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

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.

Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics

“…On the horizon, there are ways to use drugs and diagnostics in innovative campaigns to clear the human infectious reservoir (31), potential rollout of vaccines (32), coverage increases with existing tools (2), and more, which could get closer to elimination. However, it will require high levels of effort and funding just to maintain current gains, and the spread of pyrethroid resistance in mosquito vectors across much of Africa raises the question as to whether some of these achieved gains may in fact be reversed (33).…”

The RTS,S/AS01 malaria vaccine in children 5 to 17 months of age at first vaccination

“…Four independent groups developed mathematical models to estimate the public health impact and cost-effectiveness of RTS,S/AS01 [47]. Data from the phase III trial were used to parametrize the models.…”

“…In addition, public health impact modeling predicts that an important number of clinical and severe malaria cases and malaria deaths may be prevented by RTS,S/AS01, especially in moderate-to-high malaria transmission settings across sub-Saharan Africa. Four different models estimated that, over a 15-year time horizon, on average 1 death and approximately 230 clinical malaria cases might be prevented for every 200 children vaccinated with 4 doses of RTS,S/AS01 if implemented in regions with a P. falciparum parasitemia prevalence of 10% or more [47]. At a vaccine price of US$5 per dose, the cost per disability-adjusted life-year averted in these areas of moderate-to-high P. falciparum prevalence would be less than $100, an amount comparable to that of other malaria control measures [47].…”

“…Four different models estimated that, over a 15-year time horizon, on average 1 death and approximately 230 clinical malaria cases might be prevented for every 200 children vaccinated with 4 doses of RTS,S/AS01 if implemented in regions with a P. falciparum parasitemia prevalence of 10% or more [47]. At a vaccine price of US$5 per dose, the cost per disability-adjusted life-year averted in these areas of moderate-to-high P. falciparum prevalence would be less than $100, an amount comparable to that of other malaria control measures [47]. Whether further additional vaccine doses could extend duration of VE and increase the number of malaria cases averted still needs to be determined.…”

Assessing dengue vaccination impact: Model challenges and future directions

“…For instance, WHO is advised by the Strategic Advisory Group of Experts (SAGE) on Immunization to make global vaccine-related recommendations, with input from models that have been appraised by its advisory committee, the Immunization and Vaccines related Implementation Research Advisory Committee (IVIR-AC). Recently, the outputs of a coordinated mathematical model comparison of the potential impact of the RTS, S malaria vaccine were used in the decision-making process for WHO recommendations on the use of this vaccine [13,14]. The modelling revealed that despite the overall low efficacy, the vaccine could have a substantial additional public health impact across a broad range of settings representative of malaria parasite prevalence in Africa in the presence of other ongoing interventions.…”