Memorias do Instituto Oswaldo Cruz最新文献

{"title":"Chikungunya vaccine approval in Brazil: navigating through epidemiological challenges and immunisation strategies.","authors":"Claudia Renata Dos Santos Barros, Sandra Coccuzzo Sampaio, Maria Carolina Elias, Svetoslav Nanev Slavov","doi":"10.1590/0074-02760260088","DOIUrl":"10.1590/0074-02760260088","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) can cause acute arboviral illness, usually accompanied by severe polyarthralgia. In 2025, live-attenuated CHIKV vaccine Ixchiq® (Valneva, Saint-Herblain, France) was authorised for use in Brazil, where CHIKV often co-circulates with other arboviruses. A central public health question emerges: how should this vaccine be optimally deployed in a country characterised by hyperendemic transmission, frequent underdiagnosis, and marked regional disparities? We conducted an epidemiological analysis using notified CHIKV cases from the Notifiable Diseases Information System (SINAN) and socioeconomic indicators from the Brazilian Human Development Atlas. This framework enabled the identification of municipal clusters with shared epidemiological and socioeconomic profiles, allowing exploration of the relationship between disease notification rate and social health determinants. Our results showed that CHIKV transmission exhibited a cyclic pattern with geographic expansion toward the Southeast/South - Brazil's most densely populated regions characterised by low population immunity. Cluster analyses showed that the greatest disease burden is concentrated in socioeconomically disadvantaged municipalities, particularly in the Northeast, where healthcare disparities may further impact diagnostic capacity. Based on the obtained results, we believe in a hybrid immunisation strategy starting from high-incidence municipalities in the northeast and reaching major urban centres in the southeast in order to prevent larger outbreaks. Implementation must account also for current vaccine contraindications in high-risk groups and be guided by real-time epidemiological and entomological surveillance.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 ","pages":"e260088"},"PeriodicalIF":1.9,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684956","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":"Evaluation of the in vitro activity of synthetic derivatives of N-cyclohexyl-3-(3-methylphenyl)-1,2,4-oxadiazole-5-amine on the strain y of Trypanosoma cruzi and an in vivo toxicity study.","authors":"Yasmim Mendes Rocha, Lyanna Rodrigues Ribeiro, Gabriel Acácio de Moura, Marlos de Medeiros Chaves, João Pedro Viana Rodrigues, Emanuel Paula Magalhães, Sara Ingrid Caetano Gomes Barbosa, Lucas Soares Frota, Selene Maia de Morais, Wildson Max Barbosa da Silva, Valentina Nascimento E Melo de Oliveira, Ronaldo Nascimento de Oliveira, Alice Maria Costa Martins, Roberto Nicolete","doi":"10.1590/0074-02760250289","DOIUrl":"10.1590/0074-02760250289","url":null,"abstract":"<p><strong>Background: </strong>Chagas disease (CD) is caused by Trypanosoma cruzi. Treatment is based on benznidazole (Bz), although it has significant limitations, such as low efficacy in the chronic phase. Therefore, the search for new therapies with greater selectivity and antiparasitic activity is necessary. In this context, 1,2,4-oxadiazole stands out for its biological properties, including antiparasitic activities.</p><p><strong>Objective: </strong>To evaluate the in vitro activity of N-cyclohexyl 3-(3-methylphenyl)-1,2,4-oxadiazol-5-amine derivatives against the Y strain of T. cruzi and an in vivo toxicity study.</p><p><strong>Methods: </strong>Cytotoxicity was evaluated in LLC-MK2 cells by the MTT assay, while the antiparasitic effect on the three T. cruzi life forms was determined by counting. Flow cytometry analyses were then conducted to investigate possible death pathway mechanisms and antioxidant and antiacetylcholinesterase activities. Scanning electron microscopy (SEM) was also performed to observe morphological changes caused by the compounds. Finally, in vivo acute toxicity tests were performed on ZebraFish embryos.</p><p><strong>Results: </strong>The results presented show distinct cellular toxicity profiles in LLC-MK2 cells, in addition to demonstrating antiparasitic activity at different concentrations. In amastigotes, cytotoxic effects were stimulated. The molecules also induced an increase in reactive oxygen species and membrane damage, in addition to loss of integrity and morphological changes. The antioxidant activity revealed a high capacity for scavenging free radicals, suggesting an alteration of the redox balance of the parasite, in addition to showing inhibition of acetylcholinesterase, an important enzyme present in the formation of parasites, which choline is a constituent. In the ZebraFish model, molecule 2a showed dose-dependent embryonic toxicity, with an LC50 of 14-15 µM.</p><p><strong>Main conclusions: </strong>The calculated conclusions appear to indicate an antiparasitic effect associated with cell death mechanisms. However, further studies are needed to reduce toxicity in the animal model and increase delivery to the site of action.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 suppl 2","pages":"e250289"},"PeriodicalIF":1.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549242","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":"Association of p-glycoprotein and bile salt export pump gene polymorphisms with advanced liver disease in hepatitis C virus infected patients.","authors":"Letícia Bomfim Campos, Nathália Alves Araújo de Almeida, Marcia Maria Amendola Pires, Carlos Eduardo Brandão-Mello, Livia Melo Villar, José Júnior França de Barros, Vanessa Salete de Paula","doi":"10.1590/0074-02760250173","DOIUrl":"10.1590/0074-02760250173","url":null,"abstract":"<p><strong>Background: </strong>Single-nucleotide polymorphisms (SNPs) can influence the hepatitis C virus (HCV) infection and progression. ABCB1-gene SNPs - c.1236C>T, c.2677G>T and c.3435C>T - are associated with drug efficacy, hepatotoxicity, and liver injury. ABCB11 c.1331T>C is associated with cholestasis and altered bilirubin levels, potentially worsening liver disease.</p><p><strong>Objective: </strong>To investigate the impact of ABCB1 and ABCB11 SNPs on disease progression in chronic HCV patients.</p><p><strong>Methods: </strong>A total of 232 HCV patients unresponsive to conventional therapy were analysed. Serum samples were genotyped by quantitative polymerase chain reaction (qPCR), and the genotype and allele-based analysis was performed using RStudio.</p><p><strong>Findings: </strong>Cirrhosis was present in 59.1% of patients, along with diabetes (28.4%) and hepatic steatosis (46.1%). The most frequent ABCB1 variant allele was c.3435C>T (36.8%), followed by c.1236C>T (30.8%) and c.2677G>T (26.7%). The ABCB11 c.1331CC genotype was observed in 31.3% of the cohort. Genotypes 1236TT and 2677TT and their alleles were associated with lower total cholesterol. 2677TT genotype and 2677T allele were associated with lower high-density lipoprotein. Patients with 1331CC genotype had higher aspartate aminotransferase levels, and the 1331CC genotype was a risk factor for cirrhosis. A fully variant combined allele (1236T and 2677T and 3435T and 1331C) was associated with higher alpha-fetoprotein and lower cholesterol.</p><p><strong>Main conclusions: </strong>ABCB1 and ABCB11 SNPs are associated with worse clinical outcomes in HCV, underscoring their relevance in disease monitoring.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121 ","pages":"e250173"},"PeriodicalIF":1.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549692","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":"Cladistics of South American Triatoma (Hemiptera: Reduviidae): a morphological overview of T. infestans complex.","authors":"João Paulo Sales Oliveira-Correia, Hélcio Reinaldo Gil-Santana, Cleber Galvão","doi":"10.1590/0074-02760250293","DOIUrl":"10.1590/0074-02760250293","url":null,"abstract":"<p><strong>Background: </strong>Triatoma infestans complex comprises 39 species of South American triatomines, organised into different subcomplexes. These species act as vectors of the protozoan Trypanosoma cruzi, the etiological agent of Chagas disease. However, the evolutionary relationships among the subcomplexes remain unresolved.</p><p><strong>Objectives: </strong>In this study, we present the most comprehensive morphological cladistic analysis of these species to date.</p><p><strong>Methods: </strong>Phylogenetic relationships were examined in a new analysis based on morphological data. We analysed a data matrix comprising 48 terminal taxa and 72 morphological characters, coded under implicit parsimony weights, with a range of concavities (k1-80).</p><p><strong>Findings: </strong>Our results indicate that the T. infestans and Triatoma rubrovaria subcomplexes constitute monophyletic groups, while Triatoma brasiliensis, Triatoma matogrossensis and Triatoma sordida subcomplexes are merophyletic. We also confirm that Triatoma maculata does not belong to the homonymous subcomplex.</p><p><strong>Main conclusions: </strong>The study presents the first cladistic analysis and provides a solid foundation for understanding phylogenetic relationships within of the T. infestans complex.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"121Suppl. 1 Suppl. 1","pages":"e250293"},"PeriodicalIF":1.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549245","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":"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}

{"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}

{"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}

{"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}

{"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}

{"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}