Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.

BACKGROUND: A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB, administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or placebo. The primary analysis was conducted in the per-protocol population, which included only participants who received all four doses of vaccine or placebo within the visit windows, with secondary analyses performed in the intention-to-treat population, which included all participants who underwent randomization. RESULTS: Among the 1513 participants in the per-protocol population, severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal-schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence interval [CI], 44 to 91) in the neonatal-schedule group (P<0.001), 51% (95% CI, 7 to 76) in the infant-schedule group (P=0.03), and 63% (95% CI, 34 to 80) in the neonatal-schedule and infant-schedule groups combined (combined vaccine group) (P<0.001). Similar results were observed in the intention-to-treat analysis (1649 participants); the vaccine efficacy was 68% (95% CI, 35 to 86) in the neonatal-schedule group (P=0.001), 52% (95% CI, 11 to 76) in the infant-schedule group (P=0.02), and 60% (95% CI, 31 to 76) in the combined vaccine group (P<0.001). Vaccine response, as evidenced by serum immune response or shedding of RV3-BB in the stool, occurred in 78 of 83 participants (94%) in the neonatal-schedule group and in 83 of 84 participants (99%) in the infant-schedule group. The incidence of adverse events was similar across the groups. No episodes of intussusception occurred within the 21-day risk period after administration of any dose of vaccine or placebo, and one episode of intussusception occurred 114 days after the third dose of vaccine in the infant-schedule group. CONCLUSIONS: RV3-BB was efficacious in preventing severe rotavirus gastroenteritis when administered according to a neonatal or an infant schedule in Indonesia. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612001282875 .).

Human Neonatal Rotavirus Vaccine (RV3-BB) Produces Vaccine Take Irrespective of Histo-Blood Group Antigen Status.

BACKGROUND: VP4 [P] genotype binding specificities of rotaviruses and differential expression of histo-blood group antigens (HBGAs) between populations may contribute to reduced efficacy against severe rotavirus disease. P[6]-based rotavirus vaccines could broaden protection in such settings, particularly in Africa, where the Lewis-negative phenotype and P[6] rotavirus strains are common. METHODS: The association between HBGA status and G3P[6] rotavirus vaccine (RV3-BB) take was investigated in a phase 2A study of RV3-BB vaccine involving 46 individuals in Dunedin, New Zealand, during 2012-2014. FUT2 and FUT3 genotypes were determined from DNA extracted from stool specimens, and frequencies of positive cumulative vaccine take, defined as an RV3-BB serum immune response (either immunoglobulin A or serum neutralizing antibody) and/or stool excretion of the vaccine strain, stratified by HBGA status were determined. RESULTS: RV3-BB produced positive cumulative vaccine take in 29 of 32 individuals (91%) who expressed a functional FUT2 enzyme (the secretor group), 13 of 13 (100%) who were FUT2 null (the nonsecretor group), and 1 of 1 with reduced FUT2 activity (i.e., a weak secretor); in 37 of 40 individuals (93%) who expressed a functional FUT3 enzyme (the Lewis-positive group) and 3 of 3 who were FUT3 null (the Lewis-negative group); and in 25 of 28 Lewis-positive secretors (89%), 12 of 12 Lewis-positive nonsecretors (100%), 2 of 2 Lewis-negative secretors, and 1 of 1 Lewis-negative weak secretor. CONCLUSIONS: RV3-BB produced positive cumulative vaccine take irrespective of HBGA status. RV3-BB has the potential to provide an improved level of protection in settings where P[6] rotavirus disease is endemic, irrespective of the HBGA profile of the population.

Variation of Gut Mucosal Microbiome With Anti-Saccharomyces cerevisiae Antibody Status in Pediatric Crohn Disease.

OBJECTIVES: Crohn disease (CD) is a chronic relapsing condition possibly caused by a dysbiotic microbiome. Approximately 30% to 60% of patients with CD have anti-Saccharomyces cerevisiae antibody (ASCA), but any association with gut microbiota is unexplored. We hypothesized that ASCA positivity would predict a signature microbial status and clinical phenotype. METHODS: Ileocolonic mucosal biopsies were obtained from children with CD (n = 135), and controls without inflammatory bowel disease (n = 45). Comparison was made between ASCA status, microbial diversity, and clinical characteristics. RESULTS: ASCA was highly specific but poorly sensitive for the diagnosis of CD. In patients with CD, ASCA positivity was associated with older age (≥10 years), ileocolonic disease, and long-term risk of surgery. Microbial alpha and beta diversity were similar in patients with CD with or without ASCA, but significantly less when compared to noninflammatory bowel disease controls. Microbial richness was similar across all 3 groups. Fourteen bacterial species were associated with ASCA-positive patients with CD and 14 species with ASCA-negative patients (P < 0.05). After using a false discovery rate correction Ruminococcus torques and bacterium Yersinia enterocolitica 61 remained significantly associated with CD ASCA positivity (P = 0.0178), whereas Enterobacter cloacae and Faecalibacterium prausnitzii were significantly associated with CD ASCA negativity (P = 0.0178 and 0.0342). CONCLUSION: ASCA-positive and ASCA-negative patients with CD have significant differences in gut microbiome composition, which could possibly be influencing the phenotype of the disease.

The Impact of Rotavirus Vaccines on Genotype Diversity: A Comprehensive Analysis of 2 Decades of Australian Surveillance Data.

Background: Introduction of rotavirus vaccines into national immunization programs (NIPs) could result in strain selection due to vaccine-induced selective pressure. This study describes the distribution and diversity of rotavirus genotypes before and after rotavirus vaccine introduction into the Australian NIP. State-based vaccine selection facilitated a unique comparison of diversity in RotaTeq and Rotarix vaccine states. Methods: From 1995 to 2015, the Australian Rotavirus Surveillance Program conducted genotypic analysis on 13051 rotavirus-positive samples from children <5 years of age, hospitalized with acute gastroenteritis. Rotavirus G and P genotypes were determined using serological and heminested multiplex reverse-transcription polymerase chain reaction assays. Results: G1P[8] was the dominant genotype nationally in the prevaccine era (1995-2006). Following vaccine introduction (2007-2015), greater genotype diversity was observed with fluctuating genotype dominance. Genotype distribution varied based on the vaccine implemented, with G12P[8] dominant in states using RotaTeq, and equine-like G3P[8] and G2P[4] dominant in states and territories using Rotarix. Conclusions: 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.

Identification of strains of RotaTeq rotavirus vaccine in infants with gastroenteritis following routine vaccination.

BACKGROUND: RotaTeq vaccine was introduced into the Australian National Immunisation Program in 2007. This study identified and characterised rotavirus strains excreted by infants who presented with symptoms of gastroenteritis following recent RotaTeq vaccination. METHODS: Fecal samples (N = 61) from children who developed gastroenteritis following recent RotaTeq vaccination were forwarded to the Australian Rotavirus Surveillance Program (ARSP). RotaTeq-positive samples were genotyped and regions of the VP3, VP4, VP6, and VP7 genes were sequenced. Also, 460 rotavirus-positive ARSP routine surveillance samples were analyzed by dot-blot Northern hybridization to detect RotaTeq vaccine-derived strains circulating in the community. RESULTS: Thirteen of the 61 samples collected from infants developing gastroenteritis after RotaTeq vaccination contained vaccine-derived (vd) rotavirus strains. Of these, 4 contained a vdG1P[8] strain derived by reassortment between the G1P[5] and G6P[8] parental vaccine strains. Northern hybridization analysis of 460 surveillance samples identified 3 samples that contained RotaTeq vaccine-derived strains, including 2 vdG1P[8] reassortant vaccine strains. CONCLUSIONS: During replication and excretion of RotaTeq vaccine, reassortment of parental strains can occur. Shedding of RotaTeq vaccine strains in 7 of 13 infants was associated with underlying medical conditions that may have altered their immune function. The benefits of vaccination outweigh any small risk of vaccine-associated gastroenteritis.

Histo-blood group antigen profile of Australian Aboriginal children and seropositivity following oral rotavirus vaccination.

BACKGROUND: Histo-blood group antigens (HBGAs) may influence immune responses to rotavirus vaccination. METHODS: HBGA phenotyping was determined by detection of antigens A, B, H and Lewis a and b in saliva using enzyme-linked immunosorbent assay. Secretor status was confirmed by lectin antigen assay if A, B and H antigens were negative or borderline (OD ± 0.1 of threshold of detection). PCR-RFLP analysis was used to identify the FUT2 'G428A' mutation in a subset. Rotavirus seropositivity was defined as serum anti-rotavirus IgA ≥ 20 AU/mL. RESULTS: Of 156 children, 119 (76 %) were secretors, 129 (83 %) were Lewis antigen positive, and 105 (67 %) were rotavirus IgA seropositive. Eighty-seven of 119 (73 %) secretors were rotavirus seropositive, versus 4/9 (44 %) weak secretors and 13/27 (48 %) non-secretors. CONCLUSIONS: Most Australian Aboriginal children were secretor and Lewis antigen positive. Non-secretor children were less likely to be seropositive to rotavirus antibodies following vaccination, but this phenotype was less common. HBGA status is unlikely to fully explain underperformance of rotavirus vaccines among Australian Aboriginal children.

Neonatal rotavirus vaccine (RV3-BB) immunogenicity and safety in a neonatal and infant administration schedule in Malawi: a randomised, double-blind, four-arm parallel group dose-ranging study.

BACKGROUND: Rotavirus vaccines reduce rotavirus-related deaths and hospitalisations but are less effective in high child mortality countries. The human RV3-BB neonatal G3P[6] rotavirus vaccine administered in a neonatal schedule was efficacious in reducing severe rotavirus gastroenteritis in Indonesia but had not yet been evaluated in African infants. METHODS: We did a phase 2, randomised, double-blind, parallel group dose-ranging study of three doses of oral RV3-BB rotavirus vaccine in infants in three primary health centres in Blantyre, Malawi. Healthy infants less than 6 days of age with a birthweight 2·5 to 4·0 kg were randomly assigned (1:1:1:1) into one of four treatment groups: neonatal vaccine group, which included high-titre (1·0 × 107 focus-forming unit [FFU] per mL), mid-titre (3·0 × 106 FFU per mL), or low-titre (1·0 × 106 FFU per mL); and infant vaccine group, which included high-titre (1·0 × 107 FFU per mL) using a computer generated code (block size of four), stratified by birth (singleton vs multiple). Neonates received their three doses at 0-5 days to 10 weeks and infants at 6-14 weeks. Investigators, participant families, and laboratory staff were masked to group allocation. Anti-rotavirus IgA seroconversion and vaccine take (IgA seroconversion and stool shedding) were evaluated. Safety was assessed in all participants who received at least one dose of vaccine or placebo. The primary outcome was the cumulative IgA seroconversion 4 weeks after three doses of RV3-BB in the neonatal schedule in the high-titre, mid-titre, and low-titre groups in the per protocol population, with its 95% CI. With the high-titre group as the active control group, we did a non-inferiority analysis of the proportion of participants with IgA seroconversion in the mid-titre and low-titre groups, using a non-inferiority margin of less than 20%. This trial is registered at ClinicalTrials.gov (NCT03483116). FINDINGS: Between Sept 17, 2018, and Jan 27, 2020, 711 participants recruited were randomly assigned into four treatment groups (neonatal schedule high titre n=178, mid titre n=179, low titre n=175, or infant schedule high titre n=179). In the neonatal schedule, cumulative IgA seroconversion 4 weeks after three doses of RV3-BB was observed in 79 (57%) of 139 participants in the high-titre group, 80 (57%) of 141 participants in the mid-titre group, and 57 (41%) of 138 participants in the low-titre group and at 18 weeks in 100 (72%) of 139 participants in the high-titre group, 96 (67%) of 143 participants in the mid-titre group, and 86 (62%) of 138 of participants in the low-titre. No difference in cumulative IgA seroconversion 4 weeks after three doses of RV3-BB was observed between high-titre and mid-titre groups in the neonatal schedule (difference in response rate 0·001 [95%CI -0·115 to 0·117]), fulfilling the criteria for non-inferiority. In the infant schedule group 82 (59%) of 139 participants had a cumulative IgA seroconversion 4 weeks after three doses of RV3-BB at 18 weeks. Cumulative vaccine take was detected in 483 (85%) of 565 participants at 18 weeks. Three doses of RV3-BB were well tolerated with no difference in adverse events among treatment groups: 67 (39%) of 170 participants had at least one adverse event in the high titre group, 68 (40%) of 172 participants had at least one adverse event in the mid titre group, and 69 (41%) of 169 participants had at least one adverse event in the low titre group. INTERPRETATION: RV3-BB was well tolerated and immunogenic when co-administered with Expanded Programme on Immunisation vaccines in a neonatal or infant schedule. A lower titre (mid-titre) vaccine generated similar IgA seroconversion to the high-titre vaccine presenting an opportunity to enhance manufacturing capacity and reduce costs. Neonatal administration of the RV3-BB vaccine has the potential to improve protection against rotavirus disease in children in a high-child mortality country in Africa. FUNDING: Bill & Melinda Gates Foundation, Australian Tropical Medicine Commercialisation Grant.

The Microbiome in Paediatric Crohn's Disease-A Longitudinal, Prospective, Single-Centre Study.

BACKGROUND AND AIMS: The gut mucosa is the principal site where Crohn's disease [CD] inflammation occurs. Limited information is available about the gut mucosal microbiome during CD relapse and remission. The aim of our study was to characterize specific changes in the gut microbiome during relapse and remission in a large single-centre paediatric CD cohort. METHODS: We analysed the microbiome of 345 biopsies from 204 patients, including 88 CD first diagnosis [CDFD] patients, 38 relapse [CDRL] patients, 12 remission [CDRM] patients, and 66 controls. Species identification was conducted using oligotyping in combination with ARB/SILVA taxonomic annotation. RESULTS: We observed 45 bacteria to differ between CDFD samples and controls with statistical significance, with Fusobacterium being the most implicated species in CDFD patients. We also identified gender-specific differences in CD. Five species showed a strong association with CDRL patients and 10 species with CDRM patients. Three taxa showed a positive co-occurrence across the two groups. Hespellia porcina [closest taxonomic neighbour to Clostridium oroticum] was the most strongly associated with CDRL samples. Interestingly, Fusobacterium was not part of the CDRL-associated taxa group. Faecalibacterium prausnitzii was equally present in CDFD and control samples. CONCLUSION: This is the first study that has investigated the gut mucosal microbiome in a paediatric CD cohort with longitudinal sampling. Importantly, the microbiome of patients in CDRM did not return to a healthy control state. Neither did the microbiome of patients with CDRL return to the profile seen at CDFD.

Molecular characterisation of rotavirus strains detected during a clinical trial of the human neonatal rotavirus vaccine (RV3-BB) in Indonesia.

BACKGROUND: The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. The aim of the current study was to characterise the rotavirus strains causing gastroenteritis during the Indonesian Phase IIb efficacy trial. METHODS: A randomized, double-blind placebo-controlled trial involving 1649 participants was conducted from January 2013 to July 2016 in Central Java and Yogyakarta, Indonesia. Participants received three doses of oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), or the first dose given at ∼8 weeks after birth (infant schedule), or placebo (placebo schedule). Stool samples from episodes of gastroenteritis were tested for rotavirus using EIA testing, positive samples were genotyped by RT-PCR. Full genome sequencing was performed on two representative rotavirus strains. RESULTS: There were 1110 episodes of acute gastroenteritis of any severity, 105 episodes were confirmed as rotavirus gastroenteritis by EIA testing. The most common genotype identified was G3P[8] (90/105), the majority (52/56) of severe (Vesikari score ≥11) rotavirus gastroenteritis episodes were due to the G3P[8] strain. Full genome analysis of two representative G3P[8] samples demonstrated the strain was an inter-genogroup reassortant, containing an equine-like G3 VP7, P[8] VP4 and a genogroup 2 backbone I2-R2-C2-M2-A2-N2-T2-E2-H2. The complete genome of the Indonesian equine-like G3P[8] strain demonstrated highest genetic identity to G3P[8] strains circulating in Hungary and Spain. CONCLUSIONS: The dominant circulating strain during the Indonesian Phase IIb efficacy trial of the RV3-BB vaccine was an equine-like G3P[8] strain. The equine-like G3P[8] strain is an emerging cause of severe gastroenteritis in Indonesia and in other regions.

Serological responses to rotavirus NSP2 following administration of RV3-BB human neonatal rotavirus vaccine.

Serum rotavirus IgA responses are an imperfect non-mechanistic correlate of protection, and the lack of an accurate serological marker is a challenge to the development of new rotavirus vaccines. Serological responses to rotavirus NSP2 occur following wild-type infection; however, it is unknown if serological responses to NSP2 occur following administration of rotavirus vaccines. The phase IIa immunogenicity trial of RV3-BB provided an opportunity to investigate the serological responses to NSP2 following vaccination. Healthy, full-term babies (n = 96) were previously recruited as part of a phase IIa safety and immunogenicity trial in Dunedin, New Zealand between January 2012 and April 2014. Participants received three doses of oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Serum IgA and IgG antibody responses to total RV3-BB and NSP2 protein (RV3-BB) were assessed using ELISA. Despite significant serum IgA response against total RV3-BB, we were unable to demonstrate a significant serological response to NSP2 in participants receiving RV3-BB when compared to placebo. Heterotypic antibodies against multiple NSP2 genotypes were detected following RV3-BB vaccination. Our data demonstrates that while serological responses to NSP2 were detectable in a subset of participants, it is a less useful marker when compared to total rotavirus serum IgA response.

Rotavirus shedding following administration of RV3-BB human neonatal rotavirus vaccine.

The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. A phase IIa safety and immunogenicity trial was undertaken in Dunedin, New Zealand between January 2012 and April 2014. Healthy, full-term (≥ 36 weeks gestation) babies, who were 0-5 d old were randomly assigned (1:1:1) to receive 3 doses of oral RV3-BB vaccine with the first dose given at 0-5 d after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Vaccine take (serum immune response or stool shedding of vaccine virus after any dose) was detected after 3 doses of RV3-BB vaccine in >90% of participants when the first dose was administered in the neonatal and infant schedules. The aim of the current study was to characterize RV3-BB shedding and virus replication following administration of RV3-BB in a neonatal and infant vaccination schedule. Shedding was defined as detection of rotavirus by VP6 reverse transcription polymerase chain reaction (RT-PCR) in stool on days 3-7 after administration of RV3-BB. Shedding of rotavirus was highest following vaccination at 8 weeks of age in both neonatal and infant schedules (19/30 and 17/27, respectively). Rotavirus was detected in stool on days 3-7, after at least one dose of RV3-BB, in 70% (21/30) of neonate, 78% (21/27) of infant and 3% (1/32) placebo participants. In participants who shed RV3-BB, rotavirus was detectable in stool on day 1 following RV3-BB administration and remained positive until day 4-5 after administration. The distinct pattern of RV3-BB stool viral load demonstrated using a NSP3 quantitative qRT-PCR in participants who shed RV3-BB, suggests that detection of RV3-BB at day 3-7 was the result of replication rather than passage through the gastrointestinal tract.

Surveillance and molecular characterization of group A rotaviruses in Goroka, Papua New Guinea.

In this study, we investigated the molecular epidemiology of group A rotaviruses in cases of acute gastroenteritis in Goroka, Papua New Guinea. From April 2008 through November 2010, 813 diarrheal stool samples were collected from children < 5 years of age hospitalized with acute gastroenteritis. Rotavirus antigen was detected in 31.2% of samples using a commercial enzyme-linked immunosorbent assay. Genotyping revealed the presence of the globally circulating strains G1P[8] (50.0%), G3P[8] (23.0%), and G2P[4] (8.2%). The globally emerging strains G9 and G12 were detected in 1.2% and 6.1% of samples, respectively. Mixed infections were detected in a high proportion of samples (11.9%), with 9.0% and 3.7% of samples displaying multiple G and P genotypes, respectively.

Phylogenetic analysis of rotavirus A NSP2 gene sequences and evidence of intragenic recombination.

The rotavirus non-structural protein NSP2 is one of the earliest and most abundant viral proteins produced during infection. This protein has multiple essential roles in the replication cycle involving RNA binding, viroplasm formation, helicase and can hydrolyse the γ-phosphate of RNA and NTPs acting as an RTPase and NTPase. In studying sequences from rotavirus strains isolated in Australia between 1984 and 2009, the NSP2 gene was seen to be highly conserved and clustered with defined NSP2 genotypes N1 and N2 according to the full genome based rotavirus classification system. Phylogenetic analysis indicated that NSP2 gene sequences isolated from Australian rotavirus strains formed four distinct lineages. Temporal variation was observed in several clusters during the 26 year period, with lineage D identified throughout the entire study period and lineage A only detected since 1999. Phylogenetic analysis and dendrograms identified NSP2 genes that exhibited reassortment between different virus VP7 genotypes, as well as a sequence from a human strain that grouped closely with the NSP2 genes of bovine rotavirus strains. This study also identified a sequence that fell between lineages and exhibited evidence of recombination, the first time that intergenic recombination has been detected in a NSP2 gene sequence. This study increases the understanding of the evolution mechanisms of NSP2 in view of improved vaccine design.

Australian Rotavirus Surveillance Program annual report, 2010/11.

The Australian Rotavirus Surveillance Program together with collaborating laboratories Australia-wide conducts a laboratory based rotavirus surveillance program. This report describes the genotypes of rotavirus strains responsible for the hospitalisation of children with acute gastroenteritis during 1 July 2010 to 30 June 2011. This report represents the fourth year of surveillance following introduction of rotavirus vaccines into the National Immunisation Program. One thousand one hundred and twenty-seven faecal samples were referred to the centre for G and P genotype analysis using hemi-nested multiplex reverse transcription-polymerase chain reaction. Eight hundred and sixteen samples were confirmed as rotavirus positive. Of these, 551 were collected from children under 5 years of age, while 265 were from older children and adults. Genotype analysis revealed that a change in the dominant type occurred in this reporting period, such that genotype G2P[4] was the dominant type nationally, representing 51% of samples, followed by genotype G1P[8] (26.1%). Genotypes G3P[8] represented 11% of samples while G4P[8] re-emerged as an important genotype, and was identified in 6% of samples. Uncommon rotavirus G and P combinations continue to be identified, with G2P[8] and G9P[4] identified during this survey. Differences in genotype distribution based on vaccine usage continue to be evident in Australian states. This survey continues to highlight the fluctuations in rotavirus genotypes, with an annual change in dominant genotypes suggesting a more dynamic wild-type population.

Distribution of rotavirus genotypes after introduction of rotavirus vaccines, Rotarix® and RotaTeq®, into the National Immunization Program of Australia.

BACKGROUND: Rotavirus vaccines, RotaTeq and Rotarix, were introduced into the Australian National Immunization Program on July 1, 2007. The simultaneous introduction in different Australian states and territories provides a unique opportunity to compare the affect of each vaccine on the types of circulating rotavirus strains. This report describes the rotavirus genotypes responsible for the hospitalization of children during the first 2-year period after vaccine introduction. METHODS: A total of 764 rotavirus-associated diarrheal cases were collected from children presenting to hospital in 10 Australian centers. Rotavirus genotype was determined using reverse transcription polymerase chain reaction assays. RESULTS: G1P[8] was the dominant genotype nationally (52%), followed by G2P[4] (19.8%), G9P[8] (12.2%), and G3P[8] (11%). Differences in the prevalence rates of G2P[4] and G3P[8] were seen in the various states. G2P[4] strains were more prevalent in states using Rotarix, whereas G3P[8] strains were more prevalent in states using RotaTeq. CONCLUSIONS: Differences in rotavirus genotypes were observed across Australia, which suggest that different immune pressures are exerted by the different vaccines, but do not necessarily imply lack of protection by either vaccine. These differences may simply be related to the variation that can occur because of natural annual fluctuation in rotavirus strain prevalence.

Australian Rotavirus Surveillance Program: annual report, 2009/2010.

The Australian Rotavirus Surveillance Program together with 15 collaborating laboratories Australia-wide conducts a laboratory based rotavirus surveillance program. This report describes the genotypes of rotavirus strains responsible for the hospitalisation of children with acute gastroenteritis during the period 1 July 2009 to 30 June 2010, the 3rd year of surveillance following introduction of rotavirus vaccines into the National Immunisation Program. Seven hundred and seventy-eight faecal samples were referred to the centre for G and P genotype analysis using hemi-nested multiplex reverse transcription-polymerase chain reaction. Of the 422 confirmed as rotavirus positive, genotype G1P[8] was the dominant type nationally, representing 49.3%, followed by genotype G2P[4] (21.1%). Genotypes G3P[8], G4P[8] and G9P[8] each represented less than 3% of circulating strains nationally. The dominance of G1P[8] was in part associated with a large outbreak of severe gastroenteritis in the Northern Territory in 2010. The identification of uncommon rotavirus genotype combinations has increased since vaccine introduction, with G1P[4], G2P[8] and G9P[4] identified during this survey. Single strains of G1P[6] and G4P[6] were identified during this study period. This survey continues to highlight the fluctuations in rotavirus genotypes, and results from this survey suggest there is limited genotype selection based on vaccine usage. However, the large G1P[8] outbreak of gastroenteritis in the Northern Territory may have resulted from vaccine pressure on wild-type strains.

Australian Rotavirus Surveillance Program annual report, 2008/2009.

The Australian Rotavirus Surveillance Program together with collaborating laboratories Australia-wide, conducts a laboratory based rotavirus surveillance program. This report describes the genotypes of rotavirus strains responsible for the hospitalisation of children with acute gastroenteritis during the period 1 July 2008 to 30 June 2009, the second year of surveillance following introduction of rotavirus vaccine into the National Immunisation Program. Five hundred and ninety-two faecal samples from across Australia were examined for G and P genotype using hemi-nested multiplex reverse transcription-polymerase chain reaction assays. Of the 445 confirmed as rotavirus positive, genotype G2P[4] was the dominant type nationally, representing 50.3%, followed by genotype G1P[8] (22.5%). Genotypes G3P[8], G4P[8] and G9P[8] each represented less than 5% of circulating strains nationally. Uncommon rotavirus genotype combinations, including G1P[4] (n = 6), G4P[4] (n = 2) and single strains of G1P[6] and G3P[6] were identified during this study period. The national dominance of G2P[4] was associated with a large outbreak of severe gastroenteritis in Alice Springs in early 2009. This is the first report to describe G2P[4] as the dominant genotype nationally. Whether vaccine pressure has resulted in emergence of this genotype is not yet known.

Rotavirus strain surveillance--an Australian perspective of strains causing disease in hospitalised children from 1997 to 2007.

This study documents rotavirus strains causing severe disease in Australian children during the pre-vaccine era. During the period 1997-2007, rotavirus strains from national multi-centre hospital-based surveillance in Australia were analysed for G and P types. G1P[8] was the dominant genotype identified during the 11-year study, with intermittent peaks associated with genotypes G2P[4], G3P[8] and G9P[8]. The results provide baseline information of the G and P genotypes causing disease in Australian children, and highlight the unpredictable changes in genotype incidence that can occur on both a local and national level. To be optimally effective, rotavirus vaccines must prevent disease caused by all common rotavirus genotypes.

The burden of hospitalised rotavirus infections in Fiji.

Rotavirus is the most common cause of acute severe dehydrating diarrhoea in young children worldwide. We describe the burden of rotavirus disease and the rotavirus types causing it in the largest city in Fiji. During 2006 and 2007, 592 children under 5 years of age were admitted to hospital in Suva, Fiji with acute diarrhoea. Of the 454 children for whom a stool specimen was tested, 39% were positive for rotavirus and the predominant strain found was the serotype G3[P8]. There is a significant burden of disease due to rotavirus in Fiji and the introduction of rotavirus vaccines into the national immunization schedule may drastically reduce inpatient diarrhoeal disease.