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Rotavirus is the major cause of severe, dehydrating infantile gastroenteritis. Infection is limited to the gut, but the relative roles of serum and secretory copro-immunoglobulin A (IgA) in protection are unclear. Specific copro-IgA is predictive of duodenal antirotaviral IgA and correlates with virus-neutralizing coproantibody. Copro-IgA conversion is a more sensitive marker of rotavirus reinfection than seroconversion. We measured rotavirus reinfections by copro-IgA conversion prospectively in 35 children recruited at a time of severe rotavirus illness. The children were followed up longitudinally for 14 to 31 months to determine whether high coproantibody levels correlated with clinical protection against rotavirus disease. Ninety-four percent of the children experienced reinfection, and 38% developed persistent elevations in specific copro-IgA termed plateaus. Plateau children had a higher mean annual rate of rotavirus infection and a lower ratio of symptomatic to total number of rotavirus reinfections than did nonplateau children. The annual rates of rotavirus infection and disease were significantly higher outside the plateau than inside it in children experiencing antirotavirus copro-IgA plateaus. Frequent rotavirus infection of children appears to stimulate production of a specific copro-IgA plateau which correlates with protection against an excess of infection and symptomatic disease.

Equine group A rotaviruses isolated over a 10-year period in New York State, New Jersey, Kentucky, and Texas were compared serotypically and electropherotypically. All isolates were determined to be serotype 3 by reaction with hyperimmune antiserum to the serotype 3 H-2 strain of equine rotavirus. All displayed RNA electrophoretic migration patterns related to that of the H-2 strain but distinct from that of serotype 5 strain H-1. A serologic survey of 184 mares in Kentucky, which was done to determine the incidence of H-1 and H-2 infections, showed geometric mean serum neutralizing titers to the H-2 strain of equine rotavirus to be significantly higher than those to the H-1 strain. These data suggest that the serotype 3 H-2 strain is the dominant equine rotavirus in Kentucky and perhaps elsewhere in the United States. We were unable to produce confirmational evidence that the H-1 strain occurs as a natural infection in the United States.

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Bovine colostrum with rotavirus-neutralizing activity was fed for 10 days to two groups of piglets, one of which was inoculated intranasally with a rotavirus of porcine origin. A third group, which did not receive colostrum, was also inoculated with the virus, and these piglets developed diarrhea, excreted rotavirus in the feces, and died 6 days after infection. In contrast, the infected piglets fed with bovine colostrum remained healthy, although they developed antibody to rotavirus. Twenty-seven days after the primary inoculation, piglets in the colostrum-fed groups were inoculated intranasally with virus. Those in the previously unexposed group became clinically ill and excreted rotavirus, whereas those which had experienced a previous subclinical infection (the colostrum-fed, virus-inoculated group) remained healthy. It was concluded that bovine colostrum protected piglets from the clinical effects of a porcine rotavirus and that these animals developed an immunity which prevented subsequent disease.

Three sequential serum samples collected from each of 20 young children with a naturally acquired primary rotavirus infection were assayed by the radioimmunoprecipitation technique for immunoglobulin G antibodies to rotavirus structural and nonstructural proteins of the four major human rotavirus serotypes G1, P1A; G2, P1B; G3, P2; and G4, P2. Fourteen children were infected with a serotype G1 rotavirus strain and six children were infected with a serotype G4 rotavirus strain. Sera were collected from each child in the acute and convalescent periods postinfection and also approximately 4 months later. Serum immune responses to rotavirus core antigens VP2 and VP3, to the major inner capsid antigen VP6, to nonstructural proteins NS35, NS28, and NS26, and to the outer capsid neutralization antigen VP4 of all test strains were detected in the majority of patients. These responses do not appear to be influenced by the G type or P type of the rotavirus strain used in the reactions. Homologous responses to the main neutralization antigen VP7 were detected in 93% of patients with serotype G1 infections and 50% of patients with serotype G4 infections. Heterologous VP7 responses were less frequently detected and were restricted to G1, G3, and G4 serotype rotavirus strains. No responses to VP7 of the serotype G2 rotavirus strain were detected in any patients. Heterotypic immune responses to the neutralization antigens, at least following serotype G1 and G4 infections, therefore appear to consist primarily of responses to VP4 rather than to VP7.

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Background Approximately 39% of the global diarrhoea deaths in children aged 5 years may be attributable to rotavirus infection. Two rotavirus vaccines were recently introduced to the market, with evidence of efficacy in the USA, Europe and Latin America. We sought to estimate the effectiveness of these vaccines against rotavirus morbidity and mortality.

Methods We conducted a systematic review of published efficacy and effectiveness trials of rotavirus vaccines. Study descriptors and outcome measures were abstracted into standardized tables and the quality of each study was graded. We performed meta-analyses for any outcome with two or more data points, and used child health epidemiology reference group (CHERG) Rules for Evidence Review to estimate the effect of the vaccine on rotavirus mortality.

Results We identified six papers for abstraction, reporting results from four studies. No studies reported diarrhoea or rotavirus deaths, but all studies showed reductions in hospitalizations due to rotavirus or diarrhoea of any aetiology, severe and any rotavirus infections and diarrhoea episodes of any aetiology in children who received rotavirus vaccine compared with placebo. Effectiveness against very severe rotavirus infection best approximated effectiveness against the fraction of diarrhoea deaths attributable to rotavirus, and was estimated to be 74% (95% confidence interval: 35–90%).

Conclusions Rotavirus vaccines are efficacious against rotavirus morbidity and mortality and have the potential to substantially reduce child mortality in low-income countries if implemented appropriately.

Rotavirus, the most common diarrheal pathogen in children worldwide, causes approximately one third of diarrhea-associated hospitalizations and 800,000 deaths per year. Because natural infection reduces the incidence and severity of subsequent episodes, rotavirus diarrhea might be controlled through vaccination. Serotypespecific immunity may play a role in protection from disease. Tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) (which contains a rhesus rotavirus with serotype G3 specificity and reassortant rhesus-human rotaviruses with G1, G2, and G4 specificity) provides coverage against the four common serotypes of human rotavirus. In clinical trials in industrialized countries, RRV-TV conferred 49% to 68% protection against any rotavirus diarrhea and 61% to 100% protection against severe disease. This vaccine was licensed by the U.S. Food and Drug Administration on August 31, 1998, and should be cost-effective in reducing diarrheal diseases in industrialized countries. The vaccine's efficacy and cost-effectiveness in developing countries should be evaluated.

Background:

Rotaviruses cause diarrhea in infants and young children worldwide. Rotavirus outer capsid protein, VP7 is major neutralizing antigen that is important component of subunit vaccine to prevent rotavirus infection. Many efforts have been done to produce recombinant VP7 that maintain native characteristics. We used baculovirus expression system to produce rotavirus VP7 protein and to study its immunogenicity.

Methods:

Simian rotavirus SA11 full-length VP7 ORF was cloned into a cloning plasmid and then the cloned gene was inserted into the linear DNA of baculovirus Autographa californica Nuclear Polyhedrosis Virus (AcNPV) downstream of the polyhedrin promoter by in vitro recombination reactions. The expressed VP7 in the insect cells was recognized by rabbit hyperimmune serum raised against SA11 rotavirus by Immunofluorescence and western blotting assays. Rabbits were immunized subcutaneously by cell extracts expressing VP7 protein.

Results:

Reactivity with anti-rotavirus antibody suggested that expressed VP7 protein had native antigenic determinants. Injection of recombinant VP7 in rabbits elicited the production of serum antibodies, which were able to recognize VP7 protein from SA11 rotavirus by Western blotting test and neutralized SA11 rotavirus in cell culture.

Conclusion:

Recombinant outer capsid glycoprotein (VP7) of rotavirus expressed in insect cells induces neutralizing antibodies in rabbits and may be a candidate of rotavirus vaccine.

A case-control epidemiological study was conducted to determine whether an increased diagnostic rate for group A rotavirus in swine herds in Ontario was associated with specific management factors. The number of new herds tested per year and the proportion of new positive herds increased between 1994 and 1997. Herd size was larger and weaning age was younger in rotavirus-positive herds compared with rotavirus-negative herds. Pigs raised in all-in all-out nurseries were 3.4 times more likely to have a positive group A rotavirus diagnosis than pigs in continuous flow facilities. This study demonstrates that the changes seen in group A rotavirus disease herd status in Ontario are associated with changes in farm management practices, including farm expansion, early weaning, and all-in all-out production.

The local and systemic humoral immune responses to rotavirus were studied in six conventional neonatal calves. Attenuated bovine rotavirus was administered either orally or directly into an isolated intestinal loop. The parameters monitored were neutralizing rotavirus antibody in serum, immunofluorescent and neutralizing rotavirus antibody in intestinal loop washings, and rotavirus antibody-producing cells in intestinal mucosa. An antibody response was observed in the serum and intestinal secretions from one calf only. Viral replication was not detected in the isolated intestinal loop. Rotavirus antibody-producing cells were found in the intestinal mucosa of five calves. Double staining revealed that most of these cells produced antibody of the immunoglobulin A class. The conclusions were: (i) a previously described system to detect rotavirus antibody-producing cells can be used to study immune responses in neonatal calves, (ii) the class or subclass of antibody in rotavirus antibody-producing cells can be determined by double immunofluorescent staining, (iii) neonatal calves respond to rotavirus inoculation with a local immunoglobulin A response, and (iv) most of the rotavirus antibody-producing cells are located in the mucosa of the proximal small intestine.

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Background

Kawasaki Syndrome (KS) is an uncommon childhood disease with unknown etiology. It has been suggested that rotavirus infection may play a causative role in the development of KS.

Methods

To examine potential temporal associations between KS and rotavirus infection, seasonal patterns of KS- and rotavirus-associated hospitalizations among children in California and New York during 2000-2005 were compared.

Results

Rotavirus hospital admissions were markedly winter seasonal, with very few summer hospitalizations. KS hospitalizations occurred year-round but also peaked slightly during winter and spring.

Conclusion

The strong winter seasonal pattern of rotavirus clearly differed from the year-round pattern of KS hospitalizations. While the present study cannot completely rule out rotavirus as having a role in the development of KS, other agents must be involved in the etiology of KS.

We determined the levels of group A common and neutralizing antibodies against human rotavirus in paired serum specimens obtained from 38 infants within 12 days of the onset of diarrhea. Thirty of the infants excreted rotavirus in stools, and eight did not. Nine patients (30%) with rotavirus diarrhea and seven patients (88%) with diarrhea due to other causes had detectable levels (greater than or equal to 1: 80) of immunoglobulin (IgG) common antibodies in acute-phase sera. All the patients with rotavirus diarrhea showed at least fourfold rises in titers of IgG or IgM common antibodies or both, while only two control patients showed significant rises in either IgG or IgM common antibodies in their convalescent-phase sera. Of the 19 patients excreting "short" electropherotypes of rotavirus, 18 showed at least fourfold rises in titers of neutralizing antibodies against serotype 2 human rotavirus but not against serotype 1, 3, or 4. Nine of the ten patients excreting "long" electropherotypes showed significant rises in neutralizing antibodies against serotype 3, and the other patient showed a significant rise in neutralizing antibodies against serotype 1. One patient excreted long and short electropherotypes simultaneously, and he also showed a significant rise in neutralizing antibodies against serotype 2 and 3 viruses. The control patients with diarrhea did not show significant changes in titers of antibodies against any of the serotypes. These results demonstrated that the neutralizing antibody response within 2 weeks after clinical onset is specific for the infecting serotype of rotavirus.

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Studies were carried out during an outbreak of rotavirus type 2 infection in a neonatal nursery to determine the protective role of antibodies in cord blood and breast milk. The range, distribution, and geometric mean titres of rotavirus-specific antibody in the cord blood were similar among rotavirus-positive and rotavirus-negative neonates, and the amount of virus excreted did not correlate with antibody levels. Despite the protective effect of breast feeding, the pattern of rotavirus-specific IgA and IgG antibodies in the expressed breast milk of mothers of babies who were rotavirus excreters and non-excreters was similar. Nevertheless, a higher proportion of expressed breast milk samples contained rotavirus-specific IgA group 2 (92%) and type 2 (97%) specific antibodies than type I (67%) antibodies, and the geometric mean titres of group 2 and type 2 specific antibodies were tenfold higher than type I antibodies. Among breast-fed babies who excreted rotavirus there was no correlation between type 2 rotavirus-specific IgA antibodies in expressed breast milk and the amount of neonatal virus excretion. These studies suggest that factors other than the rotavirus antibodies in expressed breast milk are of importance in preventing rotavirus infection in newborn infants.

A cell culture immunofluorescence (CCIF) assay was optimized for detection of porcine pararotavirus (group C rotavirus) in intestinal contents. The greatest viral infectivity was observed when MA104 cells (5 days after subculturing) were rinsed and refed in serum-free medium before inoculation, pancreatin was added to the inocula, and the inocula were centrifuged onto the cells. Gentamicin treatment of pararotavirus samples to reduce bacterial contamination also reduced the viral infectivity of these samples for MA104 cells. An indirect CCIF assay was used to determine the prevalence of pararotavirus and rotavirus antibodies in pig sera. In pigs from four herds, pararotavirus antibodies were detected in 100% (68 of 68) of adults and 59% (24 of 41) of weanling pigs, while 86% (24 of 28) of nursing pigs from 12 herds had pararotavirus antibodies. The physicochemical properties of pararotavirus were examined and compared with those of group A rotaviruses by using the CCIF assay to quantitate in vitro changes in viral infectivity. Pararotavirus was inactivated (greater than or equal to 99% reduction in titer) by heating to 56 degrees C for 30 min, was slightly labile at pH 3 (16 to 34% reduction in titer), and was stable at pH 5 (0 to 17% reduction in titer) and in either (3 to 19% reduction in titer). One group A rotavirus (Gottfried strain) was stable at 56 degrees C (0% reduction in titer), whereas the OSU strain of group A rotavirus was inactivated at this temperature (99% reduction in titer).

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Background

Rotavirus still remains the major cause of diarrhea in children below 5 years. No data on rotavirus epidemiology is available in the Northern regions of Cameroon. We aimed to determine the prevalence of group A rotavirus (RVA) in children below 5 years with diarrhea in two regions of Northern Cameroon (North West and Far North Regions) so as to improve our knowledge on the burden of rotavirus disease for imminent introduction of a rotavirus vaccine.

Methods

Stool samples were collected during 2010 and 2011 from 390 children below 5 years presenting with diarrhea in four hospitals in Northern Cameroon and were screened for rotavirus group A by reverse transcription-polymerase chain reaction.

Results

This study revealed that 42.8% of the children below 5 years had group A rotavirus infection, 46.5% in the Far North region while the North West had a prevalence of 33.9%. Of the 252 hospitalized and the 138 outpatient children, 124(49.2%) and 43(31.2%) (P=0.00085), respectively, were positive for group A rotavirus. Children below 24 months were most affected (44.7%), while the age group 49-60 months had the lowest prevalence (25%). The RVA prevalence was 44.6% in the urban and 28.9% in the rural settings of our study. It was observed that the proportion of children with diarrhea who had rotavirus accompanied with fever and vomiting in the outpatient group and inpatient group were 13.0% and 28.6% respectively, P=0.03.

Conclusion

This study showed high incidence of rotavirus infection especially among hospitalized children in Northern Cameroon, suggesting that rotavirus is a major cause of childhood morbidity and mortality in this area.

The effect of circulating passive antibody on immunity to bovine rotavirus infections in neonatal calves was investigated. In the first experiment, rotavirus antibody titers in the small intestinal lumina of 5- and 10-day-old calves with a wide range of serum rotavirus antibody titers were determined. Neutralizing antibody was present in the small intestinal lumina in titers that correlated with the calves' serum titers (r = +0.84, P less than 0.01). Immunoglobulin G1 was the predominant isotype of intestinal luminal rotavirus antibody. Calves not fed colostrum during the absorptive period lacked rotavirus antibody in circulation and in the intestinal lumen at 7 days of age, even when they were fed large volumes of colostrum with a high rotavirus antibody titer at 48 h after birth. Therefore, rotavirus antibody is not retained in the intestinal lumen for 5 days following a colostrum meal, and the luminal antibody in the 5- and 10-day-old seropositive calves were probably derived from circulating antibody. In a second experiment, calves were passively immunized by subcutaneous injection of colostral whey with a high immunoglobulin G1 rotavirus antibody titer and challenged with virulent bovine rotavirus 48 h later. The passively immunized calves were protected from rotavirus infection and diarrhea compared with calves with comparable serum immunoglobulin concentrations but with lower serum rotavirus with lower serum rotavirus antibody titers. The results of these experiments indicate that circulating immunoglobulin G1 antibody appears in the gastrointestinal tract of neonatal calves and that circulating rotavirus antibody can prevent infection and diarrhea after rotavirus challenge.

We determined titers of group A rotavirus common antibodies and neutralizing antibodies against serotypes 1 to 4 of prototype human rotavirus (HRV) in cord blood and serum specimens obtained from 38 infants at 4-month intervals from birth until 2 years of age. Nineteen of the infants developed one episode of HRV diarrhea each, and they were matched by age and birth weight with the other 19 infants, who did not develop HRV diarrhea during the follow-up period. We estimated the incidence rate of HRV infection for the two groups of infants combined to be a minimum of 1.34 episodes per infant per year, which is 22 times more common than the occurrence of overt disease caused by the virus in this community. The infection occurred constantly throughout the first 2 years of infancy, whereas all but one of the 19 episodes of overt disease occurred before 12 months of age. Seven of these overt episodes were preceded by at least one episode of subclinical infection earlier, and the other seven were probably due to primary HRV infection. The remaining five episodes occurred before 4 months of age, so that we could not ascertain whether they were due to primary infections because of the presence of maternal antibodies. We showed that levels of HRV antibodies in serum specimens obtained before clinical onset of diarrhea varied widely, and, for most infants in the diarrheal group, levels of these antibodies were similar to those in the serum specimens obtained at the same times from the corresponding age- and birth weight-matched control infants. Nevertheless, the age at which overt disease caused by HRV was most prevalent coincided with the time when the maternal antibodies had declined to low levels but the infants had not yet acquired high titers of these antibodies in their sera.

Elevated levels of prostaglandins (PGs), products of cyclooxygenases (COXs), are found in the plasma and stool of rotavirus-infected children. We sought to determine the role of COXs, PGs, and the signal transduction pathways involved in rotavirus infection to elucidate possible new targets for antiviral therapy. Human intestinal Caco-2 cells were infected with human rotavirus Wa or simian rotavirus SA-11. COX-2 mRNA expression and secreted PGE2 levels were determined at different time points postinfection, and the effect of COX inhibitors on rotavirus infection was studied by an immunofluorescence assay (IFA). To reveal the signal transduction pathways involved, the effect of MEK, protein kinase A (PKA), p38 mitogen-activated protein kinase (MAPK), and NF-κB inhibitors on rotavirus infection was analyzed. In infected Caco-2 cells, increased COX-2 mRNA expression and secreted PGE2 levels were detected. Indomethacin (inhibiting both COX-1 and COX-2) and specific COX-1 and COX-2 inhibitors reduced rotavirus infection by 85 and 50%, respectively, as measured by an IFA. Indomethacin reduced virus infection at a postbinding step early in the infection cycle, inhibiting virus protein synthesis. Indomethacin did not seem to affect viral RNA synthesis. Inhibitors of MEK, PKA, p38 MAPK, and NF-κB decreased rotavirus infection by at least 40%. PGE2 counteracted the effect of the COX and PKA inhibitors but not of the MEK, p38 MAPK, and NF-κB inhibitors. Conclusively, COXs and PGE2 are important mediators of rotavirus infection at a postbinding step. The ERK1/2 pathway mediated by PKA is involved in COX induction by rotavirus infection. MAPK and NF-κB pathways are involved in rotavirus infection but in a PGE2-independent manner. This report offers new perspectives in the search for therapeutic agents in treatment of severe rotavirus-mediated diarrhea in children.

Group A rotaviruses are major pathogens causing acute gastroenteritis in children and animals. To determine if group A rotavirus replicates and induces disease in rats, antibody-negative Lewis neonatal or adult rats were inoculated orally with tissue culture-adapted human (Wa, WI61, and HAL1166), simian (rhesus rotavirus [RRV] and SA11), bovine (WC3), lapine (ALA), or porcine (OSU) rotavirus strains, wild-type murine (ECwt) rotavirus strain, or phosphate-buffered saline (PBS). Rotavirus infection in rats was evaluated by (i) clinical findings, (ii) virus antigen shedding or infectious virus titers in the feces or intestinal contents measured by enzyme-linked immunosorbent assay or fluorescent-focus assay, (iii) histopathological changes in the small intestine, (iv) distribution of rotavirus antigen in small-intestine sections by immunofluorescence, and (v) growth rate. Rotavirus infection of 5-day-old but not ≥21-day-old rats resulted in diarrhea that lasted from 1 to 10 days postinoculation. The severity of disease and spread of infection to naÏve littermates differed depending on the virus strain used for inoculation. The duration of virus antigen shedding following infection was considerably prolonged (up to 10 days) in neonatal rats compared to that in 21-day-old rats (1 or 2 days). Based on lack of virus antigen shedding and disease induction, the murine ECwt rotavirus was the only strain tested that did not infect rats. Histopathological changes in the small-intestine mucosa of 5-day-old RRV-inoculated rats but not of PBS-inoculated rats was limited to extensive enterocyte vacuolation in the ileum. In RRV-inoculated neonatal rats, rotavirus antigen was detected in the epithelial cells on the upper half of the intestinal villi of the jejunum and ileum. In addition, infection of neonatal rats with RRV but not with PBS resulted in reduced weight gain. Rats infected with group A rotaviruses provide a new animal model with unique features amenable to investigate rotavirus pathogenesis and the molecular mechanisms of intestinal development, including physiological factors that may regulate age-dependent rotavirus-induced diarrhea.

Background

Rotavirus infection is the most common cause of severe, dehydrating, gastroenteritis among children worldwide. In developing countries, approximately 1440 children die from rotavirus infections each day, with an estimated 527,000 annually. In infants, rotavirus is estimated to cause more than 2 million hospitalizations every year depending on the income level of the country.

The purpose of this study was to estimate the proportion of rotavirus gastroenteritis and identify the distribution of circulating G and P genotype rotavirus strains among children consulting several dispensaries in the region of Monastir (outpatients departments) or admitted to Monastir University Hospital (inpatients department) with acute gastroenteritis.

Methods

This study was undertaken during a 3-year period from April 2007 to April 2010 in Tunisian children under 13 suffering from acute gastroenteritis. Group A rotaviruses were detected in stools by ELISA and genotyped using multiplex reverse transcription PCRs with type-specific primers on the basis of their outer capsid proteins. Statistical analyses were performed with SPSS software, version 19.

Results

Of the 435 stool samples from children with acute gastroenteritis, 27.6% were positive for rotavirus A. The predominant G type was G1 (37.5%), followed by G3 (25%), G2 (17.5%), G4 (12.5%), G9 (2.5%) and three mixed-G infections G3G4 (2.5%) were identified.

Only P[8] (80.8%), P[4] (16.7%) and P[9] (0.8%) genotypes were found. The predominant single G/P combination was G1P[8] (37.5%), followed by G3P[8] (25%), G2P[4] (16.7%), G4P[8] (12.5%), G9P[8] (1.7%) and one case of the unusual combination G9P[9] (0.8%). The G-mixed types G3G4 combined with P[8] (2.5%). Infants less than 3 months of age were most frequently affected. The prevalence of rotavirus infection peaked in the winter season, when temperatures were low, and decreased in summer.

Conclusions

Rotavirus gastroenteritis is a common disease associated with significant morbidity, mortality, and economic burden. Epidemiological knowledge of rotavirus is critical for the development of effective preventive measures, including vaccines.

These data will help to make informed decisions as to whether rotavirus vaccine should be considered for inclusion in Tunisia's National Immunisation Programme.

Rotavirus causes severe morbidity in developed countries and frequent deaths (≥500,000 per year) in less-developed countries. Historically, four serotypes—G1, G2, G3, and G4—have predominated; they are distinguished by one of two surface neutralization antigens (VP7). However, in 1983 and 1984 we described a new rotavirus serotype, designated G9, in five children hospitalized for diarrhea in Philadelphia, Pa. G9 rotavirus was not identified again in the Western Hemisphere until it caused ca. 50% of the rotavirus disease detected in Philadelphia in the 1995-1996 season. This outbreak allowed us to question whether a rotavirus strain completely new to a well-studied community would target either very young infants or older children, cause especially severe disease, or completely displace previously extant serotypes. We observed a significant excess of G9 infections in younger infants (especially in those <6 months old) that might be attributed to the lack of G9-specific antibodies in mothers. Of further note, six of the seven oldest patients with rotavirus diarrhea were infected with the G9 strains (not significant). However, the age distribution of children with rotavirus did not differ over a 5-year study period regardless of the infecting serotype. Patients with diarrhea associated with G9 strains did not have disease more severe than that caused by the G1, G2, or G3 serotype. G9 strains did not displace the other serotypes but were virtually completely replaced by G1 or G2 serotypes in the three subsequent rotavirus seasons. We conclude that the abrupt appearance of this novel rotavirus serotype did not present a special threat to public health in the community.

Aims: To describe the epidemiology of intussusception and its relation to rotavirus associated hospitalisation in New Zealand.

Methods: National hospital discharge data between January 1998 and June 2003 for all children younger than 3 years of age with intussusception were reviewed. Independently, children from the same age group, admitted to eight paediatric units with rotavirus gastroenteritis between May 1998 and May 2000, were identified prospectively. Epidemiological characteristics of cases with intussusception were compared with those of hospitalised rotavirus disease.

Results: During the 5.5 year study period, there were 277 cases of intussusception and no deaths. Most (72%) occurred in the first year of life (age adjusted incident rate 65 per 100 000 child-years, 95% CI 56 to 74). Risk of intussusception was less in females (risk ratio 0.58; 95% CI 0.43 to 0.78) and for Maori (risk ratio 0.52; 95% CI 0.35 to 0.77) when compared with European infants. In contrast to hospitalised rotavirus cases, intussusception peaked at a younger age and lacked seasonality.

Conclusions: This study provides national baseline data on intussusception for future rotavirus vaccine programmes in New Zealand. Wild-type rotaviruses do not appear to have a major role in triggering intussusception. Prospective surveillance systems, using standardised case definitions and nested case-control methodology, are needed to further our understanding of the aetiology and epidemiology of intussusception.

Immunoglobulin A (IgA) is the primary immune response induced in the intestine by rotavirus infection, but vaccination with virus-like particles induces predominantly IgG, not IgA. To definitively assess the role of IgA in protection from rotavirus infection, IgA knockout mice, which are devoid of serum and secretory IgA, were infected and then rechallenged with murine rotavirus at either 6 weeks or 10 months. Following primary rotavirus infection, IgA knockout mice cleared virus as effectively as IgA normal control mice. Rotavirus-infected IgA knockout mice produced no serum or fecal IgA but did have high levels of antirotavirus serum IgG and IgM and fecal IgG, whereas IgA normal control mice made both serum IgA and IgG and fecal IgA. Both IgA normal and IgA knockout mice were totally protected from rotavirus challenge at 42 days. Ten months following a primary infection, both IgA normal and knockout mice still had high levels of serum and fecal antirotavirus antibody and were totally protected from rotavirus challenge. To determine if compensatory mechanisms other than IgG were responsible for protection from rotavirus infection in IgA knockout mice, mice were depleted of CD4+ T cells or CD8+ T cells. No changes in the level of protection were seen in depleted mice. These data show that fecal or systemic IgA is not essential for protection from rotavirus infection and suggest that in the absence of IgA, IgG may play a significant role in protection from mucosal pathogens.

Background

Rotavirus is the most common cause of gastroenteritis in young children worldwide. The aim of the study was to assess the health outcomes and the economic impact of a universal rotavirus vaccination programme with RotaTeq, the pentavalent rotavirus vaccine, versus no vaccination programme in Spain.

Methods

A birth cohort was followed up to the age of 5 using a cohort model. Epidemiological parameters were taken from the REVEAL study (a prospective epidemiological study conducted in Spain, 2004-2005) and from the literature. Direct and indirect costs were assessed from the national healthcare payer and societal perspectives by combining health care resource utilisation collected in REVEAL study and unit costs from official sources. RotaTeq per protocol efficacy data was taken from a large worldwide rotavirus clinical trial (70,000 children). Health outcomes included home care cases, General Practioner (GP)/Paediatrician, emergency department visits, hospitalisations and nosocomial infections.

Results

The model estimates that the introduction of a universal rotavirus vaccination programme with RotaTeq (90% coverage rate) would reduce the rotavirus gastroenteritis (RVGE) burden by 75% in Spain; 53,692 home care cases, 35,187 GP/Paediatrician visits, 34,287 emergency department visits, 10,987 hospitalisations and 2,053 nosocomial infections would be avoided. The introduction of RotaTeq would avoid about 76% of RVGE-related costs from both perspectives: €22 million from the national health system perspective and €38 million from the societal perspective.

Conclusions

A rotavirus vaccination programme with RotaTeq would reduce significantly the important medical and economic burden of RVGE in Spain.

Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. In 1999, a highly efficacious rotavirus vaccine licensed in the United States, RotaShield, was withdrawn from the market after 14 months because of its association with intussusception. Two new live, oral, attenuated rotavirus vaccines were licensed in 2006: the pentavalent bovine-human reassortant vaccine (RotaTeq) and the monovalent human rotavirus vaccine (Rotarix). Both vaccines have demonstrated very good safety and efficacy profiles in large clinical trials in western industrialized countries and in Latin America. Careful surveillance has not revealed any increased risk of intussusception in the vaccinated groups with either vaccine. The new rotavirus vaccines are now introduced for routine use in a number of industrialized and developing countries. These new safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.

OBJECTIVE:

To measure the economic cost of rotavirus-associated diarrhea for a selected group of families, in a nonexperimental setting, and to estimate the factors that influence these costs.

DESIGN:

Use and other socioeconomic data from a family survey (the Pediatric Rotavirus Epidemiology Study for Immunization) of children who tested positive for rotavirus were collected for the metropolitan Toronto and Peel regions of Ontario during the rotavirus season of 1997-1998. Service costs were estimated from provider data. A statistical regression analysis was used to explain the variances of provincial health care costs, prescription drug costs and indirect (work-loss) costs.

SETTING:

Data were collected in hospitals, emergency rooms, paediatric practices, primary care clinics and licensed daycare centres. Hospital coverage was wide, but community coverage was not.

PATIENTS AND OTHER PARTICIPANTS:

Children with diarrhea were tested for rotavirus. Those who tested positive and whose parents consented for their children to participate were included in the study.

INTERVENTIONS:

None

MAIN OUTCOME MEASURES:

The main outcomes were provincial health care costs, drug costs, nonmedical costs and the number of days of work missed by parents per child, as well as factors that determine these costs.

RESULTS:

Children in the most severe category incurred costs of $2,663/person, and those in the least severe categories incurred costs of approximately $350/person. The most important determinant to explain provincial health care costs was the number of health problems that the child had before having rotavirus. Costs due to work loss of parents were considerable for children in all severity groups and were influenced by family working conditions.

CONCLUSIONS:

When considering the economic implications of rotavirus, prior health status should be considered and indirect costs should be recognized for their importance.