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Flashcards in Mycobacteria Deck (35)

Mycobacteria species

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


M tuberculosis overview

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


M. tuberculosis staining

-mycobacteria gram stain poorly, but stain with acid fast
1) Cover smear with carbolfushsin. Steam over boiling water for 8 mins
2) After slide has cooled colorize with acid-alcohol for 15-20secs
3) Stop decolorization action of acid-rinsing briefly with water
4) Counterstain with methylene blue for 30 secs
5) Rinse briefly with water to remove excess methylene blue
6) Blot dry with bibulous paper. Examine directly under oil immersion


M. tuberculosis characteristics

-grows in vitro but slowly and with special nutrients
-humans are natural host and reservoir
-can be intra- or extracellular
-mycobacteria produce no toxins
-drug resistance is chromosomal, no plasmids
-resistant to acid and alkali, environmentally hardy
-obligate aerobe
-pathogenic in guinea pigs- important for lab tests


Important structural componenets of M. tuberculosis

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


M. tuberculosis pathogenesis

-transmitted through inhalation of infected aerosols, rarely transdermal or GI infection
-extremely infectious: <10 organsims cause disease
-alveolar macrophages phagocytose the inhaled bacilli but are unable to kill the intracellular mycobacteria
-proliferates within mononuclear phagocytes traveling to extrapulmonary sites where it can establish latent or active infection in lymph nodes, kidney, bones, meninges
-swallowing infectious sputum infects GI


Immunosuppression and M. tuberculosis

-immunocompetent hosts develop latent/dorment infection: only 5-10% lifetime risk of active TB
-current or later immunosuppression allows reactivation
-Non-TB infections may activate quiescent TB:


Cell mediated immune response in M. tuberculosis

-a CMI response terminates the unimpeded growth of M. tuberculosis 2-3 weeks after initial infection
-CD4 helper T cells activate some infected macrophages to kill intracellular bacteria
-CD8 suppressor T cells lyse other infected macrophages -> caseating granulomas ("tubercules")
-mycobacteria cannot continue to grow within these granulomas, so the infectious process pauses (latency)
-TNF plays an important role in maintaining latency: patients receiving TNF alpha antagonists (Remicade) may reactivate


M. tuberculosis and active infections

-85% of active TB includes lungs
-Bacilli proliferate locally and spread through the lymphatics to a hilar node, forming the Ghon complex, launch from there to the bloodstream
-exudative lesion plus draining lymph nodes are the Ghon complex


Course of M. tuberculosis

-TB enters through inhalation
-TB lesion, replication
-Ghon complex (exudative lesion plus hilar node)
-infectious sputum, aerosal
-Milary TB
-TB meningitis
-TB granuloma
-Calcified TB granuloma
-reactive: Scrofula, Genitourinary, GI, Skeletal, Reactivating Pulmonary TB


Risk factors for M. tuberculosis

-For infection:
-crowded at risk environments (prisions, hospitals, homeless shelters)

For poor outcome is immunosuppression:
-Uncontrolled HIV (inadequate HAART)
-IFNgamma deficiency
-TNF-alpha antagonists (Remicade)
-Age <5 years

-TB cases in the US are at an all time low but the XDR strains are disproportionately represented


Classive active pulmonary TB

-presents with cough, weight loss ("consumption"), fever, night sweats, hemoptysis, and chest pain
-in CT cavity formation- indicates advanced infections, associated with a high bacterial load
-noncalcified round-infiltrates- may be confused with lung carcinoma


TB scrofula

-reactivation in lymph node
-painless, enlarging, or persistent mass. Cervical lymph node affected in 2/3. Systemic symptoms include fever/chills, weight loss, or malaise
-~95% of mycobacterial cervical infections in adults are caused by Mycobacterium tuberculosis
-Peds: trend is reversed: 92% of cases due to atypical mycobacterium


Genitourinary TB

-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 tuberculosis is usually secondary to renal tuberculous infection



-visualize by magnetic resonance imaging (MRI)
-CSF tests also useful


Skeletal TB

-arthritis of one joint
-Pott disease (spinal infection)- back pain, stiffness, paralysis of lower extremities
-if suspect Pott, CT/MRI but do not delay treatment: paralysis can become permanent



-CT scan show mesenteric lymphadenopathy with a hypoattenuating center suggestive of necrosis
-exploratory surgery
-can increase now with the raw milk movement


Miliary TB

-1.5% of TB cases
-hematogenous spread of TB throughout body, many tiny noncalcified 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 in very young and old (65y)
-fatal if untreated


TB meningitis

-develops in 5-10% of children younger than 2 years
-nuchal rigidity
-altered deep tendon reflexes
-cranial nerve palsies
-Brudzinski's neck sign: because of inflammation when lift childs neck the knees pop up


TB skin test

-purified protein derivative
-positivity develops 2-10 weeks post infection
-alternative: IFNgamma release assay using TB peptides (IGRA) blood test doesn't require 2nd visit and is specific for TB, not vaccine
-either PPD or IRA may be false negative if patient is badly immunosuppressed or late in the course of TB
-HIV+ patients must be regularly screened for TB and vice versa
-15mm: positive, 10mm: positive if have risk factors, 5mm: positive if has deficient CMI


Lab identification of TB

-acid fast staining of sputum- positive but some smear negative are still infectious
-culture: liquid media, takes 2 weeks
-begin susceptibility testing, but results take weeks


TB treatment

-isolate infectious patients, negative pressure, high-efficiency masks
-4 drug regiment featuring isoniazid
-for MDR-TB need to use 4-6 drugs
-take 3-6 months, (9-12 if CNS involvement)
-Directly Observed Therapy is recommended- nurses watch them take it
-pregnant women should have monthly ALT monitoring


TB prevention

-good housing and nutrition
-semieffective vaccine availible


BCG vaccine

-M. tuberculosis prevention
-live attenuated M. bovis
-prevents up to 70% of symptomatic infectious (wide batch variation)
-seldom used in the US
-watch for 3-6 mm PPD+ if vaccinated abroad or in military, can differentiate with IGRA
-not for immunocompromised


Atypical Mycobacteria overview

-cause neither TB nor leprosy
-environmentally acquired
-PPD, TST usually negative
-less aggressive infections, not lethal in guinea pigs
-systemic disease very rare without predisposing condition
-cuteneous infection most likely in immunocompetent adults, scrofula in children


Group 1: Photochromogens

-produce pigment when grown in light
-M. kansasii is environmental in Midwest, Texas, England produces pulmonary/systemic disease most closely resembling TB, killed by same antibiotics
-M. marinum found in fresh and salt water, forms "fish tank" granulomatous, ulcerating lesions on abrasions exposed swimming water or aquariums, treat with tetracycline
-the most common atypical mycobacterial infection


Group 2: Scotochromogens

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


Group 3: Nonchromogens

-no pigment
1) M. avium/ M. intracellulare are very difficult to distinguish, jointly called MAI, MAC
-cause pulmonary disease indistinguishable from TB in severely immunocompromised pateitns
-environmentally widespread, found in soil and water
-high drug resistant, use claritheomycin in combinatin with ethambutal, rifabutin, or cipro


Group 4: Rapidly Growing Mycobacteria

-no pigment
-culturable in <1 week
-M fortuitum/ M clelonei:
-found in soil and water
-cause problems in immunocompromised, prosthetic hips, indwelling catheters, puncture wounds
-treat with amikacin+doxyclin plus surgical excision of site

M. abscesssus:
-chronic lung infections, skin, bone joints
-highly antibiotic resistant

M. smegmatis: normal flora under foreskin


M. leprae Bacteriology

-Not culturable
-reservoirs are humans (major) and armadillos (minor)
-14 day doubling time; slowest growing human pathogen
-prefers 30C for growth, sticks to periphery of humans
-genetically, appears to be a stripped-down version of M. tuberculosis


M. leprae Pathogenesis

-causes leprosy, aka Hansen Disease
-symptoms from both infection and immune respnonse
-worldwide incidence is at historic lows, but Leprosy is still deemed a public health problem in 9 countries; they account for 85% of reported cases
-~150 cases/yr in the US
-transmission is unclear- requires prolonged contact with infectious case, rare zoonosis from armadillos
-extremely long incubation: months to 50 years
-most commn sequel of exposure is asymptomatic seroconversion: only 5-10% of population is immunologically susceptible to symptoms


Paucibacillary leprosy= tuberculoid form

-vigorous CMI contains disease (CD4+, Th1) but causes immunogenic problems
-<5 dry skin lesions containing few bacteria
-asymmetric immunogenic peripheral nerve damage
-lepromatin PPD (+)


Multibacillary leprosy= lepromatous form

-inadequate CMI response (useless Th2, nonprotective antibodies)
-extensive skin involvement: >6 lesions, infiltrated nodules & plaques, bacilli may be visible on smears from lesion fluid
-symmetric peripheral nerve damage from bacterial growth in Schwann cells
-Lepromatin PPD-


Lepromin skin test

-not diagnostic of exposure; used to determine patient's ability to raise immune response


M. leprae treatment

-Tuberculoid: dapsone+ rifampin, 2 yrs
-Lepromatous: dapson + rifampin +clofazimine, 2 years + (until lesions are free of organism)

Peds: prophylaxis with dapsone if exposed