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Flashcards in Mycobacteria Deck (42):


-NOT mycoplasma
-M tuberculosis
-atypical mycobacteria
-M leprae


M tuberculosis intro

-has existed as a human disease since at least 3000 BC
-the most common infectious cause of mortality worldwide
->1/3 world pop infected
-was on the decline due to effective antibiotic treatment (4 drug regimens featuring isoniazid) until AIDS epidemic
-multidrug resistant (MDR) and extensively drug resistant (XDR) are becoming a public health emergency in US and abroad


M. tuberculosis bacteriology

-mycobacterium gram stain very poorly but are almost uniquely acid fas
-cell wall has some peptidoglycan, arabinogalactin, and mycolic acid-makes it waxy
-grows very slowly in vitro and needs special nutrients
-humans are natural host and reservoir
-very slow growing even in human
-can be intra or extracellular
-produce no toxins
-drug resistance is chromosomal, no known plasmids
-resistant to acid and alkali-environmentally hardy
-important structural components
-pathogenic in guinea pigs
-strictly aerobic


acid fast staining

1. cover smear with carbolfuchsin. Steam over boiling water for 8 minutes, add additional stain if it boils off
2. after cooling decolorize with acid alcohol for 15-20 sec
3. stop decolorization action with water
4. counterstain with methylene blue for 30 sec
5. rinse briefly with water to remove excess methylene blue
6. blot dry with lens paper and examine with oil immersion
-pos will be pink, neg will be blue


important structural components of M tuberculosis

-mycolic acid-acid fastness
-phosphatides-caseation necrosis
-cord factor (trehalose dimycolate)-virulence, microscopic serpentine appearance


M. tuberculosis pathogenesis

-transmitted primarily by inhalation of infected aerosols; rarely transdermal or GI infection
-aerosols are extremely infectious-ID50 t kill


pathogenesis 2

-proliferates within mononuclear phagocytes, traveling to extrapulmonary sites, where it can establish latent (immunocompetent) or active (peds, HIV+, immunosenescence) extrapulmonary infection in:
-lymph nodes
-swallowing infectious sputum infects GI


pathogenesis 3

-immunocompetent hosts develop latent/dormant infection-only 5-10% lifetime risk for active TB
-current or later immunosuppression allows reactivation
-non TB infections may activate quiescent TB-measles, varicella, pertussis


pathogenesis 4

-CMI response terminates the unimpeded growth of M tuberculosis 2-3 weeks after initial infection
-CD4 T cells activate some infected macrophages to kill intracellular bacteria (TH1)
-CD8 T cells lyse other infected macrophages-creates caseating granulomas-TB can live there even though we keep sending ROS in
-also called tubercules


pathogenesis 5

-mycobacteria cannot continue to grow within these granulomas, so the infectious process pauses (latency)
-TNF plays an important role in maintaining latency-TNFa antagonists may reactivate-Remicade


pathogenesis 6

-85% of active TB includes lungs
-bacilli proliferate locally and spread through lymphatics to a hilar node, forming the Ghon complex, launch from there to the bloodstream


Ghon complex

-parenchymal focus and a hilar lymph node lesions
-exudative lesion plus hilar node


TB pathway

-enters through inhalation and infects lungs
-forms lesions and replication
-forms Ghon complex
-spreads to GI via swallowing
-can get into blood
-in immunocompromised patient can cause meningitis or miliary TB
-in healthy forms granulomas (in places with high pO2)
-granulomas calcify
-can later become reactivated and infectious



-reactivated neck node


Genitourinary TB

-reactivated in kidney/ GU



-reactivated in GI
-used to get from M Bovus-unpasteurized milk


skeletal TB

-reactivated in skeletal system


risk factors for infection

-crowded at risk environments
-prisons, hospitals, homeless shelters


risk factor for poor outcome

-uncontrolled HIV
-IFNgamma deficiency
-TNFa antagonists
-age <5


diagnosis-classic active TB

-present with cough, weight loss, fever, night sweats, hemoptysis chest pain
-may not be able to see acid fast pos in sputum
-chest radiograph
-cavity formation, indicates advanced infectoin, associated with a high bacterial load
-noncalcified round infilrations-may be confused with lung carcinoma


diagnosis of scrofula

-painless, enlarging or persistent mass
-cervical lymph node affected in 2/3
-systemic symptoms include fever/chills, weight loss, malaise
-~95% of mycobacterial cervical infections in adults caused by M TB
-in peds trend is reversed-92% of cases due to atypical mycobacterium-acquired by putting contaminated objects in their mouths


GU diagnosis

-most common site for extrapulmonary infection
-TB almost always reaches the kidneys during the primary infection but does not present clinically; may be 20 years of latency before symptoms
-genital TB secondary to renal TB


CNS diagnosis

-MRI, CSF tests


skeletal TB diagnosis

-arthritis of one joint
-pott disease (spinal infection)-back pain, stiffness, paralysis of lower extremities
-don't delay treatment


GI diagnosis

-radiograph for calcified granulomas
-CT scans show lymphadenopathy with hypoattenuating center suggestive of necrosis
-exploratory surgery


miliary TB

-1.5% of TB cases
-hematogenous spread of TB throughout the body
-many tiny non calcified foci of infection appear like millet seeds in lung on chest xray
-miliary form more likely to develop right after primary infection, less likely as a reactivation
-highest risk is very young and old
-fatal if untreated


TB meningitis

-develops in 5-10% of children under 2
-nuchal rigidity
-altered deep tendon relfexes
-cranial nerve palsies
-Brudzinski's neck sign



-tests for exposure
-2-10 weeks post infection
-can use IFNgamma release assay using TB peptides-1 office visit and specific for TB, not vaccine
-either PPD for IGRA may be false neg if patient is badly immunosuppressed or late in course of TB
-HIV pts must be regularly screened for TB and vice versa
-results depend on history



-drugs for at least 3 mo-6 or 12 if CNS
-monitor pregnant woman blood



-good housing and nutrition are disproportionately helpful- healthy CMI drives TB latent
-population load of TB can be significantly decreased by improved standard of living even without access to antibiotics


BCG vaccine

-live attenuated M bovis
-prevents up to 70% of symptomatic infections
-seldom used in US
-watch for 3-6mm PPD+ if vaccinated abroad or in military-can differentiate with IGRA
-not for immunocompromised


atypical mycobacteria

-cause neither TB nor leprosy
-environmentally acquired
-PPD TST usually neg
-less aggressive infections
-systemic disease very rare without predisposing condition-HIV, cancer, old age, infected surgical site, diabetes, lung disease
-cutaneous infection most likely in immunocompetent adults, scrofula in children



-produce pigment when grown in light
-M kansaii is environmental in midwest, texas and england-pulm/systemic disease most closely resembling TB, killed by same antibiotics
-M marinum in fresh and salt water- fish tank granulomatous ulcerating lesions on abrasions exposed to swimming water or aquariums-tetracycline



-produce pigment when grown in dark or light
-M scrofulaceum produces scrofula
-reservoir is water, can be harmless in resp tract
-fix by surgically removing affected nodes



-M avium/M intracellulare difficult to distinguish, MAI MAC
-cause pulm disease indistinguishable from TB in severely immunocompromised patients
-environmentally widespread, found in soil and water
-highly drug resistant, use clarithromycin in combination with ethambutol, rifabutin or cipro


rapidly growing mycobacteria

-culturable in less than 1 week
-M fortuitum/ chelonei- found in soil and water, cause problems in immunocompromised, prosthetic hips, indwelling catheters, puncture wounds-amikacin and doxy plus excision
-M abscessus-environmental, chronic lung infections, skin, bone joints- antibiotic resistant
-Smegmatis:normal flora under foreskin


M leprae

-not culturable
-reservoirs are humans and armadillos
-14 day doubling time, slowest growing human pathogen
-prefers 30 C for growth-periphery of humans
-genetically appears to be stripped version of M TB


M Leprae pathogenesis

-causes leprosy/ Hansen disease
-symptoms from both infection and immune response
-worldwide incidence at historic lows, but still deemed PH prob in 9 countries-84% of cases
-150 cases/ year in US


leprae pathogenesis 2

-exact mechanism unclear
-requires prolonged contact with infectious cases
-rare zoonosis from armadillos
-extremely long incubation period-months to 50 years
-most common sequel of exposure is asymptomatic seroconversion, only 5-10% pop believed to be immunologically susceptible to symptoms



-Paucibacillary-tuberculoid-CMI works with CD4 and TH1 but we react to immune system-6 lesions, infiltrated nodules and plaques, bacilli visible on smears
-symmetric peripheral nerve damage from bacterial growth in Schwann cells
-lepromatin PPD-


lep PPD

-tests whether immune response it there-milder cases are PPD +


leprosy treatment

-tuberculoid is dapsone and rifapin, 2 years
-lepromatous is dapsone and rifampin and clofazimine, 2 years
-peds is prophylaxis with dapsone if exposed