Assessing the best time interval between doses in a two-dose vaccination regimen to reduce the number of deaths in an ongoing epidemic of SARS-CoV-2.

The SARS-CoV-2 pandemic is a major concern all over the world and, as vaccines became available at the end of 2020, optimal vaccination strategies were subjected to intense investigation. Considering their critical role in reducing disease burden, the increasing demand outpacing production, and that most currently approved vaccines follow a two-dose regimen, the cost-effectiveness of delaying the second dose to increment the coverage of the population receiving the first dose is often debated. Finding the best solution is complex due to the trade-off between vaccinating more people with lower level of protection and guaranteeing higher protection to a fewer number of individuals. Here we present a novel extended age-structured SEIR mathematical model that includes a two-dose vaccination schedule with a between-doses delay modelled through delay differential equations and linear optimization of vaccination rates. By maintaining the minimum stock of vaccines under a given production rate, we evaluate the dose interval that minimizes the number of deaths. We found that the best strategy depends on an interplay between the vaccine production rate and the relative efficacy of the first dose. In the scenario of low first-dose efficacy, it is always better to vaccinate the second dose as soon as possible, while for high first-dose efficacy, the best strategy of time window depends on the production rate and also on second-dose efficacy provided by each type of vaccine. We also found that the rate of spread of the infection does not affect significantly the thresholds of the best window, but is an important factor in the absolute number of total deaths. These conclusions point to the need to carefully take into account both vaccine characteristics and roll-out speed to optimize the outcome of vaccination strategies.

Epidemiology and molecular characterization of Neisseria lactamica carried in 11-19 years old students in Salvador, Brazil.

Neisseria lactamica is a nonpathogenic commensal bacterium that is potentially associated with the development of natural immunity against N. meningitidis. However, the genetic variation present in natural populations of N. lactamica has not been fully investigated. To better understand its epidemiology and genetic variation, we studied N. lactamica carriage in 1200 students aged 11-19 years old in Salvador, Brazil. The carriage prevalence was 4.5% (54/1200), with no statistical difference among sex and age, although we observed a trend towards higher carriage prevalence among 11-year-old individuals. Whole genome sequence analysis revealed a high genetic diversity among the isolates, with the presence of 32 different STs, 28 (87.5%) of which were new. A total of 21/50 (42%) isolates belonged to three different clonal complexes. While none of the isolates contained nadA or fHpb alleles, we detected 21 FetA variants, 20 NhbA variants and two variants of PorB. The data provide detailed information on circulating N. lactamica isolates in adolescents in Brazil and are complementary to studies in other countries.

Risk analysis for the reintroduction and transmission of measles in the post-elimination period in the Americas.

OBJECTIVE: To propose and test a model for analyzing municipalities' level of risk of reintroduction and transmission of the measles virus in the post-elimination period in the Americas. METHODS: An ecological-analytical study was conducted using data on the measles epidemic that occurred in 2013-2015 in northeastern Brazil. The variables for analysis were selected after an extensive review of scientific literature on the risk of importation of measles cases. A univariate analysis considering the presence or absence of confirmed cases of measles in 184 municipalities in the state of Ceará, Brazil, was carried out to evaluate the association between the dependent variable and 23 independent variables, grouped into four categories: 1) characteristics of the municipalities; 2) quality indicators for immunization programs and epidemiological surveillance; 3) organizational structure for the public health response; and 4) selected impact indicators. A P value < 0.05 was considered significant. All variables with P < 0.200 were analyzed using multivariate logistic regression. Based on the results, the municipalities were categorized by four levels of risk ("low," "medium," "high," and "very high"). RESULTS: The model sensitivity was 95% for concordance between municipalities classified as "high risk" and "very high risk" and those that had an epidemic between 2013 and 2015 in Ceará. Of the 38 municipalities that had an epidemic, 76% (29/38) were classified as "high risk" and "very high risk"; 146 municipalities did not report cases (P < 0.0002). CONCLUSIONS: Given the imminent risk of reintroduction of measles circulation in the post-elimination period in the Americas, this model may be useful in identifying areas at greater risk for reintroduction and continued transmission of measles. Knowledge of vulnerable areas could trigger appropriate surveillance and monitoring to prevent sustained transmission.

Rubella virus genotype 1G and echovirus 9 as etiologic agents of exanthematous diseases in Brazil: insights from phylogenetic analysis.

The aim of the present study was to identify the rubella virus (RV) and enterovirus (EV) genotypes detected during the Epidemiological Surveillance on Exanthematic Febrile Diseases (VIGIFEX) study and to perform phylogenetic analysis. Ten RV- and four EV-positive oropharyngeal samples isolated from cell culture were subjected to RT-PCR and sequencing. Genotype 1G and echovirus 9 (E-9) was identified in RV- and EV-positive samples, respectively. The RV 1G genotype has been persisting in Brazil since 2000-2001. No evidence of E-9 being involved in exanthematic illness in Brazil has been reported previously. Differential laboratory diagnosis is essential for management of rash and fever disease.

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.

Risks of low vaccination coverage and strategies to prevent the resurgence of vaccine-preventable diseases in infants in the COVID-19 pandemic scenario: recommendations for Latin America and the Caribbean by the group of experts on infant immunization for Latin America.

INTRODUCTION: The WHO 2030 Immunization Agenda (IA-2030) harmonizes immunization activity plans at community, national, regional and global levels. Additionally, medical societies play an important role. The Latin American Group of Experts on Infant Immunization, established in 2018, advises on the harmonization, update, and optimization of infant vaccination programs in Latin America and the Caribbean (LAC). In September 2021, 41 such experts from 13 LAC countries met to develop recommendations for increasing regional vaccination coverage to avoid the reemergence of vaccine-preventable diseases and/or the occurrence of outbreaks. AREAS COVERED: The following items were evaluated: (i) immunization challenges before and during the COVID-19 pandemic; (ii) the status of current immunization programs, particularly infant pertussis and polio vaccination; (iii) possible solutions for overcoming vaccination challenges and achieving regional vaccination coverage targets. EXPERT OPINION/COMMENTARY: Medical societies provide valuable recommendations to guide and update vaccination schedules. In the LAC region, possible strategies to achieve target vaccination rates include the use of combination vaccines, strengthening surveillance systems, improving school attendance, advancing vaccine education and confidence, striving for vaccination equity, widening operational capacity, creating strategic alliances, and strengthening the role of medical groups. It is hoped that these recommendations will be implemented in the LAC region.

Characteristics and clinical outcomes of COVID-19 in children: a hospital-based surveillance study in Latin America's hardest-hit city.

Background: In 2020, Brazil became the epicentre of the coronavirus disease (COVID-19) pandemic in Latin America, resulting in an unparalleled health catastrophe. Nevertheless, comprehensive clinical reports in Brazilian children are not available. Methods: This retrospective, hospital-based, active surveillance study was performed to identify paediatric patients with COVID-19 who presented at a private academic medical centre in a large urban area between March 2020 and March 2021. Clinical and demographic information was analysed for those requiring hospitalization, those with severe illness and those with clinical syndromes. Results: In total, 964 symptomatic cases were evaluated; of these, 17.7% required hospitalization, and 27.5% of hospitalized cases were classified as severe/critical. Acute bronchiolitis and pneumonia were the most common causes of hospitalization among the severe cases. Twenty-seven hospitalized children fulfilled the diagnostic criteria for multi-system inflammatory syndrome (median age 29 months; 85.2% cases were non-severe). A significant co-existing condition was present in 29% of hospitalized children. The risk of hospitalization was higher in children with at least one comorbidity, children aged <2 years and obese children. Increased risk of severe disease was described among those with leukopenia, leukocytosis or any significant comorbidity. No deaths occurred among the study population. Conclusion: Although most children with COVID-19 experienced mild disease, and no deaths occurred among the study population, a significant proportion of cases required hospitalization and developed severe illness. Obesity, young age, underlying comorbidity, leukopenia and leukocytosis were risk factors for hospitalization or severe disease.

Prevalence, Risk Factors and Vaccine Response against Hepatitis B in People Aged 50 Years or Older.

Universal immunization against hepatitis B has contributed to reducing incidence of the disease, but older individuals remain susceptible to acquiring the hepatitis B virus worldwide. Thus, this study aimed to investigate the epidemiology of HBV infection in individuals aged 50 years and over in central Brazil and to evaluate the immunogenicity of the monovalent vaccine against hepatitis B in this age group using two vaccine regimens. METHOD: Initially, a cross-sectional and analytical study was carried out to investigate the epidemiology of hepatitis B. Then, individuals without proof of vaccination for hepatitis B were recruited for a phase IV randomized and controlled clinical trial using two vaccine regimens: Intervention Regimen (IR) (three doses of 40 µg at months 0, 1 and 6) vs. Comparison Regimen (CR) (three doses of 20 µg at months 0, 1 and 6). RESULTS: The overall prevalence of exposure to HBV was 16.6% (95% CI: 14.0%-9.5%). In the clinical trial, statistical differences in protective titers were observed (p = 0.007; IR 96% vs. CR 86%) and the geometric mean of anti-HBs titers was higher in individuals who received the IR (518.2 mIU/mL vs. 260.2 mIU/mL). In addition, the proportion of high responders was higher among those who received the IR (65.3%). CONCLUSION: reinforced doses should be used in individuals aged 50 years or older to overcome the lower efficacy of the vaccine against hepatitis B.

Etiologies of rash and fever illnesses in Campinas, Brazil.

BACKGROUND: Few population-based studies of infectious etiologies of fever-rash illnesses have been conducted. This study reports on enhanced febrile-rash illness surveillance in Campinas, Brazil, a setting of low measles and rubella virus transmission. METHODS: Cases of febrile-rash illnesses in individuals aged <40 years that occurred during the period 1 May 2003-30 May 2004 were reported. Blood samples were collected for laboratory diagnostic confirmation, which included testing for adenovirus, dengue virus, Epstein-Barr virus (EBV), enterovirus, human herpes virus 6 (HHV6), measles virus, parvovirus-B19, Rickettsia rickettsii, rubella virus, and group A streptococci (GAS) infections. Notification rates were compared with the prestudy period. RESULTS: A total of 1248 cases were notified, of which 519 (42%) had laboratory diagnosis. Of these, HHV-6 (312 cases), EBV (66 cases), parvovirus (30 cases), rubella virus (30 cases), and GAS (30 cases) were the most frequent causes of infection. Only 10 rubella cases met the rubella clinical case definition currently in use. Notification rates were higher during the study than in the prestudy period (181 vs 52.3 cases per 100,000 population aged <40 years). CONCLUSIONS: Stimulating a passive surveillance system enhanced its sensitivity and resulted in additional rubella cases detected. In settings with rubella elimination goals, rubella testing may be considered for all cases of febrile-rash illness, regardless of suspected clinical diagnosis.

A case-control study to determine the effectiveness of a tetravalent dengue vaccine in the state of Paraná, Brazil.

Background: The Brazilian state of Paraná conducted a mass vaccination campaign against dengue with the tetravalent attenuated vaccine CYD-TDV. The campaign targeted thirty endemic municipalities. The objective of this study was to assess the effectiveness of CYD-TDV in preventing symptomatic virologically confirmed dengue cases according to specific age groups in five of the municipalities. Methods: A case-control study was carried out in the five most populous municipalities targeted by the vaccination, with a vaccine uptake of 25%. Symptomatic dengue cases were identified by the municipal health departments. The age groups targeted were 15-18 and 19-27 in four municipalities and 9-14 and 28-44 in one municipality. All cases were confirmed by real time reverse transcription quantitative polymerase chain reaction (RT-qPCR). For each case, two controls were selected: a neighbourhood control and a workplace or school/college control, matched by age group. A conditional logistic regression model was used to determine the odds ratio for vaccination and the vaccine effectiveness. Findings: Study participants included 618 RT-qPCR-confirmed dengue cases and 1,236 matched controls (with a non-reactive dengue IgM serologic test). Vaccine effectiveness against dengue due to any serotype was 11·1% (95% CI: -19·0%; 33·6%). Effectiveness against DENV-1 was 33·3% (95% CI: -5·0%; 57·6%) and against DENV-2 was -56·7% (95% CI: -142·2%; -5·0%). No DENV-3 was detected. The vaccine was significantly effective in the prevention of DENV-4 cases (VE = 93·3%; 95% CI: 47·7%; 99·2%). Interpretation: CYD-TDV was effective in the prevention of symptomatic cases due to DENV-4, but not due to any serotype. The low dengue seroprevalence in the target population could possibly be related to these results. Funding: This study was supported through a grant to the Sabin Vaccine Institute from Sanofi-Pasteur. Sanofi-Pasteur had no role in the study design, protocol development, data collection, analysis, or publication of results.

Emergence of Neisseria meningitidis W South American sublineage strain variant in Brazil: disease and carriage.

Introduction. Invasive meningococcal disease is a major health problem, impacting morbidity and mortality worldwide. Exploratory genomics has revealed insights into adaptation, transmissibility and virulence to elucidate endemic, outbreaks or epidemics caused by Neisseria meningitidis serogroup W (MenW) strains.Gap Statement. Limited information on the genomics of Neisseria meningitis serogroup W ST11/cc11 is available from emerging countries, especially in contemporary isolates.Aim. To (i) describe the antigenic diversity and distribution of genetic lineages of N. meningitidis serogroup W circulating in Brazil; (ii) study the carriage prevalence of hypervirulent clones in adolescents students and (iii) analyse the potential risk factors for meningococcal carriage.Methodology. Using whole-genome sequencing, we analysed the genomic diversity of 92 invasive N. meningitidis serogroup W isolates circulating in Brazil from 2016 to 2019. A cross-sectional survey of meningococcal carriage was conducted in 2019, in the city of Florianópolis, Brazil, among a representative sample of 538 students.Results. A predominance (58.5 %, 41/82) of ST11/cc11 presenting PorB2-144, PorA VR1-5, VR2-2, FetA 1-1, and a novel fHbp peptide 1241 was found on invasive N. meningitidis W isolates, on the other hand, a high diversity of clonal complexes was found among carriage isolates. The overall carriage rate was 7.5 % (40/538). A total of 28 of 538 swab samples collected were culture positive for N. meningitidis, including four serogroup/genogroup B isolates (14.8 %;4/27), 1 serogroup/genogroup Y isolate (3.7 %;1/27), 22 (81.5 %; 22/27) non-groupable isolates. No MenW isolate was identified among carriages isolates.Conclusion. This report describes the emergence of the new MenW ST11/cc11 South America sublineage variant, named here, 2016 strain, carrying a novel fHbp peptide 1241, but its emergence, was not associated with an increased MenW carriage prevalence. Continuous surveillance is necessary to ascertain the role of this sublineage diversification and how its emergence can impact transmission.

Can living in the surroundings of a petrochemical complex be a risk factor for autoimmune thyroid disease?

BACKGROUND: Based on a suspicion raised by a health professional and due to a subsequent legal request, a cross-sectional study was made with a comparison group to investigate a possible excess of Hashimoto's thyroiditis-HT and antibodies-ATA in the surroundings of a Petrochemical Complex. METHODS: People of both sexes aged over 20 years were investigated in a random sample of residents in the area surrounding the Petrochemical Complex. Controls were investigated in an area with steel industries. In the areas searched, participants were chosen randomly and stratified a priori by sex and age group. As a result, 90.5% of the expected sample was obtained, totaling 1533 individuals. HT and ATA prevalences were compared by the chi-square test. Logistic regression was used to control the possible confounding factors for HT and ATA. RESULTS: Both TH (9.3%) and ATA (17.6%) prevalences were higher in the Petrochemical Complex area than in the control area (3.9% and 10.3%, respectively). After controlling the possible confounding factors, the POR for living in the surroundings of the Complex and presenting HT was 2.39 (CI95%: 1.42-4.03). According to the ATA criterion, the POR for living in the surroundings of the Complex was 1.78 (CI95%: 1.23-2.60). CONCLUSIONS: The authors have found higher prevalence and risk of developing thyroiditis and anti-thyroid antibodies among residents of areas surrounding the Petrochemical Complex and think these findings need to be further studied in similar areas.

Molecular characterization of Neisseria meningitidis isolates recovered from 11-19-year-old meningococcal carriers in Salvador, Brazil.

Characterization of meningococci isolated from the pharynx is essential towards understanding the dynamics of meningococcal carriage and disease. Meningococcal isolates, collected from adolescents resident in Salvador, Brazil during 2014, were characterized by multilocus sequence typing, genotyping or whole-genome sequencing. Most were nongroupable (61.0%), followed by genogroups B (11.9%) and Y (8.5%). We identified 34 different sequence types (STs), eight were new STs, distributed among 14 clonal complexes (cc), cc1136 represented 20.3% of the nongroupable isolates. The porA and fetA genotypes included P1.18,25-37 (11.9%), P1.18-1,3 (10.2%); F5-5 (23.7%), F4-66 (16.9%) and F1-7 (13.6%). The porB class 3 protein and the fHbp subfamily A (variants 2 and 3) genotypes were found in 93.0 and 71.0% of the isolates, respectively. NHBA was present in all isolates, and while most lacked NadA (94.9%), we detected the hyperinvasive lineages B:P1.19,15:F5-1:ST-639 (cc32); C:P1.22,14-6:F3-9:ST-3780 (cc103) and W:P1.5,2:F1-1:ST-11 (cc11). This is the first report on the genetic diversity and vaccine antigen prevalence among N. meningitidis carriage isolates in the Northeast of Brazil. This study highlights the need for ongoing characterization of meningococcal isolates following the introduction of vaccines and for determining public health intervention strategies.

Meningococcal Carriage among Adolescents after Mass Meningococcal C Conjugate Vaccination Campaigns in Salvador, Brazil.

Neisseria meningitidis is a commensal bacterium of the human nasopharynx. In rare cases, it penetrates the mucosa, entering the blood stream and causing various forms of disease. Meningococcal conjugate vaccines can prevent invasive disease not only by direct effect in vaccinated individuals but also by herd protection, preventing acquisition of carriage, which interrupts transmission and leads to protection of unvaccinated persons. In 2010 in Salvador, Brazil, an outbreak of group C meningococcal disease led to a mass meningococcal serogroup C conjugate vaccination drive, targeting those <5 and 10-24 years of age. The present study aimed to estimate the prevalence of and identify factors associated with N. meningitidis carriage among adolescents from Salvador, Brazil, in the post-vaccination period. In spring 2014, we performed a cross-sectional study involving 1,200 public school students aged 11-19 years old. Oropharyngeal swabs were collected to identify N. meningitidis. Of the 59 colonized participants, 36 (61.0%) carried non-groupable N. meningitidis, while genogroup B (11.9%), Y (8.5%), E (6.8%), Z (5.1%), C (3.4%), and W (3.4%) were also detected. The overall prevalence of N. meningitidis carriage was 4.9% (95% confidence interval [CI], 3.6-6.1%); the prevalence of N. meningitidis genogroup C was 0.17% (95% CI, 0.0-0.40%). There was no difference by age. Factors associated with carriage were having only one, shared, bedroom in the household (PR, 2.02; 95% CI, 0.99-4.12, p = 0.05); the mother being the only smoker in the home (PR, 2.48; 95% CI, 1.16-5.29; p = 0.01); and going to pubs/parties more than 5 times/month (PR, 2.61; 95% CI, 1.38-4.92; p = 0.02). Our findings show that the N. meningitidis carriage rate in adolescents from Salvador, Bahia, is low and is potentially influenced by the low prevalence of N. meningitidis genogroup C. However, continued surveillance is important to identify changes in the dynamics of N. meningitidis, including the emergence of diseases due to a non-C serogroup.

[Meningococcal disease in São Paulo, Brazil, in the 20th century: epidemiological characteristics]. / A doença meningocócica em São Paulo, Brasil, no século XX: características epidemiológicas.

This study analyzes the epidemiological behavior of meningococcal disease in the city of São Paulo, Brazil, over the course of the 20th century. Applying data from patient records, death certificates, and epidemiological surveillance, the authors describe trends in the disease throughout the century, seasonal variations, and incidence distribution by area, age, and gender. The temporal trends show constant incidence during endemic periods, interrupted by epidemic events. Four epidemic events during the last century occurred in circumstances of serious social disturbances and were caused by serogroups A (the first two), A and C, and B and C, respectively. Seasonal variations involved aggravation during autumn and winter throughout the entire century. Geographic distribution followed the displacement of the poor population in the urban territory. Age and gender distribution remained unaltered during all the endemic periods, showing an increased risk associated with younger age. The epidemic periods (except for the last) showed major alterations in age and gender distribution, with an increased risk among young people and youth adults and occurrence in all age brackets.

Indirect cohort analysis of 10-valent pneumococcal conjugate vaccine effectiveness against vaccine-type and vaccine-related invasive pneumococcal disease.

We applied the indirect cohort method to estimate effectiveness of 10-valent pneumococcal conjugate vaccine (PCV10) among young children in Brazil. Cases of invasive pneumococcal disease (IPD), i.e., Streptococcus pneumoniae, detected in normally sterile fluid identified through laboratory-based surveillance and previously enrolled in a matched case-control effectiveness study are included. We estimated PCV10 effectiveness using multivariable logistic regression comparing PCV10 vaccination among children with vaccine-type or vaccine-related IPD vs. children with non-vaccine-type disease. The adjusted effectiveness of ≥ 1 doses against vaccine-type (72.8%, 95% confidence interval [CI] [44.1, 86.7]) and vaccine-related (61.3%, 95%CI [14.5, 82.5]) IPD were similar to the effectiveness observed in the original case-control study (which required enrollment >1200 controls). We also found significant protection of ≥ 1 dose against individual vaccine serotypes (14, 6B, 23F, 18C) and against vaccine-related serotype 19A. The indirect cohort methods leverages existing surveillance is a feasible approach for evaluating pneumococcal conjugate vaccines, particularly in resource-limited settings.

Effectiveness of ten-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in Brazil: a matched case-control study.

BACKGROUND: In March 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10), which was licensed based on non-inferiority of immunological correlates of protection compared with the seven-valent vaccine. The schedule comprised three primary doses at ages 2 months, 4 months, and 6 months, and a booster dose at age 12 months. A single catch-up dose was offered for children aged 12-23 months at the time of introduction. We assessed PCV10 effectiveness against invasive pneumococcal disease in Brazilian children. METHODS: Invasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid, or another normally sterile site, was identified in children age-eligible for at least one PCV10 dose through laboratory-based and hospital-based surveillance in ten states in Brazil from March 1, 2010, until Dec 31, 2012. We aimed to identify four age-matched and neighbourhood-matched controls for each case. We used conditional logistic regression and calculated PCV10 effectiveness as (1-adjusted matched odds ratio) × 100% for vaccine-type and vaccine-related serotypes (ie, in the same serogroup as a vaccine serotype). FINDINGS: In 316 cases (median age 13·2 months, range 2·6-53·1) and 1219 controls (13·3 months, 2·6-53·1), the adjusted effectiveness of an age-appropriate PCV10 schedule was 83·8% (95% CI 65·9-92·3) against vaccine serotypes, and 77·9% (41·0-91·7) against vaccine-related serotypes. Serotype-specific effectiveness was shown for the two most common vaccine serotypes-14 (87·7%, 60·8-96·1) and 6B (82·8%, 23·8-96·1)-and serotype 19A (82·2%, 10·7-96·4), a serotype related to vaccine serotype 19F. A single catch-up dose in children aged 12-23 months was effective against vaccine-type disease (68·0%, 17·6-87·6). No significant effectiveness was shown against non-vaccine serotypes for age-appropriate or catch-up schedules. INTERPRETATION: In the routine immunisation programme in Brazil, PCV10 prevents invasive disease caused by vaccine serotypes. PCV10 might provide cross-protection against some vaccine-related serotypes. FUNDING: Brazilian Ministry of Health, Pan-American Health Organization, and US Centers for Disease Control and Prevention.

Sources of pertussis infection in young babies from São Paulo State, Brazil.

Household contacts are important sources of Bordetella pertussis in infants. A total of 353 household contacts of 97 index cases were evaluated for pertussis by culture and polymerase chain reaction. Twenty eight contacts were positive (8.0%). The presence of symptoms did not influence the rate of diagnosed bacteriologic pertussis in communicants. We conclude that contacts with an index case can be positive for B. pertussis independently of the presence of symptoms.

Uptake of oral rotavirus vaccine and timeliness of routine immunization in Brazil's National Immunization Program.

INTRODUCTION: In March, 2006, oral rotavirus vaccine was added to Brazil's infant immunization schedule with recommended upper age limits for initiating (by age 14 weeks) and completing (by age 24 weeks) the two-dose series to minimize age-specific risk of intussusception following rotavirus vaccination. Several years after introduction, estimated coverage with rotavirus vaccine (83%) was lower compared to coverage for other recommended childhood immunizations (≥94%). METHODS: We analyzed data from Brazil's national immunization program on uptake of oral rotavirus vaccine by geographic region and compared administrative coverage estimates for first and second doses of oral rotavirus vaccine (Rota1 and Rota2) with first and second doses of diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP-Hib1 and DTP-Hib2). For 27 Brazilian cities, we compared differences between estimated rotavirus and DTP-Hib coverage in 2010 with delayed receipt of DTP-Hib vaccine among a cohort of children surveyed before rotavirus introduction. RESULTS: In 2010, infant vaccination coverage was 99.0% for DTP-Hib1 versus 95.2% for Rota1 (3.8% difference), and 98.4% for DTP-Hib2 versus 83.0% for Rota2 (15.4% difference), with substantial regional variation. Differences between DTP-Hib and rotavirus vaccination coverage in Brazilian cities correlated with delay in DTP-Hib vaccination among children surveyed. Age restrictions for initiating and completing the rotavirus vaccination series likely contributed to lower coverage with rotavirus vaccine in Brazil. CONCLUSION: To maximize benefits of rotavirus vaccination, strategies are needed to improve timeliness of routine immunizations; monitoring rotavirus vaccine uptake and intussusception risk is needed to guide further recommendations for rotavirus vaccination.

The current situation of meningococcal disease in Latin America and recommendations for a new case definition from the Global Meningococcal Initiative.

The Global Meningococcal Initiative (GMI) is an international group of scientists and clinicians with expertise in meningococcal disease (MD). It promotes MD prevention through education and research. Given geographic differences in disease epidemiology, prevention strategies (e.g., vaccination) should be country-specific to ensure local needs are met. However, regional policies/recommendations and standardized disease diagnostic criteria should be implemented to improve surveillance and control strategies, and allow for more robust data comparisons. Consequently, the GMI convened a meeting with Latin American representatives to discuss the burden of MD and vaccination practices/policies, and consider if the global GMI recommendations could be tailored. The group determined that as robust, uniform epidemiologic data are required to make informed health-policy decisions, it would be useful to first summarize the regional situation herein (including disease surveillance, case definitions, epidemiology, vaccination and outbreak control strategies) and then determine a consensus-based meningococcal case definition for use throughout the region.