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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

Guerra Mendoza, Yolanda and Garric, Elodie and Leach, Amanda and Lievens, Marc and Ofori-Anyinam, Opokua and Pirçon, Jean-Yves and Stegmann, Jens-Ulrich and Vandoolaeghe, Pascale and Otieno, Lucas and Otieno, Walter and Owusu-Agyei, Seth and Sacarlal, Jahit and Masoud, Nahya Salim and Sorgho, Hermann and Tanner, Marcel and Tinto, Halidou and Valea, Innocent and Mtoro, Ali Takadir and Njuguna, Patricia and Oneko, Martina and Otieno, Godfrey Allan and Otieno, Kephas and Gesase, Samwel and Hamel, Mary J. and Hoffman, Irving and Kaali, Seyram and Kamthunzi, Portia and Kremsner, Peter and Lanaspa, Miguel and Lell, Bertrand and Lusingu, John and Malabeja, Anangisye and Aide, Pedro and Akoo, Pauline and Ansong, Daniel and Asante, Kwaku Poku and Berkley, James A. and Adjei, Samuel and Agbenyega, Tsiri and Agnandji, Selidji Todagbe and 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.

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Malaria Vaccines (Tanner)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Health Interventions > Malaria Vaccines (Tanner)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Tanner, Marcel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Landes Bioscience
ISSN:2164-554X
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:02 Dec 2019 10:52
Deposited On:02 Dec 2019 10:52

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