Term
| m tuberculosis is sensitive to what? |
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Definition
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Term
| what 3 things determine how infectious TB is? |
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Definition
| 1. intensity of exposure 2. host susceptibility (immunosuppression, renal disease, diabetes, malnutrition, genetic conditions - NRAMP, HLA) 3. source factors (infectious burden , site of infection , strain variation, NOT related to source immunosuppression) |
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Term
| what infected area (TB) predisposes to infectiousness the most? |
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Definition
| laryngeal > cavitary > noncavitary pulmonary >>> extrapulmonary (rare case of inf after wound irrigation) |
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Term
| how do we follow the spread of TB? |
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Definition
| use restriction fragment length polymorphisms to identify strains (20-40% of the time the isolates are of an identical type (clusters) representing recent transmission; 1-2% of the time reflect intra-lab cross-contamination) |
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Term
| TB: what is exogenous disease? |
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Definition
| development of clinical disease within 1-2 years of infection (5% of infected people) |
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Term
| TB: what is primary disease? |
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Definition
| after infection with m. tuberculosis, patient progresses rapidly to clinical illness - subtle lower lobe infiltrate with adenopathy (1% of infected people - mostly immunocompromised and young children) |
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Term
| TB: what is endogenous/re-activation disease? |
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Definition
| development of symptomatic illness from 2 years to decades after initial infection (viable tb bacilli that had persisted in dormant state begin to multiply and elicit a vigorous immune response usually in the apical/posterior segments of the lung altho disease can occur at any site of initial bacillemia). happens in 5% of infected people |
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Term
| what are teh risk factors for reactivation of tb? |
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Definition
| hiv, immunosuppression, advanced age, silicosis, gastrectomy/malnutrition, diabetes |
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Term
| tb: what is reinfection and who's at risk? |
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Definition
| NEW pulmonary tb in someone with prior hx of tb (unique first and second isolates). AIDS+, and immunocompetent in high endemic regions |
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Term
| what host defense is responsible for granuloma/caseation formation? |
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Definition
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Term
| why arent antibodies to tb protective? |
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Definition
| m. tuberculosis is largely an intracellular pathogen |
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Term
| how does our body kill m. tuberculosis? |
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Definition
| mature TH1 cells produce IFNg --> phagolysosomes (acidic, destroy mtb), NO (free radicals kill mtb), stimulates macrophages to produce TNF (recruits monocytes that differentiate into epithelioid histiocytes, making granulomas) |
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Term
| what are epithelioid giant cells made from? |
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Definition
| activated macrophages (activated by CD4 T cells, NK cells and gamma delta T cells) |
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Term
| cavity formation in tb is a clinical manifestation of what process? |
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Definition
| liquefaction necrosis of caseous material in center of granulomas. caseous material softens and liquefies --> intense multiplication of bacilli iwth bronchial communication |
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Term
| what is the effect of HIV on TB clinical presentation? |
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Definition
| more unusual/atypical esp with low CD4. pattern of disease more like primary disease than adult form. less cavitation, less upper lobe involvement, less ppd reactivity, more lymphadenopathy, more dissemination |
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Term
| what makes quantiferon different from PPD and what is it? |
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Definition
| blood test, measuring IFNg in patients blood stimulated with M. tuberculosis specific antigens (not found in BCG), thus prior bcg vaccination will not make this test positive, but TB tx makes this test less reliable, so use for screening in asymptomatic patients |
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Term
| what does acid fast mean? |
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Definition
| organisms resist decolorization in the presence of acid (d/t unique cell walls, which contain mycolic acids) |
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Term
| whats the method of the acid fast stain (kinyoun technique)? |
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Definition
| carbol-fuschin x3min, decolorize with 3% hcl-alcohol (degrades all other bac cell walls), counterstainw ith methylene blue or fluorochrome |
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Term
| why isnt the acid fast stain specific? |
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Definition
| bc its specific for mycobacterial disaese but not necessarily m. tb, bc all mycobac stain similarly (m tb forms serpentine cords) |
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Term
| what is the gold standard for identification and susceptibility testing of m tb? |
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Definition
| culture on solid agar - high accuracy, but takes 3-6 weeks. allows us to distinguish m tb from other mycobacteria |
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Term
| what is a quicker alternative to culturing m tb on solid agar? |
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Definition
| radiometric/liquid media - detects growth by utilization of 14C palmitate and conversion to 14CO2 (10-21 days) |
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Term
| what is the limitation of nucleic acid amplification methods in detecting tb? |
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Definition
| it's sensitive and specific, but limited in practice to detecting HIGH-INOCULUM disease (sputum +) |
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Term
| what are the current tx recommendations for adults with fully susceptible isolates of mtb? |
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Definition
| INH, RIF and pyrazinamide for 2 months, then INH and RIF for 4-7 additional months. 98% cure if pt compliant. add ethambutol in first 2 months if local drug resistance rate is >4% |
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Term
| how long does it take to determine drug resistance in mtb? |
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Definition
| solid media takes 2-4 weeks; liquid media takes 7-10 days but is only used for the 5 main antibiotics |
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Term
| how does mtb acquire drug resistance? |
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Definition
| mutation of the drug target/enzyme required for drug action (NO plasmids or transferable elements) |
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Term
| how do we define multiple drug resistant tb? |
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Definition
| resistant to INH and rifampin |
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Term
| how do we define extremely drug resistant mtb? |
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Definition
| resistant to inh, rifampin as well as a quinolone and 1 of 3 injectable second line drugs (prevalence: 2% worldwide) |
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Term
| what is the effect of bcg? |
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Definition
| decrease in miliary and CNS disease in pediatric population (60-80%); decrease in pulmonary infection (50%, but great geographic variability) |
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Term
| patients with silicosis have ___x lifetime risk of tb vs other pts |
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Definition
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Term
| ppd+ hiv+ pts develop tb at a rate of ___% per year |
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Definition
| 10% per year (vs normal pt 10% lifetime risk), this is 140x lifetime risk of tb |
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Term
| who are high risk groups of people for getting TB? |
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Definition
| silicosis, HIV+, fibrotic cxr, diabetes, end stage kidney disease, malnutrition |
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Term
| for which people is a ppd induration of 5mm or greater considered a +? |
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Definition
| (high risk group) HIV+, people living in close contact with someone who's infected, people with CXR that shows fibrotic scarring, people using high dose steroids or organ transplant |
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Term
| what is the group of people for which a ppd induration of 10 mm or greater is considered +? |
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Definition
| (intermediate risk) medical conditions that increase risk (diabetes, end stage kidney disease, malnutrition), increased chance of having recent exposure (endemic area in past 5 years, living in nursing home etc) |
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Term
| what groups of people have ppd induration >15mm as considered +? |
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Definition
| low risk - people with no known risk for tb |
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Term
| where would someone come into contact with m. leprae? |
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Definition
| tropics, esp india, east africa, brazil |
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Term
| how do we become infected with m. leprae? |
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Definition
| prolonged contact with nasal secretions or skin |
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Term
| what are the 2 subtypes of disease assoc with m. leprae infection? |
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Definition
| tuberculoid (TT) = TH1; lepromatous (LL) = TH2 |
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Term
| what leads to the notorious loss of limbs in m. leprae disease? |
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Definition
| sensory neuropathy --> minor trauma leads to infections/gangrene --> loss of limbs |
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Term
| compare clinical presentation of TT vs LL (tuberculoid vs lepromatous) m. leprae disease? |
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Definition
| TT = palpable peripheral nerve swelling, anesthetic plaques, scant bacilli, many granulomas (immune-mediated pathology --> strong response to lepromin skin test); LL = diffuse skin lesions, nasal mucosal and cartilage destruction, diffuse neural damage, many bacilli, poorly formed granulomas (bacterially-mediated damage --> no response to lepromin skin test) |
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Term
| what is the tx regimen for TT m. leprae disease? |
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Definition
| dapsone + monthly supervised rifampin for 6 months |
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Term
| what is the tx for LL m leprae disease? complications of tx? |
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Definition
| dapsone + clofazamine and montlhy rifampin for 2 years. when we treat LL m leprae, the immune system suddenly recognizes all the quiescent bugs --> disturbing flares of inflammation i.e. erythema nodosum leprosum (painful, immune-mediated nodules). tx this with prednisone or thalidomide |
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Term
| how do we get infected with m. avium/m.intracellulare? |
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Definition
| ingestion and inhalation from contaminated water or soil (environmental reservoirs) |
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Term
| what are the 3 clinical syndromes associated with MAI infection? |
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Definition
| tb-like lung disease, disseminated disease, scrofula |
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Term
| describe who's at risk for TB-like lung disease associated with MAI disease? |
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Definition
| (40% d/t m intracellulare) older male patients with prior TB, bronchiectasis or other lung disease (COPD); thin middle aged women with no underlying disease except often scoliosis |
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Term
| describe who's at risk for disseminated disease associated with MAI infection |
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Definition
| AIDS+ (cd count <75-100) almost always d/t m.avium |
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Term
| what are the clinical features of MAI disseminated disease? |
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Definition
| fever, fatigue, anorexia, diarrhea, diffuse lympahdenopathy, infiltration of liver bone marrrow small bowel., cytopenias |
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Term
| what is the tx for MAI disease? |
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Definition
| newer macrolides (clarithromycin, azithromycin), rifabutin, ethambutol, quinolones, clofazamine, amikacin. multi-drug regimens. rx for life. (surgery for localized disease, and prophylaxis for AIDS+ with CD4<100) |
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Term
| describe what nocardia looks like (what stains, and what morphology)? |
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Definition
| aerobic, weakly afb+, gram+, thin, filamentous, branched rods |
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Term
| where do we come into contact with nocardia? who's at risk? |
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Definition
| soil (soil saprophyte) causing opportunistic infection in immunocompromised |
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Term
| what does nocardia cause clinically? |
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Definition
| necrotizing, suppurative nodular lesions (not granulomatous) in lung (50%), cns (30%), subQ (15%) |
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Term
| what is the tx for nocardia? |
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Definition
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Term
| describe characteristics of the actinomyces organism |
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Definition
| anaerobic, non-acidfast ,gram+, appear as clumps of branched filaments together with host immune cells forming grossly visible yellowish "sulfur granules" |
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Term
| where do we find actinomyces and what do they clinically cause? |
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Definition
| they are normal constituents of oral/gi/gu flora. traverse mucosal barriers? --> large expanding mass lesions with draining sinuses in either neck (lumpy jaw, 55%), lung (15%), abdomen and pelvis (20%) especially several years after IUD placement in women |
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Term
| which patients are at risk for actinomyces? |
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Definition
| women several years after IUD placement, immunocompetent patients |
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Term
| what do actinomyces look like on histological stain? |
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Definition
| suppurative, fibrotic, non-granulomatous histology. mimics tumors with rare metastases |
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Term
| how do we dx actinomyces? |
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Definition
| bx showing sulfur granules, rarely by anaerobic culture |
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Term
| what is the tx for actinomyces? |
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Definition
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