Tuberculosis

Question 1

what is tb.
how is it spread?
where is it a problem?

Answer 1

• Is infectious disease caused be Mycobacterium Tuberculosis (rod-shaped, aerobic)
• Spread by inhalation of mycobacterium-containing nuclei in air
• Problem in overcrowded living conditions

Question 2

how does body defend against TB (ahmed’s favourite points)

Answer 2

• *Tubercle bacillus has no known antigens to stimulate early immunogluobulin response. Rather, host mounts a delayed-type cell-mediated immune response
• *This delayed response plays dominant role in walling of the tubercle bacilli and preventing development of active TB.
• *Those with impaired cell-mediate immunity more likely to develop active BC

Question 3

what does a positive TB test indicate

Answer 3

• Positive TB test does not mean person has active TB – results from cell-mediated immune response and implies person is infected

Question 4

canadian stats regarding TB

Answer 4

Canadian statistics
• World’s foremost cause of death from single infectious agent
• In Canada, approx 1600 new cases and 750 deaths d/t TB in 2003
• Introduction of antibiotics to western countries in 1950s attributed with decline in prevalence
• TB in Canada most common amoung foreign-born persons (68% of cases in 2003)
• Higher incidence in North (both aboriginal and non-aboriginal people)
• More drug resistant cases emerging

Question 5

general info about the bacterium

Answer 5

• TB bacteria have special waxy capsule that makes them more resistant to destruction
• Do not form spores
• Can persist in old necrotic and calcified lesions and remain capable of reinitiating growth
• Can infect any part of body but lungs most frequently involved
• Strict aerobes so thrive where most oxygen – why infect upper lobe or upper parts of lower lobes of lung

Question 6

etiology of TB and mode of transmission

Answer 6

• 2 kinds of TB pose threat to humans: M Tuberculosis hominis(human TB) and M. tubculosisbovis(bovine TB)
• Other kinds exist but much less virulent so only able to affect severely immuno-compromised (HIV)

• BOVINE TB
o Transmitted by drinking milk of infected cows
o Initially affects GI tract
o Has been eradicated in most of world d/t strict controls on dairy herds and pasteurization

• HUMAN TB
o Transmitted by droplet nuclei harbored in resp secretions of persons with active TB
o Droplets by sneezing, coughing, and talking; evaporate into air and remain suspended, carried by air currents
o Risk inc with crowded housing

Question 7

what is special about TB that prevents easy degradation

Answer 7

their cell wall lipids prevent phagosomes and lysosomes from fusing

Question 8

what causes the damage in TB infection

Answer 8

the body’s hypersensitivity reaction not the infection cause the caseating necrosis and cavitation

Question 9

initial response to TB infect

how long until IR is effective

Answer 9

• Macrophages can’t kill bacteria right away but mount cell-mediated IR that contains infection (probably by signaling with cytokines??)
o Infected macrophages degrade mycobacteria and present their antigens to T lymphocytes
o T cells in turn stimulate macrophages to inc lytic enzymes and ability to kill bacteria
o These lytic enzymes damage lung tissue
• Takes 3-6 weeks for IR to be effective. Is made up of population of activated T cells and activated macrophages capable of ingesting and destroying bacilli

Question 10

in pt with intact cell mediated immunity what is the result of the IR

Answer 10

• Ghon focus= grey-white confined granulomatous lesion (area of inflammation) that contains the tubercle bacilli, modified macrophages, and other immune cells; is the result of the cell-mediated IR in people with intact cell-mediated immunity
o Usually located in subpleural area in lower area of upper lobes or upper area of lower lobes
o Hypersensitivity rxn causes it to undergo soft caseous (cheeselike) necrosis when number of organisms is high
o Simultaneously, bacilli (free or inside macrophages) drain in lymph to tracheobronchial lymph nodes of effected lung and cause formation of caseous granulomas
o

Question 11

in pt with intact cell mediated immunity what is the result of the IR (more summarized)

Answer 11

ghon focus usually in lobes.
Have hypersensitivity rxn->caseating necrosis
-caseous granulomas form in lymph from TB

Question 12

what happens after formation of ghon focus (combining what happened earlier)

once this is formed what can happen with it

Answer 12

the combo of primary lung lesion and lymph node granuloma=ghon complex

(this shrinks and scars (which is visible on radioraphy) but some organisms may still be viable and recur when immune defenses are down (change from primary TB to econdary TB)

Question 13

primary TB patho

Answer 13

• Type that develops in those previously unexposed
• Inhale droplet nuclei ->dev latent infection (T cells and macrophages contain bacteria in granulomas)
• Don’t have active disease, cannot transmit it to others

Question 14

how does one get 2ary TB

who does this occur in

Answer 14

• reinfection or reactivation of what was a healed primary lesion
• often in people with impaired defenses

Question 15

are pts with 1ary TB contagious

Answer 15

no
-unless their IR is inadequate

• In approx 5% of newly infected people (those with HIV and disorders of cell mediated immunity): IR is inadequate, develop progressive primary TB with continued destruction of lung tissue and spread to multiple sites in lung
• Onset can be insidious or abrupt; as progresses, gains access to sputum and person can now spread disease

Question 16

nice summary of TB what could happen if you have primary tb (from the chart)

Answer 16

1’ tb->cell mediated H response (this goes either into development f ell mediated immunity(youd now have a positive skin test) and reinfection so 2’ TB or…)->granulomatous inflm response->ghon complex->healed dormant lesions

from the ghon complex you can hav progressive or disseminated TB

from a healed dormant lesion you can have reactivated TB

both of the above are 2’ TB

Question 17

mnfts of primary TB

Answer 17

• Primary = fever, weight loss, fatigue and night sweats (with insidious onset, non-specific); or high fever, pleuritis, and lymphadenitis (w abrupt onset)

Question 18

mnfts of secondary TB

Answer 18

• Secondary = low-grade fever, night sweats, easy fatigability, anorexia, weight loss, cough (first dry, then productive with purulent or blood-tinged sputum)

Question 19

what is unique about secondary TB mnfts

Answer 19

cough (that might have blood in it)

anorexia

Question 20

unique about primary TB mnfts

Answer 20

pleuritis and lymphadenitis

Question 21

diagnositc methods vs screening methods

Answer 21

dx: culture (of sputum etc) and genotyping
screening: TB skin test and radiography

Question 22

medical mgmt summary

Answer 22

• use multiple drugs
• want to prevent resistance
• need long term tx
• chemo
• INH, rifampin, pyrazinamide, ethambutol, streptomycin
• INH is most popular

• Antimycobacterial tx used for two groups: those with active TB and those who have contact with cases of active TB (therefore at risk)

Question 23

immunizations and TB

who is it good for

Answer 23

• BCG (Bacillus Calmette-Guerin) vaccine used for those at high risk of infection
• Is attenuated strain of bovine strain
• Given only to those who are negative for TB tests, will give person positives for ~10yrs following
• Not recommended for widespread use, variable results and problem with detecting latent TB
• Considered for: aboriginal individuals in communities at high risk, health care workers with pt’s with drug resistant strains, or travellers spending extensive time in areas with high resistant TB incidence.