Abstract
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 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 language | English |
|---|---|
| Pages (from-to) | 367-375 |
| Number of pages | 9 |
| Journal | The Lancet |
| Volume | 387 |
| Issue number | 10016 |
| DOIs | |
| Publication status | Published - 23 Jan 2016 |
Bibliographical note
Funding Information:Imperial College London and Swiss Tropical and Public Health Institute received funding from the PATH Malaria Vaccine Initiative and the Bill & Melinda Gates Foundation. Work done by the Institute for Disease Modeling was funded by the Global Good Fund of Bellevue, WA, USA. The London School of Hygiene & Tropical Medicine (SF, MJ) received funding from WHO and GAVI, the Vaccine Alliance. Imperial College London received additional fellowship (JTG, MTW) and centre (ACG) funding from the Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID concordat agreement. No funding was provided by GlaxoSmithKline Biologicals SA to the non-GSK modelling groups or the comparison process as a whole. We thank Vasee Moorthy and Raymond Hutubessy (WHO, Geneva, Switzerland) for their role in bringing this consortium together and initiating the work outlined in this report; members of the WHO Joint Technical Expert Group on malaria vaccine modelling subgroup for their constructive comments; and Alison Reynolds for her support in undertaking this work. Calculations for OpenMalaria were done at the Centre for Scientifi c Computing (sciCORE) at the University of Basel, Switzerland, and we thank the many volunteers who made their computers available via www.malariacontrol.net for the simulations.
Funding Information:
Imperial College London and Swiss Tropical and Public Health Institute received funding from the PATH Malaria Vaccine Initiative and the Bill & Melinda Gates Foundation. Work done by the Institute for Disease Modeling was funded by the Global Good Fund of Bellevue, WA, USA. The London School of Hygiene & Tropical Medicine (SF, MJ) received funding from WHO and GAVI, the Vaccine Alliance. Imperial College London received additional fellowship (JTG, MTW) and centre (ACG) funding from the Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID concordat agreement. No funding was provided by GlaxoSmithKline Biologicals SA to the non-GSK modelling groups or the comparison process as a whole. We thank Vasee Moorthy and Raymond Hutubessy (WHO, Geneva, Switzerland) for their role in bringing this consortium together and initiating the work outlined in this report; members of the WHO Joint Technical Expert Group on malaria vaccine modelling subgroup for their constructive comments; and Alison Reynolds for her support in undertaking this work. Calculations for OpenMalaria were done at the Centre for Scientific Computing (sciCORE) at the University of Basel, Switzerland, and we thank the many volunteers who made their computers available via www.malariacontrol.net for the simulations.
Publisher Copyright:
© 2016 Penny et al. Open Access article distributed under the terms of CC BY.
