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The ORVAC Trial - A phase IV, double-blind, randomised, placebo-controlled clinical trial to optimise the delivery of RV1 rotavirus vaccine to Northern Territory Aboriginal infants

Investigators: Julie Marsh, Mark Jones, Nelly Newall, Tom Snelling

External collaborators: Ross Andrews (Menzies School of Health Research), Carl Kirwood (Bill and Melinda Gates Foundation), Margaret Danchin (Murdoch Children's Research Institute), Amanda Leach (Menzies School of Health Research), Bianca Middleton (Menzies School of Health Research)

Diarrhoea kills more than half a million children under five years old every year, predominantly in resource-poor settings. Rotavirus is the leading cause of severe, dehydrating diarrhoeal disease in children, and accounts for almost one-third of these deaths. In Australia, NT Aboriginal children have experienced rates of hospitalization for rotavirus gastroenteritis more than 10 times higher than other Australian children.

The development of oral attenuated rotavirus vaccines with high efficacy against severe rotavirus disease in field trials was a major step forward in the battle to reduce the global burden of diarrhoeal disease. Unfortunately, work by our group and others has shown that rotavirus vaccines have significantly lower efficacy, and more rapid waning of protection, in low-resource settings and also among Australian Indigenous Infants.(4, 5) While overall rates of rotavirus disease have decreased, the ratio of hospitalisations for Indigenous versus non- Indigenous children has increased since vaccine introduction.

This trial seeks to evaluate whether the inclusion of a third dose of RV1 between 6 and 12 months of age will improve the effectiveness of rotavirus vaccination amongst Aboriginal children. We propose that this is a safe, effective and imminently implementable solution to redress the excess burden of gastroenteritis among NT Aboriginal children. This trial is currently enrolling participants in the top end of the Northern Territory.