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Background: High rates of breakthrough rotavirus gastroenteritis have been reported among Aboriginal children living in rural and remote Australia despite receipt of two doses of oral rotavirus vaccine. Histo-blood group antigens (HBGAs) may mediate rotavirus genotype-dependent differences in susceptibility to rotavirus infection and immune responses to rotavirus vaccination. Methods: HBGA phenotype – Lewis and secretor status - was determined by enzyme immunoassay of saliva samples obtained from Australian Aboriginal children who were enrolled at age 6 to <12 months in a randomised clinical trial of an additional (booster) dose of oral rotavirus vaccine. Participants had received the routine two-dose schedule of oral rotavirus vaccine administered at age 6 weeks and 4 months. Non-secretor phenotype was confirmed by DNA extraction to identify FUT2 ‘G428A’ mutation. Rotavirus seropositivity was defined as serum anti-rotavirus IgA ≥ 20 AU/mL measured by ELISA on enrolment. 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. Eighty-nine of 129 (69%) Lewis antigen positive children were rotavirus seropositive versus 10 of 19 (53%) of those who were Lewis antigen negative. Conclusions Most Australian Aboriginal children were secretor and Lewis antigen positive. Non-secretor children were less likely to be seropositive for rotavirus following vaccination, but this phenotype was less common. HBGA status is unlikely to fully explain the underperformance of rotavirus vaccine at a population level among Australian Aboriginal children.

INTRODUCTION: Rotavirus vaccines were introduced into the Australian National Immunisation Program in 2007. Despite this, Northern Territory Indigenous children continue to be hospitalised with rotavirus at a rate more than 20 times higher than non-Indigenous children in other Australian jurisdictions, with evidence of waning protection in the second year of life. We hypothesised that scheduling an additional (third) dose of oral human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to <12 months would improve protection against clinically significant all-cause gastroenteritis. METHODS AND ANALYSIS: This Bayesian adaptive clinical trial will investigate whether routinely scheduling an additional dose of Rotarix for Australian Indigenous children aged 6 to <12 months old confers significantly better protection against clinically important all-cause gastroenteritis than the current two-dose schedule at 2 and 4 months old. There are two coprimary endpoints: (1) seroconversion from baseline serum anti-rotavirus immunoglobulin A (IgA) titre <20 U/mL prior to an additional dose of Rotarix/placebo to serum anti-rotavirus IgA titre >20 U/mL following the administration of the additional dose of Rotarix/placebo and (2) time from randomisation to medical attendance (up to age 36 months old) for which the primary reason is acute gastroenteritis/diarrhoea. Secondary endpoints include the change in anti-rotavirus IgA log titre, time to hospitalisation for all-cause diarrhoea and for rotavirus-confirmed gastroenteritis/diarrhoea, and rotavirus notification. Analysis will be based on Bayesian inference with adaptive sample size. ETHICS, REGISTRATION AND DISSEMINATION: Ethics approval has been granted by Central Australian Human Research Ethics Committee (HREC-16-426) and Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC-2016-2658). Study investigators will ensure the trial is conducted in acc

This report is the user-guide to the content and application of the national scale Stream Sediment Geochemistry maps produced by the British Geological Survey (BGS) at a 500m grid. This map release, referred to as ‘BGS_SedGC_500m’, provides the spatial distribution of element concentrations across the United Kingdom as measured and interpolated from the chemical analysis of stream sediments. The purpose of this user guide is to enable those downloading this dataset to have a better appreciation of how the dataset has been created and therefore a better understanding of the potential applications and limitations that the dataset may have.

This report details work carried out under NERC grants NE/M008339/1 and NE/NO13026/1 which were collaborations between the British Geological Survey and Yorkshire Water, with an additional knowledge transfer component involving Scottish Water and Dŵr Cymru Welsh Water. The work examines whether models developed using environmental, topographical and geohazard information could complement existing management tools, and increase the understanding as to how pipe networks of different materials interact with their broader environment. This can be seen as a first step in identifying ways in which greater resilience could be built into pipe networks.

Rotavirus is a ubiquitous double-stranded RNA virus responsible for most cases of infantile gastroenteritis. It infects pancreatic islets in vitro and is implicated as a trigger of autoimmune destruction of islet beta cells leading to type 1 diabetes, but pancreatic pathology secondary to rotavirus infection in vivo has not been documented. To address this issue, we inoculated 3 week-old C57Bl/6 mice at weaning with rhesus rotavirus, which is closely related to human rotaviruses and known to infect mouse islets in vitro. Virus was quantified in tissues by culture-isolation and enzyme-linked immunosorbent assay. A requirement for viral double stranded RNA was investigated in toll-like receptor 3 (TLR3)-deficient mice. Cell proliferation and apoptosis, and insulin expression, were analyzed by immunohistochemistry. Following rotavirus inoculation by gavage, two phases of mild, transient hyperglycemia were observed beginning after 2 and 8 days. In the first phase, widespread apoptosis of pancreatic cells was associated with a decrease in pancreas mass and insulin production, without detectable virus in the pancreas. These effects were mimicked by injection of the double-stranded RNA mimic, polyinosinic-polycytidylic acid, and were TLR3-dependent. By the second phase, the pancreas had regenerated but islets were smaller than normal and viral antigen was then detected in the pancreas for several days. These findings directly demonstrate pathogenic effects of rotavirus infection on the pancreas in vivo, mediated initially by the interaction of rotavirus double-stranded RNA with TLR3.

© 2014 Elsevier B.V. Outbreaks of rotavirus diarrhea cause a large disease burden in the Alice Springs region of the Northern Territory, Australia. The introduction of the rotavirus vaccine Rotarix® has been associated with an increase in detection of G2P[4] strains in many countries. However, G2P[4] emergence has also been observed in vaccine-naive countries, suggesting a general global increase in the circulation of G2P[4] strains.A G2P[4] rotavirus outbreak occurred in 2009, 28. months after the introduction of the Rotarix® vaccine and 43 children were hospitalized. Pre-vaccine introduction, G2P[4] strains were observed associated with large outbreaks in 1999 and 2004. To determine the genetic relationship between these strains whole genome sequence analysis was conducted on representative strains from each of the G2P[4] outbreaks, in 1999, 2004 and 2009. Phylogenetic analysis revealed the majority of genes from 2009 outbreak strain clustered with contemporary global strains, while the VP7 gene clustered with contemporary and older strains and was antigenically distinct to the majority of contemporary global G2P[4] strains; suggesting the strain was an intragenogroup reassortant. The 1999 and 2009 strains appear to share similar evolutionary origins, and both had a high degree of genetic identity to previously identified Australian and global strains. Conversely, the 2004 outbreak strain was more divergent in comparison to Australian and global strains.The 1999 and 2004 outbreaks likely occurred due to the accumulation of immunologically naïve children in the population following low levels of G2P[4] rotavirus disease in the community in the years prior to each outbreak. The 2009 outbreak was associated with moderate vaccine coverage in the population and vaccine efficacy against the strain was low. The circulation of this unusual strain in the population combined with low vaccine coverage and diminished vaccine efficacy likely contributed to the outbreak occurri

In 2010, a large outbreak of rotavirus gastroenteritis occurred in the Alice Springs region of the Northern Territory, Australia. The outbreak occurred 43 months after the introduction of the G1P[8] rotavirus vaccine Rotarix®. Forty-three infants were hospitalized during the outbreak and analysis of fecal samples from each infant revealed a G1P[8] rotavirus strain. The outbreak strain was adapted to cell culture and neutralization assays were performed using VP7 and VP4 neutralizing monoclonal antibodies. The outbreak strain exhibited a distinct neutralization resistance pattern compared to the Rotarix® vaccine strain. Whole genome sequencing of the 2010 outbreak virus strain demonstrated numerous amino acid differences compared to the Rotarix® vaccine strain in the characterized neutralization epitopes of the VP7 and VP4 proteins. Phylogenetic analysis of the outbreak strain revealed a close genetic relationship to global strains, in particular RVA/Human-wt/BEL/BE0098/2009/ G1P[8] and RVA/Human-wt/BEL/BE00038/2008/G1P[8] for numerous genes. The 2010 outbreak strain was likely introduced from a globally circulating population of strains rather than evolving from an endemic Australian strain. The outbreak strain possessed antigenic differences in the VP7 and VP4 proteins compared to the Rotarix® vaccine strain. The outbreak was associated with moderate vaccine coverage and possibly low vaccine take in the population. © 2014 SSCC. All rights reserved.

© 2014 Elsevier Inc. Little is known about the population of eukaryotic viruses in the human gut ("virome") or the potential role it may play in disease. We used a metagenomic approach to define and compare the eukaryotic viromes in pediatric diarrhea cohorts from two locations (Melbourne and Northern Territory, Australia). We detected viruses known to cause diarrhea, non-pathogenic enteric viruses, viruses not associated with an enteric reservoir, viruses of plants, and novel viruses. Viromes from Northern Territory children contained more viral families per sample than viromes from Melbourne, which could be attributed largely to an increased number of sequences from the families Adenoviridae and Picornaviridae (genus enterovirus). qRT-PCR/PCR confirmed the increased prevalence of adenoviruses and enteroviruses. Testing of additional diarrhea cohorts by qRT-PCR/PCR demonstrated statistically different prevalences in different geographic sites. These findings raise the question of whether the virome plays a role in enteric diseases and conditions that vary with geography.

A large rotavirus gastroenteritis outbreak occurred in the Alice Springs region of the Northern Territory, Australia from the 12th of March until the 11th of July 2007. The outbreak occurred five months after the introduction of the Rotarix™ vaccine. Electropherotype and sequence analysis demonstrated that a single G9P[8] strain was responsible for the outbreak and that the strain remained highly conserved during the outbreak period. The outbreak strain contained amino acid changes in regions of the VP7 and NSP4 genes, with known biological function, when compared to previously characterised G9P[8] strains from Australia and other international locations. The recent vaccine introduction was unlikely to have influenced genotype selection in this setting. Importantly, Rotarix™ vaccine was highly effective against the G9P[8] outbreak strain.

A large rotavirus gastroenteritis outbreak occurred in the Alice Springs region of the Northern Territory, Australia from the 12th of March until the 11th of July 2007. The outbreak occurred five months after the introduction of the Rotarix™ vaccine. Electropherotype and sequence analysis demonstrated that a single G9P[8] strain was responsible for the outbreak and that the strain remained highly conserved during the outbreak period. The outbreak strain contained amino acid changes in regions of the VP7 and NSP4 genes, with known biological function, when compared to previously characterised G9P[8] strains from Australia and other international locations. The recent vaccine introduction was unlikely to have influenced genotype selection in this setting. Importantly, Rotarix™ vaccine was highly effective against the G9P[8] outbreak strain. © 2011 Elsevier Ltd.

Summary: The human rotavirus vaccine was evaluated during an outbreak of rotavirus G2P[4] infection in central Australia. No overall protective effect against hospitalization was demonstrated, raising concerns over the durability of vaccine protection against heterotypic strains. Background: Two and a half years after commencing routine vaccination with human rotavirus vaccine, an outbreak of rotavirus G2P[4] infection occurred in central Australia. Vaccine effectiveness against a P[8]-containing strain (G9P[8] ) had been demonstrated previously in this setting. This subsequent outbreak provided the opportunity to evaluate vaccine effectiveness against hospitalizations for a non-vaccine-related genotype in the same population. Methods: A case-control study was nested within a cohort of vaccine-eligible children listed on a populationbased immunization register. Children with rotavirus-confirmed gastroenteritis were individually matched by date of birth and Indigenous status with 4 control subjects. Results: Forty-one cases met the inclusion criteria, and 21 were severe cases among infants aged < 12 months. Nineteen (46%) of 41 case patients had received 2 doses of human rotavirus vaccine, compared with 87 (53%) of 164 control subjects. Vaccine effectiveness against rotavirus-related hospitalization was 19% (odds ratio,.81; 95% confidence interval,.32-2.05) for 2 doses compared with none. On secondary analysis, there was evidence of a protective effect against disease complicated by acidosis in the subset of infants aged < 12 months (odds ratio,.15; 95% confidence interval,.03-.84). Conclusions. Evidence was not found for an overall protective effect of human rotavirus vaccine against hospitalization for rotavirus disease in this setting. Post hoc analyses suggested a protective effect against severe disease in young infants. © The Author 2011.

Twenty-one intussusception (IS)-associated and 59 temporally linked adenoviral isolates from clinical infections were compared. Species C (15/21 IS- and 32/59 non-IS-associated isolates) dominated. Of these, serotype 2 (AdV-2) (7/15 IS-associated isolates) and serotype 1 (AdV-1) (16/32 non-IS-associated isolates) were the most commonly identified serotypes. DNA restriction analysis of AdV-2 isolates identified six genomic types; of these, type D2 (3/7 IS- and 8/11 non-IS-associated isolates) was the dominant type after BamHI and SmaI digestion. IS-associated isolates are similar to circulating non-IS-associated strains.

During 2001, an outbreak of severe acute gastroenteritis swept through Central and northern Australia and caused serious disruption to health services. We tracked and characterized the rotavirus strain implicated in the outbreak. Comparison of the electropherotypes of outbreak samples suggested that one G9P[8] strain was likely responsible for the outbreak. Samples were obtained from geographically distinct regions of Australia where the epidemic had occurred. The outbreak strains showed identical nucleotide sequences in genes encoding three rotavirus proteins, VP7, VP8, and NSP4, but they were distinct from G9P[8] strains isolated in previous years. Several of the amino acid substitutions on the VP7 and NSP4 proteins were identified in regions known to influence function and may have contributed to the emergence and increased dominance of the outbreak strains. Rotavirus serotype surveillance should continue with methods capable of identifying new and emerging types.