Paediatrics (RCH) - Research Publications
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ItemVale Professor Ruth Frances Bishop AC 1933-2022(CSIRO PUBLISHING, 2022)
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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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ItemNeonatal 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(ELSEVIER SCI LTD, 2022-05)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.
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ItemRotavirus Disease and Genotype Diversity in Older Children and Adults in Australia(OXFORD UNIV PRESS INC, 2022-06-15)BACKGROUND: Rotavirus is a major cause of gastroenteritis in children <5 years of age. The disease burden in older children, adults, and the elderly is underappreciated. This study describes rotavirus disease and genotypic diversity in the Australian population comprising children ≥5 years of age and adults. METHODS: Rotavirus positive fecal samples were collected from laboratories Australia-wide participating in the Australian Rotavirus Surveillance Program between 2010 and 2018. Rotavirus samples were genotyped using a heminested multiplex reverse-transcription polymerase chain reaction. Notification data from the National Notifiable Diseases Surveillance System were also analyzed. RESULTS: Rotavirus disease was highest in children aged 5-9 years and adults ≥85 years. G2P[4] was the dominant genotype in the population ≥5 years of age. Genotype distribution fluctuated annually and genotypic diversity varied among different age groups. Geographical differences in genotype distribution were observed based on the rotavirus vaccine administered to infants <1 year of age. CONCLUSIONS: This study revealed a substantial burden of rotavirus disease in the population ≥5 years of age, particularly in children 5-9 years and the elderly. This study highlights the continued need for rotavirus surveillance across the population, despite the implementation of efficacious vaccines.
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ItemRotavirus serotype G9P[8] and acute gastroenteritis outbreak in children, Northern Australia(CENTER DISEASE CONTROL, 2004-09)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.
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ItemThe burden of hospitalised rotavirus infections in Fiji(ELSEVIER SCI LTD, 2009-11-20)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.