The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P[8]), and in states and territories using Rotarix (equine-like G3P[8] and G2P[4]), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains circulating in Australia.
BackgroundA birth dose strategy using a neonatal rotavirus vaccine to target early prevention of rotavirus disease may address remaining barriers to global vaccine implementation.MethodsWe conducted a randomized, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) to prevent rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB administered in a neonatal schedule at 0-5 days, 8 and 14 weeks or infant schedule at 8, 14 and 18 weeks, or placebo. Laboratory-confirmed rotavirus gastroenteritis was graded using a modified Vesikari score. The primary analysis was efficacy against severe rotavirus gastroenteritis from two weeks after all doses to 18 months in the combined vaccine group (neonatal and infant schedule) compared with placebo.ResultsVaccine efficacy against severe rotavirus gastroenteritis to 18 months was 63% in the combined vaccine group (95% CI 34, 80; p<0.001), 75% in the neonatal vaccine group (95% confidence interval [CI] 44, 91; p<0.001) and 51% in the infant vaccine group (95% CI 7, 76; p=0.03) in the per protocol analysis, with similar results in the intention-to-treat analysis. Vaccine efficacy to 12 months was 94% in the neonatal vaccine group (95%CI 56, 99; p=0.006). Vaccine take occurred in 78/83 (94%) in the neonatal vaccine group and 83/84 (99%) in the infant vaccine group. The vaccine was well tolerated, with similar incidence of adverse events in vaccine and placebo recipients.ConclusionRV3-BB was efficacious, immunogenic and well-tolerated when administered in a neonatal or infant schedule in Indonesia.
The prevalence and genetic diversity of human caliciviruses causing sporadic cases of acute gastroenteritis in young children hospitalized in a large pediatric hospital in Melbourne, Australia over 5 years (incorporating January 1998-December 2002) was studied by reverse transcription and sequence analysis of part of the polymerase gene. The overall prevalence of calicivirus infection in children aged <5 years during the 5 year study was 9.2% (113/1,233), with 95% of the strains belonging to the Norovirus genera. Strains of the norovirus G11-4 cluster were the most common type identified in 4 of the 5 years studied (1998, 1999, 2001, and 2002), with strains of norovirus cluster G11-5 the most common type during 2000. Additional norovirus genetic clusters GI-3, GII-1, GII-2, GII-3, GII-6, and GII-7, were also identified, but comprised only 17/94 of norovirus genogroup II strains. Five sapovirus strains were also identified. These results highlight the divergence of norovirus strains identified in a pediatric population.
Rotaviruses are the major cause of severe gastroenteritis in young children worldwide. Vaccines are being developed to reduce the huge impact of the disease caused by rotavirus infection. The first vaccines were developed to provide specific protection against the four predominant serotypes of rotavirus, G1 to G4 (29), as these have been the most common serotypes causing severe disease in children globally since 1973 (40). Recent epidemiological studies in Bangladesh (49), Brazil (23, 32, 44), India (1), the United States (24, 42), and Malawi (13) show that other G types (G5, G6, G8, G9, and G10) can be identified as causes of severe disease and are of emerging importance in some communities. Serotype G9 is recognized as the most widespread of the "emerging" serotypes and has been identified since 1996 as a frequent cause of severe disease in hospitalized children in the United States, Japan, India, Bangladesh, France, Italy, Malawi, Nigeria, Australia, China, Thailand, and the United Kingdom (3,7,8,12,19,26,34,37,39,41,42,47,49,50).The rotavirus genome is composed of 11 segments of double-stranded RNA located inside the core of a triple-layered structure. The outer capsid proteins VP4 and VP7 elicit neutralizing antibody immune responses, creating both serotypespecific and cross-reactive immunity (18). Antigenic differences in VP4 and VP7 are the basis of the G (VP7 glycoprotein) and P (protease-activated VP4 protein) serotypes. To date, 9 P and 10 G serotypes have been identified in humans by cross-neutralization tests (18,46,48). Unlike rotavirus G typing, there are two designations of rotavirus type P because of incomplete agreement between the P serotype (based on enzyme immunoassay [EIA] reactivities) and the P genotype (based on sequence similarity). The P genotypes are in brackets, whereas the P serotypes are open numbers. Epidemiological studies have shown that serotypes G1, G2, G3, and G4, associated with P1A (8) or P1B (4), have been the most common serotypes causing severe disease in children globally over the last 20 years (35,40). Genetic and antigenic variation has been recorded within the G1, G2, G3, and G4 serotypes (38). There is evidence that G9 strains are more susceptible to reassortment, and hence to genetic change, than are these other serotypes (27,49). The increasing prevalence of G9 strains worldwide makes it important to continue molecular epidemiological studies of their occurrence and genetic and antigenic variability.The emergence and persistence of serotype G9 has had a major impact on health care services in Australia (33,34). This
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