ORCID Profile
0000-0002-5449-4988
Current Organisations
Alder Hey Children's NHS Foundation Trust
,
University of Liverpool
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Publications
Immunogenicity of a third scheduled dose of rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis: a phase IV, double-blind, randomised, placebo-controlled clinical trial
Publisher: Cold Spring Harbor Laboratory
Date: 27-09-2021
DOI: 10.1101/2021.09.26.21264122
Abstract: The oral rotavirus vaccine, Rotarix (GlaxoSmithKline), is licensed for use in infants as two doses in the first six months of life. For infants living in settings with high child-mortality, and also for rural and remote Australian Aboriginal infants, clinical protection conferred by two doses of Rotarix appears to be reduced. We assessed the effect of an additional dose of Rotarix on vaccine immune responses among Aboriginal children who are 6 to 12 months old. ORVAC is a two-stage, double-blind, randomised, placebo-controlled trial conducted across regional urban and remote locations of Australia’s Northern Territory. Aboriginal children 6 to 12 months old who had received one or two prior doses of Rotarix were randomised 1:1 to receive an additional dose of Rotarix or matched placebo. The primary immunological endpoint was seroresponse defined as an anti-rotavirus IgA level ≥ 20 AU/mL, approximately one month following Rotarix or placebo. ClinicalTrials.gov ( NCT02941107 ). Between March 2018 and August 2020, 253 infants were enrolled. Of these, 178 infants (70%) had analysable serological results after follow-up 89 randomised to Rotarix and 89 to placebo. The proportion with a seroresponse was 85% after Rotarix compared to 71% after placebo the probability of a higher rate of seroresponse in the Rotarix than the placebo arm was 99%. There were no occurrences of intussusception or any serious adverse events attributed to Rotarix or placebo in the 28 days following the additional dose of Rotarix or placebo. An additional dose of Rotarix among Australian Aboriginal infants 6 to 12 months old increased the proportion with a vaccine seroresponse. If it can be proven that this translates into better protection against disease, scheduling an additional dose may be a viable strategy for further reducing the global burden of rotavirus disease. NHMRC (GNT1086952). Rotavirus vaccine programs have reduced the global burden of gastroenteritis disease among young children, but rotavirus still causes ,000 child deaths each year. A recent systematic review in the Lancet Global Healt h found that the effectiveness of oral rotavirus vaccines is variable, from 45 – 58% in settings with high child mortality to 83%-85% in settings with low child mortality. In high child mortality settings there is also evidence of waning effectiveness after 12 months old. Reduced vaccine effectiveness has also been reported among Australian Aboriginal children. Previous trials have failed to demonstrate improved rotavirus vaccine effectiveness with strategies such as withholding breastfeeding, or co-administering vaccines with probiotics or zinc. Pre-licensure studies of Rotarix in Africa did not clearly indicate whether a three-dose Rotarix schedule had benefit over a two-dose schedule, although all vaccine doses were given before infants were six months old when maternal antibodies may impede vaccine responses. Trials in Bangladesh and Mali found that a third Rotarix dose given after 6 months old improved the immune response to vaccine. In the first stage of our novel two-stage randomised clinical trial, we showed that scheduling an additional Rotarix dose for remote Australian Aboriginal infants after 6 months old increased the proportion with evidence of vaccine seroresponse. Scheduling an additional dose of Rotarix after 6 months old is feasible, and trials in three settings have now demonstrated that it improves immune responses. Trials should now be conducted in a number of high burden settings to determine whether this strategy results in improved clinical protection against severe gastroenteritis.
Whole genome sequence analysis of Shigella from Malawi identifies fluoroquinolone resistance
Publisher: Microbiology Society
Date: 04-05-2021
Abstract: Increasing antimicrobial resistance and limited alternative treatments have led to fluoroquinolone-resistant Shigella strain inclusion on the WHO global priority pathogens list. In this study we characterized multiple Shigella isolates from Malawi with whole genome sequence analysis, identifying the acquirable fluoroquinolone resistance determinant qnrS1 .
Vaccines for preventing rotavirus diarrhoea: vaccines in use
Publisher: Wiley
Date: 26-03-2019
Related Organisations
Liverpool School Of Tropical Medicine
Location: United Kingdom of Great Britain and Northern Ireland
Manchester Medical School, University Of Manchester
Location: United Kingdom of Great Britain and Northern Ireland
The Royal College Of Pathologists
Location: United Kingdom of Great Britain and Northern Ireland
Royal College Of Paediatrics And Child Health
Location: United Kingdom of Great Britain and Northern Ireland
Alder Hey Children's NHS Foundation Trust
Location: United Kingdom of Great Britain and Northern Ireland
Advance HE
Location: United Kingdom of Great Britain and Northern Ireland
Royal College Of Physicians
Location: United Kingdom of Great Britain and Northern Ireland
University Of Liverpool
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Nigel Cunliffe.