Norovirus gastroenteritis in young children receiving human rotavirus vaccine.

We explored whether human rotavirus vaccine had any efficacy against norovirus (NV)-associated gastroenteritis in young children. In an efficacy trial of rotavirus vaccine, 405 infants were immunized with a human rotavirus vaccine or placebo at a ratio of 2:1, and prospectively followed for acute gastroenteritis (AGE) from approximately 2 months to 2 y of age. Multiplex real-time reverse transcription polymerase chain reaction (Mrt RT-PCR) assays were used for detection and quantitation of NVs of genogroup I (GI) and genogroup II (GII) in stool specimens. NVs were detected in 155 (32%) of 485 episodes of AGE. Of these, NV was the only gastroenteritis virus detected in the stools in 142 (29%) episodes. GI and GII NVs were found in 12% and 88% of the cases, respectively. NV as the only gastroenteritis virus was detected in 36% of the infants in the rotavirus vaccine group and 27% in the placebo group. The clinical severity of NV-associated AGE in the vaccine and placebo recipients was not different. NVs were the most common etiologic agents of AGE in children under 2 y of age. Human rotavirus vaccine did not protect against NV gastroenteritis.

Safety, efficacy, and immunogenicity of 2 doses of bovine-human (UK) and rhesus-rhesus-human rotavirus reassortant tetravalent vaccines in Finnish children.

BACKGROUND: Live oral rhesus-rhesus-human rotavirus reassortant tetravalent (RRV-TV) vaccine was efficacious against rotavirus gastroenteritis but was withdrawn because of a rare association with intussusception. A corresponding tetravalent (types G1, G2, G3, and G4) reassortant vaccine based on bovine-human (UK) rotavirus reassortant tetravalent (BRV-TV) vaccine was developed concurrently. METHODS: Before the withdrawal of RRV-TV vaccine, parallel placebo-controlled trials of BRV-TV vaccine (observer blinded) versus RRV-TV vaccine (double blinded) with a 2 : 1 ratio of vaccine : placebo were conducted in Finland in a total of 510 infants. Two doses of study vaccine or placebo were administered at ages 3 and 5 months. RESULTS: The first dose of RRV-TV vaccine was followed by a significant excess rate of febrile reactions (36%), whereas the rate of fever after the administration of BRV-TV vaccine did not differ significantly from that in the placebo group. Neither vaccine induced diarrhea. A seroresponse was detected in 97% of BRV-TV vaccine recipients and 94% of RRV-TV vaccine recipients. Both vaccines were equally effective, with 68%-69% efficacy against any and 88%-100% efficacy against severe rotavirus gastroenteritis during the first epidemic season. CONCLUSIONS: BRV-TV vaccine is a promising new candidate rotavirus vaccine, with low reactogenicity and high efficacy. Two doses of BRV-TV or RRV-TV vaccine are sufficient for the induction of protection against severe rotavirus disease.

Viral etiology and incidence of acute gastroenteritis in young children attending day-care centers.

BACKGROUND: The purpose of the study was to investigate the frequency, morbidity and cause of acute gastroenteritis in children attending day-care centers in Denmark. METHODS: Children with acute diarrhea (> or =2 consecutive loose stools in 24 hours, with duration of < or =7 days), recruited from 19 day-care centers, were included. Gastroenteritis viruses, group A rotavirus, sapoviruses, noroviruses and astroviruses were detected with reverse transcription-polymerase chain reaction assays. In addition, stool specimens were cultured for bacterial pathogens. Children who were brought to the clinic with acute diarrhea underwent a medical evaluation, including an estimation of dehydration. RESULTS: Two hundred seven children (median age, 20.1 months; range, 9-44 months) were enrolled. During the 6-month study period, 98 diarrheal episodes in 95 children were reported. Of these, 48 were reported retrospectively in telephone interviews. The incidence of acute diarrheal episodes was 0.08 episode per child per month. A viral etiologic agent was identified in 69% of cases. Rotaviruses were identified in 17 cases (40%), sapoviruses in 8 (19%) and astroviruses in 3 (7%). One patient had a coinfection with rotavirus and astrovirus. Campylobacter jejuni was detected in 2 patients and Clostridium difficile was found in 5 patients, all coinfected with a virus. In clinical assessments, 9 patients (18%) showed signs of dehydration and were given oral rehydration solution; 6 of these were hospitalized. CONCLUSIONS: Acute diarrhea among children attending day-care centers was common in wintertime. Rotaviruses were, expectedly, the most common causative agents, but sapoviruses were second to rotaviruses as etiologic agents in this population.

Efficacy of RIX4414 live attenuated human rotavirus vaccine in Finnish infants.

BACKGROUND: Rotavirus gastroenteritis, a major cause of mortality and morbidity worldwide, is a vaccine-preventable disease. New safe and effective candidate rotavirus vaccines are needed to replace the withdrawn rhesus rotavirus-based oral vaccine. METHODS: We evaluated a monovalent human rotavirus vaccine, serotype G1, strain RIX4414, for efficacy, immunogenicity and safety in a randomized, double blind, placebo-controlled trial in Finland. We randomly allocated 405 healthy infants to receive 2 doses of vaccine or placebo (ratio 2:1) at approximately 2 and 4 months of age. The infants were followed during 2 rotavirus epidemic seasons (2000-2002) for acute gastroenteritis. Rotaviruses in diarrheal stool samples were primarily detected by enzyme-linked immunosorbent assay and confirmed and G-typed by reverse transciption-polymerase chain reaction. RESULTS: The vaccine was well-tolerated. No vaccine-related serious adverse events were observed during the study period. Rotavirus IgA (enzyme-linked immunosorbent assay) seroconversion rate was 80% after 2 doses. Thirty-eight cases of rotavirus gastroenteritis were detected during the entire follow-up period; 35 of these were of the G1 type. RIX4414 vaccine significantly decreased the occurrence of any rotavirus compared with placebo. Efficacy during the first rotavirus epidemic season was 73% [95% confidence interval (95% CI), 27-91%] and 90% (95% CI 10-100%) against any and severe rotavirus gastroenteritis, respectively, and during the entire follow-up period 72% (95% CI 42-87%) against any and 85% (95% CI 42-97%) against severe rotavirus gastroenteritis (P < 0.05 for all comparisons). CONCLUSIONS: RIX4414 strain of G1 human rotavirus vaccine was well-tolerated, immunogenic and efficacious in infants against rotavirus gastroenteritis during a 2-year period. To further increase vaccine "take" and efficacy, a higher dose of this vaccine may be considered for future efficacy trials.