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Mycobacterial Infections
Downstate > MS2 Respiratory Block > Lecture 10 Mycobacterial Infections
51
Medical
Graduate
01/30/2011

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Term
What 5 factors determine infectiousness?
Definition
intensity of exposure, infectious burden, site of infection, strain variant, host susceptibility
Term
Purpose of RFLP in TB?
Definition
identify strain isolates and follow transmission
Term
How does TB avoid phagocytic clearance?
Definition
inhibits acidification, inhibits phago-lysosome fusion, resistant to ROS
Term
TB spreads to lymph nodes at ___wks; bacteremia occurs at __ wks; CMI and DTH develop at ___ wks
Definition
LNs at 2-4 wks; bacteremia at 6-8 wks; CMI and DTH at 2-8wks
Term
What percentage of infected people develop primary TB?
Definition
5%
Term
What are the 2 ways a person can develop secondary TB?
Definition
reactivation or reinfection
Term
What are risk factors for reactivation?
Definition
HIV, advanced age, silicosis, malnutrition, diabetes
Term
What cells and cytokines characterize the immune response to TB?
Definition

CD4, NK cells, macrophages:

CD4 --IFNg--> activate macrophages into epithelioid histiocytes, which form granulomas; macrophages --IL-12--> activate T cells, which release IFNg, TNF-a, ROS, and NOS

Term
What characterizes the caseous center of a granuloma that inhibits bacterial growth?
Definition
low pH, low O2, avascular
Term
Ghon complex = ?
Definition
lesion of initial site of TB infection + lymph node involvement
Term
What are the 3 states a granuloma can progress to?
Definition

-> calcified (healed)

-> fibrosis: but this can be reactivated

-> cavitate: via liquefactive necrosis, is highly infectious

Term
How do primary and secondary TB differ in lung location and lymph node involvement?
Definition
primary TB: lower to middle lobes, no cavities, lymph nodes are involved // secondary TB: apical lung sites, cavities, no lymph node involvement
Term
Pott's disease
Definition
osteomyelitis or thoracic spine with anterior vertebral body involvement; an extrapulmonary manifestation of TB (12%)
Term
scrofula
Definition
cervical lymphadenopathy, more common in children; an extrapulmonary manifestation of TB (27%)
Term
miliary TB
Definition
disseminated TB after primary infection; common in HIV pts; PPD+ (50%); affects eyes, liver, lung, bone, etc.
Term
how does HIV affect TB presentation in terms of lung involvement, lymph nodes, systemic manifestations, and PPD?
Definition
less apical involvement, fewer cavitations, more lymphadenopathy, more dissemination (bacteremia, miliary TB), negative PPD
Term
what tests are used to diagnose TB and how long do they take?
Definition
acid-fast smear: <1d; liquid culture: 1-3wks; culture 2-6wks; PCR: 1d // PPD is used for screening
Term
What are the pros and cons of using Quantiferon as a screening tool?
Definition
pro: does not give false positive in pts with BCG vaccine; con: becomes negative after TB treatment
Term
How is the Kinyoun technique done? What organisms will stain positive?
Definition
stain with carbol-fuchsin or fluorochrome, wash, counterstain with methylene blue; Mycobacterium, Nocardia, some Corynebacteria will stain positive
Term
What component of the bacterial cell wall allows resistance to decolorization in the presence of acid?
Definition
mycolic acid: long chain fatty acids
Term
What diagnostic test is best used as a measure of infectivity?
Definition
acid-fast: indicates high inoculum (10^4 bacilli/ml)
Term
Without treatment, what percentage of patients with TB disease die? Are persistent shedders? Are spontaneously cured?
Definition
50% die in 5y; 30% shed; 20% spontaneously cure (if no cavitations)
Term
What is the treatment regimen for non-drug resistant TB?
Definition
isoniazide (INH), rifampin, and pyrazinamide for 2mo, then INH and rifampin for 4-7mo
Term
What methods are used to detect drug resistance and how long do they take?
Definition
culture: 2-4wks; liquid culture: 7-10d; PCR: for rifampin only, 1d
Term
MDR TB occurs because of [new mutations/plasmid]
Definition
new mutations
Term

MDR TB is defined by resistance to...

XDR TB is defined by resistance to...

Definition

MDR TB: rifampin, INH

XDR: rifampin, INH, fluoroquinolones + kanamycin, amikacin, OR capreomycin

Term
What is the best way to prevent MDR/XDR TB?
Definition
DOT--effective but expensive
Term
BCG vaccine
Definition
live, attenuated M. bovis; provides ~5y protection
Term
prophylactic INH is indicated for...
Definition
high risk populations: recent converts, pts with silicosis, fibrotic CXRs, ESRD, HIV, diabetics
Term
What defines a positive PPD?
Definition
>5mm in HIV pts, >10mm in high risk populations (diabetics, underserved, ESRD, healthcare workers, etc.), >15mm for general population
Term
hepatotoxicity from TB treatment is most frequent in __
Definition
alcoholics and elderly
Term
booster phenomenon
Definition
repeated PPD testing can boost latent anti-TB activity, appearing to be a "recent converter"
Term
What institutional controls are used to control TB spread?
Definition
negative pressure room, N-95 masks
Term
M. leprae is grown in ___
Definition
mouse foot pad or armadillo
Term
pathogenesis and clinical presentation of tuberculoid leprosy
Definition
TT: anesthetic skin plaques, peripheral nerve swelling, many granulomas, lepromin skin test+; no limb loss; Th1 (CMI, IL-12, IFNg)
Term
pathogenesis and clinical presentation of lepromatous leprosy (LL)
Definition
LL: skin lesions, limb loss, neuropathies, leonine facies, lepromin skin test (-); Th2 (Ab, IL-4, IL-10)
Term
leprosy tx
Definition

TT: dapsone, rifampin

LL: dapsone, rifampin, clofazamine

Term
AE of LL tx (rifampin, dapsone, and clofazamine)
Definition
erythema nodosum leprosum; tx with prednisone or thalidomide
Term
reservoir for MAI
Definition
water, soil
Term
typical demographic of MAI
Definition
older male with hx of TB, bronchiectasis or COPD; or thin middle-aged female with no underlying disease except scoliosis
Term
CT shows "tree-in-bud"; dx?
Definition
MAI
Term
what are the 2 clinical presentations of MAI characterized by?
Definition

1. TB-like: cavitations

2. disseminated MAI: HIV pts; disseminates to liver, bone, small bowel; scrofula; poorly formed granulomas

Term
tx for MAI
Definition
macrolides+rifampin+ethambutol indefinitely or 1-2y for lung disease
Term
when is prophylaxis for MAI indicated?
Definition
AIDS pts with CD4<100
Term
brain abscesses, no granulomas; tx with sulfa drugs; dx?
Definition
Nocardia
Term
Gram+, aerobic, weakly AFB-positive, thin filamentous branched rods
Definition
Nocardia
Term
Gram+, not acid fast, anaerobic; clumps of branched filaments
Definition
Actinomyces
Term
pt has IUD; biopsy shows yellow sulfur granules; bug?
Definition
Actinomyces
Term
"lumpy jaw" that looks like tumors; tx with penicillin; dx?
Definition
Actinomyces
Term
1. necrotizing, suppurative, nongranulomatous lesions in lung and CNS; bug?
2. suppurative, fibrotic, nongranulomatous lesions in neck and abdomen; bug?
Definition
1. Nocardia
2. Actinomyces
Term
prophylaxis regimens for MAI
Definition
1x/day rifabutin, 2x/day clarithromycin, or weekly azithromycin
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