Tuberculosis

Question 1

What areas of world have highest rates of TB?

Answer 1

Subsaharan Africa and Asia

Question 2

What caused increase in TB in US in 1980’s? (5 things)

Answer 2

HIV, Asian immigration, increased homelessness, decreased public health spending, increased drug resistance.

Question 3

What organisms causes TB?
Gram?
Oxygen preference?
Transmission
2 main virulence factors
Reservoir

Answer 3

Mycobacterium tuberculosis
Gram positive
Obligate aerobic, preferring high O2 levels.
Transmitted via small droplet aerosols
Virulence factors: 1) being able to multiply in macrophages. 2) my colic acid forms waxy coating on cell wall, preventing phagosome-lysosome interactions and oxidative killing.
Humans are only natural reservoir

Question 4

Cord factor

Answer 4

Surface glycolipid on M tb that triggers Th1 response and enhances survival w/in macrophages.

Question 5

Steps of intracellular invasion

6 steps

Answer 5

1) Taken up by mannose / complement receptors on macrophages.
2) Prevents fusion w/ lysozyme and inhibits ROS damage.
3) Prevents apoptosis of host cell.
4) Blocks IFNg receptor to prevent intracellular killing.
5) TNF release attracts more macrophages –> increased spread. TNF also causes systemic sxs (fever, aches)
6) Infected macrophages may travel to lymph nodes –> bacteremia –> infection of other organs.

Question 6

When is CMI response initiated?

What specific type of response is it?

Answer 6

CMI initiated when 1000-10000 cells accumulate.

Delayed-type hypersensitivity (type IV)

Question 7

What percentage of people exposed to TB become infected?
Of those infected, what percentage have active disease?
What percentage have sxs in first 2 years, compared to later?

Answer 7

10-30% of people exposed get infected.
Only 10% of those infected have active disease.
5% develop sxs in 1st 2 years. 5% later.

Question 8

What is #1 killer of pxs w/ HIV?

Answer 8

TB

Question 9

Disseminated / Miliary TB
What is it?
Population

Answer 9

Serious form that spreads through blood to multiple body sites.
Most common in young kids and HIV pxs.

Question 10

IRIS
What does it stand for?
What is it?

Answer 10

Immune Reconstitution Inflammatory Syndrome

Occurs in HIV pxs when CD4 cells reactivate w/ tx –> pathological inflammation.

Question 11

Mycobacterium Avian Complex (MAC)

Answer 11

Bird disease that infects HIV pxs

Question 12

Infected TB pxs w/ increased risk of sxs

Answer 12

HIV, diabetes, CKD, silicosis, immunosuppression, less than 4 y/o

Question 13

Sxs of TB (5 things)

Answer 13

Chronic cough, fevers, night sweats, weight loss, anorexia. More common in parts of lung w/ low perfusion and high ventilation (upper lobes).

Question 14

TB skin test
What is injected?
What type of rxn is it?
2 parts of biphasic response
Cytokines that trigger erythema
Highest risk pxs and size of induration
Causes of false negatives
Causes of false positives

Answer 14

Purified protein derivative (PPD)
Delayed type hypersensitivity rxns (type IV)
Biphasic: non-specific rxn early. Specific rxn (Th1 mediated) w/in 48-72 hrs.
IFNg and TNF –> capillary leak –> erythema and induration
Highest risk pxs: HIV, recent contact w/ active TB px, fibrotic changes on CXR, chronic prednisone use, and organ transplant
False neg due to immunocompromised pxs, booster phenomenon, and IL-10 effect.
False pos due to endemic NTM and prior BCG vaccination

Question 15

IGRA
What dose it stand for?
How does it work?

Answer 15

IFNg Release Assays

Expose T cells to TB in vitro. If T cells were previously primed, they release a ton of IFNg.

Question 16

What is required to diagnose TB?

What is not sufficient to rule out TB?

Answer 16

Need positive sputum smear or biopsy.

TST, IGRA, and negative CXR in HIV pxs cannot rule out TB.

Question 17

What can be used to speed up culture detection from 7 weeks to 1 week?

Answer 17

Liquid media

Question 18

What should you do before starting tx for TB?

Answer 18

Assess for active disease (isolate them)
Do CXR (isolate and get sputum sample if positive.
Assume pxs w/ chronic respiratory sxs have active TB until ruled out.
Consider extrapulmonary TB

Question 19

Why should you treat latent TB?
How long?
Are pxs contagious?

Answer 19

Decreases risk of progression to active disease by 70%
Tx for 9 months
Not contagious

Question 20

How long does it take to not be contagious anymore after starting tx for active disease?

Answer 20

2 weeks

Question 21

Risk of isoniazid
Risk population
What is forbidden while on this drug?

Answer 21

Hepatotoxicity seen in elderly, pregnant women, and postpartum women.
Do NOT drink alcohol.

Question 22

4 1st line drugs

Answer 22

Isoniazid, rifampin, ethambutol, and pyrazinamide

Question 23

Resistant TB

Answer 23

Either isoniazid or rifampin.

Isoniazid more common.

Question 24

Multi-drug resistant TB

Risks for MDR TB

Answer 24

Both isoniazid and rifampin

Risks for MDR: prior therapy, foreign born, HIV, cavitary TB

Question 25

Extensively drug resistant TB

Answer 25

All 1st line, 1 FQ, and at least 1 injectable 2nd line.

Question 26

Types of resistance testing

Answer 26

Biochemical - most accurate but takes weeks

Molecular - done directly on cultures w/in 1-2 days.

Question 27

TB vaccine
What is it?
What's it derived from?
How does it work?
Contraindication

Answer 27

BCG
From Mycobacterium bovis
Does not prevent infection, but induces more rapid response by macrophages to prevent bacteremia.
Live vaccine so contraindicated in pregnancy and immunocompromised pxs.

Question 28

What organism causes leprosy?

What is leprosy?

Answer 28

Mycobacterium leprae

Leprosy is a chronic granulomatous disease of the peripheral nerves and superficial tissues.

Question 29

What accounts for far more cases of disease than TB?
Where is it found?
Direct contact transmission?

Answer 29

Non-TB mycobacteria
Found in water.
No person-to-person contact transmission.