Yolanda Hernández, María Elena Marson, Marisa Liliana Fernández, Omar Sued, Claudia Frola, Santiago Perez Lloret, Pedro Cahn, Nilda Graciela Prado, Guido Enrique Mastrantonio Garrido, Sergio Sosa-Estani
{"title":"Pharmacokinetics of two pharmaceutical presentations of benznidazole in adult Trypanosoma cruzi infected population.","authors":"Yolanda Hernández, María Elena Marson, Marisa Liliana Fernández, Omar Sued, Claudia Frola, Santiago Perez Lloret, Pedro Cahn, Nilda Graciela Prado, Guido Enrique Mastrantonio Garrido, Sergio Sosa-Estani","doi":"10.1590/0074-02760240177","DOIUrl":"10.1590/0074-02760240177","url":null,"abstract":"<p><strong>Background: </strong>Benznidazole (BNZ) is the primary treatment for Chagas disease. While pharmacokinetic studies of BNZ began in the 1970s, its metabolism and excretion are not fully understood. Alternatives like Benznidazol Lafepe® and Abarax® have replaced the original Radanil®.</p><p><strong>Objectives: </strong>To compare the pharmacokinetic profiles of both currently available formulations of BNZ in adults with chronic Trypanosoma cruzi infection.</p><p><strong>Methods: </strong>The study involved 13 subjects each one receiving 100 mg of both presentations one week apart. Blood samples were collected over 48 hours post-administration to analyse BNZ concentration and calculate pharmacokinetic parameters.</p><p><strong>Findings: </strong>The analysis showed that both presentations had similar maximum plasma concentration and time to reach maximum plasma concentration values. Area under curve (AUC) values were slightly lower in Abarax® than Benznidazol Lafepe®. High intra-individual variability was observed, attributed to erratic absorption patterns with multiple peaks in concentration-time curves. The half-life values for both formulations were 9.1 and 8.0 h, respectively, with a significant intra-individual variability over 30%.</p><p><strong>Main conclusions: </strong>The mean difference in the AUC was lower than 10%, but exceeded the 90% confidence interval for the higher bioequivalence limit. Despite the high variability that confirms erratic absorption, the pharmacokinetic parameters of both formulations were within expected ranges.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240177"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573415","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}
{"title":"Congenital Zika virus infection in laboratory animals: a comparative review highlights translational studies on the maternal-foetal interface.","authors":"Noemi Rovaris Gardinali, Renato Sergio Marchevsky, Yara Cavalcante Vieira, Marcelo Pelajo-Machado, Tatiana Kugelmeier, Juliana Gil Melgaço, Márcio Pinto Castro, Jaqueline Mendes de Oliveira, Marcelo Alves Pinto","doi":"10.1590/0074-02760240125","DOIUrl":"10.1590/0074-02760240125","url":null,"abstract":"<p><p>The 2015-16 Zika virus (ZIKV) epidemic has posed unprecedented concern for maternal-infant health, mainly due to the substantial risk of microcephaly and other neurological birth abnormalities associated with congenital ZIKV syndrome (CZS). As licenced vaccines and effective antivirals are still unavailable, attention has been focused on post-delivery in vitro or translational in vivo studies to understand the impact of maternal ZIKV infection on placentation and neurodevelopmental consequences for the foetus. Here, we review clinical and translational studies highlighting ZIKV-induced maternal-foetal interface dysfunction, adding to our previous observations of experimental ZIKV vertical transmission to pregnant rhesus monkeys and newly published post-epidemic findings about the theme. This comparative review focuses on the mechanisms by which the virus has a cytopathic effect on trophoblasts and macrophages during placentation in humans, nonhuman primates, and rodent transgenic models, crosses the placental barrier, replicates, and establishes a persistent uteroplacental infection. When considering the mechanism of ZIKV-induced birth defects in humans and other susceptible hosts, it becomes apparent how the various stages of the ZIKV cycle in the host (both the parent and offspring) unfold. This understanding presents specific opportunities for pharmacological intervention and the development of preventative vaccines.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240125"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573411","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}
Adeilton Alves Brandão, Ana Carolina P Vicente, Ricardo Lourenço-de-Oliveira
{"title":"Article series: from the first issue of Mem Inst Oswaldo Cruz (1909) to the present (2024).","authors":"Adeilton Alves Brandão, Ana Carolina P Vicente, Ricardo Lourenço-de-Oliveira","doi":"10.1590/0074-02760240250","DOIUrl":"10.1590/0074-02760240250","url":null,"abstract":"","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240250"},"PeriodicalIF":2.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502303","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}
Erika Martins Braga, Francisco Carlos Ferreira, Irène Landau
{"title":"From the first descriptions to recent advances: 115 years of reptile Plasmodium research in the Neotropics.","authors":"Erika Martins Braga, Francisco Carlos Ferreira, Irène Landau","doi":"10.1590/0074-02760240217","DOIUrl":"10.1590/0074-02760240217","url":null,"abstract":"<p><p>Haemosporida research started in the 19th century with the description of Plasmodium and other related parasites infecting mammals and birds. Here, we highlight the pioneering contributions of Henrique Aragão and Arthur Neiva in describing the first two Plasmodium species in lizards from the New World, Plasmodium diploglossi and Plasmodium tropiduri, published in the first printed issue of Memórias do Instituto Oswaldo Cruz in April 1909. We use these discoveries as a background to explore some historical and taxonomic aspects of Plasmodium species infecting reptiles, with a particular emphasis on the advancements made over the past 115 years in the Neotropics. Our review underscores the complexities and persistent challenges in the taxonomic classification of reptile haemosporidians and discusses some scientific advances in the field that improved our understanding of the biology and evolution of these parasites.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240217"},"PeriodicalIF":2.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502313","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}
Christian R González, Daniel Rafael Miranda-Esquivel
{"title":"Cladistic analysis and redefinition of the Dasybasis Macquart s. str. (Diptera: Tabanidae) in the Neotropical region.","authors":"Christian R González, Daniel Rafael Miranda-Esquivel","doi":"10.1590/0074-02760240245","DOIUrl":"10.1590/0074-02760240245","url":null,"abstract":"<p><strong>Background: </strong>The works of Lutz & Neiva, published 115 years ago in the Memórias do Instituto Oswaldo Cruz, are pioneering for the study of Neotropical Tabanidae. These studies emphasised the importance of biological collections and the description of species from the exploration of South American areas. Dasybasis Macquart, 1847 has traditionally been considered a large genus of tabanids restricted to the Australasian, Neotropical, and Andean regions. Dasybasis species exhibit a high degree of morphological similarity, making specific differentiation challenging. Moreover, some of these features are also present in other taxa, suggesting that they may not be homologous characters and should not be used to define the genus.</p><p><strong>Objectives: </strong>This study aimed to assess the monophyly of Dasybasis and establish its major monophyletic groups.</p><p><strong>Methods: </strong>We conducted an implied weighting analysis using morphological characters, and wing landmarks from 91 terminal species.</p><p><strong>Findings: </strong>For the total evidence analyses, aligning with either Tabanus Linnaeus or Dasybasis appendiculata Macquart yielded slightly different trees. Classical morphology and total evidence topology aligned with D. appendiculata are the same, while differing from the total evidence topology aligned with Tabanus in two nodes.</p><p><strong>Main conclusions: </strong>Our results indicate that Dasybasis was not a monophyletic group, and that this name should be restricted to species with a distribution in Australasia; while Neotropical Dasybasis species are recovered in different clades. The genera Archiplatius, Pseudoselasoma, and Stypommia are revalidated. This study provides a revised phylogenetic framework for \"Dasybasis\" and related taxa, highlighting the need for a more nuanced understanding of morphological character evolution within the tribe Diachlorini.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240245"},"PeriodicalIF":2.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502305","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}
Igor Vasconcelos Rocha, Matheus Filgueira Bezerra, Marise Sobreira, Alzira Maria Paiva de Almeida
{"title":"125 years of the plague in Brazil: lessons learnt, historical insights and contemporary challenges.","authors":"Igor Vasconcelos Rocha, Matheus Filgueira Bezerra, Marise Sobreira, Alzira Maria Paiva de Almeida","doi":"10.1590/0074-02760240220","DOIUrl":"10.1590/0074-02760240220","url":null,"abstract":"<p><p>The history of the plague, caused by Yersinia pestis, is marked by some of the most devastating pandemics. Its arrival in Brazil on the turn of the 19-20th century led to significant public health challenges and responses. Here, we discuss a comprehensive perspective on the history of the plague in Brazil, emphasising epidemiological trends, public health responses and scientific advances. Understanding the history of the plague in Brazil provides valuable insights into infectious disease control. The study highlights the importance of early detection, robust public health infrastructure, and ongoing research, emphasising the lasting influence of epidemic diseases on society.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240220"},"PeriodicalIF":2.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502302","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}
Maria Anice Mureb Sallum, Thiago Salomão de Azevedo, Jan Evelyn Conn, Ricardo Lourenço-de-Oliveira
{"title":"Distribution of Anophelinae (Diptera: Culicidae) and challenges for malaria elimination in Brazil.","authors":"Maria Anice Mureb Sallum, Thiago Salomão de Azevedo, Jan Evelyn Conn, Ricardo Lourenço-de-Oliveira","doi":"10.1590/0074-02760240247","DOIUrl":"10.1590/0074-02760240247","url":null,"abstract":"<p><p>In 1909, Arthur Neiva published an article titled \"Contribuição para os estudos dos dipteros. Observação sobre a biolojia e sistematica das anofelinas brasileiras e suas relações com o impaludismo\", highlighting the biology, ecology, and distribution of Anophelinae mosquitoes and the need for more taxonomic studies in Brazil. This came 11 years after Ronald Ross and Grassi demonstrated mosquito roles in transmitting Plasmodium to birds and humans. Despite considerable advances in the understanding of Anophelinae species, knowledge remains insufficient given the complexity of Brazil's ecosystems, the intensified anthropogenic environmental changes since the mid-20th century, and the persistent public health challenges posed by malaria. This perspective article presents the distribution of Plasmodium vectors and potential vector species in Brazil using climate variables and a maximum entropy model. Geographical distribution maps of Anophelinae species, including putative species, are provided. The article also discusses the current knowledge of vector species distribution in relation to Brazil's malaria elimination plan, along with the ecological and anthropogenic factors influencing vector distribution.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240247"},"PeriodicalIF":2.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502306","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}
{"title":"Free-living amoebae: a journey into historical aspects and to current discoveries.","authors":"Helena Lúcia Carneiro Santos","doi":"10.1590/0074-02760240246","DOIUrl":"10.1590/0074-02760240246","url":null,"abstract":"<p><p>Free-living amoebas (FLA) are ubiquitous protists found in the environment. They have shown exceptional resistance to environmental challenges and play significant roles in controlling microbial populations through their predatory behaviour and microbicidal activity in both soil and aquatic ecosystems environments. However, although rare, a limited group of FLA can cause serious infections in the central nervous system and other diseases, particularly in immunocompromised individuals with high mortality rates. They can also cause keratitis in otherwise healthy individuals. This review offers a comprehensive overview of freshwater naked amoebae but does not cover all aspects in detail. Its goal is to provide a historical context for our current understanding while addressing the most critical elements of FLA biology, their pathogenic potential, and their interactions with important human pathogens.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240246"},"PeriodicalIF":2.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502307","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}
Rahamah Sheu-Idrees, Gabriel Vitor de Lima Marques, Pedro Augusto Lemos Santana, Lucas Abreu Diniz, Daniela de Melo Resende, Saidi Odoma, Omodamiro Olorunshola, Rafaela Salgado Ferreira, Silvane Maria Fonseca Murta, Vinícius Gonçalves Maltarollo, Renata Barbosa de Oliveira
{"title":"Investigation of the activity of 4-aminoquinolines as cysteine protease inhibitors with application in the treatment of Chagas disease.","authors":"Rahamah Sheu-Idrees, Gabriel Vitor de Lima Marques, Pedro Augusto Lemos Santana, Lucas Abreu Diniz, Daniela de Melo Resende, Saidi Odoma, Omodamiro Olorunshola, Rafaela Salgado Ferreira, Silvane Maria Fonseca Murta, Vinícius Gonçalves Maltarollo, Renata Barbosa de Oliveira","doi":"10.1590/0074-02760240161","DOIUrl":"10.1590/0074-02760240161","url":null,"abstract":"<p><strong>Background: </strong>Chagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi. The current drugs used to treat these diseases have limited efficacy and produce severe side effects. 4-aminoquinoline derivatives were shown to be a promising class of inhibitors of cysteine proteases cruzain and TbrCATL.</p><p><strong>Objectives: </strong>To evaluate the trypanocidal activity of a new series of aminoquinolines as potential inhibitors of cruzain and TbrCATL.</p><p><strong>Methods: </strong>Three aminoquinolines were synthesised and their in vitro activity was evaluated against cruzain and TbrCATL as well as against amastigotes and trypomastigotes forms of T. cruzi. In silico studies were also carried out to try to understand the experimental results.</p><p><strong>Findings: </strong>Compound 5 showed promising activity against cruzain and TbrCATL, with better performance than E60, the reference drug. Compound 5 inhibited cruzain and TbrCATL at IC50 of 23 µM ±3 and 29 µM ±1, respectively, but this inhibition showed characteristics of promiscuous inhibition by colloidal aggregation. On the other hand, the compound 4 showed to be more promising activity against T. cruzi with IC50 2.57 µM ± 0.03 lower than the reference drug benznidazole 3.8 µM.</p><p><strong>Main conclusions: </strong>The results of this study can guide new drug development for the treatment of trypanosomiasis.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240161"},"PeriodicalIF":2.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399522","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}
Claudia Veira, Diego Benítez, Leticia Pérez-Díaz, Guzmán Álvarez, Hugo Cerecetto, Elena Aguilera
{"title":"Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours.","authors":"Claudia Veira, Diego Benítez, Leticia Pérez-Díaz, Guzmán Álvarez, Hugo Cerecetto, Elena Aguilera","doi":"10.1590/0074-02760240183","DOIUrl":"10.1590/0074-02760240183","url":null,"abstract":"<p><strong>Background: </strong>The neglected illness Chagas disease is treated with limited efficacy and adverse effects by old drugs. Due to the low interest of pharmaceutical industry in targeting economically depressed-patients, repurposing is a tool that should be applied because it can introduce new anti-Chagas entities into the clinic at reduced costs.</p><p><strong>Objectives: </strong>To investigate the repurposing/combination of medicines strategies as anti-Chagas treatment.</p><p><strong>Methods: </strong>Epimastigotes, trypomastigotes and amastigotes of Trypanosoma cruzi were in vitro exposed to 28 Uruguayan-approved medicines not previously tested, 28 FDA-approved medicines previously evaluated, and three reference agents. Parasite inhibition was assessed and for the best drugs, in pairs-isobolographic studies, looking for synergism/additivity/antagonism, were done. Macrophages were used to study selectivity. For some relevant agents, we analysed whether medicines mammals´ action mechanisms are operative in epimastigotes-T. cruzi.</p><p><strong>Findings: </strong>From the anti-epimastigotes monotherapy-screening, we found that 18% of them showed better/comparable activities than references. Additionally, for the binary-combinations 8% were additive, 4% were synergic and the rest showed antagonism. Favourably, in macrophages-cytotoxicity four of the binary-combinations were antagonists. Naftazone and pinaverium bromide, not previously tested against T. cruzi, maintained their activity against trypomastigotes and amastigotes. The identified action mechanisms open the door to new strategies designing anti-T. cruzi drugs.</p><p><strong>Main conclusions: </strong>Using approved-medicines is a good strategy for new anti-Chagas treatments.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240183"},"PeriodicalIF":2.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399524","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}