Potential impact of vaccination for a scenario with cross-protection only (A–D) and a scenario combining cross-protection & cross-enhancement (E–H).

<p>The two scenarios are those which calibration results are reported <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051244#pone-0051244-g004" target="_blank">Figure 4</a> (Model S2.2C, S2.4C).</p

Results of dengue surveillance in Southern Vietnam.

<p>a. Reported DHF incidence from 1972 to 2007 (per 100,000 inhabitants). b. Reported dengue incidence for <15 years old and 15+ years old individual per level of severity (per 100,000 inhabitants) c. based on reported incidence and serotype distribution of isolated virus (about 1% of reported cases are subject to virus isolation) d. Seasonality in vector (Aedes Aegypti) density and monthly DHF incidence. Seasonality was assessed through locally weighted scatterplot smoothing <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051244#pone.0051244-Cleveland1" target="_blank">[61]</a>. Data derived from the surveillance system of dengue in Southern Vietnam coordinated by the Pasteur Institute in Ho Chi Minh.</p

Results of a prospective cohort study in Long Xuen [<b>34</b>].

<p>a. Age and serotype specific seroprevalence rate observed in a prospective cohort study performed in An Giang from (2004–2007) b. DF, DHF and DSS incidence observed in 3–15 year-old children.</p

Flow diagram of the infection and vaccination process.

<p>Rounded rectangles correspond to compartments and ellipses to factors influencing the transition from one compartment to another. For clarity, the representation in human hosts is limited to serotype 1 but each individual is characterized by their status for each of the four serotypes.</p

Simulated and observed evolution of annual dengue incidence for different scenarios of serotype interactions: Model simulation with short term cross-protection only (A,B), Model simulation with cross-enhancement only (C,D), Model simulation with cross-protection & cross-enhancement (E,F).

<p>Wavelet analysis for observed data (G) and observed annual DHF/DSS incidence corrected for under-reporting (H). Footnotes of panels A, C, E: 1. Increased susceptibility and severity in case of secondary infection 2. Dominant period assessed using Fourier power spectrum over 36 consecutive years, 3. Median, minimum and maximum 4. The basic reproduction number reported is the annual average (average vector density and daily biting rates). In Wavelet analysis for observed data (G), the power has been scaled by the global wavelet spectrum. The cross-hatched region is the cone of influence, where zero padding has reduced the variance. Black contour is the 10% significance level <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051244#pone.0051244-Torrence1" target="_blank">[41]</a>. The 36 years of available data were duplicated to improve comparability with model results (H).</p

Assessment of benefits and risks associated with dengue vaccination at the individual and population levels: a dynamic modeling approach

<p><b>Background</b>: A case-cohort study, using a novel assay and data from three dengue vaccine efficacy trials, highlighted differences in vaccination outcomes according to baseline serostatus. Based on these results, we explored, with a model, the benefits and risks associated with vaccination.</p> <p><b>Research design and methods</b>: Parameters of a previously developed transmission model were estimated with subject-level data from a case-cohort study. The model was used to assess vaccination outcomes for a range of transmission settings over 5–30 years, with or without indirect protection.</p> <p><b>Main outcome measures</b>: Symptomatic dengue cases, dengue hospitalizations, and severe dengue cases.</p> <p><b>Results</b>: The model is consistent with previous results indicating a transitory period at increased risk for dengue-seronegative vaccine recipients (setting-dependent duration) and long-term benefits for dengue-seropositive recipients. At the population level, benefits to seropositive individuals over 10 years outweighed the risk to those seronegative in moderate to high transmission settings (≥50% seropositivity at age 9), especially in high transmission settings (no excess hospitalizations in dengue-seronegative for ≥80% seropositivity at age 9). Results were more favorable when longer time horizons or indirect protection were considered.</p> <p><b>Conclusions</b>: Results indicate a public health benefit associated with dengue vaccination especially in high-transmission settings, even with the initial excess risks to dengue-seronegative patients which diminish over time.</p

Additional file 3: of Some extensions in continuous models for immunological correlates of protection

Illustrative SAS code to create the datasets reconstructed from published sources and fit models. (DOCX 50 kb

Distribution of outcomes in case of exposure.

<p>Distribution of outcomes in case of contact with an infectious person according to immunological status. Values for susceptible, immune and natural waning are taken from <i>Van Rie et al.</i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006284#pone.0006284-Coudeville1" target="_blank">[25]</a>. Values for vaccine-related compartments are estimated using <i>Bisgard et al.</i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006284#pone.0006284-Bisgard2" target="_blank">[<i>31</i>]</a> and <i>Ward et al.</i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006284#pone.0006284-Ward1" target="_blank">[10]</a>. Figures in parentheses define the range used in the sensitivity analysis.</p

Key parameters in the epidemiological model.

<p>Key parameters in the epidemiological model.</p

Variation in pertussis incidence and costs according to the age at which the adult booster dose is administered (Childhood vaccination+adolescent+cocoon+1 booster dose for adult vaccination - steady-state situation).

<p>Variation in pertussis incidence and costs according to the age at which the adult booster dose is administered (Childhood vaccination+adolescent+cocoon+1 booster dose for adult vaccination - steady-state situation).</p