Publications by authors named "Carl Kirkwood"

Oral vaccines have several advantages compared with parenteral administration: they can be relatively cheap to produce in high quantities, easier to administer, and induce intestinal mucosal immunity that can protect against infection. These characteristics have led to successful use of oral vaccines against rotavirus, polio, and cholera. Unfortunately, oral vaccines for all three diseases have demonstrated lower performance in the highest-burden settings where they are most needed.

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The 2nd International Hepatitis E Virus Symposium was held on April 28 and 29, 2023, in London, UK. The conference was hosted by the International Vaccine Institute and brought together key clinicians, researchers, and private and public stakeholders for a dedicated forum on hepatitis E virus (HEV). The scientific program spanned multiple facets of HEV, from updates on clinical research and diagnostic advances to vaccine development.

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Rotavirus is the most common pathogen causing pediatric diarrhea and an important cause of morbidity and mortality in low- and middle-income countries. Previous evidence suggests that the introduction of rotavirus vaccines in national immunization schedules resulted in dramatic declines in disease burden but may also be changing the rotavirus genetic landscape and driving the emergence of new genotypes. We report genotype data of more than 16,000 rotavirus isolates from 40 countries participating in the Global Rotavirus Surveillance Network.

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Article Synopsis
  • Hepatitis E virus (HEV) is a common cause of liver infection, mostly mild, but can be very serious for some groups like pregnant women.
  • The study looked at HEV outbreaks from 2011 to 2022 by reviewing over 1,300 reports and found 44 outbreaks in 19 countries.
  • Many reports were missing important information, such as who got sick, how many people died, and what safety measures helped, making it hard to understand the full impact of HEV.
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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.

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Article Synopsis
  • Africa experiences the highest rates of diarrheal deaths in the world, emphasizing a serious public health issue.
  • High vaccination rates for rotavirus across Africa have shown positive effects in reducing diarrheal diseases.
  • However, there is still a need to enhance rotavirus vaccine coverage and improve access to essential health services like medical care, oral rehydration therapy, and better water and sanitation facilities.
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The 2nd Next Generation Rotavirus Vaccine Developers Meeting, sponsored by PATH and the Bill and Melinda Gates Foundation, was held in London, UK (7-8 June 2022), and attended by vaccine developers and researchers to discuss advancements in the development of next-generation rotavirus vaccines and to consider issues surrounding vaccine acceptability, introduction, and uptake. Presentations included updates on rotavirus disease burden, the impact of currently licensed oral vaccines, various platforms and approaches for next generation rotavirus vaccines, strategies for combination pediatric vaccines, and the value proposition for novel parenteral rotavirus vaccines. This report summarizes the information shared at the convening and poses various topics worthy of further exploration.

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Background: Rotarix (GlaxoSmithKline) oral rotavirus vaccine is licensed as 2 doses in the first 6 months of life. In settings with high child mortality rates, clinical protection conferred by 2 doses of Rotarix is reduced. We assessed vaccine immune response when an additional dose of Rotarix was given to Australian Aboriginal children 6 to <12 months old.

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Background: In 2012, Fiji became the first independent Pacific island country to introduce rotavirus vaccine. We describe the impact of rotavirus vaccine on all-cause diarrhoea admissions in all ages, and rotavirus diarrhoea in children <5 years of age.

Methods: An observational study was conducted retrospectively on all admissions to the public tertiary hospitals in Fiji (2007-2018) and prospectively on all rotavirus-positive diarrhoea admissions in children <5 years at two hospital sites (2006-2018, and 2010-2015), along with rotavirus diarrhoea outpatient presentations at one secondary public hospital (2010-2015).

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Background: Rotavirus infections of neonatal and older pigs are widely reported. Analysis of rotavirus group C prevalence and diversity has not previously been reported for Australian pig farms.

Methods: Twenty-seven farms with or without diarrhoea present among neonatal or older pigs were enrolled across eastern Australia.

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Introduction: Hepatitis E virus (HEV) is an important cause of enterically transmitted viral hepatitis and a significant contributor to maternal mortality in endemic regions around the world, yet the global response has been limited. HEV is a disease of poverty, and the populations experiencing the greatest burden of HEV-associated illness are not benefitting from existing interventions, including WASH strategies and immunization.

Areas Covered: Though a vaccine exists (HEV 239, Hecolin®, Xiamen Innovax Biotech, China), it is only licensed and available in the private market in China and has yet to be prequalified by the WHO for use in endemic settings and outbreaks.

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Despite the contribution of currently licensed live, oral rotavirus vaccines (LORVs) to alleviating the burden of severe disease and death from rotavirus gastroenteritis, those vaccines have proven less efficacious in resource-limited settings than in high- and middle-income countries. It has been proposed that the residual burden of rotavirus disease might be overcome with parenterally administered vaccines, or next-generation rotavirus vaccines (NGRV). To better define the progress of development of these vaccines, a meeting of vaccine developers and manufacturers engaged in NGRV research and development was convened in Geneva in June 2019.

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Rotavirus G1P[8] strains account for more than half of the group A rotavirus (RVA) infections in children under five years of age, globally. A total of 103 stool samples previously characterized as G1P[8] and collected seven years before and seven years after introducing the Rotarix vaccine in South Africa were processed for whole-genome sequencing. All the strains analyzed had a Wa-like constellation (G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1).

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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.

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Background: Microbial factors are likely to be involved in the recurrence of Crohn's disease (CD) after bowel resection. We investigated the luminal microbiota before and longitudinally after surgery, in relation to disease recurrence, using 16S metagenomic techniques.

Methods: In the prospective Post-Operative Crohn's Endoscopic Recurrence (POCER) study, fecal samples were obtained before surgery and 6, 12, and 18 months after surgery from 130 CD patients.

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Background: Placental or breast milk maternal antibodies can potentially reduce oral rotavirus vaccine efficacy in developing countries. We aimed to examine the relationship between the level of rotavirus specific immunoglobulin A (IgA) and neutralising antibodies (NA) in colostrum and breast milk and cord IgG, with cumulative vaccine take following one and three doses of oral RV3-BB rotavirus vaccine within a Phase IIb trial in Indonesia.

Methods: 196 infants received three doses of RV3-BB in a randomized, double-blinded trial, using a neonatal schedule (first dose at 0-5 days of age, n = 61), an infant schedule (first dose at ~ 8 weeks of age, n = 67) or placebo (n = 68).

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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.

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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.

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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.

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Background: Rotavirus (RV) is a leading cause of severe gastroenteritis globally and can cause substantial morbidity associated with gastroenteritis in children <5 years of age. Orally administered live-attenuated RV vaccines offer protection against disease but vaccination efforts have been hampered by high manufacturing costs and the need to maintain a cold chain.

Methods: A subset of Vero cell host genes was identified by siRNA that when knocked down increased RV replication and these anti-viral host genes were individually deleted using CRISPR-Cas9.

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Background: The RV3-BB human neonatal rotavirus vaccine was developed to provide protection from severe rotavirus disease from birth. The aim of this study was to investigate the potential for mutual interference in the immunogenicity of oral polio vaccine (OPV) and RV3-BB.

Methods: A randomized, placebo-controlled trial involving 1649 participants was conducted from January 2013 to July 2016 in Central Java and Yogyakarta, Indonesia.

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Purpose Of Review: As of 2019, four rotavirus vaccines have been prequalified by the WHO for use worldwide. This review highlights current knowledge regarding rotavirus vaccines available, and provides a brief summary of the rotavirus vaccine pipeline.

Recent Findings: Data generated from use of currently available products supports their effectiveness and impact in diverse settings.

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Rotavirus is a major cause of diarrhea in Indonesian children. However, rotavirus vaccines have not been introduced in the national immunization program of Indonesia. Understanding the genetic diversity and conserved antigenic regions of circulating strains are therefore essential to assess the potential efficacy of rotavirus vaccines.

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Objectives: The incidence of pediatric inflammatory bowel disease (IBD) is increasing worldwide. Ecological studies show higher incidence in regions at higher latitude or lower ambient ultraviolet radiation; individual-level associations with sun exposure have not been assessed.

Methods: We recruited children (0-17 years) with IBD from 2 large hospitals in Melbourne, Australia.

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