Details

Autor(en) / Beteiligte

• Olotu, Ally, Dr
• Lusingu, John, PhD
• Leach, Amanda, MRCPCH
• Lievens, Marc, MSc
• Vekemans, Johan, PhD
• Msham, Salum, MD
• Lang, Trudie, PhD
• Gould, Jayne, PhD
• Dubois, Marie-Claude, MSc
• Jongert, Erik, PhD
• Vansadia, Preeti, MHS
• Carter, Terrell, MHS
• Njuguna, Patricia, MMeD
• Awuondo, Ken O, HND
• Malabeja, Anangisye, MD
• Abdul, Omar, MD
• Gesase, Samwel, MD
• Mturi, Neema, MRCPaed
• Drakeley, Chris J, PhD
• Savarese, Barbara, RN
• Villafana, Tonya, PhD
• Lapierre, Didier, PhD
• Ballou, W Ripley, MD
• Cohen, Joe, PhD
• Lemnge, Martha M, PhD
• Peshu, Norbert, MBChB
• Marsh, Kevin, FRCP
• Riley, Eleanor M, PhD
• von Seidlein, Lorenz, PhD
• Bejon, Philip, PhD

Titel

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

Ist Teil von

• The Lancet infectious diseases, 2011-02, Vol.11 (2), p.102-109

Ort / Verlag

London: Elsevier Ltd

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Summary 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. Funding PATH Malaria Vaccine Initiative (MVI), GlaxoSmithKline.