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Inhalation-Acquired Infections
Chapter 20
43
Biology
Professional
02/22/2012

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Term
Which model pathogens are Inhalation-Acquired?
Definition
1) Adenovirus

2) Haemophilus influenzae

3) Mycoplasma pneumoniae
Term
Which types of specific infections are predisposed by

1) CNS injury (Traumatic or Cerebral palsy)
2) T cell injury
3) Humoral deficiency
Definition
1) Muscle/nerve dysfunction prevents airway protection leading to
- Aspiration pneumonia
- Abscesses with ENDOGENOUS flora (anaerobic streptococci, fusobacterium)

2) Exogenous opportunistic pathogens (P. jiroveci, CMV)

3) Bacterial pneumonia with common pathogens (encapsulated- no opsonization)
Term
What generalizations can be made about upper respiratory infections (above the larynx)?
Definition
1) Viral> Bacterial

2) Endogenous flora including S. pneumonia. H. influenzae and M. Catarrhalis.

3) Local spread to obstructed ears and sinuses
Term
What generalizations can be made about lower respiratory infections?
Definition
#1 cause of death in developing world

1) Viral> bacterial

2) Aspiration>inhalation

3) Systemic spread
Term
What characteristics define Adenovirus structure?
Definition
Epidemic outbreak + Immune compromise= ADENOVIRUS!

1) Non-enveloped, dsDNA virus

2) Cocksackievirus/adenovirus receptor (CAR) is used by A, C-F (****Fiber type dictates specificity*****!)
Term
Which clinical diseases is Adenovirus Serotype 3 associated with?
Definition
1) Resp infection in adults

2) Pharyngoconjunctivitis

3) Conjunctivitis
Term
When might you expect to see AV serotypes 40 and 41?
Definition
Gastroenteritis
Term
Which AV serotype is the only one that is not common to both Adult Respiratory Infections and Pharyngoconjunctivitis?
Definition
4

3,7 and 14 are common to both
Term
What is the reservoir and method of transmission of Adenovirus?
Definition
1) Humans only (5-10% of resp. infections)

2) Direct contact with
- Resp. secretions/droplets (direct aspiration is very serious)
- GI secretions
- Waterborne (rare for pharyngoconjunctival fever)
Term
Explain Adenovirus pathogenesis.
Definition
- Binds to epithelial/lymphoid cells, enters, and lytic infection causes viremia and dissemination (can become chronic and/or oncogenic)
Term
What 3 forms of AV infection are there?
Definition
1) Lytic
2) Chronic/latent form in tonsils and other lymphoid tissues 3) Oncogenic transformation.
Term
What are the virulence factors associated with AV?
Definition
E1A/B (hijack host resources, E3 (immune evasion) and Cytopathic effect

1) Early mRNAs (E1A and E1B) hijack host growth resources.
- inhibit host cell RNA transport and translation

2) Immune evasion by blocking cell signaling (E3)
- block apoptosis, interferon and MHC synthesis.

3) Cell destruction (Cytopathic)
Term
Which AV serotypes are associated with Enteritis, and which are associated with Age?
Definition
1) 40 and 41 with enteritis
2) 1 and 2 with pediatric URI and LRI
3) 4 and 7 with military recruits
Term
What types of AV infection manifest via nosocomal transmission?
Definition
Epidemic keratoconjunctivitis
Term
How do you diagnose a case of AV?
Definition
for Test, it it PCR!!

1) Culture (definitive but $$$)

2) Shell vial (NOT FOR GI)

3)** Serum Ab (for outbreaks, but >> false positives**

4) **Ag detection (ocular and GI, but limited for others with poor sensitivity)**

5) PCR
Term
How do you treat a case of AV?
Definition
Remember, this is contagious!

1) Primary is supportive care

2) Cidofovir in immunosuppressed patients

3) 4/7 vaccine for military was available but discontinued.
Term
What population is most susceptible to Haemophilus influenzae infection?
Definition
Toddlers who are not vaccinated= H. influenzae!

Look for stiffness, fever and possibly Meningitis.
Term
What are the different clinically relevant Haemophilus species?
Definition
All are SMALL gram-negative, pleomorphic coccobacilli

1) H. parainfluenzae (pneumonia, endocarditis)

2) H. ducreyi (STI)

3) H aegypticus (conjunctivits)
Term
What conditions are required for H. influenzae growth in erythrocytes?
Definition
Encapsulated and nonencapsulated strains

1) Factor X (hematin)
2) Factor V (NAD)

They grow on chocolate agar, but NOT BLOOD AGAR.
Term
What is the reservoir and method of transmission of Haemophilus influenzae?
Definition
1) Humans are sole reservoir

2) Transmitted through respiratory droplets

- type b in children in developing world

- 20-80% in adults in non-typeable, but they have antibodies to encapsulated strains (protective antibodies prevent colonization AND infection)
Term
How does. Haemophilus. influenzae present in the pediatric population?
Definition
OM, epiglottis, pneumonia and meningitis

1) #1 cause of OM with advancing b-lactam resistance (nontypable)

2) Epiglottis (type b) with swollen upper airway compromise (emergency!)- treat with amox/clavanulate

3) Pneumonia (type b) is 80% of pediatric pneumonia, often preceded by viral infection.

4) Meningitis/bacteremia (type b)- hearing loss, CNS seeding and mortality

5) 2-4 are rare because of Hib vaccine
Term
How does. H. influenzae present in the adult population?
Definition
Arise from nontypeable strains

1) OM and sinusitis

2) Meningitis is rare

3) **** Lower respiratory infections (COPD and chronic bronchitis)... Pneumonia can also develop in risky patients.
Term
What virulence factors are associated with H. influenzae?
Definition
Capsule, LOS, IgA-protease, Pilli, Iron-stealing, Transformation

1) Polysacharide capsule for immune evasion (phagocytosis/complement/promotes invation)

- Polyribose ribosyl phosphate (PRP) is type b (Hib)

2) Endotoxin (LOS) acts as adhesin in resp. epithelium and promotes inflammation and sepsis in invasive disease.

3) IgA protease

4) Pili and afimbrial adhesins

5) Obtains Iron from heme and transferin

6) Genetic transformation
Term
What is the general course of H. influenzae pathogenesis?
Definition
1) Transmission (droplet and carriers)

2) Colonization (if not protective Ab) with LOS, Adhesins, IgA protease and Iron uptake

3) Infection (if viral infection, Environmental factors or humoral deficiency)

-Local (OM, Pneumonia, Sinusitis)
-Invasive (Capsule! Bacteremia, Meningitis)
Term
What is the most critical determinant in Invasive H. influenzae infection?
Definition
The capsule! PRP in Hib

-Leads to bacteremia and meningitis
Term
How would you diagnose an expected case of H. influenzae infection?
Definition
Gram Stain and Culture (Choc vs. Blood)

1) Gram Stain from the right place (pleomorphic gram-negative coccobacilli)
-CSF of unimmunized neonate
-Middle ear fluid from toddler
-Sputum from elderly person with COPD and bronchitis

2) Culture on CHOCOLATE AGAR

3) Latex particle agglutination for Hib capsule antigen

4) Serotyping (OUTBREAK CONTROL)
Term
How do you treat a case of H. influenzae?
Definition
1) Cephalosporins or Amoxicillin/Clavulanate

2) Local (oral therapy)
Invasive (IV)

3) Carriers are important for Hib, so treat contacts with rifampin (doesn't prevent index cases!)
Term
How is H. influenzae prevented?
Definition
1) 1985 had good immunity, but not under 18 months

2) Hilleman's solution- Polysacharide conjugated to protein vaccine (PRP-OMP)

- T/B cell immunity
- Boostable
- Nearly eradicated Hib
Term
A patient presents with Persistent coughing, Erythemia maultiforme + (rash) and Anemia (pallor).

What is the problem?
Definition
Mycoplasma pneumoniae!

- Prokaryote w/o cell wall
- Sterols in cell membrane
- Size of myxovirus (only thing smaller than Chlamydia)
Term
What makes M. pneumoniae a "wierdo" pathogen?
Definition
- Prokaryote w/o cell wall
- Sterols in cell membrane
- Size of myxovirus
Term
What clinical symptoms are associated with M. pneumoniae infection?
Definition
Rarely Invasive UR and LR disease

1) Erythema multiforme
2) Hemolytic anemia
3) Thrombotic thrombocytopeniic purpura
4) Bell's palsy.
Term
What is the reservoir and method of transmission of Mycoplasma pneumoniae?
Definition
1) Restricted to humans (adults > children)

2) Respiratory droplets only colonize respiratory epithelium and NOT ALVEOLI (unlike Adenovirus), and can cause outbreaks
Term
Explain M. pneumoniae pathogenesis.
Definition
1) Attaches to respiratory epithelium with adhesins (P1/41 organelle)

2) Damages epithelium

- CARDS toxin (ADP-ribosylating cytotoxin) causes epithelial damage and asthma

- Peroxides

3) Inflammation
Term
How do you diagnose a case of M. pneumoniae?
Definition
Majority are asymptomatic (70-90%!)

1) Clinical symptoms (atypical pneumonia, EM, anemia)
2) Serology (many false positives)
3) PCR (LRT>URT)********
4) Cold agglutinins (specific but insensitive)
5) Culture not useful
Term
How do you treat a case of M. pneumoniae?
Definition
Once identified by anemia, erythema multiforme and cough.

EVIDENCE OF EFFECTIVENESS LACKING

B-lactams won't work- need to target INSIDE CELL

1) Ribosome-Tetracyclines and Macrolides (static)
2) DNA-Flouroquinolones (cidal)

**prophylaxis with Azithromicin during outbreak**
Term
How can you prevent/manage an M. pneumonia outbreak. vs. a Haemophilus influenza outbreak?
Definition
M. pneumo- Prophylaxis with Azithromicin during outbreak

H. influenzae- Prophylaxis with rifampin
Term
What common pathogens cause OM?
Definition
1) Strep. pneumo
2) Nontypeable H. influenzae
3) Moraxella cattharhalis
Term
What common pathogens cause Rhinitis?
Definition
1) Rhinoviruses (Picornavirae)
2) Coronaviruses (SARS)
Term
What common pathogens cause acute Pharyngitis?
Definition
1) Strep pyrogenes

2) Corynebacterium diphtherium (gram + rods)

3) Adenovirus
Term
What common pathogens cause Epiglottitis?
Definition
H. influenzae type b
Term
What common pathogens cause Acute bronchitis?
Definition
1) Influenzae
2) Mycoplasma pneumoniae
3) Bordatella pertussis
4) Adenovirus
Term
Which pathogens are primarily inhaled?
Definition
1) Histoplasma
2) Legionella,
3) Tuberculosis
4) Anthrax
5) Tularemia
Term
How would an AV or M. pneumonia infection appear on a thoracic X-ray?
Definition
Interstitially.

Not a typical Lobar distribution!
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