#5 Respiratory Tract Infections II – Flashcards

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question
What organism causes diptheria?
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Corynebacterium diphtheriae, a gram-positive rod that is non-motile and non-spore forming
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How does Corynebacterium diphtheriae appear in a stained slide?
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As "chinese letter" patterns or side by side in "palisides", grows in aerobic conditions on blood agar (selective media are Tinsdale agar and Loeffler’s serum)
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Why is Tinsdale agar medium useful for detection of C. diphtheriae?
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It is both selective and differential via potassium tellurite, inhibits gram negative and most upper respiratory flora except C. diphtheriae
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How does C. diphtheriae appear on Tinsdale agar?
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Dull grey or black colonies due to potassium tellurite
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Why is Loeffler's medium useful for growing C. diphtheriae?
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Enriched, non-selective medium, enhances the production of metachromatic granules within the cells of the organisms which are visible with methylene blue strain
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How is diptheria contracted?
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Humans are primary reservoir, route of infection is by inhalation of droplets or organism by infected materials
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What are the symptoms of diphtheria?
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Starts with respiratory symptoms, sore throat, loss of appetite, low-grade fever, fatigue and malaise, characteristic membrane of the tonsils and pharynx marked by greyish patches, involves distal organs, kidney, heart, and nervous system once it enters the blood
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What makes up the grey-white membrane that covers the tonsils and pharynx in diphtheria patients?
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Clotted blood along with epithelial cells of the host mucus membrane and the leukocytes that are recruited in the process of inflammation and killed by the exotoxins of C. diphtheriae, Exotoxins inhibit the protein synthesis of the host cell and thereby causing death of the cells
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How is diphtheria diagnosed?
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Entirely clinical, direct smear is not reliable, must be isolated and cultured in Tinsdale medium
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How is diphtheria treated?
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Prevented via diphtheria toxoid vaccine which requires a booster every 10 years, treated with anti-serum against diphtheria toxin, treated also with penicillin or erythromycin, mortality rate is high
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What organism causes Hemophilus influenzae pneumonia
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Haemophilus are tiny gram-negative coccobacilli which grows best on chocolate-agar medium, may be capsulated or non-capsulated (capsulated are typed a through f), Type b capsule is a polymer of ribose, ribitol, and phosphate, called polyribitol phosphate (PRP), highly associated with virulence
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What does H. influenza require to grown on medium?
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Hematin (x factor) and NAD (nicotine adenamide diphosphate, V factor)
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How is H. influenza contracted?
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Nasopharyngeal colonization is common, trasmission is from person to person, children under 2 suffer most from meningitis, children 2-5 suffer from epiglottitis and pneumonia
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Which strains of H. influenza are invasive?
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Only capsulated strains, pili and adhesins bind to epithelial cells, no exotoxins, capsule inhibits opsonization and phagocytosis
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What are the characteristics of epiglottitis and pneumonia?
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Sudden onset with fever, sore throat, hoarseness, muffled cough, severe prostration, inflamed epiglottis, and obstruction of airway, shortness of breath, retraction of intercostal muscles
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How is H. influenza diagnosed?
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Clinical findings and gram smear, confirmed by isolation, Coccobacillus growing on chocholate agar but not on blood agar strongly suggest Hemophilus
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How is H. influenza treated?
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Vaccination, current practice is to start with a third generation cephalosporin, may be changed to ampicillin if susceptibility tests indicate that the infecting strain is susceptible
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What are the characteristics of H. influenza immunity?
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Anticapsular antibody is generated, which are bactericidal in the presence of complement, infants are protected by maternal antibody up to 6 months of age, antibody response to Hib PRP is poor in children less than 18 months of age
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What organism causes whooping cough?
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Bordetella pertussis, a very small gram-negative rod; sometimes look like coccobacillus (confusing with Haemophilus), strictly encapsulated and aerobic, sensitive to sunlight and drying
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What kind of medium can grow Bordetella pertussis?
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Special medium supplemented with nicotinamide and other additives such as charcoal, which is thought to neutralize the effect of inhibitory compounds present in standard bacteriological media, slow growth, colony looks like tiny drops of mercury
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How is whooping cough contracted?
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Generally an infant disease (though adults are susceptible), spread by airborne droplet nuclei produced in the early stages, no seasonal pattern
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What are the stages of whooping cough?
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Catarrhal, paroxysmal, and convalescent
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What characterizes the caterrhal stage of whooping cough?
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Profuse and mucoid rhinorrhea for 1-2 weeks, malaise, fever, sneezing, and anorexia. Pertussis is most communicable in this stage
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What characterizes the paroxysmal stage of whooping cough?
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Episodes of paroxysmal coughing for 2-4 weeks, an inspiratory whoop (produced by rapidly drawn air through the narrowed glottis) follows a series of cough; a terrible condition for the infants and young children (marked lymphocytosis: 40,000/mm3)
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What characterizes the convalescent stage of whooping cough?
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Other symptoms gradually subside
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What are the toxins employed by B. pertussis?
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Pertussis toxin, adenylate toxin, and tracheal cytotoxin
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What are the characteristics of pertussis toxin?
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it is an A-B toxin and thus have a binding (B) component and an active (A) component which ADP ribosylates a G protien that affect adenylate cyclase activity; hence increasing the cAMP levels
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What are the characteristics of adenylate toxin?
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Catalyzes the conversion of host cell ATP to cAMP; hence increased levels of cAMP
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What are the characteristics of tracheal cytotoxin?
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Is a fragment of cell wall peptidoglycan released by multiplying bacterial cells; along with endotoxin, TC produces NO which cause the death of ciliated cell
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What is the mechanism of action of pertussis toxin?
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The Ptx has two components A and B and hence is an A-B toxin. the B portion attaches to the receptors on the cells and is left behind, whereas, the A portion enters the cells. The A portion becomes an activated ADP ribosylating enzyme. The G protein, responsible for regulating the cAMP synthesis, is inactivated by the A portion of Ptx toxin, hence, uncontrolled production of cAMP. Increase in cAMP leads to marked increase in mucus secretion. Decrease killing ability of phagocytes, massive release of lymphocytes into blood, ineffective NK cells
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How is whooping cough (B. pertussis) contracted?
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Enters respiratory tract and attaches to cilia of epithelial cells via binding subunits of pertussis toxin, pili, pertactin, and filamentous hemagglutinin. Respiratory tract then colonized by B. pertussis, cilia is immobilized and sloughed off
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What are the effects of lacking a ciliary blanket in the respiratory tract due to whooping cough?
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Persistent cough is only removal mechanism of the lungs, mucus plugs can block bronchioles. paroxysmal coughing may cause brain hemorrhage and seizures, patient may die from ensuing pneumonia (though secondary infection is more common cause of death)
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How is whooping cough diagnosed?
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Isolation of organism and characteristic growth on charcoal blood agar with cephalosporin, best during catarrhal phase. Direct fluorescent antibody (DFA) technique is a rapid method of diagnosis- best during paroxysmal phase
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How is whooping cough treated?
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Vaccine, Erythromycin or clarithromycin are effective if given at the early phase of infection (catarrhal phase), antibiotics kill the bacteria but do not remove the toxins, immunity is not lifelong but second attacks are less severe
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What organism causes tuberculosis?
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Mycobacterium tuberculosis, slender acid-fast, rod-shaped bacterium, strictly aerobic and do not form spore, gram positive, cell wall has complex glycolipids, highly resistant to drying, disinfectants, strong acids, and alkali due to hydrophobic lipid surface. Killed by pasteurization
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What are the products of M. tuberculosis?
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Niacin, heat sensitive catalase (negative at 68F, active at body temp)
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How is the sputum produced by patients infected with M. tuberculosis stained?
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Screened using auramine-rhodamine fluorescent stain, fluoresce a bright apple green, no antibody necessary, positives are confirmed by acid-fast stain
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What is the rate of growth of M. tuberculosis?
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Slow generation time >12 hrs, requires 4-6 weeks to appear as colony in culture
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What type of patients constitute the majority of the patient population?
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Non-white and poor elderly people, immunosuppressed are susceptible
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What is the route of infection of M. tuberculosis?
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Via respiratory tract, Coughing in public, inadequate ventilation and overcrowding are important transmission factors
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What test is used in the US for the identification of M. tuberculosis?
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Mantoeux tuberculin test with a purified protein derivative. A positive test refers to development of redness and firm swelling at the site of injection. Measurement of the infjected site is taken after 48h. The basis of the firm swelling and redness is the delayed hypersensitivity reaction (DTH)
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How do you diagnose tuberculosis?
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PPD skin test measure zone 48-72 hrs, positive if >/= 5mm in HIV+ patients or anyone with recent TB exposure, >/= 10mm in high risk population, >/= 15mm in low risk populations
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The Mantoux test is the most common question regarding
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Type IV hypersensitivity
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What is the effect of sulfatides secreted by M. tuberculosis
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Inhibit the phagosome-lysosome fusion, allowing intracellular survival (if fusion occurs, waxy nature of cell envelope reduces killing effect)
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What is the effect of cord factor (trehalose dimycolate) secreted by M. tuberculosis?
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Causes serpentine growth in vitro, inhibits leukocyte migration, disrupts mitochondrial respiration and oxidative phosphorylation
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What is the effect of tuberculin (surface protein) along with mycolic acid secreted by M. tuberculosis?
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Delayed hypersensitivity and cell-mediated immunity, granulomas and ceseation mediated by cell-mediated immunity, no exotoxins or endotoxins - damage is done by immune system
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Of those infected, what percentage progresses to clinical illness?
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<1%, the rest have latent TB which may resurface in cases of immunosuppression
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What are the different divisions of clinical tuberculosis?
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Primary, secondary (reactivation TB), and disseminated extrapulmonary tuberculosis
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What is the minimum infectious dose of TB?
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10 cells
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How does primary TB infection occur?
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Alveolar macrophages engulf TB bacteria which continue multiplying within the macrophages, after 3-4 weeks of being asymptomatic, host develops a cell-mediated immune response, causing a large influx of mononuclear cells that forms an infection site known as a tubercle
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What are tubercles?
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Granulomas that consist of a central core containing TB baceria in enlarged macrophages surrounded by an area of fibroblasts, lymphocytes, and neutrophils, often breaks down and heal by calcification
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What is Gohn's complex?
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The characteristic gross appearance with primary tuberculosis, infected area undergoes caseous (cheeselike) necrosis, free tubercle bacilli drain out of lung and forms caseous granulomas in the lymph node, can calcify
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How does secondary TB differ from primary TB?
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TB patients that recover from primary episodes of infection retain live bacteria within the healed lesion which may be reactivated later, esp with compromised immunity, patient experiences more severe symptoms, high mortality rate if untreated
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What organs are most commonly involved with the dissemination of TB bacillus to tissues outside the lung?
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Regional lymph nodes, kidneys, long bones, spine, genital tract, GI, brain and meninges (high mortality rate)
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How is TB diagnosed?
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Tuberculin test, chest x-ray, direct smear staining with Ziehl Neelsen, isolation and detection of colony growth, QuantiFERON TB gold (QFT-G) test
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What is the QuantiFERON TB gold (QFT-G) test
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An enzyme-linked immunosorbent assay (ELISA) test that detects the release of interferon-gamma (IFN-gamma) in fresh heparinized whole blood from sensitized persons when incubated with synthetic peptides that stimulate two proteins in M. tuberculosis, 6 (ESAT-6) and 10 (CFP-10)
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What are the advantages of the QFT-G test over TST?
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Results available in less than 24 hrs after testing without the need for a second visit
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How is TB prevented?
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A vaccine exists called BCG but it is not available in the US, new cases identified by TB screen test and chest x-ray
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What are the first line drugs against TB?
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Isoniazid (INH), ehtambutol, rifampin, pyrazinamide, streptomycin
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What are the second line drugs against TB?
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Para-aminosalicylic acid, ethionamide, cycloserine, fluoroquinolones, kanamycin
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Why are multiple drugs given simultaneously to treat TB?
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Helps prevent resistance development, treated with INH, rifampin, and ethambutol or pyrazinamide for 2 months, INH and rifampin only for 4-7 months, treated for 12 months if extrapulmonary lesion is present
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What should be done if resistance to one or more treatments to TB develops?
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At least 2 other anti-tubericular drugs should be added to the treatment and continued for an extended period
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What gives rise to resistant strains of TB?
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Irregular intake of medicine
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What is Mycobacterium kansii?
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TB-like symptoms, PPD test is positive, photochromogenic (forms yellow-pigmented colonies in presence of light), treated with INH, rifampin, and ethambutol
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What is Mycobacterium avium-intracellulare complex?
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A group of related acid-fast organisms that can be divided into a number of serotypes, second only to M. tuberculosis as a cause of disease in the US, manifests as cavitary pulmonary disease, cervical lymphadentitis, ostemyelitis, resistant to antitubercular drugs and may require surgery, diagnosis is bluud cultuer and DNA probes, prognosis is grave
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What is Mycobacterium scrofulaceeum?
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Forms yellow colonies in light or dark in 2 weeks, similar to M. a-i Complex, common cause of granulomatous cervical lymphadentitis in young, manifests as cervical lymph nodes, PPD test negative, treated with surgical excision
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