Instituto Adolfo Lutz

In individuals with prior dengue virus (DENV) exposure, subsequent heterotypic infection can increase the risk of severe disease. A single-dose dengue vaccine that protects against the four DENV serotypes across a wide age range and regardless of DENV serostatus is needed. Here we report the long-term safety and efficacy of Butantan dengue vaccine (Butantan-DV), a live, attenuated, tetravalent dengue vaccine, among participants ages 2-59 who were randomized 2:1 in a double-blind, placebo-controlled, phase 3 trial in Brazil. A primary objective was to evaluate vaccine efficacy (VE) against reverse transcription-PCR-positive symptomatic dengue 28 days after vaccination because of any DENV serotype, regardless of serostatus. Prespecified secondary endpoints included VE by serotype, by serostatus and against severe dengue or dengue with warning signs (combined). The primary and secondary objectives were met if the lower bound of the two-sided 95% confidence interval (CI) for VE was above 25%. Between 2016 and 2019, 16,235 participants received Butantan-DV (n = 10,259) or placebo (n = 5,976). The trial met the primary and secondary objectives. During the 5 years of follow-up, between 2016 and 2024, overall VE (95% CI) was 65.0% (57.8-71.0%). Secondary VE endpoints (95% CI) were 77.1% (67.6-83.9%) in dengue-experienced participants, 58.9% (48.0-67.6%) in dengue-naive participants, 73.0% (64.3-79.7%) against DENV-1 and 55.7% (42.3-66.1%) against DENV-2. Cases of DENV-3 or DENV-4 were not observed. VE (95% CI) against dengue with warning signs or severe dengue (secondary endpoint) was 80.5% (50.8-92.4%). The most commonly reported solicited systemic adverse event (AE) was headache (36.7% of vaccine recipients and 31.1% of placebo recipients), most of which were grade 1. The proportions of participants with unsolicited vaccine-related AEs (including serious AEs) were comparable between intervention groups. A single dose of Butantan-DV was efficacious against symptomatic virologically confirmed dengue because of DENV-1 or DENV-2, regardless of dengue serostatus at baseline, with no safety concerns observed during the 5-year follow-up (ClinicalTrials.gov: NCT02406729 ).

Transfusion-transmitted dengue remains a relevant risk during outbreaks. We report a transfusion-transmitted severe dengue case in a stem cell transplant recipient during the 2024 epidemic in Brazil, supported by phylogenetic linkage, evolving to a fatal outcome. This sentinel case highlights the potential severity of transfusion-transmitted dengue, particularly in immunocompromised hosts.

This narrative review highlights recent advances in the understanding of enterovirus infections and the main enterovirus types associated with clinical syndromes, synthesizing current knowledge of type-specific manifestations. We searched PubMed®, Scientific Electronic Library Online (SciELO), and Virtual Health Library (VHL) for articles published between 2010 and 2025. The search used descriptors and/or keywords in Portuguese and English: “enterovirus infection disease”, “enterovirus infection genotypes”, “enterovirus infection pathogenic”, and “enterovirus clinical syndromes”, focusing on recent studies addressing enterovirus infections and the types most commonly associated with clinical syndromes. A total of 78 articles were selected for analysis. The review examined the distribution of enteroviruses by species, recommended clinical specimen types for diagnosis according to clinical presentation, and the major enterovirus types and their associated clinical syndromes. Numerous studies have demonstrated the epidemic potential and genetic diversity of enteroviruses, revealing patterns of endemic circulation. However, the mechanisms underlying the ability of a wide variety of enterovirus types to infect the same tissue remain poorly understood.

We report the detection of yellow fever virus in Campinas and Ribeirao Preto city areas (two geographic areas within Sao Paulo State, Brazil) from September 2024 to February 2025. Phylogenetic analysis of six new genomes showed a re-introduction in 2022 from Midwest Brazil followed by persistence in Sao Paulo State. Continued surveillance in neotropical primates is required to prevent cases in humans.

Between December 2019 and January 2020, two patients suspected of having severe yellow fever were admitted to a tertiary healthcare facility in São Paulo, Brazil, presenting with acute hemorrhagic syndrome and neurological alterations; both cases had fatal outcomes. Upon admission, both tested negative for yellow fever viral RNA, and Sabiá virus (SABV), a New World arenavirus, was identified as the causative pathogen. To date, only four humans naturally acquired SABV infections have been confirmed, all fatal and linked to rural settings. We applied next-generation sequencing to generate complete and near-complete genomes from two patients (SP17 and SP19). Existing molecular diagnostics failed to detect SABV; therefore, new molecular tests were developed. Genetic analyses of SP17 and SP19 genomes along with other arenaviruses, revealed that the new cases were genetically diverse, showing 93-98.2% amino acid identity at the NP level among SP17, SP19, and the 1990 reference strain (SPH114202). Time-scaled phylogenetic analyses confirmed that SP17 and SP19 were not epidemiologically linked and suggested that SABV has been circulating undetected in Brazil for over a century. Additionally, homology modeling and structure-based mapping provided insights into SABV receptor-binding sequence conservation, suggesting that SABV shares similar receptor binding structure to other clade B arenaviruses, despite some amino acid variation around receptor binding site. Our findings underscore the need for retrospective and prospective surveillance of undiagnosed hemorrhagic fever cases to assess the public health impact of SABV in Brazil.