Malaria Transmission Intensity Likely Modifies RTS, S/AS01 Efficacy Due to a Rebound Effect in Ghana, Malawi, and Gabon.
Africa
GIS
geographic information system
malaria
vaccine
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
01 11 2022
01 11 2022
Historique:
received:
20
05
2022
accepted:
26
07
2022
pubmed:
29
7
2022
medline:
4
11
2022
entrez:
28
7
2022
Statut:
ppublish
Résumé
RTS,S/AS01 is the first malaria vaccine to be approved and recommended for widespread implementation by the World Health Organization (WHO). Trials reported lower vaccine efficacies in higher-incidence sites, potentially due to a "rebound" in malaria cases in vaccinated children. When naturally acquired protection in the control group rises and vaccine protection in the vaccinated wanes concurrently, malaria incidence can become greater in the vaccinated than in the control group, resulting in negative vaccine efficacies. Using data from the 2009-2014 phase III trial (NCT00866619) in Lilongwe, Malawi; Kintampo, Ghana; and Lambaréné, Gabon, we evaluate this hypothesis by estimating malaria incidence in each vaccine group over time and in varying transmission settings. After estimating transmission intensities using ecological variables, we fit models with 3-way interactions between vaccination, time, and transmission intensity. Over time, incidence decreased in the control group and increased in the vaccine group. Three-dose efficacy in the lowest-transmission-intensity group (0.25 cases per person-year [CPPY]) decreased from 88.2% to 15.0% over 4.5 years, compared with 81.6% to -27.7% in the highest-transmission-intensity group (3 CPPY). These findings suggest that interventions, including the fourth RTS,S dose, that protect vaccinated individuals during the potential rebound period should be implemented for high-transmission settings.
Sections du résumé
BACKGROUND
RTS,S/AS01 is the first malaria vaccine to be approved and recommended for widespread implementation by the World Health Organization (WHO). Trials reported lower vaccine efficacies in higher-incidence sites, potentially due to a "rebound" in malaria cases in vaccinated children. When naturally acquired protection in the control group rises and vaccine protection in the vaccinated wanes concurrently, malaria incidence can become greater in the vaccinated than in the control group, resulting in negative vaccine efficacies.
METHODS
Using data from the 2009-2014 phase III trial (NCT00866619) in Lilongwe, Malawi; Kintampo, Ghana; and Lambaréné, Gabon, we evaluate this hypothesis by estimating malaria incidence in each vaccine group over time and in varying transmission settings. After estimating transmission intensities using ecological variables, we fit models with 3-way interactions between vaccination, time, and transmission intensity.
RESULTS
Over time, incidence decreased in the control group and increased in the vaccine group. Three-dose efficacy in the lowest-transmission-intensity group (0.25 cases per person-year [CPPY]) decreased from 88.2% to 15.0% over 4.5 years, compared with 81.6% to -27.7% in the highest-transmission-intensity group (3 CPPY).
CONCLUSIONS
These findings suggest that interventions, including the fourth RTS,S dose, that protect vaccinated individuals during the potential rebound period should be implemented for high-transmission settings.
Identifiants
pubmed: 35899811
pii: 6650987
doi: 10.1093/infdis/jiac322
pmc: PMC10205900
doi:
Substances chimiques
Malaria Vaccines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1646-1656Subventions
Organisme : NIAID NIH HHS
ID : K24 AI134990
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137410
Pays : United States
Organisme : NIH HHS
ID : K24AI134990)
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Déclaration de conflit d'intérêts
Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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