Date Published: May 03, 2017
Publisher: The American Society of Tropical Medicine and Hygiene
Author(s): Eunha Shim.
The first approved dengue vaccine, CYD-TDV, a chimeric, live-attenuated, tetravalent dengue virus vaccine, was recently licensed in 13 countries, including Brazil. In light of recent vaccine approval, we modeled the cost-effectiveness of potential vaccination policies mathematically based on data from recent vaccine efficacy trials that indicated that vaccine efficacy was lower in seronegative individuals than in seropositive individuals. In our analysis, we investigated several vaccination programs, including routine vaccination, with various vaccine coverage levels and those with and without large catch-up campaigns. As it is unclear whether the vaccine protects against infection or just against disease, our model incorporated both direct and indirect effects of vaccination. We found that in the presence of vaccine-induced indirect protection, the cost-effectiveness of dengue vaccination decreased with increasing vaccine coverage levels because the marginal returns of herd immunity decreases with vaccine coverage. All routine dengue vaccination programs that we considered were cost-effective, reducing dengue incidence significantly. Specifically, a routine dengue vaccination of 9-year-olds would be cost-effective when the cost of vaccination per individual is less than $262. Furthermore, the combination of routine vaccination and large catch-up campaigns resulted in a greater reduction of dengue burden (by up to 93%) than routine vaccination alone, making it a cost-effective intervention as long as the cost per course of vaccination is $255 or less. Our results show that dengue vaccination would be cost-effective in Brazil even with a relatively low vaccine efficacy in seronegative individuals.
Dengue is a febrile illness caused by any one of the four serotypes of dengue virus (DENV-1, DENV-2, DENV-3, or DENV-4).1 The disease is transmitted from human to human through the bite of mosquitoes of the genus Aedes.2 Dengue is endemic in more than 100 countries, and nearly 4 billion people are at risk for dengue, with 390 million dengue infections occurring every year.3
Our calculated values for the annual dengue infection incidence in the absence of vaccination (2.03%) and the annual symptomatic DF incidence (1.07%) were comparable to empirical estimates (Figures 1Figure 1.Expected yearly incidence of symptomatic cases of dengue per 100,000 for the different vaccination strategies. Incidence was averaged over a 10-year period. Percentage values refer to the percent reduction in dengue cases compared with dengue incidence in the prevaccine era. Each vaccination strategy is indicated by the age of routine vaccination with its coverage levels and the target ages in the catch-up campaign. For example, R9 (70%) and 9–25 refer to a catch-up campaign of individuals from 9- to 25-year-olds followed by routine vaccination at 9-year-olds with a coverage level of 70%. For all catch-up campaigns considered, 50% vaccine coverage was assumed. and 2Figure 2.Expected yearly incidence of dengue hemorrhagic fever per million for the different vaccination strategies. Incidence was averaged over a 10-year period. Percentage values refer to the percent reduction in dengue cases compared with dengue incidence in the prevaccine era. Each vaccination strategy is indicated by the age of routine vaccination with its coverage levels and the target ages in the catch-up campaign. For example, R9 (70%) and 9–25 refers to a catch-up campaign of individuals from 9- to 25-year-olds followed by routine vaccination at 9-year-olds with a coverage level of 70%. For all catch-up campaigns considered, 50% vaccine coverage was assumed.).18,35,43 The transmission rates (βk) were chosen to capture the age distribution among the cases of dengue in Brazil; the simulated age distributions of symptomatic cases of dengue in the prevaccine era are presented (Figure 3Figure 3.Age distributions of dengue fever (DF) and dengue hemorrhagic fever (DHF) cases in the prevaccine era. Age-specific incidence rates of DF and DHF cases in the prevaccine era are presented. An annual incidence of dengue fever and DHF cases are 1.07% and 0.029%, respectively.). Before the dengue vaccine was introduced, the annual DHF incidence in Brazil was estimated to be 0.029%, resulting in a total cost of dengue at $906 million to the health-care system.
The first dengue vaccine has now been approved for use in 13 countries. However, the impact of the new dengue vaccine might be hampered by the risk of immune-mediated enhancement of disease. Specifically, the trials of CYD-TDV revealed much lower efficacy in recipients who were seronegative at the time of vaccination than in those who were seropositive to dengue virus at the time of vaccination. As a result, lower vaccine efficacies were observed in younger age groups that have not lived long enough to experience a natural infection.