Leprosy -> Mycobacteria!!! MICROM 442 Deck 18

Question 1

First bacterium identified as causing
disease in humans

Answer 1

Gerhard Armauer Hansen, 1873 (10
years before Koch’s lecture!)

Question 2

Still not cultivable in vitro

Answer 2

The ability to diagnose and treat leprosy has only recently advanced

Question 3

hosts

Answer 3

Humans and some other primates -> armadillos and eurasian red squirrels (sometimes footpads of mice but very slowly)

Question 4

Long incubation time

Answer 4

2-10 years

Question 5

• Often localized, single anesthetic skin lesions, rare thickened nerves
• Spontaneous resolution can occur
• Analogous to primary, latent, or reactivated TB (hypersensitivity reaction)

Answer 5

Tuberculoid or paucibacillary (low skin organism burden)

Question 6

• ~1015 cells per patient!
• Multiple skin lesions, usually with thickened peripheral nerves, anesthesia,
  weakness
• Spontaneous resolution does not occur
• Analogous to systemic tuberculosis (poor cell-mediated immune response)

Answer 6

Lepromatous or multibacillary (high skin organism burden)

Question 7

in regards to tuberculoid/paucivacillary and lepromatous/multibacillary

Answer 7

Many intermediate forms between these

Question 8

when exposed to m.leprae it can lead to natural resistance/asymptomatic clearance or symptomatic, symptomatic looks like?

Answer 8

-tuberculoid: cell-mediated response, granuloma formation, few organisms
-lepromatous: humoral response, foamy macrophages, many organisms

Question 9

transmission

Answer 9

• Thought to occur via aerosol route
• Exposure to animals and/or soil may be important
• Epidemiology is very difficult, given very long incubation period
  (months to decades)
• Thought that long-term, close exposure (household) is important, but not as important as…
• Genetic predisposition (minority of population)
• Some similar risk factors/mechanisms as TB- innate immunity
• Again, T cell-mediated immunity seems to differentiate patient
  groups

Question 10

pathgogenesis

Answer 10

• Particular tropism for Schwann (nerve) cells
• Thought to be due to interaction between a parasite
  glycolipid and Schwann cell surface proteins (laminins)
• Recent evidence that infection reverts Schwann cells to a
  “stem-cell-like” phenotype; dissemination?
• Also taken up by macrophages via complement
  receptor, other proteins

Question 11

diagnosis

Answer 11

Usually, diagnosis is made by clinical suspicion:
* Localized weakness and anesthesia
* Skin lesions
* Thickened nerves
* If present, positive skin smears for AFB are diagnostic

Question 12

treatment

Answer 12

• Dapsone used for a short time as monotherapy
• Guess what happened?
• Multidrug therapy is the standard
• Dapsone (DHFR inhibitor)
• Rifampin (RNA synthesis inhibitor)
• Clofazimine (DNA replication inhibitor)
• Infectiousness usually lost within 3 days
• Highly effective therapy