Guerra Mendoza, Yolanda; Garric, Elodie; Leach, Amanda; Lievens, Marc; Ofori-Anyinam, Opokua; Pirçon, Jean-Yves; Stegmann, Jens-Ulrich; Vandoolaeghe, Pascale; Otieno, Lucas; Otieno, Walter; +31 more... Owusu-Agyei, Seth; Sacarlal, Jahit; Masoud, Nahya Salim; Sorgho, Hermann; Tanner, Marcel; Tinto, Halidou; Valea, Innocent; Mtoro, Ali Takadir; Njuguna, Patricia; Oneko, Martina; Otieno, Godfrey Allan; Otieno, Kephas; Gesase, Samwel; Hamel, Mary J; Hoffman, Irving; Kaali, Seyram; Kamthunzi, Portia; Kremsner, Peter; Lanaspa, Miguel; Lell, Bertrand; Lusingu, John; Malabeja, Anangisye; Aide, Pedro; Akoo, Pauline; Ansong, Daniel; Asante, Kwaku Poku; Berkley, James A; Adjei, Samuel; Agbenyega, Tsiri; Agnandji, Selidji Todagbe; Schuerman, Lode; (2019) Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa. Human vaccines & immunotherapeutics, 15 (10). pp. 2386-2398. ISSN 2164-5515 DOI: https://doi.org/10.1080/21645515.2019.1586040
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Abstract
A phase III, double-blind, randomized, controlled trial (NCT00866619) in sub-Saharan Africa showed RTS,S/AS01 vaccine efficacy against malaria. We now present in-depth safety results from this study. 8922 children (enrolled at 5-17 months) and 6537 infants (enrolled at 6-12 weeks) were 1:1:1-randomized to receive 4 doses of RTS,S/AS01 (R3R) or non-malaria control vaccine (C3C), or 3 RTS,S/AS01 doses plus control (R3C). Aggregate safety data were reviewed by a multi-functional team. Severe malaria with Blantyre Coma Score ≤2 (cerebral malaria [CM]) and gender-specific mortality were assessed post-hoc. Serious adverse event (SAE) and fatal SAE incidences throughout the study were 24.2%-28.4% and 1.5%-2.5%, respectively across groups; 0.0%-0.3% of participants reported vaccination-related SAEs. The incidence of febrile convulsions in children was higher during the first 2-3 days post-vaccination with RTS,S/AS01 than with control vaccine, consistent with the time window of post-vaccination febrile reactions in this study (mostly the day after vaccination). A statistically significant numerical imbalance was observed for meningitis cases in children (R3R: 11, R3C: 10, C3C: 1) but not in infants. CM cases were more frequent in RTS,S/AS01-vaccinated children (R3R: 19, R3C: 24, C3C: 10) but not in infants. All-cause mortality was higher in RTS,S/AS01-vaccinated versus control girls (2.4% vs 1.3%, all ages) in our setting with low overall mortality. The observed meningitis and CM signals are considered likely chance findings, that - given their severity - warrant further evaluation in phase IV studies and WHO-led pilot implementation programs to establish the RTS,S/AS01 benefit-risk profile in real-life settings.
Item Type | Article |
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Faculty and Department |
Faculty of Infectious and Tropical Diseases > Dept of Disease Control Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
PubMed ID | 31012786 |
Elements ID | 128034 |
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Filename: Safety profile of the RTSS-AS01 malaria vaccine in infants and children_Additional data from a phase III randomized controlled trial in sub-Saharan Africa.pdf
Licence: Creative Commons: Attribution 3.0
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