Meningococcal carriage is a prerequisite for invasive infection. This cross-sectional study assessed the pharyngeal carriage prevalence in healthy subjects aged 1-24 years in Embu das Artes city, São Paulo, Brazil. Pharyngeal swabs were examined for the presence of Neisseria meningitidis. The isolates were tested for different serogroups using agglutination and polymerase chain reaction. A logistic regression model assessed any independent association between Neisseria meningitidis carriage and various risk factors. A total of 87/967 subjects (9%, 95% Confidence Interval (CI): 7.3-11.0) tested positive for N. meningitidis: 6.2% (95% CI: 3.8-9.4) in 1-4 years, 8.5% (95% CI: 5.1-13.0) in 5-9 years, 12.5% (95% CI: 7.8-18.6) in 10-14 years, 12.6% (95% CI: 7.4-19.7) in 15-19 years and 9% (95% CI: 4.9-14.9) in 20-24 years age groups. Highest carriage prevalence was observed in adolescents 10-19 years old. Serogroup C was predominant (18.4%) followed by serogroup B (12.6%). The 15-19 years age group showed a significant association between number of household members and carriers of N. meningitidis. This cross-sectional study is the first in Brazil to evaluate meningococcal carriage prevalence and associated factors in a wide age range.

Background: Rotavirus (RV) vaccine, Rotarix, was introduced into the Brazil national immunization program in 2006. To estimate population-level vaccine effect, we conducted a time-trend analysis on all-cause gastroenteritis (GE)-related death certificate-reported deaths (DCRDs), hospital deaths (HDs) and hospitalizations trends in <5-year-olds before and after RV vaccine introduction.Methods: National level all-cause GE-related death certificate [Mortality Information System] and admission (Hospital Information System) data were aggregated and analyzed. Negative-binomial regression models (adjusting for age, year and region) compared DCRDs, HDs and hospitalization trends in <5-year-olds between baseline (2001-2005) and postvaccine introduction periods (Mortality Information System: 2007-2009 and Hospital Information System: 2007-2010). Negative-binomial regression models were fitted to data for each outcome before 2006, and the predicted annual frequencies of each outcome were plotted against corresponding observed annual frequencies.Results: During the postvaccine introduction period, there was an overall age-independent GE-related DCRDs reduction (20.9%, P = 0.04) observed in children < 5 years of age; a reduction was also seen in infants < 1 year of age (20.8%, P = 0.003). Age-independent GE-related HDs and hospitalizations reductions (57.1%, P < 0.0001 and 26.6%, P < 0.0001, respectively) were observed in < 5-year-olds; HDs reductions were also observed for each age group (< 1-year-olds: 55.0%, P < 0.0001 and 1- to < 5-year-olds: 59.5%, P < 0.0001). Observed annual frequencies of GE-related DCRDs, HDs and hospitalizations were lower than the predicted value in each age group in all years after 2006.Conclusions: GE-related DCRDs, HDs and hospitalizations were significantly reduced in < 1 and in 1- to <5-year-old Brazilian children after Rotarix introduction, which provides additional evidence of the direct and indirect population-level effect of RV vaccination on GE-related mortality and morbidity in children.

The monovalent human rotavirus (RV) vaccine, RIX4414 (Rotarix™, GlaxoSmithKline Biologicals) was introduced into Brazil's Expanded Program on Immunization in March 2006. One year after vaccine introduction, the G2P[4] strain was found to be predominant, with an apparent extinction of many non‐G2 strains. This study investigated the diversity of circulating strains in the three years following RIX4414 introduction. Between May 2008 and May 2011, stool samples were collected from children aged ≥12 weeks who were hospitalized for severe lab confirmed RV‐gastroenteritis (≥3 liquid or semi‐liquid motions over a 24‐h period for <14 days, requiring ≥1 overnight hospital stay and intravenous rehydration therapy) in Belém, Brazil. RV‐gastroenteritis was detected by ELISA and the G‐ and P‐types were determined by RT‐PCR assays. During the first year of surveillance nucleotide sequencing was used for typing those samples not previously typed by RT‐PCR. A total of 1,726 of 10,030 severe gastroentertis hospitalizations (17.2%) were due to severe RVGE. G2P[4] was detected in 57.2% of circulating strains over the whole study period, however it predominated during the first 20 months from May 2008 to January 2009. G1P[8] increased in the last part of the study period from May 2010 to May 2011 and represented 36.6% (112/306) of the circulating strains. G2P[4] was the predominant RV strain circulating during the first 20 months of the study, followed by G1P[8]. These findings probably reflect a natural fluctuation in RV strains over time, rather than a vaccine‐induced selective pressure. J. Med. Virol. 87:1303–1310, 2015. © 2015 Wiley Periodicals, Inc.

Data on the burden of disease and circulation patterns of influenza B lineages for Brazil are limited. This review aims to describe the pattern of influenza B occurrence in Brazil to have a better understanding of its epidemiology and its relevance when considering seasonal influenza vaccine composition. A review of the data including analysis of international and local surveillance data as well as information from online search of databases using Medical Subject Headings terms in conjunction with screening of abstracts from scientific events was performed. Based on international epidemiologic surveillance data, moderate levels of influenza B disease (19%; 2006-2014) were observed. Of these nine years, it was possible to compare data from three years (2007, 2008 and 2013) which have information on the circulating influenza B lineage. Co-circulation of influenza B lineages was observed in all these three influenza seasons, of which, during one season, a high degree of mismatch between the vaccine lineage and the predominant circulating lineage (91.4% [2013]) was observed. Local surveillance data reveal a distinct and dynamic distribution of respiratory viruses over the years. Data from published literature and abstracts show that influenza B is a significant cause of disease with an unpredictable circulation pattern and showing trends indicating reemergence of the B/Victoria lineage. The abstracts report notable levels of co-circulation of both influenza B lineages (2000-2013). Mismatch between the Southern hemisphere vaccine and the most prevalent circulating viruses in Brazil were observed in five influenza seasons. The evidence on co-circulation of two influenza B lineages and mismatched seasons in Brazil indicates the benefit of quadrivalent influenza vaccines in conferring broader seasonal influenza protection. Additionally, improving influenza surveillance platforms in Brazil is important for monitoring disease trends and the impact of introducing seasonal influenza vaccination.

Background: Recent studies have shown an excess of chronic kidney disease (CKD) among younger adult males in the Pacific coastal region of Nicaragua and suggest a non-conventional CKD etiology in this region. These studies have been conducted in small, non-representative populations. Objectives: We conducted a large population-based cross-sectional study to estimate CKD prevalence in León, Nicaragua, and to evaluate the association between previously investigated risk factors and CKD. Methods: Estimated glomerular filtration rate, derived using the MDRD equation, was assessed to determine CKD status of 2275 León residents. Multivariable logistic regression was used to estimate adjusted prevalence odds ratios. León CKD prevalence was also standardized to the demographic distributions of the León Health and Demographic Surveillance System and the León 2005 Census. Results: CKD prevalence was 9.1%; twice as high for males (13.8%) than females (5.8%). In addition to gender, older age, rural zone, lower education level, and self-reported high blood pressure, more years of agricultural work, lija (unregulated alcohol) consumption, and higher levels of daily water consumption were significantly associated with CKD. Notably, self-reported diabetes was associated with CKD in adjusted models for females but not males. Conclusions: Our findings are comparable to those found in regional studies and further support the hypothesis of a Mesoamerican Nephropathy.

Abstract Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009). This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010–2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3–59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction). Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥2 PCV7 doses or ≥1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction. Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage.

To the Editors: Velásquez and colleagues1 show in a large Mexican cohort study that there is a small but finite risk of intussusception (IS) associated with the first dose of human rotavirus vaccine (Rotarix; GlaxoSmithKline Biologicals, Rixensart, Belgium). The number of additional cases of IS attributable to Rotarix vaccination was estimated at approximately 2 per 100,000 infants vaccinated, which is somewhat less than what was estimated for RotaShield (Wyeth, New York, NY) vaccine before its withdrawal. A study from Australia also identified a risk of similar magnitude after the first dose of both Rotarix and RotaTeq (Merck, Whitehouse Station, NJ) vaccines.2 While, unlike Mexico, the risk of IS after Rotarix could not be detected in Brazil,1 and a recent report from the United States found no increased risk for IS after RotaTeq,3 it would seem that there is no smoke without the fire. A low risk of IS is associated with the administration of the first dose of both currently licensed live oral rotavirus vaccines. Velázquez and colleagues argue that despite the small risk of IS the risk–benefit ratio remains very much in favor of universal rotavirus vaccination program because a considerable number of rotavirus-associated deaths are prevented by the vaccine.1 This is certainly true for Mexico and many other countries, but is not sufficient to convince some developed countries with little or no mortality from rotavirus that have not yet introduced a rotavirus vaccination program and view the risk of IS as a potential concern. Rather, the critical question is what can be done to reduce the risk of rotavirus vaccine–associated risk of IS, and an obvious issue is the age at the time of administration of the first dose of vaccine. The background for the importance of age lies with the RotaShield experience. According to Simonsen and colleagues, there were no cases of IS in infants vaccinated between 30 and 59 days of age (denominator 69.123), 9 cases in infants vaccinated between 60 and 89 days of age (denominator 197.144), but a much higher number and 3–4 times higher rate of cases among infants who participated in the catch-up program and received their first dose of RotaShield vaccine between ages of 90 and 159 days.4 A plausible assumption is that the lower risk of IS associated with the current live oral rotavirus vaccines would follow a similar pattern for age. In fact, a recent report from Germany has found just that an increased risk of IS was observed in infants who received the first dose of rotavirus vaccine, either RotaTeq or Rotarix, between ages 90–179 days, but not in infants less than 89 days of age at the time of vaccine administration.5 Velázquez and colleagues mention the age issue only in passing, and note that an exploratory analysis showed no increased risk of IS in infants who received the first dose after 14 weeks of age as compared with those at 14 weeks or less. They also mention that only 18.2% of IS cases were among infants who received the first dose after the recommended limit of 16 weeks of age,4 but do not report what percentage of all children received the first dose of Rotarix after the age of 16 weeks. A further question is where this “recommended” upper age limit of 16 weeks comes from. In the prelicensure trials of Rotarix (and RotaTeq), the first dose of vaccine was administered strictly between ages 6 and 12 weeks. This age range is also the still existing recommendation in the ESPID/ESPGHAN Evidence-based Recommendations for Rotavirus Vaccination in Europe.6 Many other recommendations have extended the upper age of the first dose to later than 12 weeks, but this has been done for programmatic reasons or to increase sales, without scientific evidence of safety. The latest, and worst, extension is the recent recommendation of the World Health Organization that virtually removes the upper age.7 Although many, and perhaps even most, cases of IS in Mexico happened in infants vaccinated within the age bracket of 6–12 weeks, it does not mean that the risk of IS could not be reduced by strictly following the original age recommendation. As shown by Oberle and colleagues, this alone should be sufficient to control rotavirus vaccine–associated IS in Europe.5 Consequently, all recommendation issuing bodies should unequivocally recommend the administration of the first dose of rotavirus vaccine between ages 6 and 12 weeks, or, even better, as early as possible within this age bracket. The second step, in the future, for further reduction of the risk of IS should be decreasing the lower age of the first dose to neonatal age. Neonatal dosing might be optimal for safety (for IS) without compromising efficacy, as shown by immunogenicity studies of RotaShield8 and efficacy studies of bovine rotavirus vaccine in the past.9 Neonatal studies are urgently needed for the currently licensed live oral rotavirus vaccines. Timo Vesikari, MD University of Tampere Vaccine Research Center Tampere, Finland

Objective Influenza causes severe morbidity and mortality. This systematic review aimed to assess the incidence, etiology, and resource usage for influenza in Latin America and the Caribbean.Design Meta-analytic systematic review. Arcsine transformations and DerSimonian Laird random effects model were used for meta-analyses.Setting A literature search from 1980 to 2008 in MEDLINE, Cochrane Library, EMBASE, LILACS, Ministries of Health, PAHO, proceedings, reference lists, and consulting experts.Sample We identified 1092 references, of which 31 were finally included, in addition to influenza surveillance reports. We also used information from the 10 reports from the collaborative group for epidemiological surveillance of influenza and other respiratory virus (GROG), and information retrieved from the WHO global flu database FLUNET.Main outcome measures Incidence, percentage of influenza specimens out of the total received by influenza centers and resource-use outcomes.Results A total of 483 130 specimens of patients with influenza were analyzed. Meta-analysis showed an annual rate of 36 080 (95% CI 28 550 43 610) influenza-like illness per 100 000 persons-years. The percentage of influenza out of total specimens received by influenza centers ranged between 4.66% and 15.42%, with type A the most prevalent, and A subtype H3 predominating. The mean length of stay at hospital due to influenza ranged between 5.8 12.9 days, total workdays lost due to influenza-like illnesses were 17150 days, and the mean direct cost of hospitalization was US$575 per laboratory-confirmed influenza case.Conclusions Our data show that seasonal influenza imposes a high morbidity and economic burden to the region. However, the vaccine-uptake rate has been low in this region. Population-based cohort studies are required to improve the knowledge about incidence and resource utilization, which would inform healthcare authorities for decision making.

Background: This systematic review evaluated the incidence, etiology, and use of resources in bacterial, non-tuberculosis community-acquired pneumonia (CAP) in immune-competent children aged < 5 years.Methods: Systematic searches (1980-2008) were performed using MEDLINE, Cochrane Library, EMBASE, LILACS, generic, and academic Internet searches. Regional health ministries, the Pan American Health Organization (PAHO), regional proceedings, doctoral theses, and the reference lists of included studies were also searched, and experts were consulted. Arcsine transformations and the DerSimonian-Laird random-effects model were used for proportion meta-analyses.Results: The search yielded 1220 references; 60 were included in the meta-analysis, giving a total 23 854 CAP episodes with an incidence of 919/100 000 child-years in children aged < 5 years. Streptococcus pneumoniae was the most frequently isolated agent (11.08%; 95% confidence interval (CI) 7.63 15.08), and pneumococcal serotype 14 was most prevalent (33.00%; 95% CI 25.95-40.45). Other common agents were Haemophilus influenzae and Mycoplasma pneumoniae. Health economics data on CAP in the region were scarce. About one-fourth of CAP patients required hospitalization (median length of stay 11 days, range 5-13.5 days).Conclusions: The burden of CAP was substantial, with S. pneumoniae, H. influenzae, and M. pneumoniae being the most common pathogens identified. High quality primary studies on disease incidence, use of health resources, and standardized data collection on disease burden and circulating strains are essential to provide baseline data for the future evaluation of vaccine impact. (C) 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Background: Pneumococcal conjugate vaccines (PCVs) are in the process of implementation in Latin America. Experience in developed countries has shown that they reduce the incidence of invasive and non-invasive disease. However, there is evidence that the introduction of PCVs in universal mass vaccination programs, combined with inappropriate and extensive use of antibiotics, could be associated to changes in non-PCV serotypes, including serotype 19A. We conducted a systematic review to determine the distribution of serotype 19A, burden of pneumococcal disease and antibiotic resistance in the region.Methods: We performed a systematic review of serotype 19A data from observational and randomized clinical studies in the region, conducted between 1990 and 2010, for children under 6 years. Pooled prevalence estimates from surveillance activities with confidence intervals were calculated.Results: We included 100 studies in 22 countries and extracted data from 63. These data reported 19733 serotyped invasive pneumococcal isolates, 3.8% of which were serotype 19A. Serotype 19A isolates were responsible for 2.4% acute otitis media episodes, and accounted for 4.1% and 4.4% of 4,380 nasopharyngeal isolates from healthy children and in hospital-based/sick children, respectively. This serotype was stable over the twenty years of surveillance in the region. A total of 53.7% Spn19A isolates from meningitis cases and only 14% from non meningitis were resistant to penicillin.Conclusions: Before widespread PCV implementation in this region, serotype 19A was responsible for a relatively small number of pneumococcal disease cases. With increased use of PCVs and a greater number of serotypes included, monitoring S. pneumoniae serotype distribution will be essential for understanding the epidemiology of pneumococcal disease.

Rotavirus (RV) is the leading cause of severe gastroenteritis (GE) among infants and young children worldwide, accounting for 453,000 deaths in children aged <5years. In Latin America rotavirus causes an estimated 15,000 deaths annually and accounts for 20–70% of acute gastroenteritis cases requiring hospitalization. This results in an estimated annual cost of approximately US$86 million. The most common G type has been G1 (∼50%), followed by G4, G3 and G9, although regional and temporal variations are significant. There are currently two effective rotavirus vaccines: a single-strain, human attenuated-based (RotarixTM, GlaxoSmithKline Biologicals), and a five-strain, bovine-human reassortant vaccine (RotaTeqTM, Merck and Company). The pioneering strategy behind the development and licensure of RotarixTM was part of a new paradigm for global vaccine research and development focusing on introduction first in countries with greatest medical needs. Rotarix™ demonstrated high efficacy and a good safety profile in Phase II and III clinical trials performed in Latin America. In the pivotal phase III study involving 11 Latin American countries a 2-year efficacy of 81% (95% CI: 71–87) was achieved against severe rotavirus acute gastroenteritis. A high protective efficacy was observed against severe rotavirus gastroenteritis caused by G1 and non-G1 strains. RotarixTM proved to be safe regarding intussusception (IS) in a two-dose vaccine schedule beginning at 6–12weeks of age.

Background: Non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae are major causes of bacterial acute otitis media (AOM). Data regarding AOM are limited in Latin America. This is the first active surveillance in a private setting in Venezuela to characterize the bacterial etiology of AOM in children < 5 years of age.Methods: Between December 2008 and December 2009, 91 AOM episodes (including sporadic, recurrent and treatment failures) were studied in 87 children enrolled into a medical center in Caracas, Venezuela. Middle ear fluid samples were collected either by tympanocentesis or spontaneous otorrhea swab sampling method. Standard laboratory and microbiological techniques were used to identify bacteria and test for antimicrobial resistance. The results were interpreted according to Clinical Laboratory Standards Institute (CLSI) 2009 for non-meningitis isolates. All statistical analyses were performed using SAS 9.1 and Microsoft Excel (for graphical purposes).Results: Overall, bacteria were cultured from 69.2% (63 of the 91 episodes); at least one pathogen (S. pneumoniae, H. influenzae, S. pyogenes or M. catarrhalis) was cultured from 65.9% (60/91) of episodes. H. influenzae (55.5%; 35/63 episodes) and S. pneumoniae (34.9%; 22/63 episodes) were the most frequently reported bacteria. Among H. influenzae isolates, 62.9% (22/35 episodes) were non-capsulated (NTHi) and 31.4% (11/35 episodes) were capsulated including types d, a, c and f, across all age groups. Low antibiotic resistance for H. influenzae was observed to amoxicillin/ampicillin (5.7%; 2/35 samples). NTHi was isolated in four of the six H. influenzae positive samples (66.7%) from recurrent episodes.Conclusions: We found H. influenzae and S. pneumoniae to be the main pathogens causing AOM in Venezuela. Pneumococcal conjugate vaccines with efficacy against these bacterial pathogens may have the potential to maximize protection against AOM.

The efficacy of licensed rotavirus vaccines has only been shown against certain rotavirus group A (RV-A) types. It is critical to understand the burden of rotavirus gastroenteritis (RVGE) and its prevalent types to assess the potential impact of these vaccines in Latin America and the Caribbean (LA&C). We performed a systematic review and meta-analyses of all the available evidence reported from 1990 to 2009 on the burden of rotavirus disease and strains circulating in LA&C. Eligible studies-185 country-level reports, 174 951 faecal samples-were selected from MEDLINE, Cochrane Library, EMBASE, LILACS, regional Ministries of Health, PAHO, regional proceedings, doctoral theses, reference lists of included studies and consulting experts. Arc-sine transformations and DerSimonian-Laird random-effects model were used for meta-analyses. The proportion of gastroenteritis cases due to rotavirus was 24.3% (95% CI 22.3-26.4) and the incidence of RVGE was 170 per 1000 children-years (95% CI 130-210). We estimated a global annual mortality for 22 countries of 88.2 (95% CI 79.3-97.1) deaths per 100 000 under 5 years (47 000 deaths). The most common G type detected was G1 (34.2%), followed by G9 (14.6%), and G2 (14.4%). The most common P types detected were P[8] (56.2%), P[4] (22.1%) and P[1] 5.4%, and the most prevalent P-G type associations were P[8]G1 17.9%, P[4]G2 9.1% and P[8]G9 8.8%. In the last 10 years, G9 circulation increased remarkably and G5 almost disappeared. More recently, G12 appeared and P[4]G2 re-emerged. To our knowledge, this is the first meta-analysis of rotavirus infection and burden of disease in LA&C. Copyright (C) 2011 John Wiley & Sons, Ltd.

BACKGROUND:Acute otitis media (AOM) is one of the most common childhood diseases requiring antimicrobial prescription in pre-school children. This systematic review aimed to estimate the AOM incidence, bacterial etiology and use of resources in children aged <6 years in Latin America and the Caribbean (LA&C). METHODS:A systematic search using keywords otitis or middle ear and inflammation was performed for articles published during 1988-2008 in MEDLINE, Cochrane Library, EMBASE, LILACS, generic and academic internet searches, Ministries of Health, PAHO, regional proceedings, reference lists and consulting experts. Pairs of reviewers independently selected articles and assessed their methodological quality with a checklist of essential items from the STROBE statement according to pre-specified criteria. Studies involving immune-competent children with AOM were considered. Arcsine transformations were used for proportion meta-analyses. RESULTS:Annual AOM incidence in four studies in children aged <5 years ranged from 1,171-36,000 episodes/100,000 children. Meta-analysis on etiology and pneumococcal serotypes included 18 studies and 125, 519 children with AOM from six LA&C countries. Meta-analysis per serotype showed that Streptococcus pneumoniae (32.4%; 95%CI=27.1-38.0%) and Haemophilus influenzae (26%; 95%CI=19.5-33.1%), including non-typeable H. influenzae (18.3%; 95%CI=9.5-33.1%) were the most prevalent. The most commonly observed pneumococcal serotype was 19F (24.0%; 95% CI 17.0-32.0%). Data on use of health resources were scarce. CONCLUSIONS:Streptococcus pneumoniae and H. influenzae were the most frequent AOM bacterial pathogens, consistent with the international literature from other regions. Future studies on AOM incidence and health resources usage will help better define the impact of this disease.