Tuberculosis

Question 1

Primary TB infection

initial infection with ____

almost always occurs where?

in immunocompetent individuals, most primary infections do not develop into active disease, resulting in state of ___

Answer 1

MTB

in respiratory tract

latent tuberculosisi infection

Question 2

Define latent TB infection vs. active TB

Answer 2

latent TB = infected with MTB but no active diseases

active TB = active disease due to reactiv of MTB

Question 3

TB was declining until 1984-1994 when unexpected incr due to what?

Answer 3

1) HIV
2) decline in public health infrastructure
3) incr # of immigrants in US
4) noscomial/institutional outbreaks

Question 4

most people infected with
MTB( do or do not) develop active disease

process of TB infection

Answer 4

do not

1) TB exposure
2) but then get primary TB infection and infection cleared spontaneously unless you have HIV or infant and you get progressive primary (active) TB
3) latent TB infection due to reactivation of TB

Question 5

Chronology of TB pathogenesis

Answer 5

1) Ingest resident alveolar macrophage
2) undergo phagosome-lysosome fusion and MTB killed

or

3) apoptotic death of macrophages –> MTB killed

or

4) mutliplication of MTB with necrosis death of macrophages –> MTB survives, released extracellularly and taken up by macrophages

Question 6

Chronology of TB pathogenesis

Step 2: symbiotic stage

Answer 6

1) necrotic macrophages release MTB
2) blood monocytes migrate into lung –> differentiate into macrophage
3) continued ingestion but no destruction of MTB
4) MTB multiplies in inactivated macrophages
5) formation of early primary tubercle

Question 7

Chronology of TB pathogenesis

Step 3

Answer 7

1) T cells from mediastinum activate macrophage to kill/prevent spread of MTB
2) granulomas form (MTB unable to multipley in solid caseous material)
3) infection contained

Question 8

why do AIDS patients keep getting recurrent MTB infection

Answer 8

CD4+ lymphopenia causes granuloma breakdown so can’t control primary or latent infection

Question 9

Chronology of TB pathogenesis

Step 4a= LTBI - cellular

Answer 9

1) Solid caseous center intact
2) any bugs that escape are ingested by highly activ macrophages

Question 10

Chronology of TB pathogenesis

Step 4b= decline in immunity –> reactiv

Answer 10

1) immunosuppression (AIDS, cancer, anti-TNFa, aging, malnutrition)
2) loss of integrity of granuloma
3) liquifaction of caseous material (caseous necrosis) –> multiply MTB
4) cavity formation
5) rupture and spread to other part of lung

Question 11

Radiographic feature of LTBI

Answer 11

1) Ranke complex = Ghon complex + calcified regional hilar or mediastinal lymph node
2) Ghon complex = calcified lung nodule due to granuloma

Question 12

Radiographic features of active TB

Answer 12

pneumonia, cavitations, destroyed lung

Question 13

1) MTB present yes/no
2) tuberculin skin test positive yes/no
3) CXR normal or not
4) sputum culture/smear normal or not
5) symptoms yes or no
6) infectious yes/no

Answer 13

Question 14

Technique of Tuberculin skin test

Answer 14

1) inject 0.1 mL of 5 tuberculin PPD creating wheal
2) after 48-72 hrs, measure diamter of induration, not erythema

Question 15

what is PPD made of?

Answer 15

culture filtrate of MTB with > 200 different myocbacterial antigens

Question 16

Criteria for positive test if

you look at > 5 mm induration, > 10 mm induration, > 15 mm induration

Answer 16

Question 17

Advantages of TST

Answer 17

Advantages = inexpensive, perform in field,

treatment of LTBI diagnosed by TST effective in preventing reactiv of TB

Question 18

Disadvantages of TST

Answer 18

1) False positivity can occur in people with BCG vaccine due to crossreactivity to PPD
2) False positivity in individuals infected with environ mycobacteria
3) False negativity in indiv with T cell depleted (AIDS, organ transplant, chemo, aging)
4) NOT SENSITIVE OR SPECIFICITY

Question 19

Distinguish between BCG vs. smallpox scar

Answer 19

BCG scar = raised center

Smallpox scar = depressed center with radiating lines to edges

Question 20

What is procedure of Quantiferon IFN gamma release assay

Answer 20

1) incubate overnight whole blood with antigens specific for MTB (ESAT-6 or CFP-10) –> decr false positive
2) meausre [IFN]g-g

–> can detect if you have memory T cells from real disease that will respond significantly when see antigens again

Question 21

What is procedure of T spot TB IFN gamma release assay

Answer 21

1) coat bottom with anti-IFNg AB
2) isolate lymphocyte and monocytes from patient’s blood
3) stim cells with ESAT-6 or CFP-10
4) if memory T cells produce more IFNg they will be dtected by antibody

Question 22

which is more sensitive in immunocompromised host, T spot TB or quantiferon

Answer 22

T spot TB because can detect indiv cells

Question 23

Advantages of IGRA over TST?

Answer 23

1) more rapid turnaround
2) more objective
3) sensitivity for LTBI is good or better than TST (T spot better than Quantiferon or TST)
4) Specificity for LTBI better than PPD

Question 24

Positive quantiferon results were ____ (more/less) predictive than TST to develop TB

Answer 24

more

TST>15 and Quantiferon >10 highest risk

Question 25

Who should be tested for LTBI (patient groups) and if positive, should be treated

Answer 25

1) HIV positive
2) anti-TNFa therapy
3) immigrants from TB prevalent regions

Question 26

Effect of HIV on TB?

Answer 26

HIV accel TB progression

TB causes 1/3 of deaths from AIDS (99% in developing countries)

Question 27

What makes HIV positive patients so susceptible to TB?

Answer 27

1) HIV
2) AIDS
3) depletion of CD4+ T cells
4) decr IL-2, IFN-g, macrophage activ, decr granuloma integrity b/c need T cells to form granulomas
5) reactiv TB

Question 28

____ account for 65% of all active TB cases in US

Answer 28

immigrants

Question 29

Effect of Vitamin D and TB

Answer 29

1) Vitamin D suppress growth of MTB in macrophages
2) vitamin D deficiency = incr risk for TB

Question 30

Why are African Amerians incr susceptibility for TB

Answer 30

Lower vitamin D levels

Question 31

mechanism of Vitamin D metabolism

Answer 31

1) Sun goes to liver
2) processed in kidney
3) produces antimicrobial peptide (cathelicidin)

Question 32

Vitamin D induces expression of cathelicidin, ______

mechanism of cathelicidin

Answer 32

antimicrobial peptide that kills MTB

MTB taken up by TLR –> bind Vitamin D receptor –> goes to nucleus –> transcribe cathelicidin that can kill TB

Question 33

Treatment for LTBI

Answer 33

9 months isoniazid (INH) or 4 months rifampin daily or 3HP (INH + rifapentene once weekly x 3 months)

Question 34

Side effects of INH

Answer 34

INH assoc hepatitis

–> risk factors = age, EtOH, pre-existing liver disease, other hepatotoxic drugs

Question 35

What is 3HP treatment?

Answer 35

INH + rifapentene once weekly for 3 months

Question 36

Substantial proportion of active TB due to ____

Answer 36

reactivation disease (from large portion of people with LTBI)

Question 37

Where to look at subjects at risk for LTBI?

Answer 37

1) absolute/relative immunodeficiency
2) health care workers
3) recent contact with active TB

Question 38

True or false

A 50 y.o. man with a heart transplant is found to have a PPD of 8 mm. He has never received treatment for LTBI. He should be started on INH for a total of 9 months.

Answer 38

True: a solid organ transplant recipient is highly immunosuppressed and should receive INH for LTBI if the PPD is ≥ 5 mm.

Question 39

True or false

A 27 y.o. medical student beginning her 3rd year clinical clerkship has a PPD induration of 7 mm. She has no medical problems. She should get 9 months of INH prophylaxis because she will be constantly exposed to patients with TB.

Answer 39

False: for a health care worker who is otherwise healthy, the criteria for positivity is ≥ 10 mm. As for all health care workers with patient contact, she should be tested yearly to monitor for PPD conversion.

Question 40

True or False

. A 55 y.o. alcoholic man has a PPD induration of 15 mm. He lives in a homeless shelter in NYC and has been incarcerated recently. He is coughing up sputum that is blood streaked. His CXR shows an upper lobe cavitary lesion that is new from 1 year ago. His sputum smear is positive for AFB but the culture at 1 week is negative. He should receive INH for 9 months.

Answer 40

False: this man likely has active TB and should be treated with a multi-drug regimen (with at least 4 drugs).

Question 41

True or false

A 45 y.o. woman with schizophrenia has a PPD induration of 16 mm. She is otherwise healthy. Due to her history of non-adherence to her medications, you should prescribe 2 months of rifampin-pyrazinamide regimen rather than the 9 months of INH.

Answer 41

False: rifampin-pyrazinamide combination for LTBI is associated with an unacceptable risk of severe hepatitis and although a 2 month regimen is easier to adhere to, this regimen should (never) be used.

Question 42

select all

In a BCG-vaccinated person, the IFNγ-release assays (Quantiferon® or T-

SPOT.TB®)…

a. are more specific than the TST.
b. are less specific than the TST.
c. have a better positive predictive value than the TST. d. have a worse positive predictive value than the TST.

Answer 42

a and c