A cross-sectional study assessing the pharyngeal carriage of Neisseria meningitidis in subjects aged 1­24 years in the city of Embu das Artes, São Paulo, Brazil

Meningococcal carriage is a prerequisite for invasive infection. This cross-sectional study assessed the pharyngeal carriage prevalence in healthy subjects aged 1­24 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): 7.3­11.0) tested positive for N. meningitidis: 6.2% (95% CI: 3.8­9.4) in 1­4 years, 8.5% (95% CI: 5.1­13.0) in 5­9 years, 12.5% (95% CI: 7.8­18.6) in 10­14 years, 12.6% (95% CI: 7.4­19.7) in 15­19 years and 9% (95% CI: 4.9­14.9) in 20­24 years age groups. Highest carriage prevalence was observed in adolescents 10­19 years old. Serogroup C was predominant (18.4%) followed by serogroup B (12.6%). The 15­19 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.

Post hoc analysis of reactogenicity trends between dose 1 and dose 2 of the adjuvanted recombinant zoster vaccine in two parallel randomized trials.

In two large clinical trials (ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]), two doses of the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster in adults ≥50 years of age. Solicited adverse events (AEs) were collected for 7 days post-each dose in a study sub-cohort. The incidence of reported solicited AEs was higher for RZV compared to placebo recipients. Since reactogenicity may contribute to a person's willingness to be vaccinated, knowing about expected reactogenicity might help keep high compliance with the second dose. This post hoc analysis assessed the intensity of solicited AEs post-dose 2 reported to the same event's intensity post-dose 1. Intensity was graded from 0 to 3, grade 3 indicating the highest severity. Of the vaccinees who did not experience a specific AE post-dose 1, 72.6-91.7% did not experience the same event after dose 2. Although the frequency of grade 3 AEs post-dose 2 was the highest in participants reporting the same AEs at grade 3 post-dose 1, 65.8-89.3% of vaccinees with grade 3 specific AEs post-dose 1 reported the same AEs at lower intensity post-dose 2. These data can help inform health-care professionals about the frequency and intensity of AEs post-dose 2 with respect to post-dose 1.

Efficacy of the adjuvanted recombinant zoster vaccine (RZV) by sex, geographic region, and geographic ancestry/ethnicity: A post-hoc analysis of the ZOE-50 and ZOE-70 randomized trials.

BACKGROUND: Herpes zoster (HZ) risk appears to vary by sex and geographic ancestry/ethnicity. METHODS: In 2 randomized clinical trials, participants received 2 doses of adjuvanted recombinant zoster vaccine (RZV) or placebo intramuscularly, 2 months apart. In this post-hoc analysis, we investigate efficacy of RZV against HZ and postherpetic neuralgia (PHN) by sex, geographic region, and geographic ancestry/ethnicity in ≥50-year-olds (ZOE-50: NCT01165177) and ≥70-year-olds (pooled data from ZOE-50 and ZOE-70: NCT01165229). RESULTS: Vaccine efficacy against HZ or PHN was similar in women and men. Across geographic regions, efficacy against HZ ranged between 95.7 and 97.2% in ≥50-year-olds, and between 87.3% and 95.1% in ≥70-year-olds; efficacy against PHN ranged between 86.8 and 100% in ≥70-year-olds. Across ancestral/ethnic groups, efficacy ranged between 88.1 and 100% against HZ and between 65.9 and 100% against PHN in ≥70-year-olds. CONCLUSIONS: While the ZOE-50/70 studies were not powered or pre-designed for these post-hoc analyses, RZV appears efficacious against HZ and PHN irrespective of sex, region, or geographic ancestry/ethnicity.

Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention.

INTRODUCTION: GSK has developed a two-dose adjuvanted recombinant zoster vaccine (Shingrix, RZV) to protect people aged ≥50 years (50+) against herpes zoster (HZ) and its complications. RZV showed >90% efficacy against HZ, sustained over 4 years of follow-up, in all studied age groups. AREAS COVERED: This article reviews the scientific rationale underlying the design of RZV; the clinical evidence demonstrating immunogenicity, safety, and efficacy in persons 50+; and the public health implications and cost-effectiveness. EXPERT COMMENTARY: A decline in varicella zoster virus (VZV) immunity is associated with increased risk of HZ in adults 50+ and immunocompromised individuals. RZV was designed to restore levels of anti-VZV cellular and humoral immunity to prevent VZV reactivation. RZV includes the recombinant gE glycoprotein antigen, and Adjuvant System AS01B which promotes cellular and antibody responses. In two Phase III studies in subjects aged 50+ and 70+ years, RZV efficacy against HZ compared to placebo was >90% and ≥89% against post-herpetic neuralgia (PHN). RZV is expected to dramatically impact HZ morbidity including its complications, and associated health-care costs. In the US population aged 50+ years, vaccination with RZV can be cost-effective compared to no vaccination and cost-saving compared to the currently available live-attenuated HZ vaccine (Zostavax, Merck).

A cross-sectional study assessing the pharyngeal carriage of Neisseria meningitidis in subjects aged 1-24 years in the city of Embu das Artes, São Paulo, Brazil

ABSTRACT 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.

Assessment of the potential public health impact of Herpes Zoster vaccination in Germany.

The aim of this study was to compare the public health impact of introducing 2 Herpes Zoster (HZ) vaccines, Zoster Vaccine Live (ZVL) versus a non-live adjuvanted subunit candidate vaccine (HZ/su), in the German population aged 50+ years split into 3 age cohorts, i.e. 50-59, 60-69 and 70+ years, respectively. A multi-cohort static Markov model was developed following age cohorts over their lifetime. Demographic data were obtained from the German federal statistical office. HZ incidence and the proportion of HZ individuals developing post-herpetic neuralgia (PHN) were derived from German specific sources. Age-specific vaccine efficacy and waning rates were based on published clinical trial data. Vaccine coverage for both vaccines was assumed to be 40%, with compliance of the second dose of the HZ/su vaccine of 70%. Sensitivity analyses were performed to assess the robustness of the results. It was estimated that, over the remaining lifetime since vaccination, the HZ/su vaccine would reduce the number of HZ cases by 725,233, 533,162 and 486,794 in the 3 age cohorts, respectively, compared with 198,477, 196,000 and 104,640, using ZVL. The number needed to vaccinate (NNV) to prevent one HZ case ranged from 8 to 11 using the HZ/su vaccine compared with 20 to 50 using ZVL. Corresponding NNV to prevent one PHN case ranged from 39 to 53 using the HZ/su vaccine compared with 94 to 198 using ZVL. Due to the higher, sustained vaccine efficacy, the candidate HZ/su vaccine demonstrated superior public health impact compared with ZVL.

A cross-sectional study assessing the pharyngeal carriage of Neisseria meningitidis in subjects aged 1-24 years in the city of Embu das Artes, São Paulo, Brazil.

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.

Sustained Decrease in Gastroenteritis-related Deaths and Hospitalizations in Children Less Than 5 Years of Age After the Introduction of Rotavirus Vaccination: A Time-Trend Analysis in Brazil (2001-2010).

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.

Patterns of influenza B circulation in Brazil and its relevance to seasonal vaccine composition

Abstract 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.

Patterns of influenza B circulation in Brazil and its relevance to seasonal vaccine composition.

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.

A population-based study of prevalence and risk factors of chronic kidney disease in León, Nicaragua.

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.

CONTEXTE: Selon de récentes études, il existerait une prévalence d'insuffisance rénale chronique (IRC) excessive chez les jeunes adultes de sexe masculin de la côte du Pacifique du Nicaragua. Ces études, qui ont été conduites sur des échantillons non représentatifs de la population, suggèrent une étiologie non classique de l'IRC dans cette région. OBJECTIFS DE L'ÉTUDE: Nous avons effectué une étude transversale portant sur un vaste échantillon de population, afin de pouvoir estimer la prévalence d'IRC dans la ville nicaraguéenne de León, d'une part, et évaluer la présence de liens entre l'IRC et certains facteurs de risque ayant été étudiés, d'autre part. MÉTHODE: Pour déterminer le statut d'IRC de 2275 résidents de la ville de León, nous avons utilisé le débit de filtration glomérulaire estimé, selon l'équation du MDRD. Une régression logistique multivariée a été utilisée pour estimer les ratios de probabilité corrigés de prévalence. La prévalence d'IRC de León a également été normalisée sur la base de la distribution démographique du Health and Demographic Surveillance System de León et avec son recensement de 2005. RÉSULTATS: La prévalence d'IRC était de 9,1%; elle était deux fois plus élevée chez les hommes (13,8%) que chez les femmes (5,8%). D'autres facteurs ont été liés de façon significative à l'IRC: la vieillesse, la vie rurale, un niveau d'éducation faible, une hypertension autodéclarée, plusieurs années de travail en agriculture, et la consommation de lija (alcool non contrôlé) et de grandes quantités d'eau. Le diabète autodéclaré était également lié à l'IRC dans les modèles ajustés chez les femmes, mais non chez les homm es. CONCLUSIONS: Nos résultats sont comparables à ceux des études locales et supportent l'hypothèse de l'existence d'une néphropathie méso-américaine.

Rotavirus strain surveillance for three years following the introduction of rotavirus vaccine into Belém, Brazil.

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.

Etiology and antimicrobial susceptibility of middle ear fluid pathogens in Costa Rican children with otitis media before and after the introduction of the 7-valent pneumococcal conjugate vaccine in the National Immunization Program: acute otitis media microbiology in Costa Rican children.

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.

Burden of influenza in Latin America and the Caribbean: a systematic review and meta-analysis.

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 17 150 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.

Postmarketing surveillance of intussusception following mass introduction of the attenuated human rotavirus vaccine in Mexico.

BACKGROUND: Mexico initiated mass vaccination with the attenuated human rotavirus vaccine (Rotarix) in 2006. This postlicensure study aimed to assess any potential temporal association between vaccination and intussusception in Mexican infants. METHODS: Prospective, active surveillance for intussusception among infants aged less than 1 year was conducted in 221 hospitals across Mexico from the Mexican Institute of Social Security between January 2008 and October 2010. The temporal association between vaccination and intussusception was assessed by self-controlled case-series analysis. RESULTS: Of the 753 episodes of intussusception reported in 750 infants, 701 were in vaccinated infants (34.5% post-dose 1, 65.5% post-dose 2). The relative incidence of intussusception within 31 days of vaccination was 1.75 (95.5% confidence interval [CI]: 1.24-2.48; P=0.001) post-dose 1 and 1.06 (95.5% CI: 0.75-1.48; P=0.75) post-dose 2. The relative incidence of intussusception within 7 days of vaccination was 6.49 post-dose 1 (95.5% CI: 4.17-10.09; P<0.001) and 1.29 post-dose 2 (95.5% CI: 0.80-2.11; P=0.29). Clustering of intussusception within 7 days of vaccination was observed post-dose 1. An attributable risk of 3 to 4 additional cases of intussusception per 100,000 vaccinated infants was estimated. CONCLUSION: This is the largest surveillance study for intussusception after rotavirus vaccination to date. A temporal increase in the risk for intussusception was seen within 7 days of administration of the first vaccine dose. It is still uncertain whether rotavirus vaccination has any impact on the overall incidence of intussusception. This finding has to be put in perspective with the well-documented substantial benefits of rotavirus vaccination.

Streptococcus pneumoniae serotype 19A in Latin America and the Caribbean: a systematic review and meta-analysis, 1990-2010.

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.

Non-capsulated and capsulated Haemophilus influenzae in children with acute otitis media in Venezuela: a prospective epidemiological study.

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.

Epidemiology of community-acquired pneumonia in children of Latin America and the Caribbean: a systematic review and meta-analysis.

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.

Impact of rotavirus vaccination on childhood gastroenteritis-related mortality and hospital discharges in Panama.

BACKGROUND: Rotavirus vaccination was introduced in Panama in March 2006. This study was carried out in order to describe the trends in gastroenteritis-related (GER) hospitalizations and mortality in children <5 years of age during the pre- and post-vaccination periods. METHODS: Data from the Expanded Program on Immunization (Ministry of Health) were used to calculate vaccine coverage. GER mortality and hospitalizations were obtained through database review of the Contraloría General de la República and hospital discharge databases of five sentinel hospitals, for the period 2000-2008. Mean rates of GER mortality and mean numbers of hospitalizations during the baseline pre-vaccination period (2000-2005) were compared to those of 2007 and 2008. RESULTS: National coverage for the second rotavirus vaccine dose increased from 30% in 2006 to 62% in 2007 and 71% in 2008, varying from 62% in the West region to 77% in the Panama region. Overall, at 2-years post-vaccine introduction, the GER mortality rate in Panama had decreased by 50% (95% confidence interval (CI) 46-54). During 2000-2005, the GER mortality rate in children (<1 year) was 73/100 000, decreasing by 45% (95% CI 40-51) in 2008. In children aged 1-4 years, the GER mortality rate was 20.3/100 000 (2000-2005), decreasing by 54% (95% CI 48-60) in 2008. The Panama region registered the highest mortality rate reduction (69%; 95% CI 58-81) for 2008. During 2008, GER hospitalizations among children <5 years of age decreased by 30% (95% CI 21-37) from the mean number of hospitalizations during 2000-2005. CONCLUSIONS: A substantial reduction in GER mortality and hospitalizations was observed following the introduction of rotavirus vaccine in Panama.