Fig 1.
Example of events that occur at the individual level (lines) at a single location (gray house shape) over the course of a single day.
Red lines correspond to individual mosquitoes, with dashed and solid lines representing host-seeking and resting states, respectively. Blue lines refer to individual people, with thin dotted lines indicating that the person is at another location at that time and thick solid lines indicating their presence at the location at that time. The thickness of the solid blue lines indicates the relative attractiveness of each person to blood feeding by mosquitoes.
Fig 2.
Relative risk of disease, RRdis, as a function of age and serostatus (blue: seronegative, red: seropositive) estimated from vaccine trial data [16].
Each line represents a distinct random draw from the distribution of these relationships. Black circles correspond to point estimates of relative risk of disease in the trial for a given age group (2–9 left, 9–16 right) and serostatus (red vs. blue), and error bars indicate 95% confidence intervals around those estimates.
Table 1.
Definitions of key terms.
Table 2.
Scenarios examined through sensitivity analysis.
As each parameter was varied from its default value, all other parameters were held at their default values. Under each parameter scenario, a separate calibration was performed prior to performing vaccination impact projections.
Fig 3.
Monthly, serotype-specific incidence of infection per capita, as estimated by Reiner et al. [49] (gray bands) and as reproduced by our calibrated model (colored bands).
Bands show the range of values in which 95% of simulated values lie for a given serotype in a given month. These values were obtained under default parameter assumptions detailed in Table 2.
Fig 4.
Proportion of the population during the period of the calibration that was not immune to a given serotype (colored), temporarily cross-immune to that serotype (light gray), or permanently immune to that serotype (dark gray).
Values shown reflect medians across 1,000 simulations drawing parameters from across the set of particles obtained through the calibration process under default parameter assumptions detailed in Table 2.
Fig 5.
Median numbers of infections on a monthly basis for each serotype, stratified by whether the infection was acquired through biting by an infectious mosquito (colored) or by exogenously driven infections (gray) that were used to seed transmission in the model.
These bands represent median values across the set of calibrated parameter values, and the colored bands are added on top of the gray bands. These values were obtained under default parameter assumptions detailed in Table 2.
Fig 6.
Relative risk of infection conditional on exposure (dashed) and of disease conditional on infection (solid) for seropositive (red) and seronegative (blue) individuals of different ages.
These relationships are shown for three different values of the parameter p that specifies the proportion of the overall efficacy against disease that is attributable to protection against infection conditional on exposure.
Fig 7.
Examples of paired time series of annual incidence of human DENV infections simulated from the model with vaccination (green) and without (black).
Prior to year 0, both simulations in each pair are identical and follow dynamics calibrated as shown in Fig 2. Beginning in year 0, routine vaccination commences in the simulation colored in green, but not in the one in black. Three different realizations are shown for each of two scenarios (left: p = 1; right: p = 0), with different outcomes from the same realization plotted in each of four sets of panels: a, d, g, and j; b, e, h, and k; c, f, i, and l.
Fig 8.
Impacts of vaccination assessed in 1,000 pairs of simulations with and without vaccination under the CYD-TDV vaccine profile.
Simulation pairs varied with respect to the proportion of vaccine efficacy due to protection from infection, p, (left column) and the quantile of estimated vaccine efficacy, q (right column). The proportions of cumulative infections averted (top row) and cumulative disease episodes averted (bottom row) were based on the number of each in the simulation without vaccination minus the number of each in the simulation with vaccination, both following 20 years of routine vaccination of 9-year olds at 80% coverage. Lines show the proportion of cumulative infections and disease episodes averted as a function of p and q, as estimated by a generalized additive model with independent smooth terms for p and q. When one of p or q is varied, the other is held constant at 0.5. Gray bands indicate 95% confidence intervals.
Fig 9.
Impacts of vaccination assessed in 1,000 pairs of simulations with and without vaccination under the generic dengue vaccine profile.
Simulation pairs varied with respect to the proportion of vaccine efficacy due to protection from infection, p, (left column) and mean vaccine efficacy, VEmean (right column). The proportion of cumulative infections averted (top row) and cumulative disease episodes averted (bottom row) were based on the number of each in the simulation without vaccination minus the number of each in the simulation with vaccination, both following 20 years of routine vaccination of 9-year olds at 80% coverage. Lines show the proportion of infections or diseases episodes averted as a function of each parameter varied on the x-axis, as estimated by a generalized additive model with independent smooth terms for each parameter. When one parameter is varied, the other is held constant at the midpoint of its range, as are VEserostatus and VEserotype. Gray bands indicate 95% confidence intervals.
Fig 10.
Summary of vaccination impact on infections and disease episodes (rows) under two sets of assumptions about vaccine profile (columns) at extreme values of parameters that varied across simulations (colors).
Bars display point estimates and 95% confidence intervals obtained from fitting generalized additive models to simulation results across the range of each parameter while holding others at the midpoints of their ranges. These values correspond to the extremes displayed in Fig 8 (p, q), Fig 9 (p, VEmean), and S23 Fig (VEserostatus, VEserotype).