PT1: Tuberculosis Pathophysiology, Microbiology and Treatment Flashcards
what bacteria causes TB
mycobacterium tuberculosis
what type of bacteria is mycobacterium tuberculosis
slow growing bacillus
what part of the body does mycobacterium tuberculosis infect
lungs (pulmonary TB)
can spread to other organs
what are the features of acid fast bacteria
cell wall is lipid rich
very hydrophobic, resistant to drying and weak disinfectants
what are the three types of mycobacterium tuberculosis
m. bovis, m. africanum, m. microti
which form of mycobacterium tuberculosis is not pathogenic
m. microti
what types of mycobacterium tuberculosis do not cause disease in immunocompetent people
m. bovis, m. africanum
what occurs in stage 1 progression of primary tuberculosis
bacilli inhaled in droplets, settle in alveoli in lung, start to grow
phagocytosed by macrophages which do not destroy bacilli, so it can survive outside the host
how many organisms are needed to cause infection in primary tuberculosis
<10 organisms
what occurs in stage 2 progression of primary tuberculosis
mycobacterium tuberculosis multiplies inside macrophages for 7-21 days
macrophages burst, incoming macrophages phagocytose released MTB
continues for 3-4 weeks
asymptomatic or mild fever
what happens in stage 3 of progression of primary tuberculosis
cell mediated response initiated, granulomas (tubercules) formed, symptoms appear
what percentage of tuberculosis progresses to latent infection
45-50%
what percentage of tuberculosis progresses to progressive infection
5-10%
what percentage of tubercolosis infections are cleared
45-50%
what occurs during stage 4 of tuberculosis progression
bacteria multiply inside macrophage; uncontrolled lysis means bacteria spread throughout the lungs
enzymes released destroy local tissue causing legions in the lung (pulmonary TB)
what are the symptoms of TB (appearing at stage 4)
cough, afternoon fever, weight loss, blood stained sputum, night sweats
how is active TB diagnosed
clinical examination, chest x-ray, sputum test (smears/cultures), molecular assays
what is the appearance of a chest x-ray for active TB
white lesions replace alveoli with scar tissue
what is the appearance of a sputum test for active TB
visualise bacteria in sputum using staining/microscopy, culture bacteria
what is the appearance of molecular assays for active TB
Xpert MTB/RIF assay
what are the methods of latent TB diagnosis
tuberculin skin test (Mantoux test), molecular tests (interferon-gamma assay)
how does a tuberculin skin test work
tuberculin injected subcutaneously into forearm
positive test is skin lesion >10mm diameter after 48-72 hours
how is TB screened for
chest x-ray, sputum test
when is TB screening compulsory
for people travelling to a country where TB is common if they are staying in the UK for >6 months
needed before visa applications
what vaccine is used to prevent TB
BCG (bacillus calmette-guerin) vaccine
what are some examples of 1st line anti-TB drugs
rifampicin, isoniazid, pyrazinamide, ethambutol
how does rifampicin work
inhibits RNA polymerase, bactericidal to all metabolising cells, oral, fully absorbed
absorption decreased by food
what are the side effects of rifampicin
liver damage, hypersensitivity, decreased activity of other drugs, red colour in body fluids
how does isoniazid work
prodrug - bactericidal to actively growing bacilli; bacteriostatic to very slow growing bacilli
decreases synthesis of mycolic acid
what are the pharmcokinetics of isoniazid
oral absorption can be reduced by cations; well distributed including CSF; metabolised in liver and excreted in kidneys
what are the side effects of isoniazid
hypersensitivity, peripheral neuropathy, liver toxicity, decreased efficacy of hormonal birth control
how does pyrazinamide work
prodrug - bactericidal to dormant bacilli; decreases synthesis of mycolic acid and damages bacterial membrane
what are the pharmacokinetics of pyrazinamide
well absorbed orally, good distribution including CSF, metabolised by liver and excreted by kidenys
what are the side effects of pyrazinamide
joint pain, liver damage, hypersensitivity
how does ethambutol work
bacteriostatic against actively growing bacilli; increases permeability by affecting synthesis of arabinogalactan in cell wall
what are the pharmacokinetics of ethambutol
well absrbed orally and well distributed; 50% excreted unchanged in urine
what are the side effects of ethambutol
optic neuritis (reversible), joint pain
what is the site of action for isoniazid
inhibits cell wall formation and only kills dividing bacilli
what is the site of action of ethambutol
bacteriostatic against actively growing TB bacilli
what is the site of action for pyrazinamide
damages/kills slowly metabolising and dormant bacilli
what is the site of action of rifampicin
kills all metabolising cells including some that are not dividing
how is active TB treated
rifampicin & isoniazid for 6-9 months
pyrazinamide & ethambutol for first two months
how is latent TB treated
specific patient groups are treated
isoniazid (6 months) or rifampicin & isoniazid (3 months)
what are some examples of 2nd line anti-TB drugs
streptomycin (aminoglycoside) capreomycin (aminoglycoside) cycloserine (neurological side effects) ciprofloxacin (quinolone) azithromycin (newer macrolide) linezolid (oxazolidinone) bedaquiline (dairy quinolone)
how does TB drug resistance occur
results from poorly managed TB care, resistance through high rate of spontaneous mutations in drug target sites and efflux
what are MDR-TB drugs
strains resistant to >2 first line drugs
what are XDR-TB drugs
strains resistant to >2 first line drugs and >3 of the six second line drugs
