Mycobacteria

Question 1

There are 150 species of Mycobacteria and some cause distinct diseases. What are the features shared by all mycobacteria?

Answer 1

Aerobic, non-spore forming bacilli
Grow slowly in culture
Cell walls contain mycolic acids: long chain fatty acids
Acid fast nature: difficult to Gram stain

Question 2

Describe the morphology of Mycobacterium tuberculosis

Answer 2

Obligate aerobic, non spore forming rods
Cell lipid content in cell wall
Stained with Ziehl-Nielsen or Kinyoun staining
Appear red against a blue background when stained

Question 3

How does M tuberculosis become drug resistant? What kinds of selection pressure contribute to emergence of resistance?

Answer 3

Resistance occurs from spontaneous chromosomal mutations at a predictably low frequency, not from interaction with other bacteria. Selection pressure occurs from antimicrobial misuse such as monotherapy or addition of a single drug to a failing regimen.

Question 4

Describe the pathogenesis of TB

Answer 4

1) Inhaled droplet containing the bacteria reaches the alveoli
2) Bacteria ingested by macrophages: may or may not evade destruction and continue to grow inside or outside the cells
3) Local inflammation defines the primary infection
4) Bacteria may spread from initial lesion to other parts of the body via the lymphatic or circulatory
5) In 3-8 weeks cellular immunity developed and the infection is controlled but the bacteria are not eradicated. In 95% of patients, the infection becomes a latent TB infection

Question 5

What are 2 ways an active infection of TB may occur in patients with a latent infection?

Answer 5

1) reactivation in a old focus in the eldery primarily due to malnutrition, diabetes etc.
2) inhalation of new bacilli (re-infection)

Question 6

How does systemic miliary TB occur? What parts of the body are typically infected?

Answer 6

When the primary focus in the lungs seed or rupture into a pulmonary vein returning to the heart. The organism can then disseminate throughout the body by circulation. The bone marrow, spleen, adrenals, kidneys are usually affected

Question 7

How is TB disease usually caused?

Answer 7

Survival and replication in macrophages
delayed hypersensitivity reaction due to tuberculo proteins
cell wall proteins causing a granulomatous lesion

Question 8

What is the tuberculin skin test? What are positive and negative tests?

Answer 8

To determine previous exposure to the tuberculo protein.
A positive test would be induration greater than 10 mm and indicates infection by TB at some point in life.
A false positive would be previous vaccination
A negative test would be no induration or induration smaller than 5 mm and indicates no infection with TB
A false negative would be recent infection with TB because the test only becomes positive after 4-6 weeks

Question 9

What are 4 diagnostic methods used for TB and which one is the most specific and sensitive?

Answer 9

Microscopy and staining, culture, PCR, Chest radiography

Culture is the most specific and sensitive: Lowenstein-Jensen media is used

Question 10

If you were testing a sample for TB, what 3 tests would you use to diagnose?

Answer 10

AFB staining, PCR and culture

Question 11

What is the choice of first line drugs against a TB infection? When would you use second line drugs?

Answer 11

1) Isoniazid and rifampicin: bactericidal effective against intra and extracellular bugs
2) pyrazinamide: bactericidal, works at acidic pH within bacterial cells only
3)Ethambutol: bacteriostatic
You would use second line drugs if resistance or toxicitiy contraindicate first line drugs

Question 12

What is the typical treatment regimen for TB infection?

Answer 12

Use a drug combination of different modes of action to delay emergence of drug resistance.
Iso-rif-pyr-eth for 2 months then inh-rif for 4 months. Patient becomes non-infective after 2-3 weeks of chemotherapy

Question 13

Why do TB infections require such a long treatment period?

Answer 13

Long doubling time of the bacilli
Intra-phagocytic survival and replication
Metabolically inactive bacilli are not killed by the drugs
Caseous material interferes with drug action

Question 14

Describe the difference between poly-resistant, multi-drug resistant and extensively drug resistant TB

Answer 14

Poly: resistant to more than one drug but not the combination of isoniazid and rifampicin
MDR: resistant to at least iso-rif
XDR: MDR plus resistance to fluorquinolones as well as one of the injectable drugs

Question 15

What are the differences of atypical mycobacteria from typical mycobacteria (TB)?

Answer 15

Colonial morphology, niacin test negative, relatively more resistant to the anti-TB drugs, diseases are typically less invasive

Question 16

Describe leprosy and the causal organism

Answer 16

Caused by mycobacterium leprae. Leprosy is a chronic, granulomatous and debilitating disease with a long incubation. The organism has a low pathogenicity/virulence and infectivity.

Question 17

Leprosy is characterized by lesions, what does the severity of the lesions depend upon and what are the 3 types of leprosy?

Answer 17

The severity leprosy lesions depends upon the cell mediated response of the person.

1) Tuberculoid leprosy: few lesions, have few bacilli and numerous lymphocytes AKA paucibacillary
2) Lempromatous leprosy: poor CMI response, many lesions, have many bacilli in lesions, AKA multibacillary
3) Borderline leprosy: intermediate CMI response, lesions inbetween Tuberculoid and lepromatous leprosy

Question 18

How is leprosy diagnosed and treated/duration of treatment?

Answer 18

Skin biopsy of lesion and PCR. Treated with Dapsom, Rifampin and Clofazimin. Paucibacillary is usually treated with antibiotics for 12 months, multibacillary for 24 months