Designing effective control of dengue with combined interventions
Historically, mosquito control programs successfully contained malaria and (in combination with vaccination) yellow fever, but recent efforts have been unable to halt dengue, chikungunya, or Zika spread. One dengue vaccine has reached licensure, with others likely to follow, but vaccines alone may be insufficient for containing dengue. Using an agent-based dengue model for Yucatan, Mexico, results from indoor residual spraying (IRS) experiments, and two competing models of vaccine performance, we investigated how IRS and vaccines, separately and together, could be expected to perform as dengue controls in an endemic setting. We considered three coverage levels (25, 50, and 75%) of prophylactic household IRS, and two vaccine mechanisms: one where the vaccine simply replaces a natural infection like a fifth dengue serotype, potentially priming naive vaccinees for a dangerous second infection; and a second, a leaky vaccine with 70% efficacy that does not wane. We found that for the first two years of a new, aggressive single intervention, whether high-coverage IRS or either vaccine with a catch-up campaign, it is easy to achieve >80% reduction in dengue cases. In the long-term (>20 years), however, even the best-performing individual interventions prevented more than 50% of cases in our model. IRS and the "fifth serotype" vaccine individually prevented fewer than 30% of cases after 20+ years. While combining IRS and the "fifth serotype" vaccine performed somewhat better than either individually, preventing 35% of cases after 20+ years, the effect was less-than-additive. The best performing strategy was IRS with the 70% efficacy vaccine, demonstrating a synergistic, greater-than-additive effect: strategies that individually prevented 20% and 50% of long-term cases individually prevented 85% of cases when combined. In the short term, when IRS was combined with the 70% efficacy vaccine with a one-time catch-up campaign, >95% of cases were prevented for the first 10 years, suggesting a plausible, if ambitious, strategy for elimination.