Mario Javier Olivera, Angela Patricia Guerra, Liliana Jazmín Cortés, Aravy Geohanna Suárez-Jurado, María de la Paz Ade, Iván Mauricio Cárdenas
{"title":"Prevalence of pfhrp2/pfhrp3 gene deletions among patients with Plasmodium falciparum malaria with false-negative in the HRP2-based rapid diagnostic test in Colombia.","authors":"Mario Javier Olivera, Angela Patricia Guerra, Liliana Jazmín Cortés, Aravy Geohanna Suárez-Jurado, María de la Paz Ade, Iván Mauricio Cárdenas","doi":"10.1590/0074-02760240134","DOIUrl":"https://doi.org/10.1590/0074-02760240134","url":null,"abstract":"<p><strong>Background: </strong>In malaria-endemic regions, rapid diagnostic tests (RDTs) play a crucial role in promptly identifying infections, especially in remote areas with limited microscopy services.</p><p><strong>Objectives: </strong>Conduct a cross-sectional, multi-site study to determine whether the local prevalence of mutations in the Plasmodium falciparum hrp2/3 genes in false-negative RDTs has reached a threshold that might require a local or national change in diagnostic strategy in accordance with the WHO guidelines (2018).</p><p><strong>Methods: </strong>Individuals were screened for P. falciparum with microscopy and HRP2-based RDT at health facilities. Discordant results between these two tests triggered diagnostic confirmation by polymerase chain reaction (PCR) and detection of the pfhrp2/pfhrp3 genes.</p><p><strong>Findings: </strong>Among the 347 patients included, false negatives constituted 4.61% (16/347). Molecular analysis revealed all 16 false negatives were P. falciparum positive with hrp2 gene present, displaying high polymorphism. However, hrp3 gene deletion was observed in 93.8% (15/16) of these cases.</p><p><strong>Main conclusions: </strong>The prevalence of false-negative RDTs is low, and these results were not linked to deletions in the hrp2 gene. This suggests that there is no immediate need to modify the RDTs used along the Colombian Pacific Coast. However, molecular surveillance for hrp2 deletions remains crucial to detect any potential increase in prevalence.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240134"},"PeriodicalIF":2.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wilker Jose Perez Gotay, Mariella Sousa Coêlho Maciel, Raphael de Oliveira Rodrigues, Cynthia Chester Cardoso, Caroline Nobre Oliveira, Artur Fontenelle Lima Montenegro, Juliana Navarro Ueda Yaochite
{"title":"X-linked polymorphisms in TLR7 and TLR8 genes are associated with protection against Chikungunya fever.","authors":"Wilker Jose Perez Gotay, Mariella Sousa Coêlho Maciel, Raphael de Oliveira Rodrigues, Cynthia Chester Cardoso, Caroline Nobre Oliveira, Artur Fontenelle Lima Montenegro, Juliana Navarro Ueda Yaochite","doi":"10.1590/0074-02760230224","DOIUrl":"https://doi.org/10.1590/0074-02760230224","url":null,"abstract":"<p><strong>Background: </strong>Chikungunya virus (CHIKV) causes an infection that leads to the activation of the innate immune response, triggering receptor pathways such as toll-like receptors (TLRs).</p><p><strong>Objective: </strong>The present study aimed to investigate the association of single nucleotide polymorphisms (SNPs) in genes encoding toll-like receptors 3, 7, and 8 and IRF5 in susceptibility to CHIKV infection and persistent joint pain.</p><p><strong>Methods: </strong>A case-control study was carried out. The study included 121 symptomatic cases, 29 asymptomatic cases, and 182 healthy controls matched for age and sex. Polymorphisms were identified by TaqMan® SNP Genotyping assays.</p><p><strong>Findings: </strong>The G allele of the TLR7 variant (rs3853839 G/C) and the G allele of TLR8 (rs3764879 G/C) were associated with protection against CHIKV infection [adjusted odd ratio (OR) = 0.64; p = 0.02 and adjusted OR = 0.54; p = 0.001, respectively]. Moreover, individuals who presented the G allele in the rs3764879 variant have a greater chance of developing the asymptomatic form (adjusted OR =2.88; p =0.004). The development of persistent joint pain was not associated with any investigated SNPs in positive anti-CHIKV IgG individuals.</p><p><strong>Main conclusions: </strong>This study identified TLR7 and TLR8 gene polymorphisms as protective factors for Chikungunya infection.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e230224"},"PeriodicalIF":2.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carla Gisele Ribeiro Garcia, Beatriz C Ribeiro, Alcinês S Souza Júnior, Lilian Jéssica P Lima, Marinete M Póvoa, Gabriel Z Laporta, Maristela G Cunha
{"title":"Assessing the spatial influence of deforestation on malaria incidence in Pará State, Amazon region, Brazil, 2008-2019.","authors":"Carla Gisele Ribeiro Garcia, Beatriz C Ribeiro, Alcinês S Souza Júnior, Lilian Jéssica P Lima, Marinete M Póvoa, Gabriel Z Laporta, Maristela G Cunha","doi":"10.1590/0074-02760240143","DOIUrl":"https://doi.org/10.1590/0074-02760240143","url":null,"abstract":"<p><strong>Background: </strong>Malaria transmission is prevalent in tropical regions and is heavily influenced by environmental factors such as deforestation, which is particularly significant in the Brazilian Amazon, especially in Pará State.</p><p><strong>Objective: </strong>This study aimed to assess the relationship between deforestation indicators and malaria incidence across all 144 municipalities in Pará.</p><p><strong>Methods: </strong>Using municipal-level data from 2008 to 2019, the study applied geographically weighted regression (GWR) to analyse spatial relationships between malaria incidence and deforestation metrics. These metrics included forest cover loss from the previous year, pastureland, forest cover, fragmentation, urbanisation, and water levels, analysed over three distinct 4-year periods. The study also incorporated poverty levels to examine their influence on municipalities with high malaria risk.</p><p><strong>Findings: </strong>During the study period, the total deforested area in Pará was 30,000 km2, with 679,846 malaria cases reported. Malaria incidence rates varied across municipalities, with stable rates in high-risk areas, and were linked to pastureland, forest loss, fragmentation, and forest cover. The GWR models effectively captured spatial heterogeneity in these interactions.</p><p><strong>Main conclusions: </strong>Malaria incidence was associated with areas of Pará State experiencing significant forest loss and fragmentation, indicating that changes in forest composition and configuration influence malaria risk.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240143"},"PeriodicalIF":2.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alejandro Luquetti Ostermayer, Fernanda Alvarenga Cardoso Medeiros, Jacqueline Araújo Domingos Iturra, Job Alves de Souza Filho, Leonardo Maia Leony, Larissa de Carvalho Medrado Vasconcelos, Liliane da Rocha Siriano, Suelene Brito do Nascimento Tavares, Vinícius Silva Belo, Andréa Silvestre de Sousa, Fred Luciano Neves Santos
{"title":"A multicentre comparative study of serological methods for diagnosing Chagas disease in Brazil.","authors":"Alejandro Luquetti Ostermayer, Fernanda Alvarenga Cardoso Medeiros, Jacqueline Araújo Domingos Iturra, Job Alves de Souza Filho, Leonardo Maia Leony, Larissa de Carvalho Medrado Vasconcelos, Liliane da Rocha Siriano, Suelene Brito do Nascimento Tavares, Vinícius Silva Belo, Andréa Silvestre de Sousa, Fred Luciano Neves Santos","doi":"10.1590/0074-02760240282","DOIUrl":"https://doi.org/10.1590/0074-02760240282","url":null,"abstract":"<p><strong>Background: </strong>Chagas disease (CD), a neglected tropical disease caused by Trypanosoma cruzi, remains a significant often underdiagnosed public health challenge in endemic regions, affecting millions globally. Accurate and timely diagnosis is critical, but the performance of existing diagnostic methods varies widely in sensitivity and specificity.</p><p><strong>Objectives: </strong>This multicentre study assessed the diagnostic performance of 17 serological assays for detecting anti-T. cruzi antibodies.</p><p><strong>Methods: </strong>Commercial enzyme immunoassays (EIA), indirect haemagglutination assays (IHA), indirect immunofluorescence assays (IIF), rapid diagnostic tests (RDT), and a chemiluminescent microparticle immunoassay (CMIA) were included in this study.</p><p><strong>Findings: </strong>Some EIA-based tests achieved 100% sensitivity, while IHAs and IIFs demonstrated reduced specificity. CMIA exhibited 100% sensitivity, highlighting its potential as a robust screening tool. Combining EIAs with IHAs or IIFs improved overall sensitivity, often surpassing 99%, although specificity remained variable. Cross-reactivity with other parasitic diseases posed challenges to specificity, particularly in assays employing crude antigens.</p><p><strong>Main conclusions: </strong>These findings emphasise the importance of tailoring diagnostic tool selection to regional epidemiological contexts and advancing antigen refinement to enhance diagnostic accuracy and accessibility, particularly in resource-limited settings.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240282"},"PeriodicalIF":2.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lissette Retana-Moreira, Elizabeth Abrahams-Sandí, Marco Ruiz-Campos, Johan Alvarado-Ocampo, Julián Castro, Jacob Lorenzo-Morales, Giovanni Sáenz-Arce, Antonio Osuna
{"title":"Detection of immunogenic protein components in excretion/secretion products of Acanthamoeba T5 using polyclonal antibodies.","authors":"Lissette Retana-Moreira, Elizabeth Abrahams-Sandí, Marco Ruiz-Campos, Johan Alvarado-Ocampo, Julián Castro, Jacob Lorenzo-Morales, Giovanni Sáenz-Arce, Antonio Osuna","doi":"10.1590/0074-02760240190","DOIUrl":"10.1590/0074-02760240190","url":null,"abstract":"<p><strong>Background: </strong>Acanthamoeba is a free-living amoeba widely distributed, responsible for keratitis and granulomatous amoebic encephalitis. The presence of virulence factors in its excretion/secretion products has been demonstrated. Characterisation of these products, including the determination of immunogenic protein components using polyclonal antibodies, could be the basis for the development of new diagnostic tools and help to understand aspects related to its pathogenesis.</p><p><strong>Objectives: </strong>To identify immunogenic protein components in Acanthamoeba conditioned medium (ACM) and extracellular vesicles (EVs) using polyclonal anti-Acanthamoeba antibodies produced in the laboratory and to evaluate the effect of these antibodies in adhesion and cytopathic effect.</p><p><strong>Methods: </strong>Excretion/secretion products were obtained after the axenic culture of a potentially pathogenic environmental Acanthamoeba T5 isolate. The presence of immunogenic components in lysates of trophozoites, ACM and EVs was determined using polyclonal anti-Acanthamoeba antibodies produced in Wistar rats. Proteomic analyses to identify the immunogenic protein components in ACM and EVs were included. Experiments to evaluate the effect of polyclonal anti-Acanthamoeba antibodies in adhesion and cytopathic effect in vitro were also performed in Vero cells.</p><p><strong>Findings: </strong>Protein recognition by anti-Acanthamoeba antibodies in lysates, ACM and EVs was demonstrated, and these components were identified using proteomics. Decreases in adhesion and cytopathic effect after the preincubation of trophozoites with antibodies, prior to the contact with cells, were observed.</p><p><strong>Main conclusion: </strong>The development of polyclonal antibodies, capable of recognising proteins related to pathogenesis in ACM and EVs, and with significant effects in adhesion, provides an important tool for the search for new therapeutic and diagnostic targets in infections caused by Acanthamoeba.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240190"},"PeriodicalIF":2.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriela Sadigurschi, Maria Cristina Caetano Kuschnir, Ewerton Alves Portela Dos Santos, Bruno Rangel Antunes da Silva, Celia Menezes Cruz Marques, Raissa Coelho de Andrade, Clarice Monteiro Vianna, Danillo Gonçalves de Barros, Mariana Torres Mazzi, Elvira Alonso Lago, Eliane Matos Dos Santos, Maria de Lourdes de Sousa Maia
{"title":"Challenges in developing new tuberculosis vaccines.","authors":"Gabriela Sadigurschi, Maria Cristina Caetano Kuschnir, Ewerton Alves Portela Dos Santos, Bruno Rangel Antunes da Silva, Celia Menezes Cruz Marques, Raissa Coelho de Andrade, Clarice Monteiro Vianna, Danillo Gonçalves de Barros, Mariana Torres Mazzi, Elvira Alonso Lago, Eliane Matos Dos Santos, Maria de Lourdes de Sousa Maia","doi":"10.1590/0074-02760240236","DOIUrl":"10.1590/0074-02760240236","url":null,"abstract":"<p><p>Tuberculosis (TB) is a preventable and curable disease caused by the bacillus Mycobacterium tuberculosis. In 2022, according to the World Health Organisation (WHO), TB was the second leading cause of death worldwide caused by a single infectious agent, after coronavirus disease (COVID-19). Brazil is ranked among the 30 countries with the highest TB burden. Currently, the neonatal Bacillus Calmette-Guérin (BCG) is the only vaccine against TB and offers significant efficacy against disseminated and meningeal disease in children. However, BCG has a limited efficacy in preventing adult-type cavitary TB, reinforcing the need for a new effective vaccine against pulmonary TB. There are currently over 22 TB vaccines under evaluation in clinical trials worldwide. Despite significant advancements, several challenges persist in developing and producing an effective TB vaccine. These include understanding the immune mechanisms that confer protection against M. tuberculosis, identifying immune correlates of protection, defining immune responses in BCG-vaccinated individuals, establishing efficacy endpoints for TB vaccine trials, and ensuring vaccine safety and effectiveness in individuals with human immunodeficiency virus (HIV), among other obstacles. Therefore, this study aims to explore the key obstacles in developing new TB vaccines and potential strategies to overcome them.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240236"},"PeriodicalIF":2.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marta de Lana, Lourena Tomazelli Suave, Júlio César Santoro de Oliveira Assis, Girley Francisco Machado de Assis, Matheus Marques Milagre, Glaucia Diniz Alessio, Renato Afonso Salgado, Olindo Assis Martins-Filho, Pedro Albajar-Viñas, Rosália Morais Torres
{"title":"Parasitological cure and clinical benefits of benznidazole treatment in patients from the Jequitinhonha Valley, MG, Brazil, with recent chronic infection by Trypanosoma cruzi II.","authors":"Marta de Lana, Lourena Tomazelli Suave, Júlio César Santoro de Oliveira Assis, Girley Francisco Machado de Assis, Matheus Marques Milagre, Glaucia Diniz Alessio, Renato Afonso Salgado, Olindo Assis Martins-Filho, Pedro Albajar-Viñas, Rosália Morais Torres","doi":"10.1590/0074-02760240229","DOIUrl":"10.1590/0074-02760240229","url":null,"abstract":"<p><strong>Background: </strong>The treatment of the early chronic phase of Chagas disease (CD) may result in high rates of parasitological cure, which may be associated with clinical benefits.</p><p><strong>Objectives: </strong>To evaluate children with CD from the Jequitinhonha Valley, MG, Brazil, treated with benznidazole (BZ), employing classic and alternative methodologies.</p><p><strong>Methods: </strong>Before and after treatment, nine individuals were examined by haemoculture, polymerase chain reaction (PCR), conventional enzyme-linked immunosorbent assay (ELISA), electrocardiogram, echocardiogram, and thoracic and gastrointestinal X-ray. Eight individuals were in the indeterminate clinical form of CD, and one was in the mild cardiac form. After treatment, all individuals were re-evaluated periodically for 4-26 years using the same methodologies cited and anti-live trypomastigotes antibodies by flow-cytometry-FC-ALTA and quantitative PCR (qPCR).</p><p><strong>Findings: </strong>The cure rate by the classic cure criteria was 33.33%. By the alternative cure criteria using FC-ALTA and qPCR, the rates of cure were 50% and 78%, respectively. Post-treatment clinical evaluations revealed stability in 5/9 and discrete clinical evolution in 4/9 individuals.</p><p><strong>Main conclusions: </strong>It was demonstrated the effectiveness of BZ treatment in recent chronic infections of CD with low or higher rates of parasitological cure according to the cure criterion used after long-term follow-up. The clinical status of the individuals remained stable or evolved slowly, suggesting clinical benefits from BZ treatment.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240229"},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Rafaela Antunes Porto, Isabela de Brito Duval, Luisa Vitor Braga do Amaral, Izabela da Silva Oliveira, João Gabriel Acioli de Siqueira, Bruno Araújo de Albuquerque, Maria Alice Guarini Rocha, Gabriela Gomes Monteiro Lemos, Marcelo Eduardo Cardozo, José Bryan da Rocha Rihs, Ricardo Toshio Fujiwara, Ana Laura Grossi de Oliveira, Ramayana Morais de Medeiros Brito, Lilian Lacerda Bueno
{"title":"Use of Brazilian flora as the main source of new antimalarials: a systematic review.","authors":"Ana Rafaela Antunes Porto, Isabela de Brito Duval, Luisa Vitor Braga do Amaral, Izabela da Silva Oliveira, João Gabriel Acioli de Siqueira, Bruno Araújo de Albuquerque, Maria Alice Guarini Rocha, Gabriela Gomes Monteiro Lemos, Marcelo Eduardo Cardozo, José Bryan da Rocha Rihs, Ricardo Toshio Fujiwara, Ana Laura Grossi de Oliveira, Ramayana Morais de Medeiros Brito, Lilian Lacerda Bueno","doi":"10.1590/0074-02760240123","DOIUrl":"10.1590/0074-02760240123","url":null,"abstract":"<p><p>Plants represent an important source of compounds for treating malaria, highlighting the rich biodiversity of Brazilian flora as a vital resource for developing new, effective antimalarial drugs. The present study sought to shed light on the search for new compounds with antimalarial activity obtained from the Brazilian flora. In this sense, a systematic review was conducted using screening techniques based on \"The Preferred Reporting Items for Systematic Reviews and Meta-Analysis\" (PRISMA) protocol. Most of the plants collected in the studies were from the Amazon Rainforest, north of Brazil. Most of the isolated compounds were from the Apocynaceae family and the alkaloids were the main compounds isolated with significant antiplasmodial activity, followed by flavonoids and phenolic compounds. The Brazilian flora can source many compounds with potential antimalarial activity that can challenge Plasmodium drug resistance. However, new studies are still needed to elucidate the natural compounds activity for future application in Malaria treatment.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240123"},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lais Alonso, Laís Flávia Nunes Lemes, George E Magoulas, Brenda de Lucena Costa, Rodrigo Saar Gomes, Miriam Leandro Dorta, Maria Laura Bolognesi, Luiz Antonio Soares Romeiro, Theodora Calogeropoulou, Antonio Alonso
{"title":"Miltefosine analogues with comparable antileishmanial activity and significantly reduced macrophage cytotoxicity.","authors":"Lais Alonso, Laís Flávia Nunes Lemes, George E Magoulas, Brenda de Lucena Costa, Rodrigo Saar Gomes, Miriam Leandro Dorta, Maria Laura Bolognesi, Luiz Antonio Soares Romeiro, Theodora Calogeropoulou, Antonio Alonso","doi":"10.1590/0074-02760240219","DOIUrl":"10.1590/0074-02760240219","url":null,"abstract":"<p><strong>Background: </strong>Miltefosine (MIL) is the only oral drug approved for leishmaniasis treatment, but its use is limited by gastrointestinal toxicity. Novel alkylphospholipid analogues may provide safer and more effective alternatives.</p><p><strong>Objectives: </strong>This study aimed to assess the antileishmanial activity, cytotoxicity, and membrane interactions of three MIL analogues TC387, TC388, and TC437 against Leishmania amazonensis.</p><p><strong>Methods: </strong>Antileishmanial and cytotoxic activities were evaluated in L. amazonensis, J774.A1 macrophages, and erythrocytes. Membrane interactions were characterized using spin-label electron paramagnetic resonance (EPR) spectroscopy.</p><p><strong>Findings: </strong>TC387, TC388, and TC437 demonstrated EC50 values of 10-16 µM for intracellular amastigotes, compared to 17 µM for MIL, with selectivity indices (SI) ranging from 43-163, significantly higher than MIL's SI of 5. EPR data revealed that the analogues increased membrane protein dynamics and caused greater disruption at the lipid-protein interface of parasite membranes relative to MIL. This disruption likely enhances pore formation, ion leakage, and reactive oxygen species (ROS) production, leading to parasite death.</p><p><strong>Main conclusions: </strong>The MIL analogues TC387, TC388, and TC437 exhibited superior SI and comparable or slightly enhanced antileishmanial activity relative to MIL, along with very low hemolytic potential. These findings support further investigation of these analogues as promising oral therapeutic candidates for leishmaniasis.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240219"},"PeriodicalIF":2.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eyleen Nabyla Alvarenga Niitsuma, Isabela de Caux Bueno, Gabriel da Rocha Fernandes, Mery Natali Silva Abreu, Francisco Carlos Félix Lana
{"title":"Anti-PGL-I seropositivity and development of leprosy in contacts: a comprehensive analysis of sociodemographic determinants, genetic susceptibility, and exposure characteristics to Mycobacterium leprae.","authors":"Eyleen Nabyla Alvarenga Niitsuma, Isabela de Caux Bueno, Gabriel da Rocha Fernandes, Mery Natali Silva Abreu, Francisco Carlos Félix Lana","doi":"10.1590/0074-02760240061","DOIUrl":"10.1590/0074-02760240061","url":null,"abstract":"<p><strong>Background: </strong>Leprosy is an infectious disease that remains hyperendemic in several Brazilian regions. Patient contacts face a higher risk for infection and illness, which can subsequently contribute to the persistence of the disease.</p><p><strong>Objective: </strong>This study investigates the risk factors associated with anti-phenolic glycolipid-I (anti-PGL-I) seropositivity and leprosy development among contacts of leprosy patients in a highly endemic region.</p><p><strong>Methods: </strong>A cohort of 629 contacts from the Almenara microregion, Minas Gerais, Brazil, was followed from 1998 to 2018. Our research group assessed risk factors, including sociodemographic determinants, bacillus exposure, and genetic susceptibility.</p><p><strong>Findings: </strong>Analysis revealed that living with a multibacillary (MB) leprosy patient [odds ratio (OR): 3.01, 95% confidence interval (CI): 1.02-8.86] and with a patient with grade II disabilities (OR: 4.43, 95% CI: 1.08-18.1) significantly increased the likelihood of anti-PGL-I seropositivity among asymptomatic contacts. Risk factors for leprosy included living with a patient in a shared residence (OR: 2.84, 95% CI: 1.21-6.67) and blood relation to the patient (OR: 2.56, 95% CI: 1.18-5.54). Notably, 98% of contacts who developed leprosy had lived with more than one patient.</p><p><strong>Main conclusions: </strong>Clinical characteristics of index patients play a critical role in infection risk among contacts. Leprosy progression appears to depend on genetic susceptibility, type of contact, and extent of bacillus exposure.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240061"},"PeriodicalIF":2.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}