Rotaviruses are recognised as the leading cause of severe gastroenteritis in
children aged less than five years in both developed and developing countries,
with highest incidence rates between 6 and 24 months of life. On a global scale,
recent estimates indicate that annually rotaviruses cause at least 500,000
deaths. A large phase III clinical trial was undertaken in 11 Latin American
countries and Finland with an attenuated, human-derived vaccine strain,
including recruitment of more than 63,000 children. This was a randomised,
double-blind, placebo-controlled trial in which more than 63,000 infants were
randomly assigned to receive two oral doses of either RIX4414 or placebo at a
proportion of 1:1. The main purposed of this study was to evaluate both
protective efficacy and safety of RIX4414. As part of the original study, 3,218
children were enrolled in Belém, Pará, to whom two doses of either vaccine or
placebo were administered at 2 and 4 months of age. A subset of infants (n =
653) was evaluated throughout 1 – 2 years in order to assess efficacy of
RIX4414 vaccine. Overall, 37 gastroenteritis episodes of severe rotavirus
gastroenteritis were recorded of which 75.6% (28/37) and 24% (9/37) in the
placebo and vaccine recipients, respectively. The level of rotavirus vaccine
protection was higher [83% (CI95% 22 – 96)] against very severe rotavirus
gastroenteritis, yielding a ≥ 15 score as calculated with a 20-point Ruuska &
Vesikari scale. The cumulative hazard of a first episode of severe gastroenteritis
was about four-fold lower in the vaccine group throughout the 2-years’ efficacy
period, as compared to the placebo group. The protection rates against severe
gastroenteritis caused by G1- and- non-G1 serotypes were 51% (CI95% -30-81)
and 82% (CI95% 37-95), respectively, denoting efficacies against rotavirus
strains both homologous and heterologous to the vaccine strain. Of importance,
the vaccine afforded significant protection [93% (CI95%47-99)] against G9
serotype which has been regarded as a globally emergent strain, besides of
being related to more severe gastroenteritis. Also reflecting a vaccine efficacy,
there was a significant reduction, by 35.3% (CI95% 11.6-52.9), in the rate of allcause
hospitalisation for gastroenteritis, a finding of potential major public
health impact. With regards to safety of RIX4414 vaccine, there were no overall
statistically significant differences when the rates of serious adverse events
were compared for vaccine group and placebo group. No cases of
intussusception were reported during the entire follow-up period, through broad
and active surveillance in paediatric clinics in the study area. Results obtained
in this study confirm previous findings from worldwide several multi-centric trials
that sustain both protective efficacy and safety of RIX4414 when administered
in a 2-dose schema to healthy infants.
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