In cases of inconclusive outcomes of resistance tests in clinical isolates, expression analysis of a set of influential genes can be beneficial to identify distinctive biomarkers between antimony-unresponsive and responsive parasites.

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Cutaneous leishmaniasis (CL) is a curable disease; however, due to various risk factors, unresponsiveness to CL treatments is inevitable. The treatment of CL has been firmly correlated with multiple determinants, such as demographical, clinical, and environmental factors, the host’s immune response, poor treatment adherence, the parasite’s genetic make-up, and Leishmania RNA virus. This study primarily focuses on the risk factors associated with different therapeutic outcomes following meglumine antimoniate (MA; Glucantime®) treatment and policy approaches to prevent unresponsiveness in CL patients with a focus on anthroponotic form (ACL). Findings suggest that effective preventive and therapeutic measures should be more vigorously implemented, particularly in endemic areas. Accordingly, extensive training is essential to monitor drug unresponsiveness regularly, especially in tropical regions where the disease is prevalent. Since humans are the fundamental reservoir host of ACL due to L. tropica, prompt detection, early diagnosis, and timely and effective treatment could help control this disease. Furthermore, major challenges and gaps remain: efficacious vaccine, new tools, and expert staff are crucial before CL can be definitively controlled.

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Background and aims:: Due to the lack of an effective vaccine and complexity of the control measures against vectors and reservoir hosts, the control of leishmaniasis depends primarily on chemotherapy. This study was aimed to assess the snake venom, Naja naja oxiana fraction 11(NNOV-F11) on L. infantum and its broad mode of action. Methods:: A wide range of in vitro advanced assays including high-performance liquid chromatography (HPLC), MTT (3-[4, 5-Dimethylthiazol-2-yl]-2, 5diphenyltetrazolium bromide; Thiazolyl blue) and macrophage assays, quantitative real-time polymerase chain reaction (qPCR), flow cytometry and enzyme-linked immunosorbent assay (ELISA) on L. infantum pro-mastigote and amastigote stages were used. IC50 values of L. infantum stages, CC50 value and apoptosis were also analyzed. Results:: The NNOV-F11 demonstrated strong antileishmanial activity against L. infantum stages in a dose-dependent man-ner compared to the untreated control group. Interleukin (IL)-12, TNF-α and iNOS genes expression as the indicators of T helper(h)1 response significantly increased; in contrast, the expression level of IL-10, as the representative of Th2 response significantly decreased (p ˂ 0.001). Reactive oxygen species (ROS) detection showed statistically a significant increase (p ˂ 0.001) after treatment with different concentrations of NNOV-F11, unlike arginase (ARG) activity which displayed a signif-icant reduction (p < 0.001). Conclusion:: NNOV-F11 possesses a potent inhibitory effect on L. infantum stages with the multifunctional and broad mode of actions which promoted the immunomodulatory role, induced ROS production, stimulated apoptotic–like mechanisms and inhibited L-ARG activity which collectively led to the parasite death. Further studies are crucial to assess the effect of the fraction NNOV-F11 on animal models or clinical settings.

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