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Background: The Old World sand fly, Phlebotomus papatasi (Scopoli), a vector of zoonotic cutaneous leishmaniasis, is usually controlled by insecticides, including anticholinesterases. Previous studies have revealed 85% amino acid sequence identity of recombinant P. papatasi acetylcholinesterase (rPpAChE1) to mosquito AChE. They identified synthetic carbamates that selectively inhibited rPpAChE1 and circumvented the G119S mutation responsible for high-level resistance to anticholinesterases. This study reports the construction, baculovirus expression, and biochemical properties of rPpAChE1 containing the F290V and F331W orthologous mutations from mosquitoes. Methods: Recombinant PpAChE1 enzymes with or without the F290V, F331W, and G119S orthologous mosquito mutations were expressed in Sf21cells utilizing the baculoviral system. Ellman assays determined changes in catalytic properties and inhibitor sensitivity resulting from wild type and mutant rPpAChE1 containing single or combinations of orthologous mosquito mutations. Results: Each of the orthologous mutations (F290V, F331W, and G119S) from mosquito AChE significantly reduced inhibition sensitivity to organophosphate or carbamate pesticides, and catalytic activity was lost when they were expressed in combination. Novel synthetic carbamates were identified that significantly inhibited the rPpAChEs expressing each of the single orthologous mosquito mutations. Conclusions: These novel carbamates could be developed as efficacious insecticides, with improved specificity and safety for use in sand fly or mosquito populations expressing the mutant AChEs. [ABSTRACT FROM AUTHOR]

Background: Leishmania infantum is the only prevalent Leishmania species in Europe and manifesting predominantly as cutaneous or visceral leishmaniasis, whereas new world species like Leishmania (L.) braziliensis are well known pathogens in mucocutaneous leishmaniasis. Mucosal leishmaniasis caused by L. infantum is a rare clinical condition with only few cases described in literature. In contrast to our case, mostly immunocompromised patients with no history of leishmaniasis are affected. Case presentation: We describe the case of a 77-year-old German male who developed an ulcerous lesion of the tongue. As oral cancer was suspected, the patient underwent surgery. After suspected diagnosis of Leishmania spp. in histopathology, the patient was referred to our department for further diagnostics and treatment. Relapse from a cutaneous leishmaniasis acquired in Spain is likely, as L. infantum could be identified as the causative agent. The patient recovered after treatment. Conclusions: Mucosal leishmaniasis caused by L. infantum is rare and usually mistaken for malignancy. As demonstrated, it can be preceded by cutaneous leishmaniasis of the immunocompetent. Due to possible dissemination systemic treatment should be applied. [ABSTRACT FROM AUTHOR]

Introduction: Cutaneous leishmaniases (CL), a wide range of cutaneous diseases caused by diverse species of Leishmania genus parasites, are among the most neglected infectious diseases. While they are non-fatal, CL are highly morbid with disfiguring lesions, which could be chronic, leaving lifelong unsightly scars; they are combined with psychological distress and social stigma. The efficiency of treatment highly depends on the infecting Leishmania species. Diagnosis is mainly based on microscopic direct examination (DE) of Giemsa-stained smears needing experienced microscopists. It can be laborious and time-consuming when the parasite load is low. DE is poorly sensitive and does not identify Leishmania species. So far, only DNA assays accurately identify the species. Despite their wide use for generic detection, PCR methods also require equipment and additional steps to identify causal Leishmania species. L. major is hyperendemic in many countries in Africa, the Middle East, and Asia, where other species co-occur with different endemicity levels according to the situations. This complicates disease management and treatment, particularly as distribution and epidemiology of leishmaniases remain poorly understood. Here, we aimed for a simple and rapid molecular diagnostic test to detect and identify L. major , a predominant CL causal species, which could be prone to become a control tool at the point of care, in endemic areas, using isothermal recombinase DNA amplification (recombinase polymerase amplification, RPA, or recombinase aided amplification, RAA) coupled to detection by the lateral flow (LF) chromatography on a PCRD cassette. Methods: To develop an L. major species-specific RPA-LF assay, computational analysis of 70 Leishmania DNA targets, identified through bibliography and database searches, selected five targets. We designed and tested 7 primer pairs/probe sets to specifically amplify L. major DNAs. First, the primers were tested for species specificity and sensitivity using basic RPA chemistry. Then, to develop RPA-coupled LF detection, we shifted to the nfo chemistry. Results: This way, we retained one set for further investigation, which confirmed it is L. major species-specific. Tested on 86 human cutaneous samples, this selected set was able to detect 100% of L. major infections in confirmed CL patients. We did not observe any cross-reactivity with lesions due to L. infantum or L. tropica. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis (CL) poses a major public health concern in Ethiopia, with lesions and scars commonly affecting exposed body parts, resulting in physical, social, and psychological consequences. This study aims to assess the psychosocial impacts of CL, shedding light on the experiences and perceptions of affected individuals, thus contributing to the knowledge on Cutaneous leishmaniasis in Ethiopia and informing public health interventions to address its psychosocial effects. Methods: Using a descriptive phenomenological design, the study explored the lived experiences of individuals with Cutaneous leishmaniasis lesions and scars. Participants were purposively selected, and data was collected through open-ended in-depth interviews. The analysis combined inductive and deductive approaches through an iterative process, developing a coding framework with seven themes (lesion & CL scar each) and subthemes, resulting in giving important insights in the psychosocial impacts of CL. NVivo 12v supported the analysis process. Result: The study unveiled negative views and misconceptions surrounding CL and its impact. Application of traditional herbal medicine for CL lesions often leads to pus formation and a foul odour, triggering negative attitudes from others, resulting in embarrassment, pain, and anxiety, leading to discomfort and isolation. The negative psychosocial attitudes associated with CL scars deeply impacted affected individuals, influencing their behaviour. This included isolation and absenteeism from school. CL scars served as unique identifiers, shaping the affected individuals' identity and self-perception. The unreceptive environment affected the participant's self-esteem and coping mechanisms. The negative impact of CL scars extended to role performance, marriage prospects, and overall happiness, particularly for females facing additional societal pressure and stigma. Conclusion: The study highlights the need for improved education and awareness about CL to reduce misconceptions and negative attitudes towards affected individuals. Additionally, more effective treatment options and integrated preventive ways should be explored to minimize the physical and psychological impact of CL on affected individuals. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis caused by Leishmania amazonensis is a significant public health issue. This study aimed to evaluate an ecofriendly, thermosensitive nanogel, developed using a low-energy, solvent-free method, incorporating F127 and Carbopol 974P copolymers, and enriched with Pectis brevipedunculata essential oil (EOPb) for its leishmanicidal and anti-inflammatory properties. The nanogel was prepared and characterized through FTIR, DLS, SEM, and AFM to confirm the incorporation of EOPb as well as its stability and rheological properties. In vitro leishmanicidal activity was evaluated on Leishmania amazonensis promastigotes, and in vivo anti-inflammatory effects were assessed using a rat paw edema model. In vitro, nGF3 (EOPb-loaded nanogel) demonstrated significant leishmanicidal activity, with promastigote mortality rates exceeding 80% at 24 h and 90% at 48 h. In vivo, nGF1, nGF2, and nGF3 exhibited anti-inflammatory effects, with nGF2 and nGF3 reducing edema by 62.7% at 2 h post-treatment. The empty nanogel (nGF0) showed minimal anti-inflammatory activity. The ecofriendly EOPb-loaded nanogel (nGF3) demonstrated strong leishmanicidal and anti-inflammatory effects, presenting a promising candidate for cutaneous leishmaniasis treatment. Further studies are necessary to explore its clinical potential. [ABSTRACT FROM AUTHOR]

The analysis of the volatile compounds released by biological samples represents a promising approach for the non-invasive diagnosis of a disease. The present study, focused on a population of dogs infected with canine leishmaniasis, aimed to decipher the volatolomic profile associated with this disease in dogs, which represent the main animal reservoir for Leishmania pathogen transmission to humans. The volatiles emitted by the breath and hair of dogs were analysed employing the gas chromatography-mass spectrometry (GC–MS) technique. The acquired chromatograms were investigated using a novel algorithm developed in this study for automated chromatographic peak detection and matching in untargeted GC–MS analysis, which includes various steps that comprise noise reduction, m/z filtering, background subtraction, peak detection, peak matching, and generation of a peak table for compounds identification. The results revealed one tentative breath volatile biomarker and five tentative hair volatile biomarkers for the cutaneous form of the disease, which is characterised by skin ulcerations. Additionally, nine tentative breath volatile biomarkers and four tentative hair volatile biomarkers were found for the visceral form of the disease, which affects internal organs such as spleen, liver and bone marrow. All tentative biomarkers identified in this study were upregulated in cutaneous leishmaniasis, while in visceral leishmaniasis, all tentative biomarkers were upregulated in the breath and only one out of four in the hair. Only one compound (glyceryl monooleate) was identified as tentative volatile biomarker for both forms of the disease, in the hair of dogs. [ABSTRACT FROM AUTHOR]

Background Usability is an important method for evaluating mobile health apps from a user perspective. Yet many publicly available apps lack adequate attention to their design, development and evaluation. Objectives To assess usability evaluation and reporting for mobile health apps targeting patients with skin diseases. Methods The protocol was registered with PROSPERO (CRD42022347184). A search strategy combined terms for usability evaluation, user experience, skin disease and mobile health apps (search date 2012–2023). Six databases (Embase, MEDLINE, CINAHL, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, Scopus) were searched, identifying 18 052 results. Nine studies (comprising nine apps) were included in the final analysis. Results Skin conditions and issues targeted included skin cancer (n = 3); sun protection (n = 3); chronic pruritus (n = 2); cutaneous leishmaniasis (n = 1); spina bifida (n = 1); and a study of acne, psoriasis, rosacea, laser treatments, actinic damage, monitoring benign moles, alopecia and inflammatory rash. All studies assessed app usability and feasibility, with the majority concluding that the apps were deemed useful and easy to use. Qualitative methods, such as usability questionnaires and semistructured interviews, were predominantly employed. Common emerging themes included ease of use and navigation, comprehensibility, security and privacy concerns, data sharing issues, customizability, costs, and the ability to track progress or self-monitor. Conclusions While smartphone apps for skin disorders show promising usability across diverse diseases, the limited literature compared with the rapid development of apps highlights the need for meticulous user-centred design and rigorous evaluation. The study emphasizes the importance of evaluating and reporting usability findings to optimize the long-term adoption of mobile health apps, particularly those targeting skin diseases. [ABSTRACT FROM AUTHOR]

• This study demonstrates the potent in vitro and ex vivo anti-leishmanial effects of hydroalcoholic Nicotiana tabacum (tobacco) extract against Leishmania major. • The extract exhibited dose- and time-dependent reductions in promastigote mortality and amastigote infection rates, with efficacy comparable to Glucantime at higher concentrations. • These findings suggest that Nicotiana tabacum extract could serve as a promising natural alternative or adjunctive therapy for leishmaniasis, particularly in drug-resistant cases. Leishmaniasis, caused by protozoa of the genus Leishmania , remains a significant public health challenge, with Leishmania major as a predominant species in cutaneous leishmaniasis in Iran. Conventional treatments, including Glucantime, are hindered by drug resistance and adverse effects, highlighting the need for effective natural alternatives. This study investigates the in vitro and ex vivo anti-leishmanial effects of hydroalcoholic tobacco leaf extract (Nicotiana tabacum) against L. major. A 70 % hydroalcoholic extract of tobacco leaves was prepared and tested at concentrations of 12.5, 50, 100, and 200 µg/mL. In vitro assays evaluated promastigote mortality, while ex vivo assays assessed macrophage infection rates. Glucantime served as the positive control. Evaluations were conducted at 24, 48, and 72 h, with data analyzed using one-way ANOVA and Tukey's post-hoc test. The tobacco extract demonstrated a dose- and time-dependent reduction in promastigote mortality and amastigote infection rates. At 200 µg/mL, its efficacy was comparable to 100 µg/mL Glucantime, particularly after 72 h. Higher extract concentrations significantly reduced both parasite viability and macrophage infection rates, suggesting its potential as a potent anti-leishmanial agent. Hydroalcoholic tobacco leaf extract shows promising anti-leishmanial activity in vitro and ex vivo, suggesting its potential as a natural alternative to conventional treatments like Glucantime. Further in vivo studies are needed to confirm these findings and explore its use in leishmaniasis therapy, particularly in cases of drug resistance. [ABSTRACT FROM AUTHOR]

Background: Mucosal leishmaniasis (ML) is a severe clinical form of leishmaniasis that is characterized by the destruction of the nasal and/or the oral mucosae and appears as a late complication in 5% to 10% of cutaneous leishmaniasis (CL) cases produced by species belonging to Leishmania (Viannia) subgenus. Some strains of Leishmania spp. carry an RNA virus known as Leishmania RNA virus (LRV) that may contribute to the appearance of ML. Methods: To examine the role of LRV type 1 (LRV1) as a risk factor associated with ML, a retrospective case-control study involving 103 patients was conducted. Cases were defined as patients with ML (n = 33), and controls corresponded to patients with CL and without mucosal lesions (n = 70). Clinical data were recorded from the patient's medical records. Cryopreserved biopsies were used to detect LRV1 and identify Leishmania species. Results: The frequency of LRV1 in the 103 patients was 16.5% (95% CI,10.4–25.12) being higher in samples from cases [33.33% (95% CI,18.89–51.76) than from controls [8.57% (95% CI, 3.82–18.10)]. L. (V.) braziliensis was identified in 63.6% of cases and 55.7% of the controls. Multivariate logistic regression indicated that infection with Leishmania spp. carrying LRV1 (OR = 6.30; 95% CI,1.52–26.10, p = 0.011) acts as risk factors for ML occurrence, while the completed treatment for the cutaneous event decreases the risk of ML (OR = 0.039; 95% CI, 0.01–0.12, p < 0.0001). Conclusions: Our data support the association between LRV1 and ML occurrence and emphasize the effect of completed treatment for CL in preventing ML. [ABSTRACT FROM AUTHOR]

Background: The vitamin D pathway contributes to the microbicidal activity of macrophages against Leishmania infection. In addition to induction of this pathway, interferon-gamma (IFNγ), interleukin (IL)-15, and IL32γ are part of a network of pro-inflammatory cytokines. The aim of this study was to evaluate single-nucleotide polymorphisms (SNPs) in the components of the vitamin D pathway and associated cytokine genes that could be related to resistance or susceptibility to American tegumentary leishmaniasis (ATL). Methods: The expressions of IFNG , IL15 , IL32 , CYP27B1 , VDR , and other pro-inflammatory cytokines TNF , IL6 , and IL17 genes were evaluated using real-time polymerase chain reaction (qPCR) in lesions of patients with localized cutaneous leishmaniasis (LCL) or mucosal leishmaniasis (ML). SNP genotypes/alleles (in IL15 , IL32 , CYP27B1 , and VDR) were evaluated by TaqMan PCR assays using DNA from the blood of patients and healthy individuals. Serum vitamin D levels were determined by chemiluminescence. Results: Vitamin D pathway-associated genes were expressed in cutaneous as well as mucosal lesions. IFNG , IL6 , and IL17 were more highly expressed in ML than in LCL. In contrast, IL32γ/CYP27B1/VDR mRNAs were mainly correlated in LCL, and IL32γ in ML makes strong connections with all cytokines. The SNP IL32 rs1555001 was less frequent in patients with ML. In addition, some SNPs appear to influence the VDR and CYP27B1 (IL15 rs10519613 and IL15 rs3775597) and IL6 (VDR rs7975232) expressions in LCL and the IL17 expression in ML (IL15 rs3775597). Gene expression was also correlated with clinical parameters, such as number of lesions (CYP27B1 mRNA) and treatment failure (VDR mRNA). In addition, one SNP was associated with treatment failure in ML (VDR rs7975232). Conclusions: Our findings suggested that some SNPs in the vitamin D pathway-associated genes can be related to resistance and therapeutic outcomes of ATL. They are promising candidates that need to be further evaluated to understand their biological effects in the control or immunopathogenesis of ATL. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) is a tropical disease that can cause chronic lesions and leave life-long scars, leading to social stigmatization and psychological disorders. Using growth factors and immunomodulatory agents that could accelerate wound healing and reduce the scar is highly demanded. Epidermal growth factor (EGF) plays an essential role in wound healing. It stimulates the proliferation of keratocytes and fibroblasts, and promotes re-epithelialization. Here, the effect of EGF in combination with Glucantime and nano-liposomal Amphotericin B (SinaAmpholeish) on the healing process of CL in BALB/c mice was investigated. Seventy-two mice were infected with Leishmania major parasites and randomly divided into eight treatment groups after the appearance of the lesion. The treatment was continued for five weeks, and lesion sizes were measured weekly. Parasite load was determined in the skin biopsies using qPCR. We found that subcutaneous injection of EGF at 4.5 μg/kg, combined with each of the two antileishmanial drugs, significantly reduced the wound size and parasite load; however, EGF at 1.5 μg/kg failed to be effective. Besides, the wound size and parasite loads were significantly lower in the SinaAmfoleish groups compared to the Glucantime groups. Among the treatment groups, EGF 4.5 μg/kg combined with SinaAmpholeish exhibited the most significant reduction in wound size and parasitic load. Our results suggest that EGF can potentiate the wound healing effect of antileishmanial drugs. Further studies are warranted to explore the beneficial effects of combining EGF with antileishmanial drugs in patients with cutaneous leishmaniasis in order to accelerate wound healing and reduce the scar. Author summary: Cutaneous leishmaniasis (CL) is a vector-borne disease caused by Leishmania that affects more than one million people worldwide each year. CL is a disfiguring disease capable of causing chronic skin ulcers that leave scars with significant social and economic impact. Although chemotherapy, such as antimonial compounds, is the pillar choice for treatment, large doses and extended treatment regimens hamper their efficacy. Application of growth factors and immunomodulatory agents for treatment of CL represents a highly favorable approach for reducing the healing time and scar. Here, we evaluated the effectiveness of subcutaneous administration of epidermal growth factor (EGF) in combination with Glucantime or nano-liposomal Amphotericin B (SinaAmpholeish) in the treatment of CL in BALB/c mice. During the five-week treatment, lesion sizes were measured weekly. At the end of the study, parasite load was determined in the skin biopsies using the qPCR method. Combination therapy of EGF at 4.5 μg/kg with either drug alone enhanced wound healing; however, treatment with EGF and SinaAmpholeish was most potent in reducing the lesion size and parasitic load. Numerous studies indicated the usefulness of EGF for wound healing in different clinical settings. Our results suggest EGF as a promising supplement to antileishmanial drugs for the treatment of CL. Further studies are needed to explore the beneficial effect of combining EGF with antileishmanial drugs in patients with cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

Leishmaniases affect millions of people around the world, caused by Leishmania parasites. Leishmania are transmitted by female sandflies from Phlebotominae subfamily during their blood meals. In mammals, promastigotes are phagocytosed mainly by macrophages, differentiate into amastigotes and multiply. For entry and survival in macrophages, Leishmania uses virulence factors such as surface glycoconjugates. Sialic acids (Sias) are found in terminal portions of glycoconjugates and play important roles in human pathogens. The importance of Sias was explored only in L. (L.) donovani, associated with visceral leishmaniasis in Africa, Asia and Europe. Thus, the aim of this study was to characterize Sias of Leishmania (L.) amazonensis and Leishmania (L.) infantum, related to cutaneous and visceral leishmaniasis in South America, respectively. For that, we analyzed by HPLC‐FLD the Sias of promastigotes of L. (L.) amazonensis LV79 and two L. (L.) infantum strains, and of L. (L.) amazonensis axenic amastigotes and amastigotes from paw lesions of infected mice. To evaluate Sias importance in promastigotes, we treated stationary phase parasites with sialidase and infected murine and human macrophages. We detected N‐Acetylneuraminic Acid in promastigotes of all strains, with greater abundance in L. (L.) infantum. We identified N‐Acetylneuraminic Acid and N‐Glycolylneuraminic acid in amastigotes recovered from paw lesion, but only N‐Acetylneuraminic Acid in axenic amastigotes. Promastigotes treated with sialidase infected less macrophages than parasites displaying total Sias. Our results demonstrate that Sias vary between Leishmania species and between L. (L.) amazonensis life stages and plays an important role in macrophage infection by L. (L.) amazonensis and L. (L.) infantum. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis is one of the neglected tropical diseases which is hard to treat. Carbon dioxide-based cryotherapy is a novel therapeutic option for cutaneous leishmaniasis in both developed and developing nations. This study aims to summarize the pooled evidence on the effectiveness of carbon dioxide-based cryotherapy for the treatment of cutaneous leishmaniasis. Methods: Searches of grey literature using Google Scholar and databases including PubMed, Scopus, EMBASE, Web of Science, and Google Scholar were conducted to find studies that reported the cure rate of cryotherapy. The search, screening, data extraction, and critical evaluation were carried out by two authors, with a third acting as a tiebreaker. To locate papers, we used Medical Subject Headings (MeSH) phrases and keywords. Between May 10 and May 13, 2023, the review protocol was developed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist. For the meta-analysis, STATA 17 was the statistical software used. The random effects model was employed to compile the effect estimates. Lastly, we used the funnel plot and Egger's test to evaluate publication bias, heterogeneity, sensitivity, and subgroup analyses. Result: Out of the 16 researches included in the review, seven papers with a total of 1,357 cases were chosen for the meta-analysis. For the treatment of cutaneous leishmaniasis, the pooled cure rate with carbon dioxide-based cryotherapy was 87.84% (95% CI: 65.92–109.77). Randomized controlled trials made up the majority of the studies that were used. The highest cure rate was seen when there were two lesions, 94.34% (95% CI:68.21–119.48), and when the size of the lesion was less than or equal to 4, 93.83% (95% CI:68.92–118.75). There was no indication of a significant publishing bias. Conclusion: Carbon dioxide-based cryotherapy revealed a high pooled efficacy. The efficacy of the CL instances was mostly dependent on the extent of the lesion and the frequency of therapy administration. To determine if this therapy is beneficial in a routine care context, a large-scale study with a sound design is necessary. Author summary: Neglected tropical diseases like cutaneous leishmaniasis are often overlooked. It can take on a variety of clinical forms and presentations. Comparably, the various causal agents and clinical forms of the treatment also vary. Both localized and systemic treatments are effective in treating localized cutaneous leishmaniasis. In most dermatological clinics, liquid nitrogen cryotherapy was the primary method employed. However, most dermatology clinics also utilize carbon dioxide-based cryotherapy sparingly, although the gynecology department uses it often for cervical cancer screening. On the other hand, the product is accessible, simple to use, painless, reasonably effective, and leaves fewer scars. Carbon dioxide cryotherapy had a pretty high pooled impact across trials, offering another accessible, easy-to-apply, and reasonably effective therapeutic option for localized cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

The course and outcome of infection with the parasitic protozoa Leishmania major depends on the host immune response which, itself, depends mainly on the cytokine milieu, especially early in the infection. It is widely accepted that INF-γ, TNF-α, and IL-12 usually favor a protective response, while IL-4, IL-5, IL-10, and IL-13 favor a pathogenic one. These and other cytokines also play a major role in Leishmania-induced hyperalgesia via two possible pathways, one involving prostaglandins and the other sympathetic amines as final mediators, preceded by a cascade of cytokines, among which TNF-α seems to play a pivotal role via a still unclear mechanism of action. This study investigates the effects of anti-TNF-α antibody (Infliximab) on L. major-induced hyperalgesia in susceptible BALB/c mice using the hot plate and tail flicks tests, as well as the levels of many cytokines in the infected paws of mice using the ELISA technique. In addition, the parasite burden was assessed using the serial dilution method. Our results show that Infliximab can reduce the induced hyperalgesia, up-regulate TNF-α, IL-1β, and keratinocyte-derived chemokine (KC), and down-regulate IL-10 and IL-17 in the paws of infected mice. Infliximab may also have beneficial effects on the prognosis of cutaneous leishmaniasis by reducing the parasite burden. [ABSTRACT FROM AUTHOR]

Introduction: Cutaneous Leishmaniasis (CL) is a zoonosis infection which is endemic in more than 100 countries in Asia, Africa, Europe and America. It was estimated that nearly 20 thousand of new cases are reported in Iran annually. This study aimed to investigate the impact of floods on the incidence of leishmaniasis in Golestan province (northeast of Iran) over nine years, from 2015 to 2023. Methods: Interrupted Time Series Analysis (ITSA) is a study design used to study the effects of an intervention, disaster, or natural event on occurrence of a disease over time. In March 2019, a major flood occurred in Golestan Province, and it had a particularly strong effect on the Gonbad Kavous county (region 1). The trend of CL incidence before and after the flood was assessed using ITSA. In addition, the flood impact on CL incidence was compared between Gonbad Kavous county (region 1) with other counties (13 counties, as the region 2). Results: Throughout the study, a total of 8953 cases were identified with 2148 (24%) infected with leishmaniasis before the flood and 6805 (76%) after that. A comparison of leishmaniasis between the two regions before and after the flood revealed a significant increase in Gonbad Kavous County following the flood. Also, in the multivariate regression analysis, the average difference in the baseline occurrence level before the flood in regions 1 and 2 was 30.3 per 105 population, which was statistically significant. Additionally, the average difference in the occurrence of leishmaniasis after the flood between the two regions was 37.3 cases per 105 population. The difference in trend of incidence between the two regions increased to 30.4 per 105 population after the flood, compared to 5.5 per 105 before the flood. Also, the long-term trend difference after the flood between the two regions has reached 27.3 per 105 population. Discussion: Natural disasters such as floods, earthquakes, and climate change can increase the spread of diseases such as leishmaniasis. Some interventional strategies are needed to decrease the risk of leishmaniasis outbreaks in flooded areas. Besides informing the community, allocating more financial resources for healthcare activities is essential. Environmental and individual protective activities, regular waste collection and disposal, and combating reservoirs and vectors are particularly crucial. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of leishmaniasis on the quality of life of patients visiting the district headquarter hospital in District Khyber, Khyber Pakhtunkhwa, Pakistan. Methods: A cross-sectional exploratory study was conducted in District Headquarter Hospital of Khyber District, Khyber Pakhtunkhwa from November 2019 to April 2020. In this study, 349 participants who consented were included by using a non-probability consecutive sampling technique. A validated questionnaire "Dermatology Life Quality Index" (DLQI) was used for data collection. Independent sample t-test and one-way ANOVA were used for mean scores comparison. Results: The mean DLQI score of cutaneous leishmania patients was 11.83 ± 3.94. Cutaneous leishmaniasis (CL) patients experienced a huge impact on their quality of life. The highest effect was observed for symptoms and feelings while the least impact was for the treatment. Statistically, no significant difference in mean DLQI score was found for gender, age, marital status, lesion activity, lesion appearance, and treatment history (p > 0.05). However, statistically, a significant difference was observed for the education, occupation, lesion location, and lesion type (p < 0.05). Conclusion: CL had a significant impact on the patient's quality of life and mental health. Further research is required to assess the impact of the treatment on QOL in CL patients. and for a better understanding of the issue and its mechanistic basis. [ABSTRACT FROM AUTHOR]

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One of the most important steps in preclinical drug discovery is to demonstrate the in vivo efficacy of potential leishmanicidal compounds and good characteristics at the level of parasite killing prior to initiating human clinical trials. This paper describes the use of dehydrothyrsiferol (DT), isolated from the red alga Laurencia viridis, in a pharmaceutical form supported on Sepigel, and the in vivo efficacy against a mouse model of cutaneous leishmaniasis. Studying the ultrastructural effect of DT was also carried out to verify the suspected damage at the cellular level and determine the severity of damages produced in the homeostasis of promastigotes. BALB/c mice infected with Leishmania amazonensis were divided into four groups: untreated mice, mice treated with miltefosine orally and mice treated topically with 1% and 0.5% DT-Sepigel; treatment was carried out for two weeks. Treatment with DT significantly reduced the parasite load in skin, liver and spleen compared with the untreated group. In addition, DT-Sepigel at the lowest concentration (0.5%) showed the best results, reducing lesion size by 87% at 3 weeks post-treatment. DT-Sepigel has demonstrated to be a potent topical treatment that, in combined drug trials, may aim at combating cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

Background/Objectives: Thiadiazine thione (THTT) has gained significant interest owing to its pharmacological potentials, particularly its antiparasitic and anti-inflammatory properties. Leishmaniasis is a clinical syndrome caused by infection with Leishmania species and is associated with an inflammatory response and nociception. The available treatments against leishmaniasis are inadequate, as they are associated with high cost, toxicity, and increased resistance. Methods: In the current study, the antileishmanial potential of five Thiadiazine thione derivatives (C1–C5) was evaluated in vivo against Leishmania tropica. Experiments were performed on BALB/c mice infected with promastigotes and treated with THTT derivatives for 15 days. Additionally, the derivatives were evaluated for their anti-inflammatory, antinociceptive, antipyretic, and antisedative properties using standardized models, including carrageenan-induced paw edema, acetic acid-induced abdominal writhes, yeast-induced fever, and white wood apparatus, respectively. Results: Of the tested derivatives, C5 exhibited the most promising results, with a 61.78% reduction in lesion size and significant decrease in parasite load. Among the derivatives, C1 showed the highest anti-inflammatory activity, with 63.66% inhibition in the paw edema test at the 5th hour post treatment. In the antipyretic assay, C1 and C5 were able to reduce body temperature to a normal level within 1 h of treatment. Furthermore, compounds C4, C2, and C1 showed high nociceptive activity, while C1 and C5 demonstrated the most notable antisedative effects (94 ± 2 and 92 ± 1, respectively), outperforming the standard drug diazepam (13 ± 1). Conclusion: These in vivo findings suggest that THTT derivatives have the potential to serve as a template for developing leishmanicidal drugs, with added anti-inflammatory and analgesic properties. [ABSTRACT FROM AUTHOR]

Objective: To compare the spatio-temporal distribution of cutaneous leishmaniasis (CL) cases with mucosal leishmaniasis (ML) cases in the state of Rio de Janeiro (RJ) between 2001 and 2011. Method: The incidence rates (IR) of CL and ML were calculated for the cases notified between 2001–2011 in the Information System of Notifiable Diseases for Rio de Janeiro (RJ, and for the municipalities of Rio de Janeiro and Angra dos Reis, with georeferencing and construction of thematic maps. A negative binomial regression model was used to assess the temporal dependency between CL and ML. Results: Higher IR of CL and ML were observed up to 2006. The cases of CL and ML increased annually concomitantly in the state of RJ and in Angra dos Reis, even when they were controlled by the CL rates of the previous year. The municipality of Rio de Janeiro presented smaller annual CL IR after the occurrence of high ML IR in the two previous years. Conclusion: The temporal association observed between CL and ML suggests that: either the mucosal lesions were already incipient from the beginning of CL manifestation, or the Leishmania species circulating in RJ is able to produce early mucosal lesions. [ABSTRACT FROM AUTHOR]

Background: Although there are several areas in southern Ethiopia environmentally favourable for cutaneous leishmaniasis (CL), studies on the existence and risk factors of CL are lacking beyond a few well-known hotspots. This study aimed to assess the prevalence and risk factors of CL in Bilala Shaye, a village in the southern Ethiopian highlands at an altitude of 2,250 meters. Methods: A cross-sectional house-to-house survey was done between July-August 2021. Those with skin lesions were clinically assessed and data on individual risk behaviour and environmental and household features were collected using questionnaires. Univariate and multivariable logistic regression models were used to identify independent risk factors of CL at a 5% significance level with two-sided P-values <0.05 considered statistically significant. Result: A total of 1012 individuals were interviewed; the median age was 23 years (interquartile range 12–50), with 7% below the age of five; 51% were female. All households had domestic animals, and for 143 (57%) households goats/sheep lived inside or around the house. Animal dung was found in the compounds of 194 (77%) households. The overall prevalence of active CL was 2.5% (95% confidence interval (CI) 1.6–3.6), reaching 6.7% (95% CI 3.6–11.2) in children between 5–12 years old. The prevalence of CL scars was 38.5% (95% CI 35.5–41.6). In multivariate analysis, the presence of animal dung in the compound (adjusted odds ratio (OR) 2.1; 95% CI: 1.3–3.5, P = 0.003) and time spent outside in the late evening in areas where hyraxes live (adjusted OR 2.4; 95% CI: 1.7–3.3, P <0.001) were identified as independent risk factors. Conclusion: This is the first report on the existence of CL in this village, with the high prevalence of CL scars indicating long-term endemicity. Further studies are needed to understand the role of animals and their dung in (peri)-domestic CL transmission. [ABSTRACT FROM AUTHOR]

Leishmania is a genus of the family Trypanosomatidae that unites obligatory parasitic flagellates causing a variety of vector-borne diseases collectively called leishmaniasis. The symptoms range from relatively innocuous skin lesions to complete failures of visceral organs. The disease is exacerbated if a parasite harbors Leishmania RNA viruses (LRVs) of the family Pseudototiviridae. Screening a novel isolate of L. braziliensis, we revealed that it possesses not a toti-, but a bunyavirus of the family Leishbuviridae. To the best of our knowledge, this is a very first discovery of a bunyavirus infecting a representative of the Leishmania subgenus Viannia. We suggest that these viruses may serve as potential factors of virulence in American leishmaniasis and encourage researchers to test leishmanial strains for the presence of not only LRVs, but also other RNA viruses. Author summary: Parasites of the genus Leishmania cause a series of neglected tropical diseases collectively known as leishmaniasis. Many isolates of these parasites possess Leishmania RNA viruses (LRVs) of the family Pseudototiviridae that increase a chance of developing more severe mucocutaneous leishmaniasis over the cutaneous form, facilitate the spread of leishamaniae, and make these flagellates more resistant to treatments. In this work, we demonstrate that pseudototiviruses are not the only infecting agents and some isolates of Leishmania may harbor other viruses, exemplified by the leishbuvirus LbrLBV1 of L. braziliensis. Because they may also be considered as potential factors of virulence, we advocate for routine testing of leishmanial strains for the presence of not only LRVs, but also other RNA viruses. [ABSTRACT FROM AUTHOR]

Background: Leishmania is the causal parasite of leishmaniasis, a neglected tropical disease affecting millions of individuals worldwide, and its dissemination is linked to climate change. Despite the complexity and effectiveness of the immune response, the parasite has developed many strategies to evade it and take control of the host cell to replicate. These evasion strategies start at early stages of infection by hijacking immune receptors to mitigate the cellular response. In this study, we examined whether Leishmania uses the Fc receptor FcγRIIA/CD32a and its downstream signaling pathways to evade the host immune response. Methods: Regarding in vivo studies, CD32a transgenic mice and the corresponding wild types were infected with Leishmania major Friedlin strain. For the in vitro experiments, BMDMs isolated from WT or CD32a transgenic mice and control or CD32a knockdown differentiated THP-1s were infected with two species of Leishmania, Leishmania major and L. tropica. Results: In vivo, expression of FcγRIIA/CD32a was found to accelerate the signs of inflammation while simultaneously preventing the formation of necrotic lesions after Leishmania infection. In infected macrophages, the presence of FcγRIIA/CD32a did not affect the secretion of proinflammatory cytokines, while the balance between ITAMa and ITAMi proteins was disturbed with improved Fyn and Lyn activation. Unexpectedly, infection with L. tropica but not L. major triggered an intracytoplasmic processing of FcγRIIA/CD32a. Conclusions: Our observations underscore the significance of FcγRIIA/CD32a in cutaneous leishmaniasis and its potential use as a therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Our work presents the whole genome sequence and phylogenetic analysis of five Leishmania RNA virus 2 (LRV2) isolates obtained from patients with cutaneous leishmaniasis (CL) in Iran. Methods: The whole genome sequencing of LRV2 was performed using a primer walking approach. The resulting sequences were analyzed for genetic and haplotype diversity, highlighting their independent evolution and significant genetic divergence. Results: The whole genome sequence of the current LRV2 showed high genetic and haplotype diversity. The study also revealed the existence of three distinct clades of LRV2, with the LRV2 sequences infecting L. major, L. aethiopica, and sauroleishmania belonging to separate lineages. These lineages have seemingly evolved independently, as the geographic distribution of their flagellate hosts does not overlap with the Leishmania species. The divergence between these three clades is attributed to considerable antiquity, leading to genetic modifications within the viruses residing in them and resulting in structural differences in their genome. Conclusions: These findings contribute to our understanding of the genetic diversity and evolution of LRVs, providing valuable insights into their role in Leishmania infections. Further investigations are needed to understand the significance of these polymorphic sites and their potential impact on viral characteristics and disease outcomes. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis is a parasitic disease that poses significant diagnostic challenges due to the variability of results and reliance on operator expertise. This study addresses the development of a system based on machine learning algorithms to detect Leishmania spp. parasite in direct smear microscopy images, contributing to the diagnosis of cutaneous leishmaniasis. Starting with acquiring and labeling 500 images, an experimental design was implemented, including preprocessing and segmentation techniques such as Otsu, local thresholding, and Iterative Global Minimum Search (IGMS) to improve parasite detection. The phenotypic features of the parasites were extracted, focusing on morphology, texture, and color. Machine learning models (ANN, SVM, and RF) optimized through Grid Search were applied for classification. The model with the best results was a Support Vector Machine (SVM), achieving a sensitivity of 91.87% and a specificity of 89.21% at the crop level. Compared with previous studies, these results highlight the relevance and consistency of the methodology used, supporting the initial hypothesis. This suggests that machine learning techniques offer a promising path toward improving the diagnosis of cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

Introduction: Leishmaniasis is a highly prevalent neglected tropical disease. It represents a significant public health concern in northern Africa, particularly in Morocco. To assess the extent of the disease at the provincial level, as well as the temporal evolution of CL cases and their geographic distribution. Methods: 834 cases of cutaneous leishmaniasis (CL) diagnosed positive by the hygiene and health laboratory of the health delegation of the province of Essaouira during the period from January 1st, 2014 to December 31st, 2023. Results and discussion: Among the 57 communes of the province, three are hyper-endemic and represent the main foci of LC; Elhanchan, Had Draa, Smimou with 66.42% of cases. Other communes with significant increases include Aguerd, with 15.6% of cases, an incidence peak of 279.7 per 100,00.0 in 2022, and Bizdad, 11.8% with an average incidence of 41.1 per 100,000. The transmission of the parasitosis continues to spread to create new outbreaks each year and reach 25 municipalities in the province which have experienced at least one positive case in 2023. Two new outbreaks appeared after 2018 in Sidi Kaouki (5% of cases) and Tidzi (5.6%). The temporal analysis shows a significant rise in cases over time, with an annual average of 83 cases. The trend paused during the COVID-19 lockdown but resumed exponentially, peaking in 2023. The overall incidence in the province increased from 11.1 per 100,000 in 2015 to 40.3 per 100,000 in 2023, with a significant rise over the study period (p < 0.001). The average incidence during this time was 18.32 per 100,000, showing considerable variability across different years. Conclusion: The spread of cutaneous leishmaniasis in the province of Essaouira is multifactorial and results from the complex interaction between vectors, parasites, the environment, and human behaviors. A better understanding of these factors is essential to developing effective disease prevention and controlling strategies. [ABSTRACT FROM AUTHOR]

Background The mechanisms that mediate immune protection in individuals with subclinical (SC) or asymptomatic infection with Leishmania braziliensis are largely unknown. Neutrophils (polymorphonuclear leukocytes [PMNs]) have been implicated in progressive symptomatic cutaneous leishmaniasis (CL), but their potential participation in maintenance of subclinical infection is unexplored. The aim of this study was to compare the phenotypic and functional profiles of PMNs in individuals with SC infection versus patients with symptomatic CL due to L braziliensis. Methods Subjects were recruited in the endemic region of Corte de Pedra, Bahia, Brazil. Surface markers to define activation status were characterized by flow cytometry. Functional responses of PMNs including phagocytic capacity, production of oxidative species, and oxidative killing of intracellular parasites were studied in vitro. Results PMNs from individuals with SC infection displayed a more activated phenotype and greater ability to control the infection than PMNs from patients with CL. In contrast, PMNs from patients with CL exhibited higher expression of HLA-DR and higher production of oxidative species than PMNs from subjects with SC infection. Conclusions PMNs from individuals with SC infection can control the infection more efficiently than PMNs from patients with CL, despite the lower production of oxidants. Our observations suggest that L braziliensis may evade microbicidal mechanisms of PMNs from patients with CL, contributing to parasite dissemination and the establishment of disease. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cutaneous leishmaniasis (CL) is a skin disease caused by Leishmania parasites. Presepsin, irisin, and apelin are biomarkers that are involved in the inflammatory response. The aim of this study was to investigate the association between serum levels of specific biomarkers, such as presepsin, apelin, and irisin, and the clinical features, location, number, and size of lesions in patients with CL. Methods: This study is a single-centre, prospective cohort study involving a total of 30 patients with skin lesions compatible with CL and 30 healthy matched controls. Age, sex, type of skin lesion, location of skin lesion, number of skin lesions, and diameter of skin lesions were recorded. The levels of presepsin, irisin, and apelin measured in the blood samples of the patient group were analysed in comparison to those in the healthy control group. Results: The findings revealed that presepsin levels were significantly elevated in the patient group compared to the controls (p = 0.000). However, no statistically significant differences were observed between the groups for irisin and apelin levels (p-values 0.096 and 0.836, respectively). A negative correlation was identified between presepsin levels and the number of skin lesions, the diameter of the largest lesion, and the total diameter of the lesions (p = 0.000). Conclusions: It appears that measuring presepsin levels in patients with CL may be beneficial. Presepsin has the potential to serve as a prognostic marker in CL, offering significant benefits in guiding clinicians in assessing disease progression and response to treatment. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a vector-borne parasitic infection induced by protozoa of the genus Leishmania. The disease spectrum ranges from skin lesions to visceral leishmaniasis, which is fatal if untreated. The cutaneous leishmaniasis is characterized by a clinical polymorphism of lesions with a broad range of severity ranging from a self-limited lesion to multiple disfiguring lesions stigmatizing the patient for life. Although iron is required for several process of Leishmania infection including survival, growth and virulence, the number of studies on host iron metabolism during this infection remains limited. Iron homeostasis in the body is finely regulated by hepcidin, a hyposideremic peptide highly expressed in the liver. In infectious contexts, hepcidin plays additionally an antimicrobial role, acting through various mechanisms such as retaining iron in tissues, modulating the immune response, and operating as a defensin against gram-negative bacteria. This review mainly summarizes the most important interconnections between iron metabolism, hepcidin and leishmaniasis. A deeper understanding of iron metabolism in this context could help in developing innovative treatment strategies that target the parasite while simultaneously reinforcing host defenses. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) is a neglected tropical disease that poses a significant public health challenge in Brazil and worldwide. Miltefosine, the only orally administered drug available for CL, was recently incorporated into Brazil's treatment protocols following recommendations by the World Health Organization (WHO) and revisions by national health authorities. While this represents an important advancement, miltefosine is associated with frequent gastrointestinal side effects and potential teratogenic risks, necessitating careful patient eligibility assessments and close clinical monitoring throughout treatment. Furthermore, the absence of national effectiveness data underscores the need for careful monitoring during large-scale implementation. This study, part of a broader implementation monitoring process, seeks to estimate the frequency, intensity, and seriousness of adverse events (AEs) associated with miltefosine. It also aims to identify factors linked to treatment discontinuation during the pilot phase of miltefosine distribution in the state of Minas Gerais, Brazil. Descriptive analyses were performed to present measures of central tendency and dispersion for the variables. Additionally, a multivariate analysis was conducted to explore relationships between explanatory variables and outcomes of interest. Between 2021 and 2023, 77.1% of patients treated with miltefosine experienced at least one AE. The rate of serious AEs related to treatment was 1.3%. Gastrointestinal symptoms were the most commonly reported AEs, followed by musculoskeletal manifestations. The most frequent laboratory alteration observed was an increase in serum creatinine, which was significantly associated with hypertension, age, and mucosal involvement of leishmaniasis. No pregnancies were recorded during the implementation period. Early treatment discontinuation rate occurred in 11.8% of cases, with discontinuation associated with age and baseline serum creatinine alterations. Half of the patients required temporary treatment interruptions or irregular dosing, extending the treatment duration beyond the planned 28 days. This pharmacovigilance model provides valuable insights, representing an approach potentially applicable to other neglected disease control programs, especially when introducing new treatment technologies. [ABSTRACT FROM AUTHOR]