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Evaluation of rotavirus vaccine effectiveness in a pediatric group practice.

Vaccines are traditionally tested under the optimal conditions of clinical trials (efficacy). However, their public health impact is better assessed under the real conditions of a clinical practice (effectiveness). The authors aimed to estimate the effectiveness of a rotavirus vaccine (rhesus rotavirus vaccine-tetravalent (RRV-TV)) to prevent rotavirus-related hospitalization among children <or=3 years of age. They reviewed computer records from an urban pediatric practice in New Orleans, Louisiana, comprising 1,413 children born between April 1, 1998, and June 1, 1999, and who would have been eligible to receive RRV-TV. They also reviewed hospital records to determine rotavirus hospitalizations for gastroenteritis during October 1998-June 2001. A total of 1,099 children were enrolled, 513 unvaccinated and 586 vaccinated. The attack rate of rotavirus hospitalization was 0.34 per 100 child-years-0.52 for unvaccinated (no doses) children, 0.20 for partially vaccinated (one or two doses) children, and 0 for fully vaccinated (three doses) children. Protective vaccine effectiveness was 70% (95% confidence interval (CI): -43, 94) among vaccinated children, 61% (95% CI: -86, 92) among partially vaccinated children, and 100% (95% CI: -120, 100) among fully vaccinated children. One episode of rotavirus-associated hospitalization was prevented per 104 infants partially vaccinated and per 64 infants fully vaccinated.

Child, Preschool↗

Evidence that protection against rotavirus diarrhea after natural infection is not dependent on serotype-specific neutralizing antibody.

This case-control study sought to determine whether protection against clinically significant rotavirus diarrhea in children aged 4-35 months correlated with titers of serum neutralizing antibody and, if so, whether this protection was serotype-specific. Titers of acute-phase sera from 156 cases of treated rotavirus diarrhea in rural Bangladesh were contrasted with titers from 312 contemporaneously selected, age-matched controls. Analyses of the culture-adapted rotaviruses from the cases revealed that 24%, 15%, 43%, and 17% belonged to serotypes 1-4, respectively. Titers of both homologous and heterologous neutralizing antibody in acute blood specimens of cases were significantly lower than those of matched controls. However, multivariate logistic regression models demonstrated that only antibody titers to heterotypic rotaviruses were independently associated with protection against rotavirus disease. These data, which indicate that the correlation of protection with neutralizing antibody titers is not serotype-specific, suggest that immunity to rotavirus disease may be mediated by other factors.

Algorithms↗

Sequential administration of two human-rhesus rotavirus reassortant strains of VP7 serotype 1 and 2 specificity to infants and young children.

Rotavirus vaccine strains representing serotypes 1 and 2 have been derived by reassortment between genes of a rhesus rotavirus master strain, MMU18006, and the gene from human viruses coding for VP7, a surface protein with neutralizing determinants. As simultaneous administration of these two human rotavirus reassortants had resulted in disappointing strain-specific immunity, these two vaccines were administered sequentially to infants and young children to assess whether immunity to both serotypes could be achieved with two monovalent doses. Following initial immunization with RRVxDS-1, a serotype 2 vaccine, 12 of 13 shed virus and showed serologic responses to multiple rotavirus proteins. However, with subsequent administration of RRVxD, serotype 1, only 2 of 12 shed virus, and an enhancement or broadening of the immune response was not uniformly seen. Although rhesus rotavirus vaccines are immunogenic with primary administration of monovalent vaccine in seronegative children, and supplemental seroresponses are seen with a second dose, other strategies or new vaccine candidates must be sought to induce immunity against the multiple serotypes of human rotavirus.

Administration, Oral↗

Passive protection against rotavirus-induced diarrhea of mouse pups born to and nursed by dams fed Bifidobacterium breve YIT4064.

Mouse pups born to and nursed by dams fed Bifidobacterium breve YIT4064 and immunized orally with rotavirus were more strongly protected against rotavirus-induced diarrhea than those born to and nursed by dams immunized with rotavirus only. The level of antirotavirus IgA in milk of dams fed B. breve YIT4064 and immunized orally with rotavirus was significantly higher than that of dams immunized with rotavirus only. The antirotavirus IgA level in feces of dams immunized orally with rotavirus was also increased by oral administration of B. breve YIT4064. These findings demonstrate that oral administration of B. breve YIT4064 enhanced antigen-specific IgA antibody in the mammary gland and in the intestine. Oral administration of B. breve YIT4064 may enhance antigen-specific IgA antibody against various pathogenic antigens taken orally and induce protection against infections in various mucosal tissues.

Age Factors↗

Influence of breast-feeding and oral poliovirus vaccine on the immunogenicity and efficacy of rotavirus vaccines.

To be practical and cost effective, rotavirus vaccines will have to be administered to infants with routine childhood vaccinations. Rotavirus vaccine studies were reviewed to evaluate the effect of breast-feeding and concurrent oral poliovirus vaccination (OPV) on the immunogenicity and efficacy of oral rotavirus vaccines. Both breast-feeding and OPV appeared to interfere, to some degree, with the serum immune response to rotavirus vaccines; however, the effects were usually not statistically significant and were largely overcome by administering three doses of rotavirus vaccine rather than one. Available data show no decrease in the protective efficacy of rotavirus vaccine in breast-fed children or in children receiving concurrent OPV, but larger sample sizes will be required to definitely rule out any effect.

Administration, Oral↗

Protection against rotavirus infections by DNA vaccination.

DNA vaccines encoding for murine rotavirus proteins VP4, VP6, or VP7 were tested in adult BALB/c mice for their ability to induce immune responses and protect against rotavirus challenge. A gene gun was used to inoculate vaccines into the epidermis. Rotavirus-specific serum antibodies, as measured by ELISA, and virus-specific cytotoxic T lymphocyte responses were generated by each of the three vaccines, but virus-neutralizing antibodies were detected only in mice that were inoculated with DNA vaccines encoding for VP4 and VP7. Efficacy of the vaccines was determined by challenge with 100 ID50 of homotypic rotavirus. Each of the three vaccines was effective in protecting mice against infection after rotavirus challenge as determined by reduction (P < .001) in virus excretion in mice receiving the DNA vaccines. These results demonstrate that DNA vaccination has potential as a new approach for control of rotavirus infections.

Animals↗

Food supplementation with milk fermented by Lactobacillus casei DN-114 001 protects suckling rats from rotavirus-associated diarrhea.

Group A rotavirus is the leading cause of diarrhea among children aged 3-36 mo worldwide. Introducing fermented milk products into the infant diet has been proposed for the prevention or treatment of rotavirus diarrhea. The preventive effect of milk fermented by the Lactobacillus casei strain DN-114 001 was studied in a model of germfree suckling rats supplemented daily from d 2 of life and infected with SA11 rotavirus at d 5 (RF group). One group was supplemented with nonfermented milk (RM) and two uninfected groups (CM and CF) received either nonfermented or fermented milk. Frequency and severity of diarrhea were observed. Rats were killed at various times from 0 to 120 h postinfection (p.i.). Bacteria were measured in the intestine, and rotavirus antigens were detected by ELISA in fecal samples and in different parts of the intestine. Histologic observations were made, including vacuolation, morphology of intestinal villi and number of mucin cells. RM rats had diarrhea for 6 d; compared with the CM group, they had alterations of the intestinal mucosa characterized by cellular vacuolation 48 and 72 h p.i. and a lower number of sulfated mucin cells 72 and 96 h p.i. (P: < 0.05). Early supplementation with fermented milk significantly decreased the clinical signs of diarrhea from 24 to 144 h p.i. (P: < 0.05) and prevented rotavirus infection in all sections of the intestine. Histologic lesions of the small intestine were greatly reduced (P: < 0.05) and the number of mucin cells remained unchanged. The data are discussed with respect to the possibility of reducing rotavirus diarrhea in young children by consumption of fermented milk.

Animals↗

Rotavirus subgroups, G serotypes, and electrophoretypes in cases of nosocomial infantile diarrhoea in Belém, Brazil.

From November 1992 to November 1994 stool samples were obtained from 237 children admitted to a public hospital in Belém. Rotaviruses were detected in 19.3 per cent (60/310) of faecal samples. Of these, 32.1 per cent (18/56), 20.9 per cent (38/181), and 5.4 per cent (4/73) were recorded in cases of nosocomial diarrhoea, community-acquired diarrhoea, and controls, respectively. Fifty-two (86.7 per cent) of the 60 rotavirus-positive specimens were subgrouped and the G serotypes of 55 (91.7 per cent) of them were determined. Subgroups I and II were detected in 50 per cent each of the 52 subgrouped strains. G type 2 was present in 46 (83.6 per cent) of the 55 serotyped samples; serotypes G1 and (mixed) G1 and G4 were found in 14.5 per cent and 1.8 per cent, respectively, of these specimens. Viral RNA electrophoresis showed 14 distinct patterns, including 56.7 per cent (34/60) and 43.3 per cent (26/60) of long and short profiles, respectively. In 40 (66.6 per cent) of the 60 rotavirus-positive faecal samples no enteropathogens other than rotavirus were detected. There was an increased incidence of rotavirus infection from July 1993 to February 1994. The rotavirus-related episodes of diarrhoea were more severe than those of other aetiology and greater clinical severity was not related to a specific G type, subgroup, or electrophoretype.

Brazil↗

Kinetics of viral replication in experimental rotavirus infection: effects of high dietary fat.

Epidemiological studies suggest that dietary fat can affect the frequency and severity of diarrhoeal illnesses in childhood. To study the effects of dietary fat on the kinetics of rotavirus antigen, 3-week-old mice of rotavirus-seronegative mothers were fed isocaloric diets with 40% of the total calories as fat [either butter (high saturated fat), olive oil (high monounsaturated fat), or corn oil (high polyunsaturated fat)] with one group on low fat (10% of calories) standard diet as controls. Seven-day-old mice from the first litter were killed and their stomach contents (milk) analyzed for total fatty acids. Seven-day-old mice from the second litter were inoculated with EDIM rotavirus, and some were killed at 48 h and others at 120 h postinoculation. The stool was removed from the distal colon of each mouse and examined for evidence of diarrhoea. The small intestine was removed, the contents washed, and the intestine divided into equal thirds. All stool and tissue samples were made to 10% (wt/vol), homogenised, and tested for rotavirus antigen by ELISA. We found that (a) dietary fat markedly altered the fatty acid profile of milk, (b) high saturated dietary fat (butter) delayed the onset of diarrhoea, reduced the excretion of rotavirus antigen in stool, and reduced mucosal antigen in the lower third of the small intestine at 120 h compared to 48 h postinoculation, (c) high polyunsaturated dietary fat initially increased the frequency of diarrhoea and viral antigen in the middle and lower segment at 120 h, followed by a reduction in rotavirus excretion in stool.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Rotavirus RNA variation during chronic infection of immunocompromised children.

Polyacrylamide gel electrophoresis was performed on RNA from rotaviruses isolated from two immunocompromised patients with prolonged rotavirus diarrhea. Extensive variations were observed in the genomes of rotaviruses isolated from each patient during a 16-week period of their illness. An animal model of rotavirus infection was used to help evaluate the results found in our patients. Individual mouse rotavirus strains were found to be stable during serial passage, but individual animals could be coinfected with more than one viral strain. The changes found in the rotavirus RNA from our patients possibly represented reinfection by different viral strains. Appropriate precautions should be observed to prevent such reinfections in immunocompromised patients.

Animals↗

Rotavirus vaccines: an update.

PURPOSE OF REVIEW: Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and has 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. RECENT FINDINGS: Rotavirus disease prevention efforts suffered a great setback in 1999 with the withdrawal of the RRV-TV vaccine less than a year after its introduction. Several new rotavirus vaccine candidates have now been developed and are undergoing clinical trials. SUMMARY: New safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.

Child, Preschool↗

Rotavirus infection and intussusception: a view from retrospect.

A live orally-administrable rhesus rotavirus (RRV) tetravalent (TV) vaccine, licensed in the U.S.A. and the European Union, was recalled from the market because it was suspected to increase the risk of intussusception during the week following immunization. In contrast, natural rotavirus infection is generally believed not to cause intussusception. Because my experience contributed to the first paper that linked intussusception with rotavirus infection, I have re-examined our own data published 22 years ago and other studies on this issue. I also made a case study of adenovirus and intussusception as a paradigm to establish an etiological association of viral infection and intussusception. My hypothesis postulated in this review is that natural infection of susceptible (or predisposed) infants with some rotavirus strains, probably serotype G3 rotaviruses, will result in an appreciable fraction of idiopathic intussusception. Thus, the number of rotavirus-induced intussusception cases may change reflecting the relative frequency of G3 strains, which I believe was much higher in the 70s than during the last two decades. The epidemiological data indicate that the RRV-TV vaccine triggers intussusception at a rate significantly higher than the background incidence rate following the week of vaccination, particularly after the first dose. In contrast, the data do not suggest that the cumulative incidence among the vaccine recipients increases accordingly, implicating that the risk of intussusception attributable to the RRV-TV vaccine may be minimal.

Adenoviridae Infections↗

Study of virus excretion in feces of diarrheic and asymptomatic calves infected with rotavirus.

Infection of calves by rotavirus could lead to diarrhea or subclinical disease. Therein, kinetic of viral excretion from a group of asymptomatic calves, previously exposed to a virulent strain of rotavirus, is compared to that of a group the calves of which had diarrhea associated with rotavirus infection. As determined by an enzyme-linked immunosorbent assay (ELISA), duration of rotavirus shedding in feces and maximum yield of virus antigen were similar within the two groups of calves. Rotaviruses isolated from the two above groups of animals were antigenically related as shown by neutralization tests, and showed a similar RNA electrophoretic profile. In conclusion, it is likely that both asymptomatic and diarrheic calves infected by rotavirus are equally a major source of contamination to contact healthy calves.

Animals↗

Verification of sensitivity and specificity of group a rotavirus detection in piglets faeces with monoclonal blocking ELISA methods.

Monoclonal antibodies to group A rotavirus Vp6 protein were prepared and used for verification of three blocking enzyme-linked immunosorbent assay (ELISA) modifications to detect rotavirus A. Selected competitive blocking ELISA (CB-ELISA) and electron microscopy (EM) were used for examination of 194 field faecal samples of piglets affected with diarrhoea. Rotavirus was detected in 43 samples (22.2%) by CB-ELISA method, whereas in 26 (13.4%) samples by EM examination. However, of 26 samples positive by EM, rotavirus A was detected by CB-ELISA in 19 (73.1%) samples; indicating the share of group A rotavirus in all cases of gastroenteritis caused by rotavirus. The sensitivity and specificity of the CB-ELISA was verified both by inclusion of control samples containing transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhoea virus (PEDV) in each analysis and by comparative examination of samples with the commercial ELISA kit. The CB-ELISA sensitivity was positively affected by examination of samples in the presence of chelating agent.

Animals↗

Severity of rotavirus infection in relation to serotype, monotype and electropherotype.

The aim of this study was to determine whether the severity of symptoms associated with rotavirus infection was related to the serotype of the infecting virus. Severity of clinical symptoms in 108 children admitted to hospital for treatment of rotavirus diarrhoea was retrospectively assessed using a scoring system for frequency and duration of vomiting and diarrhoea, degree of fever, acidosis and dehydration, and presence of electrolyte imbalance. Children were 6-30 months old and were fully weaned at onset of symptoms prior to admission to hospital. No other enteric pathogens were detected during the course of the illness. Serotypes and monotypes were identified using a panel of monoclonal antibodies. Gel electrophoresis of rotavirus RNA was performed to determine electropherotypes. Children surveyed were infected with serotype 1 (47), serotype 2 (15) or serotype 4 (46) rotaviruses. Comparisons of severity of clinical symptoms according to infecting serotype revealed no statistically significant differences between serotype 1, 2 or 4 infections. In addition, no differences were detected between different rotavirus strains within each serotype (as judged by electropherotype) including monotypes 1a or 1c. This study failed to reveal differences in virulence between rotavirus strains of different VP7 serotypes infecting young children.

Child, Preschool↗

Incidence of Norwalk-like viruses, rotavirus and adenovirus infection in patients with acute gastroenteritis in Jakarta, Indonesia.

Norwalk-like viruses (NLVs), rotavirus and adenovirus are reportedly responsible from 4 to 42% of non-bacterial acute sporadic gastroenteritis. The incidence of NLVs, adenovirus and rotavirus infections in Indonesia is unclear. A total of 402 symptomatic cases from Indonesian patients with acute gastroenteritis and 102 asymptomatic controls that tested negative for bacteria and parasites were screened for the presence of NLVs, rotavirus and adenovirus using the reverse transcriptase-polymerase chain reaction (RT-PCR), Rotaclone kits and Adenoclone kits. Specific prototype probes were used to ascertain which NLV prototypes were present in the area. NLVs were detected in 45/218 (21%), rotavirus was detected in 170/402 (42%) and adenovirus was detected in 11/273 (4%) samples examined. Genetic analysis of the RT-PCR products using specific prototype probes for NLVs indicated that the prototypes were 42% Taunton agent and 58% Hawaii/Snow Mountain agent. Comparative data on patients showed that the incidence of rotavirus infections was two times greater than the NLVs infections, and that adenovirus infections were the least prevalent. All of the control samples tested were negative for NLVs and adenoviruses, however 8/70 (11%) of the samples were positive for rotaviruses. The high incidence of enteric viral-related infections is a threat among acute diarrheic patients in Jakarta, Indonesia.

Acute Disease↗

A prospective study of rotavirus infections in neonatal and maternity wards.

The occurrence and symptomatology of rotavirus infections was studied at three maternity wards and one neonatal unit. Rotavirus was identified in 12.7% of 553 infants and 1.3% of 542 mothers at the maternity wards. Infections were more frequent in a mixed obstetric/gynecology ward than in the pure obstetric wards. Only 10% of the infants had symptomatic infections. Subgroups of rotavirus was determined in 41 infants: 22 of subgroup I and 19 of subgroup II, which is the subgroup accounting for the majority of childhood gastroenteritis. Rotavirus was found in faecal samples from 37% of the infants at the neonatal unit during an eight-month survey. A seasonal variation with most infections during colder months was seen. Subgroup determination was possible in 29 cases, 14 subgroup I and 15 subgroup II. Fifteen per cent of the infections demonstrated diarrheal symptoms. No significant difference among other clinical data registered was seen among rotavirus infected compared to the non-infected infants. We conclude that neonatal rotavirus infections occur as an endemic infection at our maternity wards possibly combined with infections due to external sources of virus in mixed wards and neonatal units.

Adult↗

Rotavirus infection among children with diarrhoea in Italy.

Despite the absence of a nationwide surveillance system for rotavirus infection, relevant information concerning the epidemiology of this pathogen in Italy can be obtained from hospital-based studies carried out since the early 1980s on patients with acute diarrhoea. A review of more than 50 papers and congress proceedings published in both international and national literature indicates that rotavirus is the most important cause of diarrhoea in Italy among young children requiring hospitalization, with a prevalence ranging from approximately 20% to 40% in different studies. Infection is predominant among children aged 6-24 months, although cases are also common in younger children and in children 2-3 y of age. Despite differences among studies in geographical area, years and age group under investigation, an increase in rotavirus cases is consistently reported in the winter months, with a peak in February through April. Although a few studies have been conducted in non-hospitalized patients, rotavirus infection is significantly less frequent among outpatients with enteritis than among inpatients. Most circulating rotavirus strains typed from 1981 to 1992 belong to serotype 1 and, to a lesser extent, 4. However, untypable rotavirus strains have been found in these years, with prevalences up to 27%, suggesting a possible spread of non-serotype 1 through 4 strains.

Child↗