Abstract
SummaryBackgroundThe phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings.MethodsWe compared four malaria transmission models and their predictions to assess vaccine cost-effectiveness and impact. We used trial data for follow-up of 32 months or longer to parameterise vaccine protection in the group aged 5–17 months. Estimates of cases, deaths, and disability-adjusted life-years (DALYs) averted were calculated over a 15 year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2–10 year olds (PfPR2–10; range 3–65%). We considered two vaccine schedules: three doses at ages 6, 7·5, and 9 months (three-dose schedule, 90% coverage) and including a fourth dose at age 27 months (four-dose schedule, 72% coverage). We estimated cost-effectiveness in the presence of existing malaria interventions for vaccine prices of US$2–10 per dose.FindingsIn regions with a PfPR2–10 of 10–65%, RTS,S/AS01 is predicted to avert a median of 93 940 (range 20 490–126 540) clinical cases and 394 (127–708) deaths for the three-dose schedule, or 116 480 (31 450–160 410) clinical cases and 484 (189–859) deaths for the four-dose schedule, per 100 000 fully vaccinated children. A positive impact is also predicted at a PfPR2–10 of 5–10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR2–10 of 10–65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of $30 (range 18–211) per clinical case averted and $80 (44–279) per DALY averted for the three-dose schedule, and of $25 (16–222) and $87 (48–244), respectively, for the four-dose schedule. Higher ICERs were estimated at low PfPR2–10 levels.InterpretationWe predict a significant public health impact and high cost-effectiveness of the RTS,S/AS01 vaccine across a wide range of settings. Decisions about implementation will need to consider levels of malaria burden, the cost-effectiveness and coverage of other malaria interventions, health priorities, financing, and the capacity of the health system to deliver the vaccine.FundingPATH Malaria Vaccine Initiative; Bill & Melinda Gates Foundation; Global Good Fund; Medical Research Council; UK Department for International Development; GAVI, the Vaccine Alliance; WHO.
Highlights
In the past 15 years, renewed investment in malaria control has led to substantial reductions in malaria worldwide.[1,2] Despite this investment, malaria remains a leading cause of morbidity and mortality.[1]
Model-estimated efficacy generally falls within the confidence intervals of the trial data for both clinical malaria and severe disease
With the four mathematical models and our assumptions about implementation of the vaccine beyond the trial sites, we estimated that the absolute vaccine impact would increase with increasing levels of malaria transmission, averting from 15–32% of all clinical cases at a PfPR2–10 of 10%, to 5–22% of clinical cases at a PfPR2–10 of 65%
Summary
In the past 15 years, renewed investment in malaria control has led to substantial reductions in malaria worldwide.[1,2] Despite this investment, malaria remains a leading cause of morbidity and mortality.[1] Investigators have completed phase 3 testing of the RTS,S/AS01 Plasmodium falciparum vaccine candidate in two age groups at 11 centres in sub-Saharan Africa.[3] Efficacy against clinical malaria was 20·3% (95% CI 13·6–26·5) in infants aged 6–12 weeks and 35·2% (30·5–39·5) in children aged 5–17 months during 32 months of follow-up. Vaccine efficacy against clinical malaria declined over time, from 45·1% (95% CI 41·4–48·7%) during months 0–20 to 16·1% (8·5–23·0%) during months 21–32 in children, and from 27·0% (21·1–32·5). In the group given a fourth dose of vaccine 18 months after the initial course, efficacy against clinical malaria was 43·9% (95% CI 39·7–47·8) in children and 27·8% (21·7–33·4) in infants over 32 months
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