The candidate malaria vaccine RTS,S/AS01E has entered phase 3 trials, but data on long-term outcomes are limited.
For 4 years, researchers 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 endpoint was clinical malaria ( temperature of greater than or equal to 37.5°C and Plasmodium falciparum parasitemia density of greater than 2500 parasites per cubic millimeter ).
Each child's exposure to malaria was estimated with the use of the distance-weighted local prevalence of malaria.
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% ( P=0.005 ) and 32.1% ( 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% ( P=0.18 ) and 24.3% ( 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% in the first year but was -0.4% in the fourth year.
Among children with a malaria-exposure index that was average or lower than average, the vaccine efficacy was 45.1%, but among children with a malaria-exposure index that was higher than average it was 15.9%.
The study has shown that the efficacy of RTS,S/AS01E vaccine over the 4-year period was 16.8%. Efficacy declined over time and with increasing malaria exposure. ( Xagena )
Olotu A et al, N Engl J Med 2013; 368:1111-1120