This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features!
Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log in
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Jan 23;387(10016):367-375.
doi: 10.1016/S0140-6736(15)00725-4. Epub 2015 Nov 6.

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

Affiliations

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 et al. Lancet. .

Abstract

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 US2ドル-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ドル per dose and a PfPR2-10 of 10-65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of 30ドル (range 18-211) per clinical case averted and 80ドル (44-279) per DALY averted for the three-dose schedule, and of 25ドル (16-222) and 87ドル (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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Observed and model-predicted vaccine efficacy against clinical and severe malaria from month 0 to study end (≥32 months) by study site in the 5–17 month age category Vaccine efficacy against all episodes of clinical malaria (primary case definition) in the three-dose group (A) and the four-dose group (B), and against severe malaria (primary case definition) in the three-dose group (C) and the four-dose group (D). Error bars show 95% CIs estimated from the trial data. *Intention-to-treat analysis.
Figure 2
Figure 2
Model predictions of clinical cases and deaths averted per 100 000 children fully vaccinated with a three-dose or four-dose immunisation schedule for a range of baseline PfPR2–10 levels Results for the three-dose (A, C) and four-dose (B, D) schedules are cumulative following 15 years of routine use of RTS,S. Bars show median estimates and error bars show 95% credible intervals. Negative cases averted at low transmission are due to stochastic variation between model runs at low prevalence, rather than to any modelled biological mechanism. PfPR2–10=parasite prevalence in 2–10 year olds.
Figure 3
Figure 3
Clinical cases averted in the vaccinated cohort at low (A) and high (B) endemicity after 15 years of routine use of RTS,S in a four-dose immunisation schedule Bars show median predictions over all four models and error bars show the range of predictions. Uncertainty within each model is not shown (see appendix pp 5–7). PfPR2–10=parasite prevalence in 2–10 year olds.
Figure 4
Figure 4
Cost per clinical case or DALY averted as a function of baseline parasite prevalence in 2–10 year olds (PfPR2–10) Results assume a vaccine price of 2ドル (A, D), 5ドル (B, E), or 10ドル (C, E) per dose. Solid lines represent a three-dose immunisation schedule and dashed lines represent a four-dose immunisation schedule. Similar estimates of incremental cost-effectiveness ratios were obtained for the three-dose and four-dose schedules because the additional public health benefit of the boosted schedule is offset by the incremental cost of implementation of the additional dose. Uncertainty estimates surrounding the models' predictions are omitted for readability but overlap. DALY=disability-adjusted life-year.

Comment in

References

    1. WHO . World malaria report 2013. World Health Organization; Geneva: 2014.
    1. Bhatt S, Weiss DJ, Cameron E. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature. 2015;526:207–211. - PMC - PubMed
    1. RTSS Clinical Trials Partnership Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet. 2015;386:31–45. - PMC - PubMed
    1. Patil AP, Okiro EA, Gething PW. Defining the relationship between Plasmodium falciparum parasite rate and clinical disease: statistical models for disease burden estimation. Malar J. 2009;8:186. - PMC - PubMed
    1. Hamel MJ, Oneko M, Williamson J. A marked reduction in mortality among participants in a clinical trial that removed barriers to care and implemented national case management guidelines. 63rd Annual meeting of the American Society of Tropical Medicine and Hygiene; New Orleans, LA; Nov 2–6, 2014. 631 (abstr).

Publication types

Substances

Full text links
Elsevier Science full text link Elsevier Science Free PMC article
Cite

AltStyle によって変換されたページ (->オリジナル) /