Tuberculosis

Question 1

TB is the leading infectious cause of death globally

Answer 1

wow

Question 2

Tuberculosis Incidence is on a __________ decline

Answer 2

(very) slow

It will take 200 years for TB incidence in high-burden countries to reach current levels in the U.S.

Question 3

risk of reactivation of LTBI

Answer 3

Half of that risk in the first 2 years after infection

Question 4

Injection of TB antigens

Answer 4

PPD- tuberculin skin test

Question 5

Interferon gamma release assays (IGRAs):

Answer 5

Detects interferon release from monocytes exposed to TB antigens

Question 6

Whom to test for latent TB infection:

Answer 6

1, High risk of exposure (i.e. infection) such as recent contact of person with TB, high prevalence countries, homeless/prisoners, HIV infection

2. High risk of disease (low immunity) if infected- HIV, end-stage renal disease or immunosuppressive meds

Question 7

what is wrong with the PPD with HIV pt.?

Answer 7

Weak cell-mediated immunity (can’t produce large reaction)

Question 8

TB requires ____________ in hospital

Answer 8

airborne isolation; (N95 mask and negative air pressure room)

Question 9

symptoms of TB

Answer 9

1. productive cough for more than 2-3 weeks
2. blood in sputum
3. weight loss
4. fevers/chills
5. nightsweats more than 2-3 weeeks

**** epi is critical!!!!

Question 10

what type of lesions do we see in lungs of TB pt.

Answer 10

apical lesions increases suspicion but TB can show up in any lobe

Question 11

pulmonary tb diagnosis

Answer 11

1. smear microscopy (only 50% sensitive)
2. TB culture (95 % sensitive but takes weeks to grow)
3. PCR (80-90% sensitive and there is immediate dx)

Question 12

multidrug restistant to TB

Answer 12

resistance to BOTH Isoniazid and Rifampicin

Question 13

resistant to Isoniazid and Rifampicin PLUS resistant to two core classes of drugs used to treat MDR TB

Answer 13

Extensively drug-resistant (XDR)

Question 14

HIV TB

Answer 14

1. more atypical presentations

2. latent TB infection is missed a lot

Question 15

ART and “treatment as prevention” for HIV without CD4 cut-offs for starting ART is likely to also have a big impact on reducing TB

Answer 15

yep

Question 16

why is TB so hard to kill?

Answer 16

thick cell wall and they are slow growing (doubling time is about 20hr in laboratory culture)

Question 17

__________have highest concentration (>108 organisms) of actively metabolizing organisms that are extracellular in a neutral or alkaline pH.

Answer 17

Cavities - very happy bacteria

Question 18

what do we form following TB infection

Answer 18

granuloma less number of bacteria than in cavities

Question 19

treatment response is dependent on

Answer 19

lesion type (very heterogeneous)

Question 20

one drug is unlikely to be effective for TB cure.

Answer 20

yep

Question 21

RIPE and what is the Order of bactericial activity

Answer 21

first line therapy:

1. rifampin
2. isoniazid
3. pyrazinamide
4. ethambutol

INH>EMB>RIF>PZA

*** INH best for rapid growth in cavitary disease.

Question 22

isoniazid MOA

Rate of elimination depends of ______________. Autosomal recessive trait can lead to deficiency in this enzyme. This will ____ INH acetylation and lead to _________ concentrations and _________ in those with the trait.

Answer 22

inhibits mycolic scid synthesis used for both latent and active

Rate of elimination depends of N-acetyltransferase-2 enzyme (NAT2). Autosomal recessive trait can lead to deficiency in this enzyme. This will slow INH acetylation and lead to higher concentrations and toxicity in those with the trait.

Question 23

Toxicities associated with isoniazid

safe in pregnancy?

Answer 23

1. peripheral neuropathy
2. elvated LFTs with hepatitis
3. lupus like syndrome
4. CNS issues
5. fever/rash/acne

safe in pregnancy

Question 24

rifampin MOA

Bactericida compared to INH.

toxicities associated

Answer 24

binds to RNA pol and prevents DNA directed mRNA synthesis

Bactericidal activity half of that of INH.

toxicities include renal and liver

Question 25

Has better activity against semi dormant populations

Answer 25

rifampin

Question 26

rifampin induces

Answer 26

p450

Question 27

PZA MOA and what is it used for? caveat

Answer 27

unknown and Best for dormant and semidormant organisms and good activity in acid pH Hepatic toxicity rare but can lead to fatal hepatic necrosis.

Question 28

Ethambutol MOA

Answer 28

inhibits arabinogalactan synthesis and it is used to prevent emergence of resistance to the other drugs used

Question 29

major issue of ethambutol

Answer 29

RETROBULBAR NEURITIS. Decreased acuity and red-green discrimination.

Question 30

Active TB treatment principles: 1. Decrease infectiousness by using _____ up front (EBA high). 2. Other drugs to__________. 3. Long duration of meds that have good sterilizing properties. 4. Most regimes ______ months long. 5. ALWAYS USE MORE THAN ONE DRUG AND NEVER ADD ONE DRUG TO FAILING REGIME.

Answer 30

1. Decrease infectiousness by using INH up front (EBA high). 2. Other drugs to prevent drug resistance. 3. Long duration of meds that have good sterilizing properties. Rifampin best with PZA (PZA for first two months only). 4. Most regimes 6 months long. 5. ALWAYS USE MORE THAN ONE DRUG AND NEVER ADD ONE DRUG TO FAILING REGIME.

Question 31

latent TB treatment

Answer 31

Patients have a much lower bacterial burden compared to active disease (104 vs 109 bacilli) only one drug is needed- isoniazid for 9 months

Question 32

drug resistance 1. MDR. Resistant to at least _______ 2. XDR-TB MDR plus r to kanamycin, amikacin or capreomycin (INJECTABLES) plus any __________ 3. TDR or XXDR (4 cases in India, 2 Italy)

Answer 32

1. MDR. Resistant to at least INH and Rifampin 2. XDR-TB MDR plus r to kanamycin, amikacin or capreomycin (INJECTABLES) plus any quinolone. 3. TDR or XXDR (4 cases in India, 2 Italy)

Question 33

what is the strategy for active TB treatment?

Answer 33

RIPE/DOTS RIPE for first two months RI for four more months

Question 34

Drug resistance is on the rise – never add just one drug at a time to a failing regimen.

Answer 34

yep