Global spread of Zika virus: Zika virus was identified in Uganda in 1947; since then, it has enveloped the tropics, causing disease of varying severity. Lessler et al. review the historical literature to remind us that Zika's neurotropism was observed in mice even before clinical case reports in Nigeria in 1953. What determines the clinical manifestations; how local conditions, vectors, genetics, and wild hosts affect transmission and geographical spread; what the best control strategy is; and how to develop effective drugs, vaccines, and diagnostics are all critical questions that are begging for data. Science , this issue p. 663

Intervention planning for dengue requires reliable estimates of dengue transmission intensity. However, current maps of dengue risk provide estimates of disease burden or the boundaries of endemicity rather than transmission intensity. We therefore developed a global high-resolution map of dengue transmission intensity by fitting environmentally driven geospatial models to geolocated force of infection estimates derived from cross-sectional serological surveys and routine case surveillance data. We assessed the impact of interventions on dengue transmission and disease using Wolbachia-infected mosquitoes and the Sanofi-Pasteur vaccine as specific examples. We predicted high transmission intensity in all continents straddling the tropics, with hot spots in South America (Colombia, Venezuela, and Brazil), Africa (western and central African countries), and Southeast Asia (Thailand, Indonesia, and the Philippines). We estimated that 105 [95% confidence interval (CI), 95 to 114] million dengue infections occur each year with 51 (95% CI, 32 to 66) million febrile disease cases. Our analysis suggests that transmission-blocking interventions such as Wolbachia, even at intermediate efficacy (50% transmission reduction), might reduce global annual disease incidence by up to 90%. The Sanofi-Pasteur vaccine, targeting only seropositive recipients, might reduce global annual disease incidence by 20 to 30%, with the greatest impact in high-transmission settings. The transmission intensity map presented here, and made available for download, may help further assessment of the impact of dengue control interventions and prioritization of global public health efforts.

Zika dynamics in South America: The infection dynamics of Zika virus (ZIKV) are difficult to characterize. Many ZIKV infections are asymptomatic, and the clinical presentation of ZIKV is nonspecific. Rodriguez-Barraqueret al.took advantage of a long-term health study under way in Salvador, Brazil, the epicenter of the recent outbreak in the Americas. They used multiple serological assays, from before and after the emergence of ZIKV in October 2015, to distinguish ZIKV immune responses from those against Dengue virus (DENV). About 73% of the population was attacked by ZIKV. The presence of preexisting antibodies to DENV was associated with less risk of ZIKV infection and fewer symptoms.Science, this issue p.607

The first approved dengue vaccine has now been licensed in six countries. We propose that this live attenuated vaccine acts like a silent natural infection in priming or boosting host immunity. A transmission dynamic model incorporating this hypothesis fits recent clinical trial data well and predicts that vaccine effectiveness depends strongly on the age group vaccinated and local transmission intensity. Vaccination in low-transmission settings may increase the incidence of more severe “secondary-like” infection and, thus, the numbers hospitalized for dengue. In moderate transmission settings, we predict positive impacts overall but increased risks of hospitalization with dengue disease for individuals who are vaccinated when seronegative. However, in high-transmission settings, vaccination benefits both the whole population and seronegative recipients. Our analysis can help inform policy-makers evaluating this and other candidate dengue vaccines.

Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine. The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%–25% (all simulations: –3%–34%) and in high-transmission settings (SP9 ≥ 70%) by 13%–25% (all simulations: 10%– 34%). These endemicity levels are representative of the participating sites in both Phase III trials. In contrast, in settings with low transmission intensity (SP9 ≤ 30%), the models predicted that vaccination could lead to a substantial increase in hospitalisation because of dengue. 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. In assessing the optimal age of vaccination, we found that targeting older children could increase the net benefit of vaccination in settings with moderate transmission intensity (SP9 = 50%). Overall, vaccination was predicted to be potentially 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. Dengvaxia has the potential to reduce the burden of dengue disease in areas of moderate to high dengue endemicity. However, the potential risks of vaccination in areas with limited exposure to dengue as well as the local costs and benefits of routine vaccination are important considerations for the inclusion of Dengvaxia into existing immunisation programmes. These results were important inputs into WHO global policy for use of this licensed dengue vaccine.