Seven-year efficacy of RTS, S/AS01 malaria vaccine among young african children

Ally Olotu, Gregory Fegan, Juliana Wambua, George Nyangweso, Amanda Leach, Marc Lievens, David C. Kaslow, Patricia Njuguna, Kevin Marsh, Philip Bejon

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    BACKGROUND: The candidate malaria vaccine RTS, S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules. 

    METHODS: We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS, S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of>2500 parasites per cubic millimeter). In an analysis that was not prespecified, the malaria exposure of each child was estimated with the use of information on the prevalence of malaria among residents within a 1-km radius of the child's home. Vaccine efficacy was defined as 1 minus the hazard ratio or the incidence-rate ratio, multiplied by 100, in the RTS, S/AS01 group versus the control group. 

    RESULTS: Over 7 years of follow-up, we identified 1002 episodes of clinical malaria among 223 children randomly assigned to the RTS, S/AS01 group and 992 episodes among 224 children randomly assigned to the control group. The vaccine efficacy, as assessed by negative binomial regression, was 4.4% (95% confidence interval [CI], -17.0 to 21.9; P = 0.66) in the intention-to-treat analysis and 7.0% (95% CI, -14.5 to 24.6; P = 0.52) in the per-protocol analysis. Vaccine efficacy waned over time (P = 0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children with higher-than-average exposure to malaria parasites (intention-to-treat analysis: -43.5%; 95% CI, -100.3 to -2.8 [P = 0.03]; per-protocol analysis: -56.8%; 95% CI, -118.7 to -12.3 [P = 0.008]). 

    CONCLUSIONS: A three-dose vaccination with RTS, S/AS01 was initially protective against clinical malaria, but this result was offset by rebound in later years in areas with higher than-average exposure to malaria parasites.

    Original languageEnglish
    Pages (from-to)2519-2529
    Number of pages11
    JournalNew England Journal of Medicine
    Volume374
    Issue number26
    DOIs
    Publication statusPublished - 30 Jun 2016

    Fingerprint

    Malaria Vaccines
    Malaria
    Confidence Intervals
    Parasites
    Vaccination
    Intention to Treat Analysis
    Vaccines
    Rabies Vaccines
    Control Groups
    Plasmodium falciparum
    RTS,S-AS01 vaccine
    Appointments and Schedules
    Temperature
    Incidence
    Infection

    Cite this

    Olotu, A., Fegan, G., Wambua, J., Nyangweso, G., Leach, A., Lievens, M., ... Bejon, P. (2016). Seven-year efficacy of RTS, S/AS01 malaria vaccine among young african children. New England Journal of Medicine, 374(26), 2519-2529. https://doi.org/10.1056/NEJMoa1515257
    Olotu, Ally ; Fegan, Gregory ; Wambua, Juliana ; Nyangweso, George ; Leach, Amanda ; Lievens, Marc ; Kaslow, David C. ; Njuguna, Patricia ; Marsh, Kevin ; Bejon, Philip. / Seven-year efficacy of RTS, S/AS01 malaria vaccine among young african children. In: New England Journal of Medicine. 2016 ; Vol. 374, No. 26. pp. 2519-2529.
    @article{f4a122a7c1174450926530d3b76a1220,
    title = "Seven-year efficacy of RTS, S/AS01 malaria vaccine among young african children",
    abstract = "BACKGROUND: The candidate malaria vaccine RTS, S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules. METHODS: We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS, S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of>2500 parasites per cubic millimeter). In an analysis that was not prespecified, the malaria exposure of each child was estimated with the use of information on the prevalence of malaria among residents within a 1-km radius of the child's home. Vaccine efficacy was defined as 1 minus the hazard ratio or the incidence-rate ratio, multiplied by 100, in the RTS, S/AS01 group versus the control group. RESULTS: Over 7 years of follow-up, we identified 1002 episodes of clinical malaria among 223 children randomly assigned to the RTS, S/AS01 group and 992 episodes among 224 children randomly assigned to the control group. The vaccine efficacy, as assessed by negative binomial regression, was 4.4{\%} (95{\%} confidence interval [CI], -17.0 to 21.9; P = 0.66) in the intention-to-treat analysis and 7.0{\%} (95{\%} CI, -14.5 to 24.6; P = 0.52) in the per-protocol analysis. Vaccine efficacy waned over time (P = 0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children with higher-than-average exposure to malaria parasites (intention-to-treat analysis: -43.5{\%}; 95{\%} CI, -100.3 to -2.8 [P = 0.03]; per-protocol analysis: -56.8{\%}; 95{\%} CI, -118.7 to -12.3 [P = 0.008]). CONCLUSIONS: A three-dose vaccination with RTS, S/AS01 was initially protective against clinical malaria, but this result was offset by rebound in later years in areas with higher than-average exposure to malaria parasites.",
    author = "Ally Olotu and Gregory Fegan and Juliana Wambua and George Nyangweso and Amanda Leach and Marc Lievens and Kaslow, {David C.} and Patricia Njuguna and Kevin Marsh and Philip Bejon",
    year = "2016",
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    doi = "10.1056/NEJMoa1515257",
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    Olotu, A, Fegan, G, Wambua, J, Nyangweso, G, Leach, A, Lievens, M, Kaslow, DC, Njuguna, P, Marsh, K & Bejon, P 2016, 'Seven-year efficacy of RTS, S/AS01 malaria vaccine among young african children', New England Journal of Medicine, vol. 374, no. 26, pp. 2519-2529. https://doi.org/10.1056/NEJMoa1515257

    Seven-year efficacy of RTS, S/AS01 malaria vaccine among young african children. / Olotu, Ally; Fegan, Gregory; Wambua, Juliana; Nyangweso, George; Leach, Amanda; Lievens, Marc; Kaslow, David C.; Njuguna, Patricia; Marsh, Kevin; Bejon, Philip.

    In: New England Journal of Medicine, Vol. 374, No. 26, 30.06.2016, p. 2519-2529.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Seven-year efficacy of RTS, S/AS01 malaria vaccine among young african children

    AU - Olotu, Ally

    AU - Fegan, Gregory

    AU - Wambua, Juliana

    AU - Nyangweso, George

    AU - Leach, Amanda

    AU - Lievens, Marc

    AU - Kaslow, David C.

    AU - Njuguna, Patricia

    AU - Marsh, Kevin

    AU - Bejon, Philip

    PY - 2016/6/30

    Y1 - 2016/6/30

    N2 - BACKGROUND: The candidate malaria vaccine RTS, S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules. METHODS: We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS, S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of>2500 parasites per cubic millimeter). In an analysis that was not prespecified, the malaria exposure of each child was estimated with the use of information on the prevalence of malaria among residents within a 1-km radius of the child's home. Vaccine efficacy was defined as 1 minus the hazard ratio or the incidence-rate ratio, multiplied by 100, in the RTS, S/AS01 group versus the control group. RESULTS: Over 7 years of follow-up, we identified 1002 episodes of clinical malaria among 223 children randomly assigned to the RTS, S/AS01 group and 992 episodes among 224 children randomly assigned to the control group. The vaccine efficacy, as assessed by negative binomial regression, was 4.4% (95% confidence interval [CI], -17.0 to 21.9; P = 0.66) in the intention-to-treat analysis and 7.0% (95% CI, -14.5 to 24.6; P = 0.52) in the per-protocol analysis. Vaccine efficacy waned over time (P = 0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children with higher-than-average exposure to malaria parasites (intention-to-treat analysis: -43.5%; 95% CI, -100.3 to -2.8 [P = 0.03]; per-protocol analysis: -56.8%; 95% CI, -118.7 to -12.3 [P = 0.008]). CONCLUSIONS: A three-dose vaccination with RTS, S/AS01 was initially protective against clinical malaria, but this result was offset by rebound in later years in areas with higher than-average exposure to malaria parasites.

    AB - BACKGROUND: The candidate malaria vaccine RTS, S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules. METHODS: We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS, S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of>2500 parasites per cubic millimeter). In an analysis that was not prespecified, the malaria exposure of each child was estimated with the use of information on the prevalence of malaria among residents within a 1-km radius of the child's home. Vaccine efficacy was defined as 1 minus the hazard ratio or the incidence-rate ratio, multiplied by 100, in the RTS, S/AS01 group versus the control group. RESULTS: Over 7 years of follow-up, we identified 1002 episodes of clinical malaria among 223 children randomly assigned to the RTS, S/AS01 group and 992 episodes among 224 children randomly assigned to the control group. The vaccine efficacy, as assessed by negative binomial regression, was 4.4% (95% confidence interval [CI], -17.0 to 21.9; P = 0.66) in the intention-to-treat analysis and 7.0% (95% CI, -14.5 to 24.6; P = 0.52) in the per-protocol analysis. Vaccine efficacy waned over time (P = 0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children with higher-than-average exposure to malaria parasites (intention-to-treat analysis: -43.5%; 95% CI, -100.3 to -2.8 [P = 0.03]; per-protocol analysis: -56.8%; 95% CI, -118.7 to -12.3 [P = 0.008]). CONCLUSIONS: A three-dose vaccination with RTS, S/AS01 was initially protective against clinical malaria, but this result was offset by rebound in later years in areas with higher than-average exposure to malaria parasites.

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    U2 - 10.1056/NEJMoa1515257

    DO - 10.1056/NEJMoa1515257

    M3 - Article

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    EP - 2529

    JO - New England Journal of Medicine

    JF - New England Journal of Medicine

    SN - 0028-4793

    IS - 26

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