5 TB & Non-TB Mycobacterial Infections

Question 1

What percentage of the world population is infected with Tuberculosis?

Answer 1

33% or 2 billion 🤯

But over 90% of healthy persons infected NEVER become ill

Question 2

Why is TB difficult to eradicate?

Answer 2

Spread of infection is a significant health problem

Rising numbers of MDR and XDR strains

Patients with inadequate treatment both remain infectious and offer opportunity for drug resistance development

Question 3

TB is a common co-infection with …

Answer 3

HIV

Question 4

How is TB transmitted?

Answer 4

Person-to-person through aerosol droplet nuclei

Question 5

What happens to infants who get TB?

Answer 5

Hematogenous dissemination

Can result in meningitis and other symptoms

Question 6

Why do older adults get TB?

Answer 6

Failure of immune system or possible deactivation of latent infection

Question 7

Factors that effect the probability of TB infection

Answer 7

Exposure environment (crowded conditions)

Duration of exposure (prolonged)

Virulence of strain (varies)

Strains vary in abx susceptibility (MDR and XDR)

Question 8

Risk factors for TB

Answer 8

Close contact of those with TB (esp children)

Residence in long-term care facility

Low income/inner city housing

Alcoholism or IVDU

Malnutrition

DM (30% increase over lifetime)

Silicosis

Immunosuppression

Question 9

What are the three species that produce human tuberculosis?

Answer 9

Mycobacterium tuberculosis

Mycobacterium bovis (cattle)
• Consumption of unpasteurized milk or contact with infected animals
• Source of BCG vaccine

Mycobacterium africanum (west African countries)
• 25% of cases
• Opportunistic infection - esp in HIV
• May be spread by food - no animal reservoirs defined

Question 10

Describe Mycobacterium tuberculosis

Answer 10

Obligates aerobe

Rod shaped (bacillus), usually slender and slightly curved

Non-motile

Heat sensitive

Intracellular growth (in alveolar macrophages)

ACID-FAST (Ziehl-Neelsen or Kinyoun stains)

Question 11

Mycobacterium tuberculosis doesn’t have classic virulence factors or toxins but these things help them out…

Answer 11

Mycolic acids in cell wall - long chain fatty acids prevent dehydration and may resist H2O2

Cord Factor - mycoside (glycolipid Mycolic acid + disaccharide)

Lipoarabinomannan (LAM) - inhibits cell-mediated immunity, scavenges reactive oxygen intermediates

Question 12

What are the potential outcomes of TB infection?

Answer 12

Immediate resolution (NO active case of TB, b/c innate immune system able to clear bacteria)

Primary disease

Progressive Primary (Active) disease

Latent Infection

Endogenous reactivating/secondary disease

Question 13

Areas surrounded by macrophages, multi-nucleated giant cells, fibroblasts and collagen fibers that harbor viable MTB cells

Answer 13

Granulomas

Structures become evident 2-6 weeks after infection

Over time, can form fibrotic tubercle and calcify (can see on CXR)

Question 14

Describe someone with Latent TB

Answer 14

Healthy

Bacteria remain viable in lesions but are inactive

Patient does not have symptoms and are no risk to spread disease

BUT TREAT THEM!

Question 15

Describe someone with deactivation or secondary TB

Answer 15

SSx present, patient is infectious

Begins insidiously - may be present weeks to months before diagnosis

Cough, weigh loss, fatigue, fever, night sweats, chest pain

Lesions
• Progression from caseous lesions with necrosis
• Erode and discharge TB bacilli into bronchi (infectious)
• Erode blood vessel —> hematogenous spread

Question 16

Tell me about military tuberculosis

Answer 16

Results from lymphohematogenous spread of primary infection or via a latent focus with subsequent spread

Question 17

How do we diagnose TB?

Answer 17

CXR consistent with TB

Skin test reactivity

Sputum stain/broth cuture to detect acid-fast bacteria

Rapid blood test based on release of IFN-gamma (stimulates isolated T-cells to produce IFN-gamma)

NEW: GeneXpert Rapid test (tests for MTB and Rifampin resistance)

Question 18

What is TB prophylaxis

Answer 18

For exposed subjects - regimen depends on HIB status and whether or not agents is drug resistant

Isoniazid x 9 months

BCG vaccination in high endemicity areas

Question 19

How is serial screen for TB usually performed?

Answer 19

Use of purified MTB protein derivative (PPD) in tuberculin skin test (Mantoux test)

Boosters identified by quick second administration

BCG recipients and NTM infections can lead to false positives

Question 20

Describe Mycobacterium avium complex (MAC)

Answer 20

Weakly gram-positive aerobic bacilli

ACID-FACT

Ubiquitous - found in water (fresh, brackish, ocean and drinking), soil, and plants

Slow growing organisms

Question 21

How are MAC infections acquired?

Answer 21

Enter body via ingestion of contaminated water or food

NO person-to-person transmission

NO patient isolation required

Opportunistic human pathogen - now the leading cause of NTM infection in HIV+ patients in US

Question 22

What is the disease spectrum like for MAC?

Answer 22

Immunocompetent patients:
• Middle-aged and older males with history of smoking, can have cavitary lesions resembling TB
• Elderly female non-smokers - can have patchy or modular x-ray (Lady Windermere’s syndrome)
• Solitary pulmonary nodule

In AIDS patients:
• DISSEMINATED DISEASE - no organ spared as immune system collapses

Question 23

How is MAC diagnosed?

Answer 23

Clinical illness consistent with NTM

Microscopy reveals acid-fast bacteria (must exclude other etiologies ie fungi and TB) - sterile site isolation of MAC significant

Chest X-rays - important for ID of pulmonary lesions

Final species ID by molecular techniques (ie PCR

Question 24

How do we treat MAC?

Answer 24

Combination Abx therapy

Take HIV status into account:

HIV (-) patients - continue until sputum cultures are negative for 1 year

HIV(+) patients w/o MAC infection - chemoprophylaxis with CD4 <50, can discontinue 3 months after CD4>100

HIV(+) patients with MAC infection
• W/o immune reconstitution = lifelong treatment
• Begin Treatment for 2 weeks then anti-HIV HAART

Question 25

New infectious epidemic among CF patients

Answer 25

Mycobacterium abscesses

Believed to be acquired from soil or water, but now seems to be spreading as epidemic between CF treatment centers

Difficult to treat in CF due to intrinsic abx resistance