Malaria Transmission Intensity Likely Modifies RTS, S/AS01 Efficacy Due to a Rebound Effect in Ghana, Malawi, and Gabon.

Autor:	Bell GJ; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA., Goel V; Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina, USA., Essone P; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon., Dosoo D; Kintampo Health Research Centre, Kintampo, Ghana., Adu B; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Mensah BA; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Gyaase S; Kintampo Health Research Centre, Kintampo, Ghana., Wiru K; Kintampo Health Research Centre, Kintampo, Ghana., Mougeni F; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon., Osei M; Kintampo Health Research Centre, Kintampo, Ghana., Minsoko P; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon., Sinai C; Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina, USA., Niaré K; Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA., Juliano JJ; Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA., Hudgens M; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA., Ghansah A; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Kamthunzi P; University of North Carolina Project, Lilongwe, Malawi., Mvalo T; University of North Carolina Project, Lilongwe, Malawi., Agnandji ST; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.; Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany., Bailey JA; Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA., Asante KP; Kintampo Health Research Centre, Kintampo, Ghana., Emch M; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.; Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2022 Nov 01; Vol. 226 (9), pp. 1646-1656.
DOI:	10.1093/infdis/jiac322
Abstrakt:	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. Competing Interests: 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. (© 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.)
Databáze:	MEDLINE
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