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).

Fig 1

Cumulative proportion of cases averted (colors) over a 10-year period (top: symptomatic, bottom: hospitalized) as a function of the sensitivity (y-axis) and specificity (x-axis) of serological screening. Each column shows results for a given transmission setting, defined by the proportion of nine-year-olds with previous DENV exposure, PE₉. Relationships at lower values of PE₉ were less smooth, due to a larger influence of stochasticity and more uncertainty in these transmission settings (S2 Fig). The strategy of vaccination without screening is represented in the top-left corner of each heatmap (sensitivity = 1, specificity = 0).

Fig 2

Per capita relative risk (colors) of symptomatic (top) and hospitalized (bottom) disease over a 10-year horizon in the first cohort of children who are screened (and, in the event of a positive result, vaccinated) as a function of the sensitivity (y-axis) and specificity (x-axis) of serological screening. Each column shows these results in a given transmission setting, defined by the proportion of nine-year-olds with previous DENV exposure, PE₉. The strategy of vaccination without screening is represented in the top-left corner of each heatmap (sensitivity = 1, specificity = 0).

Fig 3. Threshold cost of serological screening from a public payer perspective, assuming a vaccination cost of 69 USD and economic assumptions from Brazil.

Threshold costs are indicated by color as a function of sensitivity (y-axis), specificity (x-axis), and PE₉ value (columns). The value of cost_DALY is equal to per capita GDP (8,650 USD) in the top row and three times per capita GDP in the bottom row. The strategy of vaccination without screening is represented in the top-left corner of each heatmap (sensitivity = 1, specificity = 0).

Fig 4. Cost-effectiveness of the intervention from a public payer perspective, assuming one dose of vaccine (23 USD) and a fixed cost of serological screening (10 USD) under Brazil-like cost assumptions.

Cost-effectiveness according to Eq 5 is shown in green as a function of sensitivity (y-axis), specificity (x-axis), and PE₉ value (columns). The value of cost_DALY is equal to per capita GDP (8,650 USD) in the top row and three times per capita GDP in the bottom row. The strategy of vaccination without screening is represented in the top-left corner of each heatmap (sensitivity = 1, specificity = 0).

Fig 5. Threshold cost of serological screening from an individual perspective, assuming a vaccination cost of 69 USD and economic assumptions from Brazil.

Threshold costs are indicated by color as a function of sensitivity (y-axis), specificity (x-axis), and PE₉ value (columns). The value of cost_DALY is equal to per capita GDP (8,650 USD) in the top row and three times per capita GDP in the bottom row. The strategy of vaccination without screening is represented in the top-left corner of each heatmap (sensitivity = 1, specificity = 0).

Fig 6. Cost-effectiveness of the intervention from an individual perspective, assuming one dose of vaccine (23 USD) and a fixed cost of serological screening (10 USD) under Brazil-like cost assumptions.

Cost-effectiveness according to Eq 5 is shown in green as a function of sensitivity (y-axis), specificity (x-axis), and PE₉ value (columns). The value of cost_DALY is equal to per capita GDP (8,650 USD) in the top row and three times per capita GDP in the bottom row. The strategy of vaccination without screening is represented in the top-left corner of each heatmap (sensitivity = 1, specificity = 0).