Group A rotavirus gastroenteritis: post-vaccine era, genotypes and zoonotic transmission / Gastroenterite por rotavírus do grupo A: era pós-vacinal, genótipos e transmissão zoonótica

ABSTRACT This article provides a review of immunity, diagnosis, and clinical aspects of rotavirus disease. It also informs about the changes in epidemiology of diarrheal disease and genetic diversity of circulating group A rotavirus strains following the introduction of vaccines. Group A rotavirus is the major pathogen causing gastroenteritis in animals. Its segmented RNA genome can lead to the emergence of new or unusual strains in human populations via interspecies transmission and/or reassortment events.

RESUMO Este artigo fornece uma revisão sobre imunidade, diagnóstico e aspectos clínicos da doença causada por rotavírus. Também aponta as principais mudanças no perfil epidemiológico da doença diarreica e na diversidade genética das cepas circulantes de rotavírus do grupo A, após a introdução vacinal. O rotavírus do grupo A é o principal patógeno associado à gastroenterite em animais. Seu genoma RNA segmentado pode levar ao surgimento de cepas novas ou incomuns na população humana, por meio de transmissão entre espécies e eventos de rearranjo.

Avaliação da aplicação terapêutica de imunoglobulina Y em macacos cynomolgus infectados com rotavírus humano / Evaluation of therapeutic application of immunoglobulin y in cynomolgus monkeys infected with rotavirus human

O rotavírus é a causa mais frequente de gastroenterite aguda (GA) em crianças menores decinco anos de idade em todo o mundo, sendo responsável por até 200 mil mortes anualmente.Sua disseminação ocorre pelo contato pessoa-pessoa, principalmente pela via de transmissãofecal-oral. Embora haja vacinas disponíveis e em desenvolvimento para a rotavirose, medidasalternativas são necessárias como, por exemplo, nos casos de surto. Dessa forma, a utilizaçãode imunoglobulina Y (IgY) em imunoterapia passiva é justificável. A IgY é a imunoglobulinaque predomina na circulação das aves, sendo transferida por secreção ativa do sangue para agema dos ovos, a partir da qual a purificação é realizada para obtenção dos anticorposespecíficos de interesse. As vantagens apresentadas por esta metodologia incluem: fácilobtenção, baixo custo e capacidade de produção em larga escala de modo adequado a umpadrão bioético mais atual. É crescente sua aplicação em métodos de diagnóstico eimunoterapia passiva. Neste estudo, avaliamos a infectividade do rotavírus A (RVA) humanoem macacos cynomolgus (Macaca fascicularis) e a aplicação terapêutica da IgY específicaanti-rotavírus após desafio com RVA pela via oral. Os animais que receberam o tratamentoforam divididos em dois grupos: um recebeu IgY apenas pela via oral e outro pela via oral eintravenosa. Os animais foram acompanhados por cinco dias e foram avaliados sinais clínicos,carga viral sérica e fecal, hematologia e dosagem de eletrólitos séricos. Além disso, buscou-sedefinir o perfil de células do sistema imune no sangue periférico, assim como detecção decitocinas no soro dos animais, ensaios de imunofluorescência para detecção da proteína nãoestrutural do rotavírus e também das células do sistema imune em cortes congelados deintestino...

Rotavirus is the most common cause of acute gastroenteritis in children under five years oldworldwide, accounting for about 200,000 deaths per year. Its spread is due to person to personcontact, mainly through fecal-oral transmission. Although there are vaccines available forrotavirus, alternative measures are required, for example, in outbreaks. Thus, the use ofimmunoglobulin Y (IgY) in passive immunotherapy is justified. The IgY is the predominantimmunoglobulin in birds circulation, being transferred from the blood by active secretion intothe yolk of eggs from which the purification is performed to obtain the specific antibody ofinterest. The advantages presented by this methodology include: easy obtainment, low cost,and production capacity in large-scale, appropriate considering current bioethical guiderlines.IgY is increasing employed in methods of diagnosis and passive immunotherapy. This studyevaluated the infectivity of human rotavirus A (RVA) in cynomolgus monkeys (Macacafascicularis) and therapeutic function of IgY after challenge with RVA orally. The animalswere divided in two groups: one that received IgY only by oral route and the other by oral andintravenous routes. We followed up the animals for five days through clinical manifestations,serum and fecal viral load, hematology and dosage of serum electrolytes. Moreover, weinvestigated the profile of immune cells in peripheral blood, detection of cytokines in theserum, immunofluorescence assays for the detection of rotavirus non-structural protein andimmune cells in the intestine. The absence of diarrhea episodes was considered a good signfor the clinical efficacy of IgY immunotherapy, however, viral RNA was found in the stool ofsome animals. The group treated with IgY orally and intravenously was the one in which wedid not detect viral genome in faeces. As for the cell populations in peripheral blood, it wasnot observed significant difference between groups...

La carga de la enfermedad por rotavirus en niños menores de cinco años, Colombia, 2004 / Burden of rotavirus-related disease among children under five, Colombia, 2004

OBJETIVOS: Establecer un sistema de vigilancia intrahospitalaria de la diarrea en niños menores de 5 años, estimar la carga de la enfermedad por rotavirus e identificar los genotipos más frecuentes de rotavirus. MÉTODOS: Se incluyó en este estudio a niños hospitalizados por complicaciones graves de la diarrea en tres centros asistenciales de Santa Fe de Bogotá, Barranquilla y Cali, Colombia. Se utilizó un método de enzimoinmunoanálisis en fase sólida (ELISA) para la detección de rotavirus y un método de reacción en cadena de la polimerasa con transcripción inversa (RT-PCR) para la genotipificación. Se determinaron las frecuencias, la tendencia central y la dispersión de las variables. Se realizó un análisis estratificado y un análisis con dos variables, mediante una prueba de la ji2 o una prueba exacta de Fisher, o una prueba de la ji2 para evaluar la tendencia, según los datos. Se establecieron los riesgos relativos. Para el análisis de la tendencia, se utilizaron la regresión lineal, los coeficientes de correlación y los valores de P. RESULTADOS: Entre diciembre de 2003 y noviembre de 2004 se hospitalizó a 893 niños en los tres centros participantes en el estudio, de los cuales el 68 por ciento tenía entre 6 y 23 meses de edad. Un 2,7 por ciento de los pacientes ingresados presentaba un cuadro de choque hipovolémico y un 1,2 por ciento falleció. Solo un 57 por ciento de las madres había administrado a sus hijos una solución de rehidratación oral antes de la hospitalización. La infección por rotavirus motivó un 50 por ciento de las hospitalizaciones (coeficiente de correlación [r] > 0,8) y se relacionó con intolerancia a la vía oral (riesgo relativo [RR] = 1,45; intervalo de confianza del 95 por ciento [IC95 por ciento]: 1,24 - 1,69; P < 0,0000) y vómito incoercible (RR = 1,47; IC95 por ciento: 1,16 - 1,86; P < 0,01). La infección por rotavirus ocasionó una muerte por cada 2 000 niños; 16 hospitalizaciones por cada 1 000 niños y 631 consultas por cada 1 000 niños. Se identificó estacionalidad en los genotipos G1P[8], G2P[4] y G3P[8] de rotavirus, que no varió a pesar de la distancia geográfica y las diferencias de temperatura, humedad y precipitación entre las tres ciudades.CONCLUSIONES: La infección por rotavirus es una causa importante de morbilidad y mortalidad por diarrea, especialmente en los primeros años de vida, cuando los niños están más expuestos a las complicaciones graves. Es necesario que las estrategias de prevención tengan un alto impacto antes de los 6 meses de edad. La vacunación contra el rotavirus puede ser una buena estrategia complementaria de intervención. No se encontró en la literatura internacional ninguna descripción anterior de la estacionalidad de los genotipos de rotavirus. Es importante hacer estudios de costo-efectividad para favorecer la inversión de recursos según las necesidades de la población y continuar la vigilancia para ampliar el conocimiento del comportamiento de este virus.

OBJECTIVES: To establish an in-hospital surveillance system for diarrhea in children under five, to estimate the burden of rotavirus-related disease, and to identify the most common rotavirus genotypes. METHODS: Included in the study were children who were hospitalized for serious complications of diarrhea in three medical care facilities in Bogotá, Barranquilla, and Cali, Colombia. A solid-phase enzyme-linked immunosorbent assay (ELISA) was used to detect rotavirus, and reverse-transcriptase polymerase chain reaction (RT-PCR) was the genotyping method employed. The frequencies, central tendency, and dispersion of the variables were determined. Stratified analysis and bivariate analysis were performed by applying a chi squared test or Fisher's exact test, or a chi squared test for trends, depending on the type of data analyzed. Relative risks were established. For analyzing trends we performed linear regression and calculated correlation coefficients and P values. RESULTS: Between December 2003 and November 2004, 893 children were hospitalized in the three participating centers included in the study. Of these children, 68 percent were between 6 and 23 months of age; 2.7 percent of hospitalized patients showed clinical signs of hypovolemic shock, and 1.2 percent died. Only 57 percent of the mothers had given their children an oral rehydration solution before hospitalization. Rotavirus infection was the cause of 50 percent of hospitalizations (correlation coefficient [r] > 0.8) and was linked to an inability to hold down orally-ingested fluids (relative risk [RR] = 1.45; 95 percent confidence interval [95 percent CI]: 1.24 to 1.69; P < 0.0000) and to intractable vomiting (RR = 1.47; 95 percent CI: 1.16 to 1.86; P < 0.01). Rotavirus infection led to one death per 2 000 children; 16 hospitalizations per 1 000 children, and 631 medical visits per 1 000 children. A seasonal trend was noted for G1P[8], G2P[4], and G3P[8] rotavirus genotypes, and this did not vary as a result of geographic distance or differences in temperature, humidity, and rainfall among cities.CONCLUSIONS: Rotavirus infection is an important cause of morbidity and mortality from diarrhea, particularly during the first years of life, when children are more susceptible to serious complications. It is important for prevention strategies to have a high impact before 6 months of age, and vaccination against rotavirus can be a good complementary intervention strategy. No description was found in the international scientific literature of the seasonal variations in rotavirus genotypes. It is important to carry out cost-effectiveness studies in order to promote the investment of resources in accordance with population needs, and to continue surveillance activities so as to better understand how the virus behaves.

Randomized, double-blind clinical trial of a lactose-free and a lactose-containing formula in dietary management of acute childhood diarrhea.

BACKGROUND: Refeeding of artificially fed infants with lactose-containing formula after oral rehydration therapy in the treatment of acute diarrhea was concluded to be indifferent to non-lactose formula by a meta-analysis. In Thai as well as Asian infants and children with low lactase level from genetically determinant and with rotavirus infection, lactose malabsorption is most likely to occur and cause delayed recovery. The aim of this study was to compare the effect of a lactose-free and a lactose-containing formula in dietary management of acute childhood diarrhea. PATIENTS AND METHOD: A randomized, double-blind clinical trial of 80 male children, formula-fed, aged 3 to 24 months, admitted with acute watery diarrhea and mild or moderate dehydration, was carried out. All children received oral rehydration therapy for the first 4 hours. After appropriate rehydration, they were fed either a lactose-free formula (Dumex Lactose-Free Formula; treatment group, n = 40) or a lactose-containing formula (Dumex Infant Formula; control group, n = 40) in adjunction with oral rehydration solution. In addition, the infants were fed rice gruel as tolerated. Comparisons of duration of diarrhea, weight gain, vomiting, biochemical changes, stool frequency and weight and unscheduled intravenous fluid were made. RESULTS: Three children (2 treatment, and 1 control) dropped out from the study. The total number of unscheduled intravenous infusions were 6 of 80 children (7.5%), including 2 (5.0%) in the treatment group and 4 (10.0%) in the control group. Three children in the control group did not resolve from diarrhea within 7 days of treatment. Rotavirus was identified in approximately 50% of the children in each group. Using survival analysis, the median duration of diarrhea was significantly shortened by 20.5 hours in the treatment group compared to the control group (77.0 hours in the treatment group vs 97.5 hours in the control group; P = 0.002). Significantly decrease in stool frequency and increase in percent weight gain were seen in the treatment group at 24 hours. Moderate acidosis cleared up to near normal at 24 hours in the treatment group but acidosis persisted in the control group. In the rotavirus diarrhea subgroup, moderate acidosis turned to be mild in treatment group, but acidosis was unchanged with increased plasma chloride level in the control at 24 hours thus suggesting that the children in the control group might have lactose malabsorption and osmotic diarrhea. Duration of rotavirus diarrhea was shortened 23.6 hours in treatment group compared to the control (P = 0.0034). CONCLUSIONS: In this study, lactose-free formula was shown to be effective in the dietary management of acute childhood diarrhea. Duration of diarrhea was shortened, weight gain was better, and stool frequency was less when compared to lactose-containing formula. Moderate acidosis cleared up spontaneously at 24 hours. Unscheduled IV could be decreased by 50%. Children receiving lactose-free formula tolerated it well. Data of subgroup analysis of rotavirus diarrhea revealed lactose-free formula scored higher than the control group for all parameters studied.

La infección primaria sintomática con el virus de inmunodeficiencia adquirida humana tipo I / The symptomatic primary infection with the type I human immunodeficiency virus

El estudio de la infección primaria sintomática con VIH-1 permite la identificación de individuos infectados, quienes deben ser considerados desde el punto de vista de su impacto en la transmición; deben recibir asesoramiento y hacérseles seguimiento. Esta revision presenta dos trabajos recientes sobre estudios exhaustivos en siete pacientes con elevada viremia (posibilidad de transmisión de cepas citopáticas de VIH-1), existente en la infección primaria que precede a la seroconversión y durante la cual el paciente escapa al diagnóstico serológico de VIH-1 por Elisa y Western Blot

Aspectos virológicos y clínico-epidemiológicos de la infección por rotavirus: segunda parte / Virologic and clinicoepidemiologic aspects of infection by rotavirus: second part

Se tratan en el presente trabajo aspectos relacionados con la patogenia, el cuadro clínico y la inmunidad de las infecciones provocadas por rotavirus. Además, se brinda información acerca del estado actual de las investigaciones sobre la atención de vacunas sobre dichos agentes. La epidemiología y el diagnóstico de laboratorio son otros tópicos de interés que se discuten en este estudio

Statistical analysis of a rhesus rotavirus vaccine trial to assess protective effect against diarrhea in Venezuelan children of 2-4 months of age

A statistical analysis of a rhesus rotavirus vaccine (RRV) trial to assess protective effect against rotavirus diarrhea was performed in venezuelan children. A total of 302 children, aged 1 to 10 months, were studied. Factors such as vaccine antigenicity, vaccination age, severity of illness, rotavirus shedding and vaccine efficacy were evaluated in order to optimize vaccine administration. An overall efficacy of 64% was found, but in the group of infants 2-4 months of age the efficacy level was the highest (92,8%). These results were supported by the higher rates of shedding an seroresponse observed in that group of infants. It was also observed that the vaccine reduces severity of diarrheal episodes