Mycobacterium Lecture 21 Flashcards
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
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
Miliary TB
gross specimen of lung showing the cut surface covered with white nodules, which are the milary foci of tuberculosis.
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.
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
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.
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.
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
TX
Anti TB: 6 months: Rifampin, Isoniazid, Streptomycin, Ethambutol
proxphylaxis
vaccination with attenuated M. Bovis (baccilee calmette guerin (BCG))
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
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
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)
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
Treatment: leprosy
dapsone, rifampin, and clofazimine for a minimum of 2 years
control effected by prompt recognition and treatment of infected people
