Public health impact and cost effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models
Summary 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 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. 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.
The Lancet