UNASSIGNED: Despite concerted efforts in South America, these diseases continue to pose a significant burden of morbidity and mortality in endemic regions. This study aimed to analyse hospital data and investigate the hospitalisation rates of dengue fever, leishmaniasis, and malaria in Ecuador between 2015 and 2022.
UNASSIGNED: Open-access databases from the National Institute of Statistics and Censuses of Ecuador between 2015 and 2022 were analysed. Data were filtered using specific terms for each disease (ICD-10), and descriptive statistics of geographical distributions were calculated using Microsoft Excel, Stata 14.2, and Rstudio.
UNASSIGNED: Dengue had the highest burden, with 31,616 reported cases, followed by malaria (1,316) and leishmaniasis (283). From 2015 to 2022, the highest hospitalisation rate per 105 inhabitants for dengue was observed in Sucumbios province (697.2), for malaria in Pastaza province (108.4), and for leishmaniasis in Morona Santiago province (18.8). The data\'s trend analysis revealed a slight increase in dengue and mild downward trends in hospitalisation for malaria and leishmaniasis.
UNASSIGNED: The results suggest that vector-borne disease control has failed in Ecuador. Unfortunately, there was no significant trend towards a decrease in dengue, malaria, and leishmaniasis in Ecuador during the years studied. This study highlights the need to optimise sustainable vector control programs and emphasises continuous monitoring of disease incidence and control measures.

BACKGROUND: This study examined the experiences of owners of dogs with leishmaniosis who treated their dogs with daily subcutaneous meglumine antimoniate injections. The owners\' perceived ease of administering the injections, the occurrence of problems and the effects on the owners and on the dog‒owner bond were evaluated.
METHODS: Dogs prescribed meglumine antimoniate as a treatment for leishmaniosis were identified using the database of the veterinary pharmacy of the Faculty of Veterinary Medicine, Utrecht University. An online questionnaire was sent to the owners of these dogs to evaluate the perceived ease of administering the injections, the occurrence of problems and the effects on the owner and the dog-owner bond.
RESULTS: Responses were received from 64 dog owners. Most respondents (78%) reported that administering the injections was not difficult. Pain or the development of nodules at the injection site was reported in 50% and 40% of the dogs, respectively. Polyuria was reported in 44% of the dogs. Some owners reported that administering the injections had a negative impact on their psychological wellbeing (20%), and some would have liked more veterinary support (11%).
CONCLUSIONS: Some questions were answered by a limited number of people, and their responses may not be representative.
CONCLUSIONS: Dog owners remain highly motivated to persevere with meglumine antimoniate treatment and are willing to administer the injections themselves. The availability of active support when needed during the therapy cycle may further improve their acceptance of and confidence in giving the injections.

OBJECTIVE: Iran ranks among the top six countries globally with a significant incidence of Cutaneous Leishmaniasis (CL). Using planning models is one community-based intervention to promote preventive behaviors. The purpose of our study was to evaluate the effectiveness of the PRECEDE-PROCEED model (PPM) in modifying preventive behaviors related to CL in children through mother training in a community intervention.
METHODS: A randomized controlled trial based on the PPM model was conducted on 168 mothers (intervention (n = 84) and control group (n = 84) with 10 years old children in the rural areas of Iran. Mothers from 7 village areas were randomly allocated to the intervention (2 village) and control groups (5 village). The intervention group received a program comprising eight 90-minute training sessions and environmental interventions. In this study, we utilized the PPM as a framework to design the questionnaires on Leishmaniosis prevention behavior. Participants in both groups completed the questionnaires at baseline (before the intervention), immediately after the intervention, and at the 2-month follow-up. Analysis of the data was conducted utilizing SPSS20, with statistical significance set at p < 0.05.
RESULTS: Compared to the control group, the intervention group showed significant increases in knowledge, enabling factors, reinforcing factors, attitude, and preventive behaviors related to Cutaneous Leishmaniasis over time from baseline to follow-up (P < 0.001). No significant differences (P > 0.05) were observed in the alterations of the PPM construct, knowledge, and preventive behaviors within the control group from pre-intervention to follow-up.
CONCLUSIONS: Community (education and environmental) intervention based on PPM is feasible and acceptable to modify preventive behaviors of Cutaneous Leishmaniasis in children by increasing a mother\'s knowledge and attitude as well as changing enabling and reinforcing factors.
BACKGROUND: IRCT20160619028529N8.

Leishmania, the dixenous trypanosomatid parasites, are the causative agents of leishmaniasis currently divided into four subgenera: Leishmania, Viannia, Sauroleishmania, and the recently described Mundinia, consisting of six species distributed sporadically all over the world infecting humans and/or animals. These parasites infect various mammalian species and also cause serious human diseases, but their reservoirs are unknown. Thus, adequate laboratory models are needed to enable proper research of Mundinia parasites. In this complex study, we compared experimental infections of five Mundinia species (L. enriettii, L. macropodum, L. chancei, L. orientalis, and four strains of L. martiniquensis) in three rodent species: BALB/c mouse, Chinese hamster (Cricetulus griseus) and steppe lemming (Lagurus lagurus). Culture-derived parasites were inoculated intradermally into the ear pinnae and progress of infection was monitored for 20 weeks, when the tissues and organs of animals were screened for the presence and quantity of Leishmania. Xenodiagnoses with Phlebotomus duboscqi were performed at weeks 5, 10, 15 and 20 post-infection to test the infectiousness of the animals throughout the experiment. BALB/c mice showed no signs of infection and were not infectious to sand flies, while Chinese hamsters and steppe lemmings proved susceptible to all five species of Mundinia tested, showing a wide spectrum of disease signs ranging from asymptomatic to visceral. Mundinia induced significantly higher infection rates in steppe lemmings compared to Chinese hamsters, and consequently steppe lemmings were more infectious to sand flies: In all groups tested, they were infectious from the 5th to the 20th week post infection. In conclusion, we identified two rodent species, Chinese hamster (Cricetulus griseus) and steppe lemming (Lagurus lagurus), as candidates for laboratory models for Mundinia allowing detailed studies of these enigmatic parasites. Furthermore, the long-term survival of all Mundinia species in steppe lemmings and their infectiousness to vectors support the hypothesis that some rodents have the potential to serve as reservoir hosts for Mundinia.

Visceral Leishmaniasis (VL), the second neglected tropical disease caused by various Leishmania species, presents a significant public health challenge due to limited treatment options and the absence of vaccines. The agent responsible for visceral leishmaniasis, also referred to as \"black fever\" in India, is Leishmania donovani. This study focuses on L. donovani Minichromosome maintenance 10 (LdMcm10), a crucial protein in the DNA replication machinery, as a potential therapeutic target in Leishmania therapy using in silico and in vitro approaches. We employed bioinformatics tools, molecular docking, and molecular dynamics simulations to predict potential inhibitors against the target protein. The research revealed that the target protein lacks homologues in the host, emphasizing its potential as a drug target. Ligands from the DrugBank database were screened against LdMcm10 using PyRx software. The top three compounds, namely suramin, vapreotide, and pasireotide, exhibiting the best docking scores, underwent further investigation through molecular dynamic simulation and in vitro analysis. The observed structural dynamics suggested that LdMcm10-ligand complexes maintained consistent binding throughout the 300 ns simulation period, with minimal variations in their backbone. These findings suggest that these three compounds hold promise as potential lead compounds for developing new drugs against leishmaniasis. In vitro experiments also demonstrated a dose-dependent reduction in L. donovani viability for suramin, vapreotide, and pasireotide, with computed IC50 values providing quantitative metrics of their anti-leishmanial efficacy. The research offers a comprehensive understanding of LdMcm10 as a drug target and provides a foundation for further investigations and clinical exploration, ultimately advancing drug discovery strategies for leishmaniasis treatment.

UNASSIGNED: Despite many attempts to treat leishmaniasis, new approaches are necessary to reduce the burden of disease. Perovskia abrotanoides (Brazambel) has shown significant effects against Leishmania parasites in some studies. This study aimed to investigate the effects of P. abrotanoides extract topical formulation on cutaneous leishmaniasis.
UNASSIGNED: In this randomized controlled clinical trial, patients with cutaneous leishmaniasis were assigned to experimental (n = 18) and control (n = 18) groups. Both groups received intralesional meglumine antimoniate (Glucantime®). The experimental group also received 5% Brazambel extract ointment once a day. The interventions continued until the complete healing of the lesions (reepithelialization) for a maximum of 8 weeks. The clinical response, defined as complete response (reepithelialization >75%), partial response (reepithelialization 50%-75%), or treatment failure (reepithelialization <50%), was compared between the groups.
UNASSIGNED: The percentage of reepithelialization in the experimental group (4th week: 64.44 ± 25.13; 8th week: 83.85 ± 11.54) was higher than the control group (4th week: 53.97 ± 25.88; 8th week: 76.27 ± 21.67); however, the differences were not statistically significant (P = 0.252 and 0.494, respectively). Moreover, there was no significant difference between the experimental and control groups regarding the rate of complete healing (88.9% vs. 72.2%, respectively).
UNASSIGNED: The use of P. abrotanoides extract 5% topical formulation does not affect the healing of cutaneous leishmaniasis.

Parthenium hysterophorus plant has a diverse chemical profile and immense bioactive potential. It exhibits excellent pharmacological properties such as anti-cancer, anti-inflammatory, anti-malarial, microbicidal, and anti-trypanosomal. The present study aims to evaluate the anti-leishmanial potential and toxicological safety of anhydroparthenin isolated from P. hysterophorus. Anydroparthenin was extracted from the leaves of P. hysterophorus and characterized through detailed analysis of 1H, 13C NMR, and HRMS. Dye-based in vitro and ex vivo assays confirmed that anhydroparthenin significantly inhibited both promastigote and amastigote forms of the Leishmania donovani parasites. Both the cytotoxicity experiment and hemolytic assay revealed its non-toxic nature and safety index in the range of 10 to 15. Further, various mechanistic assays suggested that anhydroparthenin led to the generation of oxidative stress, intracellular ATP depletion, alterations in morphology and mitochondrial membrane potential, formation of intracellular lipid bodies, and acidic vesicles, ultimately leading to parasite death. As a dual targeting approach, computational studies and sterol quantification assays confirmed that anhydroparthenin inhibits the Sterol C-24 methyl transferase and Sterol 14-α demethylase proteins involved in the ergosterol biosynthesis in Leishmania parasites. These results suggest that anhydroparthenin could be a promising anti-leishmanial molecule and can be developed as a novel therapeutic stratagem against leishmaniasis.

UNASSIGNED: Cutaneous leishmaniasis (CL) is one of the main causes of vector-born diseases in younger population. To evaluate the association of environmental health factors on the odds of CL incidence, a case-control study was conducted in northeastern Iran.
UNASSIGNED: This study was conducted within 2020-2021 based on individual and household data from a tertiary referral center. Cases were patients diagnosed with CL by PCR method; controls were selected among the patients\' relatives, and information was obtained from a health registry system. Demographic and socioeconomic data of 1871 subjects, included age, sex, household information and environmental health factors. Multivariable models with environmental factors in various conditions and CL were separately fit by univariate and mixed multiple unconditional logistic regression.
UNASSIGNED: Participants included 617 cases (mean [SD] age, 13.62[13.72] years; 58.20% male) and 1264 controls (mean [SD] age, 16.45[15.44] years; 50.40% male). Results revealed that the use of well-water sources compared to surface water is significantly associated with CL (odds ratio [OR]=0.204; 95%CI, 0.13-0.33;P<0.001). Muddy houses, ruined buildings or wastelands and stagnant water, canals and rivers near the houses were also associated with CL (OR=3.85; 95%CI, 1.66-8.89; P=.002; OR=2.47; 95%CI, 1.76-3.47; P<.001). Besides, existence of pine tree was found to be a risk factor (OR=3.25; 95%CI, 2.12-4.99; P<.001) and similarly for the use of waste collection system (OR=4.43; 95%CI, 3.32-7.51; P<.001).
UNASSIGNED: Environmental factors related to houses were significantly associated with CL and may represent the modifiable risk factors of CL disease.

Aim: This study aimed to investigate the effects of topical liposomal clarithromycin in combination with meglumine antimoniate (Glucantime®) on cutaneous leishmaniasis (CL) lesions. Methods: This pilot, randomized, double-blinded clinical trial was conducted on patients with CL lesions. Patients were randomly assigned to two groups: the first group received liposomal clarithromycin in combination with Glucantime for 28 days, while the second group received Glucantime and a placebo. Afterward, patients were followed up at 1.5, 3, and 6 months after treatment initiation and were evaluated for recovery time, induration, and size of the lesions. Results: Sixty patients with CL lesions were divided into two separate groups with 30 members each and were examined. Within-group analysis revealed that recovery time in the clarithromycin group was 26.65 ± 5.12 days, while in the placebo group, it was 32.84 ± 24.43, which was statistically insignificant (p = 0.18). Lesion size comparison in the first and last follow-ups reduced in both groups: 7.73 ± 4.31 to 0.48 ± 0.50 in the clarithromycin group (p = 0.006) and 5.47 ± 5.83 to 0.76 ± 0.88 in the placebo group (p = 0.03). Moreover, the size of lesions in the intervention group was significantly reduced compared to that in the placebo group (p = 0.02). Recognizable induration reduction was observed in the clarithromycin group (2.60 ± 0.77 to 1.0 ± 0.00). No adverse effects attributable to clarithromycin were reported. Conclusion: The administration of liposomal clarithromycin in combination with systemic Glucantime had a significant beneficial effect on reducing lesion size in leishmaniasis. Further studies on larger populations are recommended. Systematic Review Registration: https://www.irct.ir/trial/46611.

Leishmaniasis is caused by ∼20 species of Leishmania that affects millions in endemic areas. Available therapies are not sufficient to effectively control the disease, cause severe side effects and eventually lead to drug resistance, making the discovery of novel therapeutic molecules an immediate need. Molecular target-based drug discovery, where the target is a defined molecular gene, protein or a mechanism, is a rationale driven approach for novel therapeutics. Humans obtain the essential amino acid such as threonine from dietary sources, while Leishmania synthesize it de-novo. Enzymes of the threonine biosynthesis pathway, including the rate limiting Homoserine kinase (HSK) which converts L-homoserine into ortho-phospho homoserine are thus attractive targets for rationale driven therapy. The absence of HSK in humans and its presence in Leishmania donovani enhances the opportunity to exploit HSK as a molecular target for anti-leishmanials therapeutic development. In this study, we utilize structure-based high throughput drug discovery (SBDD), followed by biochemical validation and identified two potential inhibitors (RH00038 and S02587) from Maybridge chemical library that targets L. donovani HSK. These two inhibitors effectively induced the mortality of Leishmania donovani in both amastigote and promastigote stages, with one of them being specific to parasite and twice as effective as the standard therapeutic molecule.