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
| Autor: | Seth Owusu-Agyei, Peter G. Kremsner, Marc Lievens, Yolanda Guerra Mendoza, Patricia Njuguna, Irving F. Hoffman, Mary J. Hamel, Pauline Akoo, Walter Otieno, Marcel Tanner, Lucas Otieno, Nahya Salim Masoud, Selidji T Agnandji, Miguel A. Lanaspa, Opokua Ofori-Anyinam, Portia Kamthunzi, Elodie Garric, James A. Berkley, Samuel Adjei, Jahit Sacarlal, Lode Schuerman, Seyram Kaali, Ali Mtoro, John Lusingu, Hermann Sorgho, Innocent Valea, Jens-Ulrich Stegmann, Godfrey Allan Otieno, Pascale Vandoolaeghe, Amanda J. Leach, Samwel Gesase, Kephas Otieno, Martina Oneko, Daniel Ansong, Halidou Tinto, Jean-Yves Pirçon, Bertrand Lell, Kwaku Poku Asante, Pedro Aide, Anangisye Malabeja, Tsiri Agbenyega |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Pediatrics Malaria vaccine law.invention 0302 clinical medicine Randomized controlled trial law Immunology and Allergy Medicine 030212 general & internal medicine Malaria Falciparum Children Sub-Saharan Africa Incidence Incidence (epidemiology) Vaccination meningitis 3. Good health Female cerebral malaria RTS S/AS01 vaccine Infants Meningitis Àfrica subsahariana Research Paper safety medicine.medical_specialty Fever Plasmodium falciparum 030231 tropical medicine Immunology Malaria Cerebral Seizures Febrile 03 medical and health sciences Double-Blind Method febrile convulsions Malaria Vaccines parasitic diseases Humans Adverse effect Africa South of the Sahara Immunization Schedule Vacuna de la malària Pharmacology business.industry RTS S Infant medicine.disease Vaccine efficacy (5–10): Malaria business Malaria |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Human Vaccines & Immunotherapeutics Recercat. Dipósit de la Recerca de Catalunya instname |
| ISSN: | 2164-5515 |
| Popis: | 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\xC2\xA0months) and 6537 infants (enrolled at 6-12\xC2\xA0weeks) 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 \xE2\x89\xA42 (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. |
| Databáze: | OpenAIRE |
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