# name
Efficacy and safety of RTS,S/AS01 malaria vaccine with or
                without a booster dose in infants and children in Africa: final
                results of a phase 3, individually randomised, controlled trial

# metadata.dc.description.abstract[].value
BACKGROUND: The efficacy and safety of the RTS,S/AS01 candidate
                malaria vaccine during 18 months of follow-up have been
                published previously. Herein, we report the final results from
                the same trial, including the efficacy of a booster dose.
                METHODS: From March 27, 2009, until Jan 31, 2011, children (age
                5-17 months) and young infants (age 6-12 weeks) were enrolled at
                11 centres in seven countries in sub-Saharan Africa.
                Participants were randomly assigned (1:1:1) at first vaccination
                by block randomisation with minimisation by centre to receive
                three doses of RTS,S/AS01 at months 0, 1, and 2 and a booster
                dose at month 20 (R3R group); three doses of RTS,S/AS01 and a
                dose of comparator vaccine at month 20 (R3C group); or a
                comparator vaccine at months 0, 1, 2, and 20 (C3C [control
                group]). Participants were followed up until Jan 31, 2014. Cases
                of clinical and severe malaria were captured through passive
                case detection. Serious adverse events (SAEs) were recorded.
                Analyses were by modified intention to treat and per protocol.
                The coprimary endpoints were the occurrence of malaria over 12
                months after dose 3 in each age category. In this final
                analysis, we present data for the efficacy of the booster on the
                occurrence of malaria. Vaccine efficacy (VE) against clinical
                malaria was analysed by negative binomial regression and against
                severe malaria by relative risk reduction. This trial is
                registered with ClinicalTrials.gov, number NCT00866619.
                FINDINGS: 8922 children and 6537 young infants were included in
                the modified intention-to-treat analyses. Children were followed
                up for a median of 48 months (IQR 39-50) and young infants for
                38 months (34-41) after dose 1. From month 0 until study end,
                compared with 9585 episodes of clinical malaria that met the
                primary case definition in children in the C3C group, 6616
                episodes occurred in the R3R group (VE 36.3%, 95% CI 31.8-40.5)
                and 7396 occurred in the R3C group (28.3%, 23.3-32.9); compared
                with 171 children who experienced at least one episode of severe
                malaria in the C3C group, 116 children experienced at least one
                episode of severe malaria in the R3R group (32.2%, 13.7 to 46.9)
                and 169 in the R3C group (1.1%, -23.0 to 20.5). In young
                infants, compared with 6170 episodes of clinical malaria that
                met the primary case definition in the C3C group, 4993 episodes
                occurred in the R3R group (VE 25.9%, 95% CI 19.9-31.5) and 5444
                occurred in the R3C group (18.3%, 11.7-24.4); and compared with
                116 infants who experienced at least one episode of severe
                malaria in the C3C group, 96 infants experienced at least one
                episode of severe malaria in the R3R group (17.3%, 95% CI -9.4
                to 37.5) and 104 in the R3C group (10.3%, -17.9 to 31.8). In
                children, 1774 cases of clinical malaria were averted per 1000
                children (95% CI 1387-2186) in the R3R group and 1363 per 1000
                children (995-1797) in the R3C group. The numbers of cases
                averted per 1000 young infants were 983 (95% CI 592-1337) in the
                R3R group and 558 (158-926) in the R3C group. The frequency of
                SAEs overall was balanced between groups. However, meningitis
                was reported as a SAE in 22 children: 11 in the R3R group, ten
                in the R3C group, and one in the C3C group. The incidence of
                generalised convulsive seizures within 7 days of RTS,S/AS01
                booster was 2.2 per 1000 doses in young infants and 2.5 per 1000
                doses in children. INTERPRETATION: RTS,S/AS01 prevented a
                substantial number of cases of clinical malaria over a 3-4 year
                period in young infants and children when administered with or
                without a booster dose. Efficacy was enhanced by the
                administration of a booster dose in both age categories. Thus,
                the vaccine has the potential to make a substantial contribution
                to malaria control when used in combination with other effective
                control measures, especially in areas of high transmission.
                FUNDING: GlaxoSmithKline Biologicals SA and the PATH Malaria
                Vaccine Initiative.

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
Efficacy and safety of RTS,S/AS01 malaria vaccine with or
                without a booster dose in infants and children in Africa: final
                results of a phase 3, individually randomised, controlled trial