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Definitions, characteristics, transmission modes, symptoms, causes, and control measures for mycobacterium, specifically mycobacterium tuberculosis, and tuberculosis. It covers the unique cell wall structure of mycobacterium, the definition, transmission, and symptoms of tuberculosis, as well as the primary etiologic causes, incidence, risk factors, epidemiology, laboratory testing, infection control measures, chemoprophylaxis, treatment, mechanism of action of first-line antimicrobials, directly observed therapy, and the emergence of multi-drug and extensively drug-resistant tuberculosis. Additionally, it discusses the bcg vaccine, mycobacterium avium-intracellulare complex, and leprosy.
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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
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
DEFINITION 3 person-to-personvia respiratory aerosols droplet nuclei coughingsneezingother forceful respiratory activities TERM 4
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
DEFINITION 5 prolonged productive cough sometimes w/ bloodchest painfeverfatiguenight sweatsloss of appetite & weight
Primary etiologic causes Mycobacterium tuberculosis Mycobacterium bovis Mycobacterium kansasii Mycobacterium avium-intracellulare (immunocompromised patients, especially HIV-infected) TERM 7
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
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
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
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
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
DEFINITION 17 health care worker watches patient swalloweach dose of medication WHO DOTS Program 22 high risk countries
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
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
DEFINITION 20 frequent tuberculosis-like disease in AIDS patients ~ 50% of AIDS patients develop tuberculosis ~ 40% are caused by MAI
Reservoir ubiquitous birds/animals & environment (soil & water) transmitted from environment not usually transmitted person-to-person TERM 22
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
DEFINITION 23 HANSENS DISEASE an ancient & feared disease ~ 2000 BC skeleton introduced from Asia to Europe by Alexander the Greatmutilation, rejection, & exclusion TERM 24
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
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