Dengue vaccine: local decisions, global consequences

Abstract

As new vaccines against diseases that are prevalent in low- and middle-income countries gradually become available, national health authorities are presented with new regulatory and policy challenges. The use of CYD-TDV – a chimeric tetravalent, live-attenuated dengue vaccine – was recently approved in five countries. Although promising for public health, this vaccine has only partial and heterogeneous efficacy and may have substantial adverse effects. In trials, children who were aged 2–5 years when first given CYD-TDV were seven times more likely to be hospitalized for dengue, in the third year post-vaccination, than their counterparts in the control group. As it has not been clarified whether this adverse effect is only a function of age or is determined by dengue serostatus, doubts have been cast over the long-term safety of this vaccine in seronegative individuals of any age. Any deployment of the vaccine, which should be very cautious and only considered after a rigorous evaluation of the vaccine’s risk–benefit ratio in explicit national and subnational scenarios, needs to be followed by a long-term assessment of the vaccine’s effects. Furthermore, any implementation of dengue vaccines must not weaken the political and financial support of preventive measures that can simultaneously limit the impacts of dengue and several other mosquito-borne pathogens.

Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond

“…Vaccines are available against several flaviviral infections, including for yellow fever virus (YFV), Japanese encephalitis virus (JEV), dengue virus (DENV; a tetravalent vaccine, approved in seven countries as of December 2016) 302,303 , tick-borne encephalitis virus, Louping ill virus (vaccination of sheep to prevent transmission to humans) 304 and Kyasanur Forest disease virus 305 . The efficacy, safety and durability of antiflaviviral vaccines vary widely; the long-established YFV vaccine has relatively favourable properties, such as a long-lasting effect and the infrequent development of resistance.…”

Age‐specific seroprevalence of dengue infection in Hong Kong

“…Previous trials have reported that this vaccine can reduce the incidence of symptomatic infection and hospitalization in countries with a high burden of disease . The World Health Organization recommends countries in which dengue seroprevalence is at least 70% to consider CYD‐TDV vaccination and to refrain from deploying this vaccine if seroprevalence is lower than 50% . CYD‐TDV vaccination in low‐seroprevalence populations is not recommended because of low efficacies and the increased risk of severe dengue infection in seronegative individuals.…”

The Regulation Requirement of Dengue Vaccines

“…In recent studies, age-related paterns for dengue vaccine eicacy were observed in the pooled estimated eicacies against severe dengue [17]. The prevention of dengue infection caused by four DENV serotypes in individuals mainly aged 9-45 years.…”

“…Vaccine eicacy against dengue seemed to vary according to the serotype of the infecting DENV [17]. Additional pooled eicacy, integrated safety analyses from the clinical phase III eicacy studies and the ongoing safety studies should be used to conirm the eicacy and longer term safety of dengue vaccines.…”

“…Local and global capacity for assessing the long-term safety of the dengue vaccine in post-licensing surveillance must be strengthened to meet the challenges imposed by its potentially complex performance [17].…”