B3.025 Tuberculosis Flashcards
which bacteria causes TB?
mycobacterium tuberculosis
describe the physical characteristics of m.tuberculosis
rod shaped non spore forming thin aerobic acid-fast bacilli
why is m.tuberculosis acid fast?
high content of mycolic acids
long chain cross linked fatty acids
call wall lipids
how is TB transmitted?
droplet nuclei which are aerosolized by coughing, sneezing, or speaking
TB patients with sputum that contains AFB visible by microscopy are most likely to transmit the infection
what is one of the most important factors in transmission of TB
crowding in poorly ventilated rooms
what is primary TB
clinical illness directly following infection
common among children and immunocompromised
not associated w high level transmissibility
what is secondary TB
bacilli persist for years before reactivation
frequent cavitation
more infectious
developed in 10% of infected patients, higher in those w HIV
how are TB bacilli able to survive during transmission?
small fraction reach alveoli
adhesion to macrophages
phagocytosis occurs
bacterial cell wall lipoarabinomannan inhibits phagosome-lysosome fusion and bacilli survive
bacterial factors also block host defense’s autophagy
how is TB spread within a person?
bacilli replicate within a macrophage
eventually bursts, spilling contents
infect neighboring cells
what are the two host responses to m.tuberculosis 2-4 weeks after infection?
macrophage activated CMI response
tissue damaging response
describe the macrophage activating response
T cell mediated phenomenon resulting in the activation of macrophages that capable of killing and digesting tubercle bacilli
describe the tissue damaging response
result of delayed type hypersensitivity (DTH)
destroys unactivated macrophages that contain multiple bacilli
causes caseous necrosis of involved tissues
when do granulomatous lesions form?
accumulation of large numbers of activated macrophages
some can contain the spread of mycobacteria, some cannot > leads to “latency”
what is the cellular mechanism of the TB skin test?
CD4+ T lymphocytes being attracted to skin-test site
proliferate and produce cytokines
DTH is associated with protective immunity BUT does not confer protection against reactivation
what are the two classes of clinical TB?
pulmonary
extrapulmonary
what are the two classes of pulmonary Tb
primary
secondary
primary pulmonary TB
soon after initial infection
fever, pleuritic chest pain
seen in children
middle and lower lung zones
what lesion can be formed in primary pulmonary TB?
Ghon focus
usually peripheral and accompanied by transient hilar or paratracheal lymphadenopathy
pleural effusion due to primary TB
2/3 of cases
penetration of bacilli into pleural space
secondary pulmonary TB
“adult type” TB
endogenous reactivation of distant LTBI or recent infection
apical and posterior upper lobes
satellite lesions can form due to bronchogenic spread
symptoms and signs of TB
fever night sweats weight loss anorexia malaise weakness cough in 90% of cases cough eventually becomes accompanied by sputum, sometimes w blood streaking
what % of TB cases devlop hemoptysis?
20-30%
extrapulmonary sites commonly involved in TB
lymph nodes pleura GU tract bones and joints meninges peritoneum pericardium
what happens in HIV individuals w TB?
hematogenous dissemination
key to diagnosis of TB
high index of suspicion
describe AFB microscopy in the diagnosis of TB
microscopic exam of sputum or tissue
inexpensive
low sens (40-60%)
2-3 sputum samples collected in early morning
traditional AFB microscopy method
light microscopy on specimens stained with Ziehl-Neelsen basic fuchsin dyes
modern method
auramine-rhodamine staining and fluorescence microscopy
more sensitive
more expensive
nucleic acid amplification technology
rapid confirmation of TB in persons with AFB positive specimens
Xpert MTB/RIF assay
-can detect TB and rifampin resistance in <2 h
culture of m.tuberculosis
slow, 4-8 weeks
what drugs are tested in TB for resistance?
isoniazid
rifampin
what drugs are tested for when MDR-TB is found?
second line
fluoroquinoloes and injectables most commonly
what are the aims of TB treatment?
- prevent morbidity and death by curing TB while preventing the emergence of drug resistance
- to interrupt transmission by rendering patients noninfectious
what 4 drugs are considered 1st line treatment for TB?
isoniazid
rifampin
pyrazinamide
ethambutol
why are these 4 drugs recommended?
well absorbed
bactericidal activity
sterilizing activity
low rate of drug resisitance induction
treatment regimen of choice
2 month phase of all 4 drugs
4 month phase of isoniazid and rifampin
cures 90% of patients
what are the 6 classes of second line drugs
- fluoroquinolones (later generations preferred)
- injectable aminoglycosides (kanamycin, amikacin,streptomycin)
- injectable polypeptide capreomycin
- ethionamide and prothionamide
- cycloserine and terizidone
- PAS
how does TB become resistant?
spontaneous point mutations that occur at low but predictable rates
rifampin = rpoB gene
isoniazid = katG gene, inhA gene
BCG vaccine
attenuated M. bovis
efficacy ranges from 0-80%
safe and rarely causes complications
available at birth in countries with high TB prevalence
what is the most widely used screening for LTBI?
skin test with tuberculin PPD (purified protein derivative)
when are IFNy release assays used?
in setting with low TB and HIV burdens
less cross reactivity due to BCG vaccination
