Lecture 1: Mycobacterium

Question 1

Which chronic lung disease puts people at a particularly high risk for tuberculosis?

Answer 1

Silicosis

Question 2

Which critical mediator released from T_H1 cells both in LN’s and the lung enables macrophages to contain M. tuberculosis infection?

Answer 2

IFN-γ

Question 3

Which immune cells orchestrate the formation of granulomas and caseous necrosis seen in M. tuberculosis infection?

Answer 3

T_H1

Question 4

Macrophages activated by IFN-γ in M. tuberculosis infection differentiate into what?

Answer 4

“Epithelioid histiocytes” that aggregate to form granulomas; some may aggregate to form giant cells

Question 5

Pt’s with RA treated with what type of drugs are at an increased risk for tuberculosis reactivation?

Answer 5

TNF antagonist

Question 6

Which pattern of tuberculosis arises in a nonimmune host vs. previously sensitized host?

Answer 6

• Non-immune = primary TB
• Previously sensitized = secondary TB

Question 7

Secondary pulmonary tuberculosis classically involves which area of the lungs?

Answer 7

APEX of one or both lungs

Question 8

What are the systemic and pulmonary signs/sx’s associated with secondary tuberculosis?

Answer 8

• Remittent/low-grade FEVER + WEIGHT LOSS + Night sweats
• Fever appears late each afternoon and then subsides
• Sputum that at first is mucoid and later purulent; variable degree of hemoptysis

Question 9

Which laboratory diagnostic test allows for more rapid diagnosis of M. tuberculosis?

Answer 9

PCR amplification of M. tuberculosis DNA

Question 10

What remains the gold standard for confirming diagnosis of M. tuberculosis?

Answer 10

Culture

Question 11

Primary tuberculosis almost always begins in which organ and what is seen morphologically as sensitization develops?

Answer 11

• Lungs –> bacilli implant in the distal airspaces of lower part of upper lobe or upper part of lower lobe
• Gray-white inflammation w/ consolidation, know as Ghon focus –> center of focus undergoes caseous necrosis

Question 12

Ghon complex seen in primary TB is a combination of what?

Answer 12

Parenchymal lung lesion (Ghon focus)+LN involvement

Question 13

Cell-mediated immunity typically controls the primary TB infection leading to what morphological change in the Ghon complex, which is often followed by what radiologically detectable change?

Answer 13

Ghon complex undergoes progressive fibrosis, followed by radiologically detectable calcification (Ranke complex)

Question 14

Which subset of pt’s do NOT form the characteristic granulomas associated with primary TB and instead have macrophages loaded with many bacilli?

Answer 14

Immunocompromised

Question 15

What is a risk factor in HIV infected pt’s before starting HAART which increases risk for developing tuberculosis?

Answer 15

Low CD4 count

Question 16

Systemic miliary tuberculosis is most prominent in which organs/structures?

Answer 16

• Liver
• Bone marrow (osteomyelitis)
• Spleen
• Adrenals (Addison diseas)
• Meninges (tuberculous meningitis)
• Kidneys (renal tuberculosis)
• Fallopian tubes (salpingitis) and Epididymis

Question 17

With progressive pulmonary tuberculosis, the pleural cavity is almost invariably involved, and what 3 complications may be seen here?

Answer 17

• Pleural effusions
• Tuberculous empyema
• Obliterative fibrous pleuritis

Question 18

When the vertebrae are affected by isolated tuberculosis this is known as what?

Parapsinal “cold” abscesses in these pt’s may track along tissue planes and present how clinically?

Answer 18

• Pott disease
• Present as abdominal or pelvic mass

Question 19

What is the most frequent presentation of extra-pulmonary tuberculosis (aka what is most often affected)?

Answer 19

Lymphadenitis

Question 20

How does lymphadenitis and the presentation differ in HIV-negative vs. HIV-positive pt’s with active tuberculosis?

Answer 20

• HIV-negative = lymphadenitis tends to be unifocal and localized
• HIV-positive = tends to be multifocal disease w/ systemic sx’s, and either pulmonary or other organ involvement

Question 21

Granulomatous inflammation leading to ulceration of the overlying mucosa and eventually healing strictures associated with intestinal tuberculosis is most often seen in which segment of the intestine?

Answer 21

Ileum

Question 22

What is the stain, shape, motility and oxygen dependence of M. tuberculosis?

Answer 22

Weakly gram (+) rod, NON-motile, obligate aerobe

Question 23

How is TB required and what is unique about this mode of transmission?

Answer 23

Aerosolized transmission; droplets can remain suspended for hours!

Question 24

Which virulence factor of M. tuberculosis inhibits neutrophil migration and damages mitochondria; releases cachectin causing weight loss?

Answer 24

Cord factor

Question 25

Which lobes of lung involved in primary TB?

Answer 25

**Middle** and **lower** lobes

Question 26

Which virulence factor of *M. tuberculosis* inhibits the phagosome from fusing with the lysosome?

Answer 26

Sulfatides

Question 27

A person with a postive PPD skin test is considered to have what?

Answer 27

**Latent** TB

Question 28

A positive PPD skin test is defined as what?

Answer 28

**Area of induration** (hardness) that is **greater** than a pre-defined size **after 48 hours!**

Question 29

A positive PPD skin test will be present in which 3 situations?

Answer 29

- Pt with **active** infection - Pt with **latent** infection - Pt who was **cured** of their infection

Question 30

What is the BCG vaccine **made from** and why is it given; why you should be weary about it when giving a PPD test for TB?

Answer 30

- Made from ***M. bovis*** - Given in high prevelnace areas for prevention of **severe** forms of **disseminated** TB in **children** - May cause a **false (+) PPD** test

Question 31

What is anergy and what may it be caused by?

Answer 31

- **Anergic** = lack normal immune response due to.. **- Steroid use, malnutrition**, **AIDS**, etc.

Question 32

If the typical healing by fibrosis and/or calcification seen with primary TB does not occur and instead progresses to primary progressive TB what are 3 patterns of injury which may be seen?

Answer 32

- **Primary** caseous pneumonia - **Tuberculosis** bronchopneumonia --\> 2' to **bronchogenic** spread - **Miliary** tuberculosis --\> 2' to **hematogenous** spread

Question 33

What is the common CXR finding for secondary TB?

Answer 33

**APICAL** and **posterior** segment involvement, **pulmonary cavitation** present

Question 34

What is another name for the PPD test?

Answer 34

**Mantoux skin test**

Question 35

In which 4 situations will an induration of ≥5mm be considered a positive PPD test?

Answer 35

- **HIV** - **Close contact** w/ **actively** infected person - **CXR** w/ **fibrotic changes** consistent w/ **TB** - **Immunosuppression** (**TNF-alpha inhibitors**, **chronic glucocorticoids**, **chemotherapy**, and **organ transplant**)

Question 36

What are 4 situations where an induration of ≥10mm is considered a positive result from a PPD test?

Answer 36

- **Pt w/ clinical conditions that ↑ risk of reactivation:** silicosis, DM, chronic renal failure w/ dialysis, malginancies, malnourished, IV drug abuse - **Children \<4** - **From country of high prevalence** - **Residents/employees** in **high risk** **setting**: jail, healthcare, mycobacterium labs, homeless shelters

Question 37

What are 4 causes of false positive PPD tests?

Answer 37

- **Previous BCG** vaccine - Infections w/ **non**tuberculosis mycobacterium - **Incorrect** administration of TST - **Incorrect** interpretation

Question 38

What are 6 causes of false negative PPD test?

Answer 38

- **Anergy** - **Recent** TB **exposure** (not enough time to generate response) - **Age \<6 months** - Very **old** TB - **Recent live virus vaccine** for infxn w/ virus (**measles, chicken pox**) - **Overwhelming** TB infection

Question 39

What is the **initial** staining used to **screen** for *M. tuberculosis*?

Answer 39

- **Initial screen** = **Auramine-rhodamine stain** (utilizes fluorescent microscopy)

Question 40

Which 2 stains are **confirmatory** for TB?

Answer 40

- **Ziehl-Neelsen** stain - **Kinyon** stain

Question 41

XDR-TB (aka extremely drug resistant) is defined as resistance to what?

Answer 41

- **Isoniazid** - **Rifampin** - a **Fluoroquinolone** - An **injectable** agent (such as an **aminoglycoside**)

Question 42

What is the most common cause of fever of unknown origin in AIDS patients?

Answer 42

Mycobacterium Avium Complex (MAC)

Question 43

How does mycobacterium avium complex present in AIDS patients?

Answer 43

Disseminated infection w/ **fever**, **weight loss**, **hepatitis**, and **diarrhea**

Question 44

Which 2 immunocompetent patient populations may be affected by mycobacterium avium complex and what is seen in each?

Answer 44

- **Upper lung cavitary** disease in **elderly smokers** - **Middle** and **lower** lung **nodular** and **bronchiectatic** disease in **middle-aged female non-smokers**

Question 45

Which virulence factor of *M. tuberculosis* is used for Fe²⁺ acquisition?

Answer 45

Siderophore

Question 46

Which drug is added to TB regimen for drug resistant forms?

Answer 46

Streptomycin

Question 47

What is the most common extrapulmonary manifestation of *M. tuberculosis?*

Answer 47

**Lymphadenitis** --\> Scrofula

Question 48

If a pt showing no signs of pulmonary TB receives a PPD test with induration of 12mm and has a hx of BCG vaccination; what is the next best step in management of this pt?

Answer 48

Interferon-gamma release assay

Question 49

What are 2 lab findings of the aspirate taken from a pleural effusion caused by TB; what stage of TB infection are pleural effusions most commonly associated with?

Answer 49

- **Adenosine** **deaminase** and **IFN-gamma** - Associated with **primary progressive TB**

Question 50

*Mycobacterium kansasii* is most commonly seen in whom; is endemic in which areas of the US?

Answer 50

- **Older pt's** with **underlying lung disease** or **long term smokers** - **M\>\>W** - **Endemic**: Midwest and SW United States

Question 51

What is the tx and duration for *Mycobacterium kansasii?*

Answer 51

**Rifampin** + **isoniazid** + **ethambutol** for at least **18 months!!!**