Paediatrics (RCH) - Research Publications
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ItemHisto-blood Group Antigen status of Australian Aboriginal children and seropositivity following oral rotavirus vaccination( 2022)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.
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ItemThe feasibility of SARS-CoV-2 surveillance using wastewater and environmental sampling in Indonesia(PUBLIC LIBRARY SCIENCE, 2022-10-14)BACKGROUND: Wastewater-based epidemiology (WBE) surveillance as an early warning system (EWS) for monitoring community transmission of SARS-CoV-2 in low- and middle-income country (LMIC) settings, where diagnostic testing capacity is limited, needs further exploration. We explored the feasibility to conduct a WBE surveillance in Indonesia, one of the global epicenters of the COVID-19 pandemic in the middle of 2021, with the fourth largest population in the world where sewer and non-sewered sewage systems are implemented. The feasibility and resource capacity to collect samples on a weekly or fortnightly basis with grab and/or passive sampling methods, as well as to conduct qualitative and quantitative identification of SARS-CoV-2 ribonucleic acid (RNA) using real-time RT-PCR (RT-qPCR) testing of environmental samples were explored. MATERIALS AND METHODS: We initiated a routine surveillance of wastewater and environmental sampling at three predetermined districts in Special Region of Yogyakarta Province. Water samples were collected from central and community wastewater treatment plants (WWTPs), including manholes flowing to the central WWTP, and additional soil samples were collected for the near source tracking (NST) locations (i.e., public spaces where people congregate). RESULTS: We began collecting samples in the Delta wave of the COVID-19 pandemic in Indonesia in July 2021. From a 10-week period, 54% (296/544) of wastewater and environmental samples were positive for SARS-CoV-2 RNA. The sample positivity rate decreased in proportion with the reported incidence of COVID-19 clinical cases in the community. The highest positivity rate of 77% in week 1, was obtained for samples collected in July 2021 and decreased to 25% in week 10 by the end of September 2021. CONCLUSION: A WBE surveillance system for SARS-CoV-2 in Indonesia is feasible to monitor the community burden of infections. Future studies testing the potential of WBE and EWS for signaling early outbreaks of SARS-CoV-2 transmissions in this setting are required.
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ItemVale Professor Ruth Frances Bishop AC 1933-2022(CSIRO PUBLISHING, 2022)
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ItemVirology and immune dynamics reveal high household transmission of ancestral SARS-CoV-2 strain(WILEY, 2022-07)BACKGROUND: Household studies are crucial for understanding the transmission of SARS-CoV-2 infection, which may be underestimated from PCR testing of respiratory samples alone. We aim to combine the assessment of household mitigation measures; nasopharyngeal, saliva, and stool PCR testing; along with mucosal and systemic SARS-CoV-2-specific antibodies, to comprehensively characterize SARS-CoV-2 infection and transmission in households. METHODS: Between March and September 2020, we obtained samples from 92 participants in 26 households in Melbourne, Australia, in a 4-week period following the onset of infection with ancestral SARS-CoV-2 variants. RESULTS: The secondary attack rate was 36% (24/66) when using nasopharyngeal swab (NPS) PCR positivity alone. However, when respiratory and nonrespiratory samples were combined with antibody responses in blood and saliva, the secondary attack rate was 76% (50/66). SARS-CoV-2 viral load of the index case and household isolation measures were key factors that determine secondary transmission. In 27% (7/26) of households, all family members tested positive by NPS for SARS-CoV-2 and were characterized by lower respiratory Ct values than low transmission families (Median 22.62 vs. 32.91; IQR 17.06-28.67 vs. 30.37-34.24). High transmission families were associated with enhanced plasma antibody responses to multiple SARS-CoV-2 antigens and the presence of neutralizing antibodies. Three distinguishing saliva SARS-CoV-2 antibody features were identified according to age (IgA1 to Spike 1, IgA1 to nucleocapsid protein (NP)), suggesting that adults and children generate distinct mucosal antibody responses during the acute phase of infection. CONCLUSION: Utilizing respiratory and nonrespiratory PCR testing, along with the measurement of SARS-CoV-2-specific local and systemic antibodies, provides a more accurate assessment of infection within households and highlights some of the immunological differences in response between children and adults.
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ItemEvolutionary changes between pre- and post- vaccine South African group A G2P[4] rotavirus strains, 2003-2017(MICROBIOLOGY SOC, 2022-04)The transient upsurge of G2P[4] group A rotavirus (RVA) after Rotarix vaccine introduction in several countries has been a matter of concern. To gain insight into the diversity and evolution of G2P[4] strains in South Africa pre- and post-RVA vaccination introduction, whole-genome sequencing was performed for RVA positive faecal specimens collected between 2003 and 2017 and samples previously sequenced were obtained from GenBank (n=103; 56 pre- and 47 post-vaccine). Pre-vaccine G2 sequences predominantly clustered within sub-lineage IVa-1. In contrast, post-vaccine G2 sequences clustered mainly within sub-lineage IVa-3, whereby a radical amino acid (AA) substitution, S15F, was observed between the two sub-lineages. Pre-vaccine P[4] sequences predominantly segregated within sub-lineage IVa while post-vaccine sequences clustered mostly within sub-lineage IVb, with a radical AA substitution R162G. Both S15F and R162G occurred outside recognised antigenic sites. The AA residue at position 15 is found within the signal sequence domain of Viral Protein 7 (VP7) involved in translocation of VP7 into endoplasmic reticulum during infection process. The 162 AA residue lies within the hemagglutination domain of Viral Protein 4 (VP4) engaged in interaction with sialic acid-containing structure during attachment to the target cell. Free energy change analysis on VP7 indicated accumulation of stable point mutations in both antigenic and non-antigenic regions. The segregation of South African G2P[4] strains into pre- and post-vaccination sub-lineages is likely due to erstwhile hypothesized stepwise lineage/sub-lineage evolution of G2P[4] strains rather than RVA vaccine introduction. Our findings reinforce the need for continuous whole-genome RVA surveillance and investigation of contribution of AA substitutions in understanding the dynamic G2P[4] epidemiology.
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ItemNo Preview AvailableAustralian Rotavirus Surveillance Program: Annual Report, 2020(AUSTRALIAN GOVERNMENT, DEPT HEALTH & AGEING, 2021-11-30)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.
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ItemGenetic diversity of respiratory enteroviruses and rhinoviruses in febrile adults, Singapore, 2007-2013(WILEY, 2020-01)To understand the genetic diversity and patterns of circulation of rhinoviruses (RV) and enteroviruses (EV) in Singapore, we retrospectively screened 2950 nasal swab samples collected from adults presenting to primary care services with signs of febrile illness in Singapore during 2007-2013 using sequencing and phylogenetic methods. Through sequencing and phylogenetic analysis, our results show the year-round circulation of the three rhinovirus species, A, B, and C. A diverse set of RV/EV serotypes were detected in Singapore with a predominance of RV-A in all years, whereas serotypes EV-C A21 and EV-D68 were only sporadically detected. This study highlights the previously unrecognized diversity and burden in the adult population in Singapore.
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ItemWhole Genome Characterization and Evolutionary Analysis of G1P[8] Rotavirus A Strains during the Pre- and Post-Vaccine Periods in Mozambique (2012-2017)(MDPI, 2020-12)Mozambique introduced the Rotarix® vaccine (GSK Biologicals, Rixensart, Belgium) into the National Immunization Program in September 2015. Although G1P[8] was one of the most prevalent genotypes between 2012 and 2017 in Mozambique, no complete genomes had been sequenced to date. Here we report whole genome sequence analysis for 36 G1P[8] strains using an Illumina MiSeq platform. All strains exhibited a Wa-like genetic backbone (G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1). Phylogenetic analysis showed that most of the Mozambican strains clustered closely together in a conserved clade for the entire genome. No distinct clustering for pre- and post-vaccine strains were observed. These findings may suggest no selective pressure by the introduction of the Rotarix® vaccine in 2015. Two strains (HJM1646 and HGM0544) showed varied clustering for the entire genome, suggesting reassortment, whereas a further strain obtained from a rural area (MAN0033) clustered separately for all gene segments. Bayesian analysis for the VP7 and VP4 encoding gene segments supported the phylogenetic analysis and indicated a possible introduction from India around 2011.7 and 2013.0 for the main Mozambican clade. Continued monitoring of rotavirus strains in the post-vaccine period is required to fully understand the impact of vaccine introduction on the diversity and evolution of rotavirus strains.
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ItemRotavirus surveillance informs diarrhoea disease burden in the WHO Western-Pacific region(CSIRO PUBLISHING, 2021)The surveillance of enteric pathogens is critical in assessing the burden of diarrhoeal disease and informing vaccine programs. Surveillance supported by the World Health Organization in Fiji, Vietnam, the Lao People’s Democratic Republic, and the Philippines previously focussed on rotavirus. There is potential to expand surveillance to encompass a variety of enteric pathogens to inform vaccine development for norovirus, enterotoxigenic Escherichia coli and Shigella.
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ItemLineage-specific protection and immune imprinting shape the age distributions of influenza B cases(NATURE PORTFOLIO, 2021-07-14)How a history of influenza virus infections contributes to protection is not fully understood, but such protection might explain the contrasting age distributions of cases of the two lineages of influenza B, B/Victoria and B/Yamagata. Fitting a statistical model to those distributions using surveillance data from New Zealand, we found they could be explained by historical changes in lineage frequencies combined with cross-protection between strains of the same lineage. We found additional protection against B/Yamagata in people for whom it was their first influenza B infection, similar to the immune imprinting observed in influenza A. While the data were not informative about B/Victoria imprinting, B/Yamagata imprinting could explain the fewer B/Yamagata than B/Victoria cases in cohorts born in the 1990s and the bimodal age distribution of B/Yamagata cases. Longitudinal studies can test if these forms of protection inferred from historical data extend to more recent strains and other populations.