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1

Tuberculosis (TB)

M. Tuberculosis infects 1/3 of the world's population. 8 million new cases occur each year, and approximately 2 million deaths each year.

TB is second only to HIV as a cause of death worldwide resulting from a single infectious agent.

nearly 6% of all infant death, and 20% of adult death are caused by TB

two factors essential for its rapid spread and crowded living conditionns and a population with little innate resistance

the fatality rate of untreated TB is 50%

a resurgence of new TB cases has set off a panic

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Key facts about TB

TB is caused by M. Tuberculosis, a slow growing, acid fast obligate aerobe that invades macrophages

transmitted by inhalation or ingestion

two forms: primary TB a usually mild disease; and a secondary TB, a disease caused by reactivation of dormant organisms.

damage in the primary form: formation of granulomas followed by caseation. in immunocompormised indiviuals, this proceeds to miliary TB with dissemination to other body sites, bone marrow, spleen, kidney, and CNS

damage in the secondary form: caused by delayed type hypersensitivity reaction to reactivated organisms

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Miliary TB

gross specimen of lung showing the cut surface covered with white nodules, which are the milary foci of tuberculosis.

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MTB

an obilagte aerobic rod with G+ like cell wall

the infections are caused by aerosols

resistance to drying and chemicals

waxes in cell wall

grows very slowly in vitro and in vivo

acid fast stain to see.

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Characteristics of mycobacterium tuberculosis

acid fastness unique acidic waxes surround bacterium composed of mycolic acid (beta hydroxy fatty acid linked to murein). affects permeability of cell.

resistance to drying and cehmicals. Highly resistant to germicides

slow growth generation time is about 13 hours. may be a result of inability of nutriets to get into the cell. Laboratory cultures are usually incubated up to 8 weeks.

transmission occurs when there is prolonged close contact between susceptible person and a person with an active case of TB

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Virulence factors of mycobacterium tuberculosis

grow inside macrophages and monocytes

probably prevents phagosome/lysosome fusion but there is some evidence indicating that M. TB. escapes the phagosome (MHC class I assciated cytotoxic T cell response)

LLO homologue (hemolysin) has been cloned from MTB, which allows escape from a phagocytic vesicle

MTB prevents acidicifaction of the phagosome. Presumably by counteracting ATPase-dependent acidification by producing NH4.

mycolic acids produced are toxic, could act by stimulating immune response.

TNF alpha provoked by cell wall components cause lung damage.

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Diagnosis of mycobacterium tuberculosis

careful history

direct examination of sputum or exudates-acid fast stain

chest x ray

tuberculin skin test (PPD) composed of purified protein derivativ of the mycobacterium cell wall. O.1 ug (5 tuberculin units) injected intradermally reads 48 hours after injection. Positive PPD can be detected 3-4 weeks after infection.

caveats: immunocompormised/aids pts. may not react. cross reactive to other mycobacteria sp. foreign nationals who received BCG are PPD +

cultivation of organism 3 to 8 weeks, PCR may be used in future.

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AIDS and TB

TB kills more rapidly in AIDS pts, sometimes within months

incidence is 500x greater than general population. Fatality rate is 80%

more likely to develop extrapulmonary disease, lmph nodes, genitourinary, CNS

miliary TB

Reduced CD4 t cell number does not allow macrophages to be activated

respond to treatment as normal pts if caught in time

more susceptible to MAI infections, 8% have MAI

systemic infections involve multiple systems

MAI is inherently more drug resistant

current therapy enlists combinations of new macolides, rifabutin, ethambutol, clofazimine, or fluoroquinolones

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TX

Anti TB: 6 months: Rifampin, Isoniazid, Streptomycin, Ethambutol

proxphylaxis

vaccination with attenuated M. Bovis (baccilee calmette guerin (BCG))

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mycobacterium avium intracellulare complex (MAI)

grow slightly faster than MTB, acid fast bacilli found in macophages

found worldwide in soil and water. Us: southeast, pacific coast, and north central regions

second only to TB in significance and frequency

MAI is the most common cause of mycobacterial disease in AIDS patients in the US (terminal stages of their immune disorder)

causes systemic infections in HIV patients

diagnosis made most readily by blood culture

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Mycobacterium kansasii

photochromogenic mycobacterium forming a yellow pigmented colonies following 2 weeks of incubation in the presence of light

more prevalent since Mtb has declined. Most common in Il, Ok, Tx. affecting urban residents. 3% of mycobacterial infections in U.S.

causes cavitary pulmonary disease, cervical lymphadenitis and skin infections. HIV patients with CD4 counts less than 200 cell/ul

PD positive, resembles tuberculosis

prolonged chemotherapy with isoniazid, rifampin, and ethambutanol

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Mycobacterium leprae

rare in us (~ 250 cases a year) 12 million worldwide. 62% in asia, 34% in africa. fewer than 10% of US cases are US natives. Largest number of cases in california, hawaii, texas, and louisiana

endemic disease has been demonstrated in armadillos

unable to be grown on laboratory medium. Hence, laboratory confirmation requires histopathology consisten with clincal disease. And skin test reactivity to lepromin or the presence of acid-fast bacilli in skin lesions

infection is manifested by two different presentations

tuberculoid leprosy-miler and self limiting disease (CMI)

lepratomous leprosy severest form of leprosy (NO CMI)

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Lepromatous leprosy

multibacillary. growth of bacteria relatively unimpeded. Lesions show dense infiltration. Large numbers of bacilli reach bloodstream.

skin lesions are diffuse, extensive, depiliated, extensive tissue destruction

cell mediated immuniy id deficient Th2 response

infectivity: high

analogous to miliar TB

nonreactive to lepromin

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Treatment: leprosy

dapsone, rifampin, and clofazimine for a minimum of 2 years

control effected by prompt recognition and treatment of infected people