No abstract

A large placebo-controlled efficacy trial of the rhesus tetravalent (RRV-TV) and serotype G1 monovalent (RRV-S1) rotavirus vaccines was conducted in 1991-1992 at 24 sites across the United States. Protection was 49% and 54% against all diarrhea but 80% and 69% against very severe gastroenteritis for the two vaccines, respectively. Post-vaccination neutralizing antibody titers to the G1 Wa strain, whose VP7 protein is nearly identical to that of the D strain of rotavirus contained in both vaccines, did not correlate with protection against subsequent illness with G1 strains. This result raised the possibility that in infants who developed post-vaccination neutralizing antibody to Wa, breakthrough (i.e., vaccine failure-the occurrence of rotavirus diarrhea after immunization) may have been due to infection by G1 strains that were sufficiently antigenically distinct from the vaccine strain to evade the neutralizing antibodies elicited by vaccination. To test this hypothesis, we initially compared post-vaccination neutralizing antibody titers of vaccinees against Wa and G1 breakthrough strains using sera from subjects who experienced breakthrough. Post-immunization neutralizing antibody titers to Wa elicited by vaccination were significantly (P< 0.001) greater than to the breakthrough strains subsequently obtained from these subjects. This difference did not, however, correlate with lack of protection since similar differences in titer to Wa and breakthrough strains were found using post-vaccination sera from vaccinees who either experienced asymptomatic rotavirus infections or no infections. To determine the genetic basis for these differences, we compared the VP7 gene sequences of Wa with vaccine strain D, 12 G1 breakthrough strains, and 3 G1 control strains isolated during the same trial from placebo recipients. All breakthrough strains were distinct from Wa and D in antigenically important regions throughout the VP7 protein, but these differences were conserved between breakthrough and placebo strains. Furthermore, a comparative analysis of the deduced amino sequences form VP7 genes of G1 rotaviruses from 12 countries indicated that four distinct lineages have evolved. All breakthrough and control strains from the U.S. vaccine trial were in a lineage different from strain D, the serotype G1 vaccine strain. Although the overall results do not support our original hypothesis that immune selection of antigenically distinct escape mutants led to vaccine breakthrough in subjects with a neutralization response to Wa, it cannot be excluded that breakthrough could be partially due to antigenic differences in the VP7 proteins of currently circulating G1 strains.

Human rotaviruses from the states of Rio de Janeiro, São Paulo and Pará of Brazil were analysed by RNA electrophoresis. At least some bands characteristic of rotavirus double-stranded RNA were detected in 138 (86.8%) of 159 faecal samples in which the presence of rotavirus had been demonstrated by enzyme immunoassay. Of the RNA-positive samples, 18 (13.0%) were classified as subgroup 1, 94 (68.1%) as subgroup 2, and 26 (18.8%) could not be classified due to absence of visible bands 10 and 11. Subgroup 2 was more frequent in the three states. All strains of subgroup 1 detected in Rio de Janeiro were associated with a single short-lived school outbreak. All strains of subgroup 1 resembled each other in electrophoretic pattern, irrespective of geographical origin, although minor differences could be detected by co-electrophoresis. Subgroup 2, on the other hand, showed a great degree of electrophoretic heterogeneity and could be divided into several sub-categories.

From December 1982 to March 1986 a group of 80 children between 0 and 3 years old who lived in the peripheral area of Belém, Brazil, were followed up for episodes of diarrhoea. A total of 441 diarrhoeal episodes were recorded and 36 (8.2%) were associated with rotavirus. This agent was the only pathogen in 50% of rotavirus-related episodes of acute diarrhoea, and strains were characterized by analysis of RNA in polyacrylamide gels. Forty-one belonged to subgroup II (long pattern) and five to subgroup I. Reinfections by rotavirus were noted in 12 children involving either the same or different subgroups. Ten distinct electrophoretypes were detected in the study period and the predominant one had the '1N2L' profile. The cumulative age-specific attack rate for diarrhoea reached 2.8 by the end of the first year of life; a frequency of 2.3 episodes of diarrhoea per child per year was observed throughout the complete investigation. In comparing the age-specific attack rates for diarrhoea between breast-fed and bottle-fed children, a peak at 6 months of age was noted in the former, and at 1 month in the latter. A comparison by Fischer's exact test (P = 0.21) provided no evidence for protection against clinical rotavirus disease by maternal milk. By the same test, however (P = 0.021), we found significant evidence that early rotavirus infections were more likely to be asymptomatic and that infections after 4 months were more likely to be symptomatic. The clinical picture in children with rotavirus-related diarrhoea was more severe than in those suffering from acute diarrhoea due to another agent.

The prevalence and potential zoonotic transmission of group C rotavirus (RVC) were examined by testing fecal samples collected from children during a longitudinal study that was carried out in the outskirts of Belém, Brazil, from December 1982 to March 1986. The study involved a group of 30 children who were followed from birth to 3 years. Of the 77 samples tested from 29 children, 5 (6.5%) were positive for human and 3 (4%) for porcine RVC by using nested PCR assay with primers specific for VP6 gene of human or porcine RVC and by Southern hybridization using a probe specific for VP6 gene of both human and porcine RVC. In addition, a total of 59 fecal specimens from the 30th child were tested, 1 (1.7%) and 14 (23.7%) were positive for human and porcine RVC, respectively. Partial nucleotide sequences of VP6 gene demonstrated that the six human strains detected in Brazil were homologous with other human RVC, and 14 of the 17 porcine RVC strains examined showed a complete homology among themselves but differed slightly from the porcine Cowden strain, suggesting that a single porcine RVC strain was circulating in Belém. This study is the first to provide evidence for transmission of RVC from swine to human. They also indicate that both human and porcine RVC were endemic in Belém.

No abstract

Objective: To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. Methods: A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10 4.7 focus forming units-FFU), 196 (10 5.2 FFU), 194 (10 5.8 FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of ≥ 11 defined as severe GE. Results: The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (10 5.8 FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (10 5.8 FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain. Conclusions: RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diptheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV. J Pediatr (Rio J). 2007;83(3):217-224: Rotavirus, gastroenteritis, vaccine, efficacy.

A total of 614 fecal specimens were obtained during a survey for rotavirus infection conducted between May 1996 and May 1998 among 437 newborns admitted to special care nurseries at a public hospital in the urban area of Belém, Brazil. Routine stool samples were taken weekly from all babies up to the age of 28 days. Overall, 51 (11.7%) of the neonates excreted rotaviruses while in hospital, of whom 42 (82.3%) developed asymptomatic nosocomial infection; nosocomial infection was also proved in five of the nine patients with diarrhea. Three distinct RNA profiles were detected, of which one short electropherotyping pattern was far more frequent ( approximately 90% of the strains). Using monoclonal antibody-based enzyme immunoassays, 32 (62.7%) of the rotavirus-positive strains were classified as G2, and 1 (1.9%) as mixed G1 and G2. A G serotype could not be assigned to 18 (35.3%) of the isolates. A reverse transcription-polymerase chain reaction was used for determining the VP4 type-specificity of a subset of 28 rotavirus-positive samples. Characterization of the VP7-genotype specificity was also sought for 18 of these latter strains. Overall, P[6] and G2 genotypes were identified in 93% and 94% of tested samples respectively, with results being further confirmed by Southern hybridization. Although surveillance was conducted during a 25-month period, 50 (98%) of 51 rotavirus isolates clustered between January and December 1997. The earliest [P6]G2 rotavirus infections were detected by late January 1997, involving two (13- and 14-day-old) babies admitted with acute diarrhea. Thereafter, strains bearing these genotype specificities were identified among five infants with hospital-acquired gastroenteritis, followed by 16 others who were infected asymptomatically. This is the first report from Brazil describing nosocomial transmission of P[6]G2 rotavirus strains among neonates.