Costos de hospitalización por diarrea en niños durante el período de circulación de rotavirus en el Noroeste Argentino / Hospitalization costs associated with diarrhea among children during the period of rotavirus circulation in the Northwest region of Argentina

Objetivo. Evaluar los costos médicos directos, gastos de bolsillo y costos indirectos en casos de diarrea aguda hospitalizada en <5 años, en el Hospital de Niños Héctor Quintana de la provincia de Jujuy, durante el período de circulación de rotavirus en la región Noroeste de Argentina. Métodos. Estudio de corte trasversal de costos de enfermedad. Fueron incluidos todos los niños hospitalizados <5 años con diagnóstico de diarrea aguda y deshidratación durante el período de circulación de rotavirus, entre el 1/5/2013 y el 31/10/2013. La evaluación de costos médicos directos se realizó mediante la revisión de historias clínicas, y los gastos de bolsillo y costos indirectos, mediante una encuesta. Para el intervalo de confianza del 95% del costo promedio por paciente, se realizó un análisis probabilístico de 10 000 simulaciones por remuestreo (boostraping). Resultados. Fueron enrolados 105 casos. La edad promedio fue de 18 meses (desvío estándar 12); 62 (59%) fueron varones. El costo médico directo, gasto de bolsillo y pérdida de dinero por lucro cesante promedio por caso fue de AR$ 3413, 6 (2856, 35-3970, 93) (USD 577, 59), AR$ 134, 92 (85, 95-213, 57) (USD 22, 82) y de AR$ 301 (223, 28380, 02) (USD 50, 93), respectivamente. El total del costo por evento hospitalizado fue de AR$ 3849, 52 (3298-4402, 25) (USD 651, 35). Conclusiones. El valor de costo total por evento hospitalizado se encuentra dentro de lo esperado para Latinoamérica. La distribución de costos presenta una proporción importante de costos médicos directos en relación con los gastos de bolsillo (3, 5%) y costos indirectos (7, 8%).

Objective. To assess direct medical costs, out-of-pocket expenses, and indirect costs in cases of hospitalizations for acute diarrhea among children <5 years of age at Hospital de Niños "Héctor Quintana" in the province of Jujuy during the period of rotavirus circulation in the Northwest region of Argentina. Methods. Cross-sectional study on disease-related costs. All children <5 years of age, hospitalized with the diagnosis of acute diarrhea and dehydration during the period of rotavirus circulation between May 1st and October 31st of 2013, were included. The assessment of direct medical costs was done by reviewing medical records whereas out-of-pocket expenses and indirect costs were determined using a survey. For the 95% confidence interval of the average cost per patient, a probabilistic bootstrapping analysis of 10 000 simulations by resampling was done. Results. One hundred and five patients were enrolled. Their average age was 18 months (standard deviation: 12); 62 (59%) were boys. The average direct medical cost, out-of-pocket expense, and lost income per case was ARS 3413.6 (2856.35-3970.93) (USD 577.59), ARS 134.92 (85.95-213.57) (USD 22.82), and ARS 301 (223.28380.02) (USD 50.93), respectively. The total cost per hospitalization event was ARS 3849.52 (32984402.25) (USD 651.35). Conclusions. The total cost per hospitalization event was within what is expected for Latin America. Costs are broken down into direct medical costs (significant share), compared to out-of-pocket expenses (3.5%) and indirect costs (7.8%).

Identification of co-infection by rotavirus and parvovirus in dogs with gastroenteritis in Mexico

ABSTRACT This is the first report on circulating canine rotavirus in Mexico. Fifty samples from dogs with gastroenteritis were analyzed used polymerase chain reaction and reverse transcription polymerase chain reaction in order to identify parvovirus and rotavirus, respectively; 7% of dogs were infected with rotavirus exclusively, while 14% were co-infected with both rotavirus and parvovirus; clinical signs in co-infected dogs were more severe.

Diversity of group A rotavirus genes detected in the Triângulo Mineiro region, Minas Gerais, Brazil

ABSTRACT Group A rotaviruses are the main causative agent of infantile gastroenteritis. The segmented nature of the viral genome allows reassortment of genome segments, which can generate genetic variants. In this study, we characterized the diversity of the VP7, VP4 (VP8*), VP6, NSP4, and NSP5 genes of the rotaviruses that circulated from 2005 to 2011 in the Triângulo Mineiro (TM) region of Brazil. Samples with genotypes G2 (sublineages IVa-1 and IVa-3), G1 (sublineage I-A), G9 (lineage III), G12 (lineages II and III), G8 (lineage II), G3 (lineage III), P[4] (sublineages IVa and IVb), P[8] (sublineages P[8]-3.6, P[8]-3.3, and P[8]-3.1), I2 (lineage VII), E2 (lineages VI, XII, and X), and H2 (lineage III) were identified. The associations found in the samples were G1, G9, or G12 with P[8]-I1-E1-H1; G2 or G8 with P[4]-I2-E2-H2; G12 with I3-E3-H6; and G3 with P[4]-I2-E3-H3 (previously unreported combination). Reassortment events in G2P[4] strains and an apparent pattern of temporal segregation within the lineages were observed. Five TM samples contained genes that exhibited high nucleotide and amino acid identities with strains of animal origin. The present study includes a period of pre- and post-introduction of rotavirus vaccination in all Brazilian territories, thereby serving as a basis for monitoring changes in the genetic constitution of rotaviruses. The results also contribute to the understanding of the diversity and evolution of rotaviruses in a global context.

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.

Adenoviruses of canine and human origins in stool samples from free-living pampas foxes (Lycalopex gymnocercus) and crab-eating foxes (Cerdocyon thous) in São Francisco de Paula, Rio dos Sinos basin / Adenovírus de origens canina e humana em fezes de graxains (Lycalopex gymnocercus) e cachorros-do-mato (Cerdocyon thous) de vida livre em São Francisco de Paula, bacia do Rio dos Sinos

The spread of enteric viruses of domestic animals and human beings to wild species can be facilitated by the resistance of these viruses on the environment and their ability to be transmitted by water and contaminated food. The health status of the populations of pampas foxes (Lycalopex gymnocercus) and crab-eating foxes (Cerdocyon thous) is largely unknown and the landscapes occupied by these animals in southern Brazil have been threatened by human occupation and expansion of agriculture. In this work, the search of genomes of human and canine adenoviruses in feces from these wild carnivores was used to track the dissemination of domestic animals and human pathogens to the free-living populations in a wildlife reserve located in southern Brazil. This was performed by virus-specific differential real-time polymerase chain reactions (qPCR) on stool specimens, avoiding capture and additional stress to the animals. Genus-specific conventional reverse-transcriptase PCR (RT-PCR) was complementarily performed aiming the detection of enteroviruses (EV) and rotaviruses (RV) on these same samples. HAdV genomes were found on 14 out of the 17 (82.35%) stool samples analysed, whereas CAV was found co-infecting 5 of these samples. RV genomes were detected on 7 of the 17 samples (41.18%) and all samples were negative for EV. The results point to the dispersion of HAdV and RV at a high rate to these species of South American wild carnivores, which can be an effect of growing anthropisation of the habitat of these animals.

A disseminação de vírus entéricos de animais domésticos e seres humanos para espécies selvagens pode ser facilitada pela resistência desses vírus no ambiente e sua capacidade de ser transmitida por água e alimentos contaminados. O estado de saúde das populações de Graxains-do-campo (Lycalopex gymnocercus) e Cachorros-do-mato (Cerdocyon thous) é em grande parte desconhecida e as paisagens ocupadas por estes animais no sul do Brasil têm sido ameaçadas pela ocupação humana e a expansão da agricultura. Neste trabalho, utilizou-se a pesquisa de genomas de adenovírus humanos (HAdV ) e caninos (CAV-1 e -2) em amostras fezes desses carnívoros selvagens com vistas a diagnosticar a disseminação de patógenos de animais domésticos e seres humanos às populações de vida livre em uma reserva de vida selvagem, localizado no sul do Brasil. Foram realizadas reações em cadeia da polimerase diferenciais e em tempo real (qPCR) de adenovírus específicos em amostras de fezes, evitando a captura e estresse adicional para os animais. PCRs gênero-específicas convencionais com transcrição reversa prévia (RT-PCR) foram ainda realizadas visando a detecção de enterovírus (EV) e rotavírus (RV) nestas mesmas amostras. Genomas de HAdV foram encontrados em 14 a 17 amostras de fezes (82.35%) analisados, Considerando que o CAV foi encontrado coinfectando 5 destas amostras. Genomas de RV foram detectados em 7 das 17 amostras (41.18%) e todas as amostras foram negativas para EV. Os resultados apontam para a dispersão de HAdV e RV em uma taxa elevada para estas espécies de carnívoros selvagens sul-americanas, que podem ser um efeito da crescente antropização do habitat desses animais.

Phylogenetic analysis of human group C rotavirus circulating in Brazil reveals a potential unique NSP4 genetic variant and high similarity with Asian strains

Group C rotaviruses (RVC) cause gastroenteritis in humans and animals worldwide, and the evidence for a possible zoonotic role has been recently provided. To gain information on the genetic diversity and relationships between human and animal RVC, we sequenced the VP4, VP7, and NSP4 genes of 12, 19, and 15 human strains, respectively, detected in São Paulo state during historical (1988 and 1993) and recent (2007 and 2008) Brazilian rotavirus surveillance. All RVC strains analyzed in the present study grouped into human genotype (G4-P[2]-E2), and did not show any evidence of animal ancestry. Phylogenetic analysis showed that RVC samples detected in 1988 and 1993 clustered together with strains from distinct continents, indicating that historical RVC strains circulating in São Paulo were closely related to those strains circulating worldwide. All three genes (VP7, VP4 and NSP4) of São Paulo RVC strains isolated in 2007-2008 exhibited close phylogenetic relationship with human RVC strains isolated in China and Japan, suggesting that they are genetically linked, and that a gene flow could be occurring between this Asian countries and Brazil. We identified two distinct clusters in the NSP4 phylogenetic tree. One cluster formed exclusively by human Brazilian strains detected in 1997 and 2003-2004 in Rio de Janeiro, Bahia, and Rio Grande do Sul states (Subgroup II) previously described in a different study, that displayed low sequence identities to other human strains formerly published, and to the Brazilian RVC strains (Subgroup I) characterized in the present study. These data suggests the circulation of two genetic profiles of the NSP4 gene in Brazil. High sequence diversity in NSP4 gene was previously reported in Asia, and additional diversity in NSP4 RVC strains spreading in the world should be expected. More in-depth molecular and epidemiological analysis of human RVC throughout the world will be needed to understand their diversity and clarify their evolution, as well as to develop classifications schemes.

Rotavirus genotypes and the indigenous children of Brazilian midwest in the vaccine era, 2008-2012: footprints of animal genome

World group A rotavirus (RVA) surveillance data provides useful estimates of the disease burden, however, indigenous population might require special consideration. The aim of this study was to describe the results of G­ and P­types from Brazilian native children ≤3 years. Furthermore, selected strains have been analyzed for the VP7, VP6, VP4, and NSP4 encoding genes in order to gain insight into genetic variability of Brazilian strains. A total of 149 samples, collected during 2008­2012, were tested for RVA using ELISA and PAGE, following by RT­PCR and sequencing. RVA infection was detected in 8.7% of samples (13/149). Genotype G2P[4] was detected in 2008 and 2010, G8P[6] in 2009, and G3P[8] in 2011. The phylogenetic analysis of the VP7 and VP4 genes grouped the Brazilian G2P[4] and G3P[8] strains within the lineages currently circulating in humans worldwide. However, the phylogenetic analysis of the VP6 and NSP4 from the Brazilian G2P[4] strains, and the VP7 and NSP4 from the Brazilian G3P[8] strains suggest a distant common ancestor with different animal strains (bovine, caprine, and porcine). The epidemiological and genetic information obtained in the present study is expected to provide an updated understanding of RVA genotypes circulating in the native infant population, and to formulate policies for the use of RVA vaccines in indigenous Brazilian people. Moreover, these results highlight the great diversity of human RVA strains circulating in Brazil, and an in­depth surveillance of human and animal RVA will lead to a better understanding of the complex dynamics of RVA evolution

Epidemiologia das rotaviroses antes e após a introdução da vacina / Rotavirus epidemiology before and after vaccine introduction

OBJETIVOS: Avaliar a prevalência e a circulação dos genótipos de rotavírus, antes e após a introdução da vacina oral contra rotavírus humano, bem como verificar uma possível mudança na faixa etária de ocorrência da infecção pelo RV-A. MÉTODOS: Trata-se de um estudo transversal realizado no período de 2002 a 2011, em Juiz de Fora, MG. Foram avaliados 1.144 espécimes fecais diarreicos, obtidos de crianças de 0 a cinco anos não hospitalizadas, que foram analisadas por PAGE e RT-PCR. Os dados relativos à prevalência e distribuição etária dos casos de rotavirose foram analisados pelo teste χ2 (p < 0,05), utilizando-se o programa SPSS, versão 13.0. RESULTADOS: Infecções por rotavírus foram detectadas em 9,35% (107/1.144) das amostras, com prevalências variando de 11,12% (90/809) no período pré-vacinal a 5,07% (17/335) no pós-vacinal (p = 0,001). Dentre as amostras caracterizadas, os genótipos mais frequentemente detectados foram G1P[6] (6/33 = 18,2%) no período 2002-2005 e G2P[4] no ano de 2006 (11/33 = 33,3%) e no período 2007-2011 (5/33 = 15,2%). Observou-se, ainda, uma redução significativa no número de casos de rotavirose em crianças de 0 a 36 meses, após a introdução da vacina. CONCLUSÕES: O estudo revelou queda significativa na prevalência de rotavírus, principalmente na faixa etária de 0 a 36 meses, no período 2007-2011, bem como redução na circulação do genótipo G1.

OBJECTIVES: To evaluate the prevalence and circulation of rotavirus genotypes before and after the introduction of oral vaccine against human rotavirus (OVHR), and to check for a possible change in the age of occurence of the infection by RV-A. METHODS: This was a cross-sectional study conducted between 2002-2011, in the city of Juiz de Fora, state of Minas Gerais, Brazil. A total of 1,144 diarrheal stool specimens were obtained from nonhospitalized children aged between 0 and 5 years, and analyzed by polyacrylamide gel electrophoresis and reverse-transcription polymerase chain reaction for genotype characterization. Data on prevalence and age distribution of rotavirus cases were analyzed through the chi-squared test (p < 0.05), using SPSS, release 13.0. RESULTS: Rotavirus infection was detected in 9.35% (107/1,144) samples, with prevalence rates ranging from 11.12% (90/809) in the pre-vaccine to 5.07% (17/335) in the post-vaccine period (p = 0.001). Among the samples tested, the most frequently detected genotypes were G1P[6] (6/33 = 18.2%) in the period between 2002 and 2005 and G2P[4] in 2006 (11/33 = 33.3%) and in the period between 2007 and 2011 (5/33 = 15.2%). There was also a significant reduction in the number of cases of rotavirus disease in children aged between 0 and 36 months after the vaccine introduction. CONCLUSIONS: The study evidenced a significant decrease in the prevalence of rotavirus, mainly in children aged between 0 and 36 months in the 2007-2011 period, as well as a reduction in G1 genotype circulation.

Caracterização molecular dos genótipos do rotavírus em pacientes pediátricos imunossuprimidos e não imunossuprimidos / Molecular characterization of rotavirus genotypes in immunosuppressed and non-immunosuppressed pediatric patients

OBJETIVO: Descrever a variabilidade genotípica do rotavírus grupo A (RVA) encontrado em pacientes pediátricos imunocompetentes e imunocomprometidos tratados no Hospital de Clínicas/Universidade Federal do Paraná (HC/UFPR), Curitiba, Paraná. MÉTODOS: Foi realizado um estudo transversal com 1.140 amostras de fezes coletadas, de abril de 2001 a dezembro de 2008, em pacientes ambulatoriais e pacientes hospitalizados com gastroenterite aguda encaminhados ao hospital. As técnicas usadas foram o método da aglutinação do látex e imunoensaio enzimático para diagnóstico de RVA. Foi realizada transcrição reversa, seguida por PCR multiplex semi-nested e sequência de nucleotídeos para caracterização do genótipo. Foram relatados dados de combinações de genótipos, clínicos, epidemiológicos, laboratoriais e sobre a presença de infecções hospitalares. RESULTADOS: Foi analisado um total de 80 amostras de fezes positivas para rotavírus. As associações mais frequentes entre os genótipos G e P foram: G4 P[8] (38,9%), G1 P[8] (30,5%), G9 P[8] (13,9%), G2 P[4] (6.9 %) e G3 P[8] 1,4%). O genótipo prevalente foi G2 P[4] depois da implementação da vacina nos anos de 2006 e 2008. Verificou-se que um total de 62,5% das crianças com idade abaixo de 12 meses estavam infectadas. Destas, 55,6% tinham grave desidratação, e 26,7% precisaram de cuidados intensivos. Encontrou-se uma frequência de 12,5% de infecções hospitalares. Não se observou correlação entre o genótipo e a gravidade da infecção nos pacientes estudados. CONCLUSÃO: As infecções por RVA podem associar-se a manifestações clínicas graves e é crucial a vigilância da variabilidade genotípica desse vírus para monitorizar a emergência de novas cepas e o impacto da imunização nesses pacientes.

OBJECTIVE: To describe the genotypic variability of group A rotavirus (RVA) found in immunosuppressed and non-immunosuppressed pediatric patients treated at the Hospital de Clínicas da Universidade Federal do Paraná (HC-UFPR), Curitiba, Paraná. METHODS: A cross-sectional study was conducted with 1,140 stool samples collected from April, 2001 to December, 2008 in outpatients and hospitalized patients with acute gastroenteritis referred to the hospital. RVA diagnosis was performed through the latex agglutination method and enzyme immunoassay. Reverse transcription followed by multiplex hemi-nested polymerase chain reaction (PCR) and nucleotide sequencing were used for genotype characterization. Genotype combinations, clinical data, epidemiological data, laboratory data, and presence of hospital-acquired infections were reported. RESULTS: A total of 80 rotavirus-positive stool samples were analyzed. The most frequent associations between genotypes G and P were: G4 P[8] (38.9%), G1 P[8] (30.5%), G9 P[8] (13.9%), G2 P[4] (6.9%), and G3 P[8] (1.4%). G2 P[4] was the most prevalent genotype after the vaccine implementation in the years 2006 and 2008. A total of 62.5% of children aged less than 12 months were found to be infected. Of these, 55.6% had severe dehydration and 26.7% needed intensive care. A frequency of 12.5% of nosocomial infections was found. No correlation was observed between genotype and severity of infection in the study patients. CONCLUSION: RVA infections can be associated with severe clinical manifestations, and the surveillance of genotypic variability of this virus is crucial to monitor the emergence of new strains and the impact of the immunization in these patients.

Diversidad genotípica de rotavirus grupo A: correlación entre el tipo G3 y severidad de la infección. Valencia, Venezuela / Genetic diversity of rotavirus group A: correlation between G3 type and severity of the infection. Valencia, Venezuela

La variabilidad genética y antigénica de los rotavirus (RV) parece tener implicaciones en la severidad de la infección, pero los estudios no son concluyentes. Por este motivo, en el presente trabajo se compararon las medias de severidad entre los episodios de diarrea causados por RV tipo G1 y G3, durante el período 2001-2005, en la Ciudad Hospitalaria “Dr. Enrique Tejera” de Valencia, Venezuela. RV se detectó por ELISA, los tipos G y P por RT-PCR. La severidad de la infección se estimó utilizando el sistema de Ruuska-Vesikari, las medias de severidad se compararon mediante la prueba t de Student (2 colas, 95%IC). RV se detectó en 24,5% (3.193/13.026) de los pacientes. G3 fue más frecuente (50,3%), seguido por G1 (39,2%), G9 (6,2%), G2 (0,6%), G4 (0,6%) y 3,1% mixtos (G1+G3). El 87,3% de las muestras resultaron P[8], 10,9% P[4] y 1,8% P[6]. Al comparar los episodios G1 y G3, no se observaron diferencias significativas (P>0,05) entre los grupos etarios, frecuencia de desnutridos, deshidratación y lactancia materna. Sin embargo, el grupo G3 se caracterizó por presencia significativa (P< 0,05) de fiebre, episodios con una duración ≥ 6 días, 6 o más evacuaciones en 24 horas y 3 o más días con vómitos. La media de severidad para los episodios G3 (11,1) fue mayor significativamente (P<0,05) a la G1 (7,8). Estos resultados muestran la asociación de G3 con diarreas severas y apoyan la importancia de conocer la variabilidad y frecuencia de los tipos virales para medir el impacto de las vacunas antirotavirus.

Genetic and antigenic rotavirus (RV) variabilities may have implications in the severity of the infection caused by these agents; however the studies are not conclusive. For that purpose, the mean severity scores of diarrhea episodes caused by RV types G1 and G3 were compared, at Ciudad Hospitalaria “Dr. Enrique Tejera” in Valencia, Venezuela, between 2001- 2005. RV were identified by ELISA, G and P types by RT-PCR. The severity of infection was determined using the Ruuska-Vesikari system and the mean severity values were compared using the Student’s t-test (two-tailed, 95%CI). RV were detected in 24.5% of patients (3193/13026), being G3 the most common (50.3%), followed by G1 (39.2%), G9 (6.2%), G2 (0.6%), G4 (0.6%) and of mixed infection 3.1% (G1+G3). Type P[8] was present in 87.3% of samples, 10.9% P[4] and 1.8% P[6]. There were not statistically significant differences (P≥0.05) observed between the episodes caused by G1 and G3 when age, breast feeding, and degrees of malnutrition and dehydration were considered. Nevertheless, in the G3 positive group, fever, episodes of more than 6 days, 6 or more evacuations in 24 hours and 3 or more days with vomit, were observed. The mean severity score for the G3 episodes (11.1) was significantly higher (P< 0.05) than for G1 (7.8). These results show that G3 was associated with severe diarrhea, supporting the hypothesis that the knowledge of the variability and frequency of viral types is essential to measure the impact of an anti-rotavirus vaccine.

Síndrome diarreico por rotavirus en niños menores de 5 años inmunizados y no de la ciudad de Maracaibo, estado Zulia, Venezuela / Diarrheic syndrome due to rotavirus in immunized and non-immunized children under 5, in the city of Maracaibo, state of Zulia, Venezuela

La diarrea aguda es la causa más común de morbi-mortalidad infantil, donde el Rotavirus es uno de los principales agentes involucrados en las diarreas severas en niños menores de 5 años. El presente estudio tiene como objetivo determinar la presencia de rotavirus en una población infantil con cuadros diarreicos, vacunados y no vacunados que acuden a observación pediátrica del Hospital de Niños y Hospital Universitario de Maracaibo, estado Zulia en el período de Abril 2011 hasta Abril 2012, para ello se recolectaron 100 muestras de heces y para el diagnóstico se utilizó la técnica de Aglutinación Directa en partículas de Látex. Resultaron positivos un 43,6% (24/55) de niños no vacunados y 33,3% (10/30) de niños vacunados afectando principalmente a los menores de 1 año con predominio del sexo masculino con un 65,9% sobre el sexo femenino con 40%, la diarrea por el agente viral estudiado representó casi la mitad de las hospitalizaciones por gastroenteritis, encontrándose una diferencia estadística significativa de p= 0.027 en el numero de evacuaciones del cuarto día, entre niños no vacunados (5) y vacunados (3). Los resultados de esta investigación muestran la circulación de rotavirus en niños vacunados y no vacunados, es por ello importante considerar que el presente reporte tiene como fin último alertar a la comunidad médica a considerar en todo niño con gastroenteritis la posibilidad de que se trate de un cuadro por RV.

Acute diarrhea is the most common cause of morbidity and mortality in infants, where rotavirus is one of the main agents involved in severe diarrhea for children under five years. The present study aims to determine the presence of rotavirus in a vaccinated and unvaccinated pediatric population with acute diarrhea that came to the Children’s Hospital and the University Hospital of Maracaibo, State of Zulia, for observation from April 2011 to April 2012. One-hundred stool samples were collected and direct agglutination of latex particles was used for diagnosis. 43.6% of the unvaccinated children were positive (24/55) as were 33.3% (10/30) of the vaccinated children. Principally, children under 1 year were affected, predominantly males with 65.9% and females with 40%. Diarrhea due to the viral agent under study accounted for nearly half the hospitalizations for gastroenteritis. A statistically significant difference of p = 0.027 was found between the number of evacuations on the fourth day in unvaccinated (5) and vaccinated (3) children. Results of this research show rotavirus circulating in vaccinated and unvaccinated children. Therefore, the purpose of this report is to alert the medical community to consider that every child with gastroenteritis could possibly have RV.

Oral live attenuated human rotavirus vaccine (RotarixTM) offers sustained high protection against severe G9P[8] rotavirus gastroenteritis during the first two years of life in Brazilian children

In a large Phase III trial conducted in 10 Latin American countries, the safety and efficacy of the live attenuated monovalent rotavirus vaccine RIX4414 was evaluated in 15,183 healthy infants followed up during the first two years of life. Belém was the only site in Brazil included in this multicentre trial. The study in Belém included a subset of 653 infants who were followed up until 24 months of age for protection against severe rotavirus gastroenteritis. These subjects were randomly assigned in a 1:1 ratio to receive two doses of vaccine (n = 328) or two doses of placebo (n = 325) at approximately two and four months of age. Of the 653 enrolled infants, 23 dropped out during the study period. For the combined two-year period, the efficacy of RIX4414 was 72.3% [95% confidence interval (CI) 37.5-89.1%] against severe rotavirus-related gastroenteritis, reaching a protection rate of 81.8% (95% CI 36.4-96.6%) against circulating wild-type G9 rotavirus strains. It is concluded that two doses of RIX4414 are highly efficacious against severe rotavirus gastroenteritis in Belém during the first two years of life and provide high protection against the worldwide emergence and spread of G9P[8] strains.

Rotavirus genotyping in gastroenteritis cases of an infantile population from Western Brazilian Amazonia / Genotipagem de rotavírus em casos de gastrenterites de uma população infantil do oeste da Amazônia brasileira

INTRODUCTION: During the period from 2000 to 2002, 79 rotavirus-positive stool samples were collected from children presenting diarrhea in the Western Brazilian Amazon. METHODS: Molecular characterization of the G and P genotypes was performed using RT-PCR and electropherotyping analysis by polyacrylamide gel electrophoresis. RESULTS: A total of 59 samples were confirmed as group A rotavirus. A long electrophoretic profile was exhibited by the G1P[8], G3P[8], and G4P[8] genotypes. The G1P[8] genotype was found in greater proportion. The short electropherotype was exhibited only by G2 genotype strains. CONCLUSIONS: The proportion of the rotavirus genotypes observed was not different from that in other areas of Brazil. This study is the first genotyping of rotavirus in the Western Brazilian Amazon.

INTRODUÇÃO: Entre 2000 e 2002, 79 amostras positivas para rotavírus foram coletadas de crianças com diarreia na Amazônia ocidental brasileira. MÉTODOS: Para a caracterização molecular dos genótipos G e P foram realizadas as reações de RT-PCR e a análise dos eletroferotipos por eletroforese em gel de poliacrilamida (PAGE). RESULTADOS: 59 amostras foram confirmadas como pertencentes ao rotavírus grupo A. Os genótipos G1P[8], G3P[8] e G4P[8] apresentaram perfis eletroforéticos longos. O genótipo G1P[8] foi encontrado em maior proporção. O eletroferotipo curto ocorreu apenas em genótipos G2. CONCLUSÕES: A proporção dos genótipos de rotavírus observada não foi diferente de outras áreas do Brasil. Este estudo é a primeira genotipagem de rotavírus na Amazônia ocidental brasileira.

Genotipos de rotavirus aislados de niños chilenos con gastroenteritis atendidos en dos hospitales públicos: variantes virales circulantes en un país con uso limitado de vacunas anti-rotavirus / Rotavirus genotypes in children with gastroenteritis assisted in two public hospitals from Chile: viral strains circulating in a country without a universal vaccination against rotavirus

Background: Rotavirus is the main cause of severe gastroenteritis (GE) in children. Two vaccines currently available have proven efficacy against the predominant genotypes. Rotavirus genotypes vary both geographically and/or temporally. Genotype surveillance is important to monitor trends associated or not with vaccine use. Aim: To update information on rotavirus genotypes circulating in two main cities of Chile. Methodology: Between May 2009-March 2010, children < 5y of age receiving medical care for GE in two large hospitals were recruited; none of these children had received rotavirus vaccine previously. Epidemiological information was recorded in an ad-hoc form and stool samples were collected for rotavirus detection by a commercial ELISA. Genotyping was performed by semi-nested RT-PCR. Results: A total of 296/967 samples (31%) were positive for rotavirus, with a peak in November/ December mostly in children 7-24 months old (67%). G9P[8] was the predominant genotype (76%), followed for G1P[8] (6%) and G2P[4] (6%) in both cities. Conclusions: Rotavirus caused one third of GE requiring emergency room care and/or hospitalization, mostly in children within an age range susceptible to benefit from rotavirus vaccines. G9P[8], a genotype against which rotavirus vaccines have demonstrated high efficacy, was by far the most frequent rotavirus variant. Continued surveillance in Chile is crucial for providing background information on disease burden and strain diversity before the introduction of rotavirus vaccines.

Antecedentes: Rotavirus es la principal causa de gastroenteritis (GE) grave en niños. Actualmente se dispone de dos vacunas con eficacia demostrada contra los genotipos predominantes en el mundo. Los genotipos de rotavirus varían en el tiempo y de una región a otra. Es importante mantener la vigilancia de los genotipos circulantes para monitorizar las tendencias asociadas o no al uso de vacunas. Objetivo: Actualizar la información sobre genotipos de rotavirus circulantes en dos ciudades importantes de Chile (Santiago y Valparaíso). Metodología: Entre mayo 2009 y marzo 2010 se reclutaron niños bajo 5 años de edad con GE atendidos en dos hospitales; ninguno de ellos con historia previa de vacunación anti-rotavirus. Se registró información epidemiológica y se tomó muestra de deposición para detección de rotavirus mediante ELISA comercial. Se realizó genotipificación mediante RPC-TR semi-anidada. Resultados: Se detectó rotavirus en 296/967 muestras analizadas (31%), con un pico de frecuencia en noviembre/diciembre y afectando predominantemente al grupo de 7-24 meses de edad (67%). G9P[8] fue el genotipo predominante (76%), seguido por G1P[8] (6%) y G2P[4] (6%) en ambas ciudades. Conclusiones: Rotavirus causó un tercio de las GE en este grupo, afectando especialmente al grupo de edad que podría beneficiarse con la vacunación anti-rotavirus. G9P[8], una de las variantes contra las cuales las vacunas antirotavirus han demostrado alta eficacia, fue por lejos el genotipo más frecuente. Es necesario continuar la vigilancia en Chile de modo de conocer el impacto de la enfermedad y diversidad de variantes antes de la incorporación de una vacuna anti-rotavirus.

Rotavirus / Rotavirus

la infección por rotavirus es responsable de 125 millones de casos, de más 500.000 defunciones anuales y de 40% de la hospitalización por diarrea en menores de 5 años de edad. en países en desarrollo la tasa de infección es más alta en el grupo de edad de 3 a 11 meses, quienes presentan mayor letalidad producto de la desnutrición y de la dificultad para acceder oportunamente a los servicios de salud; se observa que al año de vida, 65-80 % de los niños han desarrollado anticuerpos contra el rotavirus y 95% a los 2 años. Actualmente se utilizan dos vacunas contra el rotavirus, las cuales han demostrado ser seguras, eficaces y poco relacionadas con invaginación intestinal. En venezuela, la vacuna monovalente-humana se introdujo en el Programa Ampliado de Inmunizaciones en abril de 2006. un estudio previo mostró que la administración masiva de dos dosis de esta vacuna contra el rotavirus es altamente costo-efectiva. cuatro años después en un estudio nacional se evaluó el impacto y se evidenció reducción de 50% de la tasa de mortalidad en los menores de 5 años, siendo mayor en el grupo de menores de 1 año con 55% y en el grupo de 1-4 años de 44%. sin embargo el seguimiento de este programa nos indica que las coberturas de inmunización contra rotavirus en venezuela siguen siendo bajas

Infection by rotavirus is responsible for 125 million cases, 500,000 annual deaths and 40% of hospitalizations for diarrhea in children under 5 years of age. In developing countries the rate of infection is higher in the group of 3 to 11 months of age, which present a higher lethality, product of undernourishment and difficulties to accede opportunely to health services. during the first year of life, 65 to 80%of children have developed antibodies against rotavirus and 95% will achieve this by the age of two. At the moment two vaccines against rotavirus are available, and have demonstrated to be safe, effective and with very low association with intestinal invagination. In venezuela, the monovalent-human vaccine was introduced in the extended Program of Immunizations in April of 2006. A previous study showed that the massive administration of two doses of this vaccine against rotavirus is highly cost-effective. Four years later, a national study showed a reduction of mortality rate of 50% in children under 5 years of age, 55% reduction in those less than one year and 44% reduction in the group of 1-4 years of age. nevertheless the follow up of this program indicates that immunization coverage against rotavirus in venezuela continues to be low

Caracterização molecular de cepas de rotavírus e norovírus: um estudo de 6 anos (2004-2009) / Characterization of rotavirus and norovirus strains: a 6-year study (2004-2009)

OBJETIVO: Monitorar infecções causadas por rotavírus (RV) e norovírus (NoV) em crianças hospitalizadas < 5 anos com gastroenterite aguda provenientes do estado de São Paulo durante um período de 6 anos (2004-2009). MÉTODOS: Este estudo retrospectivo foi realizado em 61 centros médicos, utilizando amostras fecais coletadas por conveniência, analisadas por ensaio imunoenzimático, eletroforese em gel de poliacrilamida, transcrição reversa seguida de reação em cadeia pela polimerase e sequenciamento para caracterização dos genótipos. RESULTADOS: Infecções por RV e NoV foram detectadas em 29,6 por cento (144/487) e 29,2 por cento (26/89) das amostras, respectivamente. Os genótipos de RV detectados com maior frequência foram: G9P[8] em 2004; G1P[8] em 2005; G9P[8] em 2006; e G2P[4] durante os anos de 2007, 2008 e 2009. A taxa de detecção diminuiu de 36,3 por cento (33/91) em 2004 para 4,2 por cento (4/95) em 2009. NoV pertencente ao genogrupo GII foi encontrado em 61,6 por cento (16/26) das amostras, e GI em 11,5 por cento (3/26). Infecções mistas por NoV e RV foram observadas em 2,2 por cento (2/89) das amostras, envolvendo as cepas GI+G9P[8] e GI+G2P[4]. CONCLUSÕES: A distribuição dos genótipos de RV variou com os anos, acompanhada pela redução no número de casos detectados. Ė necessário intensificar a vigilância pós-implantação da vacina contra RV, visando monitorar as cepas circulantes e sua eficácia contra possíveis genótipos emergentes. Os NoVs têm sido cada vez mais identificados como agentes etiológicos relevantes entre crianças hospitalizadas e exercem um papel importante na etiologia viral da gastroenterite pediátrica aguda no estado de São Paulo.

OBJECTIVE: To monitor rotavirus (RV) and norovirus (NoV) infections in hospitalized children < 5 years with acute gastroenteritis in the state of São Paulo, Brazil, during a 6-year period (2004- 2009). METHODS: This retrospective study was conducted with 61 medical centers with convenient surveillance fecal specimens, investigated by enzyme-linked immunosorbent assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis, reverse polymerase chain reaction and sequencing to genotype characterization. RESULTS: RV and NoV infections were detected in 29.6 percent (144∕487) and 29.2 percent (26/89) of the samples, respectively. The most frequent RV genotypes detected were G9P[8] in 2004; G1P[8] in 2005; G9P[8] in 2006; and G2P[4] during 2007, 2008, and 2009. Detection rate declined from 36.3 percent (33∕91) in 2004 to 4.2 percent (4/95) in 2009. NoV genogroup GII was found in 61.6 percent (16/26) of the samples, and GI in 11.5 percent (3/26). Mixed NoV-RV infections were observed in 2.2 percent (2/89) of the samples, involving GI+G9P[8] and GI+G2P[4] strains. CONCLUSIONS: Genotype distribution varied according to collection year, accompanied by a reduction in detection rate. Use of RV vaccine requires implementation of post-marketing surveillance to monitor RV strain diversity and its efficacy against possible new emerging genotypes. NoVs have been increasingly identified as relevant etiological agents among hospitalized children and play an important role in the viral etiology of pediatric acute gastroenteritis in the state of São Paulo.

Detection and characterization of human rotavirus in hospitalized patients in the cities of Ponta Grossa, Londrina and Assai - PR, Brazil

Acute diarrheal disease is still one of the major public health problems worldwide. Rotaviruses (RV) are the most important viral etiologic agents and children under five years of age are the target population. OBJECTIVE: To investigate the rate of RV infection in hospitalized patients due to acute diarrhea in the cities of Ponta Grossa, Londrina and Assai - Paraná. METHODS: Latex agglutination (LA); immunochromatography (ICG); polyacrylamide gel electrophoresis (PAGE) and negative staining electron microscopy (ME) tests were used to detect the virus. For the genotyping, RT-PCR and RT-PCR-ELISA were used, respectively, for NSP4 and VP4/VP7. RESULT: Out of 124 samples there were 69 positive stool samples for RV, for at least one of the used tests, 67 of them being RV group A (RV-A). Overall, most of the RV positive stool samples came from children under thirteen years of age. However, 12 positive cases occurred in patients aged 13 years or above, including an 81-year old patient. CONCLUSION: The data showed similar electropherotypes and genotypes G, P and NSP4 of the inland wild circulating strains of RV.

Características clínicas y epidemiológicas de la infección por rotavirus en niños de Cumaná, Venezuela / Clinical and epidemiological characteristics of rotavirus infection in children of Cumaná, Venezuela

Se estudió la tasa de detección de rotavirus humano del grupo A (RVH-A), así como su asociación con la clínica y epidemiología, en niños menores de 5 años con diarrea aguda que acudieron al Hospital Universitario “Antonio Patricio de Alcalá”, Cumaná, Venezuela, entre marzo de 2006 y septiembre de 2007. De 241 muestras fecales colectadas en este estudio, 47 (19,5%) resultaron positivas a RVH-A por ensayo inmunoenzimático y estuvieron presentes durante los 19 meses de estudio, con picos de mayor tasa de detección en los meses de marzo, abril y mayo (30,0%, 28,6% y 43,8%, respectivamente) de 2006 y septiembre (37,5%) de 2007. El 34% de los casos ocurrió en el grupo etario de 7 a 12 meses, y los varones fueron los más afectados (55,3%), así como las clases socioeconómicas obrera y marginal (72,4%). Los niños que recibieron alimentación no materna fueron mayormente infectados por RVH-A (61,7%). Se observó que la mayoría de los niños (72,3%) presentaron de 1 a 4 evacuaciones diarias, casi todas (83,0%) entre semilíquidas y líquidas, pero con pocos vómitos (38,2%) y muy pocos casos con fiebre (10,6%), sin embargo la deshidratación si resultó ser un síntoma significativo (OR=6,307; IC-95%=2,337-21,4; p = 0,0001) en los niños enfermos. Al comparar estos resultados con los de otros trabajos previos en la misma zona, se notó una disminución de la tasa de detección de RVH-A de más del doble, y los síntomas clínicos de la enfermedad rotaviral son los mismos reportados por otros autores. De 32 niños vacunados contra rotavirus, en 30 (93,8%) no se les detectó RVH-A en sus heces, y hubo una asociación significativa (OR=0,02434, IC-95%=0,0377-0,9171; p=0,037) entre los niños vacunados y la protección.

The detection rate of group A human rotavirus (HRV-A), as well as its association with clinical and epidemiological parameters, was studied in children younger than 5 years old with acute diarrhea attending to the University Hospital “Antonio Patricio de Alcalᔠof Cumaná, between march 2006 and september 2007. Of 241 fecal samples collected in this study, 47 (19.5%) were positive to HRV-A by immunoassay. Rotavirus were present throughout the study and the major detection rates were on march, april and may of 2006 (rates were 30,0%, 28,6% y 43,8%, respectively) and september of 2007 (37,5%). Thirty four percent of cases with HRV-A occurred in children of 7 - 12 months and males were the most affected (55.3%), as well as the worker and marginal socioeconomic classes (72,4%). Children that not received maternal feeding were the group mainly infected by HRV-A (61.7%). Most of the children (72.4%) had one to four evacuations/day, with few vomits (38.2%) and fever (10.6%). Almost all the feces (83.0%) had a liquid or semi-liquid aspect. When these results were compared with previous data of the same geographic area, we observed a two-fold decrease of the detection rate of HRV-A and the clinical symptoms were the same as reported by other authors. Of 32 children vaccinated against rotavirus, 30 (93.8%) did not have HVR-A in their feces and there was a significant association between the vaccinated children and protection.

Prevalência de rotavírus em crianças atendidas na rede pública de saúde do estado de Pernambuco / Rotavirus prevalence in infants and children in the public healthcare system of the state of Pernambuco

INTRODUÇÃO: Os rotavírus são considerados, importantes agentes etiológicos de gastroenterite aguda e ainda causa comum de hospitalização de crianças na faixa etária de zero a quatro anos de idade. No Brasil, a incidência de rotavírus nas crianças com gastrenterite é de 12 a 42 por cento, e a distribuição da infecção esta relacionada à sazonalidade que aparentemente ocorre em diferentes períodos e intensidade de acordo com a região de ocorrência. O estudo pesquisou rotavírus do grupo A em amostras fecais de crianças com caso suspeito atendidas na rede pública de saúde do Estado de Pernambuco. MÉTODOS: O diagnóstico foi realizado através de ensaios imunoenzimático ELISA e teste imunoquímico de aglutinação em látex. RESULTADOS: Foram estudadas 171 amostras. Destas, 33 (19,3 por cento) apresentaram positividade. Das amostras positivas 24 (72,7 por cento) eram do sexo masculino e 09 (27,3 por cento) do sexo feminino. Dentro da amostragem positiva 15,2 por cento eram vacinadas. Quando comparamos os resultados obtidos entre o teste Elisa e aglutinação pelo Látex, houve 100 por cento de concordância entre a positividade pelo Látex e o ELISA. CONCLUSÕES: A alta incidência desta infecção reforça necessidade de monitoramento desse vírus, definindo políticas de saúde relacionadas ao diagnóstico, profilaxia, melhores condições sócio-econômicas e aprimoramento da vacina.

INTRODUCTION: Rotaviruses are considered important etiological agents of acute gastroenteritis and a common cause of the hospitalization of children aged zero to four years-old. In Brazil, the incidence of rotavirus gastroenteritis in children is 12 to 42 percent and the distribution of infection is related to seasonality, which apparently occurs in different periods and intensity according to each region. The study investigated group A rotavirus in fecal samples of suspected children attended by the public health system of the State of Pernambuco. METHODS: Diagnosis was achieved by ELISA and the Latex agglutination test. RESULTS: Of the 171 samples studied, 33 (19.3 percent) presented positivity for Rotavirus A. Among positive samples, 72.7 percent belonged to male patients and 27.3 percent to female. Among the positive casuistic, 15.2 percent were vaccinated. When comparing the results obtained for the ELISA and Latex agglutination tests, 100 percent agreement between positivity by Latex agglutination and ELISA was verified. CONCLUSIONS: The high incidence of this infection reinforces the need to monitor this virus and define health policies concerning its diagnosis, prophylaxis, improvement in socioeconomic conditions and the refinement of the vaccine.