Dengue vaccination
Dengue vaccine development has been challenging because of the need to provide protection against all four dengue serotypes to avoid potentially causing antibody dependent enhancement in further infections.
There are currently two dengue vaccines which have been granted marketing authorisation. Qdenga® is available in Belgium since 2023 and can be used in certain indications. The use of Dengvaxia® is limited to seropositive people in endemic areas.
Qdenga® (TAK-003, Takeda)
- Product: Qdenga® (TAK-003), against dengue virus serotypes 1, 2, 3 and 4.
- Type: live-attenuated vaccine
- Schedule: 0.5 ml dose at a two-dose schedule with a 3 month interval. It is not advised to reduce the interval between doses. If the second dose is delayed for any reason, it is not necessary to restart the series and the second dose should be administered at the first available opportunity.
- Booster: a booster dose is currently not recommended. Some waning of vaccine efficacy was observed over the 5-year trial period, additional studies are underway to determine the use of a booster dose and its optimal timing.
- Age: although licensed from 4 years of age, it's not recommended below the age of 6 years because of the lower efficacy in this age groups (WHO).
- Route of administration: subcutaneous
- Recommendation: The Superior Health Council (SHC) recommends vaccination against Dengue with Qdenga® for people meeting all of the following criteria:
- six years of age or older
- and have been infected with any of the 4 dengue virus serotypes >6 months ago
- It is upon the clinician to evaluate whether the traveller has had dengue before, mainly based on history and potential exposure (visit to endemic region). Sometimes lab confirmation can help, but a general screening by serology is NOT recommended because of difficult interpretation due to cross reactions with other flaviviruses or vaccines. In case of doubt, please contact an infectious disease specialist.
- and long-term travellers (> 4 weeks), frequent travellers or expatriates in a dengue endemic region
- Dengue endemic regions where vaccination could be considered are the ‘darkest’ red on the dengue global consensus map. For those countries the dengue vaccine is specifically mentioned as a vaccine ‘recommended for some travellers’ in the vaccination section of the country specific pages.
Protection starts 14 days after the first dose and has been demonstrated between the first and second dose, hence, the first dose can be given up to 14 days before travel to a dengue-endemic country. To ensure the durability of the protection, a second dose is needed after a minimum interval of 3 months.
- Efficacy:
A phase 3 study showed that the cumulative efficacy three years after vaccination in healthy four- to sixteen-year-old (n=20 099) was 62.0% against virologically confirmed dengue and 83.6% against hospitalized dengue.
The overall vaccine efficacy is better in baseline seropositive then in seronegative individuals and protects better against hospitalisations then against infection in general.The vaccine efficacy varies for different serotypes, offering the best protection against DENV-2, followed by DENV-1 with immunity against DENV-1 declining more rapidly. In baseline seropositive individuals the vaccine efficacy is also good for DENV-3 infection and hospitalisation. In baseline seronegative individuals there is no vaccine efficacy for DENV-3 infection or hospitalisation. More hospitalisations and more severe dengue were observed but this was not considered statistically significant due to very small numbers. However, this signal should be monitored in the future. There are insufficient data for DENV-4 and therefore no conclusions can be drawn on efficacy and safety. - Contra-indication:
- Hypersensitivity to the active substances or to any of the excipients or hypersensitivity to a previous dose of Qdenga®.
- Individuals with symptomatic HIV infection or with asymptomatic HIV infection when accompanied by evidence of impaired immune function.
- Patients with primary or secondary acquired immunodeficiencies.
- Pregnant or breast-feeding women. Women of childbearing potential should avoid pregnancy for at least one month following vaccination. Women who intend to become pregnant should be advised to delay vaccination.
- Side effects
Mostly mild to moderate in severity and disappear within a few days. The most common side effects in more than one in five people are pain and redness at the injection site, headache, muscle pain, feeling generally unwell and weakness. Up to one in ten people may experience fever. There are no data on the use of Qdenga® in patients above 60 years of age and limited data in patients with chronic medical conditions. - Co-administration with other vaccines:
The data about co-administration with other vaccines are limited:- Hepatitis A: has been studied in adults and it may be administered concomitantly.
- Yellow fever vaccine: may be administered concomitantly. In a clinical study involving approximately 300 adult subjects who received a yellow fever vaccine together with Qdenga® there was no effect on yellow fever seroprotection rate. Dengue antibody responses were decreased but the clinical significance of this finding is unknown.
Until further data on co-administration is known an interval of four weeks with other live vaccines is recommended. If Qdenga® is given at the same time as another injectable vaccine, it should always be administered at different injection sites.
Dengvaxia® (CYD-TDV, Sanofi Pasteur)
As of December 2015 Dengvaxia® (CYD-TDV, Sanofi Pasteur) has been licensed in a small number of endemic countries. The vaccine has shown to be efficacious and safe in persons who have had a previous dengue infection, but carries an increased risk of severe dengue and hospitalizations in those who experience their first natural dengue infection after vaccination.
As such, use of the CYD-TDV vaccine is targeted for persons living in endemic areas, 9-45 years of age who have had dengue before. It is not recommended in travellers.
- Type: live- attenuated vaccine
- Schedule: 3 doses with 6 months interval
- Route of administration: subcutaneous
Additional information
- Wikitropica: background information on dengue for medical professionals
- Advisory report of the Superior Health Council on vaccination against dengue ( HGR 9739)
- Dengue and severe dengue Factsheet ( WHO 2023)
- CDC Yellow book: Travel-related Infectious Diseases- Dengue (CDC 2020)
- Dengue (CDC 2020)
- Human medicine European public assessment report (EPAR): Qdenga
References
- WHO position paper on dengue vaccines- May 2024, Weekly epidemiological record No18, 2024, 203-224
- Rivera et al. Three-year Efficacy and Safety of Takeda's Dengue Vaccine Candidate (TAK-003). Clin Infect Dis. 2022 Aug 24;75(1):107-117
- Tricou et al. Immunogenicity and safety of concomitant and sequential administration of yellow fever YF-17D vaccine and tetravalent dengue vaccine candidate TAK-003: A phase 3 randomized, controlled study. PLoS Negl Trop Dis. 2023 Mar 8;17(3):e0011124