:

The Flu (contagious respiratory illness caused by influenza)
Lower respiratory complications cause most deaths.

198

Influenza Viruses
Complications:

1. Pneumonia:
i. Primary Viral: abrupt onset, deterioration in 1-4 days
ii. Secondary Bacterial (superfinection): bacterial infection during viral recovery (viral-bacterial pneumo) or after recovery (post-influenza bacterial pneumo)x
2. Pregnancy: cause fetal loss + congenital malformation (2-3rd trimester)
3. ↑Time for shedding in elderly and immunocompromised
4. Children are at risk (↓immunity) for pneumo, meningitis, encephalitis
***Acetaminophen for fever in children; aspirin --> Reye’s (head/liver)

199

Influenza Viruses
Presentation:

Upper and lower respiratory tracts infected
1. Flu like symptoms: fever, chills, headache, fatigue, myalgia, runny nose, sore throat, and dry cough
2. Short incubation (2 days) - rapid onset
2. Systemic symptoms (fever, etc) go away, but respiratory persist
3. If pneumonia arises, hemoptysis and SOB

200

Influenza Viruses
Diagnosis:

1. Swab nasopharynx for rapid antigen detection (immunoassay)
- Titers peak at 48 hours (before symptoms, bad for spread of virus)
- No ↑Neutrophils or peripheral white cells = VIRAL
2. RT PCR
***Rule out bacterial cause; bacteria will have productive cough with ↑neutrophils and positive pneumococcal culture

201

Influenza Viruses
Treatment:

Vaccination is most important to ↓morbidity/mortality
1. Amantadine/Rimantidine: inhibit M2 ion channel (effective in Infl. A)
2. Zanamivir/Oseltamivir: NA inhibitors; prevent viral release/spread (A/B)

202

Influenza Viruses
Structure: HA

Binds host sialic acid, also on RBC so causes agglutination; Sialic acid receptors in respiratory tract allow viral entry.

203

Influenza Viruses
Structure: NA

Cleaves neuraminic acid (mucin barrier) exposing sialic acid for HA binding; on release it cleaves HA-sialic acid

204

Influenza Viruses
Structure: M2

Channel allows H+ into endosome; ↓pH = dissociation of viral protein.

205

Hantavirus Pulmonary Syndrome (HPS)
Microbiology:

Hantavirus (Bunyviridae Family)
Spherical, lipid-enveloped particles
Trisegmented, -RNA genome

206

Hantavirus Pulmonary Syndrome (HPS)
Mechanism of Disease/Virulence Factors:

- Segment: nucleocapsid protein
- Segment: RNA-dep RNA polymerase
- Segment: G1/G2 envelope proteins

207

Hantavirus Pulmonary Syndrome (HPS)
Epidemiology/Transmission:

“Airborne Infectious Disease”
1. infection from breathing air containing aerosolized rodent saliva, urine, feces.
2. Rural USA (farms, fields, forests)
3. Several hantaviruses can cause HPS; each virus
is carried by specific rodent
- Ex: Si Nombre in Deer Mouse only
4. No human-human

208

Hantavirus Pulmonary Syndrome (HPS)
Diseases:

HPS = severe, sometimes fatal respiratory disease
1. Inhaled rodent saliva/urine/feces
2. Viral load recruits lymphoblasts + macros to pulmonary tissue
3. Activated immune cells --> ↑cytokine release
4. Endothelium is activated
5. ↑Capillary permeability --> pulmonary edema

209

Hantavirus Pulmonary Syndrome (HPS)
Presentation:

Flu like symptoms --> life-threatening pneumonia
Two Stages of Disease:
1. Rapid Onset of Pulmonary Edema
- ↑Viremia at onset of disease
- Flu-like symptoms
2. Respiratory Failure + Cardiogenic Shock
- Cough, SOB, fluid accumulation, ↓BP, cardiogenic shock

210

Hantavirus Pulmonary Syndrome (HPS)
Diagnosis:

Early phase is often confused with influenza virus
Rural rodent exposure is key + tetrad
1. Thrombocytopenia
2. Leukocytosis (left shift)
3. Abnormal lymphoblasts
4. ↑HCT b/c of ultrafiltration into lungs
5. Serological testing (IgM + IgG) or RT-PCR will work

211

Hantavirus Pulmonary Syndrome (HPS)
Treatment:

No treatment, cure, vaccine; supportive care
1. Even though hypotensive, no additional volume!
2. ↑B1-adrenergic cardiostimulation for ↑BP

212

Respiratory Syncytial Virus (RSV),
Human Metapneumovirus (hMPV), and
Human Parainfluenzaviruses 1-4 (hPIVs)
Disease:

Viral pathogens of young children >> elderly/immunocompromised

213

Respiratory Syncytial Virus (RSV),
Human Metapneumovirus (hMPV), and
Human Parainfluenzaviruses 1-4 (hPIVs)
Microbiology: (for all three)

1. Enveloped, non-segmented (no ressortment),
negative-RNA
2. Tropism restricts entry to ↑/↓resp tract cells, thus
no systemic infections

214

Respiratory Syncytial Virus (RSV),
Human Metapneumovirus (hMPV), and
Human Parainfluenzaviruses 1-4 (hPIVs)
Virulence Factors:

1. Fusion Protein(F): viral entry/fusion to adjacent
cells --> syncytia
2. G: unknown gp where RSV binds; RSV can also
bind nuclein
3. HN (HA-NA): hMNV + hPIV bind here

215

Respiratory Syncytial Virus (RSV),
Human Metapneumovirus (hMPV), and
Human Parainfluenzaviruses 1-4 (hPIVs)
Mechanism of Disease

- Virus infect airway epithelium in ↑resp tract --> ↓resp tract via dendritic cells
- Cause airway inflammation, necrosis, sloughing of
epithelium, excessive mucin production, and interstitial lung infiltrates

216

Respiratory Syncytial Virus (RSV),
Human Metapneumovirus (hMPV), and
Human Parainfluenzaviruses 1-4 (hPIVs)
Epidemiology/Transmission:

1. RSV: #1 cause of ↓RT illness/pneumo in kids
2. hMPV: #2 cause of ↓resp tract illness in kids
3. hPIV3: #2 cause of pneumonia in kids
- hPIV common in elderly/immunocompromised
4. All transmit person-person via large droplets
- Very seasonal: fall/spring******
- Community emergence; not widespread (flu)

217

Respiratory Syncytial Virus (RSV)
Diseases:

RSV #1 cause of bronchiolotis + pneumonia < 1 y/o infant
1. RSV infects Nasopharnx --> LRT
2. LRT infection can be permanent (chronic lung disease or asthma)
3. Predisposing factors: Prematurity, early infection (<3 month old), lung/heart disease, SCID, ↓Oxygen supply
***RSV infections in adults are also common, just known for infants

218

Respiratory Syncytial Virus (RSV)
Presentation:

Begins with URT symptoms --> LRT symptoms in 2 days

219

Respiratory Syncytial Virus (RSV)
Diagnosis:

Culture from URT, ELISA for antigen, RT-PCR

220

Respiratory Syncytial Virus (RSV)
Treatment:

No vaccine, care is supportive (↑FiO2, fluids, bronchodilator)
1. Palvizumab: Ab for RSV (↓viral load ≠ severity)
2. Ribavirin: nucleoside analog interferes w/viral replication

221

Human Metapneumovirus (hMPV)
Diseases:

Bronchiolitis +/- pneumonia in infants/elderly

222

Human Metapneumovirus (hMPV)
Presentation:

Similar to RSV, may also see myalgia

223

Human Metapneumovirus (hMPV)
Diagnosis:

RT-PCR is best (serological is bad- most children are + by 10)

224

Human Metapneumovirus (hMPV)
Treatment:

No vaccine, supportive care

225

Respiratory Syncytial Virus (RSV),
Human Metapneumovirus (hMPV), and
Human Parainfluenzaviruses 1-4 (hPIVs)
Take Home Messages:

These viruses are ID by:
AGE OF PATIENT (kids)
SEASONALITY (late fall/early spring)

226

Human Parainfluenzaviruses 1-4 (hPIVs)
Diseases:

hPIV3 #2 cause of pneumonia + bronchiolitis in children

227

Human Parainfluenzaviruses 1-4 (hPIVs)
Presentation:

Croup, hoarseness, systemic symptoms

228

Human Parainfluenzaviruses 1-4 (hPIVs)
Diagnosis:

Culture, RT-PCR, ELISA OR ↑IgG/IgM

229

Human Parainfluenzaviruses 1-4 (hPIVs)
Treatment:

No vaccine, supportive care

230

Adenovirus (AdV)
Microbiology:

1. DS-linear-DNA in icosahedral capsid w/out an
envelope (nake nucleocapsid)
2. Viral genome/particles assembled in nuclei
3. Naked = stable against detergents, GI tract (↓pH),
and alcohol; survive outside body

231

Adenovirus (AdV)
Mechanism of Disease/Virulence Factors:

1. Serotype defined by capsid penton protein
- Attachment proteins
- Resposnible for toxic effect
- Penton-specific Abs = life long immunity against
that serotype
2. AdV hexon proteins (capsid) stimulate
complement-fixing Abs
- Do not confer immunity, but useful testing

232

Adenovirus (AdV)
Epidemiology/Transmission:

1. Transmission: inhalation of water droplets
- Fecal oral route or direct inoculation
2. Common in Kids = respiratory infections
3. Military recruits = ARD
4. Eye infections = swimming pools
5. Endemic infections = late winter/early spring

233

Adenovirus (AdV)
Diseases:

AdV leads to several disease from pharynx, conjunctiva, GI in children!
- May have link to obesity?
1. AdV replicates in oropharynx, conjunctivae, or intestine
2. AdV induces immune response --> Cell necrosis + inflammation (acute phase)
3. AdV may persist, spread (viremia), or become latent in tonsils, ADENOids, or Peyer’s Patches (shedding 6-18 months)

234

Adenovirus (AdV)
Subsequent infections are serotype specific:

- Serotypes 4 + 7 = ARD (military recruits)
- Serotypes 40-41 = GI tract infections in kids
- Serotypes 36+37 = obesity?

235

Adenovirus (AdV)
Presentation:

1. Respiratory (pharynx): cough, fever, sore throat
2. Ocular: “sand in eye” , runny nose
3. GI: diarrhea, vomiting

236

Adenovirus (AdV)
Diagnosis:

1. Culture form throat/eye/excrement for cytopathic effect in culture
2. Penton-specific Abs
3. Hemagglutination inhibition assays (HIA) b/c Abs to penton block penton’s ability to clump RBCs
4. Hexon Abs confirm presence of AdV but not serotype
5. B/c AdV persists, presence does not mean it is responsible for current symptoms; need 4x higher titer in convalescent

237

Adenovirus (AdV)
Treatment:

No virus specific therapy
1. Military receives attenuated, live vaccine where AdV-associated acute respiratory disease (serotype 4+7) occurs
2. Encapsulated serotypes 4+7 are released enterically for minor infection to develop immunity

238

Coranovirus
Microbiology:

1. Enveloped, ss RNA+ genome virus
2. RNA+ are like post-transcriptional eukaryotic
mRNA (5’-methyl cap, polyA 3‘tail)
3. No polymerase; uses host

239

Coranovirus
Mechanism of Disease/Virulence Factors:
1. S (Spike protein):

Allows binding of CoV and fusion of viral membrane with host for entry

240

Coranovirus
Mechanism of Disease/Virulence Factors:
2. HE (Hemagg-esterase):

Virus entry/exit

241

Coranovirus
Mechanism of Disease/Virulence Factors:
3. E (Envelope protein):

Integral protein in viral membrane involved in morphogenesis, assembly, budding + ion channel activity used in viral replication

242

Coranovirus
Mechanism of Disease/Virulence Factors:
4. M (Membrane protein):

Budding/envelope

243

Coranovirus
Mechanism of Disease/Virulence Factors:
5. N (Nucleocapsid):

Binds viral genome + M protein for virion assembly and budding

244

Coranovirus
Mechanism of Disease/Virulence Factors:
6. RdRp

(RNA-dep-RNA polymerase)

245

Coranovirus
Mechanism of Disease/Virulence Factors:
7. PLprox + 3CLpro:

Cleave polyprotein virus

246

Coranovirus
Epidemiology/Transmission:

1. Transmission: HCoVs spread amongst pple
- via airborne droplets w/cough, talk, or sneeze
- Direct contact w/contaminated surfaces
- SARS-CoV = mutated virus from bats that crossed
species to humans
2. Epidemiology
- Children/winter infections w/HCoV common

247

Coranovirus
Diseases:

Harmless “common cold” CoV becomes SARS!
Common Cold: CoV cause mild URI
Croup: CoV causes croup in young children
Pneumonia: uncommonly CoV can infect lower lung in elderly/children

248

Coranovirus
SARS:

Severe lower resp infections --> pneumonia
1. SARS-CoV infects Type II Pneumocytes --> diffuse alveolar damage
2. Alveolar damage --> respiratory failure --> ARDS

249

Coranovirus
SARS
Presentation:

1. Cold symptoms > GI symptoms >>> Neurosymptoms (rare)
2. SARS: 2-10 incubation --> fever --> flu-like symptoms --> respiratory symptoms + GI symptoms --> respiratory failure

250

Coranovirus
SARS
Diagnosis:

1. Common Cold: undiagnosed / self-limiting; RT-PCR for viral genome
2. SARS: recent travel to China, Taiwan

251

Coranovirus
Treatment:

No treatment of HCoVs
SARS:
1. Ventilatory support +/- anti-microbials for secondary infections

252

Coranovirus
Replication:

1. Virus enters and uncoats
2. +RNA genome is translated --> RdRp (further genome replication)
3. -RNA strands synthesized
4. -RNA strands serve as template for more +RNA progeny genome and mRNAs for translation
5. mRNAs translated --> nonreplication machinery polyproteins
6. RdRp does not proofread = variety of CoV genomes

253

Rhinovirus
Microbiology:

1. Non-enveloped, +RNA virus
2. No envelope = survive on surfaces outside body
on surfaces
3. But, Cannot survive outside nasopharynx b/c
↑ temp in lower resp/GI and ↓ pH in stomach

254

Rhinovirus
Mechanism of Disease/Virulence Factors:

1. RV serotypes based on receptor specificity:
- ICAM-1
- LDL-R
- Sialoprotein Receptors
2. 100 serotypes = no developed immunity
3. Has Viral Protease that cleaves cap-binding
complex of euk cells = shut off protein synthesis
4. But, can still replicate using host machinery via
IRES (internal ribosomal entry site) allowing
selective translation of viral proteins

255

Rhinovirus
Diseases:

RV most frequent cause of common cold (acute respiratory tract infection)

256

Rhinovirus
Presentation:

1. Infection by RV in nose --> 12-72 hr incubation while viral protease promotes viral protein synthesis in nasal cells --> viral inflammation
2. Local nasal inflammatory response to virus responsible for symptoms:
- Nasal discharge
- Sneezing
- Obstruction
- Throat infection
3. Other complaints: loss of smell and taste, cough, hoarse voice
4. Even with sore throat, no sign of pharyngitis (exudate, erythema)

257

Rhinovirus
Diagnosis:

Based upon symptoms
***If fever / systemic symptoms are present --> alternative bug!
***If erythema, edema, exudate appears in pharynx --> other bug!
***Conjunctivitis/nasal polyps --> adenovirus

258

Rhinovirus
Treatment:

1. Self-limiting; treat symptoms and limit contact
2. B/c of 100+ serotypes = no vaccine happening

259

Rhinovirus
Epidemiology/Transmission:

1. ↑ incidence in fall and spring
2. Independent of exposure to cold, Δtemp, etc
3. Transmission: exposure to infected respiratory secretions via inhaled particle
- Direct contact w/doors etc
4. Other viruses cause common cold, but w/
↑ nasopharyngitis and ↑ serious lung infection