Abstract
Background: RTS,S/AS01E is the lead candidate malaria vaccine. We recently showed efficacy against clinical falciparum malaria in 5–17 month old children, during an average of 8 months follow-up. We aimed to assess the efficacy of RTS,S/AS01E during 15 months of follow-up.
Methods: Between March, 2007, and October, 2008, we enrolled healthy children aged 5–17 months in Kilifi, Kenya, and Korogwe, Tanzania. Computer-generated block randomisation was used to randomly assign participants (1:1) to receive three doses (at month 0, 1, and 2) of either RTS,S/AS01E or human diploid-cell rabies vaccine. The primary endpoint was time to first clinical malaria episode, defined as the presence of fever (temperature ≥37·5°C) and a Plasmodium falciparum density of 2500/μL or more. Follow-up was 12 months for children from Korogwe and 15 months for children from Kilifi. Primary analysis was per protocol. In a post-hoc modelling analysis we characterised the associations between anti-circumsporozoite antibodies and protection against clinical malaria episodes. This study is registered with ClinicalTrials.gov, number NCT00380393.
Findings: 894 children were assigned, 447 in each treatment group. In the per-protocol analysis, 82 of 415 children in the RTS,S/AS01E group and 125 of 420 in the rabies vaccine group had first or only clinical malaria episode by 12 months, vaccine efficacy 39·2% (95% CI 19·5–54·1, p=0·0005). At 15 months follow-up, 58 of 209 children in the RTS,S/AS01E group and 85 of 206 in the rabies vaccine group had first or only clinical malaria episode, vaccine efficacy 45·8% (24·1–61·3, p=0·0004). At 12 months after the third dose, anti-circumsporozoite antibody titre data were available for 390 children in the RTS,S/AS01E group and 391 in the rabies group. A mean of 15 months (range 12–18 months) data were available for 172 children in the RTS,S/AS01E group and 155 in the rabies group. These titres at 1 month after the third dose were not associated with protection, but titres at 6·5 months were. The level of protection increased abruptly over a narrow range of antibody concentrations. The most common adverse events were pneumonia, febrile convulsion, gastroenteritis, and P falciparum malaria.
Interpretation: RTS,S/AS01E confers sustained efficacy for at least 15 months and shows promise as a potential public health intervention against childhood malaria in malaria endemic countries.
| Original language | English |
|---|---|
| Pages (from-to) | 961-966 |
| Number of pages | 6 |
| Journal | Lancet Infectious Diseases |
| Volume | 11 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2011 |
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Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania : a randomised controlled trial. / Olotu, Ally; Lusingu, John; Leach, Amanda; Lievens, Marc; Vekemans, Johan; msham, Salum; Lang, Trudie; Gould, Jayne; Dubois, Marie-Claude; Jongert, Erik; vansadia, Preeti; Carter, Terrell; Njuguna, Patricia; O Awuondo, Ken; Malabeja, Anangisye; Abdul, Omar; Gesase, Samwel; Mturi, Neema; Drakeley, Chris; Savarese, Barbara; Villafana, Tonya; Lapierre, Didier; Ballou, Ripley; Cohen, Joe; Lemnge, Martha; Peshu, Norbert; Marsh, Kevin; Riley, Eleanor; Von Seidlein, Lorenz; Bejon, Phillip.
In: Lancet Infectious Diseases, Vol. 11, No. 2, 2011, p. 961-966.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania
T2 - a randomised controlled trial
AU - Olotu, Ally
AU - Lusingu, John
AU - Leach, Amanda
AU - Lievens, Marc
AU - Vekemans, Johan
AU - msham, Salum
AU - Lang, Trudie
AU - Gould, Jayne
AU - Dubois, Marie-Claude
AU - Jongert, Erik
AU - vansadia, Preeti
AU - Carter, Terrell
AU - Njuguna, Patricia
AU - O Awuondo, Ken
AU - Malabeja, Anangisye
AU - Abdul, Omar
AU - Gesase, Samwel
AU - Mturi, Neema
AU - Drakeley, Chris
AU - Savarese, Barbara
AU - Villafana, Tonya
AU - Lapierre, Didier
AU - Ballou, Ripley
AU - Cohen, Joe
AU - Lemnge, Martha
AU - Peshu, Norbert
AU - Marsh, Kevin
AU - Riley, Eleanor
AU - Von Seidlein, Lorenz
AU - Bejon, Phillip
PY - 2011
Y1 - 2011
N2 - Background: RTS,S/AS01E is the lead candidate malaria vaccine. We recently showed efficacy against clinical falciparum malaria in 5–17 month old children, during an average of 8 months follow-up. We aimed to assess the efficacy of RTS,S/AS01E during 15 months of follow-up. Methods: Between March, 2007, and October, 2008, we enrolled healthy children aged 5–17 months in Kilifi, Kenya, and Korogwe, Tanzania. Computer-generated block randomisation was used to randomly assign participants (1:1) to receive three doses (at month 0, 1, and 2) of either RTS,S/AS01E or human diploid-cell rabies vaccine. The primary endpoint was time to first clinical malaria episode, defined as the presence of fever (temperature ≥37·5°C) and a Plasmodium falciparum density of 2500/μL or more. Follow-up was 12 months for children from Korogwe and 15 months for children from Kilifi. Primary analysis was per protocol. In a post-hoc modelling analysis we characterised the associations between anti-circumsporozoite antibodies and protection against clinical malaria episodes. This study is registered with ClinicalTrials.gov, number NCT00380393. Findings: 894 children were assigned, 447 in each treatment group. In the per-protocol analysis, 82 of 415 children in the RTS,S/AS01E group and 125 of 420 in the rabies vaccine group had first or only clinical malaria episode by 12 months, vaccine efficacy 39·2% (95% CI 19·5–54·1, p=0·0005). At 15 months follow-up, 58 of 209 children in the RTS,S/AS01E group and 85 of 206 in the rabies vaccine group had first or only clinical malaria episode, vaccine efficacy 45·8% (24·1–61·3, p=0·0004). At 12 months after the third dose, anti-circumsporozoite antibody titre data were available for 390 children in the RTS,S/AS01E group and 391 in the rabies group. A mean of 15 months (range 12–18 months) data were available for 172 children in the RTS,S/AS01E group and 155 in the rabies group. These titres at 1 month after the third dose were not associated with protection, but titres at 6·5 months were. The level of protection increased abruptly over a narrow range of antibody concentrations. The most common adverse events were pneumonia, febrile convulsion, gastroenteritis, and P falciparum malaria. Interpretation: RTS,S/AS01E confers sustained efficacy for at least 15 months and shows promise as a potential public health intervention against childhood malaria in malaria endemic countries.
AB - Background: RTS,S/AS01E is the lead candidate malaria vaccine. We recently showed efficacy against clinical falciparum malaria in 5–17 month old children, during an average of 8 months follow-up. We aimed to assess the efficacy of RTS,S/AS01E during 15 months of follow-up. Methods: Between March, 2007, and October, 2008, we enrolled healthy children aged 5–17 months in Kilifi, Kenya, and Korogwe, Tanzania. Computer-generated block randomisation was used to randomly assign participants (1:1) to receive three doses (at month 0, 1, and 2) of either RTS,S/AS01E or human diploid-cell rabies vaccine. The primary endpoint was time to first clinical malaria episode, defined as the presence of fever (temperature ≥37·5°C) and a Plasmodium falciparum density of 2500/μL or more. Follow-up was 12 months for children from Korogwe and 15 months for children from Kilifi. Primary analysis was per protocol. In a post-hoc modelling analysis we characterised the associations between anti-circumsporozoite antibodies and protection against clinical malaria episodes. This study is registered with ClinicalTrials.gov, number NCT00380393. Findings: 894 children were assigned, 447 in each treatment group. In the per-protocol analysis, 82 of 415 children in the RTS,S/AS01E group and 125 of 420 in the rabies vaccine group had first or only clinical malaria episode by 12 months, vaccine efficacy 39·2% (95% CI 19·5–54·1, p=0·0005). At 15 months follow-up, 58 of 209 children in the RTS,S/AS01E group and 85 of 206 in the rabies vaccine group had first or only clinical malaria episode, vaccine efficacy 45·8% (24·1–61·3, p=0·0004). At 12 months after the third dose, anti-circumsporozoite antibody titre data were available for 390 children in the RTS,S/AS01E group and 391 in the rabies group. A mean of 15 months (range 12–18 months) data were available for 172 children in the RTS,S/AS01E group and 155 in the rabies group. These titres at 1 month after the third dose were not associated with protection, but titres at 6·5 months were. The level of protection increased abruptly over a narrow range of antibody concentrations. The most common adverse events were pneumonia, febrile convulsion, gastroenteritis, and P falciparum malaria. Interpretation: RTS,S/AS01E confers sustained efficacy for at least 15 months and shows promise as a potential public health intervention against childhood malaria in malaria endemic countries.
KW - malaria vaccine
KW - rabies vaccine
KW - antibody titer
KW - article
KW - body temperature
KW - child
KW - childhood disease
KW - controlled study
KW - disease association
KW - double blind procedure
KW - drug efficacy
KW - febrile convulsion
KW - fever
KW - follow up
KW - gastroenteritis
KW - human
KW - infant
KW - Kenya
KW - major clinical study
KW - malaria
KW - malaria falciparum
KW - Plasmodium falciparum
KW - pneumonia
KW - preschool child
KW - priority journal
KW - randomized controlled trial
KW - sporozoite
KW - Tanzania
KW - Antibodies, Protozoan
KW - Blood
KW - Fever
KW - Follow-Up Studies
KW - Humans
KW - Infant
KW - Malaria Vaccines
KW - Malaria, Falciparum
KW - Protozoan Proteins
U2 - 10.1016/S1473-3099(10)70262-0
DO - 10.1016/S1473-3099(10)70262-0
M3 - Article
VL - 11
SP - 961
EP - 966
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
SN - 1473-3099
IS - 2
ER -