TB - Cross

Question 1

What type of stain is best used to detect mycobacterium tuberculosis?

Answer 1

Acid fast stain

Question 2

What property of M. tuberculosis allows it to stain like it does?

Answer 2

Mycolic acid

Question 3

What is mycolic acid and where is it found?

Answer 3

fatty acid found in the cell wall

Question 4

Virulent strains are associated with what (think virulence factor)? Where does the name come from?

Answer 4

Cord factor, due to virulent strains growing in a cord-like pattern
Avirulent strains do not have cord factor

Question 5

Cord factor MOA?

Answer 5

inhibits macrophage maturation and induces TNF-alpha release

Question 6

Besides cord factor, what is another virulence factor important to M.tuberculosis? MOA?

Answer 6

Sulfatides (surface glycolipids) inhibit phagolysosomal fusion

Question 7

Cell wall of mycobacterium has what 4 components?

Answer 7

Mycolic acids, glycolipids, arabinogalactans, free lipids

Question 8

Risk factors predisposing to TB. List as many

Answer 8

• prison (crowded conditions)
• immigrant from high burden country
• malnourished
• alcoholism
• poverty
• debilitating illness
• AIDS
• Elderly
• Certain disease: DM, Hodgkin lymphoma, CKD, malnutrition, immunosuppression; RA on TNF alpha antagonist

Question 9

What is the critical mediator that allows macrophages to contain the infection?

Answer 9

IFN-gamma

Question 10

Most important determinant of whether overt TB disease occurs?

Answer 10

Adequacy of cell mediated immunity

Question 11

Pathogenesis. Initially, MTB enters what cells via what process?

Answer 11

Enters macrophages via phagocytosis

Question 12

Pathogenesis. After MTB has entered macrophage via phagocytosis, what occurs?

Answer 12

It will inhibit the formation of the phagolysosome, allowing bacteria to replicate

Question 13

Pathogenesis. After phagolysosome has been inhibited by TB, what cytokine is produced and what does it do?

Answer 13

After phagolysosome inhibited, IL-12 is produced, stimulating a T-helper response. IFN-gamma is then produced via Th1 cells, enabling macrophages to contain the infection (forming a granuloma)

Question 14

Pathogenesis. Activated macrophages secrete what factors? What is there role?

Answer 14

Activated macrophages secrete TNF-alpha and cytokines that recruit more monocytes

Question 15

Primary infection defined as?

Answer 15

Transmission from active case to susceptible host

Question 16

Primary infections are asymptomatic or symptomatic?

Answer 16

asymptomatic, 95% of cases

Question 17

Only evidence of primary infection is?

Answer 17

fibrocalcific nodule at site of infection

Question 18

Secondary infection defined as?

Answer 18

When viable organisms remain dormant for years, reactivate to produce secondary infection (active disease)

Question 19

Secondary infection usually involves what location of lungs? Why?

Answer 19

apices of lungs. MTB is an obligate aerobe and there is better O2 content at apex of lung

Question 20

Cavitation occurs frequently in primary or secondary infection?

Answer 20

secondary

Question 21

Erythema nodosum? Prognosis good or bad? Why? Is it specific for TB?

Answer 21

Indicative of good prognosis. Sign of good cell mediated immunity/ hypersensitivity response. Not specific for TB

Question 22

What tests should be done to diagnose TB?
Which is the initial test?
List the time it takes for each one

Answer 22

Acid fast stain on sputum (initial test)
Lowenstein Jensen solid agar - 3-6 weeks
Culture in liquid media - 2 weeks
PCR or nucleic acid amplification - rapid

Question 23

What test should NOT be done to diagnose TB

Answer 23

Culture on blood agar, it will not grow

Question 24

PCR or nucleic acid amplification better for smear positive or smear negative specimens?

Answer 24

Smear positive (initially sputum will come back smear positive or negative)

Question 25

What is the 1st line choice of antibiotics for TB?

Answer 25

``` RIPE Rifampin Isoniazid Pyrazinamide Ethambutol ```

Question 26

Miliary/Disseminated TB requires RIPE treatment for how long?

Answer 26

9-12 months

Question 27

Miliary TB pathophysiology. What occurs?

Answer 27

TV invasion into bronchus or lymphatics causes spread of TB throughout the lungs (and potentially elsewhere in the body). Lungs specifically look like millet seeds on CXR, hence the name

Question 28

What subset of patients are at high risk for miliary TB?

Answer 28

HIV patients

Question 29

What other organs are commonly infected in military TB?

Answer 29

Kidneys, Liver, bone marrow, spleen

Question 30

What is the most common extra pulmonary site of miliary TB?

Answer 30

Kidneys

Question 31

Miliary TB spreading to vertebrae = ?

Answer 31

Pott Disease

Question 32

RA patients on antagonists of what cytokine are at increased risk for TB?

Answer 32

RA patients on TNF-alpha antagonists. If TNA-alpha not induced, granulomas won't form and patient will have disseminated TB = death

Question 33

Once susceptibility is confirmed, which therapy from RIPE can be discontinued

Answer 33

Ethambutol

Question 34

Multidrug resistant TB is most commonly resistant to what drugs? What subset of patients are more likely to be MDR-TB patients?

Answer 34

Isoniazid and Rifampin, AIDS patients

Question 35

TB and HIV. What is a important risk factor?

Answer 35

Low CD4 count, can't produce Th1 cells, no IL-12.

Question 36

TB and HIV. Sputum culture statistics?

Answer 36

Increased frequency of false negative sputum smears

Question 37

TB and HIV. Granuloma frequency?

Answer 37

Absence of granulomas in tissues

Question 38

TB and HIV. Compare cavitation/bronchial damage as compared to healthy non HIV patients.

Answer 38

HIV patients have reduced immune response, therefore decreased cavitation/bronchial damage and fewer acid fast bacilli in sputum

Question 39

Purified protein derivative (PPD) test can be false positive for MTB if?

Answer 39

Patient has been exposed to other mycobacterium (such as mycobacterium avium)

Question 40

What latent TB test is only specific to MTB?

Answer 40

IGRA - IFN gamma release assay

Question 41

Which latent TB test is the gold standard?

Answer 41

IGRA - IFN gamma release assay

Question 42

How can you get a false positive with the PPD test?

Answer 42

If patient has been immunized with BCG vaccine

Question 43

If patient has BCG vaccine or a non tuberculosis mycobacterium infection, what will happen to the IGRA?

Answer 43

Nothing, there are no false positives with BCG or NTB infections

Question 44

What is one case where the PPD and IGRA test can have a false negative? Why? What is this called?

Answer 44

HIV patients, can produce false negative due to lack of immune response, sometimes called anergy

Question 45

Whats is the treatment for latent TB?

Answer 45

Isoniazid for 9 months; Isoniazid and Rifapentine for 3 months

Question 46

If patient tests positive for Latent TB, what is your next step?

Answer 46

Make sure they do not have an active disease. Obtain a CXR and do a workup before you put them on medication for latent TB

Question 47

Bacillus Calmette-Guerin (BCG) vaccine used against TB contains a strain from which mycobacterial species?

Answer 47

Mycobacterium bovis

Question 48

BCG vaccine is limited in U.S to who?

Answer 48

young children in close contact with individuals with active TB and military personnel

Question 49

BCG vaccine is contraindicated in what patients?

Answer 49

Immunocompromised patients

Question 50

BCG vaccine is also used to treat what cancer?

Answer 50

Bladder cancer

Question 51

Adverse effect of Rifampin

Answer 51

Orange-red secretions (tears,urine, saliva) will stain contact lenses

Question 52

Toxicity associated with Rifampin

Answer 52

Hepatotoxicity

Question 53

Isoniazid associated with 2 types of toxicity based on what characteristic?

Answer 53

Slow acetylators of INH - neuropathy | Fast acetylators of INH - hepatotoxicity

Question 54

Pyrazinamide adverse effect?

Answer 54

hyperuricemia - leading to gout

Question 55

Ethambutol toxicity?

Answer 55

Ocular toxicity