Leishmaniasis is a neglected tropical parasitic disease with few approved medications. Cutaneous leishmaniasis (CL) is the most frequent form, responsible for 0.7 - 1.0 million new cases annually worldwide. Leukotrienes are lipid mediators of inflammation produced in response to cell damage or infection. They are subdivided into leukotriene B4 (LTB4) and cysteinyl leukotrienes LTC4 and LTD4 (Cys-LTs), depending on the enzyme responsible for their production. Recently, we showed that LTB4 could be a target for purinergic signaling controlling Leishmania amazonensis infection; however, the importance of Cys-LTs in the resolution of infection remained unknown. Mice infected with L. amazonensis are a model of CL infection and drug screening. We found that Cys-LTs control L. amazonensis infection in susceptible (BALB/c) and resistant (C57BL/6) mouse strains. In vitro, Cys-LTs significantly diminished the L. amazonensis infection index in peritoneal macrophages of BALB/c and C57BL/6 mice. In vivo, intralesional treatment with Cys-LTs reduced the lesion size and parasite loads in the infected footpads of C57BL/6 mice. The anti-leishmanial role of Cys-LTs depended on the purinergic P2X7 receptor, as infected cells lacking the receptor did not produce Cys-LTs in response to ATP. These findings suggest the therapeutic potential of LTB4 and Cys-LTs for CL treatment.

To investigate the relationship of cutaneous leishmaniasis isolates from Sri Lanka to known species, we performed DNA sequencing and microsatellite analyses. We identified Leishmania donovani as the agent of Sri Lanka cutaneous leishmaniasis and showed that these parasites are closely related to those causing visceral leishmaniasis in the Indian subcontinent.

Cutaneous leishmaniasis (CL) is a neglected tropical disease causing a range of skin lesions for which safe and efficacious drugs are lacking. Oleylphosphocholine (OLPC) is structurally similar to miltefosine and has previously demonstrated potent activity against visceral leishmaniasis. We here present the in vitro and in vivo efficacy of OLPC against CL-causing Leishmania species.

Although a great deal of knowledge has been gained from studies on the immunobiology of leishmaniasis, there is still no universally acceptable, safe, and effective vaccine against the disease. This strongly suggests that we still do not completely understand the factors that control and/or regulate the development and sustenance of anti-Leishmania immunity, particularly those associated with secondary (memory) immunity. Such an understanding is critically important for designing safe, effective, and universally acceptable vaccine against the disease. Here we review the literature on the correlate of protective anti-Leishmania immunity and vaccination strategies against leishmaniasis with a bias emphasis on experimental cutaneous leishmaniasis.

Approximately 6,000 cases of cutaneous leishmaniasis are reported annually in Colombia, a greater than twofold increase since the 1980s. Such reports certainly underestimate true incidence, and their geographic distribution is likely biased by local health service effectiveness. We investigated how well freely available environmental data explain the distribution of cases among 1,079 municipalities. For each municipality, a unique predictive logistic regression model was derived from the association among remaining municipalities between elevation, land cover (preclassified maps derived from satellite images), or both, and the odds of at least one case being reported. Land cover had greater predictive power than elevation; using both datasets improved accuracy. Fitting separate models to different ecologic zones, reflecting transmission cycle diversity, enhanced the accuracy of predictions. We derived measures that can be directly related to disease control decisions and show how results can vary, depending on the threshold selected for predicting a disease-positive municipality. The results identify areas where disease is most likely to be underreported.

In this study, we used proteomics and biological network analysis to evaluate the potential biological processes and components present in the identified proteins of biopsies from cutaneous leishmaniasis (CL) patients infected by Leishmania braziliensis in comparison with normal skin. We identified 59 proteins differently expressed in samples from infected and normal skin. Biological network analysis employing identified proteins showed the presence of networks that may be involved in the cell death mediated by cytotoxic T lymphocytes. After immunohistochemical analyses, the expression of caspase-9, caspase-3, and granzyme B was validated in the tissue and positively correlated with the lesion size in CL patients. In conclusion, this work identified differentially expressed proteins in the inflammatory site of CL, revealed enhanced expression of caspase-9, and highlighted mechanisms associated with the progression of tissue damage observed in lesions.

Cutaneous leishmaniasis (CL) is endemic in many parts of the world with a high economic and health impact. Despite many treatments that have been suggested for this zoonotic infection, there is still no definite therapy for CL. Meglumine antimony compounds are considered as a standard treatment for leishmaniasis, however, these medications have a relatively high side effect profile and not always effective. Physical modalities including cryotherapy, laser, and heat therapy have also been used for this purpose. As a source of heat therapy, different methods have been used including radiofrequency, ultrasound, infrared, exothermic crystallization thermotherapy, and microwave. We reviewed all of the articles in PubMed regarding the use of heat therapy for the treatment of CL up to January 2020. According to our literature review, heat therapy using different sources showed promising results for the treatment of CL that were comparable to meglumine antimony. In addition, heat therapy has very low side effect profiles that are localized to the treatment area suggesting this method as a safe procedure for CL therapy. This study is a brief review of the literature about the effect of heat therapy on the treatment of CL. Performing randomized clinical trials to compare different methods of heat therapy and to compare it with meglumine antimony compounds is recommended.

Cutaneous leishmaniasis (CL) is a vector-borne disease classified by the World Health Organization as one of the most neglected tropical diseases. Brazil has the highest incidence of CL in America and is one of the ten countries in the world with the highest number of cases. Understanding the spatiotemporal dynamics of CL is essential to provide guidelines for public health policies in Brazil. In the present study we used a spatial and temporal statistical approach to evaluate the dynamics of CL in Brazil.

This study establishes a proof-of-concept that a tattoo device can target intra-dermal drug delivery against cutaneous leishmaniasis (CL). The selected drug is oleylphosphocholine (OlPC) formulated as liposomes, particles known to be prone to macrophage ingestion. We first show that treatment of cultured Leishmania-infected macrophages with OlPC-liposomes results in a direct dose-dependent killing of intracellular parasites. Based on this, in vivo efficacy is demonstrated using a 10 day tattooing-mediated treatment in mice infected with L. major and L. mexicana. In both models this regimen results in rapid clinical recovery with complete regression of skin lesions by Day 28. Parasite counts and histopathology examination confirm high treatment efficacy at the parasitic level. Low amount of drug required for tattooing combined with fast clinical recovery may have a positive impact on CL patient management. This first example of tattoo-mediated drug delivery could open to new therapeutic interventions in the treatment of skin diseases.

Leishmaniasis is a major neglected tropical disease which contributes a huge economic burden on already meager economic resources. The World Health Organization (WHO) has estimated an annual incidence of 700,000--1,000,000 patients and about 20,000-30,000 deaths per year. Approximately 66,941 patients of cutaneous leishmaniasis are reported annually in the Americas. In recent years, Nicaragua has presented alarmingly high numbers of patients and elevated incidence rates. Unfortunately, there are no detailed spatial descriptions on the epidemiological situation of leishmaniasis in this country. The objective of this study is to present descriptive data about the epidemiology of leishmaniasis in Nicaragua in the context of the distribution of this neglected tropical disease (NTD) in the Americas. This paper also provides an epidemiological update on different forms of leishmaniasis found in the three administrative regions of Nicaragua and its municipalities. Health authorities from the Ministry of Health of Nicaragua (MINSA) provided the entomological and epidemiological information for the different forms of the disease from 2001 to 2018. Prevalence, incidence rates, clinical classification of disease, age groups, sex, and geographic distribution by municipality and department are described in this study. Approximately 90%-95% of the national patients corresponded to CL and 5-10% correspond to MCL. The disease is distributed in the three regions of the country, with a higher burden in the Departments of Jinotega, Matagalpa and Atlántico Norte. The municipalities with the highest proportion of patients were El Cuá (23.92%), Waslala (14.16), Santa Maria de Pantasma (9.62%), Rancho Grande (9.03%) and Siuna (7.67%). There is an expansion of spatial distribution of CL and MCL in the North Central and South Atlantic regions of the country. These results could inform interventional strategies to address the burden of leishmaniasis in Nicaragua, which would improve the likelihood of meeting the goals for the Leishmaniasis Plan of Action for the Americas.

Leishmaniasis is a neglected disease presenting cutaneous, mucosal and visceral forms and affecting an estimated 12 million mostly low-income people. Treatment of cutaneous leishmaniasis (CL) is recommended to expedite healing, reduce risk of scarring, prevent parasite dissemination to other mucocutaneous (common with New World species) or visceral forms and reduce the chance of relapse, but remains an unmet need. Available treatments are painful, prolonged (>20 days) and require hospitalisation, which increases the cost of therapy. Here we present the development of optimised topical self-nanoemulsifying drug delivery systems (SNEDDS) loaded with buparvaquone (BPQ, a hydroxynapthoquinone from the open Malaria Box) for the treatment of CL from New World species. The administration of topical BPQ-SNEDDS gels for 7 days resulted in a reduction of parasite load of 99.989 ± 0.019% similar to the decrease achieved with intralesionally administered Glucantime® (99.873 ± 0.204%) in a L. amazonensis BALB/c model. In vivo efficacy was supported by ex vivo permeability and in vivo tape stripping studies. BPQ-SNEDDS and their hydrogels demonstrated linear flux across non-infected CD-1 mouse skin ex vivo of 182.4 ± 63.0 μg cm-2 h-1 and 57.6 ± 10.8 μg cm-2 h-1 respectively localising BPQ within the skin in clinically effective concentrations (227.0 ± 45.9 μg and 103.8 ± 33.8 μg) respectively. These levels are therapeutic as BPQ-SNEDDS and their gels showed nanomolar in vitro efficacy against L. amazonensis and L. braziliensis amastigotes with excellent selectivity index toward parasites versus murine macrophages. In vivo tape stripping experiments indicated localisation of BPQ within the stratum corneum and dermis. Histology studies confirmed the reduction of parasitism and indicated healing in animals treated with BPQ-SNEDDS hydrogels. These results highlight the potential clinical capability of nano-enabled BPQ hydrogels towards a non-invasive treatment for CL.

No abstract available

Cutaneous leishmaniasis (CL) is a vector-borne disease of increasing importance in northeastern Brazil. It is known that sandflies, which spread the causative parasites, have weather-dependent population dynamics. Routinely-gathered weather data may be useful for anticipating disease risk and planning interventions.

Cutaneous Leishmaniasis (CL) is a parasitic skin disease, linked to poverty, and belonging to the group of Neglected Tropical Diseases. Depending on the severity, the type of lesions or scars, and the context, CL can lead to self- and social stigma influencing the quality of life and psychological well-being of the patient. This dimension is, however, little documented for the most common, localized form of cutaneous leishmaniasis (LCL). We aimed to describe the current knowledge on the psychological burden and the stigma related to LCL.

Visceral leishmaniasis (VL) is in elimination phase in India while cutaneous leishmaniasis (CL) is being reported from new foci. In Himachal Pradesh (HP), a foci of CL had been reported along Satluj River, but the causative agent poses a dilemma, hence the present study was undertaken in Shimla, Kullu and Kinnaur districts.

Cutaneous leishmaniasis (CL) is endemic to Israel. Previously, CL caused by Leishmania infantum had been reported in Israel only once (in 2016). We report 8 L. infantum CL cases; 7 occurred during 2020-2021. None of the patients had systemic disease. L. infantum CL may be an emerging infection in Israel.

More effective topical treatments remain an unmet need for the localized forms of cutaneous leishmaniasis (CL). The aim of this study was to evaluate the efficacy and safety of a topical berberine cream in BALB/c mice infected with Leishmania major parasites.

Zoonotic cutaneous leishmaniasis (ZCL), due to infection by Leishmania (L). major, is characterized by polymorphic clinical manifestations which could be attributed to the host's immune response. In this study we investigated the involvement of cytotoxic cells on the outcome of the disease.

Infection with certain bacteria, parasites, and viruses alters the host immune system to Leishmania major influencing disease outcome. Here, we determined the outcome of a chronic infection with Trypanosoma brucei brucei on cutaneous leishmaniasis (CL) caused by L. major. C57BL/6 mice infected with T. b. brucei were given a sub-curative treatment with diminazene aceturate then coinfected with L. major by vector bites. Our results revealed that infection with T. b. brucei controls CL pathology. Compared to controls, coinfected mice showed a significant decrease in lesion size (P < 0.05) up to 6 weeks post-infection and a significant decrease in parasite burden (P < 0.0001) at 3 weeks post-infection. Protection against L. major resulted from a non-specific activation of T cells by trypanosomes. This induced a strong immune response characterized by IFN-γ production at the site of bites and systemically, creating a hostile inflammatory environment for L. major parasites and conferring protection from CL.

Cutaneous leishmaniasis (CL) is a neglected tropical disease which affects mainly the poorest communities in developing countries. Considering the limited published information on economic impact of CL in Sri Lanka, the current study was conducted with the objective of revealing the nature and magnitude of the economic impact of CL in three selected disease endemic regions in Kurunegala District, Sri Lanka. The patient records of CL notified of relevant Medical Officer of Health (MOH) office during 2013- 2016 were obtained. Patient households were visited and data collection was done using an interviewed administered questionnaire. The majority of patients (57%) were economically active at the time of infection. Of them, 65% were the only contributors to household economy. Total median costs including both direct and indirect costs were 66.85 USD (Rs. 10,831) (IQR = 57.26 - 86.78 USD), while total median economic loss to households was 61.27 USD (Rs. 9,927) (IQR= 49.61- 75.04 USD). From provider perspective, total median cost per patient was 22.83 USD (Rs. 3,696). The mean total economic loss was denoted as 65.26 USD (Rs. 10,572) which is about 5.4% of the annual household income and 20.9% of the mean annual per capita income of the study population. Although economic impact of CL infection is not catastrophic according to current interpretation, the infection may have significant economic impacts on households when considering the mean economic loss to household as a percentage of the mean annual per capita income of the population.