Treatment and Drugs
The irony of this disease is that it is the only tropical disease, which is being treated by non-leishmanial drugs.
Why so?
Earlier, the focus was laid on drug trials/combination therapy of available non-leishmanial drugs, evaluation of diagnostic and prognostic capability of available tools. Now the emphasis is laid on novel control strategies in terms of new drug targets and vaccine candidates.
Recent developments
Where have we reached till now?
Potentially useful target enzymes, transporters, metabolites, and hypothetical proteins that are distinct to parasite and their mammalian host have been identified by Biochemical analysis and Genome sequencing of L. major, L. braziliensis, and L. infantum.
Genome mining will aid in large scale proteomics studies to generate expression profiles of Leishmania parasites and gene targets for treatment development.
Search of new potential drug targets mainly focuses on biochemical and metabolic pathways essential for parasite survival. The target enzymes of these pathways should have significant structural and functional differences from their mammalian counterparts for selective inhibition of target sites.
Targetting multiple enzymes of a metabolic pathway simultaneously may prove more usefulness and effectiveness.
Biological studies for the function of 50% of Leishmania genes are lacking.
Depends on the geographical area
Pentavalent antimonials
Its active derivate is the intracellular reduced trivalent form that forms through the alteration in parasite bioenergetic pathways and trypanothione inhibition.
Administration by intramuscular injections of 20mgSbv/kg/day up to a maximum of 1275mg over 20 or 30 days.
In the case of Old-World CL, there is no significant difference between the intralesional and intramuscular route.
Cure rate is generally high (85–95%).
First line drug
Amphotericin B
A macrolide polyene, characterised by hydrophilic polyhydroxyl and hydrophobic polyene aspects.
Binds to membrane ergosterol leading to the formation of pores, major constituent efflux and, finally, parasite cell lysis.
Intravenous infusion (7–20mg/kg up to 20 days) is an alternative treatment in all the regions where antimonial resistance has been reported.
Lipid based formulations like liposomal amphotericin B (Ambisomew) reduce the impairment of renal function by up to 50% with a therapeutic schedule of 6–21mg (VL) or 2–3mg (ML)/kg for 20 days.
Drawbacks:
Infusion related side effects and renal toxicity.
Costly drug.
Pentamidine isethionate
Used less frequently, diamine pentamidine has become of special interest in CL caused by L. guyanensis, where intralesional injections have been more efficient than with pentavalent antimonials.
Antileishmanial activity is based on the inhibition of polyamine biosynthesis and the disruption of mitochondrial membrane potential
Side effects include hypotension, diabetes mellitus and renal impairment.
Recently introduced
Miltefosine
Hexadecylphosphocholine derived from cancer therapy.
First oral treatment enabled high cure rates in Indian VL (95%) and Colombian CL (91%) when used at 100-150mg/day for 28 days.
Approved in India (2002), Germany (2004) and Columbia (2005).
L. donovani and L. panamensis are the most susceptible species.
It has completed phase IV in 2006, despite this, low cure rates were observed in CL caused by L. braziliensis or L. major and transient cures followed by relapses in DCL or HIV/LV co-infected patients.