The Strategic Advisory Group of Experts on Immunization (SAGE) has revised its recommendations on use of CYD-TDV (Dengvaxia®).
Dengue is the most frequent and rapidly spreading mosquito-borne virus. The first dengue vaccine, CYD-TDV (Dengvaxia®) is currently licensed in twenty countries. The key findings from two large Phase 3 trials involving over 30,000 participants aged 2 to 16 years included:
- Vaccine efficacy against virologically confirmed dengue, over a 25-month period from the first dose of a three-dose immunization regimen among 9-16 year olds was 65.6% and in this age-group, vaccination reduced severe dengue by 93% and dengue hospitalizations by 82%.
- An increased risk of hospitalized dengue was seen in the 2 to 5-year age group in Year 3 of follow-up.
- At the time of SAGE April 2016 meeting, this increased risk was not observed in those aged 9 years and above.
WHO issued its position on the use of CYD-TDV in July 2016 based on recommendations provided by SAGE in April 2016, principally, that countries interested in introducing the vaccine consider its use
- only in those aged 9 years and above, and
- in areas with a seroprevalence of ≥70%, and not in areas below 50%.
SAGE noted that the evidence of the absence of a safety issue in seronegative individuals aged 9 and above was based on the limited data set of 10%-20% of the trial population, and highlighted the urgent need to better describe the long-term benefit-risk ratio of CYD-TDV in seronegative individuals.
On 29 November 2017, Sanofi Pasteur announced the results of additional studies to better describe the benefit-risk in seronegative individuals. This was made possible through the use of a newly developed NS1-based antibody assay applied to blood samples taken 13 months after vaccination to retrospectively infer dengue serostatus at time of first vaccination.
The new analyses from the long-term safety follow-up indicated that:
- Overall population level benefit of vaccination remains favorable, but the vaccine performs differently in seropositive versus seronegative individuals.
- Vaccine efficacy (VE) against virologically confirmed symptomatic dengue was high among inferred baseline seropositive participants ≥9 years of age: 76% (95%CI: 63.9, to 84.0), but much lower among baseline seronegative participants: 38.8% (95%CI: –0.9 to 62.9%) in the first 25 months after the first dose of vaccine.
- There is an increased risk of hospitalized and severe dengue in seronegative individuals starting about 30 months after the first dose.
- In areas of 70% dengue seroprevalence, over a 5-year follow-up, for every 4 severe cases prevented in seropositive, there would be one excess severe case in seronegative per 1,000 vaccinees; for every 13 hospitalizations prevented in seropositive vaccinees, there would be 1 excess hospitalization in seronegative vaccinees per 1,000 vaccinees.
SAGE acknowledged that currently both “population seroprevalence criteria” and “pre-vaccination screening” are programmatically difficult approaches for achieving high population protection from dengue.
For countries considering vaccination as part of their dengue control program, a “pre-vaccination screening strategy” would be the preferred option, in which only dengue-seropositive persons are vaccinated.
Currently, the vaccine should be used within the indicated age range, which is typically 9 to 45 years of age.
CYD-TDV is recommended as a three dose series given 6 months apart.
Should a vaccine dose be delayed for any reason, it is not necessary to restart the course and the next dose in the series should be administered.
There are currently no data on the use of booster doses. Accordingly, there is no current recommendation for a booster dose.
Link to the WHO news release:
Link to WHO position paper on Dengue vaccine:
Link to Weekly Epidemiological Record discussing Dengue vaccine (No 21, 2016) (English) [PDF]:
Link to updated WHO Question and Answer related to dengue vaccine Dengvaxia and its use (updated 22 December 2017):
Link to GACVS statement on CYD-TDV (Dengvaxia) (7 December 2017):