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

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Citation

Bell, Griffin J.; Goel, Varun; Essone, Paulin; Dosoo, David; Adu, Bright; Mensah, Benedicta A.; Gyaase, Stephaney; Wiru, Kenneth; Mougeni, Fabrice; & Osei, Musah, et al. (2022). Malaria Transmission Intensity Likely Modifies RTS, S/AS01 Efficacy Due to a Rebound Effect in Ghana, Malawi, and Gabon. Journal of Infectious Diseases, 226(9), 1646-1656. PMCID: PMC10205900

Abstract

BACKGROUND: RTS, S/AS01 is the first malaria vaccine to be approved and recommended for widespread implementation by 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 three-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 CPPY) decreased from 88.02% to 14.55% over 4.5 years, compared to 81.54% to -27.48% in the highest transmission group (3 CPPY).
DISCUSSION: These findings suggest that interventions, including the fourth RTS, S dose, which protect vaccinated individuals during the potential rebound period should be implemented for high transmission settings.

URL

http://dx.doi.org/10.1093/infdis/jiac322

Reference Type

Journal Article

Year Published

2022

Journal Title

Journal of Infectious Diseases

Author(s)

Bell, Griffin J.
Goel, Varun
Essone, Paulin
Dosoo, David
Adu, Bright
Mensah, Benedicta A.
Gyaase, Stephaney
Wiru, Kenneth
Mougeni, Fabrice
Osei, Musah
Minsoko, Pamela
Sinai, Cyrus
Niaré, Karamoko
Juliano, Jonathan J.
Hudgens, Michael G.
Ghansah, Anita
Kamthunzi, Portia
Mvalo, Tisungane
Agnandji, Selidji T.
Bailey, Jeffrey A.
Asante, Kwaku P.
Emch, Michael E.

Article Type

Regular

PMCID

PMC10205900

Continent/Country

Lilongwe
Malawi
Kintampo
Ghana
Lambaréné
Gabon

ORCiD

Sinai - 0000-0003-4585-9575
Goel - 0000-0002-2933-427X
Emch - 0000-0003-2642-965X
Bell, G - 0000-0003-4367-135X