Preliminary findings from the Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE I) Study: a Randomized Controlled Trial.

Background: Studies have reported that repeated annual vaccination may influence the effectiveness of the influenza vaccination in the current season. The mechanisms underlying these differences are unclear but might include "focusing" of the adaptive immune response to older strains. Methods: We established a 5-year randomized placebo-controlled trial of repeated influenza vaccination (Flublok, Sanofi Pasteur) in adults 18-45 years of age. Participants were randomized equally between five groups, with planned annual receipt of vaccination (V) or saline placebo (P) as follows: P-P-P-P-V, P-P-P-V-V, P-P-V-V-V, P-V-V-V-V, or V-V-V-V-V. Serum samples were collected each year just before vaccination and after 30 and 182 days. A subset of sera were tested by hemagglutination inhibition assays, focus reduction neutralization tests and enzyme-linked immunosorbent assays against vaccine strains. Results: From 23 October 2020 through 11 March 2021 we enrolled and randomized 447 adults. We selected sera from 95 participants at five timepoints from the first two study years for testing. Among vaccinated individuals, antibody titers increased between days 0 and 30 against each of the vaccine strains, with substantial increases for first-time vaccinees and smaller increases for repeat vaccinees, who had higher pre-vaccination titers in year 2. There were statistically significant reductions in the proportion of participants achieving a four-fold greater rise in antibody titer for the repeat vaccinees for A(H1N1), B/Victoria and B/Yamagata, but not for influenza A(H3N2). There were no statistically significant differences between groups in geometric mean titers at day 30 or the proportions of participants with antibody titers ≥40 at day 30 for any of the vaccine strains. Conclusions: In the first two years, repeat vaccinees and first-time vaccinees had similar post-vaccination geometric mean titers to all four vaccine strains, indicative of similar levels of clinical protection. The vaccine strains of A(H1N1) and A(H3N2) were updated in year 2, providing an opportunity to explore antigenic distances between those strains in humans in subsequent years.

Extending the computational and experimental analysis of lipase active site selectivity.

Molecular docking is an important computational analysis widely used to predict the interaction of enzymes with several starting materials for developing new valuable products from several starting materials, including oils and fats. In the present study, molecular docking was used as an efficient in silico screening tool to select biocatalysts with the highest catalytic performance in butyl esters production in a solvent-free system, an eco-friendly approach, via direct esterification of free fatty acids from Licuri oil with butanol. For such purpose, three commercial lipase preparations were used to perform molecular docking studies such as Burkholderia cepacia (BCL), Porcine pancreatic (PPL), and Candida rugosa (CRL). Concurrently, the results obtained in BCL and CRL are the most efficient in the esterification process due to their higher preference for catalyzing the esterification of lauric acid, the main fatty acid found in the licuri oil composition. Meanwhile, PPL was the least efficient because it preferentially interacts with minor fatty acids. Molecular docking with the experimental results indicated the better performance in the synthesis of esters was BCL. In conclusion, experimental results analysis shows higher enzymatic productivity in esterification reactions of 1294.83 µmol/h.mg, while the CRL and PPL demonstrated the lowest performance (189.87 µmol / h.mg and 23.96 µmol / h.mg, respectively). Thus, molecular docking and experimental results indicate that BCL is a more efficient lipase to produce fatty acids and esters from licuri oil with a high content of lauric acid. In addition, this study also demonstrates the application of molecular docking as an important tool for lipase screening to achieve more sustainable production of butyl esters with a view synthesis of biolubricants.

Association of Meal Timing with Sleep Quality and Anxiety According to Chronotype: A Study of University Students.

There are several determinants of mental health symptoms, ranging from individual characteristics to social factors. Consistent with patterns in the general population, students with evening characteristics tend to exhibit more anxiety symptoms and poorer sleep quality compared to morning students. Meal timing also appears to affect sleep and may be associated with mental health symptoms. In this context, the aim of the present study was to investigate the association of the timing of the main and last meals of the day with sleep quality and anxiety levels, according to the chronotype of university students. This study was conducted in colleges in São Paulo, Brazil, and involved application of a questionnaire to 162 university students. The questionnaire collected sociodemographic information meal and study times, and included scales assessing eveningness and morningness, sleep quality, and anxiety. Students demonstrating a phase delay in both chronotype and dinner timing exhibited higher levels of anxiety compared to morning-type students. Although no associations were observed between meal timing and sleep quality, sleeping later was associated with poorer sleep quality. The study suggests that evening students and those who eat late at night are more prone to presenting mental health symptoms. More studies are needed to further investigate this association.

C1q enables influenza hemagglutinin stem binding antibodies to block viral attachment and broadens the antibody escape repertoire.

Antigenic drift, the gradual accumulation of amino acid substitutions in the influenza virus hemagglutinin (HA) receptor protein, enables viral immune evasion. Antibodies (Abs) specific for the drift-resistant HA stem region are a promising universal influenza vaccine target. Although anti-stem Abs are not believed to block viral attachment, here we show that complement component 1q (C1q), a 460-kilodalton protein with six Ab Fc-binding domains, confers attachment inhibition to anti-stem Abs and enhances their fusion and neuraminidase inhibition. As a result, virus neutralization activity in vitro is boosted up to 30-fold, and in vivo protection from influenza PR8 infection in mice is enhanced. These effects reflect increased steric hindrance and not increased Ab avidity. C1q greatly expands the anti-stem Ab viral escape repertoire to include residues throughout the HA, some of which cause antigenic alterations in the globular region or modulate HA receptor avidity. We also show that C1q enhances the neutralization activity of non-receptor binding domain anti-SARS-CoV-2 spike Abs, an effect dependent on spike density on the virion surface. These findings demonstrate that C1q can greatly expand Ab function and thereby contribute to viral evolution and immune escape.

Paradoxical imbalance between activated lymphocyte protein synthesis capacity and rapid division rate.

Rapid lymphocyte cell division places enormous demands on the protein synthesis machinery. Flow cytometric measurement of puromycylated ribosome-associated nascent chains after treating cells or mice with translation initiation inhibitors reveals that ribosomes in resting lymphocytes in vitro and in vivo elongate at typical rates for mammalian cells. Intriguingly, elongation rates can be increased up to 30% by activation in vivo or fever temperature in vitro. Resting and activated lymphocytes possess abundant monosome populations, most of which actively translate in vivo, while in vitro, nearly all can be stalled prior to activation. Quantitating lymphocyte protein mass and ribosome count reveals a paradoxically high ratio of cellular protein to ribosomes insufficient to support their rapid in vivo division, suggesting that the activated lymphocyte proteome in vivo may be generated in an unusual manner. Our findings demonstrate the importance of a global understanding of protein synthesis in lymphocytes and other rapidly dividing immune cells.

Experimental and Computational Analysis of Synthesis Conditions of Hybrid Nanoflowers for Lipase Immobilization.

This work presents a framework for evaluating hybrid nanoflowers using Burkholderia cepacia lipase. It was expanded on previous findings by testing lipase hybrid nanoflowers (hNF-lipase) formation over a wide range of pH values (5-9) and buffer concentrations (10-100 mM). The free enzyme activity was compared with that of hNF-lipase. The analysis, performed by molecular docking, described the effect of lipase interaction with copper ions. The morphological characterization of hNF-lipase was performed using scanning electron microscopy. Fourier Transform Infrared Spectroscopy performed the physical-chemical characterization. The results show that all hNF-lipase activity presented values higher than that of the free enzyme. Activity is higher at pH 7.4 and has the highest buffer concentration of 100 mM. Molecular docking analysis has been used to understand the effect of enzyme protonation on hNF-lipase formation and identify the main the main binding sites of the enzyme with copper ions. The hNF-lipase nanostructures show the shape of flowers in their micrographs from pH 6 to 8. The spectra of the nanoflowers present peaks typical of the amide regions I and II, current in lipase, and areas with P-O vibrations, confirming the presence of the phosphate group. Therefore, hNF-lipase is an efficient biocatalyst with increased catalytic activity, good nanostructure formation, and improved stability.

Hyperbaric oxygen augments susceptibility to C. difficile infection by impairing gut microbiota ability to stimulate the HIF-1α-IL-22 axis in ILC3.

Hyperbaric oxygen (HBO) therapy is a well-established method for improving tissue oxygenation and is typically used for the treatment of various inflammatory conditions, including infectious diseases. However, its effect on the intestinal mucosa, a microenvironment known to be physiologically hypoxic, remains unclear. Here, we demonstrated that daily treatment with hyperbaric oxygen affects gut microbiome composition, worsening antibiotic-induced dysbiosis. Accordingly, HBO-treated mice were more susceptible to Clostridioides difficile infection (CDI), an enteric pathogen highly associated with antibiotic-induced colitis. These observations were closely linked with a decline in the level of microbiota-derived short-chain fatty acids (SCFAs). Butyrate, a SCFA produced primarily by anaerobic microbial species, mitigated HBO-induced susceptibility to CDI and increased epithelial barrier integrity by improving group 3 innate lymphoid cell (ILC3) responses. Mice displaying tissue-specific deletion of HIF-1 in RORγt-positive cells exhibited no protective effect of butyrate during CDI. In contrast, the reinforcement of HIF-1 signaling in RORγt-positive cells through the conditional deletion of VHL mitigated disease outcome, even after HBO therapy. Taken together, we conclude that HBO induces intestinal dysbiosis and impairs the production of SCFAs affecting the HIF-1α-IL-22 axis in ILC3 and worsening the response of mice to subsequent C. difficile infection.

Perfil clínico, farmacoterapêutico e laboratorial de pacientes internados com insuficiência cardíaca aguda / Clinical, pharmacotherapeutic and laboratory profile of hospitalized patients with acute heart failure / Perfil clínico, farmacoterapéutico y de laboratorio de los pacientes hospitalizados com insuficiência cardíaca aguda

A insuficiência cardíaca aguda (ICA) é uma das causas mais comuns de internação hospitalar, associada a um alto risco de mortalidade. O tratamento atual é principalmente sintomático, sendo os exames laboratoriais realizados, a fim de complementar a avaliação clínica no diagnóstico e auxiliar no estabelecimento do perfil de risco admissional e prognóstico. Este estudo teve como objetivo caracterizar o perfil clínico, farmacoterapêutico e laboratorial de pacientes internados com insuficiência cardíaca aguda em hospital referência regional. Trata-se de um estudo transversal retrospectivo, descritivo, de abordagem quantitativa. Os participantes do estudo foram aqueles com alta médica por ICA pela classificação Internacional de Doenças (CID-10), admitidos na sala de emergência. Excluindo-se a participação de pacientes com tempo de internação inferior a 24 horas, menores de 18 anos. Para análise estatística foi usado o programa SPSS versão 21.0. Quanto ao perfil farmacoterapêutico, os medicamentos mais frequentes foram os que atuam no aparelho cardiovascular e aparelho digestivo e metabolismo, sendo a furosemida o fármaco mais frequente. A análise entre as alterações laboratoriais e a escala de ADHERE, revelou diferença estatística significativa entre os pacientes com risco baixo e risco intermediário/alto nos valores de hemoglobina (p=0,005), TGO (p=0,001), creatinina (p=0,000), ureia (p=0,000), potássio (p=0,004), TTPA (p=0,004) e RNI (p=0,021). Concluiu-se que os medicamentos frequentemente corresponderam ao tratamento recomendado no manejo inicial de pacientes com ICA. O risco de mortalidade intra-hospitalar intermediário/alto de acordo com a escala de ADHERE estavam associados com alterações laboratoriais dos pacientes com ICA.

Acute heart failure (AHF) is one of the most common causes of hospitalization, associated with a high risk of mortality. The current treatment is mainly symptomatic, and laboratory tests are carried out in order to complement the clinical evaluation in the diagnosis and help in establishing the admission and prognostic risk profile. This study aimed to characterize the clinical, pharmacotherapeutic and laboratory profile of patients hospitalized with acute heart failure in a regional reference hospital. This is a retrospective, descriptive, cross-sectional study with a quantitative approach. Study participants were those discharged due to AHF according to the International Classification of Diseases (ICD-10), admitted to the emergency room. Excluding the participation of patients with hospitalization time of less than 24 hours, under 18 years old. For statistical analysis, SPSS version 21.0 was used. As for the pharmacotherapeutic profile, the most frequent drugs were those that act on the cardiovascular and digestive systems and metabolism, with furosemide being the most frequent drug. The analysis between laboratory changes and the ADHERE scale revealed a statistically significant difference between patients at low risk and intermediate/high risk in hemoglobin (p=0.005), TGO (p=0.001), creatinine (p=0.000) values, urea (p=0.000), potassium (p=0.004), APTT (p=0.004) and INR (p=0.021). It was concluded that the medications often corresponded to the recommended treatment in the initial management of patients with AHF. Intermediate/high risk of in-hospital mortality according to the ADHERE scale were associated with laboratory alterations in patients with AHF.

La insuficiencia cardiaca aguda (ICA) es una de las causas más frecuentes de hospitalización, asociada a un alto riesgo de mortalidad. El tratamiento actual es principalmente sintomático y se realizan pruebas de laboratorio para complementar la evaluación clínica en el diagnóstico y ayudar a establecer el perfil de riesgo de ingreso y pronóstico. Este estudio tuvo como objetivo caracterizar el perfil clínico, farmacoterapéutico y de laboratorio de pacientes hospitalizados con insuficiencia cardíaca aguda en un hospital regional de referencia. Se trata de un estudio retrospectivo, descriptivo, transversal con enfoque cuantitativo. Los participantes del estudio fueron los dados de alta por ICA según la Clasificación Internacional de Enfermedades (CIE-10), ingresados en urgencias. Se excluye la participación de pacientes con tiempo de hospitalización menor a 24 horas, menores de 18 años. Para el análisis estadístico se utilizó SPSS versión 21.0. En cuanto al perfil farmacoterapéutico, los fármacos más frecuentes fueron los que actúan sobre los sistemas cardiovascular, digestivo y el metabolismo, siendo la furosemida el fármaco más frecuente. El análisis entre los cambios de laboratorio y la escala ADHERE reveló una diferencia estadísticamente significativa entre los pacientes de riesgo bajo e intermedio/alto en los valores de hemoglobina (p=0,005), TGO (p=0,001), creatinina (p=0,000), urea (p =0,000), potasio (p=0,004), APTT (p=0,004) e INR (p=0,021). Se concluyó que los medicamentos correspondían muchas veces al tratamiento recomendado en el manejo inicial de pacientes con ICA. El riesgo intermedio/alto de mortalidad hospitalaria según la escala ADHERE se asoció con alteraciones de laboratorio en pacientes con ICA.

Reverse Genetics of Dengue Virus.

Dengue virus (DENV) is one of the most important and widespread arthropod-borne viruses, causing millions of infections over the years. Considering its epidemiological importance, efforts have been directed towards understanding various aspects of DENV biology, which have been facilitated by the development of different molecular strategies for engineering viral genomes, such as reverse genetics approaches. Reverse genetic systems are a powerful tool for investigating virus-host interaction, for vaccine development, and for high-throughput screening of antiviral compounds. However, stable manipulation of DENV genomes is a major molecular challenge, especially when using conventional cloning systems. To circumvent this issue, we describe a simple and efficient yeast-based reverse genetics system to recover infectious DENV clones.

Seasonal and Regional Differences in Eating Times in a Representative Sample of the Brazilian Population.

Human food intake and its timing are a complex behavior that can be influenced by a variety of factors, some of which may vary from season to season or from region to region. In this study, our aim was to investigate the seasonal variation in food intake times, with a particular focus on how these may vary across different regions of a country. We conducted an analysis of data from 20,622 adults from the National Household Budget Survey (POF-IBGE), encompassing complete food diaries collected from individuals residing in Brazil, and thereby ensuring representation across different latitudes. Each participant's daily food intake was reported for two non-consecutive days at different times in the same week using food diaries. An ANOVA revealed a later food intake time in the evening in high-latitude regions compared to low-latitude regions. The Sidak post-hoc test showed a significant interaction effect between region and season, demonstrating a pattern of early First Intake Time and Eating Midpoint in the Northeast region during spring/summer. Additionally, we observed an independent effect of the region, as early food intake times were found in low-latitude regions. These findings offer a basis for discussing food intake times among individuals living in different regions located on distinct latitudes.

Prior vaccination promotes early activation of memory T cells and enhances immune responses during SARS-CoV-2 breakthrough infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific cluster of differentiation (CD)4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production and primary responses to nonspike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.

IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding.

The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here, we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2, or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 and BA.1 strains of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for fine-tuning effector functionality but also for binding and neutralization of antigenically drifted viruses.

Cell surface nucleocapsid protein expression: A betacoronavirus immunomodulatory strategy.

We recently reported that SARS-CoV-2 nucleocapsid (N) protein is abundantly expressed on the surface of both infected and neighboring uninfected cells, where it enables activation of Fc receptor-bearing immune cells with anti-N antibodies (Abs) and inhibits leukocyte chemotaxis by binding chemokines (CHKs). Here, we extend these findings to N from the common cold human coronavirus (HCoV)-OC43, which is also robustly expressed on the surface of infected and noninfected cells by binding heparan sulfate/heparin (HS/H). HCoV-OC43 N binds with high affinity to the same set of 11 human CHKs as SARS-CoV-2 N, but also to a nonoverlapping set of six cytokines. As with SARS-CoV-2 N, HCoV-OC43 N inhibits CXCL12ß-mediated leukocyte migration in chemotaxis assays, as do all highly pathogenic and common cold HCoV N proteins. Together, our findings indicate that cell surface HCoV N plays important evolutionarily conserved roles in manipulating host innate immunity and as a target for adaptive immunity.

Cell Surface Nucleocapsid Protein Expression: A Betacoronavirus Immunomodulatory Strategy.

We recently reported that SARS-CoV-2 Nucleocapsid (N) protein is abundantly expressed on the surface of both infected and neighboring uninfected cells, where it enables activation of Fc receptor-bearing immune cells with anti-N antibodies (Abs) and inhibits leukocyte chemotaxis by binding chemokines (CHKs). Here, we extend these findings to N from the seasonal human coronavirus (HCoV)-OC43, which is also robustly expressed on the surface of infected and non-infected cells by binding heparan-sulfate/heparin (HS/H). HCoV-OC43 N binds with high affinity to the same set of 11 human CHKs as SARS-CoV-2 N, but also to a non-overlapping set of 6 cytokines (CKs). As with SARS-CoV-2 N, HCoV-OC43 N inhibits CXCL12ß-mediated leukocyte migration in chemotaxis assays, as do all highly pathogenic and endemic HCoV N proteins. Together, our findings indicate that cell surface HCoV N plays important evolutionary conserved roles in manipulating host innate immunity and as a target for adaptive immunity.

Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies.

SARS-CoV-2 infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened Spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific CD4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production, and primary responses to non-Spike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.

Nucleoside-Modified mRNA-Based Influenza Vaccines Circumvent Problems Associated with H3N2 Vaccine Strain Egg Adaptation.

Most human influenza vaccine antigens are produced in fertilized chicken eggs. Recent H3N2 egg-based vaccine antigens have limited effectiveness, partially due to egg-adaptive substitutions that alter the antigenicity of the hemagglutinin (HA) protein. The nucleoside-modified mRNA encapsulated in lipid nanoparticles (mRNA-LNP) vaccine platform is a promising alternative for egg-based influenza vaccines because mRNA-LNP-derived antigens are not subject to adaptive pressures that arise during the production of antigens in chicken eggs. Here, we compared H3N2-specific antibody responses in mice vaccinated with either 3c.2A H3-encoding mRNA-LNP or a conventional egg-based Fluzone vaccine (which included an egg-adapted 3c.2A antigen) supplemented with an MF59-like adjuvant. We tested mRNA-LNP encoding wild-type and egg-adapted H3 antigens. We found that mRNA-LNP encoding wild-type H3 elicited antibodies that neutralized the wild-type 3c.2A H3N2 virus more effectively than antibodies elicited by mRNA-LNP encoding egg-adapted H3 or the egg-based Fluzone vaccine. mRNA-LNP expressing either wild-type or egg-adapted H3 protected mice against infection with the wild-type 3c2.A H3N2, whereas the egg-based Fluzone vaccine did not. We found that both mRNA-LNP vaccines elicited high levels of group 2 HA stalk-reactive antibodies, which likely contributed to protection in vivo. Our studies indicate that nucleoside-modified mRNA-LNP-based vaccines can circumvent problems associated with egg adaptations with recent 3c2.A H3N2 viruses. IMPORTANCE This study shows that the nucleoside-modified mRNA-LNP vaccine platform is a promising alternative for egg-based influenza vaccines. We show that mRNA-LNP vaccines expressing H3 antigens elicit high levels of antibodies in mice and protect against H3N2 influenza virus infection.

ArboAlvo: stratification method for territorial receptivity to urban arboviruses.

OBJECTIVE: To present the urban arboviruses (dengue, zika and chikungunya) stratification methodology by the territorial receptivity Index, an instrument for the surveillance and control of these diseases, which considers the heterogeneity of an intra-municipal territory. METHODS: Ecological study that uses as unit of analysis the areas covered by health centers in Belo Horizonte. For the development of a territorial receptivity index, indicators of socio-environmental determination of urban arboviruses were selected in order to integrate the analysis of main components. The resulting components were weighted by the analytic hierarchy process and combined via map algebra. RESULTS: The territorial receptivity index showed great heterogeneity of urban infrastructure conditions. The areas classified with high and very high receptivity correspond to approximately 33% of the occupied area and are mainly concentrated in the administrative planning regions of East, Northeast, North, West, and Barreiro, especially in areas surrounding the municipality. When the density of dengue cases and Aedes eggs, from 2016, were superimposed with the stratification by the index of territorial receptivity to urban arboviruses, areas of very high receptivity had a high density of cases and Aedes eggs - higher than that observed in other areas of the city, which corresponds to a very small percentage of the municipal territory (13.5%). CONCLUSION: The analyses indicate the need for the development of adequate surveillance and control actions for each context, overcoming the logic of homogeneous allocation throughout the territory.

Measles resurgence in Brazil: analysis of the 2019 epidemic in the state of São Paulo.

OBJECTIVE: To analyze the epidemiological profile of cases and the pattern of spatial diffusion of the largest measles epidemic in Brazil that occurred in the post-elimination period in the state of São Paulo. METHOD: A cross-sectional study based on confirmed measles cases in 2019. Bivariate analysis was performed for socioeconomic, clinical, and epidemiological variables, according to prior vaccination and hospitalization, combined with an analysis of spatial diffusion of cases using the Inverse Distance Weighting (IDW) method. RESULTS: Of the 15,598 confirmed cases, 2,039 were hospitalized and 17 progressed to death. The epidemic peak occurred in epidemiological week 33, after confirmation of the first case, in the epidemiological week 6. Most cases were male (52.1%), aged between 18 and 29 years (38.7%), identified as whites (70%). Young adults (39.7%) and children under five years (32.8%) were the most affected age groups. A higher proportion of previous vaccination was observed in whites as compared to Blacks, browns, yellows and indigenous people (p < 0.001), as well as in the most educated group compared to the other categories (p < 0.001). The risk of hospitalization was higher in children than in the older age group (RI = 2.19; 95%CI: 1.66-2.88), as well as in the unvaccinated than in the vaccinated (RI = 1.59; 95%CI: 1.45-1.75). The pattern of diffusion by contiguity combined with diffusion by relocation followed the urban hierarchy of the main cities' regions of influence. CONCLUSION: In addition to routine vaccination in children, the findings indicate the need for immunization campaigns for young adults. In addition, studies that seek to investigate the occurrence of clusters of vulnerable populations, prone to lower vaccination coverage, are essential to broaden the understanding of the dynamics of transmission and, thus, reorienting control strategies that ensure disease elimination.

[ARBOALVO: territorial stratification for definition of areas for prompt response by surveillance and timely control of urban arbovirus infections]. / ARBOALVO: estratificação territorial para definição de áreas de pronta resposta para vigilância e controle de arboviroses urbanas em tempo oportuno.

The study aimed to present the methodological proposal entitled "Prompt Response", modelled in the cities of Belo Horizonte (Minas Gerais State) and Natal (Rio Grande do Norte State), Brazil. The proposal aims to identify and demarcate priority areas for timely targeting of surveillance activities, aiming to reduce the intensity and velocity in the spread of epidemics in endemic urban areas. The methodology uses three variables that represent the necessary causes for the production and reproduction of dengue: notified cases (virus), Aedes eggs (vector), and population (host). This was an ecological study that used data from three information planes aggregated in finer temporal and spatial scales of 3 to 4 weeks and 400 to 600-meter grids, respectively. The prompt response areas were defined by Scan statistical analysis with definition of simultaneous spatial clusters for the three planes via the SaTScan program. In Natal, the areas defined as prompt response occupied, on average, 15.2% of the city's territory and concentrated 67.77% of the dengue cases in the period following demarcation of the prompt response areas. In Belo Horizonte, the observed proportions were 64.16% of cases in 23.23% of the territory. These results were obtained in two cities with different socioenvironmental and geographic realities and distinct epidemiological profiles, indicating that the methodology can be applied to different urban realities, allowing control programs to concentrate on reduced portions of the territory and impacting a high percentage of cases in timely fashion.

O objetivo deste trabalho foi apresentar a proposta metodológica denominada de "Pronta Resposta" modelada nas cidades de Belo Horizonte (Minas Gerais) e Natal (Rio Grande do Norte), Brasil. A metodologia visa identificar e delimitar áreas prioritárias para o direcionamento das ações de vigilância em tempo oportuno, buscando a redução da intensidade e velocidade da dispersão de epidemias em áreas urbanas endêmicas. Para tanto, a metodologia utiliza três variáveis, que representam as causas necessárias para a produção e reprodução da dengue: casos notificados (vírus), ovos de Aedes (vetor) e população (hospedeiro). Trata-se de um estudo ecológico que utilizou os dados dos três planos de informações agregados em escalas temporais e espaciais mais finas, de três a quatro semanas e grades de 400 a 600 metros respectivamente. As áreas de pronta resposta foram definidas por meio de análise estatística de varredura Scan, com definição de clusters espaciais simultâneos para os três planos por meio do programa SaTScan. Os resultados observados foram: na cidade de Natal, as áreas definidas como pronta resposta ocuparam em média 15,2% do território do município e concentraram 67,77% dos casos de dengue do período posterior ao utilizado na delimitação das áreas de pronta resposta, e em Belo Horizonte, os números observados foram de 64,16% dos casos em 23,23% do território. Esses resultados foram obtidos em duas cidades com realidades socioambientais e geográficas diferentes e com perfis epidemiológicos também distintos, apontando que a metodologia pode ser aplicada em diferentes realidades urbanas, criando a possibilidade de os programas de controle atuarem em porções reduzidas do território e impactar num alto percentual de casos em tempo oportuno.

El objetivo del trabajo fue presentar la propuesta metodológica, denominada de "Resposta Rápida", modelada en las ciudades de Belo Horizonte (Minas Gerais) y Natal (Rio Grande do Norte), Brasil. Esta última tiene como meta identificar y delimitar áreas prioritarias para la ejecución de acciones de vigilancia en el momento oportuno, buscando la reducción de la intensidad y velocidad de la dispersión de epidemias en áreas urbanas endémicas. Para tal fin, la metodología utiliza tres variables, que representan las causas necesarias para la producción y reproducción del dengue: casos notificados (virus), huevos de Aedes (vector) y población (huésped). Se trata de un estudio ecológico que utilizó los datos de los tres planos de información agregados en escalas temporales y espaciales más finas, de 3 a 4 semanas y tablas de 400 a 600 metros respectivamente. Las áreas de respuesta rápida se definieron a través del análisis estadístico de exploración Scan, con definición de clústeres espaciales simultáneos para los tres planos mediante el programa SaTScan. Los resultados observados fueron: en la ciudad de Natal, las áreas definidas como de respuesta rápida ocuparon de media un 15,2% del territorio del municipio y concentraron un 67,77% de los casos de dengue del período posterior al utilizado en la delimitación de las áreas de respuesta rápida y, en Belo Horizonte, los números observados fueron un 64,16% de los casos en un 23,23% del territorio. Estos resultados se obtuvieron en dos ciudades con realidades socioambientales y geográficas diferentes y con perfiles epidemiológicos también distintos, apuntando que la metodología se puede aplicar en diferentes realidades urbanas. Dando la posibilidad de que los programas de control actúen en secciones reducidas del territorio e impactar en un alto porcentaje de casos en el momento oportuno.

Changes in adolescents' sleep during COVID-19 outbreak reveal the inadequacy of early morning school schedules.

Objectives: The forced closure of schools during the COVID-19 outbreak imposed on adolescents a new reality of home-schooling. This new situation has affected adolescent sleep patterns due to the absence of the pressure to wake up earlier induced by school times during pandemic. This study aimed to investigate the changes in sleep and napping habits in Brazilian adolescents during the COVID-19 outbreak. Methods: A sample of 259 high school adolescents (mean age = 15.5 years) reported sleep and napping habits by means validated questionnaires in both baseline year (March-June 2019) and during COVID-19 lockdown (July 2020). Results: The tendency to eveningness was higher and daytime sleepiness was reduced during the social isolation. Time in bed (TIB) increased by more than 2 hours and sleep onset time was delayed during the pandemic. More adolescents reported getting enough TIB during the pandemic. Moreover, sleepiness during remote classes was reduced compared to that reported during traditional classes one year before. The nap habit decreased during the pandemic compared to the baseline year. Discussion: The lack of early wake-up pressure to attend school in the morning could explain the sleep improvements perceived during the COVID-19 outbreak. Therefore, parents, educators, and policy makers need to discuss more feasible school times for adolescents in order to implement these changes as soon as returning to presential/hybrid learning.