Search

Background There is limited knowledge about the stigma associated with cutaneous leishmaniasis (CL) in Sri Lanka. To ensure that leishmaniasis researchers focus on CL-associated stigma, we provide an evidence-based framework that can be used in future research. Methods We conducted a systematic review on CL-associated stigma using international evidence and carried out a multimethod qualitative study in the Anuradhapura district in Sri Lanka. Based on that, we identified manifestations of stigma, drivers and facilitators that we synthesised to develop a conceptual framework on CL-associated stigma. Results Our framework consists of drivers, facilitators and self-stigma experienced by people with CL. Stigma drivers included fear, misbeliefs and misconceptions about CL; the belief that wounds are disfiguring; the treatment burden and implied blame. Facilitators that reduced stigma included knowledge of the curability of CL and awareness that CL is not contagious. The nature of social interactions in rural communities enhanced stigma formation. We identified various enacted, felt and internalised stigma experiences of people with CL. Conclusions We developed a conceptual framework of the stigma associated with CL that can be used to develop targeted interventions to increase CL awareness, address stigma and improve the quality of life for CL patients. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells include different subsets with diverse effector capacities that are poorly understood in the context of parasitic diseases. Here, we investigated inhibitory and activating receptor expression on NK cells in patients with cutaneous leishmaniasis (CL) and explored their phenotypic and functional heterogeneity based on CD57 and NKG2C expression. The expression of CD57 identified NK cells that accumulated in CL patients and exhibited features of senescence. The CD57+ cells exhibited heightened levels of the activating receptor NKG2C and diminished expression of the inhibitory receptor NKG2A. RNA sequencing analyses based on NKG2C transcriptome have revealed two distinct profiles among CL patients associated with cytotoxic and functional genes. The CD57+NKG2C+ subset accumulated in the blood of patients and presented conspicuous features of senescence, including the expression of markers such as p16, yH2ax, and p38, as well as reduced proliferative capacity. In addition, they positively correlated with the number of days until lesion resolution. This study provides a broad understanding of the NK cell biology during Leishmania infection and reinforces the role of senescent cells in the adverse clinical outcomes of CL. Natural killer (NK) cells include different subsets with diverse effector capacities that are poorly understood in the context of parasitic diseases. This study provides a broad understanding of the NK cell biology during Leishmania infection and reinforces the role of senescent cells in the adverse clinical outcomes of cutaneous leishmaniasis. Graphical Abstract (A) NK subsets present opposite immune and senescence features in cutaneous leishmaniasis. (B) Expansion of cytotoxic NKG2C + CD57 + NK cells is associated with increased lesional healing delay. Spearman's rank correlation (ρ) between cell subsets frequencies and patient stratified by CD57 and NKG2C expression and lesional healing time (days) taken by cutaneous leishmaniasis patients. The graphs show a median with 95% confidence. The P values were calculated by comparing each treatment round set between the NK cell subsets using RM-one-way ANOVA and Benjamin and Hochberg method. *P < 0.05, **P < 0.01, ***P < 0.001. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis is atypical in Sri Lanka because Leishmania donovani, which typically causes visceral disease, is the causative agent. The origins of recently described hybrids between L. donovani and other Leishmania spp. usually responsible for cutaneous leishmaniasis remain unknown. Other endemic dermotropic Leishmania spp. have not been reported in Sri Lanka. Genome analysis of 27 clinical isolates from Sri Lanka and 32 Old World Leishmania spp. strains found 8 patient isolates clustered with L. tropica and 19 with L. donovani. The L. tropica isolates from Sri Lanka shared markers with strain LtK26 reported decades ago in India, indicating they were not products of recent interspecies hybridization. Because L. tropica was isolated from patients with leishmaniasis in Sri Lanka, our findings indicate L. donovani is not the only cause of cutaneous leishmaniasis in Sri Lanka and potentially explains a haplotype that led to interspecies dermotropic L. donovani hybrids. [ABSTRACT FROM AUTHOR]

Given the distinctive characteristics of Astragalus in the treatment of diseases and the strengthening of the immune system, for the first time, this study represents the first attempt to study the in vitro and in vivo leishmanicidal effects of chloroform extract of A. ecbatanus (AECE) on Leishmania major. The in vitro activity was determined against L. major (MHOM/AF/88/KK27). In addition, the effect of AECE on the generation of nitric oxide (NO) and the rate of macrophage infectivity was evaluated. The, antileishmanial effects of topical administration of AECE at 10 and 20 mg/kg were evaluated In vivo on cutaneous leishmaniasis in mice. The 50% inhibitory concentration (IC50) index of AECE and amphotericin B for promastigotes was found to be 76.3 and 2.78 μg/mL, respectively. The number of amastigotes exhibited a dose-dependent decline following treatment with AECE. The IC50 and 50% cytotoxic concentration (CC50) for AECE were 39.4 and 408.3 µg/ml, respectively. The extract was observed to induce the creation of NO while simultaneously reducing the level of macrophage infection. Following a four-week course of AECE therapy, the lesions of CL were observed to have healed in the infected mice. Additionally, the number of the amastigote forms of Leishmania in the CL lesions was significantly reduced followingAECE therapy in infected mice (p<0.05). These findings demonstrate the considerable inhibitory and eliminatory effects of AECE on Leishmania in vivo and in vitro. Even though we have identified some cellular mechanisms of action for AECE, e.g. reducing the infectivity rate and the induction of NO production against Leishmania parasites, further experiments are essential to identify the specific mechanisms of action, assess safety, and determine its ability in animals and human subjects. [ABSTRACT FROM AUTHOR]

Background Cutaneous leishmaniasis (CL) is most common in childhood because children are exposed to the parasite early and, unlike adults, do not have immunity to CL. Since CL is less common in geriatric patients, clinical and epidemiological data in this age group are limited. This study aims to compare the clinical and demographic characteristics of geriatric patients diagnosed with CL with young patients. Methods In this retrospective study, 622 patients aged 65 and over and 6350 patients aged 19–64, who applied to Şanlıurfa Oriental Boil Diagnosis and Treatment Center between January 2013 and February 2024 and were diagnosed with CL by parasitological examination, were included. Clinical and demographic characteristics of patients diagnosed with CL, such as age, gender, location of the lesion, lesion size, duration of the lesion, and treatments applied due to the diagnosis of CL, were recorded. Clinical and demographic characteristics of geriatric and young patients were compared. Results The mean age of elderly CL cases was 72.95 ± 6.54 years, and 65.2% were female. The most common clinical forms were ulcers (51.9%) and plaques (41%), respectively, in young and elderly patients. The most common locations of the lesions were upper limbs (54.8%) in all patients. The most preferred treatment method was intralesional (IL) meglumine antimoniate (MA) treatment (98.3%) in all patients. There were no difference between young and elderly CL cases in terms of mean number of lesions, average lesion duration, average lesion size, lesion location, clinical forms of lesions, and treatments options (P  > 0.05). Conclusions Based on the results of our study, it can be said that the clinical and demographic characteristics of CL are similar in young and old patients and systemic MA treatment shows similar clinical benefit in both age groups. In addition, it can be said that systemic MA therapy can be used safely in young patients and elderly patients without contraindications. IL MA therapy can be used in elderly patients where systemic MA therapy is contraindicated. Key message What is already known on this topic? Cutaneous leishmaniasis is less common in geriatric patients, clinical and epidemiological data in this age group are limited. What this study adds? Clinical and demographic characteristics of cutaneous leishmaniasis are similar in young and old patients, and systemic MA treatment shows similar clinical benefit in both age groups. How this study might affect research, practice, or policy? Systemic MA therapy can be used safely in young patients and elderly patients without contraindications. [ABSTRACT FROM AUTHOR]

The accurate diagnosis and identification of Leishmania species are crucial for the therapeutic selection and effective treatment of leishmaniasis. This study aims to develop and evaluate the use of high-resolution melting curve analysis (HRM)-PCR for Leishmania species identification causing visceral leishmaniasis (VL), post-kala-azar dermal leishmaniasis (PKDL) and cutaneous leishmaniasis (CL) in the Indian subcontinent. Two multi-copy targets (ITS-1 and 7SL-RNA genes) were selected, and an HRM-PCR assay was established using L. donovani, L. major, and L. tropica standard strain DNA. The assay was applied on 93 clinical samples with confirmed Leishmania infection, including VL (n = 30), PKDL (n = 50), and CL (n = 13) cases. The ITS-1 HRM-PCR assay detected as little as 0.01 pg of template DNA for L. major and up to 0.1 pg for L. donovani and L. tropica. The detection limit for the 7SL-RNA HRM-PCR was 1 pg for L. major and 10 pg for L. donovani and L. tropica. The ITS-1 HRM-PCR identified 68 out of 93 (73.11%) leishmaniasis cases, whereas 7SL-RNA HRM-PCR could only detect 18 out of 93 (19.35%) cases. A significant correlation was observed between the kDNA-based low Ct values and ITS-1 HRM-PCR positivity in the VL (p = 0.007), PKDL (p = 0.0002), and CL (p = 0.03) samples. The ITS-1 HRM-PCR assay could identify Leishmania spp. causing different clinical forms of leishmaniasis in the Indian subcontinent, providing rapid and accurate results that can guide clinical management and treatment decisions. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) is a parasitic disease that affects individuals worldwide. An epidemiological observational population–cohort study was conducted on the basis of comprehensive research on CL incidence in Saudi and non-Saudi residents. The Ministry of Health recorded the incidence of CL between January 2020 and December 2022. The chi-square test was used to analyze the data and determine CL incidence rates in age-specific incidence rates (ASIRs) and gender between Saudi and non-Saudi residents in Saudi Arabia. The study found that between 2020 and 2022, there were 2280 cases of CL in Saudi Arabia, with 1367 and 913 cases in men and women, respectively. Of Saudi nationals, 64.26% and 12.91% were male and female, respectively. The frequency of CL was higher (87.09%) among non-Saudi residents than among Saudi nationals, with a statistically significant difference (P = 0.001) between the two groups. The ASIRs for CL were higher in patients aged 15–45 years. This study revealed variations in CL incidence rates among the 13 administrative regions; Qassim, followed by Aseer, Ha'il, and Madinah, had higher rates than the other regions. These findings indicate the need for targeted interventions and public health strategies to reduce the burden on CL, particularly among non-Saudi residents. [ABSTRACT FROM AUTHOR]

Currently, no safe vaccine against leishmaniasis is available. So far, different control strategies against numerous reservoir hosts and biological vectors have not been environment-friendly and feasible. Hence, employing medicinal components and conventional drugs could be a promising approach to developing novel therapeutic alternatives. This study aimed to explore diallyl sulfide (DAS), a dynamic constituent of garlic, alone and in a mixture with meglumine antimoniate (MAT as standard drug) using in vitro and animal model experiments against Leishmania major stages. The binding affinity of DAS and four major defense elements of the immune system (iNOS, IFN-ɣ, IL-12, and TNF-α) was used to predict the predominant binding mode for molecular docking configurations. Herein, we conducted a broad range of experiments to monitor and assess DAS and MAT potential treatment outcomes. DAS, combined with MAT, displayed no cytotoxicity and employed a powerful anti-leishmanial activity, notably against the clinical stage. The function mechanism involved immunomodulation through the induction of Th1 cytokine phenotypes, triggering a high apoptotic profile, reactive oxygen species (ROS) production, and antioxidant enzymes. This combination significantly decreased cutaneous lesion diameter and parasite load in BALB/c mice. The histopathological findings performed the infiltration of inflammatory cells associated with T-lymphocytes, particularly CD4+ phenotypes, as determined by biochemical markers in alleviating the amastigote stage and improving the pathological changes in L. major infected BALB/c mice. Therefore, DAS and MAT deserve further advanced therapeutic development and should be considered as possible candidates for treating volunteer cases with cutaneous leishmaniasis in designing an upcoming clinical trial. [ABSTRACT FROM AUTHOR]

Background: Localized cutaneous leishmaniasis (LCL) is a chronic ulcerating disease. A literature review identified inconsistencies in clinical trials. The aims of this study were to reach a consensus on the most important domains to measure when assessing LCL, agree on parameters to measure the domains, and develop a tool representing a Core Outcome Set (COS), for use in clinical assessment of LCL. Methodology & principal findings: A literature review was conducted to identify any existing COS for LCL embracing agreed Outcome Domains, i.e. what to measure and any Outcome Measurement Instruments (OMIs). As no COS was available, potential outcome domains for assessment of LCL were identified through an international collaborative approach using e-consultations and virtual discussions with expert stakeholders (n = 20) from geographically different LCL endemic countries. Subsequent judgmental validation process included a face-to-face multidisciplinary stakeholders' meeting adopting the Nominal Group Technique. A final consensual agreement on outcome domains and items required to measure these domains was established. "Clinical Cure" was defined as the ideal overall "General Concept". The five Core Outcome Domains included Signs capturing clinical morphology, diameter, and induration of an index lesion with the aid of a palpability score, Treatment Efficacy assessing percentage change in size of the lesion and re-epithelialization compared to baseline, Treatment Impact which included an investigator and patient visual analogue score, and Clinical Sequelae rating pigment change, atrophic and hypertrophic/keloid scars. It was agreed that two open-ended questions should be included to capture some aspects of Health-Related Quality of Life as a means of capturing a patient-focused approach. Conclusion: LeishCOM_LCL was generated to reflect a COS for LCL. This captured demographic details, agreed outcome domains and measures to assess these domains. Validation of LeishCOM_LCL will be reported in a separate paper. Development of a Patient Reported Outcome Measure will be considered in the future. Author summary: Localized cutaneous leishmaniasis (LCL) is a chronic ulcerating disease caused by the parasite Leishmania spp. Literature review identified inconsistencies in methods and parameters used to evaluate treatment/alternative-interventions resulting in difficulties in comparing new treatment/interventions in clinical trials. In our international consensual study, we adopted the face-to-face nominal group technique and a judgment process to identify domains key to assessment of LCL. Subsequent measures for each domain were used to form a Core Outcome Set (COS). LeishCOM_LCL was developed as an outcome measure instrument (OMI) to capture the COS incorporating existing and newly developed tools. "Clinical Cure" was agreed as the "General Concept" to be captured through five domains. It was agreed that "Signs" domain should capture clinical morphology, diameter, and induration of an index lesion with the aid of a palpability score. "Treatment Efficacy" was assessed by recording percentage change in size of the lesion and re-epithelialization compared to baseline. "Treatment Impact" was reflected through an investigator and the patient visual analogue score and "Clinical Sequelae" rated pigment change, atrophic/hypertrophic scars. Two open-ended questions were included to capture some aspects of "Health-Related Quality of Life". LeishCOM_LCL also records patient demographic details and was validated in a small cohort of patients. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis is a widespread parasitic infection in Ethiopia. Few studies have been conducted on knowledge, attitudes, and prevention practice related to cutaneous leishmaniasis, and the existing studies have been mainly without qualitative support. This study aimed to assess the knowledge, attitude, prevention practice and lived experience towards cutaneous leishmaniasis and associated factors among residents of the Kutaber district, Northeast Ethiopia. Methods: A convergent parallel mixed method was conducted among 636 residents (for quantitative) and 20 in-depth interview participants (for qualitative) of the Kutaber district from July 1 to August 15, 2022. Quantitative data were entered into Epi-Data version 4.6 and exported to SPSS version 25 for cleaning and analysis. ATLAS.ti software version 8.0 was used for the analysis of qualitative data. Results: The survey respondents in Kutaber district showed good knowledge (47.5%), a positive attitude towards (54.1%) and a good prevention practice (35.3%) regarding cutaneous leishmaniasis. Residents who were unable to read and write [AOR = 0.15] had lower odds to have good knowledge about cutaneous leishmaniasis. Residents aged >54.5 years [AOR = 0.33] had lower odds to have a positive attitude towards cutaneous leishmaniasis. Males [AOR = 1.76] had a good prevention practice towards cutaneous leishmaniasis. Five main study themes were formed following the qualitative analysis of the data. Conclusion: Residents of Kutaber district have a poor overall knowledge and prevention practice towards cutaneous leishmaniasis, despite having a positive attitude. The educational status of residents and years of residence were factors significantly associated with knowledge about cutaneous leishmaniasis. Age and years of residence were factors significantly associated with attitude towards cutaneous leishmaniasis. Gender, age, and household wealth were factors significantly associated with prevention practice towards cutaneous leishmaniasis. Cutaneous leishmaniasis in Kutaber is a true health problem. Author summary: Cutaneous leishmaniasis (CL), a prevalent disease caused by an intracellular protozoan transmitted by a vector, is a serious public health issue, particularly in Kutaber district, where it causes significant physical and psychosocial problems among the residents. Even though it is not fatal, cutaneous leishmaniasis can lead to complications, lifelong scar and disfigurement, resulting in social isolation and discrimination. We showed that this is strongly associated with the district residents' poor knowledge and prevention practice towards the disease. Cutaneous leishmaniasis, a true health problem of the community, is worsened due to limited efforts of healthcare professionals, limited roles played by the media in health information communication, budget problem, low attention given from the government, lack of information dissemination, and lack of awareness. This implied that there is a need of rigorous provision of health education on the cause, transmission mechanism, intermediate host, breeding site, sandfly vector, treatment and implementation of prevention strategies. [ABSTRACT FROM AUTHOR]

Purpose: To report a rare non-endemic case of Leishmania aethiopica in Washington DC. Case report: A 68-year-old female presented for a routine examination with a complaint of right upper eyelid lesions for the past 5 months. On examination, a cluster of elevated and erythematous lesions extending from the medial canthus to the brow area of the right eye were seen. Initial treatment with Valtrex based on a suspected viral etiology failed. Although a biopsy was recommended at this time, the patient declined, and subsequent workup included nasolacrimal duct irrigation, blood work to rule out autoimmune etiology, a course of doxycycline, and an MRI, which yielded no improvement. Upon progression of the lesions into persistent plaques on the eyelids, a punch biopsy was performed, confirming leishmaniasis. The patient was then started on a 28-day course of oral miltefosine which led to complete resolution of her symptoms. Conclusion: This case underlines the importance of a broad differential including non-endemic diseases, particularly in urban areas with frequent patient travel. Furthermore, the delayed punch biopsy in this case highlights the importance of patient counseling to ensure prompt diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) is a global public health problem caused by species on the genus Leishmania and is the most prevalent clinical form of leishmaniasis. The aim of this study was to develop a new LAMP assay for Leishmania sp. based on HSP70 gene and evaluate it clinically for molecular diagnosis of CL. The study was carried out in the following stages: i) design of primers based on HSP70 gene of Leishmania sp.; ii) evaluation of detection limit and analytical specificity; iii) estimation of the accuracy of LAMP-Leish/HSP70 assay for diagnosing CL. A total of 100 skin biopsy samples from patients, comprising 60 CL cases and 40 non-cases, were analyzed in this study. One LAMP assay using HSP70 gene as molecular target were standardized, and the observed detection limit was 100fg of L. braziliensis purified DNA. The LAMP-Leish/HSP70 assay was specific for Leishmania spp. The LAMP-Leish/HSP70 assay showed an accuracy of 92%, and positivity rates were not affected by lesion onset time or parasite load. This novel LAMP assay targeting the HSP70 gene of Leishmania sp. has the potential to be a useful tool to integrate into routine diagnosis for suspected cases of CL. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by Leishmania parasites, that can cause long-term chronic disabilities. The clinical presentation of CL varies in both type and severity. CL presents as three main clinical forms: localised lesions (localised cutaneous leishmaniasis, LCL); mucocutaneous leishmaniasis (MCL) that affects the mucosa of the nose or the mouth; or as disseminated not ulcerating nodules (diffuse cutaneous leishmaniasis, DCL). Here we recruited a cohort of CL patients in a newly established leishmaniasis treatment centre (LTC) in Lay Gayint, Northwest Ethiopia, and collected detailed demographic and clinical data. The results of our study show that more males than females present to the LTC to seek diagnosis and treatment. 70.2% of CL patients presented with LCL and 20.8% with MCL. A small number of patients presented with DCL, recidivans CL (a rare form of CL where new lesions appear on the edges of CL scars) or with a combination of different clinical presentations. The duration of illness varied from 1 month to 180 months. Over a third of CL patients had additional suspected CL cases in their household. Despite the majority of CL patients having heard about CL, only a minority knew about its transmission or that it could be treated. Most CL patients lived in areas where environmental factors known to be associated with the transmission of CL were present. This work highlights that CL is an important public health problem in Lay Gayint and emphasises the urgent need for more CL awareness campaigns, better health education and better disease management practices. Author summary: Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by species of the Leishmania parasite. It causes skin lesions that can be categorised into three main clinical presentations: i) localised cutaneous leishmaniasis (LCL), with one or several ulcerated lesions; ii) mucocutaneous leishmaniasis (MCL) that affects the mucosa of the nose or the mouth; iii) disseminated CL (DCL), that is characterised by widespread nodules. While LCL usually heals spontaneously, MCL and DCL require treatment; and patients often experience relapses. CL leaves disfiguring scars, that can result in societal stigmatisation. In this study, we recruited a cohort of CL patients in a newly established leishmaniasis treatment centre (LTC) in Lay Gayint, Northwest Ethiopia, and collected detailed demographic and clinical data. We found that most CL patients presented with LCL, followed by MCL, and that more males than females present to the LTC. The duration of illness varied from 1 to 180 months. Over a third of CL patients had additional suspected CL cases in their home. Despite most patients having heard about CL, only a minority knew about its transmission or that it could be treated. This work emphasises that CL is an important public health problem in this area of Ethiopia. [ABSTRACT FROM AUTHOR]

Background: Dogs are considered the main domestic animals that may be a reservoir for Leishmania infantum, the agent of zoonotic visceral leishmaniasis (ZVL) in several countries of the world. The dog may host other Leishmania species, but its epidemiological role in the maintenance and spreading of these parasites is not completely elucidated. Zoonotic cutaneous leishmaniasis (ZCL), caused by Leishmania major, affects thousands of people every year and is particularly diffused in many countries of North Africa and Middle East Asia. In ZCL endemic countries, few reports of L. major-positive dogs have been reported, probably because most human cases occur in poor rural areas where the social role of the dog and its medical management is not well considered. The aim of the present study is to better understand the possible involvement of domestic dogs in the epidemiology of ZCL. Methods: Our research focused on a well-established endemic focus of ZCL, in the area of Echrarda, Kairouan Governorate, central Tunisia. A total of 51 dogs with no or mild clinical signs of vector borne diseases were selected in small villages where human cases of ZCL are yearly present. All dogs were sampled for the Leishmania spp. diagnosis, by using the following procedures: blood sample for serology and buffy coat quantitative polymerase chain reaction (qPCR), popliteal fine needle aspiration, and cutaneous biopsy punch for lymph node and skin qPCR. Results: The results demonstrated a high percentage (21.6%) of dogs positive at least at one or more test; the most sensitive technique was the lymph node qPCR that detected 8/11 positive dogs. Nine, out of the eleven positive dogs, resulted as infected by Leishmania infantum; ITS1-PCR-sequencing allowed Leishmania major identification in the remaining two cases, both from the popliteal lymph node samples, which can suggest a possible visceral spread of a cutaneous Leishmania species in the dog. Interestingly, one of the two L. major-positive dogs was living in the same house where 6-year-old children showed cutaneous lesions referred to as ZCL. Conclusions: To our knowledge, this is the first report of L. major-positive dogs in Tunisia, the epidemiological role of which remains under investigation. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is a metabolic disorder that causes chronic high blood sugar levels, and diabetic patients are more susceptible to infections. American cutaneous leishmaniasis is an infectious disease caused by a parasite that affects the skin and mucous membranes, leading to one or multiple ulcerative lesions. Chronic inflammation and functional changes in various organs and systems, including the immune system, are the primary causes of both diseases. Melatonin, an essential immunomodulatory, antioxidant, and neuroprotective agent, can benefit many immunological processes and infectious diseases, including leishmaniasis. Although, limited reports are available on diabetic patients with leishmaniasis. The literature suggests that melatonin may play a promising role in inflammatory disorders. This study was designed to assess melatonin levels and inflammatory mediators in diabetic patients affected by leishmaniasis. Blood samples from 25 individuals were analyzed and divided into four groups: a control group (without any diseases), a Leishmania-positive group, patients with type 2 diabetes mellitus, and patients with a combination of both diseases. This study measured the serum levels of melatonin through ELISA, while IL-4 and TNF-α were measured using flow cytometry, and C-reactive protein was measured through turbidimetry. This study found that patients with leishmaniasis significantly increased TNF-α and decreased melatonin levels. However, the group of diabetic patients with leishmaniasis showed higher melatonin levels than the control group. These observations suggest that TNF-α may influence melatonin production in patients with American cutaneous leishmaniasis, potentially contributing to the inflammatory characteristics of both diseases. [ABSTRACT FROM AUTHOR]

Leishmania amazonensis causes a clinical form called diffuse cutaneous leishmaniasis (DCL) with challenges to treatment, like low efficiency and drug toxicity. Therefore, it is necessary to investigate new therapies using less toxic leishmanicidal compounds, such as flavonoids like naringenin, and their combination with conventional drugs, such as miltefosine. Antileishmanial dose/response activity, isobologram, calculation of dose reduction index (DRI), and fractional inhibitory concentration index (FICI) tests were performed on in vitro assays using reference promastigote forms of L. amazonensis (IFLA/BR/67/PH8) to assess the combinatorial effect between naringenin and miltefosine. The in vitro results of isobologram, DRI, and FICI calculations showed that the combination of the compounds had an additive effect and was able to reduce the half maximal inhibitory concentration (IC50) of miltefosine in the promastigote forms of the parasite compared to the treatment of the drug alone. This study demonstrated in vitro the viability of a combination action of the flavonoid with the treatment with miltefosine, opening space for further investigations on the association of natural compounds with the drugs used for the treatment of L. amazonensis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Cutaneous leishmaniasis is caused by protozoan parasites of the genus leishmania. Atypical presentation and widespread progression of the lesions may be seen in an immunocompromised patient. We report a case of atypical and widespread cutaneous leishmaniasis in a young woman with breast cancer. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Scalp lesions associated with psoriasis and cutaneous leishmaniasis can be clinically indistinguishable, leading to misdiagnosis. Herein, we highlight a 70‐year‐old male initially misdiagnosed with psoriasis but subsequently confirmed to have cutaneous leishmaniasis. This emphasizes the importance of considering alternative diagnoses, especially in atypical presentations, to ensure accurate treatment. [ABSTRACT FROM AUTHOR]

Disseminated leishmaniasis (DL) is an emergent severe disease manifesting with multiple lesions. To determine the relationship between immune response and clinical and therapeutic outcomes, we studied 101 DL and 101 cutaneous leishmaniasis (CL) cases and determined cytokines and chemokines in supernatants of mononuclear cells stimulated with leishmania antigen. Patients were treated with meglumine antimoniate (20 mg/kg) for 20 days (CL) or 30 days (DL); 19 DL patients were instead treated with amphotericin B, miltefosine, or miltefosine and meglumine antimoniate. High levels of chemokine ligand 9 were associated with more severe DL. The cure rate for meglumine antimoniate was low for both DL (44%) and CL (60%), but healing time was longer in DL (p = 0.003). The lowest cure rate (22%) was found in DL patients with >100 lesions. However, meglumine antimoniate/miltefosine treatment cured all DL patients who received it; therefore, that combination should be considered as first choice therapy. [ABSTRACT FROM AUTHOR]

Purpose: This case report examines the clinical presentation, diagnosis, treatment, and outcomes of mucocutaneous leishmaniasis with primary oral involvement in HIV-positive and HIV-negative patients diagnosed in Brazil. Methods: We discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, highlighting the clinical and histopathologic diagnostic features and distinct progression patterns based on HIV status. Our findings are compared with patterns observed in other countries, emphasizing the differences between the Americas and Europe, Asia, and Africa. Results: In the Americas, particularly in Brazil, mucocutaneous leishmaniasis often presents with localized oral lesions, even in the presence of systemic immunosuppression, whereas in the Europe, Asia, and Africa, oral involvement is typically associated with visceral leishmaniasis in immunocompromised patients. These differences were due to variations in the parasite species involved. Conclusion: This comparison underscores the importance of regional and immunological factors in diagnosing and managing this neglected infectious disease. [ABSTRACT FROM AUTHOR]

The article presents a study which assessed the in vitro efficacy of the Astragalus ecbatanus extract against both the promastigote and amastigote stages of Leishmania (L.) tropica (MHOM/AF/88/KK27). Topics discussed include the prevalence of leishmaniasis among both humand and animals worldwide, effect of extract on Leishmania tropica Amastigotes, and phytochemical analysis of the Astragalus ecbatanus methanolic extract.

Cutaneous leishmaniasis (CL) poses a significant public health concern in endemic regions due to its increasing prevalence and substantial impact on affected individuals. This disease is primarily caused by the Leishmania protozoa, which are transmitted through insect bites, and it manifests as a range of symptoms, from self-healing lesions to severe disfigurement. Current treatments, which often involve the parenteral administration of antimonials, face challenges such as poor compliance and adverse effects. This study investigates the efficacy of topical formulations containing meglumine antimoniate (MA) and amphotericin B (AmB), using Sepigel as an excipient, for treating CL. In the in vivo study, BALB/c mice infected with L. amazonensis developed lesions at the injection site five weeks post-infection. Subsequently, the mice were divided into eight groups: untreated mice, mice treated orally with miltefosine, mice treated intraperitoneally with MA, and mice treated topically with 15%, 22.5%, and 30% MA-Sepigel, as well as those treated with AmB-Sepigel. Treatments were applied daily for two weeks, and the results revealed a significant reduction in lesion size and parasite burden following topical application, particularly with the AmB-Sepigel formulations and 30% MA-Sepigel. Additionally, Sepigel-based treatments demonstrated improved patient compliance and reduced toxicity compared to systemic therapies. These findings underscore the potential of Sepigel-based formulations as a promising alternative for CL treatment. They offer enhanced efficacy and tolerability, while reducing the systemic toxicity associated with conventional therapies. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutaneous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG's cytotoxic effect on bone marrow-derived macrophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction in lesion size and the decrease in parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index = 432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and resulted in parasite clearance from ears and lymph nodes. It also diminished inflammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-γ, TNF) and the regulatory cytokine IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusions: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases. [ABSTRACT FROM AUTHOR]

Introduction: Exosomes produced by the protozoan parasite Leishmania (LeishEXO) are well-established drivers of virulence, though mechanisms underlying their exacerbation of experimental leishmaniasis remain elusive. Expression of Annexin A1 (ANXA1), a protein implicated in exosome-mediated pathologies and viral internalization, has been shown to correlate with cutaneous leishmaniasis severity. Given ANXA1's regulation of myeloid cells - the canonical hosts for Leishmania - we studied the potential role of ANXA1 and its receptors FPR1/2 in exerting LeishEXO's effects. Methods: Murine and in vitro ANXA1-/- models were used to study the generation of protective TH1 responses during experimental L. major infection with and without LeishEXO. Recruitment of inflammatory cells was assessed using a peritoneal cell recruitment assay and immunophenotyping, and production of inflammatory mediators was measured using a cytokine and chemokine array. Treatment of experimental models with FPR2 antagonist WRW4 and FPR1/2 agonist WKYMVm was used to delineate the role of the FPR/ANXA1 axis in LeishEXO-mediated hyperpathogenesis. Results: We established that ANXA1 deficiency prohibits LeishEXO-mediated pathogenesis and myeloid cell infection, with minimal alterations to adaptive and innate immune phenotypes. FPR2 blockade with WRW4 similarly inhibited leishmanial hyperpathogenesis, while direct activation of FPRs with WKYMVm enhanced infection and recapitulated the LeishEXO-mediated phenotype. This research describes LeishEXO's utilization of the ANXA1/FPR axis to facilitate parasitic internalization and pathogenesis, which may be leveraged in the development of therapeutics for leishmaniasis. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis (CL) is understudied in sub-Saharan Africa. The epidemiology of CL is determined by the species involved in its transmission. Our objectives were to systematically review available data on the species of Leishmania, along with vectors and reservoirs involved in the occurrence of human cases of CL in sub-Saharan Africa, and to discuss implications for case management and future research. Methods: We systematically searched PubMed, Scopus, Cochrane and African Index Medicus. There was no restriction on language or date of publication. The review was conducted according to PRISMA guidelines and was registered on PROSPERO (CRD42022384157). Results: In total, 188 published studies and 37 reports from the grey literature were included. An upward trend was observed, with 45.7% of studies published after 2010. East Africa (55.1%) represented a much greater number of publications than West Africa (33.3%). In East Africa, the identification of reservoirs for Leishmania tropica remains unclear. This species also represents a therapeutic challenge, as it is often resistant to meglumine antimoniate. In Sudan, the presence of hybrids between Leishmania donovani and strictly cutaneous species could lead to important epidemiological changes. In Ghana, the emergence of CL in the recent past could involve rare species belonging to the Leishmania subgenus Mundinia. The area of transmission of Leishmania major could expand beyond the Sahelian zone, with scattered reports in forested areas. While the L. major–Phlebotomus duboscqi–rodent complex may not be the only cycle in the dry areas of West Africa, the role of dogs as a potential reservoir for Leishmania species with cutaneous tropism in this subregion should be clarified. Meglumine antimoniate was the most frequently reported treatment, but physical methods and systemic agents such as ketoconazole and metronidazole were also used empirically to treat L. major infections. Conclusions: Though the number of studies on the topic has increased recently, there is an important need for intersectional research to further decipher the Leishmania species involved in human cases of CL as well as the corresponding vectors and reservoirs, and environmental factors that impact transmission dynamics. The development of molecular biology in sub-Saharan Africa could help in leveraging diagnostic and research capacities and improving the management of human cases through personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Pintomyia longiflocosa is considered a vector of etiological agents of cutaneous leishmaniasis. The objective of this research was to establish the parameters of the life cycle of Pi. longiflocosa in semi-controlled conditions in a rural area of the Campoalegre municipality, Huila, Colombia. Methodology/principal findings: The life cycle of individuals of Pi. longiflocosa, obtained from two cohorts of collected, fed, and individualized females, was monitored during two different times of the year (between February and August 2020 and between July 2020 and January 2021, respectively). Determining parameters associated with the fertility and fecundity, time and attributes of development and survival, and its association with abiotic variables. The average duration of Cycle 1 (C1) and Cycle 2 (C2) was 134.9 and 148.78 days, respectively. The gonotrophic cycle of parental females presented significant differences (p-value <0.05) between C1 and C2 (8.47 and 11.42 days) as well as between fecundity and fertility parameters. The number of days it takes the development of the immature stages between the two cycles studied, also showed significant differences in the larvae II (15.21 and 22.23), larvae III (11.93 and 17.56), and pupae (24.48 and 22.9) stages. During C1, the survival rate was higher and consistent with the productivity of adult individuals (F1), compared to C2. Fecundity and fertility values were significantly higher in C2. Finally, a significant correlation between the number of individuals and temperature was evidenced in C1 while, for C2, there was a negative correlation with precipitation. Conclusions/significance: Significant differences were found in several biological and reproductive parameters between the two cycles monitored. The parameters of the life cycle of Pi. longiflocosa in its natural habitat would be influenced by environmental factors related to the annual seasonality in the sub-Andean rural area, conditioning the temporal distribution of this species and, consequently, the possible transmission of causative agents of cutaneous leishmaniasis. Author summary: Cutaneous leishmaniasis (CL) is a public health disease that affects more than 300 million people in tropical areas in the world and its causative agent is a parasite of the genus Leishmania. In recent decades, the cases in Latin America have increased, corresponding to 6% of cases in the tropical regions of the planet. An insect potential vector associated with the transmission of CL in these tropical and endemic areas is Pintomyia longiflocosa. Therefore, it is very important to investigate the environmental parameters that can influence its life cycle and its vector competence and vector capacity, aspects that are not fully known. In Colombia, an endemic focus is located in the Huila state, in a rural area of the municipality of Campoalegre, where this study was carried out. The authors found the relationship between some environmental parameters with the life cycle of Pi. longiflocosa under semi-controlled conditions in forested habitats, aspects that were not known until now. The impact of temperature, relative humidity, and precipitation on the gonotrophic cycle, fecundity, fertility, time of development and survival, was evidenced. This research provides information on the environmental conditions that directly affect the possible transmission of the agents that cause cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

Background: American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce. We describe the clinical characteristics and outcome of patients with ACL imported to a tertiary centre in Germany and determine whether species-specific therapy according to the 2014 "LeishMan" group recommendations is associated with cure. Methods: A retrospective chart review was conducted at the Charité Institute of International Health in Berlin. We analysed data on PCR-confirmed ACL cases collected between 2000 and 2023. Systemic therapy included liposomal amphotericin B, miltefosine, pentavalent antimony, ketoconazole or itraconazole. Localized therapy included perilesional pentavalent antimony or paromomycin ointment. Cure was defined as re-epithelialization of ulcers or disappearance of papular-nodular lesions after 3 months of treatment. Logistic regression models were used to quantify the effect of species-specific systemic therapy on the outcome. Results: 75 cases were analysed. Most patients were male (62%), median age was 35 years, no patient had a history of immunosuppression. The most common reason for travel was tourism (60%), the most common destination was Costa Rica (28%), the median duration of illness was 8 weeks, and most patients presented with ulcers (87%). Lesions were complex in 43%. The most common Leishmania (L.) species was L. braziliensis (28%), followed by L. panamensis (21%). 51/73 (70%) patients were cured after initial therapy and 17/21 (81%) after secondary therapy. Cure after systemic therapy was more frequent when species-specific treatment recommendations were followed (33/45; 73%), compared to when not followed, (6/17; 35%, P = 0.008). This association was independent of age, sex, previous therapy, complex lesions, and Leishmania species (adjusted OR, 5.06; 95% CI, 1.22–24.16). Conclusions: ACL is a rare, imported disease in Germany. Complex lesions were common, challenging successful therapy. This study highlights the importance of identifying the parasite species and suggests that a species-specific approach to treatment leads to better outcomes. Author summary: American cutaneous leishmaniasis is a skin disease caused by parasites that are transmitted through the bite of sandflies. It is considered as a neglected tropical disease. In non-endemic countries like Germany, this disease is rarely seen and is imported by migrants or travellers who have been infected in tropical or subtropical areas of the Americas. Experts suggest that the treatment should be given depending on the specific parasite species found in the affected skin, but there is still a scarcity of information on the optimal management strategy. We analysed 75 American cutaneous leishmaniasis cases seen between 2000 and 2023 at our German medical centre. Most patients were men, around 35 years of age, who most commonly travelled to the Americas for tourism. We found that when using systemic medications (i.e., given by mouth, injection or drip into a vein), that were recommended for the specific parasite type, patients were more likely to be cured, with a 73% success rate, compared to a mere 35% success rate when those recommendations were not followed. This highlights the importance of identifying the species that is causing the disease, and suggests that tailoring treatment to the specific parasite species increases the chances of cure. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8+ T cell responses mediate disease. Although these responses originate in the lymph node, we found that expression of the cytolytic effector molecule granzyme B was restricted to lesional CD8+ T cells in Leishmania-infected mice, suggesting that local cues within inflamed skin induced cytolytic function. Expression of Blimp-1 (Prdm1), a transcription factor necessary for cytolytic CD8+ T cell differentiation, was driven by hypoxia within the inflamed skin. Hypoxia was further enhanced by the recruitment of neutrophils that consumed oxygen to produce ROS and ultimately increased the hypoxic state and granzyme B expression in CD8+ T cells. Importantly, lesions from patients with cutaneous leishmaniasis exhibited hypoxia transcription signatures that correlated with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8+ T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as for other inflammatory skin diseases in which cytolytic CD8+ T cells contribute to pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: Rare coexistence of disease or pathology Background: Leishmaniasis is a zoonosis with worldwide prevalence that causes dermal lesions and can be serious in humans. This report presents a case of cutaneous leishmaniasis (CL) that was apparently associated with a zoonotic transmission in a peri-urban area of the city of Portoviejo, Ecuador, close to mountainous and forested sites. Case Report: For 37 years, we have studied transmission of leishmaniasis in Ecuador, and have seen a wide variety of clinical presentations of the disease caused by different strains of the parasite Leishmania in patients, including pregnant women, without marked difference among them. CL without complications causes painless lesions of different clinical aspect. The present study reports a case of a 25-year-old woman presenting with severely inflamed, disseminated, and painful lesions of CL. The patient was not given antimonial treatment; however, local cryotherapy was given, together with topical anti-inflammatory and antibiotic ointment. All the lesions were observed to heal, and no amastigotes were found in smear stains after clinical healing. Since there was no reactivation after 1.5 years of follow-up, conventional antileishmanial treatment with meglumine antimoniate was not given to the patient. Conclusions: This report shows the importance of a properly done epidemiological and clinical presumtive diagnosis, followed by parasitological confirmation, and the benefit of using an alternative treatment for vulnerable patients, such as this pregnant woman, for whom the therapy with pentavalent antimonials is not indicated. All observed lesions healed and no amastigotes were found in the smears after clinical healing. [ABSTRACT FROM AUTHOR]

Background: Characterization of the host response in cutaneous leishmaniasis (CL) through proteome profiling has gained limited insights into leishmaniasis research compared to that of the parasite. The primary objective of this study was to comprehensively analyze the proteomic profile of the skin lesions tissues in patients with CL, by mass spectrometry, and subsequent validation of these findings through immunohistochemical methods. Methods: Eight lesion specimens from leishmaniasis-confirmed patients and eight control skin biopsies were processed for proteomic profiling by mass spectrometry. Formalin-fixed paraffin-embedded lesion specimens from thirty patients and six control skin specimens were used for Immunohistochemistry (IHC) staining. Statistical analyses were carried out using SPSS software. The chi-square test was used to assess the association between the degree of staining for each marker and the clinical and pathological features. Results: Sixty-seven proteins exhibited significant differential expression between tissues of CL lesions and healthy controls (p < 0.01), representing numerous enriched biological processes within the lesion tissue, as evident by both the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Among these, the integrated endoplasmic reticulum stress response (IERSR) emerges as a pathway characterized by the up-regulated proteins in CL tissues compared to healthy skin. Expression of endoplasmic reticulum (ER) stress sensors, inositol-requiring enzyme-1 (IRE1), protein kinase RNA-like ER kinase (PERK) and activating transcription factor 6 (ATF6) in lesion tissue was validated by immunohistochemistry. Conclusions: In conclusion, proteomic profiling of skin lesions carried out as a discovery phase study revealed a multitude of probable immunological and pathological mechanisms operating in patients with CL in Sri Lanka, which needs to be further elaborated using more in-depth and targeted investigations. Further research exploring the intricate interplay between ER stress and CL pathophysiology may offer promising avenues for the development of novel diagnostic tools and therapeutic strategies in combating this disease. [ABSTRACT FROM AUTHOR]

Background Cutaneous leishmaniasis (CL) is highly prevalent in developing countries, including Pakistan. The conventional treatment for CL, meglumine antimoniate (MA), is unfortunately associated with considerable toxicity. Studies of alternative treatment options have reported inconsistent Results. This study aimed to quantitatively compare the effectiveness of intramuscular MA with oral chloroquine in the treatment of CL. Methods Patients of both genders between the ages of 06-60 years, presenting with CL lesions of less than 03 months duration were enrolled in this randomized controlled trial (RCT), carried out from August 2021 to February 2022 at the Department of Dermatology, Lady Reading Hospital, Peshawar. CL patients with a history of prior treatment and/or those with comorbidities were excluded. Eligible patients were allocated randomly into two groups, where patients in Group I were given intramuscular MA (20 mg/Kg body weight once daily for 4 weeks) while patients in Group II were given oral chloroquine (250 mg, twice daily over 4 weeks). The treatment response was assessed at 4-week follow-up after completion of the treatment. Results The enrolled CL patients (n=82) were equally divided in two groups. The age and gender was evenly distributed between the two groups. The mean patient's age in Group I and II was 36.49±13.22 years and 37.34±13.19 years, whilst the male to female ratio was 1.28 and 1.16, respectively. Results showed a significantly higher rate of complete treatment response in Group I compared to Group II (78% vs. 48.8%, p=0.006). Treatment responses in both groups were also stratified on the basis of gender and socioeconomic status. Conclusion This study indicated significantly higher efficacy of intramuscular MA compared to oral chloroquine for CL treatment. [ABSTRACT FROM AUTHOR]

Atypical presentations of cutaneous leishmaniasis include sporotrichoid leishmaniasis (LS), clinically described as a primary ulcer associated with lymphangitis and nodules, with or without ulcerated lesions along its course. In a city like Rio de Janeiro, where both leishmaniasis and sporotrichosis can coexist, this poses a significant challenge for dermatologists. Atypical presentations of cutaneous leishmaniasis include sporotrichoid leishmaniasis (LS), clinically described as a primary ulcer associated with lymphangitis and nodules, with or without ulcerated lesions along its course. In a city like Rio de Janeiro, where both leishmaniasis and sporotrichosis can coexist, this poses a significant challenge for dermatologists. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) is a neglected public health problem in developing countries including Iran. CL is caused by different species of Leishmania parasites and results in morbidity and complications in patients with active lesions. Since protozoa are intracellular parasites, cellular immunity plays an essential role in controlling the infection. Cellular immunity is induced immediately after the infection and persists for many years after recovery. Studies over the past decades have identified the important role of CD4+ T cells and their T-helper subtypes in the immune response to CL. Finding antigens capable of producing Th1-dominant immune responses can play an effective role in preventing CL. This study examines the protective role of phosphoenolpyruvate carboxykinase (PEPCK), a critical enzyme for protozoan survival and reproduction. The potential of targeting PEPCK for the development of novel prevention strategies against Chagas disease is explored. Detailed findings presented herein underscore the critical role of PEPCK as an immunogenic antigen in parasite metabolism, gluconeogenesis, and energy homeostasis. Notably, the elimination of PEPCK alters parasite metabolic activity and attenuates Leishmania pathogenicity. These results position PEPCK as a promising vaccine candidate and therapeutic target for CL, pending further validation. [ABSTRACT FROM AUTHOR]

Background: We aimed to analyze a four-year trend of Cutaneous leishmaniasis (CL) to determine risk levels and hotspots in North-central Ethiopia. Methods: This retrospective study was conducted at Boru Meda Hospital (BMH) from March to April 2023, focusing on CL patients treated at the leishmaniasis treatment center (LTC). Data collected included age, gender, CL type, and other clinical factors. Each patient's origin was traced and geographically mapped by elevation to assess CL risk levels. Results: There were a total of 573 CL patients reported from 46 districts, with a higher number of male patients (n=356) compared to female patients (n=217) (P <0.001). The median age of the patients was 21 years [15-30], with the highest number of CL cases observed among individuals aged 16 to 30 years. The majority of cases (69%) presented with localized CL (LCL). About 39% of patients had a previous treatment history for CL. A significant clustering of CL cases was observed at elevation of 2301-3300 meters above sea level (χ²:17.5; P <0.001), with the highest incidence (case notification) of 14.2/100,000 population. Conclusion: Foci of CL, were burdened at higher elevations and no clinical variation were observed between elevation differences. The majority of cases were concentrated in an area covering approximately 21.4% of the total land mass. CL continues to be a significant issue in North-central Ethiopia and has the potential to spread to new areas. [ABSTRACT FROM AUTHOR]

Background: The lack of complete protection against leishmaniasis and the challenges of anti-leishmaniasis drug treatment have made the treatment process more difficult. This study aimed to develop a new strategy for preparing a vaccine against cutaneous leishmaniasis using some of the antigenic proteins of the Leishmania parasite. Methods: This study was carried out in 2022 at Shahid Chamran University of Ahvaz, Ahvaz, Iran. After preparing suitable epitopes of the Leishmania parasite and examining their antiparasitic properties, the process of making a fusion vaccine was performed and with the help of various bioinformatics tools, physicochemical and structural properties as well as immunological and simulation properties were studied and finally optimized. Construction and cloning were performed in the E.coli K12 system and finally, the docking process was performed with Toll-like receptors (TLRs), major histocompatibility complex I (MHC-I), and MHC-II receptors. With the help of selected epitopes of the Leishmania parasite, which had a high percentage of population coverage, a stable, antigenic, and non-allergenic chimeric vaccine was predicted. Results: The results of the structural analysis of the TLR5\vaccine complex and simulation of its molecular dynamics showed a sufficiently stable binding. It also showed good potential for stimulation and production of active B cells and memory, as well as the potential for CD8+ T, CD4+ T cell production and development of Th2 and Th1-induced immune responses. Conclusion: Computational results showed that the designed immunogenic structure has the potential to adequately stimulate cellular and humoral immune responses against Leishmania parasitic disease. As a result of evaluating the effectiveness of the candidate vaccine through in vivo and in vitro immunological tests, it can be suggested as a vaccine against Leishmania major. [ABSTRACT FROM AUTHOR]

Introduction: Casiopeina III-ia (CasIII-ia) is a mixed chelate copper (II) compound capable of interacting with free radicals generated in the respiratory chain through redox reactions, producing toxic reactive oxygen species (ROS) that compromise the viability of cancer cells, bacteria and protozoa. Due to its remarkable effect on protozoa, this study evaluated the effect of CasIII-ia on Leishmania mexicana amastigotes and its potential use as a treatment for cutaneous leishmaniasis in the murine model. Methods: We analyzed the leishmanicidal effect of CasIII-ia on L. mexicana amastigotes and on their survival in bone marrow-derived macrophages. Furthermore, we evaluated the production of ROS in treated parasites and the efficacy of CasIII-ia in the treatment of mice infected with L. mexicana. Results: Our results show that CasIII-ia reduces parasite viability in a dose-dependent manner that correlates with increased ROS production. A decrease in the size of footpad lesions and in parasite loads was observed in infected mice treated with the intraperitoneal administration of CasIII-ia. Conclusions: We propose CasIII-ia as a potential drug for the treatment of cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

Objectives: In Pakistan, cutaneous leishmaniasis is an emerging tropical disease and a very high number (>70%) of children are afflicted by this marring infection. This study aimed to scrutinise the prevalence, spatial distribution and socio‐demographic and behavioural risk factors associated with cutaneous leishmaniasis in children aged <5–15 years in Khyber Pakhtunkhwa. Methods: A total of 1, 559 clinically confirmed records of children diagnosed with cutaneous leishmaniasis (January–December) from 2020 and 2022 were obtained from selected district hospitals. In addition, a risk factors‐related questionnaire was administered to 1, 011 households (400 in 2020 and 611 in 2022) in nine districts during a household survey. Results: The maximum number of cutaneous leishmaniasis cases was recorded in 2022 (n = 877, 56.25%) as compared to 2020 (n = 682, 43.75%). The hospital records showed a greater number of male patients in the 2022 cohort (n = 603, 68.76%). The highest number of cases were observed in children aged 5–9 years in 2022 (n = 282, 32.16%) and 2020 (n = 255, 37.39%). In 2020 and 2022, cutaneous leishmaniasis cases showed peak aggregation in March (n = 118, 17.3%) and January (n = 322, 36.72%). From a spatial analysis, the maximum number of cutaneous leishmaniasis cases was recorded at 59–1700 m elevation in various land‐use/land‐cover and climatic regions with quaternary alluvium rock formations. A multivariate logistic regression model analysis of risk factors from the households survey suggested that age group, socio‐economic status, construction materials of the house, use of insect repellents, Afghan refugee camps in the village/district, knowledge and biting times of sand flies, frequent use of mosquito bed nets, presence of domestic animals in the house, knowledge of the transmission period and peak month of leishmaniasis infection increased the risk of acquiring cutaneous leishmaniasis (p value < 0.05). Conclusion: Our analysis demonstrated that cutaneous leishmaniasis in children is influenced by a variety of environmental, socio‐demographic and behavioural risk factors in Khyber Pakhtunkhwa. The increase in recorded cases of cutaneous leishmaniasis in children in 2022 compared to 2020 suggests that the infection likely extended to new foci in the province. [ABSTRACT FROM AUTHOR]

American cutaneous leishmaniasis is a disease caused by protozoa of the genus Leishmania. Currently, meglumine antimoniate is the first-choice treatment for the disease. The limited efficacy and high toxicity of the drug results in the necessity to search for new active principles. Nanotechnology is gaining importance in the field, since it can provide better efficacy and lower toxicity of the drugs. The present study aimed to synthesize, characterize, and evaluate the in vitro leishmanicidal and antileukemic activity of bismuth nanoparticles (BiNPs). Promastigotes and amastigotes of L. (V.) guyanensis and L. (L.) amazonensis were exposed to BiNPs. The efficacy of the nanoparticles was determined by measurement of the parasite viability and the percentage of infected cells, while the cytotoxicity was characterized by the colorimetry. BiNPs did not induce cytotoxicity in murine peritoneal macrophages and showed better efficacy in inhibiting promastigotes (IC50 < 0.46 nM) and amastigotes of L. (L.) amazonensis. This is the first report on the leishmanicidal activity of Bi-based materials against L. (V.) guayanensis. BiNPs demonstrated significant cytotoxic activity against K562 and HL60 cells at all evaluated concentrations. While the nanoparticles also showed some cytotoxicity towards non-cancerous Vero cells, the effect was much lower compared to that on cancer cells. Treatment with BiNPs also had a significant effect on inhibiting and reducing colony formation in HL60 cells. These results indicate that bismuth nanoparticles have the potential for an inhibitory effect on the clonal expansion of cancer cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cutaneous leishmaniasis is endemic in Iran. OBJECTIVE: We sought to investigate the therapeutic outcomes and complications of treatment in patients with cutaneous leishmaniasis. METHODS: This case series enrolled patients with smear-proven cutaneous leishmaniasis who visited our center in Iran from 2018 to 2019. RESULTS: In total, 36 patients were treated with intralesional meglumine antimoniate, intramuscular meglumine antimoniate, sodium stibogluconate, and amphotericin B. Overall, this treatment was effective in 81.8 percent of patients. Relapse and treatment failure occurred in 6.1 percent and 12.1 percent of patients, respectively. Treatment with intralesional meglumine antimoniate, intramuscular meglumine antimoniate, sodium stibogluconate, and amphotericin B yielded a clearance rate of 80.8 percent, 92.3 percent, 75 percent, and 85.7 percent, respectively. Clearance was associated with a shorter time interval between injections of intralesional meglumine antimoniate (p=0.006) and relapse was associated with a longer time interval between injections (p=0.018). The average number of side effects per patient for intralesional meglumine antimoniate, sodium stibogluconate, intramuscular meglumine antimoniate, and amphotericin B was 0.62, 1.4, 1.6, and 2.8, respectively. The most common side effect of intralesional meglumine antimoniate, intramuscular meglumine antimoniate, and amphotericin B was local pain, arthralgia, and hypokalemia, respectively. LIMITATIONS: Low sample size was the limitation of this study. CONCLUSION: The cure rate of intramuscular meglumine antimoniate was higher than amphotericin B, which was higher than the cure rate of sodium stibogluconate. In patients treated with intralesional meglumine antimoniate, reducing the time interval between injections increased the clearance rate and decreased the rate of relapse. [ABSTRACT FROM AUTHOR]

Introduction: This study sought to analyze the relationships between cutaneous leishmaniasis and its epidemiological, environmental and socioeconomic conditions, in the 22 microregions of Pará state, Brazil, for the period from 2017 to 2022. Methodology: In this ecological and exploratory study, the microregions were used as spatial units because they are formed by contiguous municipalities with similar characteristics. The epidemiological, environmental, socioeconomic, and public health policy data employed were obtained from the official information systems at the Ministry of Health, National Institute for Space Research, and Brazilian Institute of Geography and Statistics. A fuzzy system was developed to identify risk factors for the disease, using Python programming language. The results were analyzed with the bivariate Global Moran spatial analysis technique. Results: It was observed that the Altamira microregion had the highest risk percentage for the disease, while Breves had the lowest, with significant differences in the relevance of its conditioning factors, mainly related to land use and cover patterns, in addition to demography and living conditions index, education and public health policies. Conclusions: The fuzzy system associated with the geostatistical technique was satisfactory for identifying areas with health vulnerability gradients related to deforestation, pasture, poverty, illiteracy, and health services coverage, as its conditioning variables. Thus, it was demonstrated that deforestation was the main risk factor for the disease. The system can also be used in environmental and epidemiological surveillance. [ABSTRACT FROM AUTHOR]

Background: Infections are complications in the wound healing process, and their treatment can lead to antibiotic overuse and bacterial resistance. Antimicrobial photodynamic therapy (aPDT) is used to treat infectious diseases caused by fungi, viruses, or bacteria. Methylene blue (MB) and its derivatives are commonly used dyes in antimicrobial photodynamic therapy (aPDT–MB). Methods: This study is a PRISMA systematic review of animal models used to discuss the usefulness and therapeutic parameters of aPDT–MB or its derivatives for treating infected skin wounds. Results: After an extensive literature review, 13 controlled trials totaling 261 animals were selected to evaluate skin infection by leishmaniasis and cutaneous bacterial and fungal infections. All studies found results favoring the use of aPDT–MB. Great variability in parameters was found for radiant exposure from 12 to 360 J/cm2, MB diluted in saline solution or distilled water, irradiation time from 40 to 3600 s, irradiance most commonly at a maximum of 100 mW/cm2, and wavelength used mainly in the 630–670 nm range. Conclusion: MB is a safe and promising agent used as a photosensitizer in aPDT for skin‐infected lesions. There is great variability in the parameters found. Comparisons concerning concentration, irradiation time, and light intensity need to be performed. [ABSTRACT FROM AUTHOR]

Introduction Post-kala-azar dermal leishmaniasis (PKDL) arises as a dermal complication following a visceral leishmaniasis (VL) infection. Current treatment options for PKDL are unsatisfactory, and there is a knowledge gap regarding the distribution of antileishmanial compounds within human skin. The present study investigated the skin distribution of miltefosine in PKDL patients, with the aim to improve the understanding of the pharmacokinetics at the skin target site in PKDL. Methods Fifty-two PKDL patients underwent treatment with liposomal amphotericin B (20 mg/kg) plus miltefosine (allometric dosing) for 21 days. Plasma concentrations of miltefosine were measured on study days 8, 15, 22 and 30, while a punch skin biopsy was taken on day 22. A physiologically based pharmacokinetic (PBPK) model was developed to evaluate the distribution of miltefosine into the skin. Results Following the allometric weight-based dosing regimen, median miltefosine concentrations on day 22 were 43.73 µg/g (IQR: 21.94–60.65 µg/g) in skin and 33.29 µg/mL (IQR: 25.9–42.58 µg/mL) in plasma. The median individual concentration ratio of skin to plasma was 1.19 (IQR: 0.79–1.9). In 87% (45/52) of patients, skin exposure was above the suggested EC90 PK target of 10.6 mg/L associated with in vitro susceptibility. Simulations indicated that the residence time of miltefosine in the skin would be more than 2-fold longer than in plasma, estimated by a mean residence time of 604 versus 266 hours, respectively. Conclusion This study provides the first accurate measurements of miltefosine penetration into the skin, demonstrating substantial exposure and prolonged retention of miltefosine within the skin. These findings support the use of miltefosine in cutaneous manifestations of leishmaniasis. In combination with parasitological and clinical data, these results are critical for the future optimization of combination therapies with miltefosine in the treatment of PKDL. [ABSTRACT FROM AUTHOR]

This article explores the field of immunology and its connection to inborn errors of immunity (IEI) and protozoa. IEI refers to a range of diseases caused by genetic defects that affect the immune system, making individuals more susceptible to infections. The article emphasizes the need to understand the characteristics of the disease and the infective agent to identify compromised immune mechanisms. It also discusses the global health challenges posed by neglected tropical diseases (NTDs) and their impact on marginalized populations. The article presents a case study of a child with an inborn error of immunity and unusual infections, highlighting the need for innovative diagnostic assays and treatment protocols. The case underscores the importance of collaboration among immunologists in Brazil to enhance diagnostic capabilities and improve patient care for uncommon infections. [Extracted from the article]

Cutaneous leishmaniasis (CL) is often considered a ‘great imitator’ and is the most common form of leishmaniasis. The Leishmania species responsible for CL varies among countries, as these species exhibit specific distribution patterns. The increased mobility of people across countries has resulted in the imported incidences of leishmaniasis caused by non-endemic species of Leishmania. During 2023, we confirmed three CL cases caused by L. major from Kerala, India, and upon detailed investigation, these were identified to be imported from the Middle East and Kazakhstan regions. This is the first report of CL caused by L. major from Kerala. The lesion morphology, detection of anti-rK 39 antibody and Leishmania parasite DNA from the blood samples were the unique observations of these cases. Kerala, being an emerging endemic zone of visceral leishmaniasis (VL) and CL, the imported incidences of leishmaniasis by non-endemic species can pose a significant threat, potentially initiating new transmission cycles of leishmaniasis caused by non-endemic species. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a neglected parasitic disease. Numerous studies suggested that nanoemulsions could improve drug delivery in the treatment of zoonotic cutaneous leishmaniasis. This study aims to determine the effect of chitosan-coated nanoemulsions of ozonated olive oil on Leishmania major promastigote/amastigote in vitro. Nanoemulsions (NEs) were prepared using a sonicator bath at 37 °C for one hour at 1000 W, followed by 24 hours of stirring at pH 5.5. The NE was then supplemented with chitosan and stirred all night long at a low speed. Droplet size, zeta potential, in vitro drug release, and cytotoxicity were examined to optimize the chitosan nanoemulsions (CNE) and chitosan ozonated nanoemulsions (CONE). CONE and CNE were found to have droplet sizes and zeta potentials of 16.86 nm, 19.03 nm, 19.7 mV, and 19.3 mV, respectively. Additionally, the final CONE's drug loading and encapsulation efficiency were determined to be 100% and 3.21%, respectively. The lower doses of CONE had no cytotoxic effects on macrophages. Additionally, it has the ability to inhibit L. major promastigote/amastigote growth. Therefore, the lower doses of the CONE formulation can inhibit the growth of promastigote and amastigote of L. major in vitro while not being toxic to macrophages. [ABSTRACT FROM AUTHOR]

Introduction: Pathogenesis of cutaneous leishmaniases involves parasite growth, persistent inflammation, and likely participation of lipoproteins (LP). The cholesteryl ester transfer protein (CETP), involved in LP remodeling, has been shown to participate in the inflammatory response and the evolution of infectious conditions. Methods: We evaluated the impact of the presence of CETP on infection by Leishmania (L.) amazonensis in an experimental model of cutaneous leishmaniasis using C57BL6/J mice transgenic for human CETP (CETP), having as control their littermates that do not express the protein, wild-type (WT) mice. The progression of the lesion after infection in the footpad was monitored for 12 weeks. Two groups of animals were formed to collect the plantar pad in the 4th and 12th week post-infection. Results: The lesion increased from the 3rd week onwards, in both groups, with a gradual decrease from the 10th week onwards in the CETP group compared to the WT group, showing a reduction in parasitism and an improvement in the healing process, a reduction in CD68+ cells, and an increase in CD163+ and CD206, characterizing a population of M2 macrophages. A reduction in ARG1+ cells and an increase in INOS+ cells were observed. During infection, the LP profile showed an increase in triglycerides in the VLDL fraction in the CETP group at 12 weeks. Gene expression revealed a decrease in the CD36 receptor in the CETP group at 12 weeks, correlating with healing and parasite reduction. In vitro, macrophages derived from bone marrow cells from CETP mice showed lower parasite load at 48 h and, a reduction in arginase activity at 4 h accompanied by increased NO production at 4 and 24 h compared to WT macrophages, corroborating the in vivo findings. Discussion: The data indicate that the presence of CETP plays an important role in resolving Leishmania (L.) amazonensis infection, reducing parasitism, and modulating the inflammatory response in controlling infection and tissue repair. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) is a tropical disease endemic in many parts of the world. Characteristic clinical manifestations of CL include the formation of ulcerative skin lesions that can inflict life-long disability if left untreated. Although drugs are available, they are unaffordable and out of reach for individuals who need them the most. Developing a highly cost-efficient CL vaccine could address this problem but such a vaccine remains unavailable. Here, we developed a chimeric influenza virus-like particle expressing the Leishmania amazonensis promastigote surface antigen (LaPSA-VLP). LaPSA-VLPs were self-assembled in Spodoptera frugiperda insect cell lines using the baculovirus expression system. After characterizing the vaccines and confirming successful VLP assembly, BALB/c mice were immunized with these vaccines for efficacy assessment. Sera acquired from mice upon subcutaneous immunization with the LaPSA-VLP specifically interacted with the L. amazonensis soluble total antigens. LaPSA-VLP-immunized mice elicited significantly greater quantities of parasite-specific IgG from the spleens, popliteal lymph nodes, and footpads than unimmunized mice. LaPSA-VLP immunization also enhanced the proliferation of B cell populations in the spleens of mice and significantly lessened the CL symptoms, notably the footpad swelling and IFN-γ-mediated inflammatory response. Overall, immunizing mice with the LaPSA-VLPs prevented mice from developing severe CL symptoms, signifying their developmental potential. [ABSTRACT FROM AUTHOR]

Understanding the distribution of tegumentary leishmaniasis (TL) in different periods enables the adequate conduction of actions at the public health level. The present study analyzes the spatiotemporal evolution of TL incidence rates in the municipalities of Brazil and identifies priority areas from 2001 to 2020. Notifications of new cases were analyzed employing space-time scan statistics and Local Indicators of Spatial Association. As TL incidence rates presented a downward trend in most Brazilian municipalities, spatiotemporal clusters of high relative risks (RR) were more frequent in the first decade of the series. There was a concentration of those clusters in the North and Northeast regions, mainly in the Legal Amazon area. More recent high-RR areas were identified in municipalities of different regions. The number of priority municipalities showed a stable trend in Brazil. There was a great concentration of such municipalities in the states of Acre, Mato Grosso, Rondônia, Pará, and Amapá, as well as large areas in Roraima, Amazonas, Maranhão, and Tocantins, and smaller areas in the states of Goiás, Ceará, Bahia, Minas Gerais, São Paulo, and Paraná. The present study contributes to the understanding of the historical evolution of TL in Brazil and subsidizes actions to combat the disease. [ABSTRACT FROM AUTHOR]

Phlebotomus argentipes is the predominant sandfly vector of leishmaniasis in the Indian subcontinent. India and Sri Lanka primarily report visceral and cutaneous leishmaniasis caused by Leishmania donovani. We compared Ph. argentipes from two locations, focusing on its morphological, molecular, and salivary protein characteristics. Sandflies were captured using CDC light traps and cattle-baited net traps. Species identification and morphological comparisons were carried out using standard taxonomic keys. DNA extracted from 12 Sri Lankan sandfly samples was PCR-amplified and sequenced for the variable region of Cytochrome oxidase subunit I. Existing DNA sequences of India from GenBank were utilized for a phylogenetic analysis between Sri Lanka and India. Salivary protein profiles were studied using SDS-PAGE, Western blot, and electrospray ionization/LC/MS/MS. The morphological similarities observed between female Ph. argentipes from India and Sri Lanka suggest the presence of Ph. argentipes var. glaucus. A phylogenetic analysis showed genetic divergence between Ph. argentipes populations, but both shared a similar salivary protein profile. A common, strong 30 kDa immunogenic band comprised PagSP05, PagSP06, and PagSP17 proteins of Ph. argentipes. The similarity between the immunogenic salivary proteins suggests their potential use as common markers for vector exposure or immune response stimulants across regions. The use of multiple samples for each category of serum would improve the comprehensiveness of the immunogenic profiles obtained. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a group of infectious diseases transmitted to humans during vector bites and caused by protozoans of the genus Leishmania. Conventional therapies face challenges due to their serious side effects, prompting research into new anti-leishmania agents. In this context, we investigated the effectiveness of morolic acid, a pentacyclic triterpene, on L. amazonensis promastigotes and amastigotes. The present study employed the MTT assay, cytokine analysis using optEIATM kits, an H2DCFDA test, and nitric oxide dosage involving nitrite production and Griess reagent. Morolic acid inhibited promastigote and axenic amastigote growth forms at IC50 values of 1.13 µM and 2.74 µM, respectively. For cytotoxicity to macrophages and VERO cells, morolic acid obtained respective CC50 values of 68.61 µM and 82.94 µM. The compound causes damage to the parasite membrane, leading to cellular leakage. In the infection assay, there was a decrease in parasite load, resulting in a CI50 of 2.56 µM. This effect was associated with immunomodulatory activity, altering macrophage structural and cellular parasite elimination mechanisms. Morolic acid proved to be an effective and selective natural compound, making it a strong candidate for future in vivo studies in cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]