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Mycobacterium
UNIQUE CELL WALL STRUCTUREHigh lipid contentmycolic acid & waxD - isoniazid targetArabinoglactan - ethambutol targetCord factor associated with virulence - toxic to mammalian cells - inhibits PMN migrationPPD purified protein derivative TERM 2
Mycobacterium tuberculosis
DEFINITION 2 aerobicslightly curved slender acid fast rods (bacilli)slow growing doubling time ~20 h 6-8 weeks for culture on solid mediaprimarily human reservoir TERM 3
Transmission of Mycobacterium
tuberculosis
DEFINITION 3 person-to-personvia respiratory aerosols droplet nuclei coughingsneezingother forceful respiratory activities TERM 4
Tuberculosis
DEFINITION 4 primary infection in the lungs (~85% of cases)may spread to many other areas of the body - lymphatics - bones & joints - meninges - genitourinary tract TERM 5
Clinical symptoms of pulmonary
tuberculosis
DEFINITION 5 prolonged productive cough sometimes w/ bloodchest painfeverfatiguenight sweatsloss of appetite & weight
Primary etiologic causes of pulmonary
tuberculosis
Primary etiologic causes Mycobacterium tuberculosis Mycobacterium bovis Mycobacterium kansasii Mycobacterium avium-intracellulare (immunocompromised patients, especially HIV-infected) TERM 7
Tuberculosis Incidence, by race/ethnicity
DEFINITION 7 CA & especially SF & LA ~60% higher Hawaii ~ 100% higher Incidence of TB has slowly declined in all racial/ethnic groups Rate in Asian/Pacific Islanders >3X higher than other races TB Rate ~10X greater in foreign-born but ~40% of cases in US-born For US Immigrants from Endemic Regionrisk of active TB greatest in 1st year TERM 8
Risk factors for tuberculosis
DEFINITION 8 (1) increased exposure to M. tuberculosis close contact with a source case same household long-term care facilities residence in high incidence locations foreign-born(2) increased risk of developing disease -HIV infection -immunosuppressive therapy - injection drug abuse -Diabetes -extremes of age - severe malnutrition TERM 9
Epidemiology of tuberculosis
DEFINITION 9 close contact exposure ~ 25-30% of individuals become infected ~ 5-15% of infected individuals develop primary pulmonary pneumonia (within 2 yrs.~ 85-95% of primary infections are asymptomatic(containment)latently colonized majority will never develop clinical tuberculosissome will develop reactivation tuberculosis later - majority of new tuberculosis cases in USA each year result from reactivation TERM 10
TUBERCULOSIS LABORATORY TESTING
DEFINITION 10 Tuberculin Skin Test (TST or Mantoux test)INF- Release Assay (IGRA)Acid Fast Bacilli (AFB) Staining poor sensitivity 45-80% 24 hour resultsNucleic Acid Amplification (NAA) Test(s) better sensitivity 24- hour resultsCulture Gold standardbut 1-8 weeks for results
Mechanism of Action of 1st-line Antimicrobials
Isoniazid - inhibits synthesis of mycolic acids - bactericidalRifampin - inhibits DNA-dependent RNA-polymerase - bactericidal, resistance develops rapidilyPyrazinamide - mechanism unknown - best activity intracellular @ acidic pHEthambutol - inhibits synthesis of arabinoglactan - bacterostatic, resistance develops rapidily TERM 17
Directly Observed Therapy (DOT)
DEFINITION 17 health care worker watches patient swalloweach dose of medication WHO DOTS Program 22 high risk countries
- 43% of world population - 80% of TB infection TERM 18
Emergence of MDR-TB, XDR-TB, & XXDR-
TB
DEFINITION 18 MDRTB - Multidrug resistant TB resistance to at least isoniazid and rifampicin,the two most powerful first-line anti-TB drugsXDRTB - Extensively drug resistant TB (MDR-TB) + resistance to (i) any fluoroquinolone, & (ii) at least 1 of 3 injectable2nd-line drugs capreomycin, kanamycin, etc.)XXDR-TB - Extremely drug resistant TB resistant to all 1st-line & all 2nd- line drugs TERM 19
Immunization
DEFINITION 19 BCG vaccine (bacillus Calmette-Gurin) live attenuated strain of Mycobacterium bovis prevents clinical tuberculosis (variable success) does not prevent infection used where incidence of tuberculosis is high not routinely used in USA incidence is low (not cost effective) interferes with use of PPD skin test for screening BCG immunization = PPD-positive TERM 20
Mycobacterium avium-intracellulare complex
(MAI or MAC)
DEFINITION 20 frequent tuberculosis-like disease in AIDS patients ~ 50% of AIDS patients develop tuberculosis ~ 40% are caused by MAI
Mycobacterium avium-intracellulare complex
- Reservoir
Reservoir ubiquitous birds/animals & environment (soil & water) transmitted from environment not usually transmitted person-to-person TERM 22
Mycobacterium avium-intracellulare complex
- Treatment / Prevention
DEFINITION 22 Treatment & Prevention resistance to anti- tuberculosis drugs is problematic prolonged multidrug therapy (as many a 6 drugs) rifabutin, clarithromycin, azithromycin, otherschemoprophylactic treatment of HIV patientsno vaccine TERM 23
Mycobacterium leprae / Leprosy
DEFINITION 23 HANSENS DISEASE an ancient & feared disease ~ 2000 BC skeleton introduced from Asia to Europe by Alexander the Greatmutilation, rejection, & exclusion TERM 24
Epidemiology of Leprosy
DEFINITION 24 1985 5.4 million registered cases ~10-12 million total cases2000 700,000 registered cases2003 457, cases2009 244,796 cases2010 211,903 casesdrugs free from WHO since 1995 ~14 million people cured & 90% drop in incidence TERM 25
Mycobacterium leprae / Leprosy -
Epidemiology
DEFINITION 25 Reservoir humans armadillosTransmission nasal secretions cut or abrasion prolonged contactnot very contagious 5% of exposed infected (lepromin skin test)2- years before symptoms occur.usually gradual progression
