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The main feature of all forms of leishmaniasis is its occurrence against the background of a disease of the host's macrophage system. A few hours after the bite of a healthy person, a local inflammatory process occurs in the area of grafting, at which time part of the promastigotes is destroyed by the lysosomal enzymes of the host organism. Cutaneous leishmaniasis develops local histocytoma with visceral leishmaniasis, leishmania begins to develop, localizing in the reticuloendothelial cells of the internal organs (liver, spleen, bone marrow and lymph nodes). The main feature of Leishmania is the presence of a kinetoplast located near the flagellum. The kinetoplast is a unique mitochondrion that can be round, oval, or rod-shaped. It is also considered an organelle with a large amount of DNA. Promastigote forms of leishmania live in the intestinal tract of Phlebotomus, while the amastigote form occurs in humans. Amastigotes enter the phlebotomus midgut when mosquitoes suck the blood of sick people and animals. [ABSTRACT FROM AUTHOR]

Canine Visceral Leishmaniasis (CVL) and Canine Monocytic Ehrlichiosis (CME) are zoonotic diseases that cause coagulation disorders, abnormalities in various organs and systems along with vasculitis. Since it was reported that the presence of co-infection may cause more severe abnormalities, this study aimed to investigate the synergistic effects of co-infection on some coagulation analytes (prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and D-Dimer). Twenty dogs, all were mixed breed, aged 2-4 years, and determined to be co-infected with CVL and CME were used. As a result of the coagulation profile analyte measurements, the values of APTT, PT, and the concentration of FIB were determined to be higher in the Co-infected Group compared to the Control Group (p<0.05). Receiver operating characteristic (ROC) analysis revealed that PT (AUC: 0.980); APTT (AUC: 0.959), FIB (AUC: 1.000), and D-dimer (AUC: 0.929) had outstanding diagnostic discrimination. As a result, it was concluded that the presence of co-infection deteriorates the coagulation profile more severely in co-infection with CVL and CME. [ABSTRACT FROM AUTHOR]

Background: The kala-azar elimination programme has resulted in a significant reduction in visceral leishmaniasis (VL) cases across the Indian Subcontinent. To detect any resurgence of transmission, a sensitive cost-effective surveillance system is required. Molecular xenomonitoring (MX), detection of pathogen DNA/RNA in vectors, provides a proxy of human infection in the lymphatic filariasis elimination programme. To determine whether MX can be used for VL surveillance in a low transmission setting, large numbers of the sand fly vector Phlebotomus argentipes are required. This study will determine the best method for capturing P. argentipes females for MX. Methodology/Principal findings: The field study was performed in two programmatic and two non-programmatic villages in Bihar, India. A total of 48 households (12/village) were recruited. Centers for Disease Control and Prevention light traps (CDC-LTs) were compared with Improved Prokopack (PKP) and mechanical vacuum aspirators (MVA) using standardised methods. Four 12x12 Latin squares, 576 collections, were attempted (12/house, 144/village,192/method). Molecular analyses of collections were conducted to confirm identification of P. argentipes and to detect human and Leishmania DNA. Operational factors, such as time burden, acceptance to householders and RNA preservation, were also considered. A total of 562 collections (97.7%) were completed with 6,809 sand flies captured. Females comprised 49.0% of captures, of which 1,934 (57.9%) were identified as P. argentipes. CDC-LTs collected 4.04 times more P. argentipes females than MVA and 3.62 times more than PKP (p<0.0001 for each). Of 21,735 mosquitoes in the same collections, no significant differences between collection methods were observed. CDC-LTs took less time to install and collect than to perform aspirations and their greater yield compensated for increased sorting time. No significant differences in Leishmania RNA detection and quantitation between methods were observed in experimentally infected sand flies maintained in conditions simulating field conditions. CDC-LTs were favoured by householders. Conclusions/Significance: CDC-LTs are the most useful collection tool of those tested for MX surveillance since they collected higher numbers of P. argentipes females without compromising mosquito captures or the preservation of RNA. However, capture rates are still low. Author summary: Molecular xenomonitoring, screening insects for pathogen DNA/RNA, may be used for surveillance of diseases transmitted by insects. Since the proportion of insects infected with pathogens is very low in areas targeted for disease elimination, large numbers of females need to be screened. We compared three different methods for collecting Phlebotomus argentipes sand fly females, the vector of parasites causing the disease visceral leishmaniasis in the Indian subcontinent, to determine which collected the largest number of females. Other factors that may also influence selection of a particular method of collection by a disease control programme, such as the time it takes to collect and sort samples, the acceptance of householders for a particular collection method and whether RNA degradation in insect samples differed between collection methods, were also considered. Centers for Disease Control and Prevention light traps (CDC-LTs) proved to be more useful than two types of aspiration methods for collecting higher numbers of sand fly females and RNA preservation was retained. Furthermore, they took less time to install than to perform aspirations and were favoured by householders. Therefore, CDC-LTs were considered to be the most suitable collection method for molecular xenomonitoring of sand flies in India. [ABSTRACT FROM AUTHOR]

Objectives: To analyse the flow of cases of visceral leishmaniasis (VL) in the state of Ceará, Brazil, between 2007 and 2021. Methods: An ecological study was conducted using a spatial approach of newly confirmed cases of VL recorded in the Notifiable Diseases Information System. We identified individuals whose municipality of diagnosis differed from that of their residence. Flow maps, constructed using Tabwin 32 and ArcMap 9.2, allowed for the identification of the volume of traffic between the municipality of residence and that of initial care. Results: There were 6775 confirmed VL cases. As a flow indicator, 178 counties had at least one resident diagnosed in another municipality in Ceará, with 2491 VL cases and an average trip of 79 km. The largest hub for receiving cases for diagnosis was the capital Fortaleza (1478 patients from 129 other municipalities), followed by Sobral, located in the northwestern region of Ceará (599 from 55 municipalities), and Barbalha, in the southern region (171 from 29 municipalities). In this southern region, 25 municipalities moved 55 people for treatment to Juazeiro do Norte and 11 municipalities moved 39 patients to Crato. A total of 255 patients with VL from 11 municipalities in other Brazilian states, mainly from the Northeast and North, were observed and notified in health services in Ceará. Conclusions: The major centres of VL diagnosis outside residence were in the cities of Fortaleza, Sobral, Barbalha, Juazeiro do Norte and Crato. There was also an outflow of cases from other municipalities located in the northeastern and northern regions of Brazil. The flows were more intense during the first triennium of the analysis and milder from 2019 to 2021. Understanding the diagnostic flow of VL helps in decision making and the development of public policies to improve the lives of the population. [ABSTRACT FROM AUTHOR]

This retrospective cohort study analysed extracellular vesicles (EVs) and microRNAs (miRNAs) excreted in canine sera from dogs with canine visceral leishmaniasis (CanVL). A total of 56 canine sera were divided into Group I (28, from healthy dogs) and Group II (28, from the same dogs, but already with CanVL). CanVL was determined by clinical and laboratory diagnoses. Canine sera were ultra‐centrifuged to recover EVs (Can‐EVs). Analyses by transmission electron microscopy, nanoparticle tracking analysis (NTA), sodium dodecyl sulfate‐poli‐acrylammide gel eletroforesis (SDS‐PAGE) and, Immunoblot confirmed the presence of (i) microvesicles/exosomes and (ii) the tetraspanins CD63 and CD9. EVs secreted by Leishmania (Leishmania) infantum‐EVs were reactive against sera from dogs with CanVL (performed by ELISA and Immunoblot). NTA analyses exhibited that concentrations of Can‐EVs from dogs with CanVL (7.78 × 1010 Can‐EVs/mL) were higher (p <.0001) than the non‐infected dogs (mean: 1.47 × 1010 Can‐EVs/mL). These results suggested that concentrations of Can‐EVs were able to distinguish dogs with CanVL from healthy dogs. The relative expressions of 11 miRNAs species (miR‐21‐5p, miR‐146a‐5p, miR‐125b‐5p, miR‐144‐3p, miR‐194‐5p, miR‐346, miR‐29c‐3p, miR‐155‐5p, miR‐24‐3p, miR‐181a‐5p, and miR‐9‐5p) were estimated in purified miRNAs of 30 canine sera. Dogs with CanVL up‐expressed miR‐21‐5p and miR‐146a‐5p when compared with healthy dogs. The other miRNA species were poorly or not expressed in canine sera. In conclusion, this study suggests that CanVL induces changes in size and concentration of Can‐EVs, as well as, the up‐expression of miR‐21‐5p and miR‐146a‐5p in infected dogs. [ABSTRACT FROM AUTHOR]

In this serum panel–based study, we evaluated the accuracy of serological tests originally developed for visceral leishmaniasis (VL), for diagnosis of mucosal leishmaniasis (ML). A total of five tests were evaluated, four of which are registered at the National Agency of Sanitary Surveillance (Agência Nacional de Vigilância Sanitária-ANVISA) (RIDASCREEN® Leishmania Ab from R-Biopharm AG., Leishmania ELISA IgG + IgM from Vircell S.L., IFI Leishmaniose Humana—BioManguinhos, and IT-LEISH® from Bio-Rad Laboratories, Inc.), and the other a direct agglutination test (DAT-LPC) prototype kit developed at Fiocruz. The panel was composed of 40 serum samples from patients with confirmed ML and 20 from patients with mucosal involvement and negative parasitological/molecular tests for leishmaniasis and confirmation of another etiology. All cases were treated from 2009 to 2016 in a referral center for leishmaniasis in Belo Horizonte, Minas Gerais, Brazil (Instituto René Rachou, Fiocruz). Diagnostic accuracy, based on the cut-off point for VL diagnosis, was 86.2% with RIDASCREEN® Leishmania Ab, 73.3% with Leishmania ELISA IgG + IgM, and 66.7% with IFI Leishmaniose Humana, while IT-LEISH® and DAT-LPC had the lowest accuracy (38.3%), despite high specificity (100% and 95%, respectively). New cut-off points defined with sera from ML patients improved accuracy from 86.2 to 89% (p = 0.64) and 73.3 to 88% (p = 0.04) for RIDASCREEN® Leishmania Ab and Leishmania ELISA IgG + IgM, respectively. Moreover, these tests presented greater sensitivity and immunoreactivity in patients with moderate/severe clinical ML forms. The data of this study suggest that ELISA assays can contribute to laboratory diagnosis, especially for patients with moderate or severe mucosal involvement. [ABSTRACT FROM AUTHOR]

Leishmania donovani causes the neglected tropical disease visceral leishmaniasis. There is currently no vaccine available to combat the disease. Therefore, chemotherapy is the only treatment option available. However, the available drugs have various adverse effects on the host. As a result, new drugs are needed to treat the disease; natural compounds can be used as an alternative to traditional drugs. This study examined apigenin, diosmin, and naringin as prospective inhibitors against the Leishmania donovani Sterol 24-C- methyltransferase enzyme (LdSMT). All three compounds have a high affinity for the LdSMT and remain stable for 100 ns during the molecular dynamics simulation. In the cell viability assays, these compounds showed excellent IC50 values, with apigenin having the best IC50 value of 16.11 µM against Leishmania donovani promastigote. The findings of this study showed that all three flavonoids could be used as a safe alternative to conventional anti-leishmanial drugs. [ABSTRACT FROM AUTHOR]

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Post kala-azar dermal leishmaniasis (PKDL) is a skin disease that usually occurs among individuals with a past history of visceral leishmaniasis (VL). PKDL cases act as a reservoir of parasites and may play a significant role in disease transmission. Hence, prompt detection and complete treatment of PKDL cases are crucial for the control and elimination of VL. The purpose of this review was to highlight the barriers to effective control and prevention of VL/PKDL as well as potential solutions in India. Main obstacles are lack of knowledge about the disease and its vector, poor treatment-seeking behaviours, ineffective vector control measures, lack of confirmatory diagnostics in endemic areas, limited drug choices, treatment noncompliance among patients, drug resistance, and a lack of an adequate number of trained personnel in the health system. Therefore, in order to control and successfully eliminate VL in the Indian subcontinent, early detection of PKDL cases, improved diagnosis and treatment, raising awareness, and effective vector control mechanisms are necessary. [ABSTRACT FROM AUTHOR]

Purpose: In Turkey, the main causative agent of visceral leishmaniasis (VL) is Leishmania. infantum and the main causative agent of cutaneous leishmaniasis (CL) is Leishmania tropica. In this study, we aimed to discuss the possible mechanisms, clinical aspects, and threat of visceralizing L. tropica. Methods: This study includes seven cases of VL caused by L. tropica.Five patients were male (71%) and four were adults (57%). Results: All the VL patients complained of fever and splenomegaly. Fatigue, pancytopenia, and hepatomegaly were present in six patients each (86%), while weight loss and gastrointestinal system (GIS) symptoms were present in 5 patients (71%). Conclusions: In this study, we have evaluated seven cases of visceralized L. tropica (VLT) in the context of the changing leishmaniasis epidemiology in Turkey. We have evaluated the possible mechanisms of visceralization; inter- and intraspecies genetic exchange with all the old world leishmaniasis agents present in the region, stress induced by inappropriate use of drugs, and possible ongoing adaptation mechanisms of Leishmania spp. The threat posed by VLT is significant as L. tropica is the most widespread and most common cause of leishmaniasis in Turkey. We do not know the vectorial capacity of the sand flies for the transmission of VLT strains or if these strains are in circulation in Turkey. Future studies should be carried out to investigate these issues as the transition of L. tropica from a mild disease-causing agent to a mortal one poses a significant public health concern for Turkey and Europe. [ABSTRACT FROM AUTHOR]

Objective: Phlebotomine sand flies are the primary vectors of leishmaniasis; visceral form of disease is transmitted mainly by species belonging to Larroussius and Adlerius subgenus. Species identification of some females in Larroussius subgenus is not easy due to the high similarity. Accurate species identification enables control operations to target only main vectors and increase understanding of ecological needs, bionomic characteristics, and behavioral traits. The purpose of current study was to use two approaches based on internal and external morphological characters to identify the wild caught of female specimens belonged to Larroussius subgenus and investigate Leishmania infection. Methods: Totally, 128 specimens belonging to Larroussius' subgenus were collected from a VL focus in northwestern Iran, species differentiation was done by two approaches proposed in literature: (1) characters of pharyngeal armature, number of Spermathecal segment, length of spermathecal neck, palpal and ascoid formulae; (2) blindly on the basis of the shape of the base of spermathecal duct. Their potential infection to Leishmania was investigated by kDNA-Nested-PCR. Results: The results of species identification were consistent based on two methods. Among three identified species, Phlebotomus perfiliewi was found to be the dominant species, followed by Ph. neglectus and Ph. tobbi. Two specimens of Ph. perfiliewi were found to be infected by Leishmania infantum, which emphasizes the role of this species in VL transmission in study area. Conclusion: It is suggested that combination of the characters used here be considered for species identification of female of Larroussius subgenus to take advantage of maximum characters, especially where species present sympatrically. [ABSTRACT FROM AUTHOR]

Leishmaniasis is an infectious disease transmitted to humans by the bite of a female sandfly. In Morocco, leishmaniasis is considered a real health concern. The aims of this study were to analyze the epidemiological situation and identify localities at risk of transmission of leishmaniasis in the province of Moulay Yaâcoub. The study was a retrospective analysis of leishmaniasis cases reported over a period of 11 years from 2005 to 2015 in Moulay Yaâcoub Province. The data were collected from the registries of the Prefectural Cell of the Moulay Yaâcoub Province Medical Delegation, Regional Directorate of Health, Fez-Meknes, and analyzed statistically. The results showed that leishmaniasis was present, with an annual average of 18.63 cases. A total of 205 cases of leishmaniasis were recorded, with 53% cutaneous leishmaniasis and 47% visceral leishmaniasis. Females were the most affected, at 53.7%, mainly by cutaneous leishmaniasis, although the difference was not statistically significant (χ² = 0.7, pvalue = 0.79). Cutaneous leishmaniasis affected all age groups, whereas visceral leishmaniasis affected only young people under 30. The communes most affected were Ain Chkef and Ain Kansara, and the difference between the proportions of cases detected in the different sites was statistically significant (χ² = 96.03, p-value < 0.05). To the best of our knowledge, this is the first time such a study has been conducted in Moulay Yaâcoub Province. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania and is transmitted through the bite of infected female sandflies. In the Mediterranean region, visceral leishmaniasis is caused by Leishmania. infantum, and it is usually responsible for symptoms such as fever, pancytopenia and enlargement of the liver and spleen. Relapse is rare in immunocompetent patients as much as the mucous involvement. We present a rare case of mucosal relapse of visceral leishmaniasis in a child with SARS-CoV-2 infection and perform an extensive review of the literature about leishmaniasis relapses in children. Atypical mucosal involvement during Leishmaniasis relapse is an eventuality in pediatric patients. Clinical follow-up and periodic PCR tests must be considered essential for the early recognition and treatment of an eventual relapse. [ABSTRACT FROM AUTHOR]

Histoplasmosis is an endemic mycosis in the Americas. However, its diagnosis is challenging due to the complexity and limited availability of conventional laboratory techniques—antigen tests, culture, and staining. Microscopic preparations often confuse with other pathogens, such as Leishmania spp. The genus Histoplasma capsulatum comprises three varieties: var. capsulatum, var. duboissi, and var. farciminosum, which cannot be distinguished using conventional techniques. An infant from a tropical region of Ecuador was hospitalized for fever, bloody diarrhea, and anemia persisting for two months. Upon admission, he received antibiotics and immunosuppressants. Histopathological examination of the lymph nodes, intestines, and bone marrow aspirate reported the presence of Leishmania-like amastigotes, and treatment was initiated with meglumine antimoniate and conventional amphotericin B. However, subsequent analysis of samples using PCR and DNA sequencing identified H. capsulatum var. capsulatum but not Leishmania. Despite fluconazole and amphotericin B, the infant succumbed to the disease. The delay in clinical and laboratory diagnosis of histoplasmosis and the use of nonspecific and ineffective drugs such as fluconazole led to disease dissemination and, ultimately, death. Implementing molecular diagnosis and antigen tests in laboratories located in endemic regions and reference hospitals is crucial. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is one of the most neglected tropical diseases and is spread mainly in impoverished regions of the world. Although many studies have focused on the host's response to Leishmania invasion, relatively less is known about the complex processes at the metabolic level, especially the metabolic alterations in the infected hosts. Methods: In this study, we conducted metabolomics analysis on the urine of golden hamsters in the presence or absence of visceral leishmaniasis (VL) using the ultra-performance liquid chromatography (UPLC) system tandem high-resolution mass spectrometer (HRMS). The metabolic characteristics of urine samples, along with the histopathological change and the parasite burden of liver and spleen tissues, were detected at 4 and 12 weeks post infection (WPI), respectively. Results: Amino acid metabolism was extensively affected at both stages of VL progression. Meanwhile, there were also distinct metabolic features at different stages. At 4 WPI, the significantly affected metabolic pathways involved alanine, aspartate and glutamate metabolism, the pentose phosphate pathway (PPP), histidine metabolism, tryptophan metabolism and tyrosine metabolism. At 12 WPI, the markedly enriched metabolic pathways were almost concentrated on amino acid metabolism, including tyrosine metabolism, taurine and hypotaurine metabolism and tryptophan metabolism. The dysregulated metabolites and metabolic pathways at 12 WPI were obviously less than those at 4 WPI. In addition, seven metabolites that were dysregulated at both stages through partial least squares-discriminant analysis (PLS-DA) and receiver-operating characteristic (ROC) tests were screened to be of diagnostic potential. The combination of these metabolites as a potential biomarker panel showed satisfactory performance in distinguishing infection groups from control groups as well as among different stages of infection. Conclusion: Our findings could provide valuable information for further understanding of the host response to Leishmania infection from the aspect of the urine metabolome. The proposed urine biomarker panel could help in the development of a novel approach for the diagnosis and prognosis of VL. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is a severe and often fatal form of leishmaniasis caused by Leishmania donovani in the Indian sub-continent. Post Kala-azar Dermal Leishmaniasis (PKDL) is a late cutaneous manifestation of VL, typically occurring after apparent cure of VL, but sometimes even without a prior history of VL in India. PKDL serves as a significant yet neglected reservoir of infection and plays a crucial role in the transmission of the disease, posing a serious threat to the VL elimination program in the Indian sub-continent. Therefore, the eradication of PKDL should be a priority within the current VL elimination program aimed at achieving a goal of less than 1 case per 10,000 in the population at the district or sub-district levels of VL endemic areas. To accomplish this, a comprehensive understanding of the pathogenesis of PKDL is essential, as well as developing strategies for disease management. This review provides an overview of the current status of diagnosis and treatment options for PKDL, highlighting our current knowledge of the immune responses underlying disease development and progression. Additionally, the review discusses the impact of PKDL on elimination programs and propose strategies to overcome this challenge and achieve the goal of elimination. By addressing the diagnostic and therapeutic gaps, optimizing surveillance and control measures, and implementing effective intervention strategies, it is possible to mitigate the burden of PKDL and facilitate the successful elimination of VL in the Indian sub-continent. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n = 5,346 and CSC-II, n = 317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble Leishmania infantum Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (p = 0.0076) and a tendency of increased CXCL9 (p = 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is a rare infectious disease observed in subtropical and tropical areas. This disease that demonstrates different clinical characteristics is caused by intracellular Leishmania protozoan. One of the important countries facing the incidence of this infectious disease is Iran. Recently, human immunodeficiency virus–Leishmania coinfection has been indicated in Iran. Case presentation: In the present case report, we show an atypical case of severe visceral leishmaniasis in a 52-year-old Iranian-Arab male with positive human immunodeficiency virus status. Leishmaniasis was detected by node biopsy and subsequently histopathology evaluations and confirmed by molecular methods. Conclusions: The current study was the first report of an atypical case of a patient with Leishmania–human immunodeficiency virus coinfection in southwestern Iran, which was not responsive to the treatment. Therefore, the health authorities should be aware of these reports, which require permanent clinical follow-up of the patients as well as effective treatments. [ABSTRACT FROM AUTHOR]

Endemic in Brazil, visceral leishmaniasis (VL) is a zoonotic infection that is among the most important parasitic diseases transmitted by vectors. Dogs are the main reservoirs of canine leishmaniasis (CanL) and their identification is used in some countries as part of disease prevention and control measures in the canine and human population. In this context, serological tests are necessary, composed of antigens capable of correctly identifying infected dogs, minimizing the number of false-negative cases. This study aimed to identify more immunoreactive peptides derived from two previously described whole proteins (rDyn-1 and rKDDR-plus) and compare their performance to the control antigens rK39 and the crude extract for the detection of dogs infected with L. infantum, especially the asymptomatic ones. The three selected peptides and a mixture of them, along with the rDyn-1, rKDDR-plus, rK39, and crude extract antigens were evaluated using indirect ELISA with sera samples from 186 dogs with CanL, being asymptomatic (n = 50), symptomatic (n = 50), co-infected (n = 19), infected with Babesia sp. (n = 7), Ehrlichia sp. (n = 6), T. cruzi (n = 20) and uninfected (n = 34). The results showed that the rDyn-1 protein and the peptide mixture had the highest sensitivity (100% and 98.32%, respectively) and specificity (97.01 and 98.51, respectively). A high degree of kappa agreement was found for rDyn-1 protein (0.977), mixed peptides (0.965), rKDDR-plus protein (0.953), K-plus peptide 1 (0.930) and Dyn-1 peptide (0.893). The mixture of peptides showed the highest likelihood (65.87). The ELISA using the mixture of peptides and the rDyn-1 protein showed high performance for CanL serodiagnosis. More mix combinations of the peptides and additional extended field tests with a larger sample size are recommended. Author summary: Canine leishmaniasis (CanL) is a parasitic zoonotic infection of dogs caused by Leishmania spp. parasites. In Brazil, CanL is among the most important vector-borne parasitic diseases. Dogs are the main reservoirs of the disease and in some countries have been regularly culled as part of government policy to control human leishmaniasis. The identification of infected dogs, regardless of the clinical condition, is necessary as part of the prevention and control measures of the disease in the canine population and consequently in the human population. In this context, it is necessary serological tests, composed of antigens capable of correctly identifying infected, asymptomatic, as well as symptomatic dogs, minimizing the number of false negative cases. Therefore, this study aimed to compare the efficacy between two previously described whole proteins (rDyn-1 and rKDDR-plus) with their more immunoreactive synthetic peptides to sera from symptomatic and asymptomatic dogs selected in immunoblotting assays and to evaluate in ELISA assays. ELISA using the rDyn-1 protein and mixed peptides showed high performance in the diagnosis of CanL. [ABSTRACT FROM AUTHOR]

We consider the transmission of visceral leishmaniasis in three populations: humans, dogs and sandflies. To investigate the effects of spatial heterogeneity and temporal periodicity on disease transmission, a nonlocal periodic reaction‐diffusion equation model is developed. We introduce the basic reproduction number R0$$ {\mathcal{R}}_0 $$ and establish the global dynamics. Numerical simulations show that (i) R0$$ {\mathcal{R}}_0 $$ is overestimated in the absence of spatial heterogeneity; (ii) R0$$ {\mathcal{R}}_0 $$ is underestimated without considering the effect of temporal seasonality; and (iii) shortening periodic delays of visceral leishmaniasis reduces the risk of disease transmission. [ABSTRACT FROM AUTHOR]

This work describes the design, synthesis, and biological activities of new selenoester derivatives and its homologs thioesters. Thirty-two compounds were developed following an economical synthetic route, achieving small molecules, with structural characteristics similar to those present in antileishmanial drugs such as miltefosine (MIL) and paromomycin (PMN). These compounds were tested in vitro against strains of Leishmania major (L. major) and Leishmania infantum (L. infantum). The L. infantum strain (causative agent of visceral leishmaniasis) exhibited the highest sensitivity. Thus, four selanylacetic acid derivatives (A4, A5, A6 and A8) presented IC50 values below 40 µM in this strain. These derivatives also demonstrated low toxicity and high selectivity in PMA-differentiated THP-1 macrophages. The A4–A6 and A8 derivatives were evaluated in order to determine their pharmacological behavior, using drug combination studies with the reference drugs amphotericin B (AMB), MIL and PMN. Compounds A6 and A8 presented a potent synergistic interaction with MIL, which is the only oral drug available for the treatment of visceral leishmaniasis. Therefore, compounds A6 and A8 present significant potential as therapeutic candidates for the treatment of leishmaniasis based on their remarkable leishmanicidal characteristics and pharmacological synergism. [ABSTRACT FROM AUTHOR]

Simple Summary: Different diagnoses for Feline leishmaniasis have been studied, mainly in endemic regions of Canine Visceral Leishmaniasis (CVL), aiming to contribute to the differentiation of diseases manifested by cats with the aim of offering the best treatment for the animal. However, the study of less invasive and sensitive diagnostic techniques can be useful concomitantly with serological techniques such as the Immunofluorescent Antibody Test (IFAT) and ELISA in epidemiological surveys. In this sense, the objective of our study was to evaluate positivity for Leishmania from material collected in a less invasive way in serologically positive and negative cats from an endemic region for CVL; through conjunctival swabs for molecular analysis by PCR, with subsequent screening of the species by the HRM technique; and confirmation by genetic sequencing. Although few samples could be detected from the conjunctival cell samples (4/36), there was a good concordance of species confirmation by the HRM technique and genetic sequencing. Of these four animals, three were confirmed as positive by the two serological techniques, which suggests that they had contact with the parasite and produced antibodies. Therefore, HRM would be an alternative as a screening technique for different species of Leishmania followed by confirmation by genetic sequencing. Background and objectives: Feline leishmaniasis (FeL) is caused by several species of parasites of the genus Leishmania. The disease can occur with the presence or absence of clinical signs, similar to those observed in other common infectious diseases. In endemic regions for FeL, the infection has been associated with dermatological lesions. Therefore, considering the search for less invasive and more effective diagnostic techniques, we aimed to investigate the presence of Leishmania spp. in domestic cats through Polymerase Chain Reaction (PCR) and high-resolution melting (HRM) analyses of conjunctival, oral, and nasal epithelial cells, and we detected the presence of anti-Leishmania IgG antibodies from serological techniques of the Immunofluorescent Antibody Test (IFAT) and ELISA. Methods: The PCR and HRM for detection of Leishmania spp. were performed on 36 samples of epithelial cells from the conjunctiva of male and female cats, collected using sterile swabs. The serological tests IFAT and ELISA were also performed. Results: The prevalence of Leishmania donovani infection was 11.1% (4/36) by PCR assay, and those results were confirmed for Leishmania species using the HRM technique. Twenty-four cats (24/36 = 66.7%) were reactive to the IFAT and twenty-two cats were reactive by the ELISA technique (22/36 = 61.1%). Interpretation and Conclusions: The use of conjunctival swabs was shown to be a non-invasive, practical, and easy-to-perform technique, and in addition to the genetic sequencing and HRM, it was able to identify the parasitic DNA of L. donovani in cats. This technique can be used for screening diagnosis in future epidemiological surveys of FeL and can be used as a complement to clinical and/or serological tests, as well as associating the clinical history of the animal, for the diagnostic conclusion. [ABSTRACT FROM AUTHOR]

• Severe visceral leishmaniasis with non-ulcerated cutaneous leishmaniasis. • A Crithidia -related parasite was isolated from bone marrow aspirate and spleen. • Whole-genome sequencing of clinical isolates suggested a novel parasite species. • Clinical implications of this trypanosomatid co-infection remain unknown in visceral leishmaniasis. [Display omitted] We report a refractory and relapsed visceral leishmaniasis case in a male child patient followed from 2016 to 2020, whose clinical isolates from multiple relapses were analyzed at the genome level. To the best of our knowledge, it is the first report that both visceral leishmaniasis and non-ulcerated cutaneous leishmaniasis have concomitantly manifested in the same patient. Importantly, sequence analysis revealed that the patient was co-infected with Leishmania infantum and a Crithidia -related parasite, which was previously found in a fatal case of visceral leishmaniasis from the same endemic region. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis is a zoonotic vector‐borne disease caused by Leishmania infantum. The infection often remains asymptomatic, though clinical forms may occur in immunosuppressed individuals. Although data on leishmaniasis in humans are available worldwide, the exposure to L. infantum of workers conducting outdoor activities has been scantly investigated, and it is limited to military personnel operating in endemic regions. This study aimed to assess the seroprevalence of L. infantum in different groups of outdoor workers and the occupational risk factors. The cross‐sectional study was performed on 229 workers including forestry guards, farmers, veterinarians, geologists and agronomists from three regions of southern Italy (i.e., Apulia, Basilicata and Campania). All serum samples were screened for L. infantum‐specific IgG/IgM by using automated indirect chemiluminescent immunoassays. Overall, 5.7% (13/229) of workers was positive to anti‐L. infantum antibodies, with the highest seroprevalence in veterinarians (13.6%). An increased occupational health surveillance for L. infantum infection in outdoor workers is essential to better understand the risk of exposure in specific jobs. Furthermore, guidelines and education along with a One Health collaboration among veterinarians, physicians, parasitologists and occupational health care professionals are crucial for the prevention of this disease. [ABSTRACT FROM AUTHOR]

In the Americas, the sandfly Lutzomyia longipalpis is the main vector of the parasitic protozoa Leishmania infantum, the etiological agent of visceral leishmaniasis (VL). The Lu. longipalpis species complex is currently discontinuously distributed across the Neotropical region, from Mexico to the north of Argentina and Uruguay. During its continental spreading, it must have adapted to several biomes and temperature amplitudes, when founder events should have contributed to the high genetic divergence and geographical structure currently observed, reinforcing the speciation process. The first report of Lu. longipalpis in Uruguay was in 2010, calling the attention of Public Health authorities. Five years later, the parasite Le. infantum was recorded and in 2015 the first case of VL in canids was reported. Hitherto seven human cases by VL have been reported in Uruguay. Here, we publish the first DNA sequences from the mitochondrial genes ND4 and CYTB of Lu. longipalpis collected in Uruguay, and we used these molecular markers to investigate their genetic variability and population structure. We described four new ND4 haplotypes in a total of 98 (4/98) and one CYTB in a total of 77 (1/77). As expected, we were able to establish that the Lu. longipalpis collected in two localities (i.e. Salto and Bella Unión) from the north of Uruguay are closely related to the populations from neighbouring countries. We also propose that the possible route for the vector arrival to the region may have been through vegetation and forest corridors of the Uruguay River system, as well as it may have benefited from landscape modifications generated by commercial forestation. The ecological‐scale processes shaping Lu. longipalpis populations, the identification of genetically homogeneous groups and the gene flow among them must be carefully investigated by using highly sensible molecular markers (i.e. genome wide SNPs) since it will help to the understanding of VL transmission and contribute to the planification of public policies on its control. [ABSTRACT FROM AUTHOR]

Visceral leishmaniosis is one recent example of a global illness that demands our best efforts at understanding. Thus, mathematical modeling may be utilized to learn more about and make better epidemic forecasts. By taking into account the Caputo and Caputo-Fabrizio derivatives, a frictional model of visceral leishmaniosis was mathematically examined based on real data from Gedaref State, Sudan. The stability analysis for Caputo and Caputo-Fabrizio derivatives is analyzed. The suggested ordinary and fractional differential mathematical models are then simulated numerically. Using the Adams-Bashforth method, numerical simulations are conducted. The results demonstrate that the Caputo-Fabrizio derivative yields more precise solutions for fractional differential equations. [ABSTRACT FROM AUTHOR]

Control of the intracellular parasite Leishmania (L.) requires the activation of strong type 1 cellular immune responses. Towards this goal, in the present study, a multiepitope chimeric protein named LiChimera was encapsulated into cationic liposomes and its protective efficacy against experimental visceral leishmaniasis was investigated. Liposomal LiChimera conferred significant protection against L. infantum as evidenced by the significantly reduced parasite loads in the spleen and liver. Protection detected in Lipo:LiChimera-immunized mice was dependent on the differentiation of long-lasting cellular immune responses and particularly the induction of antigen-specific multifunctional memory CD4+ TH1 and CD8+ T cells that persisted during infection, as evidenced by the persistent high production of IFN-γ and IL-2 and proliferation activity. Notably, protected mice were also characterized by significantly low numbers of non-regulatory CD4+ T cells able to co-produce IFN-γ and IL-10, an important population for disease establishment, as compared to non-immunized control group. Collectively, these results demonstrate that cationic liposomes containing LiChimera can be considered an effective candidate vaccine against visceral leishmaniasis. [ABSTRACT FROM AUTHOR]

Recent studies suggest that the association of antigens in microparticles increases the anti-Leishmania vaccine immunogenicity. This study aims to investigate the in situ effect of the adjuvant performance consisting of chitosan-coated poly(D,L-lactic) acid submicrometric particles (SMP) and analyze the inflammatory profile and toxicity. Two formulations were selected, SMP1, containing poly(D,L-lactide) (PLA) 1% wt/v and chitosan 1% wt/v; and SMP2, containing PLA 5% wt/v and chitosan 5% wt/v. After a single dose of the unloaded SMP1 or SMP2 in mice, the SMPs promoted cell recruitment without tissue damage. In addition, besides the myeloperoxidase (MPO) activity having demonstrated similar results among the analyzed groups, a progressive reduction in the levels of N-acetyl-β-D-glucosaminidase (NAG) until 72 h was observed for SMPs. While IL-6 levels were similar among all the analyzed groups along the kinetics, only the SMPs groups had detectable levels of TNF-α. Additionally, the Leishmania braziliensis antigen was encapsulated in SMPs (SMP1Ag and SMP2Ag), and mice were vaccinated with three doses. The immunogenicity analysis by flow cytometry demonstrated a reduction in NK (CD3−CD49+) cells in all the SMPs groups, in addition to impairment in the T cells subsets (CD3+CD4+) and CD3+CD8+) and B cells (CD19+) of the SMP2 group. The resulting data demonstrate that the chitosan-coated SMP formulations stimulate the early events of an innate immune response, suggesting their ability to increase the immunogenicity of co-administered Leishmania antigens. [ABSTRACT FROM AUTHOR]

Background: Porteirinha is endemic for visceral leishmaniasis (VL), with intense disease transmission of the disease. We evaluated the impact of canine euthanasia as a single control measure on the incidence of VL in humans and canines. Methods: A prospective observational cohort study was carried out over four years (1998–2002) in 8 of the 12 neighborhoods of the city. The dynamics of canine visceral leishmaniasis (CVL) transmission were evaluated for 2 years, before beginning the screening–culling intervention. The comparative morbidity index (CMI) was used to stratify areas with the greatest risk of CVL, and the spatial distribution of human and canine VL cases was compared using univariate and bivariate K-functions. Results: Human cases conglomerated in three neighborhoods. Spatial clusters were detected for CVL in 1998, 2000, and 2001, but not in 1999, when greater spatial dispersion occurred. The screening and culling intervention reduced the number of human VL cases and decreased the incidence of CVL, mainly in neighborhoods with a high CMI. Conclusions: The systematic euthanasia of seropositive dogs was shown to be an effective control action of the Program for Control of Visceral Leishmaniasis (PCLV) in Brazil. The fundamental role of domestic dogs in the epidemiological chain of VL was reaffirmed. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a widespread group of infectious diseases that significantly impact global health. Despite high prevalence, leishmaniasis often receives inadequate attention in the prioritization of measures targeting tropical diseases. The causative agents of leishmaniasis are protozoan parasites of the Leishmania genus, which give rise to a diverse range of clinical manifestations, including cutaneous and visceral forms. Visceral leishmaniasis (VL), the most severe form, can be life-threatening if left untreated. Parasites can spread systemically within the body, infecting a range of organs, such as the liver, spleen, bone marrow and lymph nodes. Natural reservoirs for these protozoa include rodents, dogs, foxes, jackals, and wolves, with dogs serving as the primary urban reservoir for Leishmania infantum. Dogs exhibit clinical and pathological similarities to human VL and are valuable models for studying disease progression. Both human and canine VL provoke clinical symptoms, such as organ enlargement, fever, weight loss and abnormal gamma globulin levels. Hematologic abnormalities have also been observed, including anemia, leukopenia with lymphocytosis, neutropenia, and thrombocytopenia. Studies in dogs have linked these hematologic changes in peripheral blood to alterations in the bone marrow. Mouse models of VL have also contributed significantly to our understanding of the mechanisms underlying these hematologic and bone marrow abnormalities. This review consolidates information on hematological and immunological changes in the bone marrow of humans, dogs, and mice infected with Leishmania species causing VL. It includes findings on the role of bone marrow as a source of parasite persistence in internal organs and VL development. Highlighting gaps in current knowledge, the review emphasizes the need for future research to enhance our understanding of VL and identify potential targets for novel diagnostic and therapeutic approaches.

Background: This study describes the spatial and temporal distribution between 2005 and 2020 of human and animal leishmaniasis by Leishmania infantum in European countries reporting autochthonous cases, and highlights potential activities to improve disease control. Methodology/Principal findings: It was based on a review of the scientific literature and data reported by the World Health Organization (WHO), the World Organization for Animal Health (WOAH) and the Ministries of Health, including hospital discharges in some countries. Autochthonous infections were reported in the scientific literature from 22 countries, including 13 and 21 countries reporting human and animal infections, respectively. In contrast, only 17 countries reported autochthonous human leishmaniasis cases to the WHO and 8 countries animal infections to the WOAH. The number of WOAH reported cases were 4,203, comprising 4,183 canine cases and 20 cases in wildlife. Of 8,367 WHO reported human cases, 69% were visceral leishmaniasis cases—of which 94% were autochthonous—and 31% cutaneous leishmaniasis cases—of which 53% were imported and mostly in France. The resulting cumulative incidence per 100,000 population of visceral leishmaniasis between 2005–2020, was highest in Albania (2.15 cases), followed by Montenegro, Malta, Greece, Spain and North Macedonia (0.53–0.42), Italy (0.16), Portugal (0.09) and lower in other endemic countries (0.07–0.002). However, according to hospital discharges, the estimated human leishmaniasis incidence was 0.70 in Italy and visceral leishmaniasis incidences were 0.67 in Spain and 0.41 in Portugal. Conclusions/Significance: Overall, there was no evidence of widespread increased incidence of autochthonous human leishmaniasis by L. infantum in European countries. Visceral leishmaniasis incidence followed a decreasing trend in Albania, Italy and Portugal, and peaked in Greece in 2013, 2014 and 2017, and in Spain in 2006–2007 and 2011–2013. Animal and human cutaneous leishmaniasis remain highly underreported. In humans, hospital discharge databases provide the most accurate information on visceral leishmaniasis and may be a valuable indirect source of information to identify hotspots of animal leishmaniasis. Integrated leishmaniasis surveillance and reporting following the One Health approach, needs to be enhanced in order to improve disease control. Author summary: Leishmaniasis caused by the protozoan parasite Leishmania infantum, is a zoonotic sand fly-transmitted disease endemic in southern Europe, of great medical and veterinary importance. Environmental and human-related changes affecting the risk of exposure to vectors, such as travelling of infected animals, urbanization of endemic rural areas and climate change are some examples of drivers of the epidemiology of leishmaniasis. In this paper, we review the distribution and assess the evidence of emergence of human and animal leishmaniasis between 2005 and 2020 in endemic European countries. We found autochthonous infections in every Mediterranean and Balkan countries with a highly variable incidence. However, we detected no evidence of a widespread increased incidence across Europe. Notwithstanding this, underreporting is very high for animal and cutaneous human leishmaniasis. Moreover, human hospital discharges are the most accurate source of data for estimating the incidence of severe human visceral leishmaniasis, and this could be used to identify hotspots of leishmaniasis in animal reservoirs of infection. Consequently, we encourage integrated surveillance and accurate notification of cases following the One Health approach to adopt effective strategies resulting in a better control of leishmaniasis. [ABSTRACT FROM AUTHOR]

Visceral Leishmaniasis (VL) is a neglected disease that affects between 50,000 and 90,000 new cases annually worldwide. In Brazil, VL causes about 3500 cases/per year. This chronic disease can lead to death in 90% of untreated cases. Thus, it is necessary to study safe technologies for diagnosing, treating, and controlling VL. Specialized laboratories carry out the VL diagnosis, and this step has a significant automation power through methods based on computational tools. The gold standard for detecting VL is the microscopy of material aspirated from the bone marrow to search for amastigotes. This work aims to assist in detecting amastigotes from microscopy images using deep learning techniques. The proposed methodology consists of segmenting the Leishmania parasites in the images, precisely indicating the location of the amastigotes in the image. In the detection of VL parasites, in this methodology, a Dice of 80.4% was obtained, Intersection over Union (IoU) of 75.2%, Accuracy of 99.1%, Precision of 81.5%, Sensitivity of 72.2%, Specificity of 99.6%, and Area under the Receiver Operating Characteristics Curve (AUC) of 86.5%. The results are promising and demonstrate that deep learning models trained with images of microscopy slides of biological material can precisely help the specialist detect VL in humans. [ABSTRACT FROM AUTHOR]

Background: In the Somali region of Ethiopia, visceral leishmaniasis (VL) is a public health concern. However, VL epidemiology and sand fly vectors have not been well studied in various areas of the regional state, including Denan district. Therefore, this study was conducted to determine the sero-prevalence, associated factors, and distribution of sand fly vectors of VL in Denan district, south-eastern Ethiopia. Methods: A facility-based cross-sectional study was conducted from April to September 2021 among VL patients with classic signs and symptoms visiting Denan Health Center in south-eastern Ethiopia. Using a convenience sampling method, 187 blood samples were collected from individuals who visited Denan Health Center during the study period. Blood samples were subjected to Direct Agglutination Test for the detection of antibodies to VL. A pre-tested structured questionnaire was also used to gather information on risk factors and other characteristics of knowledge and attitude assessment. Sand flies were also collected from indoor, peri-domestic, mixed forest, and termite mounds using light and sticky traps to determine the fauna and abundance. Results: The overall sero-prevalence rate was 9.63% (18/187). The sero-prevalence was significantly associated with outdoor sleeping (OR = 2.82), the presence of damp floors (OR = 7.76), and sleeping outdoor near animals (OR = 3.22). Around 53.48% of the study participants had previously heard about VL. Study participants practiced different VL control methods, including bed nets (42%), insecticide spraying (32%), smoking plant parts (14%), and environmental cleaning (8%). In total, 823 sand fly specimens, comprising 12 species in two genera (Phlebotomus and Sergentomyia), were trapped and identified. The most abundant species was Sergentomyia clydei (50.18%), followed by Phlebotomus orientalis (11.42%). Also, a higher proportion of P. orientalis was found in termite mounds (65.43%), followed by mixed forest (37.8%) and peri-domestic (20.83%) habitats. Conclusion: The study demonstrated a 9.63% sero-positivity of VL and a remarkable gap in knowledge, attitude, and practices towards VL. P. orientalis was also detected, which could be a probable vector in this area. Thus, public education should be prioritized to improve the community's awareness of VL and its public health impact. In addition, detailed epidemiological and entomological studies are recommended. [ABSTRACT FROM AUTHOR]

Leishmania donovani is the causative organism for visceral leishmaniasis. Although this parasite was discovered over a century ago, nothing is known about role of potassium channels in L. donovani. Potassium channels are known for their crucial roles in cellular functions in other organisms. Recently the presence of a calcium-activated potassium channel in L. donovani was reported which prompted us to look for other proteins which could be potassium channels and to investigate their possible physiological roles. Twenty sequences were identified in L. donovani genome and subjected to estimation of physio-chemical properties, motif analysis, localization prediction and transmembrane domain analysis. Structural predictions were also done. The channels were majorly α-helical and predominantly localized in cell membrane and lysosomes. The signature selectivity filter of potassium channel was present in all the sequences. In addition to the conventional potassium channel activity, they were associated with gene ontology terms for mitotic cell cycle, cell death, modulation by virus of host process, cell motility etc. The entire study indicates the presence of potassium channel families in L. donovani which may have involvement in several cellular pathways. Further investigations on these putative potassium channels are needed to elucidate their roles in Leishmania. [ABSTRACT FROM AUTHOR]

Eukaryotic cells have distinct membrane-enclosed organelles, each with a unique biochemical signature and specialized function. The unique identity of each organelle is greatly governed by the asymmetric distribution and regulated intracellular movement of two important biomolecules, lipids, and proteins. Non-vesicular lipid transport mediated by lipid-transfer proteins (LTPs) plays essential roles in intra-cellular lipid trafficking and cellular lipid homeostasis, while vesicular transport regulates protein trafficking. A comparative analysis of non-vesicular lipid transport machinery in protists could enhance our understanding of parasitism and basis of eukaryotic evolution. Leishmania donovani, the trypanosomatid parasite, greatly depends on receptor-ligand mediated signalling pathways for cellular differentiation, nutrient uptake, secretion of virulence factors, and pathogenesis. Lipids, despite being important signalling molecules, have intracellular transport mechanisms that are largely unexplored in L. donovani. We have identified a repertoire of sixteen (16) potential lipid transfer protein (LTP) homologs based on a domain-based search on TriTrypDB coupled with bioinformatics analyses, which signifies the presence of well-organized lipid transport machinery in this parasite. We emphasized here their evolutionary uniqueness and conservation and discussed their potential implications for parasite biology with regards to future therapeutic targets against visceral leishmaniasis. [ABSTRACT FROM AUTHOR]

Objectives 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. Methods The antileishmanial activities of OLPC were evaluated and compared with miltefosine in vitro against intracellular amastigotes of seven CL-causing species. Following the confirmation of significant in vitro activity, the performance of the maximum tolerated dose of OLPC was evaluated in an experimental murine model of CL followed by a dose–response titration and the efficacy evaluation of four OLPC formulations (two with a fast-release and two with a slow-release profile) using bioluminescent Leishmania major parasites. Results OLPC demonstrated potent in vitro activity of the same order as miltefosine in the intracellular macrophage model against a range of CL-causing species. A dose of 35 mg of OLPC/kg/day administered orally for 10 days was well-tolerated and able to reduce the parasite load in the skin of L. major -infected mice to a similar extent as the positive control paromomycin (50 mg/kg/day, intraperitoneally) in both in vivo studies. Reducing the dose of OLPC resulted in inactivity and modifying the release profile using mesoporous silica nanoparticles led to a decrease in activity when solvent-based loading was used in contrast to extrusion-based loading, which had no impact on its antileishmanial efficacy. Conclusions Together, these data suggest that OLPC could be a promising alternative to miltefosine treatment for CL. Further investigations exploring experimental models with additional Leishmania species and skin pharmacokinetic and dynamic analyses are required. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is an endemic disease in Sudan that caused by Leishmania spp. Several studies suggest neurological manifestations in visceral leishmaniasis, such as burning sensation, and weakness. This study was aimed to assess the frequency of the neurological manifestations in Visceral Leishmaniasis. Methods: This is a descriptive, prospective cohort study, was conducted in The Tropical Teaching Hospital - Khartoum for one-year duration. A pretested questionnaire contained the study variables were conducted, nerve conduction Study (NCS) and laboratory tests were done. SPSS v 26.0 was used to analyze the data. Results: Forty four percent of total patients (22/50) were symptomatic. Peripheral neuropathy was elicited in 60% (30/50), Numbness has been the most common feature 56.6% (17/30), and Weakness 26.6% (8/30) all were Axonal damage. Sensorimotor neuropathy was exhibited in 70% (21/30), pure motor neuropathy in 26.7% (8/30). Polyneuropathy was encountered in 46.6% (14/30), poly-radiculopathy in 20% (6/30) along with 23.3% (7/30) as mononeuropathy. Conclusions: peripheral neuropathy was developed in patients with visceral leishmaniasis, frequent occurrence of subclinical neurological manifestations is higher than reported. [ABSTRACT FROM AUTHOR]

Parasitic infections are associated with low education, wars and migration, absence of animal control and poor sanitation. Infections like visceral and cutaneous leishmaniasis (VL and CL), trichomoniasis, toxoplasmosis, malaria, echinococcosis and schistosomiasis are all spread worldwide and have harmful effects on individuals and societies. The aim of this survey was to identify the possible association of these infections with spatial distribution (province/governorate) and patient demographics (age and gender). According to the data collected from the Iraqi National CDC from 2019 to 2020, the predominant parasitic infections in both years were trichomoniasis and CL, followed by echinococcosis, VL and toxoplasmosis. Iraq is malaria and schistosomiasis free. The highest incidence rate of trichomoniasis was in Duhouk (2019) and Al-Dewaniya (2020) and majority of CL cases were in Diala in both 2019 and 2020. The number of echinococcosis cases was the highest in Thi-Qar (2019) and in Nineveh (2020). VL mostly affected Al-Dewaniya (2019) and Thi-Qar (2020). Toxoplasmosis scored the highest incidence rate in Basra in 2019 and 2020. All infections were higher in 2019 than in 2020, except for CL. As for age groups: echinococcosis, toxoplasmosis and trichomoniasis were higher in age group 15 – 44 years, while VL and CL was most common in 0-14 years juveniles in both years. Females were more affected than males by echinococcosis, toxoplasmosis, and trichomoniasis, while VL and CL affected males more often in the years included in this study. [ABSTRACT FROM AUTHOR]

Laryngeal leishmaniasis represents an infrequent manifestation of mucosal leishmaniasis, and even rarer is the coexistence of mucosal and visceral relapse. The present study describes the case of the simultaneous occurrence of relapsing mucosal and visceral leishmaniasis in a patient infected with human immunodeficiency virus (HIV) who was under secondary prophylaxis with liposomal amphotericin B. The clinical manifestations, diagnostic approaches employed and the treatment regimen implemented are described herein. Furthermore, the present study discusses the implications of the co-infection between leishmaniasis and HIV on the host immune response and the management strategies employed for relapsing forms. Emphasizing the necessity for the prompt initiation of targeted treatment to enhance clinical outcomes, the present study underscores the critical importance of maintaining a heightened level of suspicion for laryngeal leishmaniasis relapse in individuals with HIV exhibiting persistent laryngeal symptoms. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is caused by Leishmania donovani (Ld), and most cases occur in Brazil, East Africa, and India. The treatment for VL is limited and has many adverse effects. The development of safer and more efficacious drugs is urgently needed. Drug repurposing is one of the best processes to repurpose existing drugs. Ornithine decarboxylase (ODC) is an important target against L. donovani in the polyamine biosynthesis pathway. In this study, we have modeled the 3D structure of ODC and performed high‐throughput virtual screening of 8630 ZINC database ligands against Leishmania donovani ornithine decarboxylase (Ld ODC), selecting 45 ligands based on their high binding score. It is further validated through molecular docking simulation and the selection of the top two lead molecules (ceftaroline fosamil and rimegepant) for Molecular Dynamics (MD) simulation, Density functional theory (DFT), and molecular mechanics generalized born surface area (MMGBSA) analysis. The results showed that the binding affinities of ceftaroline fosamil, and rimegepant are, respectively, −10.719 and 10.159 kcal/mol. The docking complexes of the two lead compounds, ceftaroline fosamil, and rimegepant, with the target ODC, were found stable during molecular dynamics simulations. Furthermore, the analysis of MMGBSA revealed that these compounds had a high binding free energy. The DFT analysis showed that the top lead molecules were more reactive than the standard drug (pentamidine). In‐silico findings demonstrated that ceftaroline fosamil, and rimegepant might be recognized as potent antagonists against ODC for the treatment of VL. [ABSTRACT FROM AUTHOR]

Background: Visceral leishmaniasis (VL) is one of the most important neglected tropical diseases. The zoonotic form of VL is endemic in some areas of Iran. We aimed to determine the status of VL identified in humans and canines in different parts of Iran from 2013 to 2022. Method: A national representative cross-sectional study was conducted in 10 provinces of Iran, including the national leishmaniasis reference lab. We employed the direct agglutination test (DAT) as a reliable serological method to detect anti-Leishmania infantum antibodies in humans and animal reservoir hosts. Additionally, a narrative literature review was conducted to identify relevant studies on VL seroprevalence in Iran from 2013 to 2023. Results: The results of 21281 human and 5610 canine serum samples from 2013 to 2022 are reported. Altogether, 448 (2.1%, 95%CI: 2.0-2.3) human serum samples showed anti-L. infantum antibody levels of ≥1:3200. Of these samples, 13716 (64.5%) were collected actively, which showed a seroprevalence of 0.6% (95% CI: 0.5-0.8) and 7565 (35.5%) were collected passively, which showed a seroprevalence of 4.8% (95%CI: 4.3-5.3). Overall, 1035 (20.1%, 95%CI: 19.0-21.2) of 5160 domestic dogs (Canis familiaris) samples showed anti-L. infantum antibody levels of ≥1:320. Northwest (...,^%) and northeast (0.96%) regions had the highest human VL seroprevalence, while northwest (21.5%) and south (14.4%) regions had the highest canine VL seroprevalence. Conclusion: Zoonotic VL, an endemic parasitic disease, is still present in several different distinct areas across Iran. While human VL cases have shown a declining trend over the last decade, the prevalence of canine VL remains significant. [ABSTRACT FROM AUTHOR]

The behavior of life indicators of notified cases of Visceral Leishmaniasis (VL) in Bahia and sociodemographic factors were analyzed. The study analyzes the behavior of life indicators of notified cases of Visceral Leishmaniasis (VL) in Bahia and its correlation with sociodemographic factors. This is an analytical and retrospective study (2010 - 2020) that used the SINAN/DATASUS secondary database between. Were analyzed data on notifications, incidence, transmission, risk stratification and life indicators. During the period there were 3,573 cases of VL, highest incidence of 3.52 cases/100,000 inhabitants and sporadic transmission in most municipalities. The Annual Increment Rate (AIR) in the South and East health macro-regions showed significant values for incidence and lethality in the West, East and Center-North regions. Disability Adjusted Life Years (DALY) showed that the infected Bahian population lost 10 years of life. The analysis of individual aspects of the municipalities made it possible to identify the need to implement effective public policies at this administrative level. [ABSTRACT FROM AUTHOR]

The relationship between leishmaniasis and COVID-19 remains uncertain, with no evidence suggesting that leishmaniasis provides protection against COVID-19. Leishmaniasis, transmitted by sandflies, and COVID-19, caused by the SARS-CoV2 virus, are unrelated diseases with distinct transmission modes. It is essential to rely on established preventive measures for COVID-19, such as vaccination and hygiene practices, as leishmaniasis requires separate medical attention. Some studies suggest that visceral Leishmania-COVID-19 co-infection may reactivate asymptomatic leishmaniasis. Severe COVID-19 cases may exacerbate parasitic multiplication and organ involvement. The immunological response to visceral leishmaniasis may increase susceptibility to subsequent SARS-CoV-2 infection, emphasizing the importance of an effective immune response. Cutaneous leishmaniasis may confer cross-protection against COVID-19, particularly in tropical regions. IFN-γ plays a critical role in parasite control and antiviral defense, highlighting its importance in both diseases. Further research is needed to understand the mechanisms underlying the interaction between SARS-CoV-2 and leishmaniasis. [ABSTRACT FROM AUTHOR]

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Kala-azar, also known as visceral leishmaniasis (VL), is a disease caused by Leishmania infantum and L. donovani. Patients experience symptoms such as fever, weight loss, paleness, and enlarged liver and spleen. The disease also affects immunosuppressed individuals and has an overall mortality rate of up to 10%. This overview explores the literature on the pathogenesis of preclinical and clinical stages, including studies in vitro and in animal models, as well as complications and death. Asymptomatic infection can result in long-lasting immunity. VL develops in a minority of infected individuals when parasites overcome host defenses and multiply in tissues such as the spleen, liver, and bone marrow. Hepatosplenomegaly occurs due to hyperplasia, resulting from parasite proliferation. A systemic inflammation mediated by cytokines develops, triggering acute phase reactants from the liver. These cytokines can reach the brain, causing fever, cachexia and vomiting. Similar to sepsis, disseminated intravascular coagulation (DIC) occurs due to tissue factor overexpression. Anemia, hypergammaglobulinemia, and edema result from the acute phase response. A regulatory response and lymphocyte depletion increase the risk of bacterial superinfections, which, combined with DIC, are thought to cause death. Our understanding of VL's pathogenesis is limited, and further research is needed to elucidate the preclinical events and clinical manifestations in humans. [ABSTRACT FROM AUTHOR]

Abstract Objective Visceral leishmaniasis (VL) is an endemic parasitic disease in Latin America, and its clinical picture is aggravated in coinfections with the human immunodeficiency virus (HIV). The objective of this study was to investigate clinical factors and laboratory variables associated with VL relapse and death in VL/HIV coinfected patients. Methods A prospective longitudinal study was conducted from January 2013 to July 2020 among 169 patients coinfected with VL and HIV. The outcomes investigated were the occurrence of VL relapse and death. Chi-square test, Mann–Whitney test and logistic regression models were used for statistical analysis. Results The occurrence rates were 41.4% for VL relapse and 11.2% for death. Splenomegaly and adenomegaly were associated with the increased risk of VL relapse. Patients with VL relapse had higher levels of urea (p = .005) and creatinine (p

Background & objectives: The successful elimination program of visceral leishmaniasis (VL) in Nepal decreased the incidence to less than 1 per 10,000 population leading to the consolidation phase. However, new VL cases have been recorded from new districts, threatening the elimination goal. This study monitors the geographical spread of VL and identifies potential risk factors. Methods: VL data of 2017–2020 were obtained from the Epidemiology and Disease Control Division (EDCD) of Nepal and mapped. Telephonic interviews with 13 VL patients were conducted. Results: The incidence maps indicate that VL is spreading to new areas. The target incidence exceeded four times in hilly and twice in mountainous districts. VL cases occurred in 64 of 77 districts in all three regions (mountainous, hilly and Terai). Interviews showed a correlation between travel history (private, commercial and for studies) and the spread of VL cases to new foci. Interpretation & conclusion: One major challenge of VL elimination in the maintenance phase is the spread of infection through travelers to new foci areas, which needs to be under continuous surveillance accompanied by vector control activities. This should be confirmed by a large-scale analytical study.

Background: Different forms of leishmaniasis are important infectious diseases in Iran. While Rudbar County of Guilan Province has been introduced as a cutaneous leishmaniasis focus, there are few published data about the phlebotomine sand flies (Diptera: Psychodidae, Phlebotominae) of the province and their medical importance. Objectives: The present study is going to provide a review of sand fly-borne infections in Guilan Province and a checklist of sand flies of the province. Also, a note is presented on the name Sergentomyia murgabiensis sintoni. Materials & Methods: Using the main databases such as Web of Science, PubMed, Scopus, Google Scholar, Scientific Information Database (SID), IranMedex and Magiran which were searched up to September 2022 and reviewing the literature, the available data about the sand fly-borne diseases of Iran and Guilan Province were extracted and analyzed. Results: In total, 11 species representing two genera of sand flies, Phlebotomus and Sergentomyia, are found in Guilan Province. The checklist and distribution of sand flies of the province have been provided. All species of the genus Phlebotomus in the province are proven or suspected vectors of leishmaniasis. Sand fly-borne leishmaniasis (cutaneous and visceral), sand fly fever and lizard leishmaniasis, which are among the endemic infections of the province, are discussed. Also, a taxonomic note is presented on the name Sergentomyia murgabiensis sintoni. Conclusion: The prevalence of suspected or proven vectors of sand fly-borne diseases in Guilan Province is noteworthy. The study of the ecology of sand flies and detecting the exact vectors and reservoirs of leishmaniasis and phlebotomine fever by serological or molecular- specific tests in the province are recommended. Moreover, additional samplings of sand flies from localities, where have not been studied, are necessary.

This clinical correspondence discusses a case of massive vulval enlargement in a person living with HIV/AIDS, which was an atypical presentation of cutaneous leishmaniasis. Leishmaniasis is a protozoal infection transmitted by sandfly vectors, and HIV co-infection can result in atypical presentations. The patient, a 35-year-old female from Bihar, India, presented with vulval swelling and later developed overlying pigmented lesions. The diagnosis was confirmed through histopathology, and the patient was referred for treatment. This case highlights the importance of considering leishmaniasis as a differential diagnosis for skin lesions in immunocompromised individuals, even when the morphology is atypical. [Extracted from the article]

Drug repurposing has emerged as an effective strategy against infectious diseases such as visceral leishmaniasis. Here, we evaluated four FDA‐approved drugs–valrubicin, ciclesonide, deflazacort, and telithromycin—for their anti‐leishmanial activity on Leishmania donovani parasites, especially their ability to target the enzyme glutathione synthetase (LdGS), which enables parasite survival under oxidative stress in host macrophages. Valrubicin and ciclesonide exhibited superior inhibitory effects compared to deflazacort and telithromycin, inhibiting the promastigotes at very low concentrations, with IC50 values of 1.09 ± 0.09 μm and 2.09 ± 0.09 μm, respectively. Subsequent testing on amastigotes revealed the IC50 values of 1.74 ± 0.05 μm and 3.32 ± 0.21 μm for valrubicin and ciclesonide, respectively. Molecular and cellular level analysis further elucidated the mechanisms underlying the anti‐leishmanial activity of valrubicin and ciclesonide. [ABSTRACT FROM AUTHOR]