Which mycobacteria cause TB?
Rod shaped mycobacterium - mycobacterium tuberculosis
slow growing
prefer oxygen rich environments - e.g. the lungs
Which mycobacteria do not cause TB?
Mycobacterium leprae - causes leprosy
Tubercle Baclii includes - M. africanum, M bovis
How is TB transmitted?
inhalation of water droplets containing mycobacterium which are breathed/coughed/sneezes/sings/laughs out by an infected person
person needs to share air space with someone who is sick
healthy individuals fight off infection
NOT SPREAD BY: quick casual contact, sharing food/utensils/cigarettes/drinking containers, exchanging saliva or other body fluids, shaking hands
What does the probability that TB will be transmitted depend on?
- infectiousness of person with TB
- environment in which exposure occurs
- length of exposure
- virulence/strength of the mycobacterium
- most healthy individuals fight off infection
What is the link between HIV and TB?
If HIV positive 30-50% of having active, more difficult to diagnose, fewer bacteria expelled
Why are mycobacterial diseases hard to treat?
Bacteria can live inside the animal cells and inside macrophages which are meant to phagocytose them
How many people have been infected with TB?
1 in 3, however healthy individuals manage to contain bacteria in an inactive form so do not become ill
When do people become ill due to TB?
When it becomes active - could be as a result of anything which reduces the persons immunity (e.g. HIV, advancing age, other medical conditions)
What are the characteristics of mycobacteria?
Have complex lipid rich cell walls so resistant to decolourisation with acid (hard to stain)
Grow very slowly so hard to grow in vitro and culture
Cause chronic infections
Most resistant to commonly used antibiotics - need months/years of multidrug treatment with special agents
Intra-cellular pathogens so survive and thrive inside macrophages forming granulomas
Antibodies have no effect - cell mediated response needed
What is primary tuberculosis? How does it form a Ghon focus?
- inhaled mycobacteria settle in alveoli in middle regions where oxygen levels are high
- excite acute inflammatory response from neutrophils which phagocytose bacteria and sequester into intracellular phagosome
- in healthy individuals neutrophils destroy bacteria by releasing toxic compounds into phagosome
- immunocompromised/malnourished/ chronically infected, neutrophils unable to destroy bacteria due to thick waxy protein coat preventing penetration
- failing neutrophils release cytokines as a signal and then die forming caseous necrosis in which the bacteria survive inside of
- cytokines attract macrophages and T lymphocytes and macrophages accumulate in rings around caseous tissue and phagocytose bacteria inside but some still survive in macrophages
- macrophages fuse forming giant cells and release more cytokines attracting lymphocytes = langhan cells
- lymphocyte collar around macrophages and then fibroblast wall
- granuloma = accumulation of macrophages and other cells containing bacteria to stop spread
- Ghon focus: granuloma around TB necrotic centre
- fibroblasts deposit collagen and then calcium deposited to seal off focus
What is a Ghon Complex?
calcified ghon focus and any associated affected lymph nodes
What are some diagnostic features on an x-ray?
- opacities mainly in upper zone with patchy/nodular appearance
- cavitation
- calcification
- hilar shadowing
- diffuse nodular shadowing in military TB
What is post-primary TB?
Ghon focus formed in primary TB and if person becomes immunocompromised/malnourished alive bacteria inside may escape so symptoms recur
What is primary progressive TB?
Cannot mount a vigorous immune response, further bacterial spread, granuloma enlargement in lymph nodes
What are some clinical signs of active TB?
fever, malaise, weight loss, night sweats, cough, haemoptysis, chest pain
How is pneumonia diagnosed?
CXR
sputum swabs stained for TB
sputum samples cultured to see if mycobacteria is growing
skin test to detect immune reaction
What factors predispose reactivation?
immunosuppression - AIDS, cytotoxics malnutrition alcoholism diabetes old age
How can extrapulmonary spread occur?
15-20% of active cases of progressive primary
more commonly in immunosuppressed and young children
more than 50% of those with HIV
sites include pleura, CNS, lymphatics, genitourinary system, bones and joints
What is Ziehl-Neeson?
Special stain used for mycobacteria as strong lipid rich protein coat means they resist bleaching otherwise, show up as pink rods against normal tissue
can also use fluorescent stain
How is the Mantoux test done?
- screening method
- standard dose of tuberculin (extract of bacillus) injected intradermally and skin is viewed 48-72 hours later
- if person has been exposed bacteria mount in immune response in skin containing bacterial proteins
- measure diameter of induration across forearm
- small induration considered sign of active infection in high risk individuals
- medium sign of active in medium risk
- large sign of active in no risk
- high risk of false positives so used in conjunction only
What is the BCG?
vaccine against TB
strain of attenuated live bovine tuberculosis bacillus
M. bovis lose virulence in humans so no longer induce disease but provide some degree of immunity
0-80 effective for 15 years
effectiveness varies according to where strain was grown
How is TB treated?
- start on 4 drug regimen: isoniazid, rifampicin, pyrazinamide and either ethambutol or streptomycin
- once TB is fully susceptible ethambutol/streptomycin discontinues
- after 2 months pyrazinamide stopped and other 2 continued as daily or intermittent therapy for 4 months
- isoniazid resistance -> discontinue and continue with rifampin, pyrazinamide and ethambutol for entire 6 months
- if culture positive after 2 months extend therapy
- DOT
What is DOT?
directly observed therapy -> 2-3 times per week dosing after initial 2 weeks of daily, to avoid non-compliance as this causes resistance
What does isoniazid do?
- prevents synthesis of mycolic acid which is component in bacterial cell wall
- on its own is not sufficient
- can cause neuropathy so give vitamin B supplements
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