Rotavirus vaccination in the neonatal intensive care units: where are we? A rapid review of recent evidence.

PURPOSE OF REVIEW: Rotavirus is a leading cause of viral acute gastroenteritis in infants. Neonates hospitalized in neonatal intensive care units (NICUs) are at risk of rotavirus infections with severe outcomes. The administration of rotavirus vaccines is only recommended, in the United States and Canada, upon discharge from the NICU despite rotavirus vaccines being proven well tolerated and effective in these populations, because of risks of live-attenuated vaccine administration in immunocompromised patients and theoretical risks of rotavirus vaccine strains shedding and transmission.We aimed to summarize recent evidence regarding rotavirus vaccine administration in the NICU setting and safety of rotavirus vaccines in preterm infants. METHODS: We conducted a rapid review of the literature from the past 10 years, searching Medline and Embase, including all study types except reviews, reporting on rotavirus vaccines 1 and 5; NICU setting; shedding or transmission; safety in preterm. One reviewer performed data extraction and quality assessment. RECENT FINDINGS: Thirty-one articles were analyzed. Vaccine-derived virus shedding following rotavirus vaccines existed for nearly all infants, mostly during the first week after dose 1, but with rare transmission only described in the household setting. No case of transmission in the NICU was reported. Adverse events were mild to moderate, occurring in 10-60% of vaccinated infants. Extreme premature infants or those with underlying gastrointestinal failure requiring surgery presented with more severe adverse events. SUMMARY: Recommendations regarding rotavirus vaccine administration in the NICU should be reassessed in light of the relative safety and absence of transmission of rotavirus vaccine strains in the NICU.

Development of an in vitro immunobiotic evaluation system against rotavirus infection in bovine intestinal epitheliocytes.

The bovine intestinal epithelial cell line (BIE cells) expresses the Toll-like receptor (TLR)3 and is able to mount an antiviral immune response after the stimulation with poly(I:C). In the present study, we aimed to further characterise the antiviral defence mechanisms in BIE cells by evaluating the innate immune response triggered by rotavirus (RV) infection. In addition, we attempted to determine whether immunobiotic bifidobacteria are able to confer protection of BIE cells against RV infection by beneficially modulating the antiviral immune response. RV OSU (porcine) and UK (bovine) effectively infected BIE cells, while a significant lower capacity to infect BIE cells was observed for human (Wa) and murine (EW) RV. We observed that viral infection in BIE cells triggered TLR3/RIG-I-mediated immune responses with activation of IRF3 and TRAF3, induction of interferon beta (IFN-ß) and up-regulation of inflammatory cytokines. Our results also demonstrated that preventive treatments with Bifidobacterium infantis MCC12 or Bifidobacterium breve MCC1274 significantly reduced RV titres in infected BIE cells and differentially modulated the innate immune response. Of note, both strains significantly improved the production of the antiviral factor IFN-ß in RV-infected BIE cells. In conclusion, this work provides comprehensive information on the antiviral immune response of BIE cells against RV, that can be further studied for the development of strategies aimed to improve antiviral defences in bovine intestinal epithelial cells. Our results also demonstrate that BIE cells could be used as a newly immunobiotic evaluation system against RV infection for application in the bovine host.

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.

Dietary Lactobacillus rhamnosus GG Supplementation Improves the Mucosal Barrier Function in the Intestine of Weaned Piglets Challenged by Porcine Rotavirus.

Lactobacillus rhamnosus GG (LGG) has been regarded as a safe probiotic strain. The aim of this study was to investigate whether dietary LGG supplementation could alleviate diarrhea via improving jejunal mucosal barrier function in the weaned piglets challenged by RV, and further analyze the potential roles for apoptosis of jejunal mucosal cells and intestinal microbiota. A total of 24 crossbred barrows weaned at 21 d of age were assigned randomly to 1 of 2 diets: the basal diet and LGG supplementing diet. On day 11, all pigs were orally infused RV or the sterile essential medium. RV infusion increased the diarrhea rate, increased the RV-Ab, NSP4 and IL-2 concentrations and the Bax mRNA levels of jejunal mucosa (P<0.05), decreased the villus height, villus height: crypt depth, the sIgA, IL-4 and mucin 1 concentrations and the ZO-1, occludin and Bcl-2 mRNA levels of jejunal mucosa (P<0.05), and affected the microbiota of ileum and cecum (P<0.05) in the weaned pigs. Dietary LGG supplementation increased the villus height and villus height: crypt depth, the sIgA, IL-4, mucin 1 and mucin 2 concentrations, and the ZO-1, occludin and Bcl-2 mRNA levels of the jejunal mucosa (P<0.05) reduced the Bax mRNA levels of the jejunal mucosa (P<0.05) in weaned pigs. Furthermore, dietary LGG supplementation alleviated the increase of diarrhea rate in the weaned pigs challenged by RV (P<0.05), and relieve the effect of RV infection on the villus height, crypt depth and the villus height: crypt depth of the jejunal mucosa (P<0.05), the NSP4, sIgA, IL-2, IL-4, mucin 1 and mucin 2 concentrations of jejunal mucosa (P<0.05), the ZO-1, occludin, Bax and Bcl-2 mRNA levels of the jejunal mucosa (P<0.05), and the microbiota of ileum and cecum (P<0.05) in the weaned pigs challenged by RV. These results suggest that supplementing LGG in diets alleviated the diarrhea of weaned piglets challenged by RV via inhibiting the virus multiplication and improving the jejunal mucosal barrier function, which was possibly due to the decreasing apoptosis of jejunal mucosal cells and the improvement of intestinal microbiota.

Avian rotavirus enteritis - an updated review.

Rotaviruses (RVs) are among the leading causes of enteritis and diarrhea in a number of mammalian and avian species, and impose colossal loss to livestock and poultry industry globally. Subsequent to detection of rotavirus in mammalian hosts in 1973, avian rotavirus (AvRV) was first reported in turkey poults in USA during 1977 and since then RVs of group A (RVA), D (RVD), F (RVF) and G (RVG) have been identified around the globe. Besides RVA, other AvRV groups (RVD, RVF and RVG) may also contribute to disease. However, their significance has yet to be unraveled. Under field conditions, co-infection of AvRVs occurs with other infectious agents such as astroviruses, enteroviruses, reoviruses, paramyxovirus, adenovirus, Salmonella, Escherichia coli, cryptosporidium and Eimeria species prospering severity of disease outcome. Birds surviving to RV disease predominantly succumb to secondary bacterial infections, mostly E. coli and Salmonella spp. Recent developments in molecular tools including state-of-the-art diagnostics and vaccine development have led to advances in our understanding towards AvRVs. Development of new generation vaccines using immunogenic antigens of AvRV has to be explored and given due importance. Till now, no effective vaccines are available. Although specific as well as sensitive approaches are available to identify and characterize AvRVs, there is still need to have point-of-care detection assays to review disease burden, contemplate new directions for adopting vaccination and follow improvements in public health measures. This review discusses AvRVs, their epidemiology, pathology and pathogenesis, immunity, recent trends in diagnostics, vaccines, therapeutics as well as appropriate prevention and control strategies.

Rotavirus-associated hemophagocytic lymphohistiocytosis (HLH) after hematopoietic stem cell transplantation for familial HLH.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune regulation. HLH consists of two forms: familial and acquired, the latter which occurs in association with infection, malignancy, rheumatic disease and acquired immune deficiency. Herein, we report a case of acquired HLH in a child who had received allogeneic hematopoietic stem cell transplantation for familial HLH with UNC13D mutation. Based on microbiology, only rotavirus was identified as a possible organism triggering HLH. The patient's fulminant clinical course included acute respiratory failure, a sepsis-like pattern, disseminated intravascular coagulopathy, and rhabdomyolysis, leading to multiorgan failure and death from septic shock.

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...

HSV-1 amplicon vectors as genetic vaccines.

HSV-1 amplicon vectors have been used as platforms for the generation of genetic vaccines against both DNA and RNA viruses. Mice vaccinated with such vectors encoding structural proteins from both foot-and-mouth disease virus and rotavirus were partially protected from challenge with wild-type virus (D'Antuono et al. Vaccine 28: 7363-7372, 2010; Laimbacher et al. Mol Ther 20: 1810-1820, 2012), indicating that HSV-1 amplicon vectors are attractive tools for the development of complex and safe genetic vaccines. This chapter describes the use of HSV-1 amplicon vectors that encode individual or multiple viral structural proteins from a polycistronic transgene cassette in mammalian cells. More precisely, amplicon vectors that encode multiple structural viral proteins support the in situ production of viruslike particles (VLPs) in vector-infected cells. The expression of the viral genes is confirmed by Western blot and immune fluorescence analysis, and the generation of VLPs in vector-infected cells is demonstrated by electron microscopy.

Rotavirus vaccination in central Europe.

Each year, rotavirus (RV) infection is the leading cause of acute gastroenteritis requiring hospitalisation and of nosocomially transmitted diseases in children younger than 5 years across Central European Vaccination Awareness Group (CEVAG) countries; however, inadequate surveillance systems and lack of routine RV testing still exist in most CEVAG countries, making it difficult to accurately assess the present burden of acute RV gastroenteritis in the younger population. Furthermore, routine immunisation of infants with RV vaccines has not been implemented, and no official and uniform recommendations exist in most of the countries in these territories. The present study provides CEVAG country-specific estimates of the disease burden of RV gastroenteritis among the youngest population and presents evidence-based advice on the use of RV vaccines in the region, while providing a framework for vaccination at the national level.

Protective effects of Lactobacillus rhamnosus GG against human rotavirus-induced diarrhoea in a neonatal mouse model.

Group A human rotaviruses (RV) are a leading cause of severe dehydration and gastroenteritis in infants and young children. A large body of evidence suggests that Lactobacillus rhamnosus GG (LGG) has an effect on the incidence and severity of acute RV-induced diarrhoea; however, the timing and dosage of LGG treatment remains controversial. In the present study, a neonatal mouse model with human RV-induced diarrhoea was set up and the pathophysiological characteristics of the animals were examined. Our results indicated that RV-infected mice developed diarrhoea, accompanied by increased secretion of intestinal mucosa sIgA and serum interferon (IFN)-γ, tumour necrosis factor (TNF)-α, as well as decreased serum IgA. In addition, epithelium vacuolation was noticed in the jejunum microvillus of RV-infected mice. After intragastric administration of low (2 × 10(5) CFU), middle (2 × 10(7) CFU) or high (2 × 10(9) CFU) levels of LGG for four consecutive days before or after RV infection respectively, the RV-infected mice showed a shortened duration of diarrhoea and decreased epithelium vacuolation in the jejunum. Administration of a high dose of LGG before the RV infection was found to have better protective effects against RV infection than other regimens. This study demonstrates that the protective effects of LGG against RV-induced diarrhoea are highly correlated with the timing and dosage of LGG administration in neonatal mice.

A comparison of healthcare resource use for rotavirus and RSV between vulnerable children with co-morbidities and healthy children: a case control study.

OBJECTIVE: To quantify the differences in hospital length of stay (LOS) and cost between healthy and vulnerable children with cystic fibrosis (CF), insulin-dependent diabetes mellitus (IDDM), cancer, and epilepsy who contract rotavirus (RVGE) or respiratory syncytial virus (RSV). METHODS: Hospital Episode Statistics (HES) data were collected for England, for children <5 years old, admitted between April 2001 and March 2008, using ICD-10 codes for RVGE and RSV. Cases were identified as having RVGE and/or RSV plus CF, IDDM, cancer, or epilepsy. Healthy controls had RVGE and/or RSV only, additional controls had eczema only. Cost, hospital LOS, and demographics were collected. RESULTS: Four hundred and eighty-six (0.5%) cases and 101,784 (99.5%) healthy controls were admitted with RVGE or RSV, with 17,420 eczema controls. RVGE was present in 153 (31.5%) cases and 7532 (7.4%) healthy controls, and RSV in 333 (68.5%) cases and 94,252 (92.6%) healthy controls. Cases were older (1.1 years, SD = 1.3 years), had greater LOS (9.9 days, SD = 19.9), and cost more (£3477, SD = £7765) than healthy controls (age = 0.2, SD = 0.5, p < 0.001; LOS = 1.9 days, SD = 3.1, p < 0.001; cost = £595, SD = £727, p < 0.001). Cost for cases was 6-times greater than healthy controls (p < 0.001). Controls had a 0.3 day greater LOS (p < 0.001) with RSV, but a £17 (p = 0.085) lower mean cost than RVGE. CONCLUSION: RVGE and RSV are more serious diseases in vulnerable children, requiring more intense resource use. The importance of preventing infection in vulnerable children is underlined by hygiene and appropriate isolation and vaccination strategies. When universal vaccination is under consideration, as for rotavirus vaccines, evaluation of a vaccination programme should consider the potentially positive impact on vulnerable children. LIMITATIONS: Limitations of the study include a dependency on accurate coding, an expectation that patients are identified through laboratory testing, and the possibility of unidentified underlying conditions affecting the burden.

[Epidemiology and burden of rotavirus diarrhea in day care centers in Lyon, France]. / Epidémiologie et impact de la gastroentérite aiguë à rotavirus dans les crèches municipales de la ville de Lyon - saison 2004-2005.

Rotavirus is the main cause of severe, dehydrating diarrhoea in infants and young children. In industrialized countries, pediatric rotavirus gastroenteritis (PRGE) is responsible for high morbidity, particularly among children under 3 years of age attending day care centers (DCCs). The objectives of this study were to estimate the incidence, management and cost of PRGE in DCCs. We also described the nature of group A rotavirus genotypes. This study also compared the performance of different diagnostic techniques. The study was conducted from November 2004 to May 2005. Children aged less than 36 months, attending a participating DCC at least 4 times a week were included in the study. For any episode of acute gastroenteritis (AGE), defined as the occurrence of 3 or more watery or looser than normal stools and/or forceful vomiting within a 24 h period, a fecal specimen was tested by Elisa test IDEIA Rotavirus (Dako) and the immunochromatographic test VIKIA Rota-Adeno (BioMérieux). Sequencing by RT-PCR was performed to identify the rotavirus genotype. Among the 41 DCCs contacted, 18 (43.9%) agreed to participate. Out of 966 children, 547 attended a participating DCC at least 4 times a week and met the inclusion criteria. A total of 302 were included in the study. The clinical diagnosis of AGE was confirmed and validated, by the Elisa test, in 63 fecal specimens, of which 29 (46%) were positive for rotavirus antigen, with a predominance of P[8]G9 (86%). Our results showed good sensitivity and specificity for the VIKIA and Elisa methods when compared to RT-PCR. Among the PRGE cases, 36% were male and the median age was 12.2 months. The first rotavirus case was observed in December 2004 with a peak in January 2005. The incidence of PRGE cases was 2.2 [1.4-3.0] per 100 child-months in children aged less than 36 months of age, increasing to 3.4 per 100 child-months among children aged less than 24 months. Vomiting (P<0.0005) and behavior modification (P<0.001) were significantly more frequent for PRGE cases. A total of 85.7% PRGE cases sought medical attention. In 58.3% of these cases, at least one parent had to miss work for a mean duration of 2.1 days. The total cost of rotavirus cases seeking medical attention (with or without prescribed medication, days off work for parents or additional diaper consumption) was estimated at 275.54 euros/case. The PRGE incidence rate is similar to that estimated in European studies conducted in DDC. These findings confirm that rotavirus transmission occurs not only in DCCs but within the family. This is the first study to give an estimate of the incidence and the cost of rotavirus infection in DCCs in France.

Acute childhood diarrhoea in northern Ghana: epidemiological, clinical and microbiological characteristics.

BACKGROUND: Acute diarrhoea is a major cause of childhood morbidity and mortality in sub-Saharan Africa. Its microbiological causes and clinico-epidemiological aspects were examined during the dry season 2005/6 in Tamale, urban northern Ghana. METHODS: Stool specimens of 243 children with acute diarrhoea and of 124 control children were collected. Patients were clinically examined, and malaria and anaemia were assessed. Rota-, astro-, noro- and adenoviruses were identified by (RT-) PCR assays. Intestinal parasites were diagnosed by microscopy, stool antigen assays and PCR, and bacteria by culturing methods. RESULTS: Watery stools, fever, weakness, and sunken eyes were the most common symptoms in patients (mean age, 10 months). Malaria occurred in 15% and anaemia in 91%; underweight (22%) and wasting (19%) were frequent. Intestinal micro-organisms were isolated from 77% of patients and 53% of controls (P < 0.0001). The most common pathogens in patients were rotavirus (55%), adenovirus (28%) and norovirus (10%); intestinal parasites (5%) and bacteria (5%) were rare. Rotavirus was the only pathogen found significantly more frequently in patients than in controls (odds ratio 7.7; 95%CI, 4.2-14.2), and was associated with young age, fever and watery stools. Patients without an identified cause of diarrhoea more frequently had symptomatic malaria (25%) than those with diagnosed intestinal pathogens (12%, P = 0.02). CONCLUSION: Rotavirus-infection is the predominant cause of acute childhood diarrhoea in urban northern Ghana. The abundance of putative enteropathogens among controls may indicate prolonged excretion or limited pathogenicity. In this population with a high burden of diarrhoeal and other diseases, sanitation, health education, and rotavirus-vaccination can be expected to have substantial impact on childhood morbidity.

The burden of rotavirus-related illness among young children on the Australian health care system.

OBJECTIVE: To provide estimates of the annual number and cost of hospital admissions, emergency department (ED) visits and general practitioner (GP) visits for rotavirus (RV) related acute gastroenteritis (AGE) in young children in Australia. METHODS: Numbers of hospitalisations for AGE were determined from national hospital morbidity data from July 1998 to June 2003. The fraction of these hospitalisations that may be attributed to RV was estimated by direct linkage of hospital admissions and pathology data from hospitals in two regions of Australia and by a second indirect method using the seasonal variation of RV infection. Numbers of ED visits were estimated using statewide data from Victoria and New South Wales (NSW), and numbers of GP visits were estimated from representative sample data for GP visits. Costs of RV hospital admissions and ED visits were estimated from national hospital cost data. RESULTS: RV continues to account for around 10,000 hospitalisations annually for children aged less than five in Australia at an average cost of 1890 dollars each. There are an additional 22,000 ED visits a year where the child is not subsequently hospitalised, each at a cost of 320 dollars, and approximately 115,000 visits to GPs by children in this age group for RV-AGE at a cost of 36.60 dollars each. CONCLUSIONS: The annual cost of hospital admissions, ED visits and GP visits associated with RV infection in young children in Australia is approximately 30 million dollars. IMPLICATIONS: Vaccination against RV disease in Australia may provide substantial savings to the health care system, depending on the cost and effectiveness of an immunisation program.

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.

Nosocomial rotavirus infection in European countries: a review of the epidemiology, severity and economic burden of hospital-acquired rotavirus disease.

The data currently available on the epidemiology, severity and economic burden of nosocomial rotavirus (RV) infections in children younger than 5 years of age in the major European countries are reviewed. In most studies, RV was found to be the major etiologic agent of pediatric nosocomial diarrhea (31-87%), although the number of diarrhea cases associated with other virus infections (eg, noroviruses, astroviruses, adenoviruses) is increasing quickly and almost equals that caused by RVs. Nosocomial RV (NRV) infections are mainly associated with infants 0-5 months of age, whereas community-acquired RV disease is more prevalent in children 6-23 months of age. NRV infections are seasonal in most countries, occurring in winter; this coincides with the winter seasonal peak of other childhood virus infections (eg, respiratory syncytial virus and influenza viruses), thus placing a heavy burden on health infrastructures. A significant proportion (20-40%) of infections are asymptomatic, which contributes to the spread of the virus and might reduce the efficiency of prevention measures given as they are implemented too late. The absence of effective surveillance and of reporting of NRV infections in any of the 6 countries studied (France, Germany, Italy, Poland, Spain and the United Kingdom) results in severe underreporting of NRV cases in hospital databases and therefore in limited awareness of the importance of NRV disease at country level. The burden reported in the medical literature is potentially significant and includes temporary reduction in the quality of children's lives, increased costs associated with the additional consumption of medical resources (increased length of hospital stay) and constraints on parents'/hospital staff's professional lives. The limited robustness and comparability of studies, together with an evolving baseline caused by national changes in health care systems, do not presently allow a complete and accurate overview of NRV disease at country level to be obtained. RV is highly contagious, and the efficiency of existing prevention measures (such as handwashing, isolation and cohorting) is variable, but low at the global level because of the existence of numerous barriers to implementation (eg, lack of staff, high staff turnover, inadequate hospital infrastructure). Prevention of RV infection by mass vaccination could have a positive impact on the incidence of NRV by reducing the number of children hospitalized for gastroenteritis, therefore reducing the number of hospital cross-infections and associated costs.

Clinical application of rapid assay of interleukin-6 in influenza-associated encephalopathy.

The characteristics of influenza-associated encephalopathy is the high mortality and nimble progress with coma which appears in general cases within 48 hours. Most of patients show no abnormalities in the standard blood checks on admission or in early stage. In this study we investigated if a rapid assay of interleukin (IL)-6 is useful in influenza-associated encephalopathy in early stages. The levels of IL-6 in patients with influenza-associated encephalopathy did not show any significant difference compared with those in patients with febrile convulsion and rotavirus-associated convulsion. However the levels of IL-6 in severe cases were significantly higher than those of mild cases with influenza-associated encephalopathy. Consequently the rapid assay of serum IL-6 is useful to evaluate and decide the therapies.

Bovine colostrums: a review of clinical uses.

Bovine colostrums are the "early" milk produced by cows during the first several days post-parturition. This "early" milk has a nutrient profile and immunological composition that differs substantially from "mature" milk. Included in the nutrient profile are higher amounts of immunoglobulins, growth factors, cytokines, and nucleosides than are found in milk. Bovine colostrums are also rich in oligosaccharides, antimicrobials, and immune-regulating factors. Available evidence suggests a beneficial effect of supplementation of bovine colostrums in improving body composition, aspects of athletic performance, diarrhea in persons with immune-deficiency syndromes, NSAID-induced gastrointestinal disturbances, and aspects of the acute phase response that occurs secondary to surgery. Specific hyperimmune bovine colostrums, produced to have high neutralizing titer activity against Cryptosporidia, H. pylori, measles, rotavirus, and Shigella sp., appear to have clinical utility in conditions associated with these infectious organisms.

Pathogenesis of rotavirus gastroenteritis.

The outcome of intestinal infection with rotaviruses is more complex than initially appreciated, and it is affected by a complex interplay of host and viral factors. Rotaviruses infect intestinal enterocytes, and the early events in infection are mediated by virus-epithelial cell interactions. Diarrhoea may be caused by several mechanisms including (i) malabsorption that occurs secondary to the destruction of enterocytes, (ii) villus ischaemia and activation of the enteric nervous system that may be evoked by release of a vasoactive agent from infected epithelial cells in the absence of significant pathologic lesions or enterocyte damage, and (iii) intestinal secretion stimulated by the intracellular or extracellular action of the rotavirus non-structural protein, NSP4, a novel enterotoxin and secretory agonist with pleiotropic properties. New studies of rotavirus infection of polarized intestinal epithelial cells show that rotaviruses infect cells differently depending on whether or not they require sialic acid for initial binding, and infection alters epithelial cell functions. NSP4 also affects epithelial cell function and interactions. NSP4 (i) induces an age- and dose-dependent diarrhoeal response in young rodents that is similar to virus-induced disease, (ii) stimulates a Ca(2+)-dependent cell permeability where the secretory response is age-dependent, and (iii) alters epithelial cell integrity. Antibody to NSP4 protects mouse pups from diarrhoea induced by homotypic and heterotypic viruses. These data support a new mechanism of rotavirus-induced diarrhoea whereby a viral enterotoxin triggers a signal transduction pathway that alters epithelial cell permeability and chloride secretion. This new information about how a gastrointestinal virus causes disease demonstrates common pathogenic mechanisms for viral and bacterial pathogens not previously appreciated. These results also suggest new approaches to prevent or treat rotavirus-induced diarrhoea.

Randomised double blind study of hypotonic oral rehydration solution in diarrhoea.

A hypotonic (osmolality 224 mmol/l, sodium 60 mmol/l) oral rehydration solution (ORS) was compared with an isotonic high glucose ORS (osmolality 304 mmol/l, sodium 60 mmol/l) in children with acute diarrhoea in a randomised double blind study. The stool output and hence the mean consumption of ORS for maintenance hydration was less (p = 0.036) in patients receiving hypotonic (69 ml/kg) than isotonic (97 ml/kg) ORS. Hypotonic ORS was more effective in patients with rotavirus positive than with rotavirus negative diarrhoea.