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Background: Cutaneous leishmaniasis (CL), caused by Leishmania (L.) species, remains a neglected tropical disease in many developing countries. We and others have shown that different Leishmania species can alter the gene expression profile of human host cells. Long non-coding RNAs (lncRNAs) have been found to play a role in the pathogenesis of leishmaniasis through dysregulation of transcriptome signatures. Understanding the regulatory roles of lncRNAs in the biological networks involved in leishmaniasis can improve our understanding of the disease. Methods: Herein, we used our previous RNA sequencing data (GSE216638) to investigate the profile of lncRNAs in the skin lesions of L. tropica -infected patients. We employed the weighted gene correlation network analysis (WGCNA) algorithm to establish co-expression networks of shared genes between CL patients and infer the potential role of lncRNAs in CL patients. We identified hub genes and trans- and cis-acting lncRNAs, and carried out functional enrichment analysis on a key co-expressed module related to L. tropica -infected patients. Results: We found substantial involvement of lncRNAs in the CL patient dataset. Using the WGCNA method, we classified all included genes into seven modules, with a module (turquoise) being significantly correlated with the studied clinical traits and identified as the key module. This module was mainly involved in the "interferon gamma signaling" and "cytokine signaling" pathways. We highlighted several lncRNAs and their co-expressed mRNA pairs, like SIRPG-AS1, IL21R-AS1, IL24, and TLDC2, as hub genes of the key module. Quantitative RT-PCR validated the expression of several genes in the lesions of an independent cohort of L. tropica -infected patients. Conclusions: These findings enhance our understanding of the human skin response to L. tropica infection. Furthermore, the hub genes identified in this study are worthy of further evaluation as potential targets in the development of more effective treatments and preventive measures for CL caused by L. tropica. [ABSTRACT FROM AUTHOR]

Background: The clinical appearance of cutaneous leishmaniasis (CL) lesions located in the nasal area can be confused with many inflammatory or tumoral diseases. In this study, we aimed to determine the frequency of nasal involvement and the morphological variants of CL lesions located in the nasal region. Methods: In this retrospective study, we included patients who presented to our Skin and Venereal Diseases Clinic in the province of Şanlıurfa, located in the Southeastern Anatolia region of Turkey between September 2022 and October 2023, and were diagnosed with CL with nasal involvement. From the records of CL patients with nasal involvement in our clinic, we evaluated the clinical (lesion location, lesion type, lesion diameter, lesion duration, treatment) and demographic characteristics (age, gender). Results: Of the patients (n = 278) diagnosed with CL using microscopic examination, 34 had nasal involvement, and the nasal involvement rate was 12.2%. Nineteen (55.8%) of the patients with nasal involvement were male, and 15 (44.2%) were female. Acute CL was detected in 28 patients (16 patients with dry‐type lesions, 12 patients with wet‐type lesions), and chronic CL was detected in six patients (four patients with lupoid and two patients with recidivant type lesions). According to the frequency distribution of clinical appearance, the most common lesions were eczema‐like lesions, erysipeloid‐type lesions, rhinophyma‐like lesions, and lymphoma‐like lesions. Conclusion: Physicians working in CL‐endemic regions should strictly consider CL in the differential diagnosis of nasal lesions. Early diagnosis and treatment of CL might prevent possible scarring and mucosal spread. [ABSTRACT FROM AUTHOR]

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background: Cutaneous leishmaniasis (CL) incidence in Switzerland is rising due to factors like migration and globalization. The aim of this work was to investigate CL frequency in Switzerland and identify clinical and histopathological difficulties in diagnosing CL in a non‐endemic country. Patients and Methods: This retrospective study evaluated the clinical and histopathological characteristics of all CL cases from two dermatopathology laboratories between 2000 and 2022. Skin biopsies were histopathologically reviewed using HE, Giemsa, and immunohistochemical stain for CD1a and a specific Leishmania antibody (LA). PCR to detect Leishmania DNA was performed if sufficient tissue was available. Results: 42 cases (27 m, 15 f) were included. The correct clinical diagnosis of CL was only made in 15 (35.7%) cases. In seven (16.6%) cases, CL was missed in the initial histopathologic evaluation. Two main histopathological patterns were observed: granulomatous and pseudolymphomatous. Immunohistochemical staining with CD1a and Leishmania‐specific antibody was positive in 91% and 80% of cases, respectively. Leishmania PCR was positive in 25 of 26 cases, mainly detecting Old World species. Conclusions: CL is rare in Switzerland and often misdiagnosed clinically and histopathologically. CD1a and specific Leishmania antibody stainings are useful. CL should be considered in non‐healing ulcers, even without a history of travel to endemic areas. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate how systemic antimony treatment in cutaneous leishmaniasis (CL) patients affects biochemical, hematological, and inflammatory parameters in child and adult patient groups. Methods: A total of 50 patients (29 adults, 21 children) who received systemic meglumine antimonate (MA) treatment in the skin and venereal diseases clinic between September 2022 and January 2024 and were diagnosed with CL by microscopic examination were included in the study. The medical records of the patients were examined retrospectively. Before and after treatment, neutrophil count, leukocyte count, lymphocyte count, hemoglobin concentration, platelet count, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), mean platelet volume (MPV), amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen and serum creatinine levels were recorded. Results: In the children group, lymphocyte and platelet values decreased statistically significantly; and lipase value increased statistically significantly after treatment. In the adult group; hemoglobin, neutrophil, lymphocyte and leukocyte values decreased statistically significantly; ALT, AST, amylase, lipase, NLR and PLR values increased statistically significantly after treatment. Conclusion: Based on the data in our study, it was stated that systemic meglumine antimonate treatment may lead to an increase in pancreatic enzymes and transaminases and bone marrow suppression. We also think that patients in the adult age group should be followed more closely regarding pancreatic enzymes and kidney function tests than the pediatric age group. [ABSTRACT FROM AUTHOR]

Introduction Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. This genus comprises 32 unicellular species infecting various vertebrate hosts, transmitted via sand-fly bites from Phlebotomus and Lutzomyia. Leishmaniasis affects the skin, mucous membranes, and internal organs, manifesting as cutaneous, mucocutaneous, or visceral leishmaniasis. Approximately 350 million people across 98 countries are at risk, with an annual global prevalence of 0.2-0.4 million cases of visceral leishmaniasis and 0.7-1.2 million cases of cutaneous and mucocutaneous leishmaniasis. In Pakistan, both anthroponotic cutaneous leishmaniasis (ACL) and zoonotic cutaneous leishmaniasis (ZCL) are reported, with significant cases in urban centers and rural areas. Methodology This study aimed to obtain baseline data for leishmaniasis in the Khyber Pakhtunkhwa province of Pakistan, conducted at Lady Reading Hospital, Peshawar. Data from 684 patients (475 males and 208 females) over one year were analysed using SPSS version 20.0. The chi-square test was applied to assess the association between infection rates and demographic variables. Result Results indicated the highest infection rate (46.7%) in the age group 1-15 years, followed by 16-30 years (19.8%), 31-45 years (9.4%), 46-60 years (6.1%), and above 60 years (3.3%). Gender-wise, males had a higher prevalence rate (69.3%) compared to females (30.7%). Positive cases were more prevalent in males (83.9%) than females (84.8%), although the association between infection and gender was statistically non-significant (p = 0.784). Discussion The discussion highlights that younger individuals have a higher infection rate due to a less developed immune system. Cultural practices in the region, such as males sleeping outside without adequate protection, contribute to higher infection rates in males. Diagnostic techniques for cutaneous leishmaniasis include slit skin smears and skin biopsies, with slit skin smears offering a more convenient yet less accurate alternative. The findings are consistent with previous studies, emphasizing the need for confirmatory skin biopsies in cases of negative slit skin smears but with high clinical suspicion. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis (CL) is an endemic disease in Ethiopia, mainly caused by L. aethiopica. Limited reports are available related to histopathological features of the skin lesion caused by L. aethiopica. This study aimed to analyze the histopathological features of CL due to L. aethiopica. Materials and Methods: A similar cohort polymerase chain reaction (PCR) confirmed CL patients from a previous own study, who were prospectively enrolled from All Africa Leprosy, Tuberculosis and Rehabilitation Training (ALERT) Hospital Addis Ababa, Kela Health Center in Gurage Zone, Siliti Health Center in Silit zone of southern nations and nationalities, as well as Ankober Health Center in Amhara region was used for data analysis. The histopathology was analyzed by performing hematoxylin and eosin (H&E) staining to look for the presence of general and specific histopathology patterns of the disease. Descriptive statistics was utilized using SPSS version 26.0 (SPSS, Inc., Chicago, United States of America). Results: Amastigotes were observed in skin biopsies of 29% (n = 2) mucocutaneous leishmaniasis (MCL) and 58% (n = 6) localized cutaneous leishmaniasis (LCL) patients. Diffused inflammatory cell infiltrate was observed in the dermal compartment of 77% (n = 20) samples while the remaining 23% (n = 6) had patchy or nodular inflammatory cell infiltrate. The dominant type of inflammatory cell infiltrate in the dermal compartments is macrophages and lymphocytes with a similar proportion, 23/26 (88.5%), followed by plasma cells, 21/26 (80.8%). Among all cases, 38.5% (n = 10) of them were categorized under the Type I pattern while Types IV and V patterns were reported in 26.9% (n = 7) and 34.6% (n = 9) of the remaining samples, respectively. The study found statistically significant correlations between necrosis and MCL (p = 0.01), unorganized granulomas and LCL (p = 0.04), and the presence of eosinophils and giant cell Langerhans with MCL (p = 0.002 and p < 0.001, respectively). Conclusion: In our study, the histopathological patterns of the CL caused by L. aethiopica were shown to have a dermal change that was characterized by a domination of diffused inflammatory cell infiltrate. Most of the cell types in the infiltrate were macrophages and lymphocytes. In addition, amastigote resided in the histiocyte with a varying degree of intensity, and both the organized and unorganized granulomas were shown with a considerable proportion. [ABSTRACT FROM AUTHOR]

Background: Cutaneous Leishmaniasis (CL) is a neglected tropical disease endemic in Brazil. Morbidity and disabilities caused by CL lesions require an analysis of a Global Burden of Disease (GBD), which would help discern the impact on the Brazilian population. Herein, we assess the burden of CL and its spatial and temporal patterns in Brazil between 2001 and 2021. Methodology/Principal findings: We estimated rates per 100,000 population for years lived with disabilities (YLD), years of life lost prematurely (YLL) and disability-adjusted life years (DALY) for each year of the study, sex assigned at birth, age group, and for each municipality in Brazil. In addition, the relative changes in these metrics over time for each region and sex were determined, as well as temporal trends using segmented joinpoint regression models. Using spatiotemporal analysis tools, we created choropleth maps representing DALY, YLD and YLL for three distinct periods (P1 = 2001 to 2007; P2 = 2008 to 2014; P3 = 2015 to 2021). These maps were constructed to visualize the inferences from Bayesian spatial statistics and Moran's autocorrelation using the Poisson model. The data were obtained from the DATASUS database. Although the global burden of CL has reduced over two decades, with the continual high impact among adults aged 20 to 39 years. In turn, YLL increased over time in 40-year-old populations, while among the elderly (>60 years old) this rate almost doubled from 2010 to 2021. Regarding the region of residence, we observed an average increase of 28% in YLL in Southeast, South and Central-West. Furthermore, the global burden of CL does not have a random spatial distribution, since there was a high-risk clustering of YLD in the north of the country. Interestingly, the YLL showed a vast geographic expansion through Brazilian territory. Conclusions: This study provides a comprehensive analysis of the burden of CL in Brazil, pointing out areas of highest disease burden, where control and surveillance efforts should be undertaken. Author summary: Previous studies on the burden of Cutaneous Leishmaniasis (CL) have focused on short-term investigations and concomitant with visceral leishmaniasis (VL). This might limit a more comprehensive understanding of CL dynamics. Furthermore, in Brazilian research, there is a lack of linkage between studies and the Global Burden of Disease (GBD) along with spatial and temporal analysis techniques, especially in CL. Our data showed a reduction in DALY and YLD rates. However, there was a significant increase in YLL, predominantly among adults and the elderly, and in previously unrecorded regions. It is important to emphasize the geographical disproportion of the YLD rate, given the formation of high-risk clusters in the North and Central-West regions. These results have significant implications for public health, as well as providing valuable information for directing efforts and resources. Studying the burden of CL in Brazil is crucial because it is among the countries with the highest number of global cases. Therefore, linking this study to spatial analysis has provided new insights and territorial patterns, as well as previously unknown manifestations. Additionally, it serves as a global benchmark that can help not only Brazil but also other endemic countries understand the dynamics of this disease and determine which political and surveillance measures can be taken. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) caused by L. donovani in South-East Asian endemic countries including India, Nepal and Bangladesh has been the primary focus of the ongoing VL elimination program. With a major reduction in VL cases resulting from the elimination program during the last two decades, the efforts are now focused on the challenges posed by potential reservoirs within the asymptomatic cases, HIV-co-infection VL cases and Post Kala-azar Dermal Leishmaniasis (PKDL) cases that continue to sustain the parasite transmission cycle in known and newer endemic zones. This article brings attention to a new potential parasite reservoir in the form of atypical cutaneous leishmaniasis (ACL) cases caused by novel L. donovani genetic variants. L. donovani mediated ACL is an emerging phenomenon in recent endemic sites that now justify a need for implementing molecular surveillance tools to identify region-specific L. donovani variants with dermotropic capabilities and potential to revert to visceral disease. A timely detection of novel ACL causing L. donovani genetic lineages in South-East Asian endemic regions is necessary to halt the spread of ACL and is potentially crucial for the sustainability of the advances made by the VL elimination. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis is one of the few infectious diseases whose global prevalence is on the rise. Iran ranks among the eight most affected countries in the world. Iranian military personnel are often sent to endemic areas for cutaneous leishmaniasis without prior immunity, and they have fewer health facilities in military centers than the general population. This study aims to comprehensively investigate the situation of cutaneous leishmaniasis in Iranian military personnel across all units from 2018 to 2022 and predict the disease trend using time series analysis up to the end of 2025. Methods: We analyzed data from the Iranian Ministry of Health to perform spatiotemporal and descriptive analyses based on patient frequency. Variables examined included age distribution, cutaneous leishmaniasis types (zoonotic or anthroponotic), month of healthcare facility visits, and lesion locations. This study employed the ARIMA model (p = 2, d = 0, q = 1)(P = 3, D = 0, Q = 0), for time series analysis and forecasting the disease trend up to 36 months after 2022. Results: Over five years, 2,894 patients were reported. The Esfahan, Khuzestan, and Ilam provinces had the highest average patient counts, with hot spots primarily found in central, south, southwestern, and western Iran. Although the total number of patients with zoonotic cutaneous leishmaniasis was almost equal to anthroponotic cutaneous leishmaniasis, in high-risk provinces such as Esfahan, Khuzestan, and Ilam, the confirmed cases of zoonotic cutaneous leishmaniasis were much more than anthroponotic cutaneous leishmaniasis. patient numbers peak in October and November. Demographic analysis revealed that younger patients outnumbered older patients. Lesion locations were frequent on the forelimbs and lower limbs. The time series analysis for 36 months after 2022 indicated the seasonal pattern of the disease and predicted an upward trend after 2022. Conclusion: While overall cases have declined, provinces such as Esfahan exhibit an upward trend. The expansion of hotspots from the west and southwestern to the center and south of Iran, coupled with an increasing trend in time series analysis, suggests the potential emergence of new foci and a rise in patient numbers in the future. In provinces with high disease prevalence, preventive measures should be prioritized, particularly in Ilam, Khuzestan, and Esfahan. [ABSTRACT FROM AUTHOR]

Leishmaniasis, a disease caused by protozoan Leishmania spp., exhibits a broad range of clinical manifestations. Host resistance or susceptibility to infections is often influenced by the genetic make-up associated with natural immunity. Caspase-1, a key component of the NLRP3 inflammasome, is critical for processing pro-IL-1β into its active form, IL-1β, while CARD8 functions as an NLRP3 inflammasome inhibitor. We conducted a case–control study comparing L. guyanensis-cutaneous leishmaniasis (Lg-CL) patients with healthy individuals (HCs) by analyzing the CASP1 genetic variants rs530537A>G, rs531542C>T, rs531604A>T and rs560880G>T. Additionally, a combined analysis of CARD8rs2043211A>T with CASP1rs530537 was performed. The genotype distribution for the four variants showed no significant differences between Lg-CL patients and HCs. However, the haplotype analysis of the four CASP1 variants identified the GTTT haplotype as associated with a 19% decreased likelihood of Lg-CL development, suggesting a protective effect against disease progression. The combined analysis of CARD8 with CASP1 variants indicated that individuals homozygous for both variants (GG/TT) exhibited a 38% reduced risk of developing Lg-CL (OR = 0.62 [95%CI:0.46–0.83]) in comparison to individuals with other genotype combinations. No correlation was found between the CASP1 variant genotypes and plasma IL-1β levels. CASP1 may act as a genetic modifier in Lg-CL. [ABSTRACT FROM AUTHOR]

The lack of vaccines shows the need for alternative leishmaniasis treatments. In vitro study previously demonstrated the leishmanicidal activity of A. nitidum extracts. This study describes for the first time, the antileishmanial activity of A. nitidum extracts in infected Balb/c mice and its immunomodulatory effect. The extract (EE) was obtained by maceration of the peel powder with ethanol, which was fractionated by acid-base partition, originating the alkaloid (FA) and neutral (FN) fractions. EE and FA were analyzed using mass spectroscopy. Daily intragastric treatment was performed with EE and FA, at doses of 200 mg/kg and 400 mg/kg, in Balb/c mice with 28 days of infection by Leishmania amazonensis. A thickness gauge was used to assess the progression of the lesion and the MTT method to determine the parasite load in the spleen. The quantification of IL-10 and IFN-γ was performed by ELISA. Analysis of the mass spectrum of EE indicated the presence of the alkaloids corynantheol and yohimbine, while in FA the alkaloid dihydrocorynantheol was identified. To elucidate the mode of interaction of these alkaloids with the TR protein, molecular target of antileishmanial drugs, we used molecular modeling approaches such as docking, molecular dynamics simulations and free energy affinity. Treatment with EE for 28 days at the highest dose tested, significantly reduced the size of the lesion. EE and FA after 28 days of treatment showed dose-dependent antileishmanial activity, which reduced the parasite load in the spleen of infected mice by 42.5% and 22.1%, respectively. Both EE and FA presented immunomodulatory effect, as they decreased IL-10 expression and increased IFN-y levels. The effectiveness of A. nitidum in the treatment of cutaneous leishmaniasis was proven in this study. The results obtained in silico demonstrated that the compounds are capable of interacting with the catalytic residues of the TR. The affinity energy results demonstrated that the complexes formed are favorable for enzymatic inhibition. The alkaloids present in the plant have demonstrated not only antileishmanial activity, but also the ability to modulate the host's immune response. These promising results open perspectives for developing more effective and comprehensive treatments against cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

Pyoderma gangrenosum (PG) can be difficult to diagnose, leading to diagnostic delay which affects patient outcomes and increases health care utilization. Among different scenarios of diagnostic delay, atypical infections can mimic PG. Here, we present a case of extensive cutaneous leishmaniasis initially misdiagnosed as the superficial granulomatous variant of PG and describe diagnostic clues to aid in differentiation. [ABSTRACT FROM AUTHOR]

Cytotoxic activity is a hallmark of the immunopathogenesis in human cutaneous leishmaniasis (CL). In this study, we identified accumulation of CD4+ granzyme B producing T cells with increased cytotoxic capacity in CL lesions. These cells showed enhanced expression of activating NK receptors (NKG2D and NKG2C), diminished expression of inhibitory NKG2A, along with the upregulation of the senescence marker CD57. Notably, CD4+ T cells freshly isolated from CL lesions demonstrated remarkable capacity to mediate NL-like bystander cytolysis. Phenotypic analyses revealed that lesional CD4+ T cells are mainly composed of late-differentiated effector (CD27-CD45RA-) and terminally differentiated (senescent) TEMRA (CD27-CD45RA+) subsets. Interestingly, the TEMRA CD4+ T cells exhibited higher expression of granzyme B and CD107a. Collectively, our results provide the first evidence that senescent cytotoxic CD4+ T cells may support the skin pathology of human cutaneous leishmaniasis and, together with our previous findings, support the notion that multiple subsets of cytotoxic senescent cells may be involved in inducing the skin lesions in these patients. [ABSTRACT FROM AUTHOR]

Objectives: The role of serum cholesterol and its interactions with cytokines in human cutaneous leishmaniasis (CL) pathophysiology is unknown. This study aimed to evaluate the correlation among serum total cholesterol (TC), very-low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and cytokines (including interleukin [IL] 10), IL-12 and tumour necrosis factor-alpha [TNF-α]) in CL. The cholesterol-cytokine network was analysed to illuminate the pathogenesis of CL. Methods: This case-control study was conducted from December 2022 to March 2023 in hospitals within Baghdad and Wasit provinces, Iraq, and included CL and CL-free subjects ranging between 20-30 years of age. The serum samples were analysed via commercial kits to detect TC, IL-10, IL-12, TNF-α, VLDL-C, LDL-C, HDL-C and TG levels. Computational efforts to dissect cholesterol-protein interaction networks were employed using STITCH. Results: A total of 50 CL and 25 control subjects were included. The TC, HDL-C and LDL-C levels in CL patients were markedly lower (P = 0.0001) than in control subjects, whereas the IL-10, IL-12, TNF-α, VLDL-C and TG levels were higher in CL patients. Serum cholesterol showed no correlation with cytokines; however, a significant correlation (r = 0.57; P = 0.026) was observed between IL-12 and TNF-α. Within the cholesterol-protein network, cholesterol potentially interacted with IL-10, connecting cholesterol to modules with immunological significance, including TRAF1, TRAF2 and TNF receptor superfamily member 1B, as well as IL-10, IL-10RA and IL-12RB1. Conclusion: This study showed the alteration of lipid and lipoprotein in CL and introduced 2 immunological modules in CL, highlighting the importance of the altered cholesterolcytokine interaction network in CL. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL), caused by Leishmania braziliensis, is closely associated with a severe form of the disease, indicated by a positive Leishmania skin test (LST) that assesses and reflects the presence of immune T cells specific to Leishmania antigens. In this study, we compare the clinical, immunologic, and histopathologic features between Leishmania skin test-positive (LST+) and Leishmania skin test-negative (LST-) in CL. Compared to LST+ patients, LST- patients had larger lesions and had been sicker for longer, presented with more instances of therapeutic failure with meglumine antimonate, (MA) and the healing times were higher than LST+. While granulomas were less frequent and the parasite load was higher in LST-, there were more CD8+ T cells and an enhanced production of Granzyme B in the supernatants of biopsies from LST- subjects. This study shows that in LST-, an impairment in Th1 immune response is associated with a high parasite burden, and the pathology is mediated by CD8+ T cells and the enhanced production of Granzyme B. The abnormalities in the immunologic response in LST- patients lead to a more severe disease with a high rate of failure to therapy. [ABSTRACT FROM AUTHOR]

Copyright of Medical Journal of Babylon is the property of Wolters Kluwer India Pvt Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Phlebotomus argentipes is the established vector of leishmaniasis in the Indian sub-continent. Antibodies to sand fly salivary antigens are biomarkers for vector-host exposure in leishmaniasis-endemic regions. Ph. argentipes transmits Leishmania donovani in Sri Lanka, primarily causing cutaneous leishmaniasis (CL). Our study compared the performance of salivary gland homogenate (SGH) from a lab-reared local strain of Ph. argentipes females to a composite recombinant salivary biomarker (rPagSP02 + rPagSP06) in a CL-endemic population. Sera from 546 healthy individuals, 30 CL patients, and 15 non-endemic individuals were collected. Western blot analysis of Ph. argentipes SGH identified immunogenic bands between 15 kDa and 67 kDa, with bands of predicted molecular weight ∼of 15 kDa (SP02) and ∼28–30 kDa (SP06) as the major antibody targets. Indirect ELISAs using SGH or rPagSP02 + rPagSP06 antigens showed high sensitivity (96.7%) and specificity (100%), detecting comparable seropositivity in endemic populations. rPagSP02 + rPagSP06 exhibited enhanced discriminatory ability, supported by a strong positive correlation (r = 0.869) with SGH. Our findings indicate that the composite rPagSP02 + rPagSP06 salivary biomarker effectively identifies Ph. argentipes exposure in individuals living in Sri Lanka, showing promising potential for use in surveillance. These findings should be further validated to confirm the epidemiological applications in leishmaniasis-endemic regions. [ABSTRACT FROM AUTHOR]

Dogs are the primary reservoirs of Leishmania infantum (L. infantum), but Leishmania tropica (L. tropica) infection is also possible in dogs and can transmitted to humans. The southeast of Iran experiences a high prevalence of canine leishmaniasis (CanL), and veterinarians frequently encounter symptomatic cases. Therefore, from December 2017 to November 2022, the present case series was designed to assess the prevalence of CanL in owned dogs with cutaneous manifestations resembling CanL. A total of 500 owned dogs with dermal lesions from two endemic cities, Zabol and Kerman, were enrolled. Impression smears from skin lesions and popliteal lymph nodes were prepared from all cases, whereas blood samples were gathered from amastigote-positive dogs for serological and molecular surveys. Commercial ELISA was done on sera samples, and two-step nested PCR was used on extracted DNA to amplify variable fragments of the Leishmania species' kinetoplast DNA (kDNA). Leishman bodies were microscopically detected in 7.2% (36/500) of dermal smears. Of the 360 owned dogs from Zabol, 2 have been diagnosed with L. tropica, and 10 have been diagnosed with L. infantum. Out of 140 owned dogs from Kerman, 8 were identified with L. tropica infection, and 16 were infected with L. infantum. Molecular results revealed the presence of 750 full dual-band bases related to the L. tropica species in 10/36 (27.7%) cases, which showed a considerable increase in canine cutaneous leishmaniosis compared with previous studies in southeastern Iran. The noticeable prevalence of L. tropica in owned dogs indicated that the dog's role in cutaneous leishmaniosis should be re-evaluated as a possible animal reservoir in endemic areas. [ABSTRACT FROM AUTHOR]

Microorganisms have long been suspected to influence the outcome of immune-related syndromes, particularly autoimmune diseases. Type 1 diabetes (T1D) results from the autoimmune destruction of the insulin-producing beta cells of pancreatic islets, causing high glycemia levels. Genetics is part of its aetiology, but environmental factors, particularly infectious microorganisms, also play a role. Bacteria, viruses, and parasites influence the outcome of T1D in mice and humans. We used nonobese diabetic (NOD) mice, which spontaneously develop T1D, to investigate the influence of a parasitic infection, leishmaniasis. Leishmania amazonensis is an intracellular eukaryotic parasite that replicates predominantly in macrophages and is responsible for cutaneous leishmaniasis. The implication of Th1 immune responses in T1D and leishmaniasis led us to study this parasite in the NOD mouse model. We previously constructed osteopontin knockout mice with a NOD genetic background and demonstrated that this protein plays a role in the T1D phenotype. In addition, osteopontin (OPN) has been found to play a role in the immune response to various infectious microorganisms and to be implicated in other autoimmune conditions, such as multiple sclerosis in humans and experimental autoimmune encephalomyelitis (EAE) in mice. We present herein data demonstrating the role of OPN in the response to Leishmania in NOD mice and the influence of this parasitic infection on T1D. This exploratory study aimed to investigate the environmental infectious component of the autoimmune response, including Th1 immunity, which is common to both T1D and leishmaniasis. [ABSTRACT FROM AUTHOR]

Sterol biosynthesis requires the oxidative removal of two methyl groups from the C-4 position by sterol C-4-demethylase and one methyl group from the C-14 position by sterol C-14-demethylase. In Leishmania donovani, a CYP5122A1 (Cytochrome P450 family 5122A1) protein was recently identified as the bona fide sterol C-4 methyl oxidase catalyzing the initial steps of C-4-demethylation. Besides CYP5122A1, Leishmania parasites possess orthologs to ERG25 (ergosterol pathway gene 25), the canonical sterol C-4 methyl oxidase in Saccharomyces cerevisiae. To determine the contribution of CYP5122A1 and ERG25 in sterol biosynthesis, we assessed the essentiality of these genes in Leishmania major, which causes cutaneous leishmaniasis. Like in L. donovani, CYP5122A1 in L. major could only be deleted in the presence of a complementing episome. Even with strong negative selection, L. major chromosomal CYP5122A1-null mutants retained the complementing episome in both promastigote and amastigote stages, demonstrating its essentiality. In contrast, the L. major ERG25-null mutants were fully viable and replicative in culture and virulent in mice. Deletion and overexpression of ERG25 did not affect the sterol composition, indicating that ERG25 is not required for C-4-demethylation. These findings suggest that CYP5122A1 is the dominant and possibly only sterol C-4 methyl oxidase in Leishmania, and inhibitors of CYP5122A1 may have strong therapeutic potential against multiple Leishmania species. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by the protozoan parasite Leishmania. In Ethiopia, CL is mainly caused by Leishmania aethiopica and can present in different clinical forms. The aim of this study was to assess whether these different forms are associated with differences in parasite genetic and host systemic immune signatures. Methods: Here we analysed the whole genome sequence data for 48 clinical parasite isolates and the systemic immune signature from a cohort of CL patients, who were recruited in Nefas Mewcha, Northern Ethiopia, from January 2019 to January 2022. Results: Our results show that parasites from CL cases with different presentations in a single Ethiopian setting are from the same genetic population based on a permutation test of genome-wide similarity. Furthermore, a logistic regression test for genome wide association did not identify any individual genetic variants significantly associated with disease presentation. We also measured plasma chemokine and cytokine levels of 129 CL patients presenting with different forms of CL. None of the chemokine [eotaxin, eotaxin-3, interleukin (IL)-8, interferon (IFN)-γ-induced protein-10 (IP-10), monocyte chemoattractant protein (MCP)-1, MCP-4, macrophage-derived chemokines (MDC), macrophage inflammatory protein (MIP)-1α, MIP-1β and thymus- and activation-regulated chemokine (TARC)] or cytokine (IFN-γ, IL-1β, interleukin-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis factor-α) levels measured were significantly different between the different clinical presentations of CL, as measured by Kruskal–Wallis test. We also compared those with healthy nonendemic controls: our results show a chemokine (IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β and TARC) but not a cytokine immune signature in patients with CL as compared to healthy nonendemic controls, as measured by Mann-Whitney test. Conclusions: The results of our study did not identify a systemic immune signature or parasite genetic factors associated with different clinical presentation of CL. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis (CL) in Ethiopia and some parts of Kenya is predominantly caused by Leishmania aethiopica. While skin-slit (SS) microscopy is routinely used for CL diagnosis, more sensitive molecular tests are available. The Loopamp™ Leishmania detection kit (Loopamp) is a robust loop-mediated isothermal amplification (LAMP) assay with the potential for implementation in primary healthcare facilities. In this study, we comparatively assessed the diagnostic accuracy of four methods currently used to diagnose CL: Loopamp, kinetoplast DNA (kDNA) PCR, spliced leader RNA (SL-RNA) PCR and SS microscopy. Methods: A study on 122 stored tape disc samples of suspected CL patients was conducted in Gondar, northwestern Ethiopia. Routine SS microscopy results were obtained from all patients. Total nucleic acids were extracted from the tapes and subjected to PCR testing targeting kDNA and SL-RNA, and Loopamp. Diagnostic accuracy was calculated with SS microscopy as a reference test. The limit of detection (LoD) of Loopamp and kDNA PCR were determined for cultured L. aethiopica and Leishmania donovani. Results: Of the 122 patients, 64 (52.5%) were identified as CL cases based on SS microscopy. Although the PCR tests showed a sensitivity of 95.3% (95% confidence interval [CI] 91.6–99.1), Loopamp only had 48.4% (95% CI 39.6–57.3) sensitivity and 87.9% (95% CI 82.1–93.7) specificity. The LoD of Loopamp for L. donovani was 100-fold lower (20 fg/µl) than that for L. aethiopica (2 pg/µl). Conclusions: The Loopamp™ Leishmania detection kit is not suitable for the diagnosis of CL in Ethiopia, presumably due to a primer mismatch with the L. aethiopica 18S rRNA target. Further research is needed to develop a simple and sensitive point-of-care test that allows the decentralization of CL diagnosis in Ethiopia. [ABSTRACT FROM AUTHOR]

Neutrophils rapidly infiltrate sites of infection and possess several microbicidal strategies, such as neutrophil extracellular traps release and phagocytosis. Enhanced neutrophil infiltration is associated with higher susceptibility to Leishmania infection, but neutrophil effector response contribution to this phenotype is uncertain. Here, we show that neutrophils from susceptible BALB/c mice (B/c) produce more NETs in response to Leishmania major than those from resistant C57BL/6 mice (B6), which are more phagocytic. The absence of neutrophil elastase contributes to phagocytosis regulation. Microarray analysis shows enrichment of genes involved in NET formation (mpo, pi3kcg, il1b) in B/c, while B6 shows upregulation of genes involved in phagocytosis and cell death (Arhgap12, casp9, mlkl, FasL). scRNA-seq in L. major-infected B6 showed heterogeneity in the pool of intralesional neutrophils, and we identified the N1 subset as the putative subpopulation involved with phagocytosis. In vivo, imaging validates NET formation in infected B/c ears where NETing neutrophils were mainly uninfected cells. NET digestion in vivo augmented parasite lymphatic drainage. Hence, a balance between NET formation and phagocytosis in neutrophils may contribute to the divergent phenotype observed in these mice. Author summary: Leishmaniasis is a complex of vector-borne diseases transmitted by infected sandflies carrying Leishmania. Clinical manifestations range from cutaneous lesions to visceral disease, which can be fatal if not treated. Cutaneous Leishmaniasis is the most common clinical manifestation. Experimental models built in the early 70s have established susceptible (BALB/c) and resistant (C57BL/6) strains to Leishmania major infection. Neutrophils comprise the first line of defense against microbial invaders. Neutrophils possess powerful microbicidal tools, which can thwart most pathogens. Accordingly, genetic disorders that lead to neutropenia enhance patients' susceptibility to infections. Counterintuitively, neutrophilia is associated with enhanced susceptibility to cutaneous Leishmaniasis. Although these cells used to be considered transcriptionally rudimental, currently neutrophils have emerged as functionally plastic cells. Here, we deepened the understanding of why neutrophils are associated with susceptibility to infection in the murine model by showing that not just the influx, but the functional profile of these cells likely impacts the early response to infection and affects parasite retention in the primary site of infection, which likely contributes to shaping disease outcome. Our results provide mechanistic insights to assist in the development of target-based therapies. [ABSTRACT FROM AUTHOR]

Although among the six most common parasitic diseases, leishmaniasis is considered a neglected disease, being recognised as a serious public health burden worldwide. This fact impairs technological advancements and investments in innovative therapeutic approaches, so that commonly available drugs are still associated with low therapeutic rates and significant side effects. Pentavalent antimonials, such as Pentostan® and Glucantime®, were established as chemotherapeutic agents since the 1940s, being the first line of treatment for leishmaniasis; however, 60% of cases of leishmaniasis are resistant to pentavalent antimonials. Thus, the search for more effective therapies and new therapeutic agents with potential leishmanicidal activity is still in-demand. In this review, an overview about the disease and its pathophysiology is given, discussing the current state-of-the-art of the standard treatments and new alternatives based on drug delivery approaches, enhancing the need for more effective pharmaceutical treatments. [ABSTRACT FROM AUTHOR]

Rodents are the primary reservoir hosts for zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania major. Knowing reservoir hosts is crucial for leishmaniasis surveillance and control programs in endemic areas. In this study, we examined an archived spleen of Rattus norvegicus obtained during a pest control program in 2000 in Tehran, the capital of Iran. The sample was analyzed using polymerase chain reaction (PCR) and sequencing to determine the presence of Trypanosomatidae based on the internal transcribed spacer (ITS) 1 gene. Amplification and sequencing of the discriminative region of the ITS1 gene followed by BLAST analysis showed the highest similarity with L. major isolates. Also, the phylogenetic analysis revealed that our sample was grouped with L. major isolates retrieved from the GenBank database. This finding might support the claim that R. norvegicus acts as a potential reservoir host for L. major. Further studies, including a survey on more rodent samples as well as studying sandflies in the area, might uncover the possible presence of such pathobiological conditions in ZCL transmission in urban and suburban settings. [ABSTRACT FROM AUTHOR]

Migration routes determine exposure to endemic infections. We present a case of complex cutaneous leishmaniasis in a man with HIV infection who migrated to the United States from Haiti, where Leishmania is uncommon, acquiring leishmaniasis while on his journey via South America and Central America. His presentation included hyperpigmented, nonulcerated plaques and nodules on his extremities, chest, back, face, palms, and soles; initially he had no mucosal lesions. Infection with Leishmania panamensis was confirmed via polymerase chain reaction. He was prescribed bictegravir/tenofovir alafenamide/emtricitabine with rapid suppression of HIV and liposomal amphotericin B for diffuse cutaneous leishmaniasis with a limited initial response. He subsequently developed mucosal lesions in the setting of immune reconstitution and was retreated with amphotericin dosed for mucocutaneous disease. A thorough migration history was critical to diagnosis. This case highlights the different presentations of leishmaniasis in people with HIV and the elevated risk for treatment failure. [ABSTRACT FROM AUTHOR]

The state of Himachal Pradesh is the most endemic region for cutaneous leishmaniasis transmission in northern India. Phlebotomus adlerius longiductus and Phlebotomus Larrousisus major have a wide distribution in Himachal Pradesh (India) and mostly found in mountainous areas. There is very little data available on the identification and distribution of sand flies in Himachal Pradesh. Therefore, the present study was carried out with the aim of identifying and distinguishing the sand flies species found in endemic focus of CL in Himachal Pradesh (HP), India, using PCR and sequencing methods. Collections of sand flies were made from endemic villages of cutaneous leishmaniasis in Shimla, Kullu and Kinnaur districts of HP during 2017–2019. A total of 291 sand flies were collected and all the collected sandflies were identified morphologically. In addition, genus specific identification of 52 sand flies was carried by Polymerase Chain Reaction (PCR). The PCR amplified products were sequenced for confirmation of sand-fly species. The sequences obtained were submitted to NCBI GenBank under accession no. MT126505 to MT126510 and compared for similarities to the NCBI database. The morphological identification revealed Phlebotomus adlerius longiductus and Phlebotomus Larrousisus major. Of 291 sand flies,>99% were Phlebotomus adlerius longiductus with Phlebotomus Larrousisus major in low numbers. The sequences obtained were compared for similarities to NCBI database and showed 99–100% similarity with Phlebotomus longiductus (Parrot). The phylogenetic tree analysis showed that the isolates were geographically closest to the sand flies from Bhutan and China. The study revealed that the P. longuductus (Parrot) is the predominant species found in the CL endemic area in HP. The study confirms the identity of P. longiductus (Parrot) through molecular tools as well as morphologically. As, P. longiductus (Parrot) has been reported to transmit L.donovani, it is important to distinguish the sand-fly species using molecular tool. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a parasitic disease spread by the bite of an infected sandfly and caused by protozoan parasites of the genus Leishmania. Currently, there is no vaccine available for leishmaniasis in humans, and the existing chemotherapy methods face various clinical challenges. The majority of drugs are limited to a few toxic compounds, with some parasite strains developing resistance. Therefore, the discovery and development of a new anti‐leishmanial compound is crucial. One promising strategy involves the use of nanoparticle delivery systems to accelerate the effectiveness of existing treatments. In this study, Amphotericin B (AmB) was incorporated into functionalized carbon nanotube (f‐CNT) and evaluated for its efficacy against Leishmania major in vitro and in a BALB/c mice model. The increase in footpad thickness was measured, and real‐time PCR was used to quantify the parasite load post‐infection. Levels of nitric oxide and cytokines IL‐4 and IFN‐γ were also determined. We found that f‐CNT‐AmB significantly reduced the levels of promastigotes and amastigotes of the Leishmania parasite. The nanoparticle showed strong anti‐leishmanial activity with an IC50 of 0.00494 ± 0.00095 mg/mL for promastigotes and EC50 of 0.00294 ± 0.00065 mg/mL for amastigotes at 72 h post‐infection, without causing harm to mice macrophages. Treatment of infected BALB/c mice with f‐CNT‐AmB resulted in a significant decrease in cutaneous leishmania (CL) lesion size in the foot pad, as well as reduced Leishmania burden in both lymph nodes and spleen. The levels of nitric oxide and IFN‐γ significantly increased in the f‐CNT‐AmB treated groups. Also, our results showed that the level of IL‐4 significantly decreased after f‐CNT‐AmB treatment in comparison to other groups. In conclusion, our results demonstrate that AmB loaded into f‐CNT is significantly more effective than AmB alone in inhibiting parasite propagation and promoting a shift towards a Th1 response. [ABSTRACT FROM AUTHOR]

Background: Neglected tropical diseases (NTDs), including leishmaniasis, trypanosomiasis, and schistosomiasis, impose a significant public health burden, especially in developing countries. Despite control efforts, treatment remains challenging due to drug resistance and lack of effective therapies. Objective: This study aimed to synthesize the current research on the combination therapy and phytochemical-loaded nanosystems, which have emerged as promising strategies to enhance treatment efficacy and safety. Methods/Results: In the present review, we conducted a systematic search of the literature and identified several phytochemicals that have been employed in this way, with the notable efficacy of reducing the parasite load in the liver and spleen in cases of visceral leishmaniasis, as well as lesion size in cutaneous leishmaniasis. Furthermore, they have a synergistic effect against Trypanosoma brucei rhodesiense rhodesain; reduce inflammation, parasitic load in the myocardium, cardiac hypertrophy, and IL-15 production in Chagas disease; and affect both mature and immature stages of Schistosoma mansoni, resulting in improved outcomes compared to the administration of phytochemicals alone or with conventional drugs. Moreover, the majority of the combinations studied demonstrated enhanced solubility, efficacy, and selectivity, as well as increased immune response and reduced cytotoxicity. Conclusions: These formulations appear to offer significant therapeutic benefits, although further research is required to validate their clinical efficacy in humans and their potential to improve treatment outcomes in affected populations. [ABSTRACT FROM AUTHOR]

Our main aim was to estimate and compare the effects of six environmental variables (air temperature, soil temperature, rainfall, runoff, soil moisture, and the enhanced vegetation index) on excess cases of cutaneous leishmaniasis in Colombia. We used epidemiological data from the Colombian Public Health Surveillance System (January 2007 to December 2019). Environmental data were obtained from remote sensing sources including the National Oceanic and Atmospheric Administration, the Global Land Data Assimilation System (GLDAS), and the Moderate Resolution Imaging Spectroradiometer. Data on population were obtained from the TerriData dataset. We implemented a causal inference approach using a machine learning algorithm to estimate the causal association of the environmental variables on the monthly occurrence of excess cases of cutaneous leishmaniasis. The results showed that the largest causal association corresponded to soil moisture with a lag of 3 months, with an average increase of 8.0% (95% confidence interval [CI] 7.7–8.3%) in the occurrence of excess cases. The temperature-related variables (air temperature and soil temperature) had a positive causal effect on the excess cases of cutaneous leishmaniasis. It is noteworthy that rainfall did not have a statistically significant causal effect. This information could potentially help to monitor and control cutaneous leishmaniasis in Colombia, providing estimates of causal effects using remote sensor variables. [ABSTRACT FROM AUTHOR]

Background: Phlebotomus papatasi is considered the primary vector of Leishmania major parasites that cause zoonotic cutaneous leishmaniasis (ZCL) in the Middle East and North Africa. Phlebotomus papatasi populations have been studied extensively, revealing the existence of different genetic populations and subpopulations over its large distribution range. Genetic diversity and population structure analysis using transcriptome microsatellite markers is important to uncover the vector distribution dynamics, essential for controlling ZCL in endemic areas. Methods: In this study, we investigated the level of genetic variation using expressed sequence tag-derived simple sequence repeats (EST-SSRs) among field and colony P. papatasi samples collected from 25 different locations in 11 countries. A total of 302 P. papatasi sand fly individuals were analyzed, including at least 10 flies from each region. Results: The analysis revealed a high-level population structure expressed by five distinct populations A through E, with moderate genetic differentiation among all populations. These genetic differences in expressed genes may enable P. papatasi to adapt to different environmental conditions along its distribution range and likely affect dispersal. Conclusions: Elucidating the population structuring of P. papatasi is essential to L. major containment efforts in endemic countries. Moreover, the level of genetic variation among these populations may improve our understanding of Leishmania–sand fly interactions and contribute to the efforts of vaccine development based on P. papatasi salivary proteins. [ABSTRACT FROM AUTHOR]

Mexico's Yucatan Peninsula is an endemic area of cutaneous leishmaniasis, locally known as the chiclero's ulcer, and Mayan traditional medicine which refers to the use of Thouinia paucidentata Radlk, known as k'an chuunup. Aqueous and organic leaves extracts were evaluated against promastigotes and amastigotes of Leishmania mexicana. Toxicity tests of extracts were performed using Vero and J774A.1 macrophage cell lines. The composition of the most active extracts was analysed by GC-MS. The n-hexane and ethyl acetate extracts showed potent anti-Leishmania activity against the promastigote form, and remarkably, n-hexane extract exhibited potent activity against the amastigote form. Both extracts showed low toxicity on Vero both not on J774A.1 cells. Analysis of both bioactive extracts identified as more abundant compounds, germacrene D-4-ol and thunbergen in n-hexane, and thunbergol in ethyl acetate extracts. Our study presents T. paucidentata as anti-Leishmania phytomedicine supporting its medicinal use and contributes to the understanding of its phytochemical composition. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis, mainly cutaneous leishmaniasis (CL), is endemic in Israel. In recent years, the diagnosis of leishmaniasis has transitioned to a molecular diagnosis. Objective: To summarize all cases of leishmaniasis and the identified species seen in Israel based on molecular diagnosis. Methods: A retrospective study was performed of patients diagnosed with leishmaniasis between January 2017 and December 2022. All five medical centers in Israel in which Leishmania diagnosis is performed were included: Soroka, HaEmek, Hadassah, Rambam, and Sheba, all utilized molecular diagnostic methods. Data on the annual number of cases, species, age, and gender were retrieved. Results: During the years 2017–2022, a total of 4168 cases of leishmaniasis were diagnosed, which corresponds with ~7/100,000 inhabitants. L. (L.) major and L. (L.) tropica accounted for 84% and 14%, respectively. During the years 2020–2021, L. (L.) infantum emerged as a new form of cutaneous disease [2.7% of cases during this period]. Visceral L. (L.) infantum was found in five cases. Imported New World leishmaniasis accounted for 1% of the cases. L. (L.) major affected more males (67%) while L. (L.) tropica commonly affected more children and caused more facial lesions. Conclusions: The mean annual number of cases during these years is ~700. The dominant species is L. (L.) major. Since 2020, cutaneous L. (L.) infantum is an emerging infection in Israel. [ABSTRACT FROM AUTHOR]

Human leishmaniasis is facing important epidemiological changes in Southern Europe, driven by increased urbanization, climate changes, emerging of new animal reservoirs, shifts in human behavior and a growing population of immunocompromised and elderly individuals. In this evolving epidemiological landscape, we analyzed the clinical and epidemiological characteristics of human leishmaniasis in the Tuscany region of Central Italy. Through a multicentric retrospective analysis, we collected clinical and demographic data about all cases of leishmaniasis recorded between 2018 and 2023. We observed 176 cases of human leishmaniasis, with 128 (72.7%) visceral leishmaniasis (VL) and 47 (26.7%) cutaneous leishmaniasis (CL). Among these, 92.2% of VL and 85.1% of CL cases were autochthonous. The cumulative incidence of autochthonous human leishmaniasis was 0.22 cases per 100,000 inhabitants in 2018, but reached 1.81/100,000 in 2023. We identified three main areas of transmission: around the city of Florence (North-East Tuscany), around Grosseto city (South-West Tuscany) and Elba Island. Our findings confirm that the epidemiology of leishmaniasis is undergoing significant changes in Central Italy. Awareness towards this emerging health threat and surveillance strategies need to be improved in order to reliably assess the disease's burden. Further research is needed in a "One-Health" perspective, to clarify the epidemiological dynamics at the environmental, reservoir, vector and human levels. The role of climate change and specific climatic factors affecting the epidemiological patterns of human leishmaniasis should be assessed. Further knowledge in these fields would promote targeted control and prevention strategies at regional and national levels. [ABSTRACT FROM AUTHOR]

Background: The JAK-STAT signaling pathway is a central cascade of signal transduction for the myriad of cytokines in which dysregulation has been implicated in progression of inflammatory and infectious diseases. However, the involvement of this pathway in human cutaneous leishmaniasis (CL) due to Leishmania (L.) tropica warrants further investigation. Methods: This study sought to investigate differential gene expression of several cytokines and their associated jak-stat genes in the lesions of L. tropica-infected patients byquantitative Real-Time PCR. Further, the expression of five inhibitory immune checkpoint genes was evaluated. Results: Results showed that the gene expression levelsof both Th1 (ifng, il12, il23) and Th2 (il4, il10) types cytokines were increased in the lesion of studied patients. Further, elevated expression levels of il35, il21, il27 and il24 genes were detected in the lesions of CL patients. Notably, the expression of the majority of genes involved in JAK/STAT signaling pathway as well as checkpoint genes including pdl1, ctla4 and their corresponding receptors was increased. Conclusion: Our finding revealed dysregulation of cytokines and related jak-stat genes in the lesion of CL patients. These results highlight the need for further exploration of the functional importance of these genes in the pathogenesis of, and immunity to, CL. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL), caused by protozoan parasites of the Leishmania genus, is prevalent in tropical and subtropical regions, with important morbidity, particularly in low- to middle-income countries. Current systemic treatments, including pentavalent antimonials and miltefosine, are associated with significant toxicity, reduced efficacy, and are frequently ineffective in cases of severe or chronic CL. Immunotherapies leverage the immune system to combat microbial infection and offer a promising adjunct or alternative approach to the current standard of care for CL. However, the heterogeneous clinical presentation of CL, which is dependent on parasite species and host immunity, may require informed clinical intervention with immunotherapies. This review explores the clinical and immunological characteristics of CL, emphasising the current landscape of immunotherapies in in vivo models and clinical studies. Such immune-based interventions aim to modulate immune responses against Leishmania, with additive therapeutic effects enabling the efficacy of lower drug doses and decreasing the associated toxicity. Understanding the mechanisms that underlie immunotherapy for CL provides critical insights into developing safer and more effective treatments for this neglected tropical disease. Identifying suitable therapeutic candidates and establishing their safety and efficacy are essential steps in this process. However, the feasibility and utility of these treatments in resource-limited settings must also be considered, taking into account factors such as cost of production, temperature stability, and overall patient access. [ABSTRACT FROM AUTHOR]

Background Our objective in this study is to determine the atypical clinical presentations of cutaneous leishmaniasis (CL) patients diagnosed in Şanlıurfa province. Methods This retrospective study included 213 patients with atypical clinical presentations among 1751 patients diagnosed with CL between October 2019 and August 2022 in Şanlıurfa Oriental Boil Diagnosis and Treatment Center located in an endemic region for CL. Results We found the prevalence of atypical CL to be 12.1%. The most common atypical lesions were lupoid 21 (9.8%), erysipeloid 16 (7.5%), impetiginous 16 (7.5%), recidivan 15 (7%), eczematous 15 (7%), ecthyma-like 13 (6.1%), pyoderma gangrenous-like 12 (5.6%), and sporotrichoid 12 (5.6%). Other lesions with atypical clinical presentations: chalazion-like, verrucous, dental sinus-like, psoriasiform, zosteriform, lymphoma-like, juvenile xanthogranuloma-like, volcano-like, paronychial, basal cell carcinoma-like, squamous cell carcinoma-like, herpes labialis-like, keratoacanthoma-like, chancriform, annular, lichenoid, mastocitoma-like, keloidal, epidermoid cyst-like, kaposi sarcoma-like, scar leishmaniasis, granulomatous cheilitis-like, mycetoma-like, molluscum contagiosum-like, discoid lupus erythematosus-like, and dermatofibroma-like. Conclusions In addition to the atypical clinical presentations previously reported, we also defined dermatofibroma-like, Kaposi sarcoma-like, dental sinus-like, juvenile xanthogranuloma-like, mastocytoma-like, and epidermoid cyst-like. It should be kept in mind that CL can clinically mimic many infectious, inflammatory, and neoplastic diseases, which should be considered in the differential diagnosis of long-term non-healing lesions, especially in endemic areas. Key message What is already known on this subject: CL is known as the great imitator disease in dermatology. What this study adds: In addition to the atypical clinical presentations previously reported, we also defined dermatofibroma-like, Kaposi sarcoma-like, dental sinus-like, juvenile xanthogranuloma-like, mastocytoma-like, and epidermoid cyst-like. How this study might affect research, practice, or policy: CL can clinically mimic many infectious, inflammatory and neoplastic diseases, which should be considered in the differential diagnosis of long-term non-healing lesions, especially in endemic areas. [ABSTRACT FROM AUTHOR]

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Abstract Background Cutaneous leishmaniasis is one of the few infectious diseases whose global prevalence is on the rise. Iran ranks among the eight most affected countries in the world. Iranian military personnel are often sent to endemic areas for cutaneous leishmaniasis without prior immunity, and they have fewer health facilities in military centers than the general population. This study aims to comprehensively investigate the situation of cutaneous leishmaniasis in Iranian military personnel across all units from 2018 to 2022 and predict the disease trend using time series analysis up to the end of 2025. Methods We analyzed data from the Iranian Ministry of Health to perform spatiotemporal and descriptive analyses based on patient frequency. Variables examined included age distribution, cutaneous leishmaniasis types (zoonotic or anthroponotic), month of healthcare facility visits, and lesion locations. This study employed the ARIMA model (p = 2, d = 0, q = 1)(P = 3, D = 0, Q = 0), for time series analysis and forecasting the disease trend up to 36 months after 2022. Results Over five years, 2,894 patients were reported. The Esfahan, Khuzestan, and Ilam provinces had the highest average patient counts, with hot spots primarily found in central, south, southwestern, and western Iran. Although the total number of patients with zoonotic cutaneous leishmaniasis was almost equal to anthroponotic cutaneous leishmaniasis, in high-risk provinces such as Esfahan, Khuzestan, and Ilam, the confirmed cases of zoonotic cutaneous leishmaniasis were much more than anthroponotic cutaneous leishmaniasis. patient numbers peak in October and November. Demographic analysis revealed that younger patients outnumbered older patients. Lesion locations were frequent on the forelimbs and lower limbs. The time series analysis for 36 months after 2022 indicated the seasonal pattern of the disease and predicted an upward trend after 2022. Conclusion While overall cases have declined, provinces such as Esfahan exhibit an upward trend. The expansion of hotspots from the west and southwestern to the center and south of Iran, coupled with an increasing trend in time series analysis, suggests the potential emergence of new foci and a rise in patient numbers in the future. In provinces with high disease prevalence, preventive measures should be prioritized, particularly in Ilam, Khuzestan, and Esfahan.

Abstract Phlebotomus argentipes is the established vector of leishmaniasis in the Indian sub-continent. Antibodies to sand fly salivary antigens are biomarkers for vector-host exposure in leishmaniasis-endemic regions. Ph. argentipes transmits Leishmania donovani in Sri Lanka, primarily causing cutaneous leishmaniasis (CL). Our study compared the performance of salivary gland homogenate (SGH) from a lab-reared local strain of Ph. argentipes females to a composite recombinant salivary biomarker (rPagSP02 + rPagSP06) in a CL-endemic population. Sera from 546 healthy individuals, 30 CL patients, and 15 non-endemic individuals were collected. Western blot analysis of Ph. argentipes SGH identified immunogenic bands between 15 kDa and 67 kDa, with bands of predicted molecular weight ∼of 15 kDa (SP02) and ∼28–30 kDa (SP06) as the major antibody targets. Indirect ELISAs using SGH or rPagSP02 + rPagSP06 antigens showed high sensitivity (96.7%) and specificity (100%), detecting comparable seropositivity in endemic populations. rPagSP02 + rPagSP06 exhibited enhanced discriminatory ability, supported by a strong positive correlation (r = 0.869) with SGH. Our findings indicate that the composite rPagSP02 + rPagSP06 salivary biomarker effectively identifies Ph. argentipes exposure in individuals living in Sri Lanka, showing promising potential for use in surveillance. These findings should be further validated to confirm the epidemiological applications in leishmaniasis-endemic regions.

Abstract Dogs are the primary reservoirs of Leishmania infantum (L. infantum), but Leishmania tropica (L. tropica) infection is also possible in dogs and can transmitted to humans. The southeast of Iran experiences a high prevalence of canine leishmaniasis (CanL), and veterinarians frequently encounter symptomatic cases. Therefore, from December 2017 to November 2022, the present case series was designed to assess the prevalence of CanL in owned dogs with cutaneous manifestations resembling CanL. A total of 500 owned dogs with dermal lesions from two endemic cities, Zabol and Kerman, were enrolled. Impression smears from skin lesions and popliteal lymph nodes were prepared from all cases, whereas blood samples were gathered from amastigote-positive dogs for serological and molecular surveys. Commercial ELISA was done on sera samples, and two-step nested PCR was used on extracted DNA to amplify variable fragments of the Leishmania species’ kinetoplast DNA (kDNA). Leishman bodies were microscopically detected in 7.2% (36/500) of dermal smears. Of the 360 owned dogs from Zabol, 2 have been diagnosed with L. tropica, and 10 have been diagnosed with L. infantum. Out of 140 owned dogs from Kerman, 8 were identified with L. tropica infection, and 16 were infected with L. infantum. Molecular results revealed the presence of 750 full dual-band bases related to the L. tropica species in 10/36 (27.7%) cases, which showed a considerable increase in canine cutaneous leishmaniosis compared with previous studies in southeastern Iran. The noticeable prevalence of L. tropica in owned dogs indicated that the dog’s role in cutaneous leishmaniosis should be re-evaluated as a possible animal reservoir in endemic areas.

Abstract Background Cutaneous leishmaniasis (CL) in Ethiopia and some parts of Kenya is predominantly caused by Leishmania aethiopica. While skin-slit (SS) microscopy is routinely used for CL diagnosis, more sensitive molecular tests are available. The Loopamp™ Leishmania detection kit (Loopamp) is a robust loop-mediated isothermal amplification (LAMP) assay with the potential for implementation in primary healthcare facilities. In this study, we comparatively assessed the diagnostic accuracy of four methods currently used to diagnose CL: Loopamp, kinetoplast DNA (kDNA) PCR, spliced leader RNA (SL-RNA) PCR and SS microscopy. Methods A study on 122 stored tape disc samples of suspected CL patients was conducted in Gondar, northwestern Ethiopia. Routine SS microscopy results were obtained from all patients. Total nucleic acids were extracted from the tapes and subjected to PCR testing targeting kDNA and SL-RNA, and Loopamp. Diagnostic accuracy was calculated with SS microscopy as a reference test. The limit of detection (LoD) of Loopamp and kDNA PCR were determined for cultured L. aethiopica and Leishmania donovani. Results Of the 122 patients, 64 (52.5%) were identified as CL cases based on SS microscopy. Although the PCR tests showed a sensitivity of 95.3% (95% confidence interval [CI] 91.6–99.1), Loopamp only had 48.4% (95% CI 39.6–57.3) sensitivity and 87.9% (95% CI 82.1–93.7) specificity. The LoD of Loopamp for L. donovani was 100-fold lower (20 fg/µl) than that for L. aethiopica (2 pg/µl). Conclusions The Loopamp™ Leishmania detection kit is not suitable for the diagnosis of CL in Ethiopia, presumably due to a primer mismatch with the L. aethiopica 18S rRNA target. Further research is needed to develop a simple and sensitive point-of-care test that allows the decentralization of CL diagnosis in Ethiopia. Graphical Abstract

Abstract Background Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by the protozoan parasite Leishmania. In Ethiopia, CL is mainly caused by Leishmania aethiopica and can present in different clinical forms. The aim of this study was to assess whether these different forms are associated with differences in parasite genetic and host systemic immune signatures. Methods Here we analysed the whole genome sequence data for 48 clinical parasite isolates and the systemic immune signature from a cohort of CL patients, who were recruited in Nefas Mewcha, Northern Ethiopia, from January 2019 to January 2022. Results Our results show that parasites from CL cases with different presentations in a single Ethiopian setting are from the same genetic population based on a permutation test of genome-wide similarity. Furthermore, a logistic regression test for genome wide association did not identify any individual genetic variants significantly associated with disease presentation. We also measured plasma chemokine and cytokine levels of 129 CL patients presenting with different forms of CL. None of the chemokine [eotaxin, eotaxin-3, interleukin (IL)-8, interferon (IFN)-γ-induced protein-10 (IP-10), monocyte chemoattractant protein (MCP)-1, MCP-4, macrophage-derived chemokines (MDC), macrophage inflammatory protein (MIP)-1α, MIP-1β and thymus- and activation-regulated chemokine (TARC)] or cytokine (IFN-γ, IL-1β, interleukin-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis factor-α) levels measured were significantly different between the different clinical presentations of CL, as measured by Kruskal–Wallis test. We also compared those with healthy nonendemic controls: our results show a chemokine (IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β and TARC) but not a cytokine immune signature in patients with CL as compared to healthy nonendemic controls, as measured by Mann-Whitney test. Conclusions The results of our study did not identify a systemic immune signature or parasite genetic factors associated with different clinical presentation of CL. Graphical abstract

Background:This study evaluated the oxidative—antioxidative status of patients with cutaneous leishmaniasis (CL) and to establish the data alteration among the patients and the control. Objectives:To determine serum levels of malondialdehyde (MDA), serum uric acid (UA), and catalase enzyme as a markers of oxidative stress in the patients suffering from CL. Materials and Methods:A total of 46 patients with CL (22 males and 24 females) aged between 5 and 60 years were subjected to investigations. Out of the total sample, 42 healthy persons (28 males and 14 females) functioned as control group, patients who received anti-leishmaniasis treatment locally or systemically for their cutaneous lesions and also patients with chronic history of medical disease or drug history for systemic or dermatological diseases were not included in this study. Results:For comparative evaluation of oxidative stress markers between patients and control; there were a significant increase in lipid peroxidation marker; serum MDA and non-enzymatic antioxidant marker—serum UA in the patient group in comparison to the control group, with non-significant decrease in enzymatic antioxidant—serum catalase enzyme in patients as compared with control groups. There is negative significant relationship for decrease of catalase enzyme for patients with CL above age of 15 years. The study of the patients with CL that is, associated with secondary bacterial infection shows a significant decrease in serum catalase enzyme when compared with control group. Conclusions:1. The results of this study clearly demonstrate the importance of serum MDA as an early biochemical indicator of peroxidative damage resulting from CL. 2. Increased serum UA, and decrease in serum catalase enzyme provided a free radical scavenger’s action.

Objective: Cutaneous leishmaniasis is a parasitic skin disease transmitted by the bite of sandflies. In our region, which is endemic for this disease, there has been a great migration from a much more endemic region and population movements from our area to Türkiye and abroad. Afterward, a pandemic was experienced. Due to these two extraordinary events and the possible epidemic potential in our region, it is useful to follow-up on the disease. We aimed to contribute to the evaluation of the disease in these processes by analyzing the data of our laboratory in recent years. Methods: Between January 2019 and December 2022, samples from patients who came to our laboratory with suspected cutaneous leishmaniasis were taken, stained and examined under a microscope. Patients were evaluated in terms of age, gender, nationality, place of residence, lesion site and duration. Results: Out of the 144 examined cases, 64 (44.4%) were positive for cutaneous leishmaniasis. Among these positive cases, 40 (62.5%) were women, 24 (37.5%) were men, and 54 (84.3%) belonged to the 0-9 age group. Of those who tested positive, 54 (84.3%) were Turkish citizens and 23 (35.9%) were Syrian citizens. Fifty-four (84.3%) patients had only single lesion. While the number of applications and positivity rates remained within normal levels in 2019 and 2020, a significant decrease was observed in both from 2021 and 2022. Conclusion: Cutaneous leishmaniasis is carried by migration, decreases in large-scale isolations such as pandemics, and its spread can be prevented with correct diagnosis and treatment. Although the number of patients may change over time and place, cutaneous leishmaniasis is a disease that threatens the health of societies and should always be monitored.

Abstract 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 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 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. Graphical Abstract