Pulmonary Microbiology Flashcards
(259 cards)
1
Q
Tularemia:Francisella Tularensis
Microbiology:
A
Gram-, aerobic, non-motile, non-spore
coccobacillus
2
Q
Tularemia: Francisella Tularensis
Mechanism of disease/Virulence Factors:
A
Survives host’s innate immune response: i. ↓LPS immunostimulation ii.Capsule = complement resistance iii.↑Survival in macrophages from iglABCD transposon mutagenesis
3
Q
Tularemia: Francisella Tularensis
Epidemiology
A
Not spread person-person
- Yet, occurs in rural areas b/c infected animals
- Incubation from hours –> weeks
4
Q
Tularemia: Francisella Tularensis
Transmission: Modes of Infection:
A
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
Q
Tularemia: Francisella Tularensis
- Normal outbreak vs. Bioterrorism Use
A
i. Bioterrorism outbreak has point-source outbreak
(urban, non-agricultural city)
ii.Respiratory illness in healthy persons
6
Q
Tularemia: Francisella Tularensis
Disease Types:
A
- Ulceroglandular Tularemia (most common):
- Glandular Tularemia
- Oculoglandular Tularemia
- Oropharyngeal Tularemia
- Pneumonic Tularemia
- Typhoidal Tularemia (rare)
7
Q
Ulceroglandular Tularemia
Presentation
A
(most common):
- Skin ulcer at infection site (bug bit) - (“ulcero-”)
- Swollen glands (“glandular)
- Fever, chills, headaches, exhaustion
8
Q
Glandular Tularemia
Presentation
A
- Swollen glands (“glandular)
- Fever, chills, headaches, exhaustion
9
Q
Oculoglandular Tularemia
Presentation
A
- Swollen glands + eye pain, redness, discharge, eyelid ulcer.
10
Q
Oropharyngeal Tularemia
Presentation
A
(eating poorly cooked infected meat)
- Fever + GI symptoms (sore throat, vomit, diarrhea)
11
Q
Pneumonic Tularemia
Presentation
A
(in elderly and also with typhoidal tularemia)
- Pneumonia symptoms = cough, chest pain, difficulty breathing
12
Q
Typhoidal Tularemia (rare) Presentation
A
- Fever, exhaustion, vomit, diarrhea, pneumonia
- Enlarged liver + spleen
13
Q
Tularemia: Francisella Tularensis
Diagnosis:
A
- Blood Culture for F. Tularensis
- Serology for Tularemia (blood test measuring immune response)
- CXR (patchy infiltrates)
- PCR sampling ulcer
14
Q
Tularemia: Francisella Tularensis
Treatment:
A
Tularemia cured w/antibiotics Streptomycin and Tetracycine
15
Q
Comparing Tularemia w/
Anthrax + Plaque CXR:
A
- Anthrax: dry, nonproductive cough w/
widened mediastinum on CXR - Plague: watery/bloody productive cough w/acute
bacterial pneumonia signs on CXR - Tularemia: non-productive cough w/patchy infiltrates.
16
Q
Anthrax: Bacillus Anthrax (Ba)
Microbiology:
A
- spore forming rod
- Gram+, facultative anaerobe, non-motile
- Spore (infectious form) viable 100yrs in soil
- Spore (1-5 um) reaches lungs
17
Q
Anthrax: Bacillus Anthrax (Ba)
Mechanism of disease/Virulence Factors:
A
- Ingested by pulmonary/cutan/GI macrophage
- Surviving spores released to hilar lymph node
- Spores vegetate –> acq. virulence factors:
- Anti-phagocytic non-antigenic capsule (poly-dglutamic acid)***
18
Q
Anthrax: Bacillus Anthrax (Ba)
- AB Toxin (Anthrax Exotoxin)?
A
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
Q
Anthrax: Bacillus Anthrax (Ba)
Epidemiology/Transmission:
A
:1. Reservoir=cows; farmers safe (spores on soil)
- Imported wools/hides “Woolsorer’s Disease”
- Misdiagnosed: plague, tularemia (Category A)
20
Q
Anthrax: Bacillus Anthrax (Ba)
Disease Types/Symptoms
A
Toxins –> SWELLING, SEPSIS, NECROSIS
- Cutaneous Anthrax (natural + bioterrorism)
- Eschar (black = “Anthracis”), swelling (Edema Factor) - Inhalation Anthrax: Spores (natural + bioterrorism) - TWO PHASES
21
Q
Anthrax: Bacillus Anthrax (Ba)
Inhalation Anthrax: Spores (natural + bioterrorism) - TWO PHASES
A
- 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
Q
Anthrax: Bacillus Anthrax (Ba)
Diagnosis:
A
Culture rarely shows +Ba
- Differentiate from flu (phase 1 symptoms)
- Flu won’t have SOB, nausea, vomit; Anthrax won’t have rhinorrhea - Gram stain, immunofl. Ab stain CSF, blood smears for G+ boxcars
- NO SPORES WILL BE SEEN
23
Q
Anthrax: Bacillus Anthrax (Ba)
Treatment:
A
Incubation can be 6 weeks, leading to:
- 40 days ciprofloxacin/doxy IV prophylaxis + 1 other (ampicillin)
- Vaccine
24
Q
Yersinia Pestis (Plaque) Microbiology:
A
- 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
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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
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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)
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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
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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
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Human Metapneumovirus (hMPV)
Diseases:
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Bronchiolitis +/- pneumonia in infants/elderly
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Human Metapneumovirus (hMPV)
Presentation:
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Similar to RSV, may also see myalgia
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Human Metapneumovirus (hMPV)
Diagnosis:
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RT-PCR is best (serological is bad- most children are + by 10)
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Human Metapneumovirus (hMPV)
Treatment:
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No vaccine, supportive care
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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)
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Human Parainfluenzaviruses 1-4 (hPIVs)
| Diseases:
hPIV3 #2 cause of pneumonia + bronchiolitis in children
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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
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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
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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
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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)
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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
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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
