Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults.

BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).

Diagnosis of cystic fibrosis: a high heterogeneity of symptoms and genotypes in a Brazil population.

INTRODUCTION: In highly multiracial populations with inadequate newborn screening, knowledge of the various phenotypic presentations of Cystic Fibrosis (CF) can help reach an early diagnosis. This study aims to describe phenotypes and genotypes at the time of CF diagnosis in a state in the Northeast Region of Brazil. METHODS: Retrospective cross-sectional study. Clinical data were extracted from the medical records of CF patients. Clinical, laboratory, and genotypic characteristics were described for patients admitted to a tertiary referral center between 2007 and 2021. RESULTS: Fifty-eight (58) patients were included in the study, 53.5% of whom were diagnosed through clinical suspicion. The median age at diagnosis was 4.7 months (IQR: 1.5-14.8 months). Five patients had false-negative results in the newborn screening. Faltering growth was the most frequent clinical manifestation. Bronchiectasis and a history of pneumonia predominated in those older than ten, while thinness, underweight, and electrolyte imbalances were more frequent in children under two. Sequencing of the CFTR gene identified 27 genotypes, with at least one class I-III variant in all patients, and nine variants that are rare, previously undescribed, or have uncertain significance (619delA, T12991, K162Q, 3195del6, 1678del > T, 124del123bp, 3121-3113 A > T). The most frequent alleles were p.Phe508del, p.Gly542*, p.Arg334Trp, and p.Ser549Arg. CONCLUSIONS: Malnutrition and electrolyte imbalances were the most frequent phenotypes for children < 2 years and were associated with genotypes including 2 class I-III variants. Rare and previously undescribed variants were identified. The p.Gly542*, p.Arg334Trp, and p.Ser549Arg alleles were among the most frequent variants in this population.

Impact of Infant Milk-Type and Childhood Eating Behaviors on Functional Constipation in Preschool Children.

OBJECTIVE: To investigate the association between functional constipation, infant feeding in early infancy and eating behavior in preschool children. METHODOLOGY: A cross-sectional study was undertaken in public and private schools in the state of Sergipe (Northeast of Brazil). The sample calculation was based on a 25% estimate of constipation prevalence in Brazilian children, resulting in a sample size of 1051 children. Functional constipation was assessed using Rome IV criteria. Eating behavior was assessed using the Children's Eating Behavior Questionnaire. Adjusted odds ratios were estimated using a multivariate model. RESULTS: The prevalence of functional constipation was 23%. After adjusting for water intake, children with food fussiness were >6 times likely to have constipation (odds ratio [OR] = 6.65; 95% confidence interval [CI] 5.19-8.52). Children who were fed with cow's milk in the first 6 months of age were up to 15.2 times more likely to have functional constipation. Bottle feeding at 0-6 months of age increased the risk of functional constipation at preschool age (whole cow's milk: OR = 17.02; 95% CI 7.33-39.51, infant formula: OR = 6.35; 95% CI 3.42-11.79, mixed breastfeeding: OR = 10.83; 95% CI 4.57-25.69). CONCLUSION: Food fussiness and the use of cow's milk-based feeding bottles at 0-6 months of age were associated with functional constipation in preschool children.

Factors associated with extubation failure in very low birth weight infants: a cohort study in the northeast Brazil.

OBJECTIVES: Identifying and understanding the main risk factors associated with extubation failure of very low birthweight (VLBW) infants in different populations can subsequently help in establishing better criteria while taking decision of extubation. The aim of the study was to identify factors associated with extubation failure in VLBW infants. METHODS: A cohort study of VLBW infants who underwent their first extubation between April 2018 and December 2019 in a Neonatal Intensive Care Unit, Alagoas, Brazil, were included in this study. Extubation failure was defined as reintubation within seven days of extubation. Relative risks of predictive variables different between the extubation success group (ES) and extubation failure group (EF) were estimated with a robust Poisson regression model. RESULTS: Out of the 112 infants included, 26 (23%) cases exhibited extubation failure. Extremely low birth weight (RR 2.55, 95% CI 1.07, 6.06), mechanical ventilation duration for first extubation greater than seven days (RR 2.66, 95% CI 1.10, 6.45), vaginal delivery (RR 2.07, 95% CI 1.03, 4.18) and maternal chorioamnionitis (RR 4.89, 95% CI 1.26-18.98) remained independently associated with extubation failure. EF had a significant greater need for respiratory support, longer oxygen therapy duration, more bronchopulmonary dysplasia (BPD) and longer length of hospital stay, even when adjusted for confounding variables. CONCLUSIONS: Extremely low birth weight infants needing mechanical ventilation, wherein the duration for first extubation was longer than seven days, with vaginal delivery and maternal chorioamnionitis failed more frequently at the first attempt of extubation. And this failure increased the risk of BPD and the length of hospital stay.

Survey on the Adherence to the 2009 NASPGHAN-ESPGHAN Gastroesophageal Reflux Guidelines by Brazilian Paediatricians.

OBJECTIVE: The aim of the study was to evaluate the management of gastroesophageal reflux in children among Brazilian pediatricians and adherence to the 2009 North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN), and European Society of Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Guideline in Brazil. METHODS: An observational cross-sectional study was conducted, applying a standard questionnaire with 12 questions about gastroesophageal reflux (GER) and gastroesophageal reflux disease (GERD) management in infants, children, and adolescents to the pediatricians during the 37th Brazilian Pediatrics Congress in October, 2015. Adherence to the 2009 NASPGHAN-ESPGHAN Guideline was verified through analyses of interviewees' answers. Pediatricians' demographic and professional characteristics were screened. RESULTS: A total of 390 Brazilian pediatricians answered the questionnaire. None showed complete adherence to Guideline recommendations. GERD diagnosis by history alone was reported by 67%, irrespective of the child's age. The mean score for diagnostic adherence to the guidelines was 0.94 ±â€Š0.86 (range 0-4). Working in public health services (P = 0.026) was the only variable retained as a significant predictor of poor adherence for GER/GERD diagnosis after multivariate logistic regression analysis. No significant statistical differences were found between Brazilian regions on total score (P = 0.774). Proton pump inhibitors were prescribed by 28.4% of the pediatricians independent of child's age, and 59% use proton pump inhibitors to treat babies with unexplained crying and/or distressed behavior. CONCLUSIONS: 2009 NASPGHAN-ESPGHAN Guideline recommendations had poor adherence by Brazilian pediatricians. Studies evaluating the reasons for the poor adherence to NASPGHAN/ESPGHAN guidelines are urgently needed.

Cytokines in the management of rotavirus infection: A systematic review of in vivo studies.

OBJECTIVE: Rotavirus is a leading cause of childhood diarrhoea. Rotavirus vaccines are effective against severe rotavirus gastroenteritis, but have lower efficacy in low income countries in Africa. Anti-rotavirus treatment is not available. This study reviews the literature of animal studies evaluating whether cytokine mediated pathways of immune activation could improve rotavirus therapy. METHODS: We performed a systematic review of articles in English published from 2010 to 2016 reporting agents with in vivo antirotavirus activity for the management of rotavirus infection. The search was carried in PubMed, EMBASE, Scopus and Web of Science. Animal experiments where cytokines were investigated to assess the outcome of rotavirus therapy were included. RESULTS: A total of 869 publications were identified. Of these, 19 pertained the objectives of the review, and 11 articles described the effect of probiotics/commensals on rotavirus infection and immune responses in animals. Eight further in vivo studies evaluated the immunomodulating effects of herbs, secondary metabolites and food-derived products on cytokine responses of rotavirus-infected animals. Studies extensively reported the regulatory roles for T-helper (Th)1 (interferon gamma (IFN-γ), interleukin (IL)-2, IL-12) and Th2 (IL-4, IL-6, IL-10) cytokines responses to rotavirus pathogenesis and immunity, inhibiting rotavirus infection through suppression of inflammation by viral inhibition. CONCLUSION: Th1 and Th2 cytokines stimulate the immune system, inhibiting rotavirus binding and/or replication in animal models. Th1/Th2 cytokine responses have optimal immunomodulating effects to reduce rotavirus diarrhoea and enhance immune responses in experimental rotavirus infection.

Pharmacologic Treatment of Vitiligo in Children and Adolescents: A Systematic Review.

BACKGROUND: The true pathogenic mechanism of vitiligo is still unknown. About half of the patients with this disease have onset before the age of 20 years, making it a serious dermatologic disorder in childhood. OBJECTIVES: The objective of this study was to review the literature in a systematic way and identify the main pharmacologic treatments and outcomes in children and adolescents with vitiligo. METHODS: Four databases-the National Library of Medicine (MEDLINE-PubMed), Web of Science, Scopus, and Latin American and Caribbean Health Sciences (LILACS)-were used for the search up to January 2015. All electronic search titles, selected abstracts and full-text articles were independently reviewed by a minimum of two reviewers. RESULTS: There were 15 articles from 13 different countries: 3 were retrospective and 12 were prospective; the number of participants in the studies varied between 9 and 400, ages ranged from 0 to 18 years, and the duration of disease ranged from 1 to 17 years. The most commonly used drugs were tacrolimus alone (or combined with clobetasol), pimecrolimus, corticosteroids, and calcipotriol. Treatment duration ranged from 10 days to 6 months with a topical route of administration. CONCLUSIONS: The main outcome measurements were morphometric analysis performed using a computer program, hematologic or biochemical change, and photography (predominant). It is unclear which was the most effective treatment for vitiligo, however, it was found that these therapies are all promising in the treatment of the disease. With proper care, disease control and repigmentation, even if partial, can be achieved.

Similarities and differences between WHO criteria and two other approaches for maternal near miss diagnosis.

OBJECTIVES: To evaluate the similarities, differences and diagnostic aspects between World Health Organization (WHO) criteria and two other maternal near miss (MNM) diagnostic tools. METHODS: A cross-sectional study was conducted from June 2011 to May 2012 in two reference maternity hospitals in Aracaju, Brazil. Prospective case identification and data collection were performed and patients were classified as an MNM case according to WHO, Waterstone and literature-based criteria. The diagnostic properties and concordance of literature-based and Waterstone criteria were calculated using WHO criteria as standard. RESULTS: Of a total of 20 435 patients, 19 239 women did not have potentially life-threatening conditions, there were 17 maternal deaths, and 77 MNM cases based on the WHO criteria. Waterstone and literature-based criteria identified 404 and 959 MNM cases, respectively, most of them related to hypertensive disorders and haemorrhage. The sensitivity, specificity and accuracy in diagnosing MNM cases using Waterstone and literature-based criteria were above 90%, but Waterstone sensitivity was 48.1%. The similarities between the Waterstone and literature-based criteria were very weak compared to WHO criteria, with a positive percentage concordance below 9%. CONCLUSIONS: Although using WHO guidelines to detect MNM cases can be difficult when implemented in low-resource settings, the results from this study reinforce the importance of this tool in detecting the truly severe cases. Waterstone and literature-based criteria are not suitable for identifying indubitable MNM. However, they remain useful as a preliminary step to select potentially severe cases, mainly those related to hypertension and haemorrhage.

The Study of Cardiovascular Risk in Adolescents--ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents.

BACKGROUND: The Study of Cardiovascular Risk in Adolescents (Portuguese acronym, "ERICA") is a multicenter, school-based country-wide cross-sectional study funded by the Brazilian Ministry of Health, which aims at estimating the prevalence of cardiovascular risk factors, including those included in the definition of the metabolic syndrome, in a random sample of adolescents aged 12 to 17 years in Brazilian cities with more than 100,000 inhabitants. Approximately 85,000 students were assessed in public and private schools. Brazil is a continental country with a heterogeneous population of 190 million living in its five main geographic regions (North, Northeast, Midwest, South and Southeast). ERICA is a pioneering study that will assess the prevalence rates of cardiovascular risk factors in Brazilian adolescents using a sample with national and regional representativeness. This paper describes the rationale, design and procedures of ERICA. METHODS/DESIGN: Participants answered a self-administered questionnaire using an electronic device, in order to obtain information on demographic and lifestyle characteristics, including physical activity, smoking, alcohol intake, sleeping hours, common mental disorders and reproductive and oral health. Dietary intake was assessed using a 24-hour dietary recall. Anthropometric measures (weight, height and waist circumference) and blood pressure were also be measured. Blood was collected from a subsample of approximately 44,000 adolescents for measurements of fasting glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, glycated hemoglobin and fasting insulin. DISCUSSION: The study findings will be instrumental to the development of public policies aiming at the prevention of obesity, atherosclerotic diseases and diabetes in an adolescent population.

Stomatognathic evaluation at five years of age in children born premature and at term.

BACKGROUND: The high frequency of alterations of the stomatognathic system associated with premature birth may suggest that prematurity is an important risk factor in the development of this system. Prematurity has an incidence between 6-11% of births and is associated with factors such as genetic, maternal conditions (obstetric problems, nutritional status, infections) and antenatal care. In addition, undesirable situations, such as changes in enamel and the development of the skeletal structure, also appears to be associated with prematurity. This study aimed to look for changes in the stomatognathic system at five years of age associated with premature birth. METHODS: We estimated the prevalence of developmental disorders of the stomatognathic system in the primary dentition of preschool children at five years of age. Changes in preterm infants (n = 32) compared with term born (n = 381) were evaluated . Clinical examinations and questionnaire with sociodemographic and health of mothers and children information. Gestational age, birth weight, head circumference, Apgar score and mechanical ventilation, were collected from the medical records to birth records. The explanatory variable was preterm (<37 weeks gestational age). RESULTS: Prevalence of 7.7% of preterm infants was found. Of these, 40.6% had atresic palate, 56.2% malocclusion and 21.8% enamel hypoplasia. Forty (9.6%) children were not breastfed at the breast, and 26 (65.0%) had some type of malocclusion, showing association between not breastfeeding with an abnormal development of the stomatognathic system. The group of preterm infants showed five times more changes in head circumference and three times more mechanical ventilation use at birth. Change in head circumference at birth and mechanical ventilation has a significant association between groups of preterm and term infants. CONCLUSIONS: Mechanical ventilation at birth directly contributed to an increased risk of developmental disorders of the stomatognathic system in preterm infants, especially dental hypoplasia. Non-breastfed children had a higher risk of developing malocclusion. Alterations in head circumference were related effective on dental malocclusion. The results suggest that changes in the stomatognathic system are influenced by premature birth and points to the imperative need of using methods of preventive.

The prevalence of severe maternal morbidity and near miss and associated factors in Sergipe, Northeast Brazil.

BACKGROUND: The investigation of severe maternal morbidity (SAMM) and maternal near miss (NM) and associated risk factors is important for the global reduction of maternal mortality. This study investigated the prevalence of SAMM and NM cases and the associated risk factors in two reference maternity hospitals in a capital city in Northeast-Brazil. METHODS: A cross-sectional study with a nested case-control component was conducted from June-2011 to May-2012. Case identification was prospective and data collection was performed according to WHO criteria and definitions. Odds ratio with confidence intervals and multivariate analysis were used whenever possible. RESULTS: There were 16,243 deliveries, 1,102 SAMM cases, 77 NM cases and 17 maternal deaths. The maternal NM outcome ratio was 5.8 cases/1,000 live births (LB); the total prevalence of SAMM + NM was 72.6 cases/1,000 LB, the maternal near miss: mortality ratio was 4.5cases/1 maternal death (18% of mortality index). Management-based criteria were the most common events for NM (87.1%) and hypertensive disorders for SAMM (67.5%). Higher age, previous abortion and caesarean delivery, the non-adhesion to antenatal care, current caesarean delivery and bad perinatal results were associated with SAMM/NM. In the multivariate analysis, patient's status, previous caesarian and abortion and level of consciousness were significant when analyzed together. CONCLUSIONS: SAMM and NM situations were prevalent in the studied population and some risk factors seem to be associated with the event, particularly previous gestational antecedents. Protocols based on SAMM/NM situations can save lives and decrease maternal mortality.

Diarrhea incidence and intestinal infections among rotavirus vaccinated infants from a poor area in Brazil: a spatial analysis.

BACKGROUND: Acute diarrhea is the second leading cause of mortality among children under 5 years of age in developing countries. The pathogen most strongly associated with diarrhea is rotavirus followed by enteric pathogens such as bacteria, helminthes and protozoan. Adequate sanitation and water supply contribute to decrease acute diarrhea incidence of most etiologic agents, although vaccination remains the most important intervention to control rotavirus acute diarrhea. This study aimed to describe environmental conditions and analyze spatially the acute diarrhea and intestinal infection among rotavirus vaccinated infants from Laranjeiras-Sergipe, Brazil. METHODS: Children were enrolled between 2 and 11 months of age and followed through 12 months. Demographic, socioeconomic and environmental data were obtained from a questionnaire, and immunization data were obtained from children vaccination card. Children stool samples were collected each month in order to run laboratory analyses. The household spatial localization was obtained by using a Global Positioning System (GPS). Spatial analysis was performed using the TerraView computer program and Kernel intensity estimation. RESULTS: A total of 1,113 stool samples were collected with 80 being diarrhea associated. Diarrhea incidence rate was 0.5 ± 1.0 episodes/child/year. The overall infection rates by Ascaris lumbricoides, Endolimax nana, Giardia lamblia and rotavirus were 5.1%, 3.0%, 0.9% and 2.6%, respectively. 3.8% of diarrhea-associated stool samples were positive for rotavirus and 11.3% were positive for helminths and protozoans. There were some changes on spatial distribution of intestinal infections and diarrhea episodes along the four trimesters evaluated. CONCLUSIONS: The studied infants live equally in precarious conditions of sanitation which probably explain the significant rates of parasitic infections appearing in early life. The low acute diarrhea incidence in the studied rotavirus vaccinated population and the low number of symptomatic rotavirus infection may indicate vaccination efficacy to prevent acute diarrhea among young children in a poor environmental sanitary setting.

Infant overweight as early marker of childhood overweight in Brazil.

OBJECTIVE: To investigate infant overweight and rapid weight gain as predictors of overweight and adiposity in childhood. METHODS: Prospective, longitudinal birth cohort following 153 low-income Brazilian children. Weight, length, middle upper arm circumference (MUAC) and triceps skinfold thickness (TSF) were measured on enrolment and 6-monthly for 18 months. Anthropometric z-scores were calculated. RESULTS: Infants with overweight were >5 times likely to have MUAC z-score >2, >6 times likely to have weight-for-height/length z-score >2 and >3 times likely to have TSF z-score >2 during childhood. Children with more than two overweight episodes were 27.7 [95% confidence interval (CI) 8.1-87.9] times more likely to have MUAC z-score >2 and 13.8 (95% CI 4.4-43.9) times more likely to have TSF z-score >2 in childhood. Rapid weight gain increased 10.7 (95% CI 2.3-50.0) times the risk of childhood overweight. CONCLUSIONS: Infant overweight and rapid weight gain predict overweight and adiposity in childhood among low-income children.

Prevalence and Risk Factors for Dysphonia in Preschoolers at Five Years Old in a Capital City in the Northeast of Brazil.

GOALS: Identifying the prevalence and risk factors of childhood dysphonia in children turning 5 years old; and assess the link with the interactional, behavioral, sociodemographic, economic, and biological indicators METHOD: Analytical, transversal, nested within a birth cohort 5 years after its creation. Original cohort biologic data were recovered from the previous database. The current demographic and personal data were acquired from the official health institutions where the individuals were found. We managed to find 371 preschoolers, both sexes, enrolled in 141 public and private schools. Face-to-face interviews were performed with mothers regarding maternal and child health and biological, sociodemographic, economic, interactional-affective, and behavioral indicators. Speech therapists used the Consensus of Auditory-Perceptual Evaluation of Voice authorized for Portuguese for the perceptual-auditory judgment of children's voices. Bivariate and multivariate analyzes of the data were performed. A significance level of 5% (P < 0.05) was considered in all analyses. RESULTS: The prevalence of mild-moderate general dysphonia occurred in 26.4% of the preschoolers assessed with tense, rough, and breathy voice quality; low pitch; strong loudness and laryngeal resonance. There was a contrast between preschoolers with dysphonia, calm temperament, and family income of up to three minimum wages and those without these characteristics. We also have noted that a greater chance of dysphonia occurred in preschoolers with a calm temperament, family income of up to three minimum wages, nocturnal bruxism up to 3 years old and who did not use a pacifier. CONCLUSION: There was a high prevalence of dysphonia at 5 years old. Biological indicators have an impact on voice, while interactional, behavioral, sociodemographic, and economic indicators have a higher impact. There is a great need for investments in prevention, promotion, and vocal treatment to minimize negative socio-educational impacts and provide higher quality of life for children at greater risk for dysphonia.

Factors Associated with Weaning in Infants with Cow's Milk Allergy: A Cohort Study.

Objective: To analyze the factors associated with weaning in infants with cow's milk allergy (CMA) treated at a food allergy reference center in a state in the northeast of Brazil. Method: A prospective cohort study, with a case group (children with CMA) and two control groups (symptomatic nonallergic children [SC] and asymptomatic [AC]). At the beginning of the study, 30 children comprised the CMA group, 84 the SC group, and 52 the AC group. Survival analysis was performed to compare breastfeeding time between the three groups and an adjusted linear regression model to verify the factors associated with breastfeeding time. Results: At the beginning of the study, 33.3% of children in the CMA group, 17.1% in the SC group, and 69.6% in the AC group were exclusively breastfeeding (p = 0.005). The most common factors for weaning in children with CMA were the cow's milk elimination diet (30%), allergic symptoms in the child (20%), and breast engorgement (20%). Children who used a cup as a means of offering infant formula spent 281 more days breastfeeding compared with those who used a baby bottle (Bstd = 1.39; p = 0.031). Conclusion: Children with CMA and nonallergic gastrointestinal complaints weaned earlier compared with asymptomatic children. The main causes of weaning in CMA children were maternal difficulty adhering to the elimination diet, breast engorgement, and allergic symptoms in the child. Using a cup was the main factor associated with longer breastfeeding duration, regardless of gastrointestinal symptoms and socioeconomic factors.

Multitargeted molecular docking and dynamics simulation studies of flavonoids and volatile components from the peel of Citrus sinensis L. (Osbeck) against specific tumor protein markers.

Citrus sinensis (L.) Osbeck (Rutaceae), commonly known as the sweet orange, is a popular and widely consumed fruit with several medicinal properties. The present study aimed to perform the in silico screening of 18 flavonoids and eight volatile components from the peel of C. sinensis against apoptotic and inflammatory proteins, metalloprotease, and tumor suppressor markers. Flavonoids obtained higher probabilities than volatile components against selected anti-cancer drug targets. Hence, the data from the binding energies against the essential apoptotic and cell proliferation proteins substantiate that they may be promising compounds in developing effective candidates to block cell growth, proliferation, and induced cell death by activating the apoptotic pathway. Further, the binding stability of the selected targets and the corresponding molecules were analyzed by 100 ns molecular dynamics (MD) simulations. Chlorogenic acid has the most binding affinity against the important anti-cancer targets iNOS, MMP-9, and p53. The congruent binding mode to different drug targets focused on cancer shown by chlorogenic acid suggests that it may be a compound with significant therapeutic potential. Moreover, the binding energy predictions indicated that the compound had stable electrostatic and van der Waal energies. Thus, our data reinforce the medicinal importance of flavonoids from C. sinensis and expand the need for more studies, seeking to optimize results and amplify the impacts of further in vitro and in vivo studies. Communicated by Ramaswamy H. Sarma.

Description of vaccination coverage and hesitancy obtained by epidemiological survey of children born in 2017-2018, in Belo Horizonte and Sete Lagoas, Minas Gerais, Brazil.

OBJECTIVE: To describe vaccination coverage and hesitation for the basic children's schedule in Belo Horizonte and Sete Lagoas, Minas Gerais state, Brazil. METHODS: Population-based epidemiological surveys performed from 2020 to 2022, which estimated vaccine coverage by type of immunobiological product and full schedule (valid and ministered doses), according to socioeconomic strata; and reasons for vaccination hesitancy. RESULTS: Overall coverage with valid doses and vaccination hesitancy for at least one vaccine were, respectively, 50.2% (95%CI 44.1;56.2) and 1.6% (95%CI 0.9;2.7), in Belo Horizonte (n = 1,866), and 64.9% (95%CI 56.9;72.1) and 1.0% (95%CI 0.3;2.8), in Sete Lagoas (n = 451), with differences between socioeconomic strata. Fear of severe reactions was the main reason for vaccination hesitancy. CONCLUSION: Coverage was identified as being below recommended levels for most vaccines. Disinformation should be combated in order to avoid vaccination hesitancy. There is a pressing need to recover coverages, considering public health service access and socioeconomic disparities. MAIN RESULTS: Vaccination coverage of children up to 4 years old was 50.2% in Belo Horizonte, and 64.9% in Sete Lagoas. Fear of severe reactions and believing that vaccination against eradicated diseases is unnecessary were the main reasons for vaccination hesitancy. IMPLICATIONS FOR SERVICES: Recovery of high vaccination coverage among children, considering public health service access conditions and socioeconomic inequities. Acting on reasons for hesitancy that can assist in targeting actions. PERSPECTIVES: The multifactorial context of vaccination hesitancy demands the development of health education strategies to raise awareness about child immunization.

Racial inequalities in child vaccination and barriers to vaccination in Brazil among live births in 2017 and 2018: an analysis of a retrospective cohort of the first two years of life.

OBJECTIVE: To describe timely vaccination completion and obstacles in the first 24 months of life in Brazil, examining associations with maternal race/skin color. METHODS: Study participants were 37,801 children born in 2017 and 2018 included in the National Immunization Coverage Survey. We calculated prevalence and 95% confidence intervals for timely vaccine completeness and obstacles at 5, 12 and 24 months of life, according to maternal race/skin color. Associations were analyzed using logistic regression. RESULTS: 7.2% (95%CI 6.3;8.2) of mothers faced difficulties in taking their children to be vaccinated, and 23.4% (95%CI 21.7;25.1) were not vaccinated when taken. These proportions were 75% (95%CI 1.25;2.45) and 97% (95%CI 1.57;2.48) higher, respectively, among Black mothers. At least one vaccination was delayed among 49.9% (95%CI 47.8;51.9) and 61.1% (95%CI 59.2;63.0) of children by 5 and 12 months, respectively. These rates were higher among Black/mixed race mothers. CONCLUSION: There are racial inequalities in both the obstacles faced and in vaccination rates in Brazil. MAIN RESULTS: Marked racial inequalities were found in the obstacles to vaccination of children under 24 months in Brazil and to timely vaccination at 5 months and in the first year of life. IMPLICATIONS FOR SERVICES: Racial inequalities in the occurrence of vaccination shortcomings in health services, in the objective restrictions faced by families in taking their children to vaccination centers and in incomplete vaccination in a timely manner need to be addressed by the Brazilian National Health System. PERSPECTIVES: Equal public policies to address barriers to vaccination and qualification of health services need to be implemented. Studies need to deepen understanding of the structural determinants that lead to racial disparities.

Efficacy and safety of Butantan-DV in participants aged 2-59 years through an extended follow-up: results from a double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil.

BACKGROUND: A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. METHODS: In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2-59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18-59 years, 7-17 years, and 2-6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. FINDINGS: Of 16 363 participants assessed for eligibility, 16 235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10 259 participants) or placebo (5976 participants). 16 162 participants (Butantan-DV n=10 215; placebo n=5947) were included in the per-protocol population and 16 235 (Butantan-DV n=10 259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2-5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2-4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4-73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. INTERPRETATION: A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. FUNDING: Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Vaccination coverage and delay in vaccination of infants born in 2017 and 2018 in municipalities in the Southern region of Brazil: National Vaccination Coverage Survey 2020.

OBJECTIVE: To evaluate vaccination coverage and delay in vaccine dose administration in infants in six municipalities in the Southern region of Brazil. METHODOLOGY: National Vaccination Coverage Survey 2020, with infants born alive in 2017 and 2018, carried out from September 2020 to March 2022. Coverage of doses administered, doses administered on time and delay in dose administration were evaluated. RESULTS: For 4681 infants analyzed, coverage for vaccines recommended up to 24 months was 68.0% (95%CI 63.9;71.8%) for doses administered and 3.9% (95%CI 2.7%;5.7%) for doses administered on time. Delay time for the majority of late vaccinations was ≤ 3 months. For some boosters, 25% of vaccine administration was delayed by ≥ 6 months. CONCLUSION: In addition to tracking vaccine defaulters, strategies are needed to encourage compliance with the vaccination schedule at the recommended ages. MAIN RESULTS: Vaccination coverage for the set of vaccines recommended up to 24 months was 68.0% and 3.9% for on-time doses. Delay time for some doses exceeded six months in up to 25% of infants with delayed vaccination. IMPLICATIONS FOR SERVICES: Monitoring vaccine administration at the recommended ages is necessary, with the adoption of strategies that reinforce routine vaccination to prevent vaccination delays and abandonment. PERSPECTIVES: Primary care in surveillance and care for infants needs to reinforce actions to ensure timely vaccination. Studies to deepen knowledge of vaccination delay, determinants and strategies for their reduction are necessary.