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

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• 作者：Dr Melissa A Penny ; PhD^a ; ^b ; ^&dagger ; ; ^{melissa.penny@unibas.ch" class="auth_mail" title="E-mail the corresponding author} ; Robert Verity ; PhD^c ; ^&dagger ; ; Caitlin A Bever ; PhD^d ; ^&dagger ; ; Christophe Sauboin ; MA^e ; ^&dagger ; ; Katya Galactionova ; MA^a ; ^b ; Stefan Flasche ; PhD^f ; Michael T White ; PhD^c ; Edward A Wenger ; PhD^d ; Nicolas Van de Velde ; PhD^e ; Peter Pemberton-Ross ; PhD^a ; ^b ; Jamie T Griffin ; PhD^c ; Prof Thomas A Smith ; PhD^a ; ^b ; Philip A Eckhoff ; PhD^d ; Farzana Muhib ; MPH^g ; Mark Jit ; PhD^f ; ^h ; Prof Azra C Ghani ; PhD^c
• 刊名：The Lancet
• 出版年：2016
• 出版时间：23-29 January 2016
• 年：2016
• 卷：387
• 期：10016
• 页码：367-375
• 全文大小：528 K

文摘

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 (PfPR_2–10; 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 PfPR_2–10 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 PfPR_2–10 of 5–10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR_2–10 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 PfPR_2–10 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.