Tuberculosis

Question 1

True or false: tuberculosis is not curable

Answer 1

false
tuberculosis is preventable and curable

Question 2

Which population is impacted by tuberculosis the most in Saskatchewan?

Answer 2

Indigenous
-6x higher than the provincial rates
-42% of cases in SK living in First Nations communities

Question 3

Which organism causes tuberculosis?

Answer 3

mycobacterium tuberculosis

Question 4

How is tuberculosis spread?

Answer 4

spread is airborne via coughing or sneezing
-host inhales droplet nuclei
-close contacts most likely to be infected
-prolonged contact: risk of infection can be up to 30%

Question 5

Describe mycobacterium tuberculosis.

Answer 5

acid fast bacillus
-impervious to gram staining (can appear weakly gram +)
slow growing (doubling time 20hrs)

Question 6

What are the risk factors for tuberculosis?

Answer 6

foreign born from highly endemic area
Canadian Indigenous population
close contact
homeless
incarceration
alcoholism, IVDU, malnutrition
co-infection with HIV (synergism)

Question 7

What are the risk factors for active TB disease?

Answer 7

once infected with M. tuberculosis: lifetime risk of active TB is 10%
risk greatest during first 2 years after infection
<2yo and >65yo: greater risk of active disease
immunosuppression
HIV infected

Question 8

What increases the probability of transmission of tuberculosis?

Answer 8

# of infectious droplets per volume of air and length of time spent breathing that air
bacterial burden in source
upper lung disease in source
laryngeal disease in source
severity and amount of cough in source
crowding and poor ventilation
duration of exposure
proximity to source
delayed diagnosis and tx of source

Question 9

What is involved in the host response of a tuberculosis infection?

Answer 9

T-lymphocyte response (mainly CD4+)
-active macrophages that engulf and kill mycobacterium
TNF-a and TNF-y are important cytokines in coordinating immune response
organism has many mechanisms to evade immune response

Question 10

How does a primary infection of tuberculosis occur?

Answer 10

inhalation of droplet nuclei which reach alveoli

Question 11

What does the progression of clinical tuberculosis depend upon?

Answer 11

infecting dose (# of organisms inhaled)
virulence of the organism
cell-mediated immune response
-macrophages kill: infection controlled
-organism not killed: macrophages rupture, bacteria spill out

Question 12

What occurs roughly 3 weeks after tuberculosis infection?

Answer 12

T-lymphocytes are presented with M. tuberculosis antigen
T-cells become active and secrete INF-Y
-this stimulates macrophages to become -cidal
large # of -cidal macrophages surround the tuberculosis foci

Question 13

What is the process called for creating activated microbiocidal macrophages?

Answer 13

cell mediated immunity

Question 14

What is occurring at the same time as CMI?

Answer 14

DTH (delayed-type hypersensitivity)
-cytotoxic immune response that kills nonactivated immature macrophages that allow bacillary replication
-occurs via T lymphocytes
-released bacteria then killed by activated macrophages

Question 15

What can the inflammatory response to tuberculosis result in?

Answer 15

tissue necrosis
calcification
lymph node enlargement

Question 16

When is the tuberculin skin test positive?

Answer 16

when activated lymphocytes reach an adequate number and tissue hypersensitivity results

Question 17

Describe reactivation of disease for tuberculosis.

Answer 17

occurs in 10% of cases
most often in apices of lung (high O2, poor local immunity)
organisms within granulomas emerge and multiply extracellularly
granulomas liquefy and spread producing cavities
if untreated, destroy the lung - hypoxia, resp acidosis, death

Question 18

What are extrapulmonary sites or diseases that can be caused by tuberculosis?

Answer 18

lymphatic and pleural disease most common
bone (often vertebrae), joint, GU, meningeal
large # of organisms in bloodstream (miliary TB)=emergency
HIV (destroys CD4+ cells = depleting cells that control TB)

Question 19

What are the signs and symptoms of tuberculosis?

Answer 19

gradual onset
may not seek medical attention until hemoptysis
fever, cough, fatigue, night sweats, weight loss
Frank hemoptysis
chest exam: dullness to percussion, rales
moderate increase in WBC (mainly lymphocytes)
CXR: nodular infiltrates (apices), cavitations

Question 20

How is tuberculosis diagnosed?

Answer 20

Mantoux test (TB skin test)
-read in 48-72h
-measure the induration (bump), not redness
sputum culture and sensitivity

Question 21

In general, what is the treatment for tuberculosis?

Answer 21

isolation to prevent spread
drugs to cure
adherence: directly observed therapy (DOT)
identification of contacts

Question 22

What is required for active tuberculosis?

Answer 22

combination therapy

Question 23

Explain the differences in drug susceptibility within the 3 subpopulations of microorganisms.

Answer 23

extracellular:
-isoniazid, rifampin, streptomycin
within granulomas:
-pyrazinamide best drug
-isoniazid and rifampin
intracellular within macrophages:
-rifampin, isoniazid, quinolones

Question 24

What is the treatment for latent tuberculosis?

Answer 24

rifampin daily x 4 months (4R)
-#1 option
rifapentine and isoniazid once weekly x 3 months (3HP)
unable to use rifamycin regimen:
-isoniazid daily x 9 months (6 month is alt)

Question 25

What is the standard treatment for active tuberculosis?

Answer 25

rifampin, isoniazid, ethambutol and pyrazinamide for 2 months followed by rifampin and isoniazid for 4 months
= 6 months total

Question 26

What can be done if the bacteria is sensitive to rifampin and isoniazid?

Answer 26

ethambutol can be stopped at any time

Question 27

How long is treatment of active tuberculosis if pyrazinamide is not used?

Answer 27

9 months of isoniazid and rifampin required

Question 28

Differentiate the initial phase and continuation phase of active tuberculosis.

Answer 28

initial phase:
-3 to 4 effective drugs daily x 2 months
continuation phase:
-minimum 2 drugs, daily preferred but option of intermittent with DOT

Question 29

How long is treatment of active tuberculosis when rifampin and isoniazid are not used?

Answer 29

2 years or more

Question 30

What is the MOA of isoniazid?

Answer 30

inhibit bacterial wall synthesis
-powerful early bactericidal activity

Question 31

How should isoniazid be taken?

Answer 31

on an empty stomach

Question 32

Which patients are at higher risk of neurotoxicity with isoniazid?

Answer 32

slow acetylators
many other comorbidities

Question 33

What are the adverse effects of isoniazid?

Answer 33

elevations in transaminases common
hepatotoxicity
neurotoxicity
other: GI, rash, hematologic abnormalities

Question 34

What are drug interactions of isoniazid?

Answer 34

inhibits metabolism of phenytoin, carbamazepine, primidone, valproic acid, warfarin
-monitor and adjust doses as needed
increased risk of hepatotoxicity with acetaminophen

Question 35

What is the MOA of rifampin?

Answer 35

inhibits bacterial RNA synthesis by binding to the beta subunit of DNA-dependent RNA polymerase
-blocking RNA transcription

Question 36

How should rifampin be taken?

Answer 36

on an empty stomach

Question 37

If a strain is resistant to rifampin, what else is the strain likely resistant to?

Answer 37

isoniazid

Question 38

How long is tuberculosis treatment without rifampin?

Answer 38

minimum 12-18 months

Question 39

What are the adverse effects of rifampin?

Answer 39

liver enzyme elevations
hepatotoxicity
rash, fever, GI, colors body secretions orange/red
allergic rxn (esp with intermittent dosing)
flu-like sx
hemolytic anemia, acute renal failure

Question 40

What are the drug interactions of rifampin?

Answer 40

MANY
potent enzyme inducer, esp 3A4
-macrolides, azoles, protease inhibitors, simv, phenytoin, cyclosporine, steroids, warfarin
oral contraceptives

Question 41

What is an advantage of rifabutin?

Answer 41

less drug interactions than rifampin

Question 42

When is rifabutin preferentially used?

Answer 42

with some antivirals and immunosuppressives

Question 43

What are the adverse effects of rifabutin?

Answer 43

arthralgia, myalgia
less common:
-hepatotoxicity
-neutropenia
-thrombocytopenia
-rash
-uveitis

Question 44

What is an advantage of rifapentine?

Answer 44

longer t1/2 than rifampin

Question 45

What are the adverse effects of rifapentine?

Answer 45

rash, hematologic, arthralgias, increased liver enzymes
more hypersensitivity rxns

Question 46

How long is tuberculosis treatment when pyrazinamide is on board?

Answer 46

when used in first 2 months, shortens duration to 6 months
-not used: duration is at least 9 months

Question 47

What are the adverse effects of pyrazinamide?

Answer 47

GI, arthralgias, increased uric acid
hepatotoxicity (major, dose related)

Question 48

What is the role of ethambutol?

Answer 48

generally bacteriostatic, prevents resistance

Question 49

What are the adverse effects of ethambutol?

Answer 49

GI most common
retrobulbar neuritis

Question 50

Which drugs should be avoided while on ethambutol?

Answer 50

antacids

Question 51

What is the role of quinolones for tuberculosis?

Answer 51

alt when 1st line agent has to be d/c
-levofloxacin and moxifloxacin

Question 52

Describe the BCG vaccine.

Answer 52

attenuated, hybridized strain of M. bovis
produces subclinical infection resulting in sensitization of T lymphocytes and cross-immunity to M. tuberculosis
primary benefit: prevention of severe forms of TB in children
not routinely given in Canada with exceptions

Question 53

What are some drugs where concentration may be substantially decreased with rifamycins?

Answer 53

hormone therapy
-add a barrier method of contraception
levothyroxine
-monitor TSH
SSRIs
-may need dose increase
corticosteroids
-monitor clinically, may need dose increase
DOACs
-some combos CI
warfarin
-monitor PT, may need dose increase
methadone
-may need dose increase
anticonvulsants
-may need dose increase
antiretrovirals
-rifabutin preferred

Question 54

What are the patient monitoring parameters for tuberculosis?

Answer 54

initial: physical, weight, visual acuity, color vision testing, CXR
baseline labs:
-CBC, AST, ALT, bilirubin, SCr, HIV serology, Hep C serology, HbA1C
sputum
-for efficacy (q1-2 wks until 2 consecutive negatives)
-monthly until 2 consecutive negatives
drug sensitivity testing
adherence (DOT)
monthly weight, vision testing (EMB), CBC, SCr, AST, ALT, bilirubin
drug interactions