No 14 - 2023

New vaccine for prevention of dengue fever

Dengue fever virus belongs to the flavivirus group. Four types of dengue fever exist and infection with one type provides life-lone immunity to this type only. The incubation period ranges from 3 to 14 days, typically 3-7 days. The symptoms of dengue fever are high fever, rash, headache and myalgia, like in severe influenza. However, the majority of infections are asymptomatic or only cause a mild fever. The infection may develop into severe dengue fever (dengue haemorrhagic fever), particularly among children in endemic areas. Dengue haemorrhagic fever is a serious and potentially lethal condition presenting as high fever and a bleeding tendency. This condition is seen more frequently in cases of renewed infection with another serotype.

Transmission

The mosquito species Aedes aegypti is the primary vector and is common in the tropics and subtropics. In recent years, Aedes albopictus (Asian tiger mosquito), which is regarded a less effective vector, has been observed increasingly in the European Mediterranean countries. It bites throughout the day but is more active in the early morning hours before sunrise and in the late afternoon before sunset. The bite is painless but pruritic. The mosquito reproduces in small pools of stagnant water (empty cans, car tires, etc.), which are abundant in urban areas, particularly in slum areas. The high population density of cities combined with the mosquitoes' daytime activity contribute to a high transmission level.

Prevalence

The incidence of dengue fever has increased in recent decades, and the disease is endemic to more than 100 countries, primarily in the tropics and subtropics. It is estimated that 50 million people are infected annually, including 500,000 (1%) with severe disease resulting in approx. 22,000 deaths. The risk of infection is higher for the local population in the endemic areas than among travellers. Even so, dengue fever infections are occasionally imported to Europe, and barring malaria, dengue fever is the most frequent cause of travel-related vector-borne disease in Europe. The combination of frequent imported cases and the presence of a competent vector creates a risk of outbreaks in Southern Europe, including on the islands off the coast of North Africa. For instance, 2012-2013 saw a large dengue fever outbreak on the island of Madeira, where the Aedes albopictus mosquito is now endemic.

Prevention of dengue fever

Use of mosquito repellent containing DEET or icaridin is recommended for stays in dengue endemic areas, particularly in the early morning hours and in the late afternoon. Furthermore, a new vaccine was developed for dengue fever prevention. This vaccine was authorised by the European Medicines Agency (EMA) in December 2022 and is now available in Denmark.

Qdenga^®

Qdenga^® is a live attenuated vaccine that protects against dengue fever. The vaccine contains attenuated variants of dengue virus of serotypes 1, 2, 3 and 4 and may be given to adults, adolescents and children as from four years of age who travel to countries where the disease occurs. For more information about the affected countries, please see this map presenting dengue fever prevalence.

Qdenga^® must be administered as a 0.5 ml dose. The vaccine is given as a subcutaneous injection, preferably in the upper arm. The vaccine may not be given as an intravascular, intradermal or intramuscular injection. The vaccination course consists of two injections given at a three-month interval.

Qdenga^® must be reconstituted before vaccination. The vaccine may not be mixed by shaking, but must instead be swirled. After reconstitution, the solution should be a clear, colourless to pale yellow liquid. For more information about this, please see the summary of product characteristics or the package insert.

Vaccine side effects

The most frequent side effect to Qdenga^® (which may occur in more than one in every five persons) is pain and redness at the injection site, headache, myalgia, general malaise and drowsiness. As many as one in every ten people may present with fever. These side effects, which are typically mild to moderate and recede in the course of few days, occur less frequently after the second vaccine dose than after the first dose.

As all other new medicines, this vaccine is subjected to enhanced surveillance. This will allow quick identification of new safety information. Healthcare professionals have a duty to report all presumed side effects to the Danish Medicines Agency, which may be done at “Report a side effect ” (Danish: Meld en bivirkning).

Vaccine contraindications

The vaccine should not be used in people who have experienced a hypersensitivity reaction (allergic reaction) to a previous dose of Qdenga^®. The vaccine should also not be given to persons with a weakened immune response due to disease, medicines affecting the immune system or to persons with symptomatic HIV infection or with asymptomatic HIV infection with a low CD4 count. Furthermore, the vaccine should not be used in pregnant or breast-feeding women.

Studies reporting on the effectiveness of the vaccine

The vaccine has been shown to be effective in preventing dengue fever in children and young people for 12 months after the second shot is given. In a pivotal study conducted in Latin America and Asia, approx. 20,000 children aged 4-16 years were given Qdenga^® or a placebo (an ineffective injection). The study showed an 80% reduction in the number of fever cases caused by confirmed dengue fever among participants who had received the vaccine (61 cases among 12,700 children) compared with children who received placebo (149 cases in 6,316 children). The vaccine also reduced the number of hospitalisations due to dengue fever by 90%. In the 18 months following the second infection, 0.1% (13 of 12,700) of the children who had received the vaccine were hospitalised due to confirmed dengue fever compared with 1.0% (66 in 6,316) of the children who had received a placebo. So far, no larger studies have been conducted to determine the duration of the protection achieved beyond 12-18 months, and any need for booster vaccination has also not been established yet.

How to purchase the vaccine

The vaccine will be available for orders via the SSI website (item number 105341) and through pharmacies.

Suggested use of the vaccine

Statens Serum Institut assesses that vaccination may be considered for persons aged four years of age or older who will be staying four weeks or more in areas where dengue fever is endemic, and particularly in case of knowledge of current epidemic occurrence of the condition in which case vaccination may be considered already as from two-week stays. Vaccination should be completed, i.e. both doses be administered, no later than one week before departure. As the interval separating the two vaccines is three months, it may prove difficult in practice to give both vaccines timely before departure. Some data indicate that 80% protection may be achieved one month after the first vaccination, but the protection level after two months remains unknown; and if the traveller can be vaccinated only once before departure, he or she should be informed that the achieved protection level is suboptimal.

Particularly partly vaccinated but also fully vaccinated people should keep protecting themselves against mosquito bites by using mosquito repellents and wearing clothes that reduce the risk of mosquito bites.

(L.K. Knudsen, P.H. Andersen, Department of Infectious Disease Epidemiology and Prevention, C.S. Larsen, Danish Society of Travel Medicine, J. Kurtzhals, Danish Society for Clinical Microbiology)

31 March 2023