In Algeria, the treatment of visceral and cutaneous leishmanioses (VL and CL) has been and continues to be based on antimony-containing drugs. It is suspected that high drug selective pressure might favor the emergence of chemoresistant parasites. Although treatment failure is frequently reported during antimonial therapy of both CL and VL, antimonial resistance has never been thoroughly investigated in Algeria. Determining the level of antimonial susceptibility, amongst Leishmania transmitted in Algeria, is of great importance for the development of public health policies. Within the framework of the knowledge about the epidemiology of VL and CL amassed during the last 30 years, we sampled Leishmania isolates to determine their susceptibility to antimony. We analyzed a total of 106 isolates including 88 isolates collected between 1976 and 2013 in Algeria from humans, dogs, rodents, and phlebotomines and 18 collected from dogs in France. All the Algerian isolates were collected in 14 localities where leishmaniasis is endemic. The 50% inhibitory concentrations (IC50) of potassium antimony tartrate (the trivalent form of antimony, Sb(III)) and sodium stibogluconate (the pentavalent form of antimony, Sb(V)) were determined in promastigotes and intramacrophage amastigotes, respectively. The epidemiological cutoff (ECOFF) that allowed us to differentiate between Leishmania species causing cutaneous or visceral leishmaniases that were susceptible (S+) or insusceptible (S-) to the trivalent form of antimony was determined. The computed IC50 cutoff values were 23.83 μg/mL and 15.91 μg/mL for VL and CL, respectively. We report a trend of increasing antimony susceptibility in VL isolates during the 30-year period. In contrast, an increase in the frequency of S- phenotypes in isolates causing CL was observed during the same period. In our study, the emergence of S- phenotypes correlates with the inclusion of L. killicki (syn: L. tropica) isolates that cause cutaneous leishmaniasis and that have emerged in Algeria during the last decade. Our results provide insight into the spatiotemporal dynamics of Leishmania antimony susceptibility in Algeria. We highlight the need for the future implementation of an effective methodology to determine the antimony susceptibility status of Leishmania isolates to detect the emergence of and prevent the dissemination of drug-resistant strains. In Algeria, the treatment of visceral and cutaneous leishmaniases (VL and CL) has been and continues to be based on antimony-containing drugs. It is suspected that high drug selective pressure might favor the emergence of chemoresistant parasites. Within the framework of knowledge about the epidemiology of VL and CL amassed during the last 30 years, we sampled Leishmania isolates to analyze their susceptibility to antimony. The epidemiological cutoff (ECOFF) that allowed us to differentiate between Leishmania species causing cutaneous or visceral leishmanioses that were susceptible (S+) or insusceptible (S-) to the trivalent form of antimony was determined. The computed IC50 cutoff values were 23.83 μg/mL and 15.91 μg/mL for VL and CL, respectively. We report a trend of increasing antimony susceptibility of VL isolates during the 30-year period. In contrast, an increase in the frequency of S- phenotypes in isolates causing CL was observed during the same period. The emergence of these S- phenotypes appears to correlate with the appearance of cutaneous leishmaniasis caused by L. killicki (syn: L. tropica). We highlight the need for the future implementation of an effective methodology to determine the antimony resistance status of Leishmania isolates to detect the emergence of and prevent the dissemination of drug-resistant srains.

Oxidative stress is an important component of various diseases. It manifests as an imbalance caused by an excessive production of reactive oxygen species (ROS) which are associated with a deficit of antioxidant activity. This deficit can be the consequence of genetic factors, environmental ones, metabolic imbalance, toxicity or direct attacks by the accumulation of free radicals. These can induce metabolic dysfunction affecting biological macromolecules in their structures or activities. From a physiological perspective, the neutralization of free radicals is ensured by enzymatic, antioxidant and non-enzymatic defense systems. In the present chapter, we will focus on the endogenous enzymatic antioxidant defense system such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPxs), thioredoxin (Trx) and paraxonase which play an important role in homeostatic redox balance. Also, we will review this set of antioxidants enzymes within different pathological states such as diabetes, cancer, autoimmune diseases, cardiovascular, Alzheimer’s, Parkinson’s or parasitic diseases such as Leishmaniasis and Malaria.

Since the 20th century, numerous studies have detected or isolated parasites from the Trypanosomatidae family in various tick species. However, the status of ticks as vectors for medically or veterinary significant Trypanosoma and Leishmania remains unclear. We conducted a systematic review and meta-analysis to provide new insights into the potential vector status of these pathogens, which have significant medical and veterinary implications. We searched three databases (PubMed, Google Scholar, and Web of Science) from 1912 to June 30, 2023, resulting in 94 papers included in the qualitative analysis and 86 papers in the quantitative analysis. All identified field studies were conducted in endemic areas and investigated the presence of Trypanosoma and Leishmania parasites, DNA, or antigens in ticks. We recorded a pooled prevalence of Trypanosomatidae detection in ticks at 15.48 % [7.99–24.61 %], with significant variations depending on the year, detection method, and geographical area. Most of the infected tick species belonged to the genera Amblyomma, Hyalomma, Ixodes, and Rhipicephalus. Experimental laboratory work on transmission routes demonstrated potential vector competence in both the Argasidae and Ixodidae tick families. Although our systematic review and meta-analysis provide compelling evidence of the natural infection of ticks by Trypanosomatidae parasites, along with some evidence of non-traditional transmission routes, they do not offer conclusive evidence regarding the role of ticks as biological or mechanical vectors for Trypanosomatidae species of veterinary and medical interest. This highlights the urgent need for additional investigations to address this point.

Background: Recently, the essential oil (EO) of Ammodaucus leucotrichus has attracted particular attention in hemi-synthesis due to the reactivity of its main monoterpenes.Objective: In vitro cytotoxic and antileishmanial activities of the EO and hemi-synthesized compounds were evaluated, and an in-silico simulation was conducted.Methods: The EO was characterized by GC-MS. Two benzodiazepines (C1, C2), benzimidazole (C3), and Schiff base (C4) were hemi-synthesized by an in situ condensation of its major monoterpenes (perillaldehyde) with different amine derivatives. Synthesized compounds and the EO were evaluated for their cytotoxic activity against laryngeal carcinoma-Hep2 and rhabdomyosarcoma-RD cell lines and for their antileishmanial activity against Leishmania (L) major. Molecular docking was performed to pin the binding interactions of active molecules.Results: A significant cytotoxic effect of benzodiazepines C1 and C2 was noted against Hep2 cells (IC50/C1 = 39.48 ±0.7 μM, IC50/C2 = 48.82±1.33 μM) and RD (IC50/C1 = 15.96±1.99 μM; IC50/C2 = 74.3±2.44 μM), while the EO highly inhibited Hep2 cell lines (IC50/EO = 17.3±0.85 μg/mL). C4 strongly inhibited L. major growth with an IC50 value of 8.00±1.37 Μμ. The docking scores of ligand-C4 on L. major pteridine reductase and L. major methionyl-tRNA synthetase and ligands-(C1, C2) on the human protein kinase and epidermal growth factor kinase presented significant affinity to the receptor active sites (ΔG from -7.7 to -8.8 kcal/mol).Conclusion: The cytotoxic effect of derivatives C1, C2, and EO, as well as the anti-parasitic effect of C4, may suggest them as effective bioactive agents or pharmaceutical probes.

Introduction: Leishmaniasis is a severe disease that presents a real public health problem worldwide. Antileishmanial therapy remains expensive with intolerable side effects; therefore, it is essential to develop tolerable antileishmanial medications with a selective efficacy. Methods: In this study, the leishmanicidal activities of seven Algerian plant extracts, selected based on either ethnobotanical or ...