Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: A systematic comparison of predictions from four mathematical models

Melissa A. Penny, Robert Verity, Caitlin A. Bever, Christophe Sauboin, Katya Galactionova, Stefan Flasche, Michael T. White, Edward A. Wenger, Nicolas Van De Velde, Peter Pemberton-Ross, Jamie T. Griffin, Thomas A. Smith, Philip A. Eckhoff, Farzana Muhib, Mark Jit, Azra C. Ghani

Research output: Contribution to journalArticlepeer-review

135 Citations (Scopus)


Background: The 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. Methods: We 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. Findings: In regions with a PfPR2-10 of 10-65%, RTS,S/AS01 is predicted to avert a median of 93940 (range 20490-126540) clinical cases and 394 (127-708) deaths for the three-dose schedule, or 116480 (31450-160410) clinical cases and 484 (189-859) deaths for the four-dose schedule, per 100000 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. Interpretation: We 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. Funding PATH Malaria Vaccine Initiative; Bill & Melinda Gates Foundation; Global Good Fund; Medical Research Council; UK Department for International Development; GAVI, the Vaccine Alliance; WHO.

Original languageEnglish
Pages (from-to)367-375
Number of pages9
JournalThe Lancet
Issue number10016
Publication statusPublished - 23 Jan 2016
Externally publishedYes


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