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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]

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]

• 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

This article discusses a case of disseminated cutaneous leishmaniasis (DCL) in a 48-year-old man with idiopathic CD4 lymphocytopenia. The man had been living in Dakar, Senegal, for 20 years and had traveled to over 80 countries. After hiking in the Amazonian forest of Bolivia, he developed numerous insect bites that progressed to ulceration. He received treatment with meglumine antimoniate, but the lesions reappeared. He was later diagnosed with Leishmania braziliensis and treated with liposomal amphotericin B, which resulted in complete healing. The article provides information on the causes, treatments, and outcomes of cutaneous leishmaniasis. [Extracted from the article]

Duke Federico da Montefeltro (AD 1422-1482) is considered one of the most representative figures of the Italian Renaissance due to his military virtues and patronage of the arts. While it is probable that the disease simply regressed spontaneously, a scar formed in the area occupied by the ulceration ( I restandovi però la cicatrice i )[7] and would stay on Federico's face for the rest of his life. Since Baldi writes that Federico had a terrible disease from which he recovered just in time to have a relapse of the same, it is not unlikely that, being heavily debilitated (and likely even immunocompromised), he experienced I P. aeruginosa i septicaemia, eventually causing this cutaneous manifestation. [Extracted from the article]

Organ transplantation can lead to human visceral leishmaniasis (VL) transmission in humans. This report aims to describe the possible complications related to an atypical course of VL after kidney transplantation. A 61-year-old man who suffered end-stage renal failure received a deceased donor kidney transplant after 2 years of hemodialysis. Tacrolimus, mycophenolate mofetil, and prednisolone were used for immunosuppressive therapy, and renal function remained stable for 2.5 years. He was referred to our hospital because of fever and malaise. Physical and radiological examinations showed mild splenomegaly and cervical and inguinal lymphadenopathy. Laboratory data showed bicytopenia, elevated C-reactive protein, serum creatinine, and non-nephrotic proteinuria. Bone marrow biopsy aspiration showed no abnormality. Polymerase chain reaction confirmed the diagnosis of Leishmania infantum. Anti-leishmanial therapy was initiated with liposomal amphotericin B for 2 weeks, and the patient became clinically stable. So far, there has been no evidence of clinical or biological relapse, and kidney function is stable. Considering that VL has become increasingly widespread in immunocompromised patients in endemic regions, especially in patients with transplants, it is crucial to screen and rule out VL as a cause of infection in these patients. The probability of this problem should be considered in every patient with a transplant in endemic and nonendemic areas. Furthermore, our study showed that through timely diagnosis using noninvasive methods and standard treatments, mortality caused by this disease can be properly prevented. [ABSTRACT FROM AUTHOR]

Background: Leishmaniases are vector borne diseases caused by Leishmania spp. parasites transmitted by female sandflies (Diptera: Psychodidae) whose geographic distribution is influenced by environmental factors. Among the main tools for studying the distribution of vector species, modeling techniques are used to analyze the influence of climatic and environmental factors on the distribution of these insects and their association with human cases of the disease. Methodology/Principal findings: Here, we used a multiscale ecological niche modeling approach to assess the environmental suitability of sandfly vectors of the etiological agents of Visceral (VL) and American Cutaneous Leishmaniasis (ACL) in Piauí state, northeastern Brazil, and then evaluated their relationship with human disease incidence. For this, we obtained the geographic coordinates of the vector species Lutzomyia longipalpis and Nyssomyia whitmani through literature review, online databases and unpublished records. These data were used for the development of predictive models of the distribution of both sandflies species based on climatic and environmental variables. Finally, the environmental suitability for the presence of these vectors was compared with the incidence of both the diseases at the municipality level. The final models for each sandfly species showed good predictive powers with performance metric values of 0.889 for Lu. longipalpis and 0.776 for Ny. whitmani. The areas with greater environmental suitability for the presence of these species were concentrated in the central-north region of Piauí and coincide with the location of those municipalities presenting higher incidences of VL and ACL, situated in the central-north and extreme north of the state, respectively. The south and southeast regions of Piauí state have low incidence of these diseases and presented low environmental suitability for the presence of both vectors. Conclusions/Significance: We discuss how predictive modeling can guide entomological and epidemiological surveillances and recommend an increased supervision and control activities in Teresina (capital of the state of Piaui), Altos and Pedro II, in addition to other municipalities with similar social and environmental characteristics. Author summary: Sandflies are insects that actively participate in the transmission cycles of leishmaniasis and other diseases, and these invertebrate vectors are frequently found in areas with hot and humid climates. However, in addition to the climate, there are several factors that contribute to the occurrence of sandfly vectors, such as, the vegetation type, altitude, and land use and cover. Understanding which environmental variables are important for the presence of sandflies can help us to understand how these insects are distributed and overall, how this affects the transmission of the etiological agents of leishmaniasis. In this study, we performed a set of ecological models where environmental and climatic variables were combined in multiple scales and correlated with the presence of two sandflies species, Lutzomyia longipalpis and Nyssomyia whitmani, vectors of parasites causing visceral and cutaneous leishmaniasis, respectively. We then combined this information with human disease data to assess potential risk areas in the state of Piauí, northeast Brazil. The resulting maps showed that municipalities of the central-north region of the state have favorable environment for the occurrence of these vectors in addition to higher incidence of leishmaniasis in humans. We thus recommend that control activities should be focused on this region of the state. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) has rarely been reported in patients with chronic granulomatous disease (CGD), despite the fact that they seem more susceptible to intracellular infection. We describe a rare presentation of VL and epididymo‐orchitis in a patient with CGD, which has not been seen previously in the literature following inflammatory syndrome. [ABSTRACT FROM AUTHOR]

Post kala‐azar dermal leishmaniasis (PKDL), a sequel of apparently cured visceral leishmaniasis (VL) presents with papulonodular (polymorphic) or hypopigmented lesions (macular) and is the proposed disease reservoir. As hypopigmentation appears consistently in PKDL, especially the macular form, this study aimed to delineate immune factors that singly or in combination could contribute towards this hypopigmentation. At lesional sites, the presence of melanocytes and CD8+ T‐cells was assessed by immunohistochemistry and mRNA expression of melanogenic markers (tyrosinase, tyrosinase‐related protein‐1 and MITF) by droplet digital PCR, while plasma levels of cytokines and chemokines were measured by a multiplex assay. In comparison with skin from healthy individuals, macular PKDL demonstrated a near total absence of Melan‐A+ cells at dermal sites, while the polymorphic cases demonstrated a 3.2‐fold decrease, along with a dramatic reduction in the expression of key enzymes related to the melanogenesis signalling pathway in both forms. The levels of circulating IFN‐γ, IL‐6, IL‐2, IL‐1β, TNF‐α and IFN‐γ‐inducible chemokines (CXCL9/10/11) were elevated and was accompanied by an increased lesional infiltration of CD8+ T‐cells. The proportion of CD8+ T‐cells correlated strongly with plasma levels of IFN‐γ (r = 0.8), IL‐6 (r = 0.9, p < 0.05), IL‐2 (r = 0.7), TNF‐α (r = 0.9, p < 0.05) and IL‐1β (r = 0.7), as also with CXCL9 (r = 0.5) and CXCL10 (r = 0.6). Taken together, the absence/reduction in Melan‐A suggested hypopigmentation in PKDL was associated with the destruction of melanocytes, following the impairment of the melanogenesis pathway. Furthermore, the presence of CD8+ T‐cells and an enhanced IFN‐γ‐associated immune milieu suggested the generation of a pro‐inflammatory landscape that facilitated melanocyte dysfunction/destruction. [ABSTRACT FROM AUTHOR]

Background: The leishmaniases are a group of four vector-borne neglected tropical diseases caused by 20 species of protozoan parasites of the genus Leishmania and transmitted through a bite of infected female phlebotomine sandflies. Endemic in over 100 countries, the four types of leishmaniasis–visceral leishmaniasis (VL) (known as kala-azar), cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and post-kala-azar dermal leishmaniasis (PKDL)–put 1.6 billion people at risk. In Kenya, the extent of leishmaniasis research has not yet been systematically described. This knowledge is instrumental in identifying existing research gaps and designing appropriate interventions for diagnosis, treatment, and elimination. Methodology/Principal findings: This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to determine the state of leishmaniases research in Kenya and identify research gaps. We searched seven online databases to identify articles published until January 2022 covering VL, CL, MCL, and/or PKDL in Kenya. A total of 7,486 articles were found, of which 479 underwent full-text screening, and 269 met our eligibility criteria. Most articles covered VL only (n = 141, 52%), were published between 1980 and 1994 (n = 108, 39%), and focused on the theme of "vectors" (n = 92, 34%). The most prevalent study types were "epidemiological research" (n = 88, 33%) tied with "clinical research" (n = 88, 33%), then "basic science research" (n = 49, 18%) and "secondary research" (n = 44, 16%). Conclusion/Significance: While some studies still provide useful guidance today, most leishmaniasis research in Kenya needs to be updated and focused on prevention, co-infections, health systems/policy, and general topics, as these themes combined comprised less than 4% of published articles. Our findings also indicate minimal research on MCL (n = 1, <1%) and PKDL (n = 2, 1%). We urge researchers to renew and expand their focus on these neglected diseases in Kenya. Author summary: The leishmaniases are a group of four vector-borne neglected tropical diseases (NTDs) that are endemic in over 100 countries, putting over 1.6 billion people at risk. In Kenya, the extent of research on leishmaniasis remains unclear. Therefore, this scoping review aims to uncover and classify the body of literature on leishmaniasis in Kenya to elucidate gaps in knowledge and inform future research, related health policies, and interventions in Kenya. Through a database search, we identified 269 articles that met our eligibility criteria, which were included in our final analysis. Our analysis revealed that the majority of articles discussed VL. Most articles were published between 1980 and 1994. There was uneven distribution between the themes of published articles, with vector-related research dominating the list, followed by treatment, diagnostics, general epidemiology, and pathophysiology. The most prevalent type of study was a tie between epidemiological and clinical research, followed by basic science research and then secondary research. There is minimal research coverage on MCL and PKDL, which is as expected given the low prevalence of these diseases in Kenya. Furthermore, little research spans prevention, co-infections, health systems/policy, and general topics. [ABSTRACT FROM AUTHOR]

Lutzomyia longipalpis is known as one of the primary insect vectors of visceral leishmaniasis. For such ectothermic organisms, the ambient temperature is a critical life factor. However, the impact of temperature has been ignored in many induced‐stress situations of the vector life. Therefore, this study explored the interaction of Lu. longipalpis with temperature by evaluating its behaviour across a thermal gradient, thermographic recordings during blood‐feeding on mice, and the gene expression of heat shock proteins (HSP) when insects were exposed to extreme temperature or infected. The results showed that 72 h after blood ingestion, Lu. longipalpis became less active and preferred relatively low temperatures. However, at later stages of blood digestion, females increased their activity and remained at higher temperatures. Real‐time imaging showed that the body temperature of females can adjust rapidly to the host and remain constant until the end of blood‐feeding. Insects also increased the expression of HSP90(83) during blood‐feeding. Our findings suggest that Lu. longipalpis interacts with temperature by using its behaviour to avoid temperature‐induced physiological damage during the gonotrophic cycle. However, the expression of certain HSP might be triggered to mitigate thermal stress in situations where a behavioural response is not the best option. [ABSTRACT FROM AUTHOR]

Simple Summary: Visceral leishmaniasis is a tropical neglected disease caused by infection with Leishmania parasites. There are no human vaccines and the current drug treatments for infected patients are hampered by toxicity and the development of resistance. In our study, we have used an immunotherapeutic approach, which combines a vaccine and drug, to treat mice infected with the parasite. This involved injecting a candidate Leishmania vaccine ChimT with the adjuvant monophosphoryl lipid A (MPLA, which enhances the immune response) and a treatment drug amphotericin B (AmpB). We found that the combined immunotherapy of ChimT/MPLA/AmpB significantly reduced the number of parasites within infected internal organs of the animals and increased the production of protective antibodies. Organ toxicity was also lower with the ChimT/MPLA/AmpB immunotherapy, suggesting that the inclusion of the vaccine and adjuvant reduced the inherent toxicity of the drug. In addition, the ChimT vaccine stimulated in vitro mouse white cells to kill three different Leishmania parasites that had invaded the cells. We conclude that the combination of ChimT/MPLA/AmpB could be considered for further studies as an immunotherapy for Leishmania infection. Visceral leishmaniasis (VL) in the Americas is a chronic systemic disease caused by infection with Leishmania infantum parasites. The toxicity of antileishmanial drugs, long treatment course and limited efficacy are significant concerns that hamper adequate treatment against the disease. Studies have shown the promise of an immunotherapeutics approach, combining antileishmanial drugs to reduce the parasitism and vaccine immunogens to activate the host immune system. In the current study, we developed an immunotherapy using a recombinant T cell epitope-based chimeric protein, ChimT, previously shown to be protective against Leishmania infantum, with the adjuvant monophosphoryl lipid A (MPLA) and amphotericin B (AmpB) as the antileishmanial drug. BALB/c mice were infected with L. infantum stationary promastigotes and later they received saline or were treated with AmpB, MPLA, ChimT/Amp, ChimT/MPLA or ChimT/MPLA/AmpB. The combination of ChimT/MPLA/AmpB significantly reduced the parasite load in mouse organs (p < 0.05) and induced a Th1-type immune response, which was characterized by higher ratios of anti-ChimT and anti-parasite IgG2a:IgG1 antibodies, increased IFN-γ mRNA and IFN-γ and IL-12 cytokines and accompanied by lower levels of IL-4 and IL-10 cytokines, when compared to other treatments and controls (all p < 0.05). Organ toxicity was also lower with the ChimT/MPLA/AmpB immunotherapy, suggesting that the inclusion of the vaccine and adjuvant ameliorated the toxicity of AmpB to some degree. In addition, the ChimT vaccine alone stimulated in vitro murine macrophages to significantly kill three different internalized species of Leishmania parasites and to produce Th1-type cytokines into the culture supernatants. To conclude, our data suggest that the combination of ChimT/MPLA/AmpB could be considered for further studies as an immunotherapy for L. infantum infection. [ABSTRACT FROM AUTHOR]

Background Post–kala-azar dermal leishmaniasis (PKDL), a dermal form of the disease, occurs in some visceral leishmaniasis (VL) patients following treatment. The PKDL disease mechanism is not yet clearly understood. Here we have studied the role of dermal fibroblasts in VL and PKDL disease mechanism. Methods Dermal fibroblasts were grown from skin biopsy explants collected from individual VL and PKDL patients and healthy controls. Fibroblasts from the third passage were subjected to RNA sequencing to analyze differentially expressed genes (DEGs). Significantly important genes were further validated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Results Transcriptome analysis of PKDL versus VL identified 516 DEGs (263 were overrepresented and 253 were underrepresented in PKDL). Among the top hub genes, MMP2 , IL1B , CXCL8 , IFIH1 , NFKB1A , IL6 , ISG15 , and EGFR were underexpressed and ACTB , HSP90AA1 , RAB7A , and RPS27A were overexpressed in PKDL compared to VL. Conclusions Our data indicate that PKDL fibroblasts may present antigens through the MHC I pathway activating CD8+ T-cell mediated response, while VL fibroblasts express nuclear factor-κB (NFκB)-mediated chemokines, IL1B , IL6, and IL8, resulting in the recruitment of natural killer (NK)-cells and monocytes to the site of infection, leading to the clearance of parasite from the skin and visceralization of the disease. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is a vector-borne protozoan disease, which can be fatal if left untreated. Synthetic chemical insecticides are very effective tools for controlling of insect vectors, including the sand fly Phlebotomus argentipes, the vector of VL in the Indian subcontinent. However, repeated use of the same insecticide with increasing doses potentially can create high selection pressure and lead to tolerance and resistance development. The objective of this study was to determine the lethal concentrations and assess levels of susceptibility, diagnostic doses and times to death of laboratory-reared P. argentipes to five insecticides that are used worldwide to control vectors. Using the Center for Disease Control and Prevention (CDC) bottle bioassay, 20–30 sand flies were exposed in insecticide- coated 500-ml glass bottles. Flies were then observed for 24 hours and mortality was recorded. Dose-response survival curves were generated for each insecticide using QCal software and lethal concentrations causing 50%, 90% and 95% mortality were determined. A bioassay was also conducted to determine diagnostic doses and diagnostic times by exposing 20–30 flies in each bottle containing set concentrations of insecticide. Mortality was recorded at 10-minute intervals for 120 minutes to generate the survival curve. Phlebotomus argentipes are highly susceptible to alpha-cypermethrin, followed by deltamethrin, malathion, chlorpyrifos, and least susceptible to DDT. Also, the lowest diagnostic doses and diagnostic times were established for alpha-cypermethrin (3μg/ml for 40 minutes) to kill 100% of the flies. The susceptibility data, diagnostic doses and diagnostic times presented here will be useful as baseline reference points for future studies to assess insecticide susceptibility and resistance monitoring of field caught sand flies and to assist in surveillance as VL elimination is achieved in the region. Author summary: Synthetic chemical insecticides are mainly used for controlling sand flies via indoor residual spraying (IRS) and insecticide treated nets. Sand flies had developed resistance against DDT in endemic areas of Bihar, India, and was replaced by synthetic pyrethroids (alpha-cypermethrin) in the second phase of IRS in 2015. The substantial increase in the use of synthetic pyrethroids will potentially lead to increased resistance because DDT and pyrethroids both have the same target site. To monitor insecticide resistance in field caught sand flies, susceptibility status and diagnostic doses and times are warranted, as no diagnostic dose for resistance detection has been established for Indian sand flies. A laboratory reared P. argentipes was used to quantify insecticide susceptibility and determination of diagnostic doses and times. The CDC bottle bioassay was used with five insecticides viz., alpha-cypermethrin, deltamethrin, malathion, chlorpyrifos and DDT. Results indicate that the P. argentipes were highly susceptible to alpha-cypermethrin followed by deltamethrin, malathion, chlorpyrifos and least susceptible to DDT. This study provides critical base line reference data for further studies to assess insecticide susceptibility and resistance monitoring in field populations, as well as determining diagnostic doses and times for other insecticide susceptible sand fly populations undergoing surveillance to sustain VL elimination. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a neglected tropical disease with three main clinical types; cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). CL and MCL are considered to be highly stigmatizing due to potentially disfiguring skin pathology. CL and MCL-associated stigma are reported across the world in different contexts assimilating different definitions and interpretations. Stigma affects people with CL, particularly in terms of quality of life, accessibility to treatment, and psycho-social well-being. However, evidence on CL- and MCL-associated stigma is dispersed and yet to be synthesized. This systematic review describes the types, measurements, and implications of the stigma associated with CL and MCL and identifies any preventive strategies/interventions adopted to address the condition. This study was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) statement which is registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols PROSPERO (ID- CRD42021274925). We will perform an electronic search in MEDLINE, Embase, Scopus, PubMed, EBSCO, Web of Science, Global Index Medicus, Trip, and Cochrane Library databases, and in Google Scholar, using a customized search string. Any article that discusses any type of CL- and/or MCL-associated stigma in English, Spanish and Portuguese will be included. Articles targeting veterinary studies, sandfly vector studies, laboratory-based research and trials, articles focusing only on visceral leishmaniasis, and articles on diagnostic or treatment methods for CL and MCL will be excluded. Screening for titles and abstracts and full articles and data extraction will be conducted by two investigators. The risk of bias will be assessed through specific tools for different study types. A narrative synthesis of evidence will then follow. This review will identify the knowledge gap in CL-associated stigma and will help plan future interventions. [ABSTRACT FROM AUTHOR]

Leishmania (L.) infantum strains, isolated from varying hosts and clinical manifestations (cutaneous, visceral and canine leishmaniasis), were investigated in order to understand the genetic polymorphisms within this species in Algeria and Tunisia. Two DNA‐based typing methods were tested in order to evaluate their effectiveness against Multilocus enzyme electrophoresis (MLEE), widely considered as the reference method for Leishmania parasite typing. On the other hand, MLEE is cumbersome, high‐cost, time consuming and frequently does not detect intra‐species genetic polymorphisms. In this work, we used two molecular target regions to discriminate L. infantum strains, Internal transcribed spacer 1 (ITS1) and the cysteine proteinase B (cpb). The ITS1 region offers good resolution for Leishmania discrimination but does not spotlight intra‐species polymorphisms. In contrast, cpbE and cpbF PCR‐Sequencing demonstrated a certain variability within CL and VL Algerian and Tunisian L. infantum isolates. Following phylogenetic analyses of 44 L. infantum isolates, two main groups were identified, a group with 39 bp deletion in the cpb sequence, composed of cutaneous, visceral and canine isolates from both countries with no significant clinical or geographic distribution; these samples were typed as MON‐1, MON‐24, and MON‐80 zymodemes. A second group which presents a clear clusterization of Tunisian cutaneous strains belonging to the L. infantum MON‐24. This group, with no deletion in the mature domain of the cpb gene sequence, should be further explored with a higher number of samples. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Visceral leishmaniasis and hemophagocytic lymphohistiocytosis share many features in common and may coincide in the same patient. Timely diagnosis and management of visceral leishmaniasis could save patients from unnecessary toxic treatment. Visceral leishmaniasis and hemophagocytic lymphohistiocytosis share many clinical features in common and may coexist in the same patient. Visceral leishmaniasis should be promptly ruled out in patients coming from endemic areas before starting immunosuppressive therapy for hemophagocytic lymphohistiocytosis. The mainstay treatment, in this case, is anti‐leishmania medications preferably liposomal amphotericin‐B. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis caused by Leishmania major or L. tropica and visceral leishmaniasis caused by L. infantum have been reported in Israel. We collected Phlebotomus spp. sand flies in the Negev desert of southern Israel to identify circulating Leishmania spp. Of 22,636 trapped sand flies, 80% were P. alexandri. We sequenced Leishmania-specific internal transcribed spacer 1 fragments and K26 genes. Of 5,019 Phlebotomus female sand flies, 2.5% were Leishmania DNA–positive; 92% of infections were L. donovani. Phylogenetic analyses showed separate clustering of L. donovani and L. infantum. P. alexandri flies positive for L. donovani harbored blood meals from European hares. Leishmania DNA isolated from a patient with cutaneous leishmaniasis who lived in the survey area was identical to L. donovani from P. alexandri flies. We report circulation of L. donovani, a cause of visceral leishmaniasis, in southern Israel. Prompt diagnosis and Leishmania spp. identification are critical to prevent leishmaniasis progression. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic visceral leishmaniasis (VL) infection is a risk for transfusion safety. Leukoreduction has been an alternative for the prevention of some blood‐borne diseases, including VL. This study aimed to evaluate the role of leukoreduction of cellular blood components as a control measure for transfusional VL transmission. Research Design and Methods: A total of 161 polytransfused patients with non‐leukoreduced blood components (HNL), 95 polytransfused with leukoreduced blood components (LH), and 202 non‐transfused (NT) from endemic regions for VL and with a similar epidemiological profile. The detection of antibodies against VL was performed by ELISA and the presence of the parasite was investigated by real‐time PCR. Statistical significance was defined as p <.05. Results: When comparing three groups, ELISA results were statistically significant (p =.0065). The residual analysis of ELISA showed statistically significant for the HNL group compared to the general group (p =.002; OR: 5.6; CI: 1.7–25.8), demonstrating that individuals who received non‐leukoreduced transfusions are five times more likely to acquire Leishmania infantum infection than the general. Discussion: Higher prevalence in the group with HNL and low prevalence in those who received LH, similar to NT patients, highlight the risk of transfusional VL transmission and reinforce the role of leukoreduction in its prevention. [ABSTRACT FROM AUTHOR]

Introduction: Leishmaniasis is a major health problem and its diagnosis still represents a challenge. Since consistent evidence on the comparison of serological methods is lacking, our work aims to compare five serological tests for the diagnosis of visceral and asymptomatic leishmaniasis in southern France, a region where leishmaniasis is endemic. Methodology: Serum samples from 75 patients living in Nice, France were retrospectively analyzed. They included patients affected by visceral leishmaniasis (VL; n = 25), asymptomatic carriers (AC; n = 25) and negative controls (n = 25). Each sample was tested using two immunochromatographic tests (ICT; IT LEISH® and TruQuick IgG/IgM®), an indirect fluorescent antibody test (IFAT) and two Western Blotting (WB; LDBio BIORAD® and an in-house method). Results: Diagnosis of VL with IFAT and TruQuick® showed the highest diagnostic performance parameters. IFAT had 100% sensitivity and specificity, while TruQuick had 96% sensitivity and 100% specificity. Finally, the two tests showed high accuracy (100% for IFAT and 98% for TruQuick) for the AC group. WB LDBio® was the only method able to detect Leishmania latent infection, with a sensitivity of 92%, and a specificity of 100%, with a Negative Predictive Value (NPV) of 93%. This performance is reflected in the high accuracy of the test. Conclusions: The data obtained with TruQuick® supports its application in the rapid diagnosis of leishmaniasis in endemic areas, a feature not shown by IFAT despite its high diagnostic performance. Regarding the diagnosis of asymptomatic leishmaniasis, the best results were obtained with WB LDBio®, confirming previous studies. [ABSTRACT FROM AUTHOR]

Background Post–kala-azar dermal leishmaniasis (PKDL) is a dermal complication of visceral leishmaniasis. Oral miltefosine (MF) is the first-line treatment for PKDL patients in South Asia. This study assessed the safety and effectiveness of MF therapy after 12 months of follow-up to explore more precise data. Methods In this observational study, 300 confirmed PKDL patients were enrolled. MF with the usual dose was administered to all patients for 12 weeks and followed up for 1 year. Clinical evolution was recorded systematically by photographs at screening and at 12 weeks, 6 months, and 12 months after treatment onset. Definitive cure consisted of disappearance of skin lesions with a negative PCR at 12 weeks or with >70% of lesions, disappearing or fading at 12-month follow-up. Patients with reappearing clinical features and any positive diagnostics of PKDL during the follow-up were considered as nonresponsive. Results Among 300 patients, 286 (95.3%) completed 12 weeks of treatment. The per-protocol cure rate at 12 months was 97%, but 7 patients relapsed and 51 (17%) were lost to 12-month follow-up, resulting in a final cure rate of only 76%. Eye-related adverse events were noted in 11 (3.7%) patients and resolved in most (72.7%) within 12 months. Unfortunately, 3 patients had persistent partial vision loss. Mild to moderate gastrointestinal side effects were seen in 28% patients. Conclusions Moderate effectiveness of MF was observed in the present study. A significant number of patients developed ocular complications, and thus MF for treatment for PKDL should be suspended and replaced with a safer alternative regimen. [ABSTRACT FROM AUTHOR]

Background: The potential reservoirs of visceral leishmaniasis (VL) in South Asia include asymptomatic and relapsed cases of VL, along with patients with post kala-azar dermal leishmaniasis (PKDL). Accordingly, accurate estimation of their parasite load is pivotal for ensuring disease elimination, presently targeted for 2023. Serological tests cannot accurately detect relapses and/or monitor treatment effectiveness, and therefore, parasite antigen/nucleic acid based detection assays remain the only viable option. An excellent option is the quantitative polymerase chain reaction (qPCR) but the high cost, technical expertise and time involved precludes its wider acceptability. Accordingly, the recombinase polymerase amplification (RPA) assay operated in a mobile suitcase laboratory has emerged not simply as a diagnostic tool for leishmaniasis but also to monitor the disease burden. Methodology/Principal findings: Using total genomic DNA isolated from peripheral blood of confirmed VL cases (n = 40) and lesional biopsies of PKDL cases (n = 64), the kinetoplast-DNA based qPCR and RPA assay was performed and parasite load expressed as Cycle threshold (Ct) and Time threshold (Tt) respectively. Using qPCR as the gold standard, the diagnostic specificity and sensitivity of RPA in naïve cases of VL and PKDL was reiterated. To assess the prognostic potential of the RPA, samples were analyzed immediately at the end of treatment or ≥6 months following completion of treatment. In cases of VL, the RPA assay in terms of cure and detection of a relapse case showed 100% concordance with qPCR. In PKDL following completion of treatment, the overall detection concordance between RPA and qPCR was 92.7% (38/41). At the end of treatment for PKDL, 7 cases remained qPCR positive, whereas RPA was positive in only 4/7 cases, perhaps attributable to their low parasite load. Conclusions/Significance: This study endorsed the potential of RPA to evolve as a field applicable, molecular tool for monitoring parasite load, possibly at a point of care level and is worthy of consideration in resource limited settings. Author summary: Visceral leishmaniasis (VL) or kala-azar caused by the digenetic parasite Leishmania donovani is a fatal form of leishmaniasis, unless treated. In South Asia, approximately 10–20% of apparently cured cases of VL develop a dermal sequela termed post kala-azar dermal leishmaniasis (PKDL). It presents with macular or papulonodular lesions that harbour Leishmania parasites. Importantly, these cases of PKDL in addition to asymptomatic and relapsed VL cases serve as mobile disease reservoirs and sustain disease transmission. In macular PKDL, that presently comprise over 50% of cases, the diagnosis is particularly challenging as parasites are often not detectable by microscopy. Accordingly, development of strategies for molecular diagnosis is one of the major foci of the ongoing leishmaniasis elimination programme targeted for 2023, that aims to decrease the burden to <1/10,000 cases of VL at the block/zilla level. Serological tests have limited applicability when it is necessary to distinguish present from past infection of VL, and in cases of PKDL when the positivity maybe due to a past history of VL. An excellent option is the quantitative polymerase chain reaction (qPCR) but limitations for its wider field applicability include the high cost, technical expertise and time factor. Accordingly, an urgent need exists for availability of field applicable molecular tests. The RPA tested in this study could well be the desired game-changer as it provided accurate diagnosis of VL and PKDL, can be performed in a primary health centre, and demonstrated the potential to be a monitoring tool for parasite load after treatment, that eventually can accelerate achieving the end-goal of elimination of leishmaniasis. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is a neglected tropical disease that is globally distributed and has the potential to cause very serious illness. Prior literature highlights the emergence and spread of VL is influenced by multiple factors, such as socioeconomic status, sanitation levels or animal and human reservoirs. The study aimed to retrospectively investigate the presence and infectiousness of VL in Rio Grande do Norte (RN), Brazil between 2007 and 2020. We applied a hierarchical Bayesian approach to estimate municipality-specific relative risk of VL across space and time. The results show evidence that lower socioeconomic status is connected to higher municipality-specific VL risk. Overall, estimates reveal spatially heterogeneous VL risks in RN, with a high probability that VL risk for municipalities within the West Potiguar mesoregion are more than double the expected VL risk. Additionally, given the data available, results indicate there is a high probability of increasing VL risk in the municipalities of Natal, Patu and Pau dos Ferros. These findings demonstrate opportunities for municipality-specific public health policy interventions and warrant future research on identifying epidemiological drivers in at-risk regions. Author summary: As a neglected tropical disease (NTD), Leishmaniasis contributes to poor health outcomes, suffering, and death of vulnerable populations. Leishmania infantum or Leishmania donovani is transmitted from animals to humans through the sandfly vector and can be fatal in 5% of the cases even with treatment. Visceral leishmaniasis is a severe form of Leishmaniasis. The purpose of this study was to estimate regions of high Visceral leishmaniasis risk in Rio Grande do Norte, Brazil between 2007 and 2020 to help inform public health initiatives and potential health policy interventions for this disease. Visceral leishmaniasis is a reportable disease and therefore VL cases are documented to the Brazilian Ministry of Health database through passive surveillance. Passive surveillance data can suffer from missing information; individuals may be asymptomatic, or may not seek medical care allowing for diagnosis. When modeling disease risk from passive surveillance data, assuming there is an absence of disease in regions without documented cases can underestimate disease risk. In this paper we estimate disease risk and identify areas with high-risk and increasing infection trends over time while considering data characteristics such as missing information and high correlation of risk factors. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a tropical parasitic disease caused by Leishmania spp. They cause several presentations of illness ranging from cutaneous leishmaniasis to visceral leishmaniasis. The current arsenal of drugs to treat leishmaniasis is limited, and drug resistance further impedes the problem. Therefore, it is necessary to revisit the available information to identify an alternative or new target for treatment. The glycoprotein 63 (gp63), is a potential anti-leishmanial target that plays a significant role in host-pathogen interaction and virulence. Many studies are ongoing to develop gp63 inhibitors or use it as a vaccine target. In this review, we will discuss the potential of gp63 as a drug target. This review summarises the studies focusing on gp63 as a drug target and its inhibitors identified using in silico approaches. [Display omitted] • gp63 a potential drug and vaccine target. • Active site is conserved in all Leishmania spp. • May serve as pan drug target. • In silico studies identify its inhibitors. [ABSTRACT FROM AUTHOR]

Background: Visceral leishmaniasis (Kala-azar) is an inherently dangerous and progressive disease that can be seen in many parts of the world, including Iran. Therefore, we decided to conduct this study on children with Kala-azar in Rasht-Iran. Methods: In this descriptive study, the hospital records of all children with Kala-azar disease admitted to 17 Shahrivar Hospital, Rasht-Iran from 2009 to 2021 were reviewed. Required information were collected from patients' records and descriptive statistical analysis was done using SPSS version 24 statistical software. Results: A total of 22 children with visceral leishmaniasis were admitted to 17 Shahrivar Hospital during the study period. The average age of the children was 2.93 ± 3.32 years. Most of them (59.1%) were boys and lived in the foothills (59.1%). The most common season for children to get the disease was spring (45.5%), and the average duration of the disease until hospitalization was 16.5 ± 13.54 days. In this study, the most common clinical manifestations included fever (90.9%), splenomegaly (77.3%), hepatomegaly (50%), weakness and restlessness (27.3%), and vomiting (18.2%). The most common laboratory findings were anemia (90.9%), leukopenia (59.1%), increased erythrocyte sedimentation rate (ESR) (75%), and increased C-reactive protein (CRP) (75%). 72.7% of the children were treated with liposomal amphotericin and others with glucantime, which were all successful. Conclusion: The results of our studies were consistent with most studies in Iran and other countries. These findings can help in the diagnosis and management of children with Kalaazar and better control of the disease in the province. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is currently considered a re-emerging or emerging infection based on the geographic region. The outcome of leishmaniasis vastly depends on Leishmaniahost interaction. This preliminary study aimed to show the association of human leukocyte antigen (HLA) class I and II genes with healed and non-healed cutaneous leishmaniasis (CL), and symptomatic and asymptomatic visceral leishmaniasis (VL) compared with control groups in Iran. Methods: Ninety-five people, including 31 patients versus 64 individuals in the control group, were enrolled. Among them, 20 patients had confirmed CL based on amastigote observation, 10 had improved CL and 10 non-healed CL. Eleven patients were suffering from confirmed VL based on direct agglutination test (Five asymptomatic and six symptomatic VL cases). Besides, they were residents in an endemic area of VL in the northwest of Iran. To select a control group, it was ensured that they had no history of leishmaniasis. Peripheral blood samples were collected from each patient. After DNA extraction, HLA typing was conducted using polymerase chain reaction - sequence-specific priming (PCR-SSP). Subsequently, data were statistically analyzed by SPSS. Results: There was a statistical relationship between the presence of HLA-A26 and CL, healed CL and the existence of the B38 allele, C1 allele and symptomatic VL, as well as B1.4 allele and asymptomatic VL (P<0.05). Conclusion: This primary finding indicates that several HLA genes have a potential role in the susceptibility of Iranian people to CL and VL. [ABSTRACT FROM AUTHOR]

The role of dogs as reservoir hosts for Toscana virus (TOSV) remains undetermined. This study investigated TOSV and Leishmania infantum infections in one healthy and three infected dogs with Leishmania (A, B, C) following natural exposition to sandfly bites in a focus of zoonotic visceral leishmaniasis (ZVL) located in Northern Tunisia from June to October 2020. At the end of the exposition period, infected and healthy dogs were examined for TOSV and L. infantum infections by xenodiagnosis using a colony of Phlebotomus perniciosus. Pools of freshly engorged P. perniciosus at days 0 and those at days 7 post-feeding were screened for TOSV and L. infantum by nested PCR in the polymerase gene and kinetoplast minicircle DNA, respectively. In the exposure site, P. pernicious is the most abundant sandfly species. The infection rates of sandflies with TOSV and L. infantum were 0.10 and 0.05%, respectively. Leishmania infantum DNA and TOSV RNA were detected in P. perniciosus females fed on dog B and C, respectively. The isolation of TOSV in Vero cells was achieved from two pools containing P. perniciosus fed on dog C. No pathogens were detected in P. perniciosus females fed on dog A and on control dog. We report for the first time the reservoir competence of dog with ZVL in the transmission of TOSV to sandfly vectors in natural settings, in addition to its role as a main reservoir host of L. infantum. [ABSTRACT FROM AUTHOR]

Here, we provide an epidemiological analysis of leishmaniasis in Pernambuco, Brazil, from 2015 to 2019. Our results revealed 1,705 of American cutaneous leishmaniasis-ACL and 859 cases of visceral leishmaniasis-VL. VL and ACL affect children aged 1-4 years (23% and 3.2% of all cases, respectively) and adults aged 20-39 years (26% and 28%, respectively), mainly women. The highest percentage (54.6%) of VL cases was found in urban areas, while ACL occurred mainly in rural areas (63.2%). Individuals with a higher level of education were less affected by leishmaniasis and data on prognosis revealed good chances of clinical cure, but deaths are still recorded. These data show that preventive health actions must be developed to hinder leishmaniasis spread, reduce its impact on public health, and restore the population's life quality. This study can be useful in further elaboration of strategies to minimize leishmaniasis impacts. [ABSTRACT FROM AUTHOR]

Patients with systemic lupus erythemasus (SLE) have an increased risk of bacterial, viral, fungal or parasitic infections, especially if they are receiving immunosuppressive therapy. Leishmaniasis is a group of diseases caused by intracellular flagellate protozoan parasites belonging to the genus Leishmania. We present a 48‐year‐old female patient, diagnosed with SLE many years ago, who presented with high fever and pancytopenia. We thought that the patient's hematologic findings were related to SLE hematologic involvement. However, we investigated other possible causes when there was no response to drugs for the treatment of SLE. A second bone marrow biopsy showed Leishmania amastigotes and the patient was diagnosed with leishmaniasis. The patient was treated with liposomal amphotericin‐B (treatment completed at 40 days). She showed rapid clinical improvement and showed no signs of disease after 4 months. [ABSTRACT FROM AUTHOR]

Context: Leishmaniasis is a group of vector-borne infectious diseases caused by over 20 pathogenic Leishmania species that are endemic in many tropical and subtropical countries. The emergence of drug-resistant strains, the adverse side effects of anti-Leishmania drugs, and the absence of a preventative vaccination strategy threaten the sensitive population. Recently, many groups of researchers have exploited the field of reverse vaccinology to develop vaccines, focusing chiefly on inducing immunity against either visceral or cutaneous leishmaniasis. Methods: This present work involves retrieving twelve experimentally validated leishmanial antigenic protein sequences from the UniProt database, followed by their antigenicity profiling employing ANTIGENpro and Vaxijen 2.0 servers. MHC-binding epitopes for the same were predicted using both NetCTL 1.2 and SYFPEITHI servers, while epitopes for B cell were computed using ABCpred and BepiPred 2.0 servers. The screened epitopes with significantly higher scores were utilized for designing the vaccine construct with appropriate linkers and natural adjuvant. The secondary and tertiary structures of the synthetic peptide were determined by conditional random fields, shallow neural networks, and profile-profile threading alignment with iterative structure assembly simulations, respectively. The 3-D vaccine model was validated through CASP10-tested refinement and the MolProbity web server. Molecular docking and multi-scale normal mode analysis simulation were performed to analyze the best vaccine-TLR complex. Finally, computational immune simulation findings revealed promising cellular and humoral immune responses, suggesting that the engineered chimeric peptide is a potential broad-spectrum vaccine against visceral and cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

In this paper, we formulate and analyze a compartmental model of visceral leishmaniasis (VL). We validate our model by calibrating it to the yearly VL incidence data for India and Bangladesh. The proposed model's basic reproduction number ( R 0 ) has been derived and estimated. We have proved the existence of backward bifurcation in our system. The phenomenon of backward bifurcation has public health implications because the classical requirement of R 0 < 1 , while necessary, is no longer sufficient for effective disease control (or elimination). In such a (backward bifurcation) situation, the initial sizes of the model's subpopulations (state variables) would determine the effectiveness of disease control or elimination. As a result, it is the first attempt to represent and study VL disease dynamics using active case detection (ACD) as a control strategy, although a few experimental studies have been conducted to evaluate ACD in disease transmission. We use sensitivity analysis to investigate the effects of the model's controllable parameters for the basic reproduction number. We found that σ 1 , σ 2 , σ 3 (monitoring rate to infected individuals) have negative impacts on R 0 . The numerical result suggests that the ACD strategy can be useful for the VL elimination program. Due to a small increment in the monitoring rate, the dynamic behavior of infected individuals dramatically decreased. Successful employment of ACD strategy may reduce more than 60–80% symptomatic and post kala-azar dermal leishmaniasis (PKDL) individuals. We found that healthcare organizations should prioritize ACD in symptomatic and PKDL individuals over asymptomatic individuals. We also observed that the use of only culling effect to the reservoirs is not beneficial to society in the control of VL, but spraying of insecticides and the use of treated bednets can be effective control strategies to curtail the outbreak of the disease. [ABSTRACT FROM AUTHOR]

This article discusses the case of an 87-year-old woman who was admitted to the hospital with symptoms of weakness, fatigue, and weight loss. The patient had a history of visceral leishmaniasis, a parasitic infection, which had previously been treated with medication. However, she experienced relapses of the infection and was eventually diagnosed with diffuse large B-cell lymphoma, a type of blood cancer. The article suggests that the prolonged exposure to leishmanial antigens may have contributed to the development of the lymphoma. The case highlights the importance of considering multiple diagnoses in patients with chronic diseases and the need for further research on the potential association between leishmaniasis and lymphoma. [Extracted from the article]