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    GDAC statement on the Strategic Advisory Group of Experts’ (SAGE) updated recommendations on use of Dengvaxia®

May 11, 2018

The Strategic Advisory Group of Experts (SAGE) on Immunizations, an independent panel of experts that advises the World Health Organization (WHO), issued updated recommendations on 19 April 2018 regarding the use of Sanofi Pasteur’s dengue vaccine, Dengvaxia®.

The update was based on supplemental evidence announced by Sanofi Pasteur on 29 November 2017 which showed Dengvaxia® can increase the risk of severe dengue in people of all ages who have not had prior dengue infection (i.e., are seronegative). SAGE recommended that, in order to maximize public health impact and minimize harm, pre-vaccination screening should ideally be performed on prospective Dengvaxia® recipients, and that only those individuals having evidence of previous dengue infection (i.e., are seropositive) should be vaccinated. SAGE acknowledged that Dengvaxia® could still have an overall public health benefit in populations with high seroprevalence.

Given the current lack of optimal assays to use for widespread dengue serostatus screening, SAGE recommended that dengue IgG ELISAs could be used to test for evidence of prior dengue infection, if evaluated in the local epidemiological context. SAGE also noted that, in the absence of better assays, currently available rapid diagnostic tests (RDTs) that include an IgG component could be used to determine serostatus in settings with very high transmission.

The Global Dengue & Aedes-Transmitted Diseases Consortium (GDAC) believes SAGE’s updated recommendations are a prudent approach to implementing Dengvaxia®, while minimizing the likelihood of harm in an identifiable group of seronegative individuals. However, GDAC also recognizes that these recommendations are hampered by the current lack of accurate point-of-care serological assays. This situation may result in a large number of seropositive individuals not receiving Dengvaxia® due to lack of testing, who would otherwise benefit from the vaccine.

The SAGE recommendations underscore the critical need to address scientific and technical gaps in dengue vaccine development. An immediate priority, as pointed out by SAGE, is the need to improve point-of-care dengue serological assays, which is further complicated by co-circulating flaviviruses such as yellow fever and Zika. Additionally, there is an urgent need to better understand the mechanisms for the increased risk induced by Dengvaxia® in seronegative individuals. This will require improved coordination of ongoing efforts to define correlates of protection and enhancement of dengue vaccines, taking advantage of the increasing availability of biological samples from vaccine recipients with both positive and negative clinical outcomes.

The two other dengue vaccines currently in phase 3 trials, Butantan’s Butantan-DV and Takeda’s TDV, utilize different vaccine designs than Dengvaxia®, and may or may not have the same issues as Sanofi Pasteur’s product. Nevertheless, efficacy and long-term safety of these and other dengue vaccines in people without prior dengue infection need to be assessed carefully.

Finally, effective communication will be crucial to manage expectations about Dengvaxia®’s effectiveness and safety, and to reinforce the public’s confidence in dengue vaccines more generally. And as always, vaccination should be considered as part of an integrated effort to prevent and control dengue, which includes effective vector control strategies, robust surveillance systems, evidence-based clinical care, and strong community outreach.