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Model-based assessment of public health impact and cost-effectiveness of dengue vaccination following screening for prior exposure.

ABSTRACT: The tetravalent dengue vaccine CYD-TDV (Dengvaxia) is the first licensed vaccine against dengue, but recent findings indicate an elevated risk of severe disease among vaccinees without prior dengue virus (DENV) exposure. The World Health Organization currently recommends CYD-TDV only for individuals with serological confirmation of past DENV exposure. Our objective was to evaluate the potential health impact and cost-effectiveness of vaccination following serological screening. To do so, we used an agent-based model to simulate DENV transmission with and without vaccination over a 10-year timeframe. Across a range of values for the proportion of vaccinees with prior DENV exposure, we projected the proportion of symptomatic and hospitalized cases averted as a function of the sensitivity and specificity of serological screening. Scenarios about the cost-effectiveness of screening and vaccination were chosen to be representative of Brazil and the Philippines. We found that public health impact depended primarily on sensitivity in high-transmission settings and on specificity in low-transmission settings. Cost-effectiveness could be achievable from the perspective of a public payer provided that sensitivity and the value of a disability-adjusted life-year were both high, but only in high-transmission settings. Requirements for reducing relative risk and achieving cost-effectiveness from an individual perspective were more restricted, due to the fact that those who test negative pay for screening but receive no benefit. Our results predict that cost-effectiveness could be achieved only in high-transmission areas of dengue-endemic countries with a relatively high per capita GDP, such as Panamá (13,680 USD), Brazil (8,649 USD), México (8,201 USD), or Thailand (5,807 USD). In conclusion, vaccination with CYD-TDV following serological screening could have a positive impact in some high-transmission settings, provided that screening is highly specific (to minimize individual harm), at least moderately sensitive (to maximize population benefit), and sufficiently inexpensive (depending on the setting).

SUBMITTER: Espana G

PROVIDER: S-EPMC6625736 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Model-based assessment of public health impact and cost-effectiveness of dengue vaccination following screening for prior exposure.

España Guido G Yao Yutong Y Anderson Kathryn B KB Fitzpatrick Meagan C MC Smith David L DL Morrison Amy C AC Wilder-Smith Annelies A Scott Thomas W TW Perkins T Alex TA

PLoS neglected tropical diseases 20190701 7

The tetravalent dengue vaccine CYD-TDV (Dengvaxia) is the first licensed vaccine against dengue, but recent findings indicate an elevated risk of severe disease among vaccinees without prior dengue virus (DENV) exposure. The World Health Organization currently recommends CYD-TDV only for individuals with serological confirmation of past DENV exposure. Our objective was to evaluate the potential health impact and cost-effectiveness of vaccination following serological screening. To do so, we used ...[more]

PMID: 31260441

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Project description:BACKGROUND:Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine. METHODS AND FINDINGS:The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ? 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34%) and in high-transmission settings (SP9 ? 70%) by 13%-25% (all simulations: 10%- 34%). These endemicity levels are representative of the participating sites in both Phase III trials. In contrast, in settings with low transmission intensity (SP9 ? 30%), the models predicted that vaccination could lead to a substantial increase in hospitalisation because of dengue. Modelling reduced vaccine coverage or the addition of catch-up campaigns showed that the impact of vaccination scaled approximately linearly with the number of people vaccinated. In assessing the optimal age of vaccination, we found that targeting older children could increase the net benefit of vaccination in settings with moderate transmission intensity (SP9 = 50%). Overall, vaccination was predicted to be potentially cost-effective in most endemic settings if priced competitively. The results are based on the assumption that the vaccine acts similarly to natural infection. This assumption is consistent with the available trial results but cannot be directly validated in the absence of additional data. Furthermore, uncertainties remain regarding the level of protection provided against disease versus infection and the rate at which vaccine-induced protection declines. CONCLUSIONS:Dengvaxia has the potential to reduce the burden of dengue disease in areas of moderate to high dengue endemicity. However, the potential risks of vaccination in areas with limited exposure to dengue as well as the local costs and benefits of routine vaccination are important considerations for the inclusion of Dengvaxia into existing immunisation programmes. These results were important inputs into WHO global policy for use of this licensed dengue vaccine.

Project description:ObjectiveAccording to the third cancer plan, organised screening (OS) of cervical cancer (CC) among women aged 25-65 years should be implemented in France in the forthcoming years. The most efficient way to implement OS in the French healthcare system is yet to be determined.MethodsA microsimulation model was developed adopting a collective 'all payers' perspective. A closed cohort of women eligible for CC screening and representative in terms of age and participation in individual screening (IndScr) by annual Papanicolaou (Pap) testing every 3 years was modelled on a lifetime horizon. Different OS strategies, additive to IndScr with a 61.9% participation rate based on mailed invitations to non-participant women to perform OS were assessed. Similar modalities were applied to OS and IndScr participants. Strategies implied different screening tests (Papanicolaou (Pap) test, human papillomavirus (HPV) test and p16/Ki67 double staining) and OS periodicity.ResultsCompared with IndScr only, all OS strategies were associated with decreased cancer incidence/mortality (from 14.2%/13.5% to 22.9%/25.8%). Most strategies generated extra costs ranging from €37.9 to €1607 per eligible woman. HPV testing every 10 and 5 years were cost saving. HPV tests every 10 and 5 years were the most efficient strategies, generating more survival at lower costs than Pap-based strategies. Compared to IndScr only, an HPV test every 10 years was cost saving. The most effective strategies were p16/Ki67 as primary or HPV positive confirmation tests, with respective incremental cost-effectiveness ratios of €6 541 250 and €101 391 per life year. Pap-based strategies generated intermediary results.ConclusionOS strategies based on the HPV test appear highly efficient. However, our results rely on the assumption that women and practitioners comply with the recommended OS periodicities (3, 5, 10 years). Implementing these OS modalities will require major adaptations to the current CC screening organisation. Pap test-based strategies might be simpler to setup while preparing an appropriate implementation of more efficient OS screening modalities.

Dataset Information

Model-based assessment of public health impact and cost-effectiveness of dengue vaccination following screening for prior exposure.

Publications

Model-based assessment of public health impact and cost-effectiveness of dengue vaccination following screening for prior exposure.

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