On August 25-26, 2010, the World Health Organization held a meeting on the potential uses of mathematical modeling in dengue vaccination planning. The meeting was organized by OUCRU (Maciej Boni, Jeremy Farrar) in order to give a middle-income country perspective on how dengue vaccine might be adopted and what type of evidence would be needed to roll it out, and was co-sponsored by the Vaccine Modeling Initiative (University of Pittsburgh). The meeting was attended by WHO staff in Immunization, Vaccine and Biologicals, by modelers, epidemiologists, entomologists, virologists, and clinicians from various countries, and by members of the Sanofi-Pasteur and GSK vaccine development teams.
The meeting included updates on vaccine development. The Sanofi-Pasteur tetravalent, yellow-fever backbone, live-attenuated vaccine commenced phase 3 trials in late 2010. Phase 1 safety and immunogenicity studies were ongoing for the GSK purified, inactivated dengue vaccine candidate. Key data on immunogenicity were discussed, as the efficacy and duration of imumunity are key components that would need to be entered into mathematical models in order to predict how often vaccination needed to occur and what fraction of the population should be vaccinated.
Presentations on modeling work highlighted the need for better clinical models of dengue and more information on serotype specificity when analyzing the transmissibility and severity of different dengue strains. Severity was a key theme revisited at various points in the workshop, as the various forms of severe dengue — including dengue shock syndrome — are the key public health outcomes that need to be minimized in any tool using models to optimize dengue vaccine rollout. The clinical model is a critical component of this severity analysis, as there is still much disagreement on how often and under what circumstances secondary dengue infections progress to a severe form of dengue.
The group laid out ten urgent questions on dengue vaccination roll-out focusing on severity risks, age-targeting and demographics, logistics, and monitoring. Historical data sets were reviewed to determine if any new conclusions could be drawn from various long-term cohorts.