Caracterización clínico epidemiológica de la gastroenteritis por rotavirus. Estudio piloto. Hospital Pediátrico de Centro Habana. Noviembre 2017- abril 2018 / Clinical epidemiological characterization of rotavirus gastroenteritis. Pilot study. Paediatric Hospital of Centro Habana

La gastroenteritis causada por rotavirus constituye un importante problema de salud mundial, por lo que se recomienda incluir la vacunación contra el rotavirus en los programas de inmunización. Para evaluar el impacto de una futura introducción en Cuba de una vacuna contra este patógeno, resulta necesario crear una línea de base pre-vacunación de la carga de la gastroenteritis causada por este virus. Entre noviembre 2017 a abril 2018 se implementó en el Hospital Pediátrico de Centro Habana un sistema de vigilancia para la gastroenteritis causada por rotavirus. Se establecieron las definiciones para las categorías de caso sospechoso, probable y confirmado. Por cada niño captado se recogió una muestra de heces que se analizó con tiras rápidas y se confirmó la presencia de rotavirus por ELISA. Para determinar la severidad de la enfermedad se utilizó la escala de Vesikari. Los resultados fueron expresados en cifras absolutas y relativas, el análisis se realizó a través de la prueba de chi-cuadrado. Del total de ingresos por enfermedad diarreica aguda, el 26 por ciento cumplió los criterios de inclusión y el 46 por ciento resultó confirmado como rotavirus. El hacinamiento en el hogar y asistir al círculo infantil se comportaron como factores de riesgo. El servicio de gastroenterología absorbió la mayor carga de ingresos hospitalarios por esta causa. Los resultados mostrados validan la funcionalidad del sistema de vigilancia implementado y brindan nuevas evidencias sobre la carga de la enfermedad y la utilización de los servicios de un hospital pediátrico cubano, debido a la gastroenteritis provocada por rotavirus, lo que justifica la introducción de la vacuna(AU)

Gastroenteritis caused by rotavirus is a major global health problem, therefore it is recommended that vaccination against rotavirus be included in immunization programs. To evaluate the impact of a future introduction in Cuba of a vaccine against this pathogen, it is necessary to have a pre-vaccination baseline of the burden of gastroenteritis caused by rotavirus. Between November 2017 and April 2018, a surveillance system for gastroenteritis caused by rotavirus was implemented in the Paediatric Hospital of Centro Habana. Definitions were established for the categories of suspected, probable and confirmed cases. For each captured child, stool samples were collected, analyzed with rapid strips and confirmated by ELISA. To determine the severity of the disease, the Vesikari score was used. The results were expressed in absolute and relative figures; the analysis was performed through chi-square. Of the total admissions for acute diarrheal disease, 26 percent met the inclusion criteria and 46 percent were confirmed for rotavirus. Overcrowding at home and attending a day care center were risk factors. The gastroenterology service absorbed the greatest burden of hospital admissions for this cause. The results shown validate the role of the implemented surveillance system and provide new evidence on the burden of disease and use of services for rotavirus gastroenteritis in a cuban pediatric hospital(AU)

Expert consensus on immunoprophylaxis of childhood rotavirus gastroenteritis (2020 version) / 中华流行病学杂志

Group A rotavirus (RV) is one of the major pathogens that cause severe acute gastroenteritis and death in children under 5 years old in China. RV vaccination is the most effective measure for prevention and control of rotavirus gastroenteritis (RVGE). This consensus is developed by reviewing RV related literatures, RV disease data in China, World Health Organization(WHO) position paper on RV vaccines and expert discussion. This consensus aims to provide professional staff with scientific information on rotavirus vaccine use, and evidence for developing the immunization strategy of childhood RVGE in China.

Expert consensus on immunoprophylaxis of childhood rotavirus gastroenteritis(2020) / 中华预防医学杂志

Group A rotavirus (RV) is one of the major pathogens that cause severe acute gastroenteritis and death in children under 5 years old in China. RV vaccination is the most effective measure for prevention and control of rotavirus gastroenteritis (RVGE). This consensus is developed by reviewing RV related literatures, RV disease data in China, World Health Organization(WHO) position paper on RV vaccines and expert discussion. This consensus aims to provide professional staff with scientific information on rotavirus vaccine use, and evidences for developing the immunization strategy of childhood RVGE in China.

Panorama histórico de la enfermedad diarreica aguda en México y el futuro de su prevención / Historical overview of acute infectious diarrhea in Mexico and future preventive strategies

Resumen: Objetivo: Revisar los aspectos epidemiológicos de la enfermedad diarreica aguda (EDA) a través de la historia de México y analizar las estrategias que potencialmente podrán prevenir su aparición en la población mexicana. Material y métodos: Se realizó una búsqueda sistematizada utilizando los siguientes descriptores de las ciencias de la salud: diarrea, morbilidad, mortalidad, México y promoción de la salud de los últimos 20 años (1878-2018). Resultados: Se obtuvieron más de 8 600 artículos que fueron evaluados en función de los objetivos de la presente publicación. Conclusión: Como resultado de una revisión sistemática se observó que, gracias a las estrategias implementadas a lo largo del tiempo, se ha logrado graduar los matices de riesgo de la EDA; ello permite ahora plantear estrategias que guiarán a la prevención de ese padecimiento, de la mano de políticas que incluyan aspectos higiénico-dietéticos, innovaciones farmacéuticas y aplicaciones tecnológicas en medidas sanitarias.

Abstract: Objective: To analyze the epidemiological aspects of AID through Mexican history and the potential strategies to prevent AID in Mexican population. Materials and methods: A systematic review was performed exploring the key words, diarrhea, morbidity, mortality, Mexico, health promotion for the last 20 years (1978-2018). Results: Over 8 600 articles were obtained; all of them were evaluated to consider those follow the aim of the present work. Conclusion: The result of the performed systematic review denoted the influence of AID in Mexican public health policy the adopted actions diminished the AID's associated risks and allowed future strategies to prevent it; those actions must include hygienic and dietetic measures, pharmaceutical innovations and technological tools applied to health policies.

Impacto poblacional a 10 años de la vacunación contra rotavirus en México / Population impact of rotavirus vaccination in Mexico after 10 years

Resumen: Objetivo: Evaluar el impacto de la vacunación contra rotavirus (RV) a 10 años de su universalización sobre la morbimortalidad por enfermedad diarreica aguda (EDA) en niños mexicanos menores de cinco años. Material y métodos: Se compararon las medianas anuales de casos nuevos, defunciones y hospitalizaciones por EDA del periodo pre y posuniversalización; se calcularon reducciones absolutas y relativas, considerando significativos valores de p<0.05. Resultados: La mortalidad, hospitalizaciones y casos nuevos por EDA en menores de cinco años disminuyeron 52.6, 46 y 15.5% respectivamente, en el periodo posuniversalización. Durante la temporada de RV las reducciones en la mortalidad, hospitalizaciones y casos nuevos fueron de 66.9, 64.7 y 28.7%, respectivamente. Conclusiones: A partir de la universalización de la vacuna de RV en México, se aprecian reducciones importantes y sostenidas en la mortalidad, hospitalizaciones e incidencia por EDA, con menor impacto en esta última. El mayor impacto se observa durante la temporada de RV.

Abstract: Objective: To evaluate the impact of rotavirus (RV) vaccination after 10 years of it´s universalization on morbidity and mortality from Acute Diarrheal Disease (ADD) in mexican children under five years of age. Materials and methods: Annual median numbers for ADD new cases, hospitalizations and deaths were compared between pre and post universalization periods; absolute and relative reductions were calculated, considering p<0.05 values as significant. Results: Mortality, hospitalizations and new cases from ADD in children under five decreased 52.6, 46, and 15.5% respectively, in the posuniversalization period. During rotavirus seasons, reduction in mortality, hospitalizations and new cases was 66.9, 64.7, and 28.7% respectively. Conclusions: As of the universal introduction of RV vaccination in Mexico, significant and sustained reductions are appreciated for mortality and hospitalizations from ADD, less so for incidence. A most prominent effect is observed during the winter season.

Protocolo del Sistema Nacional de Vigilancia Epidemiológica: enfermedades transmitidas por agua y alimentos. No. 03 / Protocol of the National Epidemiological Surveillance System: water and foodborne diseases. No. 03

Estos protocolos están dirigido a personal médico, paramédico y otros profesionales que realizan acciones gerenciales y operativas de vigilancia epidemiológica en los servicios de salud del país, y están divididos en varios tomos para dar a conocer y actualizar la identificación y medidas de control para diversos padecimientos a fin de continuar con el mejoramiento de las capacidades técnicas de los trabajadores de salud, que permita planificar la prestación de servicios con decisiones partiendo de un enfoque epidemiológico comprobado, para responder a los cambios de tendencias epidemiológicas y con ello contribuir al fortalecimiento de prácticas asertivas de la salud pública de nuestro país. Las enfermedades transmitidas por alimentos y agua (ETA´s), constituyen un importante problema de Salud Pública, debido a su magnitud, trascendencia, tendencia fluctuante y aumentos en su comportamiento durante el año, lo que ha significado etapas de emergencia, re emergencia, aparición de agentes nuevos con potencial epidémico y el incremento a la resistencia a los antimicrobianos con impacto negativo económico, en grupos de población. Las enfermedades transmitidas por alimentos y agua, se registran entre las primeras diez causas de morbilidad y mortalidad en el país; evento notificado como enfermedad diarreica, con frecuencia los servicios de salud tienen poca capacidad de respuesta para identificación del agente etiológico, limitándose a implementar medidas de control eficientes de las fuentes de infección o contaminación y divulgación de acciones dirigidas a minimizan los factores de riesgo identificados.

Unintended pregnancy and its impact on childhood rotavirus immunization in Peru / Embarazo involuntario y su repercusión sobre la vacunación contra rotavirus de la niñez en Perú / Gravidez indesejada e repercussão na vacinação contra rotavírus em crianças no Peru

ABSTRACT Objective To examine the association between unintended pregnancy and inadequate rotavirus immunization in Peruvian children. Methods Utilizing cross-sectional observational data from the 2012 Demographic and Health Survey (DHS), logistic regression analysis was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association between unintended pregnancy and inadequate rotavirus immunization among children. Results Of 9 620 pregnancies in the five years preceding the survey, 5 396 of them (56.1%) were reported as unintended, of which 2 981 were mistimed (30.9%) and 2 415 (25.1%) were unwanted. A total of 5 187 children (54.9%; 95% CI = 53.8%-56.1%) were recorded to have inadequate rotavirus immunization. Maternal literacy status was found to be a significant effect modifier of the association between pregnancy intention and rotavirus immunization (P value = 0.006). Among children born to illiterate mothers, unintended pregnancy was significantly associated with increased odds of inadequate rotavirus immunization (aOR = 2.6; 95% CI = 1.2-4.4), as compared to children from intended pregnancies. Deficient rotavirus immunization was significantly predicted by inadequate polio, pneumococcal, and influenza vaccinations; having a television in the household; and less maternal education. In contrast, having received breast-feeding education was protective against inadequate rotavirus immunization. Among literate mothers, there was no association between pregnancy intention and rotavirus immunization. Conclusion Our study provides evidence that improving literacy among mothers could increase rotavirus vaccination uptake among children from unintended pregnancies.

RESUMEN Objetivo Examinar la asociación entre el embarazo involuntario y la vacunación inadecuada contra rotavirus en niños peruanos. Métodos A partir de datos de observación transversales de la Encuesta de Demografía y Salud del 2012, se empleó el análisis de regresión logística para calcular las razones de posibilidades ajustadas (aOR) y los intervalos de confianza de 95% (IC) de la asociación entre el embarazo involuntario y la inmunización inadecuada contra rotavirus en los niños. Resultados De 9 620 embarazos en los cinco años anteriores a la encuesta, 5 396 (56,1%) se reconocieron como involuntarios, de los cuales 2 981 fueron inoportunos (30,9%) y 2 415 (25,1%) fueron no deseados. Se registraron 5 187 niños (54,9%; IC de 95% = 53,8%-56,1%) con inmunización contra rotavirus inadecuada. El alfabetismo materno resultó ser un importante modificador de efecto de la asociación entre la intencionalidad del embarazo y la vacunación antirrotavírica (valor de P = 0,006). En los hijos de las mujeres analfabetas, el embarazo involuntario se asoció significativamente con mayores probabilidades de inmunización inadecuada contra rotavirus (aOR = 2,6; IC de 95% = 1,2-4,4), en comparación con los nacidos de los embarazos voluntarios. Las vacunaciones antipoliomielítica, antineumocócica y antigripal inadecuadas, tener un televisor en el hogar y una menor escolaridad materna fueron factores predictivos significativos de una inmunización antirrotavírica deficiente. Por el contrario, haber recibido instrucción respecto a la lactancia materna fue un factor protector contra la inmunización antirrotavírica inadecuada. En las madres alfabetizadas, no hubo asociación alguna entre la intencionalidad del embarazo y la inmunización contra rotavirus. Conclusiones Nuestro estudio aporta evidencia que muestra que mejorar el alfabetismo en las madres podría aumentar la captación de la vacunación antirrotavírica en los niños nacidos de embarazos involuntarios.

RESUMO Objetivo Examinar a associação entre gravidez indesejada e falta de vacinação oportuna contra rotavírus em crianças peruanas. Métodos A partir de dados observacionais transversais obtidos na Pesquisa de Demografia e Saúde 2012, foi conduzida uma análise de regressão logística para estimar razões de chances ajustadas (OR aj) e intervalos de confiança de 95% (IC 95%) para a associação entre gravidez indesejada e falta de vacinação oportuna contra rotavírus em crianças. Resultados Dentre 9.620 gravidezes ocorridas nos cinco anos anteriores à pesquisa, 5.396 (56,1%) foram referidas como não intencionadas, das quais 2.981 foram não no momento certo (30,9%) e 2.415 (25,1%) indesejadas. Registrou-se falta de vacinação oportuna contra rotavírus em 5.187 crianças ao todo (54,9%; IC 95% = 53,8%-56.1%). Verificou-se que o nível de escolaridade materna é um importante modificador de efeito da associação entre intenção de engravidar e vacinação contra rotavírus (valor de P = 0,006). Nas crianças nascidas de mães sem escolaridade, observou-se uma associação significativa entre gravidez indesejada e maior chance de falta de vacinação oportuna contra rotavírus (OR aj = 2,6; IC 95% = 1,2-4,4) quando comparadas às crianças de gravidezes intencionadas. A falta de vacinação contra rotavírus prognosticou de modo significativo a falta de vacinação oportuna contra poliomielite, doença pneumocócica e gripe; possuir televisor no domicílio e menor nível de escolaridade materna. Em contraste, receber orientação sobre o aleitamento materno foi um fator protetor contra a falta de vacinação oportuna contra rotavírus. Entre as mães com escolaridade, não se verificou associação entre intenção de engravidar e vacinação contra rotavírus. Conclusão O estudo evidencia que melhorar o nível de escolaridade materna poderia contribuir para aumentar a vacinação contra rotavírus em crianças nascidas de gravidez indesejada.

Time series investigation of changes in seasonality of acute diarrhea hospitalizations before and after rotavirus vaccine in Southern Brazil / Investigando alterações de sazonalidade nas internações por diarreia aguda antes e depois da introdução da vacina de rotavírus no Sul do Brasil / Investigando alteraciones de estacionalidad en los internamientos por diarrea aguda, antes y después de la introducción de la vacuna del rotavirus en el sur de Brasil

Abstract: Diarrhea by rotavirus is one of the main causes of mortality in children in developing countries, although the hospitalization rates (HR) for acute diarrhea have been found to have fallen since the introduction of the rotavirus vaccine. However, the patterns of the rotavirus are still not well understood and seasonal peaks occur throughout the year, with variations between countries and over time. The main objective of this study was to analyze the temporal behavior of HR caused by acute diarrhea in children under the age of one in the south of Brazil, between 2000 and 2011, and to explore changes in seasonality patters after the introduction of the vaccine against the rotavirus in 2006. Harmonic and multiscale wavelet analyses were used to detect seasonality and the points of change in the temporal scale. The statistical significance of each seasonality that was identified was tested using Fisher's test. The harmonic and wavelet analyses show annual seasonal and six-monthly patterns for HR, as well as a clear change after the introduction of the vaccine in 2006.

Resumo: A diarreia por rotavírus é uma das principais causas de mortalidade em crianças nos países em desenvolvimento, embora tenha sido observada a redução nas taxas de hospitalização (HR) por diarreias aguda desde que a vacina do rotavírus foi introduzida. A dinâmica do rotavírus, no entanto, ainda é mal compreendida e picos sazonais ocorrem durante todo o ano, com variações entre países e ao longo do tempo. O principal objetivo foi analisar o comportamento temporal das HR devido a diarreia aguda em crianças menores de um ano de idade no sul do Brasil, de 2000 a 2011, e investigar mudanças no padrão de sazonalidade após a introdução da vacina contra o rotavírus em 2006. Análises harmônica e multiescala wavelet foram utilizadas para detectar a sazonalidade e pontos de mudança na série temporal. A significância estatística de cada sazonalidade identificada foi testada pelo teste de Fisher. As análises harmônica e wavelet mostraram padrões sazonais anual e semestral das HR, bem como a nítida mudança após a introdução da vacina em 2006.

Resumen: La diarrea por rotavirus es una de las principales causas de mortalidad en niños en los países en desarrollo, aunque se haya observado una reducción en las tasas de hospitalización (HR) por diarreas agudas, desde que se introdujo la vacuna del rotavirus. La dinámica del rotavirus, no obstante, aunque está mal comprendida -y se producen picos estacionales- tiene lugar durante todo el año, con variaciones entre países y a lo largo del tiempo. El principal objetivo fue analizar el comportamiento temporal de las HR, debido a la diarrea aguda en niños menores de un año de edad en el sur de Brasil, de 2000 a 2011, e investigar cambios en el patrón de estacionalidad tras la introducción de la vacuna contra el rotavirus en 2006. Los análisis harmónico y multiescala wavelet se utilizaron para detectar la estacionalidad y puntos de cambio en la serie temporal. La significancia estadística de cada estacionalidad identificada fue testada por el test de Fisher. Los análisis harmónico y wavelet mostraron patrones estacionales anual y semestral de los HR, así como un nítido cambio tras la introducción de la vacuna en 2006.

The impact of rotavirus vaccination on emergency department visits and hospital admissions for acute diarrhea in children under 5 years / Impacto da vacinação contra rotavírus nas consultas de pronto-socorro e internações por doença diarreica aguda em crianças menores de 5 anos de idade

Summary Introduction: Acute diarrheal disease is the second cause of death in children under 5 years. In Brazil, from 2003 to 2009, acute diarrhea was responsible for nearly 100,000 hospital admissions per year and 4% of the deaths in children under 5 years. Rotavirus is the leading cause of severe acute diarrhea worldwide. In 2006, the rotavirus monovalent vaccine (RV1) was added to the Brazilian National Immunization Program. Objectives: To analyze the impact of the RV1 on emergency department (ED) visits and hospital admissions for acute diarrhea. Method: A retrospective ecologic study at the University Hospital, University of São Paulo. The study analyzed the pre-vaccine (2003–2005) and the post-vaccine (2007–2009) periods. We screened the main diagnosis of all ED attendances and hospital admissions of children under 5 years in an electronic registry system database and calculated the rates of ED visits and hospital admissions. The reduction rate was analyzed according to the following formula: reduction (%) = (1 - odds ratio) x 100. Results: The rates of ED visits for acute diarrhea was 85.8 and 80.9 per 1,000 total ED visits in the pre and post vaccination periods, respectively, resulting in 6% reduction (95CI 4 to 9%, p<0.001). The rates of hospital admissions for acute diarrhea was 40.8 per 1,000 in the pre-vaccine period and dropped to 24.9 per 1,000 hospitalizations, resulting in 40% reduction (95CI 22 to 54%, p<0.001). Conclusion: The introduction of the RV1 vaccine resulted in 6% reduction in the ED visits and 40% reduction in hospital admissions for acute diarrhea.

Resumo Introdução: a doença diarreica aguda é a segunda causa de morte em crianças abaixo de 5 anos de idade. No Brasil, entre 2003 e 2009, a diarreia aguda foi responsável por cerca de 100 mil internações por ano e por 4% das mortes em crianças abaixo de 5 anos de idade. O rotavírus é a principal etiologia de diarreia aguda grave. A vacina monovalente (RV1) contra o rotavírus foi introduzida em 2006. Objetivos: verificar o impacto da vacina monovalente contra rotavírus nas consultas de pronto-socorro e internações por doença diarreica aguda em crianças menores de 5 anos de idade. Método: foi realizado um estudo ecológico retrospectivo no Hospital Universitário da Universidade de São Paulo. O período foi dividido em pré-vacina (2003 a 2005) e pós-vacina (2007 a 2009). Foram incluídas todas as crianças abaixo de 5 anos que passaram em consulta no pronto-socorro. Foram obtidas as taxas de consultas no pronto-socorro e internações por doença diarreica aguda. A redução nas taxas foi obtida através da fórmula: redução (%) = (1 - odds ratio) x 100. Resultados: no período pré-vacina, a taxa de consultas por diarreia aguda foi de 85,8 consultas por 1.000 consultas gerais, enquanto no período pós-vacina a taxa de consultas por diarreia aguda foi 80,9 por 1.000, uma redução de 6% (IC95% 4-9, p<0,001). A taxa de internação por diarreia aguda era 40,8 internações por 1.000 e caiu para 24,9 por 1.000, redução de 40% (IC95% 22-54, p<0,001). Conclusão: após a introdução da vacina contra rotavírus houve uma redução de 6% nas consultas por diarreia aguda no pronto-socorro e de 40% nas internações por diarreia aguda.

Hospital-based surveillance of intussusception among infants / Vigilância hospitalar de intussuscepção entre neonatos

Abstract Objective: Intussusception surveillance was initiated after the nationwide introduction of live attenuated monovalent rotavirus vaccine (RV1). The objective is to assess the epidemiology of intussusception and compare the number of cases before and after the introduction of rotavirus vaccine. Methods: Cases of intussusception occurring between March 2006 and January 2008 were identified through a prospective enhanced passive surveillance system established in sentinel state hospitals. Retrospective review of medical records was used to identify cases, which occurred in sentinel hospitals between January 2001 and February 2006. Results: From 2001 to 2008, 331 intussusception cases were identified, 59.5% were male, with peak incidence among those 18–24 weeks of age. Overall <10% of cases were among infants 6–14 weeks of age (when the first dose of RV1 is administered). The most frequently observed signs or symptoms of intussusception included vomiting (89.4%), bloody stool (75.5%), and abdominal distention (71.8%). A majority (92.1%) of the case-patients required surgery for treatment; 31.8% of those who underwent surgery required bowel resection, and 13 (3.9%) died. Among the 21 hospitals that reported cases throughout the entire surveillance period (2001–2008), the number of intussusception events during 2007 (n = 26) and 2008 (n = 19) was not greater than the average annual number (n = 31, range 24–42) during baseline years 2001–2005. Conclusions: Although this analysis did not identify an increase in intussusception cases during the two years after RV1 introduction, these results support the need for special epidemiologic methods to assess the potential link between rotavirus vaccine and this very rare adverse event.

Resumo Objetivo: A vigilância da intussuscepção foi iniciada após a introdução da vacina monovalente viva atenuada contra rotavírus (RV1) em todo o país. O objetivo é avaliar a epidemiologia da intussuscepção e comparar a quantidade de casos antes e depois da introdução da vacina contra rotavírus. Métodos: Os casos de intussuscepção entre março de 2006 e janeiro de 2008 foram identificados por meio de um sistema de vigilância passivo prospectivo aprimorado estabelecido em hospitais-sentinela estaduais. A análise retrospectiva de prontuários médicos foi usada para identificar os casos que ocorreram em hospitais-sentinela entre janeiro de 2001 e fevereiro de 2006. Resultados: De 2001-2008, identificamos 331 casos de intussuscepção, 59,5% dos quais ocorreram em pacientes do sexo masculino, com pico de incidência entre aqueles com 18-24 semanas de idade. Em geral, < 10% dos casos ocorreram entre neonatos com 6-14 semanas de idade (quando a 1a dose de RV1 é administrada). Os sinais ou sintomas de intussuscepção observados com mais frequência incluíam vômito (89,4%), fezes com sangue (75,5%) e distensão abdominal (71,8%). A maioria (92,1%) dos pacientes precisou de cirurgia para o tratamento; 31,8% dos que se submeteram à cirurgia precisaram de ressecção intestinal e 13 (3,9%) vieram a óbito. Entre os 21 hospitais que relataram casos durante todo o período de vigilância (2001-2008), a quantidade de casos de intussuscepção em 2007 (n = 26) e 2008 (n = 19) não foi maior do que a quantidade média anual (31, faixa de 24-42) durante os anos-base de 2001-2005. Conclusões: Embora esta análise não tenha identificado um aumento nos casos de intussuscepção nos dois anos após a introdução da RV1, esses resultados justificam a necessidade de métodos epidemiológicos especiais para avaliar a possível associação entre a vacina contra rotavírus e esse evento adverso muito raro.

The role of human adenoviruses type 41 in acute diarrheal disease in Minas Gerais after rotavirus vaccination

Abstract Human adenovirus species F (HAdV-F) type 40 and 41 are commonly associated with acute diarrheal disease (ADD) across the world. Despite being the largest state in southeastern Brazil and having the second largest number of inhabitants, there is no information in the State of Minas Gerais regarding the role of HAdV-F in the etiology of ADD. This study was performed to determine the prevalence, to verify the epidemiological aspects of infection, and to characterize the strains of human adenoviruses (HAdV) detected. A total of 377 diarrheal fecal samples were obtained between January 2007 and August 2011 from inpatient and outpatient children of age ranging from 0 to 12 years. All samples were previously tested for rotavirus, norovirus, and astrovirus, and 314 of 377 were negative. The viral DNA was extracted, amplified using the polymerase chain reaction and the HAdV-positive samples were sequenced and phylogenetically analyzed. Statistical analyses were performed using the Chi-square test (p < 0.05), considering two conditions: the total of samples tested (377) and the total of negative samples for the remaining viruses tested (314). The overall prevalence of HAdV was 12.47% (47/377); and in 76.60% (36/47) of the positive samples, this virus was the only infectious agent detected. The phylogenetic analysis of partial sequences of 32 positive samples revealed that they all clustered with the HAdV-F type 41. The statistical analysis showed that there was no correlation between the onset of the HAdV infection and the origin of the samples (inpatients or outpatients) in the two conditions tested: the total of samples tested (p = 0.598) and the total of negative samples for the remaining viruses tested (p = 0.614). There was a significant association in the occurrence of infection in children aged 0–12 months for the condition 1 (p = 0.030) as well as condition 2 (p = 0.019). The occurrence of infections due to HAdV did not coincide with a pattern of seasonal distribution. These data indicate the significant involvement of HAdV-F type 41 in the etiology of ADD in Minas Gerais, which demonstrates the importance of other viral agents in the development of the disease after the introduction of rotavirus vaccine immunization.

Rotavirus genotypes circulating in Brazil, 2007-2012: implications for the vaccine program / Genótipos de rotavírus circulando no Brasil, 2007-2012: implicações para o Programa de Vacinação

SUMMARYRegarding public health in Brazil, a new scenario emerged with the establishment of universal rotavirus (RV) vaccination programs. Herein, the data from the five years of surveillance (2007-2012) of G- and P-type RV strains isolated from individuals with acute gastroenteritis in Brazil are reported. A total of 6,196 fecal specimens were investigated by ELISA and RT-PCR. RVs were detected in 19.1% (1,181/6,196). The peak of RV incidence moved from June-August to September. RV was detected less frequently (19.5%) among children ≤ 5 years than in older children and adolescents (6-18 years) (40.6%). Genotype distribution showed a different profile for each year: G2P[4] strains were most prevalent during 2007-2010, G9P[8] in 2011, and G12P[8] in 2012. Mixed infections (G1+G2P[4], G2+G3P[4]+P[8], G2+G12P[8]), unusual combinations (G1P[4], G2P[6]), and rare strains (G3P[3]) were also identified throughout the study period. Widespread vaccination may alter the RV seasonal pattern. The finding of RV disease affecting older children and adolescents after vaccine implementation has been reported worldwide. G2P[4] emergence most likely follows a global trend seemingly unrelated to vaccination, and G12, apparently, is emerging in the Brazilian population. The rapidly changing RV genotype patterns detected during this study illustrate a dynamic population of co-circulating wildtype RVs in Brazil.

RESUMOEm relação à saúde pública no Brasil, um novo cenário emergiu com o estabelecimento dos programas universais de vacinação contra o rotavírus (RV). Os resultados de cinco anos (2007-2012) de vigilância dos genótipos G e P de cepas de RV detectadas em indivíduos com gastroenterite aguda no Brasil são descritos no presente estudo. Um total de 6196 amostras fecais foi investigado utilizando ELISA e RT-PCR. RVs foram detectados em 19,1% (1181/6196). O pico de incidência de RV se deslocou de junho-agosto para setembro. RV foi detectado com menor frequência entre crianças ≤ 5 anos (19,5%) quando comparado às crianças mais velhas e adolescentes (6-18 anos) (40,6%). A distribuição genotípica mostrou um perfil diferente a cada ano: a cepa G2P[4] foi prevalente durante 2007-2010, G9P[8] em 2011 e G12P[8] em 2012. Infecções mistas (G1+G2P[4], G2+G3P[4]+P[8], G2+G12P[8]), combinações não usuais (G1P[4], G2P[6]) e cepas atípicas (G3P[3]) também foram identificadas em todo o período do estudo. A vacinação em massa pode alterar o padrão sazonal do RV. A tendência do RV em infectar crianças mais velhas e adolescentes após a implementação da vacina tem sido relatada em todo o mundo. A emergência de G2P[4] segue provavelmente a tendência mundial e, aparentemente, não está relacionada à vacinação. G12 também parece estar emergindo na população brasileira. As rápidas mudanças nos padrões de genótipos dos RVs observados durante o período desse estudo ilustram a existência de uma população dinâmica de cepas selvagens co-circulando no Brasil.

The effectiveness of a rotavirus vaccine in preventing hospitalizations and deaths presumably due to acute infectious diarrhea in Brazilian children: a quasi-experimental study

INTRODUCTION: Rotavirus is the main etiologic agent of acute infectious diarrhea in children worldwide. Considering that a rotavirus vaccine (G1P8, strain RIX4414) was added to the Brazilian vaccination schedule in 2006, we aimed to study its effectiveness and safety regarding intestinal intussusception. METHODS: A quasi-experimental trial was performed in which the primary outcome was the number of hospitalizations that were presumably due to acute infectious diarrhea per 100,000 children at risk (0-4 years old). The secondary outcomes included mortality due to acute infectious diarrhea and the intestinal intussusception rates in children in the same age range. We analyzed three scenarios: Health Division XIII of the State of São Paulo (DRS XIII) from 2002 to 2008, the State of São Paulo, and Brazil from 2002 to 2012. RESULTS: The averages of the hospitalization rates for 100,000 children in the pre- and post-vaccination periods were 1,413 and 959, respectively, for DRS XIII (RR=0.67), 312 and 249, respectively, for the State of São Paulo (RR=0.79), and 718 and 576, respectively, for Brazil (RR=0.8). The mortality rate per 100,000 children in the pre- and post-vaccination periods was 2.0 and 1.3, respectively, for DRS XIII (RR=0.66), 5.5 and 2.5, respectively, for the State of São Paulo (RR=0.47), and 15.0 and 8.0, respectively, for Brazil (RR=0.53). The average annual rates of intussusception for 100,000 children in DRS XIII were 28.0 and 22.0 (RR=0.77) in the pre- and post-vaccination periods, respectively. CONCLUSIONS: A monovalent rotavirus vaccine was demonstrated to be effective in preventing the hospitalizations and deaths of children that were presumably due to acute infectious diarrhea, without increasing the risk of intestinal intussusception. .

Changes in epidemiology of rotavirus in the Triângulo Mineiro region of Brazil: lack of two consecutive rotavirus seasons

Rotaviruses are the main cause of infantile acute diarrhea, and a monovalent (G1P[8]) vaccine against the virus was introduced into the Brazilian National Immunization Program for all infants in March 2006. The objectives of this study were to determine the rate and genotype distribution of rotavirus causing infantile diarrhea in the Triângulo Mineiro region of Brazil during 2011-2012 and to assess the impact of local vaccination. Fecal specimens were analyzed for detection and characterization of rotavirus using polyacrylamide gel electrophoresis, reverse transcription followed by polymerase chain reaction (PCR), and PCR-genotyping assays. Overall, rotavirus was diagnosed in 1.7% (6/348) of cases. Rotavirus positivity rates decreased 88% [95% confidence intervals (CI)=15.2, 98.3%; P=0.026] in 2011 and 78% (95%CI=30.6, 93.0%; P=0.007) in 2012 when compared with available data for baseline years (2005/2006) in Uberaba. In Uberlândia, reductions of 95.3% (95%CI=66.0, 99.4%; P=0.002) in 2011, and 94.2% (95%CI=56.4, 99.2%; P=0.004) in 2012 were also observed compared with data for 2008. The circulation of rotavirus G2P[4] strains decreased during the period under study, and strains related to the P[8] genotype reemerged in the region. This study showed a marked and sustained reduction of rotavirus-related cases, with a lack of rotavirus in the 2011 and 2012 seasons, suggesting a positive impact of the vaccination program.

Intervention analysis of introduction of rotavirus vaccine on hospital admissions rates due to acute diarrhea / Análise de intervenção da introdução da vacina do rotavirus nas taxas de internação hospitalar por diarreia aguda / Análisis de intervención en la introducción de la vacuna contra el rotavirus en las tasas de hospitalización por diarrea aguda

The aim of this study is to investigate the impact of rotavirus vaccine on hospitalization rates for acute diarrhea in children younger than 5 years old after the introduction of the vaccine in 2006. A descriptive analytical observational study was carried out of the hospitalization rates occurred between 2000 and 2011 in 22 Regional Health Centers of Paraná State, Brazil. The effect of the vaccine was assessed by applying the SARIMA/Box-Jenkins time series methodology of intervention analysis, which allows verifying the slopes of the series are different after the introduction of the vaccine and estimating the magnitude of these effects for children younger than five years of age, by age group, for each region center. It was verified a statistically significant reduction by center/month on hospitalization rates for children 1 year old and younger, with averages of 47% and 58%, respectively, in December 2011.

O objetivo desse estudo é investigar o impacto da vacina do rotavírus nas taxas de internação por diarreia aguda em crianças menores de cinco anos após a introdução da vacina em 2006. Foi realizado um estudo analítico observacional descritivo das taxas de hospitalização ocorridas entre 2000 e 2011, em 22 Centros Regionais de Saúde do Estado do Paraná, Brasil. O efeito da vacina foi avaliado por séries temporais aplicando a metodologia SARIMA/Box-Jenkins com análise da intervenção, a qual permite verificar que os declives das séries são diferentes após a introdução da vacina, bem como estimar a magnitude desses efeitos para crianças menores de cinco anos de idade, por faixa etária, para cada região. Verificou-se redução estatisticamente significativa por centro/mês nas taxas de internação por diarreia aguda para as crianças menores de 1 ano de idade e de 1 ano de idade, com médias de 47% e 58%, respectivamente, em dezembro de 2011.

El objetivo de este estudio es investigar el impacto de la vacuna contra el rotavirus en las tasas de hospitalización, relacionadas con diarrea aguda en niños menores de 5 años, después de que se introdujese la vacuna en 2006. Se trata de un estudio observacional, analítico descriptivo de las tasas de hospitalización acaecidas entre 2000 y 2011 en 22 centros regionales de salud del estado de Paraná, Brasil. El efecto de la vacuna se evaluó mediante la aplicación de la serie de tiempo SARIMA/metodología de Box-Jenkins de análisis de intervención, lo que demuestra que los declives de las series son diferentes después de la introducción de la vacuna, con el fin de estimar la magnitud de estos efectos en los niños menores 5 años de edad, por grupos de edad para cada región. Se ha encontrado una reducción estadísticamente significativa de centro/mes en las tasas de hospitalización para niños menores de 1 año de edad y de 1 año de edad, con un promedio de 47% y 58%, respectivamente, en diciembre de 2011.

Rotavirus in adults, Brazil, 2004-2011: G2P[4] dominance and potential impact on vaccination

Objectives: The aim of this study was to monitor rotavirus (RV) infections in adults >18 years with acute gastroenteritis during 2004–2011 national Brazilian RV surveillance. In addition, to characterize the RV group A (RVA) strains in order to gain insight into the supposed vaccine selective pressure imposed to Brazilian children population. Methods: A total of 2102 convenient fecal specimens were investigated by ELISA, PAGE, and RT-PCR. Results: RV was detected in 203 (9.6%) of 2102 specimens, and showed a marked peak of detection in September. RVA infection was detected in 9.4% (197/2102) and RV group C (RVC) in 0.3% (6/2102). The most frequent genotypes detected in 2004 and 2005 were G9P[8] (38.5%; 5/13) and G1P[8] (54.5%; 6/11), respectively. The dominant genotype identified from 2006 to 2011 was G2P[4] (64.4%; 116/180). Detection rate varied during the 8-year period of the study from 0.7% to 12.9%. Conclusion: The high detection rate of G2P[4] in adults provides further evidence that its dominance reflects the seasonality of RVA strains instead of the supposed selective advantage created by vaccination program. It also can be suggested that adult infections may serve as a reservoir to maintain RVA strains in childhood gastroenteritis. Considering the detection rate, the evident reduction of RVA frequency observed in children after vaccine introduction was not present in adults. .

Detecção de rotavírus do grupo A em amostras fecais: adaptação do teste de aglutinação em látex para o emprego de anticorpos IgY anti-Rotavírus A / Detection of group a rotavirus in fecal samples: adaptation of latex agglutination test for anti-rotavirus a igy antibody employment

A infecção pelo rotavírus A (RVA) é responsável por cerca de 453.000 mortes anualmente e aproximadamente 40 por cento das hospitalizações por diarreia em crianças menores de cinco anos em todo o mundo, sendo o principal causador de gastroenterite aguda nesse grupo populacional. O desenvolvimento de um método de diagnóstico rápido, barato, sensível e específico para a detecção de RVA é importante do ponto de vista epidemiológico porque permite identificar surtos no local de ocorrência. O uso da imunoglobulina Y (IgY), anticorpo purificado a partir da gema de ovo, vem crescendo nos últimos anos, devido às características vantajosas quando comparada com a imunoglobulina G (IgG), como a obtenção de anticorpos de forma não invasiva e a produção de anticorpos em grandes concentrações. Este trabalho objetivou a adaptação de um teste de diagnóstico através da substituição do anticorpo de captura IgG pela IgY específica para o antígeno de RVA (LATEXY-ROTA). Para isto 09 frangas poedeiras foram imunizadas com o RVA, os ovos foram coletados e a IgY purificada a partir da gema do ovo por polietileno glicol 6.000, seguida da purificação adicional por cromatografia de troca iônicaA IgY anti-RVA purificada foi ligada covalentemente à partículas de poliestireno e usada como insumo na adaptação de um teste de aglutinação em látex, sendo testada em um painel de amostras fecais sabidamente positivas e negativas previamente selecionadas pelo Centro Regional de Referência para Rotaviroses do Laboratório de Virologia Comparada e Ambiental (LVCA/IOC-FIOCRUZ)...

Foi obtida uma sensibilidade de 75 por cento e uma especificidade de 87,5 por cento quando o LATEXY-ROTA foi comparado com um teste imunoenzimático comercial disponível (padrão ouro). Quando comparado com dois testes comerciais de aglutinação em látex testados no painel de amostras utilizando a IgG, o LATEXY-ROTA obteve uma sensibilidade de 100 por cento e especificidade de 88,24 por cento. Baseado nos dados obtidos, sugerimos a viabilidade da substituição da IgG por IgY no ensaio de aglutinação pelo látex...

The infection by rotavirus (RV) is responsible for approximately 453,000 deaths annually and approximately 40 percent of hospitalizations by diarrhea in children under five years worldwide, being the major cause of acute gastroenteritis in this populationgroup. The development of a rapid method, inexpensive, sensitive and specific for rotavirus diagnosis is important from the disease because it allows the identification of outbreaks in the site of occurrence. The use of Immunoglobulin Y (IgY) antibodypurified from egg yolk, has been grown in recent years, due to the advantageous features compared to immunoglobulin G (IgG), as a noninvasive recovery of antibodies and production in high concentrations. The aim of this method was to adapt a diagnostic test by replacing the IgG capture antibody by specific IgY for RVAantigen (LATEXY-ROTA). For that, 09 laying hens were immunized with RVA, the eggs were collected and IgY purified from egg yolk by polyethylene glycol 6,000, followed by purification by ion exchange chromatography. The purified anti-IgY RVA was covalently bound to polystyrene particles, being tested in a panel of positive and negative fecal samples previously determined by the Rotavirus Regional ReferenceCenter of Comparative and Environmental Virology Laboratory (LVCA/IOCFIOCRUZ). A sensitivity of 75% and specificity of 85,7% was observed when the adapted test was compared to a commercial available enzyme immunoassay (goldenstandard). When compared to two commercial latex agglutination tests using the IgG tested on the panel of samples, the LATEXY-ROTA had a sensitivity of 100 percent and specificity of 88.2 percent. Based on the obtained data, we suggest the feasibility of replacing the IgG by IgY in the latex agglutination assay...

Evaluación del impacto de la vacuna contra rotavirus en Colombia usando métodos rápidos de evaluación / Impact assessment of the rotavirus vaccine in Colombia using rapid evaluation methods

OBJETIVO: Estimar la efectividad de la vacuna monovalente antirrotavírica para prevenir la hospitalización por enfermedad diarreica aguda en niños menores de 2 años en cinco ciudades de Colombia. MÉTODOS: Se realizó una encuesta poblacional sobre una muestra probabilística de niños mayores de 2 meses y menores de 24 meses de edad en cinco ciudades de Colombia (Barranquilla, Bogotá, Cali, Cartagena y Riohacha) en el período de agosto a octubre de 2010. La vacuna fue introducida en el Programa Ampliado de Inmunizaciones en enero de 2009. Se estimaron las coberturas de vacunación contra rotavirus por grupos de edad y la incidencia acumulada de hospitalización por diarrea severa, y se evaluó la magnitud de la asociación entre la vacunación con una o dos dosis de vacuna antirrotavírica y la hospitalización por diarrea, utilizando la razón de probabilidades (RP) ajustada por edad y otros factores de importancia epidemiológica. La efectividad de la vacunación se estimó usando la expresión 1 - RP. RESULTADOS: La cobertura de vacunación con una dosis de vacuna fue de 87,3%. En los 12 meses previos a la encuesta 43,2% (1 453 niños) de menores de 24 meses presentaron diarrea, y de ellos, 5,2% (174 niños) fueron hospitalizados por esta causa. La efectividad de dos dosis de vacuna antirrotavírica para prevenir la hospitalización por diarrea severa fue de 68% (intervalo de confianza de 95%: 55%-77%). CONCLUSIONES: La vacunación contra rotavirus en Colombia protege contra la hospitalización por diarrea por cualquier causa. El uso de encuestas transversales se mostró adecuado para evaluar rápidamente la efectividad de un programa de vacunación con una nueva vacuna.

OBJECTIVE: Estimate the effectiveness of the monovalent rotavirus vaccine in preventing the need to hospitalize children under 2 years old for acute diarrheal disease in five Colombian cities. METHODS:A population survey was conducted based on a probability sample of children over 2 months and under 24 months of age in five Colombian cities (Barranquilla, Bogotá, Cali, Cartagena, and Riohacha) over the period from August through October 2010. The vaccine had been introduced in the Expanded Program on Immunization in January 2009. Rotavirus vaccination coverage was estimated by age group; the cumulative incidence of hospitalization for severe diarrhea was determined; and the magnitude of correlation between vaccination with one or two doses of rotavirus vaccine and hospitalization for diarrhea was calculated using the age-adjusted probability ratio (PR) and other epidemiologically significant factors. Effectiveness of the vaccine was estimated using the expression 1-PR. RESULTS: Coverage with a single dose of the rotavirus vaccine was 87.3%. During the 12 months prior to the survey, 1 453 of the children under 24 months old in the study areas (43.2%) had presented with diarrhea, and of these, 174 (5.2%) had been hospitalized for this cause. The effectiveness of two doses of the vaccine in preventing hospitalization for severe diarrhea was 68% (CI 95% = 55%−77%). CONCLUSIONS: In Colombia, rotavirus vaccination protects against hospitalization for diarrhea due to any cause. The use of cross-sectional surveys appeared to be adequate for rapid evaluation of an immunization program's effectiveness with a new vaccine.