Projected Impact of Dengue Vaccination in Yucatán, Mexico

Abstract

Dengue vaccines will soon provide a new tool for reducing dengue disease, but the effectiveness of widespread vaccination campaigns has not yet been determined. We developed an agent-based dengue model representing movement of and transmission dynamics among people and mosquitoes in Yucatán, Mexico, and simulated various vaccine scenarios to evaluate effectiveness under those conditions. This model includes detailed spatial representation of the Yucatán population, including the location and movement of 1.8 million people between 375,000 households and 100,000 workplaces and schools. Where possible, we designed the model to use data sources with international coverage, to simplify re-parameterization for other regions. The simulation and analysis integrate 35 years of mild and severe case data (including dengue serotype when available), results of a seroprevalence survey, satellite imagery, and climatological, census, and economic data. To fit model parameters that are not directly informed by available data, such as disease reporting rates and dengue transmission parameters, we developed a parameter estimation toolkit called AbcSmc, which we have made publicly available. After fitting the simulation model to dengue case data, we forecasted transmission and assessed the relative effectiveness of several vaccination strategies over a 20 year period. Vaccine efficacy is based on phase III trial results for the Sanofi-Pasteur vaccine, Dengvaxia. We consider routine vaccination of 2, 9, or 16 year-olds, with and without a one-time catch-up campaign to age 30. Because the durability of Dengvaxia is not yet established, we consider hypothetical vaccines that confer either durable or waning immunity, and we evaluate the use of booster doses to counter waning. We find that plausible vaccination scenarios with a durable vaccine reduce annual dengue incidence by as much as 80% within five years. However, if vaccine efficacy wanes after administration, we find that there can be years with larger epidemics than would occur without any vaccination, and that vaccine booster doses are necessary to prevent this outcome.

Cost-effectiveness of dengue vaccination in Yucatán, Mexico using a dynamic dengue transmission model

“…As in our model, a two-serotype dengue model would be satisfactory in Mexico, given that a relatively steady two-serotype dominant state exists [33]. In fact, all four dengue serotypes have been observed in Mexico, but DENV-1 have been the predominant serotype since 2008, with DENV-2 representing most of the remaining cases (17% in 2009 and 16% in 2010) [18, 33]. …”

“…In a phase III randomized, controlled vaccine trials of CYD-TDV conducted in Latin American countries, the overall efficacy of the vaccine against virologically confirmed dengue cases was 64.7% (95% CI [58.7, 69.8]) [15, 16]. Furthermore, the vaccine efficacy was dependent on individuals’ serostatus, ranging from 52.5% among seronegative individuals (95% CI [5.9, 76.1]) to 81.9% among seropositive individuals (95% CI [67.2, 90.0]) [16–18]. In addition, analysis of the phase III trials of CYD-TDV indicated that an increased risk of severe disease is associated with breakthrough dengue infections in vaccinated seronegative individuals [19].…”

Benefits and risks of the Sanofi-Pasteur dengue vaccine: Modeling optimal deployment

“…However, the dependence of vaccine efficacy on prior immunity presents challenges to planning large-scale use. Other recent modeling efforts have predicted impacts of vaccination that are more beneficial than those presented here but used models that were not fit to the data from the clinical trial (32) or the long-term follow-up (30). Our analysis indicates that to maximize the population impact of vaccination and to prevent negative impacts, it will be necessary to carefully tailor vaccination strategies to local epidemiological conditions.…”

Cost-Effectiveness of Dengue Vaccination Programs in Brazil

“…In prior studies, many national vaccination strategies were tested: routine vaccination at various ages, including 9-year-olds, considering reports of pooled vaccine efficacy for 9–16 years of age,12 and catch-up immunization campaigns for various age groups 13,34. In our paper, the default policy was routine vaccination of 9-year-old children, the youngest age within the approved age range (9–45 years) for the Dengvaxia, with 70% vaccine coverage level.…”