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Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes
Published on: January 16, 2015
Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure
Ally Olotu1, Gregory Fegan, Juliana Wambua
1Centre for Geographic Medicine Research, Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Kilifi, Kenya. aolotu@kemri-wellcome.org
Insights
The RTS,S/AS01E malaria vaccine showed 16.8% efficacy over four years in children. Vaccine effectiveness decreased with time and higher malaria exposure, highlighting the need for ongoing research.
Area of Science:
- Immunology
- Tropical Medicine
- Vaccinology
Background:
- The RTS,S/AS01E malaria vaccine is in phase 3 trials, but long-term outcome data are limited.
- Understanding the sustained efficacy of malaria vaccines is crucial for public health interventions.
Purpose of the Study:
- To evaluate the long-term efficacy and effectiveness of the RTS,S/AS01E malaria vaccine in children.
- To assess how vaccine efficacy changes over time and with varying levels of malaria exposure.
Main Methods:
- A 4-year follow-up study involving children aged 5-17 months, randomly assigned to receive RTS,S/AS01E or a rabies control vaccine.
- Clinical malaria was defined as temperature ≥37.5°C with >2500 parasites/mm³ P. falciparum.
- Malaria exposure was estimated using a distance-weighted local prevalence index.
Main Results:
- Overall vaccine efficacy over 4 years was 16.8% (per-protocol analysis).
- Efficacy declined significantly over time, from 43.6% in year 1 to -0.4% in year 4.
- Vaccine effectiveness was lower in children with higher malaria exposure (15.9%) compared to those with lower exposure (45.1%).
Conclusions:
- The RTS,S/AS01E vaccine demonstrates a modest overall efficacy over a 4-year period.
- Declining efficacy over time and with increased malaria exposure necessitates further investigation into vaccine durability and potential booster strategies.
- Findings underscore the importance of long-term surveillance for malaria vaccine effectiveness.
Background:
The candidate malaria vaccine RTS,S/AS01E has entered phase 3 trials, but data on long-term outcomes are limited.
Methods:
For 4 years, we followed children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of RTS,S/AS01E vaccine (223 children) or rabies vaccine (224 controls). The end point was clinical malaria (temperature of ≥37.5°C and Plasmodium falciparum parasitemia density of >2500 parasites per cubic millimeter). Each child's exposure to malaria was estimated with the use of the distance-weighted local prevalence of malaria.
Results:
Over a period of 4 years, 118 of 223 children who received the RTS,S/AS01E vaccine and 138 of 224 of the controls had at least 1 episode of clinical malaria. Vaccine efficacies in the intention-to-treat and per-protocol analyses were 29.9% (95% confidence interval [CI], 10.3 to 45.3; P=0.005) and 32.1% (95% CI, 11.6 to 47.8; P=0.004), respectively, calculated by Cox regression. Multiple episodes were common, with 551 and 618 malarial episodes in the RTS,S/AS01E and control groups, respectively; vaccine efficacies in the intention-to-treat and per-protocol analyses were 16.8% (95% CI, -8.6 to 36.3; P=0.18) and 24.3% (95% CI, 1.9 to 41.6; P=0.04), respectively, calculated by the Andersen-Gill extension of the Cox model. For every 100 vaccinated children, 65 cases of clinical malaria were averted. Vaccine efficacy declined over time (P=0.004) and with increasing exposure to malaria (P=0.001) in the per-protocol analysis. Vaccine efficacy was 43.6% (95% CI, 15.5 to 62.3) in the first year but was -0.4% (95% CI, -32.1 to 45.3) in the fourth year. Among children with a malaria-exposure index that was average or lower than average, the vaccine efficacy was 45.1% (95% CI, 11.3 to 66.0), but among children with a malaria-exposure index that was higher than average it was 15.9% (95% CI, -11.0 to 36.4).
Conclusions:
The efficacy of RTS,S/AS01E vaccine over the 4-year period was 16.8%. Efficacy declined over time and with increasing malaria exposure. (Funded by the PATH Malaria Vaccine Initiative and Wellcome Trust; ClinicalTrials.gov number, NCT00872963.).
