Spatial and temporal modeling of the global burden of Cutaneous Leishmaniasis in Brazil: A 21-year ecological study.

Background: Cutaneous Leishmaniasis (CL) is a neglected tropical disease endemic in Brazil. Morbidity and disabilities caused by CL lesions require an analysis of a Global Burden of Disease (GBD), which would help discern the impact on the Brazilian population. Herein, we assess the burden of CL and its spatial and temporal patterns in Brazil between 2001 and 2021.

Neutrophil-mediated hypoxia drives pathogenic CD8+ T cell responses in cutaneous leishmaniasis.

Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8+ T cell responses mediate disease. Although these responses originate in the lymph node, we found that expression of the cytolytic effector molecule granzyme B was restricted to lesional CD8+ T cells in Leishmania-infected mice, suggesting that local cues within inflamed skin induced cytolytic function.

Improved Treatment Outcome Following the Use of a Wound Dressings in Cutaneous Leishmaniasis Lesions.

Leishmaniasis, caused by parasites, is a neglected tropical disease and Cutaneous Leishmaniasis (CL) is the most common form. Despite the associated toxicity and adverse effects, Meglumine antimoniate (MA) remains the first-choice treatment for CL in Brazil, pressing the need for the development of better alternatives. Bacterial NanoCellulose (BNC), a biocompatible nanomaterial, has unique properties regarding wound healing.

GMP-compliant extracellular vesicles derived from umbilical cord mesenchymal stromal cells: manufacturing and pre-clinical evaluation in ARDS treatment.

Background Aims: Extracellular vesicles (EVs) represent a new axis of intercellular communication that can be harnessed for therapeutic purposes, as cell-free therapies. The clinical application of mesenchymal stromal cell (MSC)-derived EVs, however, is still in its infancy and faces many challenges. The heterogeneity inherent to MSCs, differences among donors, tissue sources, and variations in manufacturing conditions may influence the release of EVs and their cargo, thus potentially affecting the quality and consistency of the final product.

Immunization with -Deficient Does Not Protect against Homologous Challenge.

Immunization with various species lacking induces robust immunity against a homologous and heterologous virulent challenge, making mutants a putative candidate for a leishmaniasis vaccine. Centrin is a calcium-binding cytoskeletal protein involved in centrosome duplication in higher eukaryotes and spp. lacking centrin are unable to replicate and are non-pathogenic.

Pathogenic CD8 T cell responses are driven by neutrophil-mediated hypoxia in cutaneous leishmaniasis.

Cutaneous leishmaniasis caused by parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8 T cell responses mediate disease. While these responses originate in the lymph node, we find that expression of the cytolytic effector molecule granzyme B is restricted to lesional CD8 T cells in - infected mice, suggesting that local cues within inflamed skin induce cytolytic function.

High seroprevalence of Leishmania infantum is linked to immune activation in people with HIV: a two-stage cross-sectional study in Bahia, Brazil.

Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by and investigated the virological and immunological factors associated with co-infection.

Clinical Profile and Diagnosis of Recurrent Cutaneous Leishmaniasis.

This case-control study compared the clinical profile, parasite load, polymerase chain reaction positivity, and response to therapy in patients with recurrent cutaneous leishmaniasis (RCL) with primary cutaneous leishmaniasis (CL). The RCL patients had milder diseases with lower parasite loads, a lower number of lesions, and more self-healing diseases than primary CL patients.

Discovery of pyrazolopyrrolidinones as potent, broad-spectrum inhibitors of infection.

Introduction: Leishmaniasis is a parasitic disease that affects more than 1 million people worldwide annually, predominantly in resource-limited settings. The challenge in compound development is to exhibit potent activity against the intracellular stage of the parasite (the stage present in the mammalian host) without harming the infected host cells. We have identified a compound series (pyrazolopyrrolidinones) active against the intracellular parasites of and ; the causative agents of visceral and cutaneous leishmaniasis in the Old World, respectively.

Draft Genome Sequence of the Protozoan Parasite Leishmania braziliensis Strain BA788, Isolated from a Clinical Case in Bahia State, Brazil.

The draft genome of the parasite Leishmania braziliensis strain BA788, which was isolated from a patient from Bahia state, Brazil, was sequenced using Illumina paired-end technology. The assembled genome is 33.5 Mb long and contains 7,603 genes.

Serodiagnosis and therapeutic monitoring of New-World tegumentary leishmaniasis using synthetic type-2 glycoinositolphospholipid-based neoglycoproteins.

American tegumentary leishmaniasis (TL) caused by is characterized by a spectrum of clinical presentations, ranging from localized cutaneous ulcers (CL), mucosal (ML), or disseminated (DL) disease, to a subclinical (SC) asymptomatic form. Current diagnosis based on parasite culture and/or microscopy lacks sensitivity and specificity. Previous studies showed that patients with CL and ML have very high levels of -specific anti-α-Gal antibodies.

Pioglitazone, a Peroxisome Proliferator-Activated Receptor-γ Agonist, Downregulates the Inflammatory Response in Cutaneous Leishmaniasis Patients Without Interfering in Killing by Monocytes.

Patients with cutaneous leishmaniasis (CL) due to infection have an exacerbated inflammatory response associated with tissue damage and ulcer development. An increase in the rate of patients who fail therapy with pentavalent antimony has been documented. An adjuvant therapy with an anti-inflammatory drug with the potential of killing would benefit CL patients.

Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human Neutrophils.

Visceral leishmaniasis (VL) is often associated with hematologic manifestations that may interfere with neutrophil response. Lipophosphoglycan (LPG) is a major molecule on the surface of promastigotes, which has been associated with several aspects of the parasite-vector-host interplay. Here, we investigated how LPG from (.

Immune Response to LinB13, a Lutzomyia Intermedia Salivary Protein Correlates With Disease Severity in Tegumentary Leishmaniasis.

Background: We have previously shown that seropositivity to rLinB-13, a salivary protein from Lutzomyia intermedia, predicted sand fly exposure and was associated with increased risk of developing cutaneous leishmaniasis (CL).

Methods: Here, we investigated the cellular immune response to saliva from Lu. intermedia, using rLinB-13 as a surrogate antigen in naturally exposed individuals presenting positive serology to LinB-13.

Targeted Deletion of Centrin in Using CRISPR-Cas9-Based Editing.

is the main causative agent of Tegumentary Leishmaniasis in the Americas. However, difficulties related to genome manipulation, experimental infection, and parasite growth have so far limited studies with this species. CRISPR-Cas9-based technology has made genome editing more accessible, and here we have successfully employed the LeishGEdit approach to attenuate .

A pilot and open trial to evaluate topical Bacterial Cellulose bio-curatives in the treatment of cutaneous leishmaniasis caused by L. braziliensis.

The treatment of cutaneous leishmaniasis (CL) in Brazil using pentavalent antimony (Sb) is associated with a high failure rate and long time to heal. Moreover, standard Sb treatment cures only 50-60% of the cases. In this pilot clinical trial, we evaluated the topical use of bacterial cellulose (BC) bio-curatives + Sb in the treatment of CL caused by L.

A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B.1.1.33 Circulating in Brazil.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Brazil was dominated by two lineages designated as B.1.1.

The Long Pentraxin 3 (PTX3) Suppresses Immunity to Cutaneous Leishmaniasis by Regulating CD4 T Helper Cell Response.

The long pentraxin 3 (PTX3) plays a critical role in inflammation, tissue repair, and wound healing. Here, we show that PTX3 regulates disease pathogenesis in cutaneous leishmaniasis (CL). PTX3 expression increases in skin lesions in patients and mice during CL, with higher expression correlating with severe disease.

Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment of Infection.

Background: Leishmaniasis is a neglected disease, and the current therapeutic arsenal for its treatment is seriously limited by high cost and toxicity. Nanostructured lipid carriers (NLCs) represent a promising approach due to high drug loading capacity, controlled drug release profiles and superior stability. Here, we explore the efficacy of a unique pH-sensitive amphotericin B-loaded NLC (AmB-NLC) in infection in vitro and in vivo.

Photodynamic inactivation of Leishmania braziliensis doubly sensitized with uroporphyrin and diamino-phthalocyanine activates effector functions of macrophages in vitro.

Photodynamic inactivation of Leishmania has been shown to render them non-viable, but retain their immunological activities. Installation of dual photodynamic mechanisms ensures complete inactivation of species in the Leishmania subgenus, raising the prospect of their safe and effective application as whole-cell vaccines against leishmaniasis. Here, we report the successful extension of this approach to L.

Mechanistic and biological characterisation of novel -substituted paullones targeting the biosynthesis of trypanothione in .

Trypanothione synthetase (TryS) produces -bis(glutathionyl)spermidine (or trypanothione) at the expense of ATP. Trypanothione is a metabolite unique and essential for survival and drug-resistance of trypanosomatid parasites. In this study, we report the mechanistic and biological characterisation of optimised -substituted paullone analogues with anti-TryS activity.

Generation and Characterization of a Dual-Reporter Transgenic Line Expressing eGFP and Luciferase.

In this study, we generated a transgenic strain of , an etiological agent associated with a diversity of clinical manifestations of leishmaniasis ranging from localized cutaneous to mucocutaneous to disseminated disease. Transgenic parasites expressing reporter proteins are valuable tools for studies of parasite biology, host-pathogen interactions, and anti-parasitic drug development. To this end, we constructed an line stably expressing the reporters eGFP and luciferase (eGFP-LUC .

Effects of 10-valent pneumococcal conjugate (PCV10) vaccination on the nasopharyngeal microbiome.

Pathogenic bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis, are important vaccine targets. The 10-valent pneumococcal conjugate vaccine (PCV10) acts on 10 differents S. pneumoniae serovars.