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, A; Lusingu, J; Leach, A; Lievens, M; Vekemans, J; Msham, S; Lang, T; Gould, J; Dubois, MC; Jongert, E; Vansadia, P; Carter, T; Njuguna, P; Awuondo, KO; Malabeja, A; Abdul, O; Gesase, S; Mturi, N; Drakeley, CJ; Savarese, B; Villafana, T; Lapierre, D; Ballou, WR; Cohen, J; Lemnge, MM; Peshu, N; Marsh, K; Riley, EM; von Seidlein, L; Bejon, P; (2011) 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. The Lancet infectious diseases, 11 (2). pp. 102-109. ISSN 1473-3099 DOI: 10.1016/S1473-3099(10)70262-0

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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 degrees C) and a Plasmodium falciparum density of 2500/pL 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.

Item Type: Article
Keywords: PLASMODIUM-FALCIPARUM INFECTION, DOUBLE-BLIND, DISEASE, SAFETY, Antibodies, Protozoan, blood, Blood, parasitology, Fever, diagnosis, Follow-Up Studies, Humans, Infant, Kenya, Malaria Vaccines, immunology, Malaria, Falciparum, immunology, prevention & control, Protozoan Proteins, immunology, Tanzania
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Malaria Centre
Vaccine Centre
PubMed ID: 21237715
Web of Science ID: 287120500018
URI: http://researchonline.lshtm.ac.uk/id/eprint/1107

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