Mycobacteria Flashcards
Describe mycobacteria.
Obligate aerobic G+ rod
Infections caused by aerosol droplet
Waxes in cell wall
What is primary tuberculosis?
TV caused by inhalation of aerosolized Mycobacterium spp including M. tuberculosis
Initial exposure causes primarty TB eith the formation of focal caseating necrosis in lower lung and hilar lymph nodes
Generally asymptomatic and PPD positive
What are two major risk factors for secondary TB due to reactivation?
Aging and HIV
What is the pathogenesis of secondary TB due to reactivation?
Occurs at apex of lung and can spread to any tissue
Forms cavitary foci of caseous necrosis; may also lead to miliary pulmonary TB or TB pronchopneymonia
Fevers and night sweats, cough with hemotypsis
Describe the cell envelope of mycobacteria
No outer membrane - so more closely related to G+
PG layer not as thick
Unique lipid composition
Why are the mycolic acids and lipids important?
Both structural components and virulence factors
Activates or suppresses the immune responses
What are the two subtypes of granuloma?
Noncaseating
Necrotizing or caseating
Describe TST application.
Tuberculin: Purified Protein Derivative (PPD)
Intradermal placement, 0.1 ml of tuberculin
Injection should produce a pale elevation of the skin 6-10mm
How is TST interpreted?
Two factors: Measurement and risk of progrression to active TB disease
The higher the risk for progressing to active TB, the lower the measurement cutoff for positive
What is an alternative test to PPD?
Interferon-Gamma Release Assay
Blood test that measures the amount of IFN-y produced by T cells exposed to Mtb antigens
IGRAs use peptides from Mtb antigens that are missing in BCG to stimulate T cells
How do you test for active TB disease?
Gold-standard is culture, but slow growth
AFB sputum smear can provide early indication of active TB
Tissue samples for extra-pulmonary disease
What is the best treatment for TB?
Isoniazid
Inhibits enzyme important for producing mycolic acids in the cell wall
Rapid killing for bacteria that are metabolically active, slower for non-dividing
What are treatments for besides Isoniazid?
Rifampin - RNA pol inhibitor
Pyrazinamide - active disease
Ethambutol - treat active disease when INH resistance is suspected
What is the Treatment regimen for pulmonary TB?
3 or 4 drugs for two months followed by 2 drugs for four months
RIF, INH, PZA and EMB for two months
INH and RIF for 4 months
What demographic is particularly susceptible to TB?
HIV-positive
Leading killer
What is Mycobacterium avium-intracellulare Complex?
Acid-Fast bacilli found in macrophages, grows faster than MTB
Second to TB in significance and frequency
Causes systemic infections in HIV patients
What is M. kansasii?
Causes cavitary pulmonary disease, cervical lymphadenitis and skin infections
PPD positive, resembles tuberculosis
Prolonged chemotherapy with isoniazid, rifampin and ethambutanol
What is M. leprae?
Rare in US
Infection manifested by two presentaitons:
Tuberculoid leprosy-miler and self-limiting disease (CMI)
Lepratomous leprosy-severest form of leprosy (NO CMI)
What is Tuberucloid leprosy?
Red blotchy leasions with anesthetic areas
CMI - Th1
Low infectivity
What is Lepromatous Leprosy?
Multibacillary, unimpeded bacterial growth
Skin lesions are diffuse, extensive, depiliated with extensive tissue destruction
CMI deficient, Th2 response
High infectivity
What is the treatment for leprosy?
Tuberculoid - Dapsone and rifampin
Lepromatous: Dapsone, rifampin, and clofazimine
What is the MoA for Dapsone?
Inhibits dihydropteroate synthetase
Disrupts folic acid pathways
What is the result of an IL-2 receptor deficiency?
Weak Th1 response and low levels of IFN-y
Increased susceptibility:
Disseminated Salmonella, non tuberculosis mycobacteria, BCG after vaccine
