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Piecing together the puzzle: current knowledge and open questions about the Klebsiella pneumoniae type VI secretion system (T6SS). 拼凑拼图:关于肺炎克雷伯菌VI型分泌系统(T6SS)的现有知识和悬而未决的问题。
IF 1.9 4区 医学
Memorias do Instituto Oswaldo Cruz Pub Date : 2026-07-17 eCollection Date: 2026-01-01 DOI: 10.1590/0074-02760260010
Leticia Miranda Santos Lery, Paulo Ricardo Batista
{"title":"Piecing together the puzzle: current knowledge and open questions about the Klebsiella pneumoniae type VI secretion system (T6SS).","authors":"Leticia Miranda Santos Lery, Paulo Ricardo Batista","doi":"10.1590/0074-02760260010","DOIUrl":"10.1590/0074-02760260010","url":null,"abstract":"<p><p>Klebsiella pneumoniae (Kp) is currently a top priority for the development of alternative therapeutic strategies, according to the World Health Organisation, due to serious concerns regarding infections caused by multiple drug resistant (MDR) bacteria. The convergence of hypervirulence and MDR represents a major threat to public health worldwide. Kp displays an extensive genomic diversity, reflecting a variable repertoire of resistance and virulence factors. Despite this heterogeneity, the type VI secretion system (T6SS) is encoded in most Kp-genomes and plays important roles in competition and pathogenesis. The T6SS is a large macromolecular complex assembled in the cytoplasm that spans the inner and outer membranes. Upon activation, it undergoes conformational changes allowing the delivery of effectors into the extracellular milieu or target cells. Herein, we summarise the current knowledge on the Kp-T6SS, presenting a chronological overview of published studies, discussing the mechanisms, signals, and regulators involved in T6SS expression. Next, we detail both predicted and characterised effector proteins, including Tle1, Pld1 and VgrG4. Finally, we discuss the presence of Kp-T6SS in mobile genetic elements or in clinical samples, highlighting the importance of genomic vigilance and Kp-T6SS detection in high-risk cases. This review integrates available evidence, identifies knowledge gaps, and outlines future directions.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 ","pages":"e260010"},"PeriodicalIF":1.9,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13367176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549781","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}
引用次数: 0
Advances and challenges in the search for new treatments for Chagas disease. 寻找恰加斯病新疗法的进展和挑战。
IF 1.9 4区 医学
Memorias do Instituto Oswaldo Cruz Pub Date : 2026-07-10 eCollection Date: 2026-01-01 DOI: 10.1590/0074-02760250299
Ana Maria Murta Santi, Davi Alvarenga Lima, Silvane Maria Fonseca Murta
{"title":"Advances and challenges in the search for new treatments for Chagas disease.","authors":"Ana Maria Murta Santi, Davi Alvarenga Lima, Silvane Maria Fonseca Murta","doi":"10.1590/0074-02760250299","DOIUrl":"10.1590/0074-02760250299","url":null,"abstract":"<p><p>The treatment of Chagas disease (CD) has relied for more than five decades on two drugs, benznidazole (BZ) and nifurtimox (NTX), both with significant limitations and severe adverse effects. Their limited efficacy during the chronic phase underscores the urgent need for new chemotherapeutic strategies. The pursuit of new therapeutic agents for CD is focused on identifying molecular targets essential for Trypanosoma cruzi survival that are either absent or highly divergent in human, thereby enhancing selectivity and minimising off-target toxicity. These targets exploit the parasite's unique biology at multiple levels. Key metabolic vulnerabilities include: ergosterol biosynthesis, a sterol pathway distinct from human cholesterol metabolism; glycosomal metabolism, reflecting parasite´s unique compartmentalisation of glycolysis; and redox homeostasis, which depends on trypanothione rather than glutathione. Additional promising avenues involve the parasite's genetic and epigenetic regulation, mRNA processing and translational control. Furthermore, virulence-associated factors, and specific enzymes such as type I nitroreductase (NTR-1) can be exploited for selective prodrug activation. The complex genomic organisation and pronounced plasticity of T. cruzi complicate the identification of novel therapeutic targets. The abundance of proteins annotated as hypothetical or of unknown function further obscure critical metabolic pathways that could serve as druggable targets. In this context, the discovery of new drugs for CD strategically integrates phenotypic, target-based, and computational approaches, all of which require rigorous validation through preclinical in vitro and in vivo studies. Although modern approaches have yielded several promising lead compounds, successfully controlling CD will also depend on overcoming socioeconomic and access-related barriers to ensure that new therapies reach the populations most affected by this neglected tropical disease.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 suppl 2","pages":"e250299"},"PeriodicalIF":1.9,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448084","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}
引用次数: 0
Severity of COVID-19 in hospitalised children in Espírito Santo, Brazil: a comparative analysis of pre- and post-Omicron periods. 巴西圣托Espírito住院儿童中COVID-19的严重程度:欧米克隆前后的比较分析
IF 1.9 4区 医学
Memorias do Instituto Oswaldo Cruz Pub Date : 2026-07-10 eCollection Date: 2026-01-01 DOI: 10.1590/0074-02760250018
Brena Ramos Athaydes, Mariane Vedovatti Monfardini, Juliana Santa Ardisson, Gabriela Ferreira Nunes, Rafaela Altoé de Lima, Sabrina Cavalcanti de Barros Fonseca, Rodrigo Pimentel Schade, Teodiano Freire Bastos-Filho, Edson Delatorre, Liliana Cruz Spano, Sandra Ventorin von Zeidler
{"title":"Severity of COVID-19 in hospitalised children in Espírito Santo, Brazil: a comparative analysis of pre- and post-Omicron periods.","authors":"Brena Ramos Athaydes, Mariane Vedovatti Monfardini, Juliana Santa Ardisson, Gabriela Ferreira Nunes, Rafaela Altoé de Lima, Sabrina Cavalcanti de Barros Fonseca, Rodrigo Pimentel Schade, Teodiano Freire Bastos-Filho, Edson Delatorre, Liliana Cruz Spano, Sandra Ventorin von Zeidler","doi":"10.1590/0074-02760250018","DOIUrl":"10.1590/0074-02760250018","url":null,"abstract":"<p><strong>Background: </strong>Children experience Coronavirus disease 2019 (COVID-19) often with milder symptoms but severe outcomes.</p><p><strong>Objectives: </strong>To compare clinical, epidemiological and viral load profiles of hospitalised paediatric COVID-19 cases before and after the emergence of the Omicron variant in Espírito Santo, Brazil, and to explore factors associated with hospitalisation duration.</p><p><strong>Methods: </strong>This cross-sectional observational study included 54 hospitalised children with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, grouped according to epidemiological period: G1 (2020-2021) and G2 (2022). Viral load was quantified by reverse transcription real-time polymerase chain reaction (RT-qPCR), and whole-genome sequencing was performed using Nanopore technology. Group comparisons used chi-square/Fisher's exact tests and Mann-Whitney U tests. Cox regression was applied in an exploratory manner to identify factors associated with hospitalisation duration.</p><p><strong>Findings: </strong>The median age was 19.5 months and 68.5% were male. Comorbidities were present in 65% of the cohort, with no significant differences between groups. Children in G1 were more often hospitalised for respiratory syndromes, while G2 had a longer intensive care unit (ICU) stay. More than half of the patients required oxygen support, and those needing oxygen at admission were younger. Viral load was higher in G1 than in G2. In the multivariable Cox model, comorbidities [aHR = 0.47; 95% confidence interval (CI): 0.26-0.86] and male sex (aHR = 0.47; 95% CI: 0.25-0.89) were associated with prolonged hospitalisation. Sequencing identified five SARS-CoV-2 lineages (P.1., B.1.1., BA.1*, BQ.1.1, and BE.9), reflecting the transition from pre-Omicron to Omicron periods.</p><p><strong>Main conclusions: </strong>The pre-Omicron period was marked by higher viral loads and distinct clinical patterns compared with the Omicron period. Comorbidities and male sex were associated with prolonged hospitalisation. These findings should be interpreted as exploratory and hypothesis-generating given the limited cohort size.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 ","pages":"e250018"},"PeriodicalIF":1.9,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13363245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448000","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}
引用次数: 0
Comparative bioavailability of three benznidazole formulations in healthy individuals: a randomised study. 三种苯并硝唑制剂在健康个体中的比较生物利用度:一项随机研究。
IF 1.9 4区 医学
Memorias do Instituto Oswaldo Cruz Pub Date : 2026-07-10 eCollection Date: 2026-01-01 DOI: 10.1590/0074-02760250307
Gabriel Parreiras Estolano da Silveira, Laís Bastos da Fonseca, Rita Estrela, Douglas Pereira Pinto, João Fellipe Garcia Medeiros de Araújo, Luiz Villarinho Pereira Mendes, Eloan Pinheiro, Fernanda de Souza Nogueira Sardinha Mendes, Debbie Vermeij, Andréa Silvestre de Sousa
{"title":"Comparative bioavailability of three benznidazole formulations in healthy individuals: a randomised study.","authors":"Gabriel Parreiras Estolano da Silveira, Laís Bastos da Fonseca, Rita Estrela, Douglas Pereira Pinto, João Fellipe Garcia Medeiros de Araújo, Luiz Villarinho Pereira Mendes, Eloan Pinheiro, Fernanda de Souza Nogueira Sardinha Mendes, Debbie Vermeij, Andréa Silvestre de Sousa","doi":"10.1590/0074-02760250307","DOIUrl":"10.1590/0074-02760250307","url":null,"abstract":"<p><strong>Background: </strong>Benznidazole (BZN) has been used for more than fifty years in the treatment of Chagas disease (CD). It is produced by only three pharmaceutical companies worldwide: Lafepe (Brazil); Elea (Argentina) and Liconsa (Spain). The therapeutic interchangeability among these products has never been evaluated.</p><p><strong>Objectives: </strong>To assess bioequivalence between three 100 mg BZN formulations.</p><p><strong>Methods: </strong>Pharmaceutical equivalence, with dissolution testing, was assessed prior to the bioequivalence study. For bioequivalence, healthy adult participants received 100 mg of BZN formulations after meal, in a randomised clinical trial. Blood BZN concentrations were measured. Pharmacokinetic parameters were determined by non-compartmental analysis.</p><p><strong>Findings: </strong>The BZN Liconsa demonstrated faster in vitro dissolution. However, bioavailability was not different between formulations. The mean area under the curve (AUC)84h values were 49431.22 h*ng/mL (SD = 9938.53) to Lafepe, 48974.38 h*ng/mL (SD = 10304.67) to Elea and 48204.17 h*ng/mL (SD = 9342.18) to Liconsa. The mean Cmax values were 2339.23 ng/mL (SD = 445.53) for Lafepe, 2209.04 ng/mL (SD = 448.02) for Elea and 2303.90 ng/mL (SD = 431.41) for Liconsa. The mean tmax was not different between formulations. AUC were higher in women for Elea (20%) and Lafepe (27%). The adverse events did not differ between sexes.</p><p><strong>Main conclusions: </strong>The 100 mg BZN formulations demonstrated bioequivalence.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 suppl 2","pages":"e250307"},"PeriodicalIF":1.9,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448119","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}
引用次数: 0
Evidence of insecticide resistance in Aedes aegypti populations of Suriname: first report of malathion resistance and presence of the kdr mutations V410L, V1016I and F1534C. 苏里南埃及伊蚊种群杀虫剂抗性的证据:首次报告马拉硫磷抗性和kdr突变V410L、V1016I和F1534C的存在
IF 1.9 4区 医学
Memorias do Instituto Oswaldo Cruz Pub Date : 2026-07-10 eCollection Date: 2026-01-01 DOI: 10.1590/0074-02760250335
Kartika Doerdjan-Ramoutar, Jerry Toelsie, Amandine Guidez, Treyanti Soekhoe, Jean-Bernard Duchemin
{"title":"Evidence of insecticide resistance in Aedes aegypti populations of Suriname: first report of malathion resistance and presence of the kdr mutations V410L, V1016I and F1534C.","authors":"Kartika Doerdjan-Ramoutar, Jerry Toelsie, Amandine Guidez, Treyanti Soekhoe, Jean-Bernard Duchemin","doi":"10.1590/0074-02760250335","DOIUrl":"10.1590/0074-02760250335","url":null,"abstract":"<p><strong>Background: </strong>Dengue outbreaks pose a significant public health risk in Suriname, with challenges in mosquito surveillance and limited data on insecticide resistance hampering control efforts.</p><p><strong>Objectives: </strong>To investigate the resistance status and involved mechanisms of Aedes aegypti mosquitoes for malathion and λ-cyhalothrin insecticides.</p><p><strong>Methods: </strong>The Centres for Disease Control and Prevention (CDC) bottle bioassay was used to test the resistance phenotypic status of Ae. aegypti while the occurrence and frequency of knockdown resistance (kdr) mutations were accessed by TaqMan genotype assays for the sites 410L (Valine/Leucine), 1016I (Valine/Isoleucine), and 1534C (Phenylalanine/Cysteine).</p><p><strong>Findings: </strong>Results showed resistance to malathion in the Blauwgrond population, with other regions exhibiting reduced susceptibility based on mortality rates between 89% and 94%. Very low mortality rates indicate resistance to λ-cyhalothrin in all tested areas. Knockdown resistance (kdr) mutations were detected at high frequencies. The triple homozygous kdr genotype leucine/leucine, isoleucine/isoleucine, cysteine/cysteine (LL/II/CC) predominated (84.2%), while the wild-type genotype was found only in 1.8% of the samples.</p><p><strong>Main conclusion: </strong>This study reports the first detection of malathion resistance in Ae. aegypti from Suriname and confirms high levels of resistance to λ-cyhalothrin, possibly driven by kdr gene mutations. The results emphasise the importance of sustained surveillance and continued research on resistance mechanisms to guide effective and evidence-based vector control strategies.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 ","pages":"e250335"},"PeriodicalIF":1.9,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447948","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}
引用次数: 0
Determinants of HIV-1 virologic suppression in HIV-associated tuberculosis in Brazil. 巴西hiv相关结核中HIV-1病毒学抑制的决定因素
IF 1.9 4区 医学
Memorias do Instituto Oswaldo Cruz Pub Date : 2026-07-10 eCollection Date: 2026-01-01 DOI: 10.1590/0074-02760250090
Felipe Ridolfi, Gustavo Amorim, David W Haas, Maria Arriaga, Cody Staats, Marcelo Cordeiro-Santos, Afrânio L Kritski, Marina C Figueiredo, Bruno B Andrade, Timothy R Sterling, Valeria C Rolla, Aline Benjamin, Flavia M Sant'Anna, Jamile Garcia de Oliveira, João Marin, Adriana Rezende, Anna Cristina Carvalho, Michael Rocha, Betânia Nogueira, Alexandra Brito, Renata Spener, Megan Turner
{"title":"Determinants of HIV-1 virologic suppression in HIV-associated tuberculosis in Brazil.","authors":"Felipe Ridolfi, Gustavo Amorim, David W Haas, Maria Arriaga, Cody Staats, Marcelo Cordeiro-Santos, Afrânio L Kritski, Marina C Figueiredo, Bruno B Andrade, Timothy R Sterling, Valeria C Rolla, Aline Benjamin, Flavia M Sant'Anna, Jamile Garcia de Oliveira, João Marin, Adriana Rezende, Anna Cristina Carvalho, Michael Rocha, Betânia Nogueira, Alexandra Brito, Renata Spener, Megan Turner","doi":"10.1590/0074-02760250090","DOIUrl":"10.1590/0074-02760250090","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis/human immunodeficiency virus (TB/HIV) coinfection is associated with advanced HIV disease and variable responses to antiretroviral therapy (ART).</p><p><strong>Objectives: </strong>We examined whether baseline HIV severity markers, ART regimes, or human genetic variants influenced HIV-1 virologic suppression in HIV-associated TB.</p><p><strong>Methods: </strong>We included TB/HIV participants from Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil study, who received standard TB therapy and antiretroviral treatment. The primary endpoint was HIV-1 virologic suppression (≤ 1,000 copies/mL); Baseline characteristics, viral load (VL), CD4 cell count, timing of ART initiation, and ART regimens were included. We genotyped UGT1A1 (rs887829; integrase strand transfer inhibitor-related) and CYP2B6 [rs3745274, rs28399499, rs4803419; efavirenz (EFZ)-related]; all have defined normal, intermediate, and slow genotypes. Genotyping was performed by MassARRAY iPLEX Gold; Kaplan-Meier curves compared time-to-suppression with log-rank tests; Cox proportional hazards models estimated hazard ratios.</p><p><strong>Findings: </strong>Among 194 participants, 68% (n = 132) achieved virologic suppression (≤ 1,000 copies/mL). Median time-to-suppression: 84 days [95% confidence interval (CI): 42-125]. Participants with higher baseline viral load (BVL) (≥ 5 log10 copies/mL) had delayed suppression compared with those with lower VL (< 5 log10; log-rank χ² = 75.9; p < 0.001). Individuals with CD4 ≤ 200 cells/µL suppressed more slowly than those with CD4 > 200 cells/µL (log-rank χ² = 29.6; p < 0.001). Participants starting ART before TB treatment achieved suppression faster than ART-naïve individuals (32 vs. 147 days; log-rank χ² = 48.5; p < 0.001). Higher BVL was associated with reduced hazard of suppression [adjusted hazard ratio (aHR) = 0.67; 95% CI: 0.61-0.75], while higher baseline CD4 count increased the hazard of suppression (per 100 cells/µL: aHR = 1.11; 95% CI: 1.01-1.21). ART-naïve status was associated with lower hazard of suppression in univariate analysis (Hazard Ratio = 0.51; 95% CI: 0.36-0.72) but not after adjustment. ART regimen class and pharmacogenetic metabolizer profiles were not significantly associated with virologic suppression.</p><p><strong>Main conclusions: </strong>BVL and CD4 count were the strongest determinants of virologic suppression in TB/HIV patients. Suppression rates were low, and neither ART regimen nor pharmacogenetic profiles significantly influenced the likelihood of suppression.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 ","pages":"e250090"},"PeriodicalIF":1.9,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447978","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}
引用次数: 0
Dengue virus serotype 4 infection in human fatal cases: histopathological investigationFIRST REVIEW ROUND - REVIEWERS COMMENTSREVIEWERS COMMENTS. 人死亡病例中登革热病毒血清4型感染:组织病理学调查第一轮综述-评论者评论评论者评论
IF 1.9 4区 医学
Memorias do Instituto Oswaldo Cruz Pub Date : 2026-06-22 eCollection Date: 2026-01-01 DOI: 10.1590/0074-02760250248
Arthur da Costa Rasinhas, Gabriela Cardoso Caldas, Ana Luisa Teixeira de Almeida, Fernanda Cunha Jácome, Marcos Alexandre Nunes da Silva, Milla Bezerra Paiva, Kíssila Rabelo, Jorge José de Carvalho, Felipe de Andrade Vieira Alves, Emília Tomé de Sousa, Ortrud Monika Barth, Flavia Barreto Dos Santos
{"title":"Dengue virus serotype 4 infection in human fatal cases: histopathological investigationFIRST REVIEW ROUND - REVIEWERS COMMENTSREVIEWERS COMMENTS.","authors":"Arthur da Costa Rasinhas, Gabriela Cardoso Caldas, Ana Luisa Teixeira de Almeida, Fernanda Cunha Jácome, Marcos Alexandre Nunes da Silva, Milla Bezerra Paiva, Kíssila Rabelo, Jorge José de Carvalho, Felipe de Andrade Vieira Alves, Emília Tomé de Sousa, Ortrud Monika Barth, Flavia Barreto Dos Santos","doi":"10.1590/0074-02760250248","DOIUrl":"10.1590/0074-02760250248","url":null,"abstract":"<p><strong>Background: </strong>Dengue, the disease caused by dengue virus (DENV), is responsible for over 300 million cases worldwide. Although DENV-4 usually presents with milder symptoms, some cases can result in death.</p><p><strong>Objectives: </strong>The present study aims to characterise the immunohistopathological profile of hepatic, pulmonary, cardiac and renal involvement in fatal cases of DENV-4 that occurred between 2011 and 2013 in Brazil.</p><p><strong>Methods: </strong>To this end, tissue samples from the patients were subjected to histopathological analysis using bright-field microscopy and cytokine detection by immunohistochemistry.</p><p><strong>Findings: </strong>Cells stained for tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were observed in the liver, lungs and kidneys. In the liver, the most common finding was periportal necrosis, along with steatosis and mononuclear cell infiltration. In the lungs, pneumocyte necrosis was only observed in areas of alveolar oedema. Septal and alveolar haemorrhage were present, along with thickening of the alveolar walls. In the kidneys, glomerular capillary congestion was observed in most of the analysed cases. Inflammatory cell infiltration was observed in the cortical region, along with proximal and distal tubule necrosis. Finally, in the heart, despite limited local cytokine expression, the cardiac tissue remained morphologically preserved.</p><p><strong>Main conclusions: </strong>Although the findings reported in this study are consistent with those described in fatal dengue cases, the absence of cardiac alterations indicates that DENV-4 may cause a milder infection in this organ.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 ","pages":"e250248"},"PeriodicalIF":1.9,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308739","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}
引用次数: 0
Chromosome level genome assembly of the World Health standards Leishmania (Viannia) guyanensis M4147 and L. (V.) shawi M8408 using a hybrid sequencing approachFIRST REVIEW ROUND - REVIEWERS' COMMENTSREVIEWERS' COMMENTS. 采用杂交测序方法对世界卫生标准利什曼原虫(Viannia) guyanensis M4147和L. (V.) shawi M8408染色体水平基因组进行组装
IF 1.9 4区 医学
Memorias do Instituto Oswaldo Cruz Pub Date : 2026-06-19 eCollection Date: 2026-01-01 DOI: 10.1590/0074-02760250270
Percy Omar Túllume-Vergara, Ana Carolina Stocco de Lima, Claudia Maria de Castro Gomes, Bruna Santos Lima, Sinval Pinto Brandão-Filho, Fernando Tobias Silveira, Jeffrey J Shaw, João Marcelo Pereira Alves
{"title":"Chromosome level genome assembly of the World Health standards Leishmania (Viannia) guyanensis M4147 and L. (V.) shawi M8408 using a hybrid sequencing approachFIRST REVIEW ROUND - REVIEWERS' COMMENTSREVIEWERS' COMMENTS.","authors":"Percy Omar Túllume-Vergara, Ana Carolina Stocco de Lima, Claudia Maria de Castro Gomes, Bruna Santos Lima, Sinval Pinto Brandão-Filho, Fernando Tobias Silveira, Jeffrey J Shaw, João Marcelo Pereira Alves","doi":"10.1590/0074-02760250270","DOIUrl":"10.1590/0074-02760250270","url":null,"abstract":"<p><strong>Background: </strong>The Leishmania (Viannia) subgenus contains important pathogens that cause a variety of different clinical forms of cutaneous leishmaniasis in the Americas. Their response to antimonial chemotherapy differs according to species. Having high-quality genomic resources of these species is a significant step towards investigating and understanding these factors.</p><p><strong>Objectives: </strong>This study aims to characterise the main genomic features of L. (V.) guyanensis strain MHOM/BR/75/M4147 and L. (V.) shawi strain MCEB/BR/84/M8408.</p><p><strong>Methods: </strong>Genomes were sequenced combining short- and long-read sequencing platforms and assembled, scaffolded, and polished using Flye2, Ragtag, and Pilon, respectively. Annotations were performed using mainly similarity and profile search methods, and phylogenetic analyses were performed using the maximum likelihood (ML) and Bayesian inference approaches, using IQ-TREE and MrBayes, respectively.</p><p><strong>Findings: </strong>De novo assembly produced genome sizes of 32.27 Mb for L. guyanensis and 32.41 Mb for L. shawi, and predicted 8,505 and 8,592 protein-coding genes, respectively. Phylogenetic analysis based on these assemblies confidently places L. guyanensis and L. shawi as the closest known relatives to L. panamensis within the Viannia clade.</p><p><strong>Main conclusions: </strong>These genomes will increase the knowledge about the subgenus L. (Viannia) in the Americas and also represent valuable information for future comparative studies with other human pathogenic Leishmania spp.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 ","pages":"e250270"},"PeriodicalIF":1.9,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308820","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}
引用次数: 0
Uptake and survival of Leishmania amazonensis in Acanthamoeba: an adequate model organism?FIRST REVIEW ROUND - REVIEWERS' COMMENTSREVIEWERS' COMMENTSREVIEWERS' COMMENTS. 棘阿米巴原虫对亚马逊利什曼原虫的吸收和存活:一个合适的模式生物?第一轮审查——审稿人的评论——审稿人的评论——审稿人的评论。
IF 1.9 4区 医学
Memorias do Instituto Oswaldo Cruz Pub Date : 2026-06-19 eCollection Date: 2026-01-01 DOI: 10.1590/0074-02760250253
Leonardo Fernandes Geres, Pedro Henrique Gallo Francisco, Diullia de Andrade Machado, Francisco Breno Silva Teófilo, Marcelo Brocchi, Selma Giorgio
{"title":"Uptake and survival of Leishmania amazonensis in Acanthamoeba: an adequate model organism?FIRST REVIEW ROUND - REVIEWERS' COMMENTSREVIEWERS' COMMENTSREVIEWERS' COMMENTS.","authors":"Leonardo Fernandes Geres, Pedro Henrique Gallo Francisco, Diullia de Andrade Machado, Francisco Breno Silva Teófilo, Marcelo Brocchi, Selma Giorgio","doi":"10.1590/0074-02760250253","DOIUrl":"10.1590/0074-02760250253","url":null,"abstract":"<p><strong>Background: </strong>Research on Leishmania pathogenesis, as well as drug and vaccine discovery, primarily relies on complex mammalian models that raise ethical concerns. To overcome these limitations, we tested a simpler and more accessible experimental system. In this study, we examined the interaction between Leishmania amazonensis and Acanthamoeba, a widespread free-living protozoan that interacts with various microorganisms.</p><p><strong>Objectives: </strong>To provide a deeper morphological and kinetic characterisation of the interaction between L. amazonensis and Acanthamoeba.</p><p><strong>Methods: </strong>The parasite interaction was characterised using light microscopy, fluorescence microscopy, scanning electron microscopy (SEM), confocal microscopy, and live-cell imaging.</p><p><strong>Findings: </strong>Co-culture was most optimal in RPMI medium at 26ºC. L. amazonensis promastigotes invaded Acanthamoeba trophozoites via their flagellum; trophozoites phagocytosed parasites through acanthopodia. Inside the amoeba, L. amazonensis became rounded and shortened, with no visible flagellum. These forms, isolated after 3 h of co-culture, differentiated back into promastigotes and were viable. The percentage of amoebas with L. amazonensis decreased over time.</p><p><strong>Main conclusions: </strong>Acanthamoeba trophozoites can interact and clear out L. amazonensis. This model is unsuited for sustained infection studies necessary for drug screening. However, it could be an effective model for exploring cellular leishmanicidal mechanisms.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 ","pages":"e250253"},"PeriodicalIF":1.9,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308817","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}
引用次数: 0
Coexistence of monogamy and polygyny in Triatoma infestans: fine-scale genealogical structure reveals complex social structures within domestic colonies in the Bolivian Chaco 寄生三角瘤中一夫一妻制和一夫多妻制的共存:玻利维亚查科的精细谱系结构揭示了国内殖民地内复杂的社会结构。
IF 1.9 4区 医学
Memorias do Instituto Oswaldo Cruz Pub Date : 2026-06-15 eCollection Date: 2026-01-01 DOI: 10.1590/0074-02760250355
Alex Juan Cornejo Pinto, Rolando Sánchez, Frédéric Lardeux
{"title":"Coexistence of monogamy and polygyny in Triatoma infestans: fine-scale genealogical structure reveals complex social structures within domestic colonies in the Bolivian Chaco","authors":"Alex Juan Cornejo Pinto, Rolando Sánchez, Frédéric Lardeux","doi":"10.1590/0074-02760250355","DOIUrl":"10.1590/0074-02760250355","url":null,"abstract":"<p><strong>Background: </strong>Persistent reinfestation of Triatoma infestans in the Gran Chaco undermines Chagas disease (CD) control. While insecticide resistance is a known factor, the fine-scale social and demographic structure of vector colonies remains poorly understood.</p><p><strong>Objectives: </strong>To analyse the micro-geographic genetic structure, mating systems, and demographic history of T. infestans in a rural community in the Bolivian Chaco.</p><p><strong>Methods: </strong>We genotyped 381 individuals from three neighbouring structures (domiciliary and peridomestic) using eight highly polymorphic microsatellite loci (expected heterozygosity, HE = 0.675). Genealogical relationships were reconstructed using maximum likelihood (ML) analysis (COLONY), and demographic history was inferred through heterozygosity tests.</p><p><strong>Findings: </strong>The infestation comprised 42 distinct full-sibling families nested within a single colony. We observed a stark dichotomy: two dominant families (> 80 individuals) exhibited monogamy and signs of distinct demographic histories (one in expansion, one recovering from a bottleneck), while 40 minor families showed high promiscuity (polygyny/polyandry). Finite growth rates varied significantly (λ = 1.03 vs 1.22), evidencing active intra-colonial competition.</p><p><strong>Main conclusions: </strong>Domestic populations are not random aggregates, but complex mosaics of coexisting lineages with different adaptive strategies. The dominance of monogamous families suggests a priority effect advantage, while the \"tail\" of promiscuous minor families represents a cryptic reservoir. Effective control must account for this structural resilience, as surviving minor lineages could rapidly recolonise the niche.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 ","pages":"e250355"},"PeriodicalIF":1.9,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13268354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265226","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}
引用次数: 0
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