ABSTRACT
The control of Leishmania infection relies primarily on chemotherapy till date. Resistance to pentavalent antimonials, which have been the recommended drugs to treat cutaneous and visceral leishmaniasis, is now widespread in Indian subcontinents. New drug formulations like amphotericin B, its lipid formulations, and miltefosine have shown great efficacy to treat leishmaniasis but their high cost and therapeutic complications limit their usefulness. In addition, irregular and inappropriate uses of these second line drugs in endemic regions like state of Bihar, India threaten resistance development in the parasite. In context to the limited drug options and unavailability of either preventive or prophylactic candidates, there is a pressing need to develop true antileishmanial drugs to reduce the disease burden of this debilitating endemic disease. Notwithstanding significant progress of leishmanial research during last few decades, identification and characterization of novel drugs and drug targets are far from satisfactory. This review will initially describe current drug regimens and later will provide an overview on few important biochemical and enzymatic machineries that could be utilized as putative drug targets for generation of true antileishmanial drugs.
Subject(s)
Humans , Aminoquinolines , Therapeutic Uses , Amphotericin B , Therapeutic Uses , Antigens, Protozoan , Allergy and Immunology , Antimony Sodium Gluconate , Therapeutic Uses , Antiprotozoal Agents , Therapeutic Uses , Caspase Inhibitors , Cyclin-Dependent Kinases , Drug Discovery , Enzyme Inhibitors , Therapeutic Uses , Folic Acid Antagonists , Therapeutic Uses , Leishmaniasis , Drug Therapy , Macrophages , Allergy and Immunology , Microbodies , Mitogen-Activated Protein Kinase Kinases , Metabolism , Paromomycin , Therapeutic Uses , Pentamidine , Therapeutic Uses , Phosphorylcholine , Therapeutic Uses , Polyamines , Metabolism , Protease Inhibitors , Therapeutic Uses , Sterols , Sulfhydryl Compounds , Metabolism , Topoisomerase Inhibitors , Therapeutic UsesABSTRACT
OBJECTIVE@#To detect leishmanial antigens in pre and post treated urine of visceral leishmaniasis (VL) patients.@*METHODS@#Urine and serum sample from three VL patients were collected. Ammonium sulphate precipitation and purification of urine sample was done for proteins isolation. SDS PAGE of proteins was done followed by western blotting, with the patient's pre and post treatment serum.@*RESULTS@#Eight proteins of molecular weights 17 kDa, 25 kDa, 28 kDa, 42 kDa, 47 kDa, 54 kDa, 60 kDa and 85 kDa were detected in the urine of VL patients before treatment. After treatment with miltefosine, none of the above proteins was detected in urine samples. The western blot analysis with pre treatment serum confirmed the antigenicity of four urinary proteins of molecular weights 25 kDa, 28 kDa, 54 kDa and 60 kDa. The seropositivity with 25 kDa and 28 kDa antigens was negative with serum obtained after the completion of treatment.@*CONCLUSIONS@#In the context to unavailability of a prognostic tool, urinary leishmanial antigens may offer a better choice and may also be useful as immunoprophylactic candidates.