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Flashcards in Tuberculosis Deck (42):

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 ___


in respiratory tract

latent tuberculosisi infection


Define latent TB infection vs. active TB

latent TB = infected with MTB but no active diseases

active TB = active disease due to reactiv of MTB


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

1) HIV

2) decline in public health infrastructure

3) incr # of immigrants in US

4) noscomial/institutional outbreaks


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


process of TB infection

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


Chronology of TB pathogenesis

1) Ingest resident alveolar macrophage

2) undergo phagosome-lysosome fusion and MTB killed


3) apoptotic death of macrophages --> MTB killed


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


Chronology of TB pathogenesis

Step 2: symbiotic stage

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


Chronology of TB pathogenesis

Step 3

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


why do AIDS patients keep getting recurrent MTB infection

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


Chronology of TB pathogenesis

Step 4a= LTBI - cellular

1) Solid caseous center intact

2) any bugs that escape are ingested by highly activ macrophages



Chronology of TB pathogenesis

Step 4b= decline in immunity --> reactiv

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


Radiographic feature of LTBI

1) Ranke complex = Ghon complex + calcified regional hilar or mediastinal lymph node

2) Ghon complex = calcified lung nodule due to granuloma

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Radiographic features of active TB

pneumonia, cavitations, destroyed lung


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


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Technique of Tuberculin skin test

1) inject 0.1 mL of 5 tuberculin PPD creating wheal

2) after 48-72 hrs, measure diamter of induration, not erythema


what is PPD made of?

culture filtrate of MTB with > 200 different myocbacterial antigens


Criteria for positive test if

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

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Advantages of TST

Advantages = inexpensive, perform in field,

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



Disadvantages of TST

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)



Distinguish between BCG vs. smallpox scar

BCG scar = raised center

Smallpox scar = depressed center with radiating lines to edges


What is procedure of Quantiferon IFN gamma release assay

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


What is procedure of T spot TB IFN gamma release assay

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


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

T spot TB because can detect indiv cells


Advantages of IGRA over TST?

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


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


TST>15 and Quantiferon >10 highest risk


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

1) HIV positive

2) anti-TNFa therapy

3) immigrants from TB prevalent regions


Effect of HIV on TB?

HIV accel TB progression

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


What makes HIV positive patients so susceptible to TB?

1) HIV


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


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



Effect of Vitamin D and TB

1) Vitamin D suppress growth of MTB in macrophages

2) vitamin D deficiency = incr risk for TB


Why are African Amerians incr susceptibility for TB

Lower vitamin D levels


mechanism of Vitamin D metabolism

1) Sun goes to liver

2) processed in kidney

3) produces antimicrobial peptide (cathelicidin)


Vitamin D induces expression of cathelicidin, ______

mechanism of cathelicidin

antimicrobial peptide that kills MTB



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


Treatment for LTBI

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


Side effects of INH

INH assoc hepatitis

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


What is 3HP treatment?

INH + rifapentene once weekly for 3 months


Substantial proportion of active TB due to ____

reactivation disease (from large portion of people with LTBI)


Where to look at subjects at risk for LTBI?

1) absolute/relative immunodeficiency

2) health care workers

3) recent contact with active TB


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.

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


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.

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.


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.

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


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.

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.


select all

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


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.

a and c