 | Yolanda Guerra Mendoza, Elodie Garric, Amanda Leach, Marc Lievens, Opokua Ofori-Anyinam, Jean-Yves Pirc con, Jens-Ulrich Stegmann, Pascale Vandoolaeghe, Lucas Otieno, Walter Otieno, Seth Owusu-Agyei, Jahit Sacarlal, Nahya Salim Masoud, Hermann Sorgho, Marcel Tanner, Halidou Tinto, Innocent Valea, Ali Takadir Mtoro, Patricia Njuguna, Martina Oneko, Godfrey Allan Otieno, Kephas Otieno, Samwel Gesase, Mary J Hamel, Irving Hoffman, Seyram Kaali, Portia Kamthunzi, Peter Kremsner, Miguel Lanaspa, Bertrand Lell, John Lusingu, Anangisye Malabeja, Pedro Aide, Pauline Akoo, Daniel Ansong, Kwaku Poku Asante, James A Berkley, Samuel Adjei, Tsiri Agbenyega, Selidji Todagbe Agnandji, Lode Schuerman 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 (Journal Article) In: Hum. Vaccin. Immunother., vol. 15, no. 10, pp. 2386–2398, 2019, ISSN: 2164-554X 2164-5515. @article{Guerra_Mendoza2019-at,
title = {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},
author = {Yolanda Guerra Mendoza and Elodie Garric and Amanda Leach and Marc Lievens and Opokua Ofori-Anyinam and Jean-Yves Pirc con and Jens-Ulrich Stegmann and Pascale Vandoolaeghe and Lucas Otieno and Walter Otieno and Seth Owusu-Agyei and Jahit Sacarlal and Nahya Salim Masoud and Hermann Sorgho and Marcel Tanner and Halidou Tinto and Innocent Valea and Ali Takadir Mtoro and Patricia Njuguna and Martina Oneko and Godfrey Allan Otieno and Kephas Otieno and Samwel Gesase and Mary J Hamel and Irving Hoffman and Seyram Kaali and Portia Kamthunzi and Peter Kremsner and Miguel Lanaspa and Bertrand Lell and John Lusingu and Anangisye Malabeja and Pedro Aide and Pauline Akoo and Daniel Ansong and Kwaku Poku Asante and James A Berkley and Samuel Adjei and Tsiri Agbenyega and Selidji Todagbe Agnandji and Lode Schuerman},
doi = {10.1080/21645515.2019.1586040},
issn = {2164-554X 2164-5515},
year = {2019},
date = {2019-04-01},
urldate = {2019-04-01},
journal = {Hum. Vaccin. Immunother.},
volume = {15},
number = {10},
pages = {2386--2398},
publisher = {Informa UK Limited},
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 $\leq$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.},
keywords = {(5-10): Malaria; RTS, S/AS01 vaccine; cerebral malaria; febrile convulsions; meningitis; safety},
pubstate = {published},
tppubtype = {article}
}
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 $łeq$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. |
