Dengue vaccination strategy – Role of the Qdenga vaccine - Recommend

Dengue fever is a viral disease transmitted to humans by the bite of female mosquitoes of the genus Aedes.

The Qdenga vaccine, which obtained a European marketing authorisation (MA) in December 2022 for the prevention of dengue disease in individuals from 4 years of age, was evaluated by the HAS at the request of the French Ministry of Health (DGS). The French National Council for Public Health (HCSP) was consulted in parallel to formulate recommendations for travellers.

Who are the targets of these recommendations?

They are aimed at public authorities.

What are the objectives of this recommendation? 

The objective of this recommendation is to determine the role of the Qdenga vaccine (manufactured by Takeda) in the dengue vaccination strategy in the general population, in metropolitan France and overseas France.

Factors taken into account for the assessment

• To develop these recommendations, the HAS took into account the following:
   
• epidemiological indicators of dengue over the past ten years in overseas France (French Caribbean, French Guiana, Mayotte, Reunion Island), as well as the burden of dengue in different population groups during the most recent outbreaks in these regions,
• data from clinical trials concerning the efficacy, immunogenicity, safety and tolerability of the Qdenga vaccine,
• the first safety data obtained from real-world use of the vaccine,
• the relevance of the results of serological tests performed in laboratories, assessed in view of the circulation of flaviviruses in overseas France and the seroprevalence of dengue in these regions,
• the results of the public consultation process,
• the position of the members of the working group, and that of the experts interviewed.

Main conclusions of the recommendation

The HAS recommends the implementation of dengue vaccination with the Qdenga vaccine in French territories in America (French Caribbean and French Guiana), as well as in Mayotte and Reunion Island.

• In children and adolescents 6 to 16 years old living in these regions, including those with sickle cell disease or presenting other comorbidities, whose parents or legal guardians are able to produce documented evidence of previous dengue infection, i.e. biologically confirmed in a laboratory (RT-PCR, NS1 antigen testing, IgM/IgG serology) OR clinically diagnosed in a dengue outbreak context and recorded in the health record, for the child/adolescent to be vaccinated. In the absence of any documented evidence of previous dengue infection, an ELISA or EIA serological test may be performed in a laboratory prior to vaccination in order to determine the serological status of the child/adolescent. However, the HAS specifies that it does not recommend the routine performance of pre-vaccination screening.

• In individuals aged 17 to 60 years presenting comorbidities (sickle cell disease, complicated hypertension, diabetes, obesity, kidney failure, chronic cardiopulmonary disease, other haemoglobinopathies, thrombocytopathies), with or without a history of dengue, living in these regions, given the high risk of severe forms of dengue in this population, including in the event of primary dengue, due to the risk of decompensation of these comorbidities.

The recommended vaccination schedule consists of two doses of vaccine given three months apart. The need for a booster dose has not yet been established.

The HAS recommends that the vaccination schedule be implemented in an inter-epidemic period. In the event of recent dengue infection, it is recommended to wait a period of six months before the first injection of Qdenga vaccine.

Given that cases of anaphylactic reactions have been reported during the real-world use of Qdenga in vaccinated individuals with no history of anaphylaxis, the HAS recommends that physicians performing this vaccination be prepared to treat any anaphylactic reaction that might occur following administration of the vaccine. It is recommended that all vaccinated individuals be kept under observation for at least 15 minutes following injection.

Since this is a live attenuated vaccine, it should be noted that the contraindications are indicated in the summary of product characteristics (SmPC) of the Qdenga vaccine. [1] It is important to recall that Qdenga is contraindicated in immunocompromised individuals, and in pregnant or breastfeeding women.

The HAS emphasises the fact that people vaccinated with Qdenga must continue to take personal protection measures against mosquito bites (repellents, long clothing, mosquito nets, etc.); vector control remains an essential method of prevention in dengue control programmes.

The HAS suggests that information materials tailored to each population group concerned (parents, adults, healthcare professionals) by this vaccination be developed and made available to the persons concerned.

The HAS reiterates the need to have access to recent seroprevalence studies in the general population, conducted on the basis of age, and in the post-epidemic period, to determine the intensity of dengue transmission in French overseas regions (using the indicators proposed by WHO, such as seroprevalence in children and peak hospital admissions as a function of age).

These recommendations may be updated in line with developments in scientific knowledge and evolutions in the epidemiological indicators.

Summary of populations, by age and health status, eligible for vaccination with Qdenga, in overseas France: French Caribbean, French Guiana, Reunion island, Mayotte 

[1] European Medicines Agency. Qdenga powder and solvent for solution for injection. Qdenga powder and solvent for solution for injection in pre-filled syringe. Summary of Product Characteristics. Amsterdam: AEM; 2022. https://www.ema.europa.eu/fr/documents/product-information/qdenga-epar-product-information_fr.pdf