Leishmania Chemotherapy

Question 1

Current drugs in use

Answer 1

Pentavalent antimonials (SbV)
Amphotericin B
AmBisome
Miltefosine
Pentamidine

Question 2

Drugs for leishmaniasis in clinical trials

Answer 2

Miltefosine
Paromomycin
Other amphotericin B lipid formulations

Question 3

Pentavalentantimonials (SbV)

Answer 3

Used for VL and CL
Adverse side effects
Mode of action: zinc-finger protein, tryoanotione reductase, type I DNA topoisomerase, ribose-containing biomolecules

Question 4

Amphotericin B

Answer 4

Polyene antibiotic
Originally a fungal infection treatment, active against leishmania
Binds to ergosterol (sterol found in the cell membrane)

Question 5

AmBisome

Answer 5

Liposomal amphotericin B
Must be infused intravenously
Targeted to site of infection, helps reduce toxicity
Used for VL in South Asia

Question 6

Miltefosine

Answer 6

Synthetic alkylphospholipid
Oral administration
Long course of treatment
Less effective in treating VL in East Africa vs South Asia

Question 7

Miltefosine Potential Modes of Action

Answer 7

Ⓐ Lipid membrane perturbation
Ⓑ Apoptotic-like cell death
Ⓒ Mitochondrial effects
Ⓓ Immunomodulatory effects

Question 8

Paromomycin

Answer 8

Natural product
Aminoglycoside antibiotic
Poor oral absorption - I.V. or I.M. for VL
Topical formulation for CL

Question 9

Drug co-administration - VL

Answer 9

Increase activity through use of drugs with additive/synergistic activity
Reduce required doses → reduce toxicity
Reduce length of treatment → improved compliance
Reduce selection of resistant variants – protect effective drugs

Question 10

Current treatments for cutaneous leishmaniasis

Answer 10

For “uncomplicated” CL/LCL

1st line
– Intralesional SbV

2nd line 
– Parenteral amphotericin B (Fungizone or AmBisome) 
– Parenteral pentamidine (L. guyanesis) 
– Miltefosine (Oral) 
– Thermotherapy 
– Topical paromomycin

Question 11

Mechanical Therapy

Answer 11

Thermotherapy - contradictory evidence of efficacy

Cryotherapy