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Mycobacterium characteristics Gram (+) rods acid-fast can NOT be stained by normal methods (use acid-fast stain) "beaded" appearance (lipid-rich wall "wax" repels aniline dye) slow growing intracellular obligate aerobes lipid-rich cell wall ("wax") mycobacterium subspecies facultative intracellular Mycobacterium tuberculosis (grows best at 35-37°C) Mycobacterium marinum (must tell lab, grows @ 30°C) obligate intracellular can NOT be cultured in lab Mycobacterium leprae Mycobacterium Tuberculosis virulence factors cell wall lipids: block fusion of phagosomes & lysosomes in alveolar macrophages Mycobacterium Tuberculosis diseases · primary tuberculosis infection - replicate in alveolar macrophages (like facultative intracellular parasites) - escape from macrophages, attract other macrophages and lymphocytes potential outcomes from primary infection · healing immune response: most common, occurs in 90% of those with intact CMI - "granulomatous" cell-mediated response ends the infection - some organisms may remain walled off in "ghon complex" (caseous granuloma) · progressive primary infection: common in children <5; 10% of CMI-intact adults - erosion of granuloma into airway (result of ghon focus enlargement) - typically occurs in the mid lung region · special case: military tuberculosis - infection at multiple sites (RES, marrow, lungs - sites with sinuses, capillary beds) - characteristic lesion: small, yellowish lesion resembling millet seed · secondary ("cavitary") tuberculosis infection - disease in person who has mounted cell-mediated response to M. tuberculosis - can be one of the following two situations: - reactivation of latent organisms - new infection in patient with previous infection - usually in posterior, upper lobes of lung (in contrast to primary infection) - mechanism of cavity formation: - proliferating bacteria incite enhanced cell-mediated response - cell-mediated immune response leads to tissue necrosis, cavitation TB clinical diagnosis history components that are key: - country of origin - recollection of exposure (e.g. family members) - poverty, crowded conditions - health-care worker · symptoms of active tuberculosis disease: - low-grade fever - night sweats - weight loss - productive cough - blood in sputum (hemoptysis) · TST skin test: IM injection purified protein derivative from M. tuberculosis cultures - meant to elicit evidence of a primed cellular response (type IV hypersensitivity) - after 48-72 hrs, determine if induration (hardened area) present at injection site - induration would be due to migration of macrophages and T-cells to injection site - if present, measure diameter in mm and interpret based on guideline - redness (erythema) ALONE at injection site is NOT a positive reaction - positive TST test indicates EXPOSURE, but NOT necessarily active disease Mycobacterium Tuberculosis treatment 4 or 5 specified agents simultaneously - until specimen susceptibility is known - multi-drug resistance is a major issue Mycobacterium Tuberculosis resistance · develops spontaneously by mutation · combined therapy reduces odds of resistance mutation rates - higher for isoniazid (10-5) than streptomycin (10-6) - lowest for isoniazid + streptomycin combo (10-11) most likely results of diff. treatment regimens - isoniazid alone: resistant mutants survive - streptomycin alone: resistant mutants survive - isoniazid + streptomycin: all cavity bacteria killed Mycobacterium Tuberculosis epidemiology - 10% adults* develop active disease in lifetime - * adults without prophylaxis - HIV co-infection: 8% risk per year of active disease - latent infection: weak immunity can make it active - mostly controlled in US and W. Europe - 50% of rest of world is infected - 3 million deaths per year - world: most common ID cause of death Mycobacterium Tuberculosis transmission - respiratory droplets and respiratory nuclei - actively infected pt is ridiculously contagious! - <10 infectious rods needed for infection - actively-infected: 3000 infectious nuclei per cough Mycobacterium Tuberculosis lab diagnosis · sample - 3 morning sputums over 10-day period - do NOT use swabs, mycobacteria will cling - NaOH does both digestion + decontamination · culture - still the mainstay (said in lecture, not syllabus) - liquid media is the best medium · stained smears - concentrated: more sensititive, harder to find - direct: much less sensitive, always available · acid fast stains - fluorochrome stain is best stain method - uses auramine + rhodamine dyes - note: NOT an "immunofluorescence" technique · identification - ss-DNA probe complimentary to bacterial RNA - does NOT involve PCR; related to culture · amplification - PCR/TMA - approved for "smear positive" specimens only - approved for pts with NO prior TB history only · susceptibility testing - absolutely necessary for initial isolate - use for: therapy failure or non-compliance - US: "M. tuberculosis" = "M. tuberculosis complex" tuberculoid leprosy pathological features - cause: positive CMI (delayed hypersensitivity) reaction to lepromin antigen - lesions: macules, large plaques w/ raised red edges and pale, dry hairless centers - usually on face, trunk, limbs - lesion pathology: granulomatous (epithelioid + giant cells, lymphocytes) - lesions contain FEW mycobacterium leprae organisms - nerve involvement: variable patchy invasion of peripheral nerve - results in loss of sensation (anesthesias) in these areas clinical course - usually indolent, slow progressing and healing - usually non-contagious lepromatous leprosy pathological features - cause: negative, deficient CMI, with resulting anergy to lepromin antigen - lesions: leonine facies, diffuse symmetric thickening of loose skin - lesion pathology: "foamy" macrophages, FEW lymphocytes - thickening usually affects loose skin of lips, forehead and ears - lesions contain MANY mycobacterium leprae organisms - may also be: destruction of nasal bones, septum, digits and atrophy of testicles clinical course - usually results in disfigurement, loss of digits - much more contagious than the tuberculoid form tb clinical diagnosis - clinical picture, history, country of origin Mycobacterium Leprae treatment - therapy available - therapy must continue for years Mycobacterium Leprae epidemiology - rare in US, but 10-12 million cases worldwide - children more susceptible to infection than adults - main reservoir: infected humans Mycobacterium Leprae transmission - tuberculoid leprosy: - usually not contagious (too few organisms) - lepromatous leprosy: - nasal secretions
nasal mucosa or break in skin Mycobacterium Leprae lab diagnosis · stain, NOT culture - scrapings of infected tissue (nose, ear lobes) - lepromatous form: many acid-fast bacilli seen - tuberculoid form: not many acid-fast bacilli - may require think skin biopsy