Development of a murine infection model with Leishmania killicki, responsible for cutaneous Leishmaniosis in Algeria : application in pharmacology

In Algeria, Leishmania infantum, Leishmania major, and Leishmania killicki (Leishmania tropica) are responsible for cutaneous leishmaniosis. We established a murine model of L. killicki infection to investigate its infective capacity, some immunophysiopathological aspects, and its suitability for pharmacological purposes. Following the injection of L. major or L. killicki metacyclic promastigotes in the ear dermis of BALB/c mice, the course of infection was followed. The infection with L. killicki caused slower lesion formation than with L. major. The presence of L. killicki or L. major DNA and parasites was detected in the ear dermis and in lymph nodes, spleen, and liver. Lesions induced by L. killicki were nonulcerative in their aspect, whereas those caused by L. major were highly ulcerative and necrotic, which matches well with the lesion phenotype reported in humans for L. killicki and L. major, respectively. The treatment of L. killicki lesions by injection of Glucantime (R) significantly reduced the lesion thickness and parasite burden. Ear dermal injection of BALB/c mice constitutes a model to study lesions physiopathology caused by L. killicki and presents interest for in vivo screening of new compounds against this pathogen, emerging in Algeria

Leishmania antimony resistance/ susceptibility in Algerian foci

Algeria is one of the most endemic countries for cutaneous and visceral forms of eishmaniosis.Strikingly, with more than 21,000 annual cases of cutaneous leishmaniosis recorded in 2010, the disease has a major public health impact. For all forms of leishmaniosis, the fi rst line treatment relies on antimonial containing drug i.e.,Glucantime®, developed during the 1950’s. As early as 1986, antimonial treatment failure was reported during&nbsp; utaneous leishmaniosis treatment. Linked to this therapeutic failure, Leishmania strains displaying a low susceptibility towards antimonials were isolated. Nevertheless,in Algeria, antimonial formulations still remain the first line drug for all clinical forms of leishmaniosis. Therefore, an urgent need of knowledge on the baseline antimony susceptibility status of parasites strains in Algeria is required. These pieces of knowledge will shed light not only on the prevalence of antimony resistance in this area but also on underlying factors triggering this drug resistance in natural populations.Here, we performed a review of the literature on what is known about epidemiology, treatment failure,and antimony-resistance, in Algeria. We bring information on underlying mechanisms acting in antimony resistant parasites and discuss their potential to be used for diagnostic purpose. This analysis will help to set up protocols aiming at detecting antimony resistant strains in Algeria and to test the risk of transmission,two steps that are essential to define public health policy in Algeria.</p

Synthesis of aminophenylhydroxamate and aminobenzylhydroxamate derivatives and in vitro screening for antiparasitic and histone deacetylase inhibitory activity

A series of aminophenylhydroxamates and aminobenzylhydroxamates were synthesized and screened for their antiparasitic activity against Leishmania, Trypanosoma, and Toxoplasma. Their anti-histone deacetylase (HDAC) potency was determined. Moderate to no antileishmanial or antitrypanosomal activity was found (IC50 > 10 μM) that contrast with the highly efficient anti-Toxoplasma activity (IC50 < 1.0 μM) of these compounds. The antiparasitic activity of the synthetized compounds correlates well with their HDAC inhibitory activity. The best-performing compound (named 363) express a high anti-HDAC6 inhibitory activity (IC50 of 0.045 ± 0.015 μM) a moderate cytotoxicity and a high anti-Toxoplasma activity in the range of known anti-Toxoplasma compounds (IC50 of 0.35–2.25 μM). The calculated selectivity index (10–300 using different human cell lines) of the compound 363 makes it a lead compound for the future development of anti-Toxoplasma molecules

Development of a murine infection model with Leishmania killicki, responsible for cutaneouslLeishmaniosis in Algeria : application in pharmacology

In Algeria, Leishmania infantum, Leishmania major, and Leishmania killicki (Leishmania tropica) are responsible for cutaneous leishmaniosis. We established a murine model of L. killicki infection to investigate its infective capacity, some immunophysiopathological aspects, and its suitability for pharmacological purposes. Following the injection of L. major or L. killicki metacyclic promastigotes in the ear dermis of BALB/c mice, the course of infection was followed. The infection with L. killicki caused slower lesion formation than with L. major. The presence of L. killicki or L. major DNA and parasites was detected in the ear dermis and in lymph nodes, spleen, and liver. Lesions induced by L. killicki were nonulcerative in their aspect, whereas those caused by L. major were highly ulcerative and necrotic, which matches well with the lesion phenotype reported in humans for L. killicki and L. major, respectively. The treatment of L. killicki lesions by injection of Glucantime (R) significantly reduced the lesion thickness and parasite burden. Ear dermal injection of BALB/c mice constitutes a model to study lesions physiopathology caused by L. killicki and presents interest for in vivo screening of new compounds against this pathogen, emerging in Algeria