WHO-recommended dengue vaccine most potent in high-transmission settings
Dengvaxia, a recombinant, live-attenuated dengue vaccine, has the potential to bring down the number of hospitalizations by 13 to 25 percent and be cost-effective in areas of moderate-to-high dengue endemicity, according to a model comparison study.
In contrast, Dengvaxia might increase the incidence of severe illness in areas with low transmission or limited exposure to dengue.
The efficacy of the dengue had been shown in large phase III trials across Asia and Latin America over the first 25 months following vaccination. However, data collected in the longer-term follow-up phase had raised concerns about a potential rise in hospitalization risk of subsequent dengue infections, particularly among young, dengue-naïve vaccinees, researchers said.
Eight independent modelling groups predicted the long-term safety, public health impact and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterized by seroprevalence levels among 9-year-olds (SP9). The default vaccination policy was routing vaccination of 9-year-old children in a three-dose schedule at 80 percent coverage.
The outcomes included the impact of vaccination on infections, symptomatic dengue, hospitalized dengue, deaths and cost-effectiveness over a 30-year postvaccination period. Case definitions were chosen in accordance with the phase III trials.
According to predictions of all models, the default vaccination policy would lessen the burden of dengue disease for the population by 6 to 25 percent (all simulations: –3 to 34 percent) in setting with moderate to high dengue endemicity (SP9 ≥50 percent) and by 13 to 25 percent (all simulations: 10 to 34 percent) in high-transmission settings (SP9 ≥70 percent). [PLoS Med 2016;doi:10.1371/journal.pmed.1002181]
On the other hand, the models predicted that vaccination had the potential to substantially increase hospitalizations due to dengue in areas with low transmission intensity (SP9 ≥30 percent).
“Modelling reduced vaccine coverage or the addition of catch-up campaigns showed that the impact of vaccination scaled approximately linearly with the number of people vaccinated,” researchers said.
Assessment of the optimal vaccination age demonstrated that targeting older children could improve the net benefit of vaccination in settings with moderate transmission intensity (SP9=50 percent). Overall, the models predicted that vaccination could be cost-effective in most endemic settings if priced competitively.
“The results are based on the assumption that the vaccine acts similarly to natural infection. This assumption is consistent with the available trial results but cannot be directly validated in the absence of additional data. Furthermore, uncertainties remain regarding the level of protection provided against disease versus infection and the rate at which vaccine-induced protection declines,” researchers noted.
Dengvaxia had recently been recommended by the World Health Organization in areas where dengue is common.
Researchers further noted that the results could guide countries on the general suitability of introducing the dengue vaccine, but local demographics, heterogeneities in endemicity and health system costs had to be taken into consideration.