Search Results (1,016)

Vector-borne parasitic diseases (VBPDs), including malaria, schistosomiasis, leishmaniasis, Chagas disease, African trypanosomiasis, lymphatic filariasis, and onchocerciasis, impose a significant global health burden. This study analyzes the global disease burden of VBPDs from 1990 to 2021 using Global Burden of Disease (GBD) 2021 data and projects trends to 2036. Metrics include prevalence, deaths, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) across regions, sexes, age groups, and Socio-demographic Index (SDI) levels. Key findings reveal persistent disparities: malaria dominated the burden (42% of cases, 96.5% of deaths), disproportionately affecting sub-Saharan Africa. Schistosomiasis ranked second in prevalence (36.5%). While African trypanosomiasis, Chagas disease, lymphatic filariasis, and onchocerciasis declined significantly, leishmaniasis showed rising prevalence (EAPC = 0.713). Low-SDI regions bore the highest burden, linked to environmental, socioeconomic, and healthcare access challenges. Males exhibited greater DALY burdens than females, attributed to occupational exposure. Age disparities were evident: children under five faced high malaria mortality and leishmaniasis DALY peaks, while older adults experienced complications from diseases like Chagas and schistosomiasis. ARIMA modeling forecasts divergent trends: lymphatic filariasis prevalence nears elimination by 2029, but leishmaniasis burden rises across all metrics. Despite overall progress, VBPDs remain critical public health threats, exacerbated by climate change, drug resistance, and uneven resource distribution. Targeted interventions are urgently needed, prioritizing vector control in endemic areas, enhanced surveillance for leishmaniasis, gender- and age-specific strategies, and optimized resource allocation in low-SDI regions. This analysis provides a foundation for evidence-based policy and precision public health efforts to achieve elimination targets and advance global health equity. Full article

Background/Objectives: Leishmania spp. are protozoan parasites transmitted by female sandflies (Phlebotomus or Lutzomyia). Clinical manifestations depend on species and host immunity. While cutaneous and visceral forms prevail, mucocutaneous involvement—particularly isolated nasal septum leishmaniasis—is rare and frequently misdiagnosed as an inflammatory, infectious, or neoplastic condition. Risk factors associated with mucocutaneous leishmaniasis include systemic or local immunodeficiency, prior renal transplantation, treatment with chronic inhaled steroids, residence in endemic areas or travel to such regions, and previous Leishmania infections. Immunosuppressed patients are at higher risk for atypical presentations and delayed diagnosis, which can result in extensive tissue destruction. Early clinical suspicion, histopathological confirmation, and prompt therapy are essential to prevent permanent mucosal damage. Therefore, a multidisciplinary approach is needed for adequate evaluation and effective treatment. Methods: A 67-year-old man with rheumatoid arthritis on methotrexate reported a two-year history of right-sided nasal obstruction and ulceration that failed to respond to antibiotics. He did not present systemic symptoms. Results: Facial CT revealed a septal deviation; the patient underwent septoplasty, and biopsy confirmed Leishmania amastigotes. Serology (rK39 immunochromatographic test) was positive. He was treated with liposomal amphotericin B at 4 mg/kg/day for five days, followed by miltefosine at 100 mg/day orally for 14 days. At an eight-week follow-up, the nasal mucosa was fully healed, obstruction was resolved, and there was no evidence of recurrence. Conclusions: Although nasal septum leishmaniasis is uncommon, it should be considered in the differential diagnosis of chronic nasal lesions, especially in immunocompromised patients or those from endemic regions. Definitive diagnosis requires biopsy with histological or molecular confirmation. Combined liposomal amphotericin B and miltefosine therapy yields high cure rates and prevents mucosal destruction. Early recognition is critical to avoid diagnostic delays and long-term sequelae. Full article

Background/Objectives: Leishmaniasis is an infectious disease caused by digenetic protozoa of the genus Leishmania, transmitted by infected female sandflies of the Phlebotominae subfamily. Current treatments are limited, relying on drugs that were not specifically developed for this disease and are often associated with high toxicity and elevated costs. Among alternative therapeutic strategies, antifolate compounds have been investigated due to their ability to inhibit dihydrofolate reductase (DHFR), an enzyme essential for folate metabolism in the parasite. However, the parasite circumvents DHFR inhibition through the activity of pteridine reductase-1 (PTR-1), which maintains folate reduction and ensures parasite survival. In this context, this study aimed to identify potential PTR-1 inhibitors in Leishmania major through in silico approaches. Methods: The methodology included virtual screening of molecular databases, Tanimoto similarity analysis, pharmacokinetic and toxicological predictions, and biological activity evaluation in silico. The most promising compounds were further analyzed via molecular docking. Results: The virtual screening resulted in 474 molecules, of which 4 structures (M601, M692, M700, and M703) showed high potential as PTR-1 inhibitors in Leishmania major throughout all stages of the methodology employed, especially in the results of molecular docking where they exhibited strong binding affinities and significant interactions with key residues of the target enzymes. Conclusions: This work provides a solid foundation for advancing these molecules into experimental validation, contributing to the development of safer and more effective therapeutic alternatives for the treatment of leishmaniasis. Full article

Background: Worldwide, the number of cases of parasitic diseases has been increasing; however, available treatments have variable adverse effects and low efficacy, mainly in Neglected Tropical Diseases such as Chagas disease and Leishmaniasis. Therefore, the development of new and more effective antiparasitic drugs is important. Natural products are the source of secondary metabolites with different biological activities, such as antibacterial, anticancer, anti-inflammatory, and antiparasitic. Objectives: In this work, secondary metabolites (phenols and terpenes) from natural products were selected to be evaluated against the epimastigotes of NINOA and A1 strains of Trypanosoma cruzi and the promastigotes of M379 strain and FCQEPS native isolate of Leishmania mexicana. Additionally, their cytotoxicity and selectivity index were determined. Methods: Eighteen secondary metabolites were evaluated in vitro against T. cruzi epimastigotes and L. mexicana promastigotes; additionally, their cytotoxicity on the J774.2 macrophage cell line was determined. Results: The compounds l-(-)-menthol (14, IC₅₀ = 24.52 µM) and β-citronellol (11, IC₅₀ = 21.54 µM) had higher trypanocidal activity than the reference drug (benznidazole) against NINOA and A1 strains of T. cruzi, respectively. On the other hand, para-anisyl alcohol (4, IC₅₀ = 34.89 µM) had higher leishmanicidal activity than the reference drug (glucantime^®) against M379 and the FCQEPS native isolate of L. mexicana. Finally, in silico, the determination of their pharmacokinetic and toxicological properties showed that they are promising candidates for oral and topical uses. Conclusions: This study opens the possibility of using secondary metabolites as scaffolds for access to the development of new molecules for the treatment of parasite diseases. Full article

Leishmaniasis is caused by protozoan parasites from the genus Leishmania and remains one of the major threats to global health, impacting millions of people worldwide as well as animals including dogs. Several treatments have been used for managing leishmaniasis; nevertheless, drug resistance has emerged as an important obstacle to disease control. Therefore, there is an urgent need to discover new therapeutic targets. The aim of this work was to study the role played by the breast cancer associated 1 C-terminal (BRCT) domain from LmjPES protein (Pescadillo ribosomal biogenesis factor) in Leishmania major‘s pathogenesis through the construction of novel genomic tools. For this purpose, Leishmania integrative plasmids that were able to express the BRCT domain from LmjPES and a hypothetical defective LmjPES lacking this BRCT domain were constructed. It was observed that the overexpression of the aforementioned BRCT domain in L. major dysregulated the mRNA expression of 152 genes (95 up-regulated and 57 down-regulated) in respect to control parasites. Furthermore, clustering studies of these altered genes revealed an enrichment in genes related to metabolic processes, transporter activity, response to stimuli, and protein folding, which are categories described to be associated with the metacyclogenesis process and parasite survival. Interestingly, these genes reached normal levels of expression in parasites transfected with a defective LmjPES (a mutated gene lacking the coding sequence of the BRCT domain). In addition, it was found that the footpad of mice inoculated with LmjPES BRCT-overexpressing parasites had significantly greater inflammation compared to the size of the footpad of animals infected with the control parasites. Based on all these results, it was suggested that the BRCT domain from LmjPES might play a role in L. major‘s infection process and pathogenesis. Full article

Cutaneous Leishmaniasis (CL) is a tropical disease endemic in many regions of Latin America. Its clinical diagnosis is often supported by histopathological analysis of skin biopsies; however, parasite detection by microscopy can be challenging, particularly in chronic or pauciparasitic lesions, leading to inconclusive results. Objective: This study aimed to evaluate the utility of polymerase chain reaction (PCR) as a confirmatory diagnostic tool for CL in formalin-fixed, paraffin-embedded (FFPE) biopsies with inconclusive histopathology. Methods: We analyzed 16 FFPE skin biopsy samples from patients with clinical suspicion of CL. All cases underwent routine histopathological evaluation using hematoxylin and eosin staining and were classified as inconclusive. DNA was extracted and PCR was performed, targeting the ITS1 and miniexon regions of Leishmania spp. Results: PCR successfully amplified Leishmania DNA in 8 (50%) out of 16 samples when both targets were utilized, confirming infection. These findings highlight the additional benefits of molecular tools in cases with inconclusive histopathology, thereby enhancing diagnostic accuracy and enabling species-level identification in certain instances. Conclusions: PCR proved to be a valuable diagnostic complement to histopathology in clinically and histologically suspected cases of CL without visible parasites. Its implementation may improve diagnostic accuracy and timely treatment in endemic areas. Full article

Background: First-line treatments for cutaneous leishmaniasis (CL), including topical agents, are often limited in cases of complicated disease involving multiple, facial, or treatment-resistant lesions. Data on intravenous liposomal amphotericin B (L-AmB) are scarce, especially in children. We report our experience using L-AmB to treat pediatric CL, focusing on treatment rationale, safety, and clinical effectiveness. Methods: A retrospective case series. Diagnosis was confirmed by PCR. Data on demographics, clinical presentation, treatment rationale, adverse events, lab findings, and outcomes, during treatment and follow-up, were collected. Results: Twenty-seven children were included, most (96%) with Leishmania major. The mean number of lesions per child was 5.71 ± 6.19. All had facial involvement; 41% nasal and 15% eyelid. Most lesions were ulcerated (78%). Prior treatment failure was common (78%), with the use of topical antimicrobials, liposomal amphotericin gel, and paromomycin-containing ointments (59%, 38%, 19%, respectively). Twenty-four children (89%) completed treatment successfully. Adverse events occurred in 41% of cases but were mostly mild and reversible: flushing, rash, shortness of breath, and vomiting (11%, each). One case of transient renal impairment and one case with neutropenia were recorded. Early improvement was noted by day 10, with 50% (n = 12) of cases exhibiting crust falling/reduced ulceration and a 50% lesion size reduction. By day 30–90, 92% achieved substantial healing without the need for further therapy. Nevertheless, scarring was noted in 79% of cases. Conclusions: L-AmB treatment appears to be safe and effective for pediatric CL, particularly in cases with facial lesions or prior treatment failure. Clinical improvement was notable, although scarring was common. Full article

Leishmaniases are neglected tropical diseases caused by protozoan parasites of the Leishmania genus, with a significant global health burden, particularly in low-income regions. The parasites rely on a unique thiol-based redox system centered on trypanothione, which is essential for survival under oxidative stress encountered during their life cycle in both insect vectors and mammalian hosts. Given the absence of mammalian analogs, the trypanothione system represents an attractive target for antileishmanial drug development. However, accurate quantification of the reduced and oxidized forms of trypanothione has been challenging due to its instability and structural similarity between redox states. Here, we developed and validated a rapid, sensitive liquid chromatography–mass spectrometry (LC-MS) method for assessing the trypanothione redox state in Leishmania infantum. By incorporating N-ethylmaleimide as a thiol-blocking agent during sample preparation, the native redox state was preserved, enabling precise measurement of the reduced-to-oxidized ratio. Our approach demonstrated high sensitivity (nanomolar range), a rapid analysis time (5 min/sample), and robustness across various conditions. Moreover, we validated the method’s relevance in detecting oxidative stress and response to the trypanothione reductase inhibitor auranofin. This LC-MS technique provides a valuable tool for exploring Leishmania redox biology and supports the discovery of redox-targeting therapies against leishmaniasis. Full article

Objective: Visceral leishmaniasis (VL), a Neglected Tropical Disease caused by Leishmania donovani, remains insufficiently addressed by current therapies due to high toxicity, poor efficacy, and immunosuppressive complications. This study aimed to identify and characterize repurposed drugs that simultaneously target parasite-encoded and host-associated mechanisms essential for VL pathogenesis. Methods: Two complementary in silico drug repurposing strategies were employed. The first method utilized electron–ion interaction potential (EIIP) screening followed by molecular docking and molecular dynamics (MD) simulations targeting two L. donovani proteins: Rab5a and pteridine reductase 1 (PTR1). The second approach employed network-based drug repurposing using the Drugst.One platform, prioritizing candidates via STAT3-associated gene networks. Predicted drug–target complexes were validated by 100 ns MD simulations, and pharmacokinetic parameters were assessed via ADMET profiling using QikProp v7.0 and SwissADME web server. Results: Entecavir and valganciclovir showed strong binding to Rab5a and PTR1, respectively, with Glide Scores of −9.36 and −9.10 kcal/mol, and corresponding MM-GBSA ΔG_bind values of −14.00 and −13.25 kcal/mol, confirming their stable interactions and repurposing potential. Network-based analysis identified nifuroxazide as the top candidate targeting the host JAK2/TYK2–STAT3 axis, with high stability confirmed in MD simulations. Nifuroxazide also displayed the most favorable ADMET profile, including oral bioavailability, membrane permeability, and absence of PAINS alerts. Conclusions: This study highlights the potential of guanine analogs such as entecavir and valganciclovir, and the nitrofuran derivative nifuroxazide, as promising multi-target drug repurposing candidates for VL. Their mechanisms support a dual strategy targeting both parasite biology and host immunoregulation, warranting further preclinical investigation. Full article

Canine visceral leishmaniasis (CVL) is a major zoonosis that poses a growing challenge to public health services, as successful disease management requires sensitive, specific, and rapid diagnostic methods capable of identifying infected animals even at a subclinical level. The objective of this study was to evaluate the performance of the recombinant chimeric protein rMELEISH3 as an antigen in ELISA assays for the robust diagnosis of CVL. The protein was expressed in a bacterial system, purified by affinity chromatography, and evaluated through a series of serological assays using serum samples from dogs infected with Leishmania infantum. ROC curve analysis revealed a diagnostic sensitivity of 96.4%, a specificity of 100%, and an area under the curve of 0.996, indicating excellent discriminatory power. Furthermore, rMELEISH3 was recognized by antibodies present in the serum of dogs with low parasite loads, reinforcing the diagnostic potential of the assay in asymptomatic cases. It is concluded that the use of the recombinant antigen rMELEISH3 could significantly contribute to the improvement of CVL surveillance and control programs in endemic areas of Brazil and other countries, by offering a safe, reproducible and effective alternative to the methods currently recommended for the serological diagnosis of the disease. Full article

Leishmaniasis, a vector-borne neglected tropical disease, affects over 6.2 million people globally. Case acquisition is increasingly recognized in the United States, and in Texas, most reported cases are locally acquired and speciated to Leishmania mexicana. We conducted a scoping literature review to systematically assess contemporary research on Leishmania in humans, animals, reservoir hosts, or vectors in Texas after 2000. Out of 22 eligible studies, the most prevalent themes were case reports, followed by studies on domestic animals, reservoirs, and vectors, with several studies bridging multiple disciplines. Climate change, urbanization, and habitat encroachment appear to be driving the northward expansion of L. mexicana, which is primarily attributed to shifts in the habitats of key vectors (Lutzomyia anthophora) and reservoirs (Neotoma spp.). Leishmania appears to be expanding into new areas, with potential for further spread. As ecological conditions evolve, strengthening surveillance and clinician awareness is crucial to understanding disease risk and improving early detection and treatment in affected communities. Full article

Human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is a complex parasitic disease marked by dynamic host–parasite interactions and immunomodulation. Extracellular vesicles (EV) derived from immune cells have emerged as key mediators of intercellular communication and potential biomarkers in infectious diseases. In this study, we combined a modified lymphocyte proliferation assay with nano-flow cytometry to quantify and phenotype EV released by CD4⁺, CD8⁺, and CD14⁺ cells in PBMC cultures from CL patients at different clinical stages: before treatment (PBT), during treatment (PDT), and post-treatment (PET) with antimonial. Healthy individuals (HI) were included as physiological controls. Upon stimulation with L. (V.) braziliensis antigens, we observed a distinct modulation of EV subsets. In the PBT group, CD4⁺ and CD14⁺ EV were significantly reduced, while CD8⁺ EV remained elevated. During PDT and PET, EV concentrations were restored across all subsets. These findings suggest that L. (V.) braziliensis selectively modulates the release of immune cell–derived EV, possibly as an immune evasion mechanism. The restoration of EV release following antimonial therapy highlights their potential as sensitive biomarkers for disease activity and treatment monitoring. This study offers novel insights into the immunoregulatory roles of EV in CL and underscores their relevance in host–parasite interactions. Full article

This article describes a new software architecture for the non-invasive detection of canine leishmaniasis disease. The proposed platform combines gas-sensing technologies, artificial intelligence (AI), and modular cloud-based software components to identify disease-specific volatile organic compounds (VOCs) found in dog breath and hair samples. The system, which has a multi-tier architecture that includes data collection, pre-processing, machine learning-based analysis, diagnosis-request processing, and user interfaces for veterinarians, faculty researchers, and dog owners, has been integrated into a Li-ion Power website plug-in. The primary goal of implementing the proposed platform is to detect parasites at any point they are infectious to a host. This includes detecting parasites at all stages of their life cycle, where they can infect a new host. In addition, this is crucial for accurate diagnosis, effective treatment, and preventing further transmission. Full article

Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW 267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic^® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 µg/g/cm² of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC₅₀ for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 µg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. Full article

Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus, whose 2020 outbreak was characterized as a pandemic by the World Health Organization. Restriction measures changed healthcare delivery, with telehealth providing a viable alternative throughout the pandemic. This study analyzed a telemedicine platform database with the goal of developing a diagnostic prediction model for COVID-19 patients. This is a longitudinal study of patients seen on the Conexa Saúde telemedicine platform in 2022. A multiple binary logistic regression model of controls (negative confirmation for COVID-19 or confirmation of other influenza-like illness) versus COVID-19 was developed to obtain an odds ratio (OR) and a 95% confidence interval (CI). In the final binary logistic regression model, six factors were considered significant: presence of rhinorrhea, ocular symptoms, abdominal pain, rhinosinusopathy, and wheezing/asthma and bronchospasm were more frequent in controls, thus indicating a greater chance of flu-like illnesses than COVID-19. The presence of tiredness and fatigue was three times more prevalent in COVID-19 cases (OR = 3.631; CI = 1.138–11.581; p-value = 0.029). Our findings suggest potential predictors associated with influenza-like illness and COVID-19 that may distinguish between these infections. Full article