Dengue, also known as “break-bone fever”, is the most prevalent arbovirus. Arboviruses are viruses that are transmitted by arthropods, such as mosquitoes.
There are four dengue virus serotypes: DENV-1, DENV-2, DENV-3 and DENV-4. It is possible to get infected by each serotype. Recovery from an infection by one serotype is believed to provide lifelong immunity against that specific serotype. However cross-immunity to other serotypes is only partial and temporary. Subsequent infections (secondary infection) by other serotypes increases the risk of developing severe dengue.
Dengue is transmitted to humans through the bite of an infectious female Aedes mosquito. Mosquitos become infected when they bite a person infected with the virus, once infectious the mosquito is capable of transmitting the virus during subsequent blood meals during the rest of its life. Febrile patients should avoid mosquito bites to reduce the risk of further transmission.
The primary vectors are Aedes aegypti, and to a lesser extent Aedes albopictus. These mosquito species can also transmit chikungunya, yellow fever and Zika viruses.
Aedes aegypti is a day-time feeder, the peak biting periods are early in the morning and in the afternoon until the evening before sunset.
They lay eggs in natural containers such as tree holes. Nowadays they are well adapted to urban environments and larval habitats are often man-made containers like buckets, discarded containers, used tyres, storm water drains etc., thus making dengue an insidious disease in densely populated urban areas.
Dengue begins after an incubation period of four to ten days (with a range of 3 to 14 days) after the bite from an infectious mosquito.
Most dengue infections are asymptomatic. It is estimated that one in four will develop symptoms. The most common presentations is a mild to moderate flu-like illness.
Dengue begins abruptly with symptoms like fever, severe headache, pain behind the eyes, muscle and joint pains, nausea, vomiting, swollen glands or a rash. It usually last two to seven days. Often, but not exclusively, a biphasic pattern is present with an initial three to four days of fever followed by improvement with a recrudescent of the fever on day five to six. Frequently a red rash, macular exanthem comparable with measles, is seen.
There is no specific treatment available. Supportive care such as fever reducers and pain killers can be taken to control the symptoms, the best option is paracetamol. It’s advised to avoid non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin (acetylsalicylic acid) because of their anticoagulant properties.
Approximately one in twenty patients with dengue virus disease progress to develop a severe-life threatening diseases called ‘severe dengue’. It is a potentially deadly complication due to plasma leaking, severe bleeding, and/or organ impairment. Severe dengue has a high risk of death when not managed appropriately, early recognition and promptly initiating intensive support therapy can reduce the risk of death.
Severe dengue is very rare in travellers and expatriates. It can occur during infection with any of the four dengue serotypes. It is more common among infants and individuals who are infected for the second time with a different serotype (secondary dengue virus infections). The most widely cited hypothesis for this occurrence is antibody-dependent enhancement of disease. It occurs when non-neutralizing anti-dengue virus antibodies bind to but do not neutralize an infecting dengue virus. This virus-antibody complex allows for enhanced viral entry into host cells, specifically dendritic cells and macrophages. Once inside the cell, the virus replicates and generates higher virus titers in the blood than when anti-dengue virus antibody is not present, which results in a ‘cytokine storm’ and ultimately leading to more severe disease.
Dengue is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas. There is usually no risk above an altitude of 2000metres.
Dengue outbreaks are occurring in many countries of the world in the Americas, Africa, the Middle East, Asia, and the Pacific Islands. Asia represents around seventy percent of the global burden of disease.View the map
Dengue is common in Belgian travellers, but severe dengue, hospitalisation or death because of dengue is rare. Travellers at risk for dengue should be advised on:
- mosquito bite prevention: which consists of a combination of mosquito-repellent measures especially during daytime
Vaccination against dengue
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® and Dengvaxia®. The use of Dengvaxia® is limited to seropositive people in endemic areas. Qdenga® is available in Belgium and can be used in certain indications.
Qdenga® (TAK-003, Takeda)
As of December 2022 Qdenga® has been granted marketing authorization in the European Union for the prevention of dengue disease in individuals from four years of age.
Product: Qdenga® (TAK-003), against dengue virus serotypes 1,2,3 and 4
Type: live-attenuated vaccine
Schedule: adults, adolescents and children from 4 years of age: 0.5ml dose at a two-dose schedule with 3 months interval (0 and 3 months). The need for a booster dose has not been established.
Route of administration: subcutaneous
Indication: The Superior Health Council (SHC) recommends vaccination against Dengue with Qdenga® for: people residing for a period of more than 4 weeks, long-term travellers (> 4 weeks) or frequent travellers from four years of age meeting all 3 of the following criteria:
- having had dengue before (based on history or laboratory confirmed*)
- travelling to a dengue endemic region**
- receiving both priming doses before departure
*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.
**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.
Qdenga® is currently not recommended for long-term or frequent travellers to endemic regions:
- who did not have a previous dengue infection
- who had dengue before and meets one (or more) of the 3 criteria below:
- cannot get two priming doses (day 0 - month 3) before departure
- leaves for a short trip
- who have a medical contra-indication for live attenuated vaccines
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.
- 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
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
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