Rotavirus genotypes in children under five years hospitalized with diarrhea in low and middle-income countries: Results from the WHO-coordinated Global Rotavirus Surveillance Network.

Rotavirus is the most common pathogen causing pediatric diarrhea and an important cause of morbidity and mortality in low- and middle-income countries. Previous evidence suggests that the introduction of rotavirus vaccines in national immunization schedules resulted in dramatic declines in disease burden but may also be changing the rotavirus genetic landscape and driving the emergence of new genotypes. We report genotype data of more than 16,000 rotavirus isolates from 40 countries participating in the Global Rotavirus Surveillance Network. Data from a convenience sample of children under five years of age hospitalized with acute watery diarrhea who tested positive for rotavirus were included. Country results were weighted by their estimated rotavirus disease burden to estimate regional genotype distributions. Globally, the most frequent genotypes identified after weighting were G1P[8] (31%), G1P[6] (8%) and G3P[8] (8%). Genotypes varied across WHO Regions and between countries that had and had not introduced rotavirus vaccine. G1P[8] was less frequent among African (36 vs 20%) and European (33 vs 8%) countries that had introduced rotavirus vaccines as compared to countries that had not introduced. Our results describe differences in the distribution of the most common rotavirus genotypes in children with diarrhea in low- and middle-income countries. G1P[8] was less frequent in countries that had introduced the rotavirus vaccine while different strains are emerging or re-emerging in different regions.

Reductions in Childhood Pneumonia Mortality After Vaccination in the United States.

BACKGROUND: We aim to estimate the magnitude of the reduction in pneumococcal pneumonia and meningitis mortality after the mass introduction of pneumococcal conjugate vaccine (PCV)7 and PCV13 in children in the United States. METHODS: We assessed the trends in mortality rates from pneumococcal pneumonia and meningitis, in the United States between 1994 and 2017. We fitted an interrupted time-series negative binomial regression model (adjusted by trend, seasonality, PCV7/PCV13 coverage, and H. influenzae type b vaccine coverage) to estimate the counterfactual rates without vaccination. We reported a percent reduction in mortality estimates relative to the projected no-vaccination scenario, using the formula 1 minus the incidence risk ratio, with 95% confidence intervals (CIs). RESULTS: Between 1994 and 1999 (the prevaccination period), the all-cause pneumonia mortality rate for 0-1-month-old children was 2.55 per 100,00 pop., whereas for 2-11 months-old children, this rate was 0.82 deaths per 100,000 pop. During the PCV7-period in 0-59-month-old children in the United States, the adjusted reduction of all-cause pneumonia was 13% (95% CI: 4-21) and 19% (95% CI: 0-33) of all-cause meningitis For PCV13, the reductions in this age group were 21% (95% CI: 4-35) for all-cause pneumonia mortality and 22% (95% CI: -19 to 48) for all-cause meningitis mortality. PCV13 had greater reductions of all-cause pneumonia than PCV13 in 6-11-month-old infants. CONCLUSIONS: The universal introduction of PCV7, and later PCV13, for children 0-59 months old in the United States was associated with decreases in mortality due to all-cause pneumonia.

Diarrheal Deaths After the Introduction of Rotavirus Vaccination in 4 Countries.

BACKGROUND: We aim in our analysis to estimate the reduction of diarrhea-related mortality rates after introduction of a rotavirus vaccine in subregions of 4 Latin American countries. METHODS: We selected diarrhea-related deaths from individual-level data from death certificates in Brazil, Colombia, Ecuador, and Mexico. Counts were aggregated by region, year and month, and age group for each country. We ran an interrupted time-series analysis using Poisson regression to obtain seasonal and trend-adjusted estimates of impact. Results are reported as percentages (1 - mortality rate ratio). RESULTS: We found a reduction in diarrhea-related mortality in children <5 years old of 18% (95% confidence interval [CI], 15 to 20) for Mexico, 39% (95% CI, 35 to 44) for Colombia, 19 (95% CI, 17 to 22) for Brazil, and -26% (95% CI, -40 to -14) for Ecuador. Using wavelet analyses, we found a reduction of 6- and 12-month seasonality in Brazil, Colombia, and Mexico. We also found that the increased reduction of diarrhea-related deaths was larger with greater prevaccine burden of diarrhea in infants. CONCLUSIONS: Our findings and available evidence support the recommendation from the World Health Organization for the monovalent and/or pentavalent rotavirus vaccine in countries worldwide. We found an increased benefit in those settings with a higher burden of infant diarrhea-related deaths.

Immunization stress-related responses presenting as psychogenic non-epileptic seizures following HPV vaccination in Rio Branco, Brazil.

IMPORTANCE: The absence of a positive diagnosis of psychogenic non-epileptic seizures (PNES) in immunization stress-related response (ISRR) clusters may have not only a direct impact on affected patients' health but may also reduce compliance to national vaccination programs. It is therefore crucial to develop efficient diagnostic tools and a feasible proposal for proper communication and treatment of ISRR. PURPOSE: To explore the psychogenic nature of patients' convulsive seizures in a suspected outbreak of an ISRR cluster following human papillomavirus vaccination in Rio Branco, Brazil. METHODS: Twelve patients with convulsive seizures were submitted to prolonged intensive video-electroencephalography monitoring, brain magnetic resonance imaging, cerebrospinal fluid diagnostic testing, laboratory subsidiary examinations, and complete neurological and psychiatric evaluations. RESULTS: Ten patients received the positive diagnosis of PNES, and two patients received the diagnosis of idiopathic generalized epilepsy. No biological association was found between the HPV vaccine and the clinical problems presented by the patients. CONCLUSIONS: Prolonged VEEG monitoring can contribute significantly to the positive diagnosis of PNES in ISRR clusters and to avoid hesitancy to vaccinate.

Identifying signatures of the impact of rotavirus vaccines on hospitalizations using sentinel surveillance data from Latin American countries.

BACKGROUND: Passive surveillance data are often the only available source of data that can be used to evaluate the population-level impact of vaccination, but such data often suffer from important limitations such as changes in surveillance efforts. This study provides an example of how to identify important signatures of rotavirus vaccine impact, including evaluating the overall effectiveness and changes in rotavirus seasonal dynamics. METHODS: We used data from a standardized sentinel rotavirus surveillance network in six Latin American countries (Bolivia, El Salvador, Guatemala, Honduras, Paraguay, and Venezuela) from 2004 to 2017. A random-effects model was used to evaluate changes in the proportion of rotavirus-associated hospitalizations following vaccine introduction. Harmonic regression models were used to estimate vaccine impact on the number of rotavirus hospitalizations, controlling for trends in rotavirus-negative cases. Changes to rotavirus seasonality were evaluated using center of gravity analysis, wavelet analysis, and harmonic regression. RESULTS: All countries observed declines in the proportion of rotavirus-positive acute diarrhea samples with a mean reduction of 16% (95% confidence interval: 10-22%). We estimate that each 10% increase in vaccine coverage was associated with declines in the number of rotavirus-positive cases, ranging from 4.3% (1.3-7.2%) in Honduras to 21.4% (16.8-25.9%) in Venezuela. The strength of the seasonal peak in rotavirus incidence became smaller after vaccine introduction in Guatemala, Honduras, and Venezuela. Seasonal peaks also shifted later in the surveillance year, especially in higher-mortality countries. CONCLUSIONS: The combination of methods we applied have different strengths that allow us to identify common signatures of rotavirus vaccine impact.

Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008-16: findings from the Global Rotavirus Surveillance Network.

BACKGROUND: Rotavirus vaccine use in national immunisation programmes has led to declines in hospital admissions for rotavirus gastroenteritis among children; however, the global impact of rotavirus vaccine introduction has not been described using primary data. We describe the impact of rotavirus vaccine introduction on admissions for acute rotavirus gastroenteritis in primarily low-income and middle-income countries, using 9 years of data from the WHO-coordinated Global Rotavirus Surveillance Network (GRSN). METHODS: Between Jan 1, 2008, and Dec 31, 2016, children younger than 5 years of age who were admitted to hospital with acute gastroenteritis were prospectively enrolled in GRSN sites. We included sites that enrolled children and collected stool specimens monthly and tested at least 100 specimens annually in the impact analysis, with a separate analysis taking into account site continuity. We compared proportions of acute gastroenteritis cases positive for rotavirus in the pre-vaccine and post-vaccine periods and calculated mean proportion changes for WHO regions, with 95% CIs; these findings were then compared with interrupted time series analyses. We did further sensitivity analyses to account for rotavirus vaccination coverage levels and sites that collected specimens for at least 11 months per year and tested at least 80 specimens per year. We also analysed the age distribution of rotavirus-positive cases before and after vaccine introduction. FINDINGS: 403 140 children younger than 5 years of age admitted to hospital with acute gastroenteritis from 349 sites in 82 countries were enrolled over the study period, of whom 132 736 (32·9%) were positive for rotavirus. We included 305 789 children from 198 sites in 69 countries in the impact analysis. In countries that had not introduced rotavirus vaccine in their national immunisation programmes, rotavirus was detected in 38·0% (95% CI 4·8-73·4) of admissions for acute gastroenteritis annually whereas in those that have introduced the vaccine, rotavirus was detected in 23·0% (0·7-57·7) of admissions for acute gastroenteritis, showing a 39·6% (35·4-43·8) relative decline following introduction. Interrupted time series analyses confirmed these findings. Reductions by WHO regions ranged from 26·4% (15·0-37·8) in the Eastern Mediterranean Region to 55·2% (43·0-67·4) in the European Region and were sustained in nine countries (contributing up to 31 sites) for 6-10 years. The age distribution of children with rotavirus gastroenteritis shifted towards older children after rotavirus vaccine introduction. INTERPRETATION: A significant and sustained reduction in the proportion of hospital admissions for acute gastroenteritis due to rotavirus was seen among children younger than 5 years in GRSN sites following rotavirus vaccine introduction. These findings highlight the need to incorporate rotavirus vaccines into immunisation programmes in countries that have not yet introduced them and underline the importance of high-quality surveillance. FUNDING: The GRSN receives funding from Gavi, the Vaccine Alliance and the US Centers for Disease Control and Prevention. No specific funding was provided for this Article.

Effectiveness of 13-pneumococcal conjugate vaccine (PCV13) against invasive pneumococcal disease in children in the Dominican Republic.

BACKGROUND: Limited data are available on the effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) in resource-poor settings and PCV naïve populations. The Dominican Republic introduced PCV13 in September 2013 using a 2 + 1 schedule (2, 4, and 12 months) without a catch-up campaign. We evaluated PCV13 effectiveness against vaccine-type (VT) invasive pneumococcal disease (IPD) among children in the Dominican Republic. METHODS: We conducted a matched case-control study. A case-patient was defined as VT-IPD identified by culture or polymerase chain reaction (PCR) from a normally sterile-site in a hospitalized child who was age-eligible to have received ≥1 PCV13 dose. Four age- and neighborhood-matched controls were enrolled for each case-patient. We collected demographic, vaccination history, and risk factor data. Conditional logistic regression was performed. Vaccine effectiveness was calculated as (1- adjusted matched odds ratio for vaccination) X 100%. RESULTS: We enrolled 39 case-patients and 149 matched-controls. Most case-patients had pneumonia with pleural effusion (64%), followed by meningitis (28%) and septicemia (13%). The most common pneumococcal serotypes identified included 14 (18%), 3 (13%), 19A (10%), and 1 (8%). Fewer case-patients had ≥1 PCV13 dose as compared to controls (61.5% vs. 80.0%; p = 0.006). Adjusting for malnutrition and socioeconomic status, VE of ≥1 PCV13 dose compared to no doses was 67.2% (95% CI: 2.3% to 90.0%). Only 44% of controls were up-to-date for PCV13, suggesting low vaccine coverage in the population. CONCLUSIONS: We found that PCV13 provided individual protection against VT-IPD in this resource-poor setting with a PCV-naïve population, despite low PCV13 coverage. Expanding vaccination coverage might increase PCV13 impact.

Impact and effectiveness of meningococcal vaccines: a review

[ABSTRACT]. Objectives. To summarize and critically evaluate the evidence on the impact and effectiveness of meningococcal vaccination programs around the world in order to inform decision-making in Latin America and the Caribbean. Methods. A review of the literature was conducted following several components of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed Central® was searched for papers published in any language from January 1999 – March 2017. Results. In all, 32 studies were included, most of which evaluated the meningococcal C conjugate vaccine. Fourteen studies measured effectiveness and 30 measured impact. The effectiveness of polysaccharide vaccines was 65% – 83.7% (different age groups), while the effectiveness of the conjugate vaccines was 66% – 100%. Incidence decline of laboratory-confirmed meningococcal disease for the conjugate vaccine ranged from 77% – 100% among different ages groups. The only study that evaluated the protein subunit vaccine reported a vaccine effectiveness of 82.9%. Conclusions. The studies reviewed show impact and effectiveness of both polysaccharide vaccines and conjugate vaccines on vaccine-serogroup meningococcal disease. The conjugate vaccines, however, show higher impact and effectiveness with longer-lasting protection over the polysaccharide vaccines. Given the variance in potential use of a meningococcal vaccine, epidemiological surveillance systems should be strengthened to inform national decisions.

[RESUMEN]. Objetivos. Resumir y evaluar críticamente los datos científicos sobre la repercusión y la eficacia de los programas de vacunación antimeningocócica en todo el mundo para orientar la toma de decisiones en América Latina y el Caribe. Métodos. Se realizó un examen de la bibliografía siguiendo varios componentes de las directrices correspondientes a los elementos de notificación preferidos para revisiones sistemáticas y metanálisis. Se hicieron búsquedas en PubMed Central® para encontrar documentos publicados en cualquier idioma desde enero de 1999 hasta marzo del 2017. Resultados. En total, se incluyeron 32 estudios, en cuya mayoría se evaluaba la vacuna antimeningocócica conjugada contra el serotipo C. En 14 estudios se midió la efectividad y en 30, el impacto. La efectividad de las vacunas polisacarídeas se encontraba entre 65% y 83,7% (grupos etarios diferentes), mientras que la de las vacunas conjugadas, entre 66% y 100%. Gracias a la vacuna conjugada, la disminución de la incidencia de la enfermedad meningocócica confirmada en laboratorio varió entre 77% y 100% en diferentes grupos etarios. En el único estudio en el que se evaluó la vacuna de subunidades proteínicas se notificó que su efectividad era de 82,9%. Conclusiones. Los estudios examinados muestran el impacto y la efectividad tanto de las vacunas polisacarídeas como de las vacunas conjugadas en relación con la enfermedad meningocócica causada por los serotipos utilizados en las vacunas. Sin embargo, las vacunas conjugadas demuestran que tienen un mayor impacto y efectividad que las vacunas polisacarídeas para dar una protección más duradera. En vista de la varianza del posible uso de una vacuna antimeningocócica, se deben fortalecer los sistemas de vigilancia epidemiológica para orientar las decisiones nacionales.

[RESUMO]. Objetivos. Sumarizar e analisar de maneira crítica as evidências sobre o impacto e a efetividade dos programas de vacinação contra doença meningocócica em todo o mundo para subsidiar a tomada de decisão na América Latina e no Caribe. Métodos. Uma revisão da literatura científica foi realizada de acordo com varios componentes das diretrizes dos Principais itens para relatar revisões sistemáticas e meta-análises (PRISMA). Foi feita uma pesquisa da base de dados PubMed Central® em busca de estudos publicados em qualquer idioma de janeiro de 1999 a março de 2017. Resultados. Trinta e dois estudos foram selecionados, sendo que a maioria avaliou a vacina conjugada contra o meningococo C. Quatorze artigos avaliaram a efetividade da vacina e 30, o impacto. A efetividade das vacinas polissacarídicas foi de 65% a 83,7% (em diferentes faixas etárias) e a das vacinas conjugadas foi de 66% a 100%. A redução com o uso da vacina conjugada da incidência de doença meningocócica confirmada por laboratório variou de 77% a 100% em diferentes faixas etárias. O único estudo que avaliou a vacina de subunidade proteica informou uma efetividade de 82,9%. Conclusões. Os estudos examinados indicam impacto e efetividade da vacina polissacarídica e da vacina conjugada para doença meningocócica do respectivo sorogrupo vacinal. As vacinas conjugadas demonstram maior impacto e efetividade e proteção mais duradoura em relação às vacinas polissacarídicas. Diante da variação do uso em potencial da vacina meningocócica, os sistemas de vigilância epidemiológica devem ser reforçados visando subsidiar a tomada de decisão das autoridades nacionais.

Knowing the scope of meningococcal disease in Latin America

[ABSTRACT]. Opportunities for strengthening surveillance of meningococcal disease exist between and within countries in Latin America. In August of 2015, a workshop was convened in the city of São Paulo, Brazil, to address the following objectives: 1) to review meningococcal disease burden and vaccine use in Latin America; 2) to evaluate the effectiveness of current meningococcal surveillance practices in the region; 3) to identify challenges to meningococcal surveillance in the region; and 4) to outline steps for strengthening meningococcal surveillance and disease control in the region. Based on the workshop’s discussions, recommendations for strengthening surveillance and controlling meningococcal disease in Latin America focus on improving: a) laboratory capabilities for diagnostic testing; b) communication regarding epidemiologic- and laboratory-based analyses; c) communication during outbreaks; d) monitoring of long-term disease outcomes; e) knowledge of vaccines against serogroup B disease; and f) criteria for defining and controlling meningococcal outbreaks. Overall, improving surveillance will help guide strategies for meningococcal disease prevention and control in Latin America.

[RESUMEN]. Existen distintas oportunidades para reforzar los procedimientos de vigilancia de la enfermedad meningocócica entre los países de América Latina y dentro de ellos. En agosto del 2015, se llevó a cabo un taller en la ciudad de São Paulo (Brasil) en el que se trataron los siguientes puntos: 1) examen de la carga de la enfermedad meningocócica y el uso de la vacuna en América Latina; 2) evaluación de la eficacia de los actuales procedimientos de vigilancia de la enfermedad meningocócica en la región; 3) especificación de los retos para la vigilancia de la enfermedad meningocócica en la región; y 4) definición de los pasos para fortalecer los procedimientos de vigilancia de la enfermedad meningocócica y el control de esta enfermedad en la región. Como resultado del taller se formularon recomendaciones para reforzar los procedimientos de vigilancia y control de la enfermedad meningocócica en América Latina que hacían hincapié en mejorar: a) las capacidades de laboratorio con respecto a las pruebas diagnósticas; b) la comunicación sobre los análisis epidemiológicos y de laboratorio; c) la comunicación durante los brotes; d) el seguimiento de las consecuencias de la enfermedad a largo plazo; e) el conocimiento sobre las vacunas contra la enfermedad causada por el serogrupo B; y f) los criterios para definir y controlar los brotes meningocócicos. En términos generales, la mejora de los procedimientos de vigilancia ayudará a delinear las estrategias para la prevención y el control de la enfermedad meningocócica en América Latina.

[RESUMO]. Existem oportunidades para o reforço da vigilância da doença meningocócica entre os países e em cada país na América Latina. Em agosto de 2015, foi realizado um seminário na cidade de São Paulo, Brasil, com os seguintes objetivos: 1) avaliar a carga da doença meningocócica e o uso da vacina na América Latina; 2) avaliar a eficácia das atuais práticas de vigilância da doença meningocócica na Região; 3) identificar os desafios para a vigilância meningocócica na Região e 4) definir medidas para reforçar a vigilância da doença meningocócica e o controle da doença na Região. Partindo dos debates realizados durante o seminário, foram feitas as seguintes recomendações para reforçar a vigilância e o controle da doença meningocócica na América Latina, dando-se ênfase a melhorar: a) a infraestrutura laboratorial para exames diagnósticos; b) a comunicação das análises epidemiológicas e laboratoriais; c) a comunicação nos surtos; d) o monitoramento dos desfechos da doença a longo prazo; e) o conhecimento sobre as vacinas contra o meningococo do sorogrupo B e f) os critérios para definir e controlar os surtos de doença meningocócica. Em geral, a melhoria da vigilância contribuirá para orientar as estratégias para prevenção e controle da doença meningocócica na América Latina.

Knowing the scope of meningococcal disease in Latin America.

Opportunities for strengthening surveillance of meningococcal disease exist between and within countries in Latin America. In August of 2015, a workshop was convened in the city of São Paulo, Brazil, to address the following objectives: 1) to review meningococcal disease burden and vaccine use in Latin America; 2) to evaluate the effectiveness of current meningococcal surveillance practices in the region; 3) to identify challenges to meningococcal surveillance in the region; and 4) to outline steps for strengthening meningococcal surveillance and disease control in the region. Based on the workshop's discussions, recommendations for strengthening surveillance and controlling meningococcal disease in Latin America focus on improving: a) laboratory capabilities for diagnostic testing; b) communication regarding epidemiologic- and laboratory-based analyses; c) communication during outbreaks; d) monitoring of long-term disease outcomes; e) knowledge of vaccines against serogroup B disease; and f) criteria for defining and controlling meningococcal outbreaks. Overall, improving surveillance will help guide strategies for meningococcal disease prevention and control in Latin America.

Existen distintas oportunidades para reforzar los procedimientos de vigilancia de la enfermedad meningocócica entre los países de América Latina y dentro de ellos. En agosto del 2015, se llevó a cabo un taller en la ciudad de São Paulo (Brasil) en el que se trataron los siguientes puntos: 1) examen de la carga de la enfermedad meningocócica y el uso de la vacuna en América Latina; 2) evaluación de la eficacia de los actuales procedimientos de vigilancia de la enfermedad meningocócica en la región; 3) especificación de los retos para la vigilancia de la enfermedad meningocócica en la región; y 4) definición de los pasos para fortalecer los procedimientos de vigilancia de la enfermedad meningocócica y el control de esta enfermedad en la región. Como resultado del taller se formularon recomendaciones para reforzar los procedimientos de vigilancia y control de la enfermedad meningocócica en América Latina que hacían hincapié en mejorar: a) las capacidades de laboratorio con respecto a las pruebas diagnósticas; b) la comunicación sobre los análisis epidemiológicos y de laboratorio; c) la comunicación durante los brotes; d) el seguimiento de las consecuencias de la enfermedad a largo plazo; e) el conocimiento sobre las vacunas contra la enfermedad causada por el serogrupo B; y f) los criterios para definir y controlar los brotes meningocócicos. En términos generales, la mejora de los procedimientos de vigilancia ayudará a delinear las estrategias para la prevención y el control de la enfermedad meningocócica en América Latina.

Existem oportunidades para o reforço da vigilância da doença meningocócica entre os países e em cada país na América Latina. Em agosto de 2015, foi realizado um seminário na cidade de São Paulo, Brasil, com os seguintes objetivos: 1) avaliar a carga da doença meningocócica e o uso da vacina na América Latina; 2) avaliar a eficácia das atuais práticas de vigilância da doença meningocócica na Região; 3) identificar os desafios para a vigilância meningocócica na Região e 4) definir medidas para reforçar a vigilância da doença meningocócica e o controle da doença na Região. Partindo dos debates realizados durante o seminário, foram feitas as seguintes recomendações para reforçar a vigilância e o controle da doença meningocócica na América Latina, dando-se ênfase a melhorar: a) a infraestrutura laboratorial para exames diagnósticos; b) a comunicação das análises epidemiológicas e laboratoriais; c) a comunicação nos surtos; d) o monitoramento dos desfechos da doença a longo prazo; e) o conhecimento sobre as vacinas contra o meningococo do sorogrupo B e f) os critérios para definir e controlar os surtos de doença meningocócica. Em geral, a melhoria da vigilância contribuirá para orientar as estratégias para prevenção e controle da doença meningocócica na América Latina.

Impact and Effectiveness of 10 and 13-Valent Pneumococcal Conjugate Vaccines on Hospitalization and Mortality in Children Aged Less than 5 Years in Latin American Countries: A Systematic Review.

BACKGROUND: Several Latin American and Caribbean (LAC) countries have introduced pneumococcal conjugate vaccine (PCV-10 or PCV-13) in their routine national immunization programs. OBJECTIVES: We aimed to summarize the evidence of PCV impact and effectiveness in children under 5 years old in the LAC Region. METHODS: We conducted a systematic review of the literature on impact or effectiveness of PCVs on deaths or hospitalizations due to invasive pneumococcal disease (IPD), pneumonia, meningitis and sepsis. We searched Medline, WoS, Lilacs, Scopus, Central and gray literature published in any language from 2009 to January 2016. We included studies addressing the outcomes of interest in children in the target age group, and with the following designs: randomized trials, cohort or case-control, interrupted time series with at least three data points before and after the intervention, and before-after studies. Screening of citations, data extraction, and risk of bias assessment were conducted in duplicate by independent reviewers, according to the study protocol registered on PROSPERO. Descriptive analysis of the effectiveness measurements and sensitivity analysis were conducted. Effectiveness is reported as 1-OR or 1-RR for case control or cohort/clinical trials, and as percent change of disease incidence rates for before-after studies. RESULTS: We identified 1,085 citations, 892 from databases and 193 from other sources. Of these, 22 were further analyzed. Studies were from Brazil, Chile, Uruguay, Argentina, Peru and Nicaragua. Effectiveness ranged from 8.8-37.8% for hospitalizations due to X-ray confirmed pneumonia, 7.4-20.6% for clinical pneumonia, and 13.3-87.7% for meningitis hospitalizations, and 56-83.3% for IPD hospitalization, varying by age, outcome definition, type of vaccine and study design. CONCLUSIONS: Available evidence to date indicates significant impact of both PCV-10 and PCV-13 in the outcomes studied, with no evidence of the superiority of one vaccine over the other on pneumonia, IPD or meningitis hospitalization reduction in children under 5 years old.

Effectiveness of Pentavalent Rotavirus Vaccine Against a Diverse Range of Circulating Strains in Nicaragua.

BACKGROUND: Because >60 rotavirus strains have been reported worldwide, concerns exist about strain replacement after the introduction of rotavirus vaccines, particularly in developing countries with diverse strains and lower efficacy. METHODS: We used the case-control design in 4 hospitals in Nicaragua to assess strain-specific vaccine effectiveness (VE) of a pentavalent rotavirus vaccine (RotaTeq) against rotavirus diarrhea. Cases were identified through prospective strain surveillance with reverse transcription-polymerase chain reaction for 3 years among children hospitalized for diarrhea, and controls were children negative for rotavirus. RESULTS: We enrolled 1178 case-patients, 1082 (92%) with G and P typing, and 4927 controls. A different strain predominated each year with increasing age of the vaccine-eligible cohort during the study period: G2P[4] in 2008 (97%; mean age, 11.9 months), G1P[8] in 2009 (55%; mean age, 17.0 months), and G3P[8] in 2010 (78%; mean age, 17.3 months). Overall VE was 45% (95% confidence interval, 25%-59%). Regardless of the strain, VE estimates were 12%-79% lower among children aged ≥12 months relative to those 6-11 months of age. The lower VE for G3P[8] was related to the higher mean age of cases (17.3 months) compared with the G2P[4] strains (11.9 months), with a significant trend (R(2)= 0.819;P< .001) of declining effectiveness with increasing mean age of the cases. CONCLUSIONS: Introduction of RotaTeq did not result in sustained emergence of any particular strain in Nicaragua. Variation in strain-specific effectiveness was due to an age-related decline in effectiveness rather than differences in protection against the observed strains.

Pneumococcal conjugate vaccine introduction in Latin America and the Caribbean: progress and lessons learned.

In Latin America and the Caribbean, pneumococcus has been estimated to cause 12,000-28,000 deaths, 182,000 hospitalizations, and 1.4 million clinic visits annually. Countries in the Americas have been among the first developing nations to introduce pneumococcal conjugate vaccines into their Expanded Programs on Immunization, with 34 countries and territories having introduced these vaccines as of September 2015. Lessons learned for successful vaccine introduction include the importance of coordination between political and technical decision makers, adjustments to the cold chain prior to vaccine introduction, and the need for detailed plans addressing the financial and technical sustainability of introduction. Though many questions on the Pneumococcal Conjugate Vaccine remain unanswered, the experience of the Americas suggests that the vaccines can be introduced quickly and effectively.

Catching-up with pentavalent vaccine: Exploring reasons behind lower rotavirus vaccine coverage in El Salvador.

Rotavirus vaccine was introduced in El Salvador in 2006 and is recommended to be given concomitantly with DTP-HepB-Haemophilus influenzae type b (pentavalent) vaccine at ages 2 months (upper age limit 15 weeks) and 4 months (upper age limit 8 months) of age. However, rotavirus vaccination coverage continues to lag behind that of pentavalent vaccine, even in years when national rotavirus vaccine stock-outs have not occurred. We analyzed factors associated with receipt of oral rotavirus vaccine among children who received at least 2 doses of pentavalent vaccine in a stratified cluster survey of children aged 24-59 months conducted in El Salvador in 2011. Vaccine doses included were documented on vaccination cards (94.4%) or in health facility records (5.6%). Logistic regression and survival analysis were used to assess factors associated with vaccination status and age at vaccination. Receipt of pentavalent vaccine by age 15 weeks was associated with rotavirus vaccination (OR: 5.1; 95% CI 2.7, 9.4), and receipt of the second pentavalent dose by age 32 weeks was associated with receipt of two rotavirus vaccine doses (OR: 5.0; 95% CI 2.1-12.3). Timely coverage with the first pentavalent vaccine dose was 88.2% in the 2007 cohort and 91.1% in the 2008 cohort (p=0.04). Children born in 2009, when a four-month national rotavirus vaccine stock-out occurred, had an older median age of receipt of rotavirus vaccine and were less likely to receive rotavirus on the same date as the same dose of pentavalent vaccine than children born in 2007 and 2008. Upper age limit recommendations for rotavirus vaccine administration contributed to suboptimal vaccination coverage. Survey data suggest that late rotavirus vaccination and co-administration with later doses of pentavalent vaccine among children born in 2009 helped increase rotavirus vaccine coverage following shortages.

Effect of rotavirus vaccine on childhood diarrhea mortality in five Latin American countries.

BACKGROUND: The aim of this study was to estimate the association between rotavirus vaccine (RV) introduction and reduction of all-cause diarrhea death rates among children in five Latin American countries that introduced RV in 2006. METHODS: Diarrhea mortality data was gathered from 2002 until 2009 from the Pan American Health Organization Mortality Database for five "vaccine adopter" countries (Brazil, El Salvador, Mexico, Nicaragua, and Panama) that introduced RV in 2006 and four "control" countries (Argentina, Chile, Costa Rica, and Paraguay) that did not introduce RV by 2009. Time trend analyses were carried out, and effects and 95% confidence intervals (CI) were estimated. RESULTS: Each of the five vaccine adopter countries, except Panama, showed a significant trend in declining mortality rates during the post-vaccine period from 2006 to 2009, whereas no decline was seen in control countries during these years. Furthermore, trends of reduction of all-cause diarrhea mortality in both children <1 year of age and <5 years of age were greater in the post-vaccination period compared with the pre-vaccine period in all vaccine adopter countries (except for Nicaragua), whereas in control countries, a reverse pattern was seen with greater reduction in the early years from 2002 to 2005 versus 2006-2009. An estimatedtotal of 1777 of annual under-5 deaths were avoided in Brazil, El Salvador, Mexico, and Nicaragua during the post-vaccination period. CONCLUSION: All vaccine adopter countries, except Panama, showed a significant decrease in all-cause diarrhea-related deaths after RV implementation, even after adjusting for declining trends over time in diarrhea mortality. These data strongly support continuous efforts to increase vaccination coverage of RV vaccines, particularly in countries with high levels of child mortality from diarrhea.

Rotavirus vaccine effectiveness in Latin American and Caribbean countries: A systematic review and meta-analysis.

INTRODUCTION: There are two group A rotavirus (RVA) vaccines available worldwide since 2006: monovalent (Rotarix(®), RV1) and pentavalent (RotaTeq(®), RV5). Currently, 16 countries and 1 territory in Latin America and the Caribbean (LAC) have introduced RVA vaccines and since their introduction several impact and effectiveness studies have been conducted in different countries. The purpose of this study was to assess RVA vaccine effectiveness in LAC countries. METHODOLOGY: We conducted a systematic review and meta-analysis of studies in children under-five who were admitted with laboratory-confirmed RVA diarrhea. We searched Medline, WOS, LILACS, Scopus, and other sources from 2006 to October 2013. Two independent evaluators identified the studies that met predefined selection criteria and extracted relevant information according to a protocol. Pooled estimates were obtained with fixed and random-effects models and stratified according to selected effect modifiers. RESULTS: Of the 806 articles meeting the initial criteria, 8 case-control studies which involved 27,713 participants (6265 cases and 21,448 controls) were included in the final analyses. The pooled estimates were calculated using different types of controls, leading to different degrees of effectiveness. The effectiveness of two doses of RV1 against rotavirus-related hospitalizations ranged from 63.5% (95% CI: 39.2-78.0) to 72.2% (95%CI: 60.9-80.2). Effectiveness ranged from 75.4% (95%CI: 64.6-82.9) to 81.8% (CI 95%:72.3-88.1) among infants <12 months for RV1, and from 56.5% (95%CI: 26.2-74.3) to 66.4% (95%CI: 54.1-75.5) for infants >12 months. The RV5 effectiveness for diarrhea with a Vesikari score >11 in infants 6 to 11 months old ranged from 76.1% (95%CI: 57.6-86.6) to 88.8% (95%CI: 78.3-94.3). Also, it showed 63.5% (95%CI: 29.4-82.6) of effectiveness against G2P [4]. CONCLUSION: RVA vaccines consistently showed protection against diarrhea-related hospitalizations in LAC. Results were more robust for RV1. Effectiveness was shown with different types of controls, but appeared somewhat higher with community controls. Effectiveness was higher among infants <12 months and lower in older children.

Reduced rotavirus vaccine effectiveness among children born during the rotavirus season: a pooled analysis of 5 case-control studies from the Americas.

Using data from rotavirus vaccine effectiveness (VE) studies, we assessed whether rotavirus season modifies rotavirus VE in infants. In the first year of life, adjusted VE was 72% for children born during rotavirus season and 84% for children born in other months (P = .01). Seasonal factors may interfere with vaccine performance.

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.

Effectiveness of the 7-valent pneumococcal conjugate vaccine against vaccine-type invasive disease among children in Uruguay: an evaluation using existing data.

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine immunization program in Uruguay in March 2008 with a 2-dose primary series (given at 2 and 4 months) plus a booster (at 12 months) and a catch-up campaign (two doses given at 15 and 17 months). We used a case-control methodology and existing laboratory surveillance and immunization registry data from Uruguay to evaluate PCV7 effectiveness against vaccine-type invasive pneumococcal disease (VT-IPD). Cases of VT-IPD (with pneumococcus obtained from a normally sterile site) were identified through the National Reference Laboratory. Age- and neighborhood-matched controls were obtained through a national immunization registry in which all children are enrolled at birth regardless of vaccine receipt; all eligible controls were included. Immunization status of cases and controls was assessed through the immunization registry, and conditional logistic regression was used to calculate PCV7 effectiveness. Between April 2008 and February 2010, 44 cases of VT-IPD among children<5 years were identified; 43 (98%) of those children were located in the registry. Among located case patients, 7 (16.3%) were age-eligible to have received at least one dose of PCV7. A total of 637 matched controls were included. Vaccine effectiveness was 91.3% (95% CI: 46.4, 98.6) for ≥ 1 PCV7 doses and 94.8% (95% CI: 43.1, 99.5) for ≥ 2 PCV7 doses. Using existing data we demonstrated high effectiveness of PCV7 against VT-IPD in Uruguay-a middle-income country using a 2-dose primary series plus a booster dose and a limited catch-up campaign. These data also highlight the utility of surveillance and high-quality immunization registries for evaluating the effectiveness of vaccines.

Effectiveness of monovalent rotavirus vaccine in Bolivia: case-control study.

OBJECTIVE: To evaluate the effectiveness of two doses of a monovalent rotavirus vaccine (RV1) against hospital admission for rotavirus in Bolivia. DESIGN: Case-control study. SETTING: Six hospitals in Bolivia, between March 2010 and June 2011. PARTICIPANTS: 400 hospital admissions for rotavirus, 1200 non-diarrhea hospital controls, and 718 rotavirus negative hospital controls. MAIN OUTCOME MEASURES: Odds of antecedent vaccination between case patients and controls; effectiveness of vaccination ((1-adjusted odds ratio)×100), adjusted for age and other confounders; and stratified effectiveness by dose, disease severity, age group, and serotype. RESULTS: In comparison with non-diarrhea controls, case patients were more likely to be male and attend day care but less likely to have chronic underlying illness, higher level maternal education, and telephones and computers in their home. Rotavirus negative controls were somewhat more similar to case patients but also were more likely to be male and attend day care and less likely to have higher level maternal education and computers in their homes. The adjusted effectiveness of RV1 against hospital admission for rotavirus was 69% (95% confidence interval 54% to 79%) with rotavirus negative controls and 77% (65% to 84%) with non-diarrhea controls. The effectiveness of one dose of RV1 was 36% and 56%, respectively. With both control groups, protection was sustained through two years of life, with similar efficacy against hospital admission among children under 1 year (64% and 77%) and over 1 year of age (72% and 76%). RV1 provided significant protection against diverse serotypes, partially and fully heterotypic to the G1P[8] vaccine. Effectiveness using the two control groups was 80% and 85% against G9P[8], 74% and 93%% against G3P[8], 59% and 69% against G2P[4], and 80% and 87% against G9P[6] strains. CONCLUSION: The monovalent rotavirus vaccine conferred high protection against hospital admission for diarrhea due to rotavirus in Bolivian children. Protection was sustained through two years of life against diverse serotypes different from the vaccine strain.