Ferroptosis and Nrf-2 signaling: a redox tug of war in leishmaniasis pathogenesis and host directed therapy.

Thymol's antileishmanial activity and its impact on host cytokine profiles: In vitro and ex vivo studies on Leishmania tropica.

The Dermatology Life Quality Index (DLQI) is a widely used instrument to assess the health-related quality of life associated with skin conditions. Afan Oromo is spoken by 40% of Ethiopians. Objectives This study aimed to translate, culturally adapt and validate the DLQI in Afan Oromo. This study was nested in a large hospital-based cohort study of cutaneous leishmaniasis (CL). Forward-backward translation followed by content validity, responsiveness to change, known group comparison, and convergent and discriminant validity were done. Internal consistency and inter-rater reliability were assessed using Cronbach's alpha and intraclass correlation coefficient (ICC), respectively. The DLQI showed acceptable content validity with modified kappa between 0.8 and 1.0. One hundred individuals with confirmed active CL with a mean (SD) age of 36.81 (17.46) years, were interviewed using the translated draft of the Afan Oromo DLQI. The DLQI mean (SD) score was 11.93 (7.32). The instrument showed excellent internal consistency with a Cronbach alpha of 0.87 and inter-rater reliability ICC of 0.96. The median DLQI scores were significantly different between those with different physicians determined severity (P = 0.01) and lesion size (P = 0.004). There was high convergent validity (0.74-0.93). DLQI scores on day 90 were significantly lower than scores at enrolment prior to treatment (P = 0.0001). This translation of the DLQI to Afan Oromo is a valid and reliable patient-reported outcome measure instrument for research or clinical practice.

Cutaneous leishmaniasis (CL) is a major public health concern in Iran and particularly in Isfahan Province. Although numerous studies have determined the phlebotomine sand-fly fauna and CL occurrence in this region, no dedicated investigation of sand fly spatial distribution and Risk mapping has been conducted in recent years. Furthermore, no previous study has systematically assessed leishmaniasis vectors across 19 distinct sites in this provinceover a continuous five-year period from 2019 to 2023. Therefore, this study conducted comprehensive entomological surveillance to determine sand fly species composition, seasonal activity, and high-risk transmission zones for C in this endemic area. This retrospective study conducted on sand fly entomological surveillance in 10 counties of Isfahan Province from 2019 to 2023, utilising sticky traps for sand fly collection. Collected specimens were identified morphologically, and species distribution, seasonal activity, and abundance trends were analysed using statistical methods. Spatiotemporal maps were created using GIS tools to assess the geographic patterns of sand fly populations. A total of 17,453 specimenswere collected, with Sergentomyia sintoni (48.0%) and Phlebotomus papatasi (30.0%) being the most abundant species. The highest sand fly abundance was recorded in 2022. Seasonal activity patterns varied by species, with S. sintoni and Ph. Papatasi exhibiting bimodal peaks in June and August. The majority of specimens (96.5%) were collected from outdoors, which indicates the exophilic behaviour of sand flies. Our findings establish an essential basis for public health decision-making and support the formulation of targeted, cost-effective, and ecologically responsible interventions to reduce sand fly populations and mitigate the spread of sand fly-borne diseases.

A conceptual model for healthcare-seeking research and interventions in cutaneous leishmaniasis.

In Spain, Leishmania infantum causes both cutaneous (CL) and visceral leishmaniasis (VL). This study aimed to analyse trends in the clinical presentation, diagnosis, management, and epidemiology of leishmaniasis at Severo Ochoa University Hospital in Leganés, an endemic area in Southern Madrid affected by Europe’s largest outbreak (2009–2015). A retrospective study was conducted, including all confirmed cases from January 1992 to December 2024, using clinical records. Cases were stratified into pre-outbreak, outbreak, and post-outbreak periods. A total of 151 cases were identified, including 129 VL, 21 CL, and 1 simultaneous VL/CL. VL predominated among adults during the HIV epidemic, later shifting to elderly and non-HIV immunosuppressed patients, while paediatric cases remained stable. Diagnostic methods evolved from bone marrow microscopy, culture, and IFAT to molecular and chemiluminescence assays. VL treatment also evolved, with amphotericin B gradually replacing meglumine antimoniate as first-line VL treatment. Most patients required hospitalisation, with 8.5% mortality, mainly among immunocompromised or elderly individuals. A persistent concentration of cases near recently urbanised areas adjacent to the parks of Polvoranca and Bosquesur was observed. Despite advances in diagnosis and therapy, endemic transmission and underreporting continue, highlighting the need for ongoing surveillance and preventive measures. Hospital record review proved useful for monitoring compliance with mandatory VL notification, though its applicability to cutaneous cases remains limited.

Systematic review on the epidemiology, diagnostics and management of leishmaniasis recidivans.

Background/Objectives: Cutaneous leishmaniasis (CL) remains a major neglected tropical disease, and current chemotherapeutic options are limited by toxicity and emerging resistance. Repurposing azole antifungals is a promising approach, as they target ergosterol biosynthesis, a pathway also essential in Leishmania spp. This study investigated the antileishmanial potential of econazole through in vitro and in vivo assays. Methods: Econazole activity was evaluated against Leishmania amazonensis promastigotes and intracellular amastigotes using MTT and luminescence-based methods. Cytotoxicity in NCTC cells was determined to calculate the selectivity index (SI). Drug interactions with miltefosine were assessed by fixed-ratio isobologram analysis. In vivo efficacy was examined in BALB/c mice infected with L. amazonensis and orally treated with econazole (2.5, 5, or 10 mg/kg/day) for 28 days. Lesion development and parasite burden were monitored. Molecular docking simulations were performed using SwissDock. Results: Econazole showed potent in vitro activity, with EC50 values of 8.9 µM for promastigotes and 11 µM for intracellular amastigotes, and a CC50 of 31 µM. Isobologram analysis revealed additive interactions with miltefosine (ΣFIC 0.5–1.2; mean 0.95). In vivo, econazole reduced lesion size and parasite load, achieving up to 75% reduction at 10 mg/kg/day. Docking results suggested that econazole may inhibit sterol biosynthesis, potentially through interaction with 14α-demethylase. Conclusions: These findings provide the first evidence of econazole activity against L. amazonensis in vitro and in vivo. Its exploratory efficacy and compatibility with miltefosine support further investigation of econazole as a repurposed candidate for CL, including optimization of dosing strategies and combination regimens.

Improving Leishmania isolation in field conditions: Efficacy of caspofungin against yeasts contamination.

Sand Flies and Cutaneous Leishmaniasis in Imo State, South Eastern Nigeria: Prevalence of Leishmaniasis and Impact of Sociodemographic Factors

Cutaneous leishmaniasis is a zoonotic disease caused by Leishmania parasites and leads to chronic, non-healing skin lesions. Although current drugs can control the disease, their use is limited by systemic side effects, low efficacy, and inadequate lesion penetration. Therefore, innovative local delivery systems are required to enhance drug penetration and reduce systemic toxicity. To address these challenges, silver nanoparticles (AgNPs) were synthesized using propolis extract through a green synthesis approach, and a tri-layer wound dressing composed of polyvinyl alcohol and gelatin containing synthesized AgNPs and Glucantime was fabricated by electrospinning. Characterization (SEM-EDX, FTIR, TGA) confirmed uniform morphology, chemical structure, and thermal stability; the wound dressing exhibited hydrophilicity, antioxidant activity, and biphasic release. Biological evaluations against Leishmania tropica demonstrated significant antiparasitic activity. Promastigote viability decreased from 76.3% in neat fibers to 31.6% in nanofibers containing AgNPs and 7.9% in tri-layer nanofibers containing both AgNPs and Glucantime. Similarly, the amastigote infection index dropped from 410 in controls to 250 in neat nanofibers, 204 in AgNPs-containing nanofibers, and 22 in tri-layer nanofibers containing AgNPs and Glucantime. The tri-layer nanofibers demonstrated enhanced antileishmanial activity over AgNPs-containing fibers, confirming synergistic efficacy. All nanofibers were biocompatible, supporting their use as a safe platform for cutaneous leishmaniasis treatment.

Leishmaniasis, a widespread, neglected infectious disease with limited effective treatments and increasing drug resistance, demands innovative therapeutic approaches. In this study, we report the fabrication of pentamidine (PTM)-loaded polycaprolactone (PCL) nanofibers using solution blow spinning (SBS) as a potential topical delivery system for cutaneous leishmaniasis (CL). Homogeneous PCL fiber mats were produced using a simple SBS set-up with a commercial airbrush after optimizing several working parameters. Drug release studies demonstrated sustained PTM release profile over time, which was mechanistically modeled by utilizing the complete nanofiber diameter distribution, obtained from SEM analysis of the blow-spun material. FTIR and XRD analyses were performed to investigate the drug–polymer interactions, revealing molecularly dispersed PTM at low-proportion drug/polymers and partial crystallinity at high loadings. The released PTM exhibited significant leishmanicidal activity against Leishmania major promastigotes. Biological investigations showed that SBS-formulated PTM treatment was consistent with the downregulation of parasite genes involved in cell division and DNA replication (cycA, cyc6, pcna, top2, mcm4) and upregulation of the drug response gene (prp1). The controlled delivery of PTM within SBS-fabricated PCL nanofibers provides an effective therapeutic approach to tackle CL and, through the incorporation of additional drugs, could be extended to address a broader range of cutaneous infections.

Treatment-Refractory New World Cutaneous Leishmaniasis Misdiagnosed as Recurrent Cellulitis in a UK Traveler Returning From the Amazon

Leishmania RNA virus 2 (LRV2) has emerged as a potential molecular co-determinant of clinical outcomes in Leishmania major infections, particularly within the Old-World cutaneous leishmaniasis (CL) belt. Recent molecular investigations from Iran and adjacent endemic regions (2024-2025) have revealed extensive LRV2 diversity and phylogeographic structure. However, the lack of standardized assays, incomplete clinical metadata, and inconsistent reporting frameworks have hindered translation of detection findings into actionable public-health insights. This commentary synthesizes these findings and proposes a six-point, standards-based micro-protocol for harmonizing molecular detection, metadata collection, and clinical outcome recording, aimed at enhancing decision-useful surveillance and global comparability.

Cutaneous leishmaniasis (CL) is a neglected tropical disease with substantial physical, psychological, and social consequences, particularly in endemic, resource-limited settings. This study assessed the impact of CL on health-related quality of life (HRQoL) and patient satisfaction with care in an endemic region of Syria. A cross-sectional study was conducted from May 1 to July 1, 2024 in Damascus University Hospital for Dermatology, Aleppo University Hospital, and two Ministry of Health CL treatment centers in Aleppo, Syria. HRQoL was measured using the dermatology life quality index (DLQI), and patient satisfaction using patient satisfaction questionnaire short form (PSQ-18). Sociodemographic and clinical characteristics were collected. Data were analyzed using SPSS (version 29). Medians and interquartile ranges (IQR) were used to describe non-normally distributed variables. Statistical tests included the Mann-Whitney U, Kruskal-Wallis, and Spearman's rank correlation. A P-value < 0.05 was considered significant. A total of 353 patients (55.9% female; median age 33years) participated. The median DLQI score showed modest impairment, with the Symptoms and Feelings domain most affected (median 2, IQR 1-3; 87.5% scoring > 0). Female sex was significantly associated with higher Symptoms and Feelings (P = 0.018) and Personal Relationships (P = 0.020) scores. Head/neck lesions were significantly associated with worse Personal Relationships scores (P = 0.014). Satisfaction was generally high, with the highest median scores in Technical Quality (median 16, IQR 14-17) and Accessibility and Convenience (median 14, IQR 12-16). Urban residence was associated with higher General Satisfaction (P < 0.001), while number of treatment visits negatively correlated with Accessibility and Convenience (ρ = - 0.112, P = 0.035). CL in Syria imposes measurable psychosocial and functional burdens, particularly among women and those with visible lesions. Despite overall high satisfaction with care, disparities related to geography and treatment logistics persist. Addressing psychosocial needs and inequities in care accessibility may improve patient outcomes endemic settings.

Recent reports of Leishmania donovani causing cutaneous leishmaniasis (CL) in Nepal have revived a key question in disease ecology: when does a disease truly emerge, and when is it simply newly recognized? Apparent emergence likely reflects underdiagnosis rather than parasite evolution. These cases have likely gone unnoticed because surveillance programs and clinical awareness have historically centered on VL in this L. donovani –endemic region. As leishmaniasis expands into previously non-endemic areas, physicians encountering unfamiliar lesions are prompted to investigate and identify the etiological agent, revealing not a new parasite variant, but the geographic and diagnostic expansion of a known one previously unrecognized by the healthcare system. Epidemiological “emergence,” in this context, stems less from parasite evolution than from the intersection of changing disease ecology, improved diagnostics, and shifting clinical attention. We hypothesize that cutaneous leishmaniasis due to L. donovani in Nepal represents a detection-driven phenomenon rather than a novel biological event.

Cutaneous leishmaniasis is the most common form of the vector borne parasitic disease, causing skin lesion and ulcer. Several studies have reported the resistance of cutaneous leishmaniasis parasite to antimonial drugs. Hence, there is a need to develop cheaper and effective alternative therapies for resistance breakdown. In the current study we report the effectiveness of Teucrium stocksianum extract mediated green synthesized zinc oxide nanoparticles (ZnONPs) against Leishmania tropica (KMU25), a causative species of cutaneous leishmanaisis. ZnONPs was successfully synthesised at 70°C by continuous stirring (2h) of aqueous extract (5mg/mL) and Zinc acetate solution (2g/50 mL, pH: 8) in 1:9. The characterization of these NPs showed a UV-Vis surface plasmon resonance at 365nm, hexagonal morphology with irregular shapes through scanning electron microscopy, average crystal size 21.48 ± 5.2nm through XRD analysis and the complex metabolites attachments to the surface of the particles was confirmed by FTIR. The DPPH (2,2-diphenyl-1-picrylhydrazyl) assay-based antioxidant activity showed 50% free radical scavenging at 624.94µg/mL and 798.45µg/mL for extract and ZnONPs, respectively. The hemolysis assay revealed moderate cytotoxicity with a LD50 value of 3807.54µg/mL and 1537.16µg/mL for the extract and ZnONPs, respectively. The antileishmanial activities were examined at different concentration (50, 100, 250, 500, and 1000µg/mL) using MTT cell viability assays. The LD50 values 1895.63µg/mL (for extract) and 837.07µg/mL (for extract mediated ZnONPs) were estimated, showing enhanced antileishmanial activity of ZnONPs compared to the extract. Moreover, the ZnONPs were nontoxic towards normal RBCs, making it a potential candidate as an interesting topical nanomedicine against cutaneous leishmaniasis.

Cutaneous diseases in returning travelers encompass a wide spectrum of etiologies and often pose diagnostic challenges. We present the cases of a 50-year-old man and a 57-year-old woman who presented with a 3-month history of erythematous, ulcerated plaques with well-defined elevated borders and a necrotic center on the lower limbs that began 3 weeks after returning from vacation in Costa Rica. Cutaneous biopsy revealed epidermal ulceration and extensive caseating granulomas throughout the full thickness of the dermis. Giemsa staining revealed no amastigotes. Microbiological examinations identified Leishmania braziliensis and excluded mycobacteria and fungi. The diagnosis of cutaneous leishmaniasis was established. Owing to clinical severity and antimonial unavailability, the man was treated with liposomal amphotericin B. The woman underwent surgical excision of the single lesion, along with oral fluconazole. Complete resolution was documented in both patients. These cases, which posed diagnostic and therapeutic challenges, highlight that cutaneous leishmaniasis, in all its versatile and often perplexing presentations, is a parasitic infection that should always be considered in dermatologic patients returning from vacation in endemic countries.

Evaluation of IgG anti-L. tropica antibody response as a biomarker for cutaneous leishmaniasis using ELISA in endemic regions of Pakistan.

A qPCR-based strategy for differential diagnosis of visceral and cutaneous leishmaniasis in humans and dogs.