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.).

A critical analysis of serogroup B meningococcal disease burden in Brazil (2001-2015): implications for public health decisions.

The recent licensure of two different serogroup B recombinant protein meningococcal vaccines in Brazil emphasizes the importance of a better knowledge of the real burden of serogroup B meningococcal (MenB) disease to establish evidence-based vaccination policies. We performed an observational, descriptive study, from 2001 to 2015, analyzing the incidence and case fatality rates (CFR) of MenB disease in Brazil, according to age group and region. In the absence of any vaccine use targeting MenB disease, a significant decline of 90% in the overall incidence rates of MenB disease was observed (from 0.55 cases/100,000 habitants in 2001 to 0.05 in 2015), with declines found in all age groups during the study period. The highest incidence rates were consistently observed in infants and children 1-4 year of age, whereas adults ≥ 60 years experienced the highest CFR (33.9%). The proportion of cases with serogroup identified increased from 37.1% in 2001 to 51.5% in 2015. Despite an improvement in recent years, the quality of diagnosis is highly heterogeneous in the diverse regions, presenting important deficiencies that still prevent the possibility of a robust and reliable analysis of the burden of the meningococcal disease in Brazil. Based on the findings of this study and taking in account the unlikely indirect effect associated with the use of the new recombinant serogroup B protein vaccines, infants < 1 year is the age group to be prioritized when considering the implementation of routine immunization programmes with MenB vaccines.

Measles outbreak response decision-making under uncertainty: a retrospective analysis.

Resurgent outbreaks of vaccine-preventable diseases that have previously been controlled or eliminated have been observed in many settings. Reactive vaccination campaigns may successfully control outbreaks but must necessarily be implemented in the face of considerable uncertainty. Real-time surveillance may provide critical information about at-risk population and optimal vaccination targets, but may itself be limited by the specificity of disease confirmation. We propose an integrated modelling approach that synthesizes historical demographic and vaccination data with real-time outbreak surveillance via a dynamic transmission model and an age-specific disease confirmation model. We apply this framework to data from the 1996-1997 measles outbreak in São Paulo, Brazil. To simulate the information available to decision-makers, we truncated the surveillance data to what would have been available at 1 or 2 months prior to the realized interventions. We use the model, fitted to real-time observations, to evaluate the likelihood that candidate age-targeted interventions could control the outbreak. Using only data available prior to the interventions, we estimate that a significant excess of susceptible adults would prevent child-targeted campaigns from controlling the outbreak and that failing to account for age-specific confirmation rates would underestimate the importance of adult-targeted vaccination.

Prevalence, risk factors and molecular characteristics of meningococcal carriage among brazilian adolescents

BACKGROUND: In 2010, introduction of the meningococcal C conjugate vaccine in Brazil for children <2 years provided an immediate reduction in the incidence rates of disease among the age groups targeted for the vaccine, but no early impact was observed in unvaccinated age groups. Knowledge about meningococcal carriage is crucial for improving our understanding of the disease epidemiology and for designing effective vaccination programs. Taking in account the very limited published data currently available describing meningococcal carriage in Brazil, we performed a study to evaluate the prevalence of Neisseria meningitidis carriage among adolescent students. METHODS: A cross-sectional study was conducted in 2012 to assess the prevalence of meningococcal carriage among a representative sample of 1208 students 11­19 years of age in Campinas, Brazil. Genotypic and phenotypic characterization of isolated carriage strains and the effect of potential risk factors for carriage were also analyzed. Results: The overall carriage prevalence was 9.9% (95% confidence interval, 8.3­11.8%), with dominance of serogroup C (1.32%), followed by serogroups B (0.99%), E (0.74%), Y (0.49%) and W (0.25%). A lower level of education of the parents was independently associated with a higher risk of carriage. A high diversity of genotypes was found among carriage strains. CONCLUSIONS: The evidence gathered during this study provides estimates of carriage prevalence in Brazilian adolescents, showing an unusually high dominance of serogroup C. These results have important implications in future strategies to optimize the impact of the current meningococcal C vaccination program in Brazil

Prevalence, Risk Factors and Molecular Characteristics of Meningococcal Carriage Among Brazilian Adolescents.

BACKGROUND: In 2010, introduction of the meningococcal C conjugate vaccine in Brazil for children <2 years provided an immediate reduction in the incidence rates of disease among the age groups targeted for the vaccine, but no early impact was observed in unvaccinated age groups. Knowledge about meningococcal carriage is crucial for improving our understanding of the disease epidemiology and for designing effective vaccination programs. Taking in account the very limited published data currently available describing meningococcal carriage in Brazil, we performed a study to evaluate the prevalence of Neisseria meningitidis carriage among adolescent students. METHODS: A cross-sectional study was conducted in 2012 to assess the prevalence of meningococcal carriage among a representative sample of 1208 students 11-19 years of age in Campinas, Brazil. Genotypic and phenotypic characterization of isolated carriage strains and the effect of potential risk factors for carriage were also analyzed. RESULTS: The overall carriage prevalence was 9.9% (95% confidence interval, 8.3-11.8%), with dominance of serogroup C (1.32%), followed by serogroups B (0.99%), E (0.74%), Y (0.49%) and W (0.25%). A lower level of education of the parents was independently associated with a higher risk of carriage. A high diversity of genotypes was found among carriage strains. CONCLUSIONS: The evidence gathered during this study provides estimates of carriage prevalence in Brazilian adolescents, showing an unusually high dominance of serogroup C. These results have important implications in future strategies to optimize the impact of the current meningococcal C vaccination program in Brazil.

Carriage rate and effects of vaccination after outbreaks of serogroup C meningococcal disease, Brazil, 2010.

During 2010, outbreaks of serogroup C meningococcal (MenC) disease occurred in 2 oil refineries in São Paulo State, Brazil, leading to mass vaccination of employees at 1 refinery with a meningococcal polysaccharide A/C vaccine. A cross-sectional study was conducted to assess the prevalence of meningococci carriage among workers at both refineries and to investigate the effect of vaccination on and the risk factors for pharyngeal carriage of meningococci. Among the vaccinated and nonvaccinated workers, rates of overall meningococci carriage (21.4% and 21.6%, respectively) and of MenC carriage (6.3% and 4.9%, respectively) were similar. However, a MenC strain belonging to the sequence type103 complex predominated and was responsible for the increased incidence of meningococcal disease in Brazil. A low education level was associated with higher risk of meningococci carriage. Polysaccharide vaccination did not affect carriage or interrupt transmission of the epidemic strain. These findings will help inform future vaccination strategies.