Exam #4: Lower Respiratory Infections III Flashcards
Describe the characteristics of Mycobacteria tuberculosis.
- Weakly gram (+)
- Acid fast rods (Ziehl-Neelsen or Kinyou stain)
- Lipid rich cell wall
Describe the cell wall of Mycobacteria tuberculosis. What is unique about the cell wall?
The cell wall of mycobacteria is lipid rich & responsible for acid fast staining. Specifically, the cell wall contains:
1) Arabinogalactan
2) Lipoarabinomannin
3) Mycolic acids
4) Mycolic acid associated glycolipids
What does Mycobacteria tuberculosis cause?
TB
What is the #1 bacteria causing infection in the world?
Mycobacterium tuberculosis (Mtb)
Globally, where is TB most endemic?
Sub-Saharan Africa
What is the reservoir for Mycobacterium tuberculosis (Mtb)?
Humans
How is Mycobacterium tuberculosis (Mtb) transmitted?
Person to person transmission via respiratory aerosol droplets
How does Mycobacterium tuberculosis (Mtb) cause infection?
1) Mycobacteria tuberculosis inhaled & enters alveolus
2) Bacteria is then by alveolar macrophages;
3) Replication occurs in alveolar macrophages & lymphocytes are recruited to the site of infection
4) Incoming macrophages are unable to clear the Mycobacteria tuberculosis infection & consequently the body form a “wall of macrophages” surrounding the bacteria
What is primary TB?
- Mycobacteria tuberculosis enters the lungs & travels to the alveoli
- Asymptomatic (or maybe minor symptoms) but capable of spread
What is active TB?
- Mycobacteria tuberculosis enters the body & evades killing & granuloma formation
- Spread of TB to other parts of the lung & systemic spread
What is latent TB?
- Inability of the immune system to kill Mycobacteria tuberculosis
- CD4+, CD8+, & NK cells surround Mycobacteria tuberculosis & macrophages
- This becomes necrotic & is referred to as “caseous necrosis” because it is the texture of soft white cheese
- A granuloma forms and prevents further spread
How is TB reactivated?
- Immunocompromising event leads to “reactivation” of TB
- Aging i.e. senescence of the immune system
Why is CMI considered to be a double-edged sword in TB?
- CMI controls TB infection by leading to granuloma formation
- However, when granulomas do not prevent the spread of Mycobacteria tuberculosis, or granuloma does not completely wall off TB, then the majority of the pathology that is seen is in response to the immune response to the organism, NOT tissue destruction from a toxin produced by the organism
What is miliary TB?
Disseminated or extrapulmonary TB
- Granuloma formation outside of the lung
- Looks like “millet seeds,” hence the name “miliary”
What are the symptoms of primary TB?
Often asymptomatic
What are the symptoms of active TB?
- Fatigue
- Weight loss
- Weakness
- Fever
- Night sweats
- Chest pain
- Dyspnea
- Cough
- Hemoptysis (necrosis of lung is the source of blood)
What are the symptoms of reactivation TB?
- Patients can often be asymptomatic for 2-3 years and be infectious
- Symptoms are similar to / the same as active TB
- In reactivation TB, on CXR, the granuloma falls apart & Mycobacteria tuberculosis moves to other parts of the lung–also, it can be aerosolized & transmitted to other people
How is latent TB diagnosed?
- Rapid lab test i.e. PPD
- CXR
(Ghon Focus= calcified granulmona outside of hilar lymph node
Ghon Complex= calcified granulmona outside of hilar lymph node & in lymph node)
How is active or reactivation TB diagnosed?
1) Clinical symptoms
2) Rapid lab tests
3) CXR
- See the granuloma start to fall apart
- See a lobar pneumonia in apical posterior segments of the upper lobes
- Cavitation
What is the difference between a Ghon focus & Ghon complex?
Ghon Focus= lesion/ granuloma seen on CXR as is calcifies in the lung
Ghon Complex= lesion seen in lung & affection hilar lymph node
What is a PPD?
- Tuberculin skin test
- Involves an intra-dermal injection of purified protein derivatives (PPD), which come from the TB cell wall
What is the BCG-vaccine?
TB vaccine
Will people vaccinated with a BCG-vaccine test positive on PPD?
Yes–every time
What is the IFN-y release assay? What patient population is it best for?
- Better test for vaccinated individuals
- IFN-y release by T-cells is measured in whole blood stimulated with Mycobacteria tuberculosis antigen
What other lab techniques are available to test for TB in addition to PPD & IFN-y?
1) Ziehl-Neelsen/ Kinyoun stain
- Acid fast staining methods; NOT specific for TB
2) PCR (expensive)
3) Culture
What are some of the drawbacks of TB culture?
- Mtb is very slow growing, which leads to contamination issues
- Preparation with KOH or NaOH treatment improves contamination
How is TB treated?
2 months of:
- Isoniazid (INH)
- ethambutol
- pyrazinamide
- rifampin
26 months of:
- INH
- rifampin
What is INH associated with? What are the compliance issues associated with INH?
- INH is a prodrug that is administered to patients w/ TB
- Its metabolite inhibits mycolic acid synthesis
- However, it is hepatotoxic & associated with many adverse effects
*Because it has to be taken for >26 months, there are significant patient compliance issues
What is the BCG vaccine?
- Mycobacterium bovis vaccine that is used in endemic countries
- Cow strain of TB that is slightly infectious to humans
Where are people vaccinated against TB? Why?
Most of Europe, Asia, Africa, South & Central America because this is where TB is endemic
*Not American & Netherlands because it is not completely protective & vaccinated individuals test positive on test & require v. expensive & complicated INF-y test
What is the connection between TB & AIDS?
- Primary infection with TB is more likely in HIV patients
- Progression to active TB is more likely in HIV infected
- Reactivation risk is higher in HIV patients
- Multi- and extended-drug resistant strains of TB have a high incidence in HIV patients
*TB & AIDS are the leading causes of premature death in the world
What are nontuberculosis mycobacteria?
Atypical mycobacteria including:
- Mycobacterium avium-intracellulare, which is a complex of several mycobacteria that results in pulmonary infection resembling TB in immunocompromised patients
- Mycobacterium kanassii, which is more common in the elderly, chronic granulomatous disease, and COPD patients
What are the symptoms of laryngitis, tracheitis, & epiglotitis?
- Hoarseness
- Burning retrosternal pain
Note that the larynx & trachea have non-expandable cartilage rings in the wall; inflammation & swelling of mucous membranes can lead to life-threatening obstruction in children
What bacteria cause laryngitis, tracheitis, & epiglotitis?
- GAS
- Haemophilus influenzae
- Staphylococcus aureus
List the characteristics of haemophilus influenzae sterotype B (HiB).
- Gram (-)
- Coccobacilli
- Requires NAD+ & hematin (NAD+= factors V & X= hematin) for growth (chocolate agar)
- Some capsulated, some not
- Capsule is composed of polyribosylribitol phosphate (PRP)
- Type B is the most pathogenic
*Remember when a child has the flu, Mom goes to the five (V) & dime (X) to buy some chocolate (agar),
What is PRP?
- Polyribosylribitol phosphate
- A polysaccharide that forms the capsule of HiB
Important because it is part of the HiB vaccine
What diseases can HiB cause?
Remember hAEMOPhilus A= septic arthritis E= epiglotittis M= meningitis O= OM P= pneumonia
How is HiB transmitted?
- Respiratory droplets or direct contact with respiratory secretions
- Mostly pediatric (mostly unvaccinated)
What are the virulence factors assocaited with HiB?
- PRP
- LPS
- IgA protease
How is HiB infection diagnosed?
Gram staining & culture of:
- blood
- nasopharungeal swab
- sputum
- spinal fluid
How is HiB infection treated?
Severe case= Broad-spectrum cephalosporin
Less severe case= amoxicillin
What is the HiB vaccine?
A conjugate vaccine containing the type B capsular polysaccharide, PRP
What is bacterial bronchitis?
Inflammation of the tracheobronchial tree
What is the most common agent of bacterial bronchitis? What are the virulence factors associated with this causative agent?
Mycoplasma pneumoniae
- P1 Adhesin
What are the symptoms of bacterial bronchitis?
Dry cough that can lead to atypical pneumonia
What is pertussis?
Whooping cough or paroxysmal cough due to an increase respiratory secretions & decreased mucociliary clearance
What causes pertussis?
Bordetella pertussis
What are the characterstics of Bordetella pertussis?
- Gram (-) coccobacilli
- Fastidious
- Adheres to ciliated respiratory mucosa
Describe the presentation of pertussis.
1) Incubation period of 7-10 days without symptoms
2) Catarrhal= 1-2 weeks (like common cold)
- Rhinorrhea
- Malaise
- Fever
- Sneezing
- Anorexia
3) Paroxysmal= 2-4 weeks
- Repetitive cough with whoops
- Vomiting (post-tussive emesis)
- Leukocytosis
4) Convalescent= 3-4 weeks+
- Secondary complications with lessened cough severity
- Pneumonia, seizures, encephalopathy
What are the virulence factors associated with pertussis?
Major adhesins=
- Filamentous hemagglutinin, which binds to ciliated epithelial cells
Major toxins=
- Pertussis toxin that causes an increase in respiratory secretions & paroxysmal cough
Describe the mechanism of action of the pertussis toxin.
- AB toxin
- Active portion leads to a gratuitous activation of adenylate cyclase & consequently increased host cell cAMP–>increased respiratory secretions
How is pertussis diagnosed?
Clinically with lab tests to confirm
- Culture (Bordet-Gengou agar)
- PCR*
- Microscopy
- Serology
How is pertussis treated?
- Supportive therapy
- Macrolides (azithromycin & clarithromycin)
How is pertussis prevented?
Vaccination with DTaP i.e. acellular pertussis
- Vaccine contains detoxified pertussis toxin
