Factsheet about dengue

Dengue

Dengue is a mosquito-borne viral disease widely spread in tropical and subtropical regions. The disease is transmitted by Aedes mosquitoes, which breed in the peridomestic environment. While most of the clinical cases present a febrile illness, severe forms including hemorrhagic fevers and shock with fatalities are reported. As dengue is a “viral hemorrhagic fever”, the disease is under European surveillance.  It is by far the most important mosquito-borne viral disease affecting humans worldwide; tens of millions of cases occur each year resulting in approximately 20,000-25,000 deaths mainly in children. There are four serologically distinct dengue viruses, so people living in a dengue-endemic area can have several dengue infections in their lifetime. Dengue is endemic in most of the European Overseas Countries, Territories and Departments located in tropical areas. In continental Europe limited outbreaks may occur in areas infested by Aedes albopictus, an invasive mosquito species that spread over the past twenty years.

Case definition

Clinical Criteria

— Fever

Laboratory Criteria

1. Probable case

— Detection of dengue specific IgM antibodies in a single serum sample

2. Confirmed case

At least one of the following five:

— Isolation of a dengue virus from a clinical specimen;

— Detection of dengue viral nucleic acid from a clinical specimen;

— Detection of dengue viral antigen from a clinical specimen;

— Detection of dengue specific IgM antibodies in a single serum sample AND confirmation by neutralization;

— Seroconversion or four-fold antibody titre increase of dengue specific antibodies in paired serum samples

Epidemiological Criteria

History of travel to, or residence in an area with documented on-going transmission of dengue, within the two-week period prior to the onset of symptoms

Case Classification

1. Possible case NA

2. Probable case

Any person meeting the clinical and the epidemiological criteria, and the laboratory criteria for a probable case

3. Confirmed case
 Any person meeting the laboratory criteria for a confirmed case

The pathogen

• Dengue is caused by a virus of the Flaviviridae family, Flavivirus genus which includes viruses such as yellow fever, West Nile and tick-borne encephalitis.
• There are four distinct dengue viruses without cross immunity. People can have up to four dengue infections in their lifetime. It is fairly widely accepted that all four viruses are of Asian origin.

Clinical features

• Up to 40–80% of all dengue infections are asymptomatic.
• Commonly reported clinical symptoms include sudden onset of high fever, severe headache and retro-orbital pain, myalgia, arthralgia, a maculo-papular rash and minor haemorrhage. Fever and other symptoms often follow a ‘saddleback’ sequence, with a brief remission after the third day. Illness rarely lasts for more than ten days, but convalescence can be prolonged and debilitating.
• A portion of cases, usually < 5%, can be severe and a fraction of these may be fatal. Most severe cases and fatalities occur among children and adolescents. Severe dengue — commonly referred to as ‘Dengue haemorrhagic fever/Dengue shock syndrome (DHF/DSS)’ to distinguish it from ‘classic’ dengue fever (DF) — is characterised by an increase of vascular permeability that can lead to life-threatening hypovolemic shock.
• The causes of this severe dengue condition have been debated for decades, but remain unresolved. A hotly contested hypothesis is that after a ‘primary’ infection with one serotype, ‘secondary’ infections by one or more of the other serotypes can precipitate ‘antibody dependant enhancement’ (ADE). Resolution of this issue is hampered by the absence of a reliable animal model. In addition, controversy remains with regards to the validity of a graded set of criteria to categorise severity. Both issues are of prime importance for the management and treatment of patients, and to future acceptance of dengue vaccines.

Transmission

• The incubation period ranges from 3 to 14 days, with an average of 4–7 days.
• Viraemia reaches high titres on the day before onset of symptoms and is generally high enough to infect mosquitoes for the next four days.
• Immunity to any of the four serotypes is probably life-long, but this does not confer protective immunity to the other three serotypes.
• Humans are the main amplifying host of the virus. In tropical and sub-tropical urban areas, the viruses are maintained in a human/mosquito cycle.
• Bites from infected mosquitoes are the only mode of transmission.
• Mosquitoes acquire the virus when they feed on a viraemic host, after which (in a susceptible species) the virus infects many tissues, including the salivary glands. While it can be a matter of weeks (and many blood meals) to become infective, the mosquitoes are infected for life. New infections in humans can occur when saliva that contains virus is injected into a non-immune host during subsequent blood meals. The ‘extrinsic incubation period’, the time required for the mosquito to become infective, is about ten days at 27°C.
• There is some evidence that forest monkeys are involved in a ‘jungle cycle’ with forest mosquitoes serving as vectors in south-eastern Asia and western Africa. However, there is no evidence that these viruses are responsible for large epidemics.
• The virus circulates between humans in village and urban areas. Dengue is essentially a village and urban disease because its principal vector, Aedes aegypti, is abundant in the peridomestic environment. The species is a highly effective vector: it feeds almost exclusively on humans, breeds in small man-made articles that contain water, rests inside buildings and is rarely found more than 50 meters from human habitation. Its biting habits tend to be diurnal.
• A second species, the Asian tiger mosquito, Aedes albopictus, can be common in the peridomestic environment, particularly in urban areas with abundant vegetation. It is widely regarded, however, as a ‘secondary’ vector because it is not host-specific; blood-meals are taken from animals that are not susceptible to the dengue virus and therefore do not participate in the transmission cycle. Nevertheless, epidemics have occurred in places where this mosquito was the only vector species present.
• Aedes aegypti was once present in Europe and responsible for large epidemics of yellow fever and dengue. Its disappearance after World War II has never been explained. Currently it is present in Madeira and it is conceivable that it could become re-established and widespread in Europe.
• The Aedes albopictus mosquito present in southern Europe is well adapted to winter temperatures, and is likely to extend its range northwards. It is already a major nuisance in several Mediterranean countries, and was responsible for autochthonous cases of dengue in France and Croatia in 2010.

Diagnostics

• Dengue viral genome can be detected by RT-PCR in blood specimens up to day five of illness.
• Another approach is the detection of the non-structural-1 (NS1) dengue antigen up to day four post-onset. However sensitivity of the assay is depending on the serotype.
• Determination of the dengue serotype and genotype is important for epidemiological studies; co-circulation of different dengue serotypes during an outbreak is not uncommon.
• Viral isolation is done for research purposes.
• Serological diagnosis can be performed by detection of dengue IgM antibodies in serum specimen from day 5–6 of illness, or detection of a four-fold rise of specific IgG antibody titre on a pair of sera (acute and convalescent specimens).
• In a secondary dengue infection, dengue IgM antibodies usually appear earlier from day 2–3 post onset and with a shorter duration. An increase of dengue IgG titre has to be measured.
• Serological cross-reactions between dengue viruses and closely related flaviviruses are reported.

Case management and treatment

• Supportive therapy is the only option, with strict avoidance of aspirin and other anticoagulants

Epidemiology

• Dengue is endemic in more than 100 countries in Africa, the Americas, South-East Asia, the Western Pacific and the eastern Mediterranean. ECDC monitors the current dengue transmission worldwide.
• Dengue viruses are highly mobile, transported by infected travellers; all four serotypes now co-circulate in many cities around the world. The number of dengue cases has been increasing dramatically in the past few decades and large outbreaks have been reported.
• Imported cases of dengue are frequently reported by travellers returning to the EU from endemic areas and may generate a local transmission in areas where the vector is present. In August 2010, several autochthonous cases (mild cases) were reported in Croatia and France in areas infested by Aedes albopictus. Cases in France were detected through enhanced surveillance. Following this outbreak, several sporadic events of local transmission have been reported in Europe.
• The last dengue epidemics in the European continent dated from 1927–28 in Greece, with high mortality and Aedes aegypti as mosquito vector.
• Through entomological surveillance, distribution maps of potential dengue vectors in Europe are regularly updated. The presence of Aedes aegypti in Madeira is a main concern.
• Enhanced surveillance of dengue in areas where potential vectors are present during the mosquito season is crucial for an early detection and appropriate vector and disease control measures.
• Early detection of infectious dengue patients is important to prevent local transmission in areas where the vector is present and active. Dengue is a notifiable disease in the EU and information is collected through the TESSy system.

Public health control measures

• A licensed dengue vaccine targeting people with previous exposure to dengue virus has recently been put on the market.
• Integrated vector management program aiming to reduce mosquito vector density in a sustainable manner is of primary importance. Intersectoral collaboration and efficient public communication strategy to ensure community participation are required for sustainable vector control program.
• Activities supporting the reduction of mosquito breeding sites in outdoor/indoor areas by draining or discarding sources of standing water at the community level include:
  • removal of all open containers  with stagnant water in and surrounding houses on a regular basis (flower plates and pots, used tyres, tree-holes and rock pools), or, if that is not possible, treatment with larvicides),
  • tight coverage of water containers, barrels, wells and water storage tanks,
  • wide use of window/door screens by the population.
• Measures aiming to control larvae and adult mosquito vector population can be applied in an outbreak situation.
• In affected outbreak areas, elimination of adult mosquitoes through aerial spraying with insecticides can be considered.

Infection control, personal protection and prevention

• Prevention is also based on protection against mosquito bites. Aedes mosquitoes have diurnal biting activities in both indoor and outdoor environments. Therefore, personal protection measures should be applied all day, especially during the hours of the highest mosquito activity (mid-morning, late afternoon to twilight). Personal protective measures against mosquito bites include the use of mosquito bed nets (preferably insecticide-treated nets), sleeping or resting in screened or air-conditioned rooms, the wearing of clothes that cover most of the body, and the use of mosquito repellent in accordance with the instructions indicated on the product label.
• Travellers, especially children, pregnant women, and people with immune disorders or severe chronic illnesses, should consult their doctor or seek advice from a travel clinic to receive personalised recommendations on use of repellents and protection before travelling;
• Similar protective measures apply to a symptomatic patient in order to prevent transmitting the disease to non-infected mosquitoes.
• More information on mosquitoes can be found here: Aedes albopictus and Aedes aegypti.

Advice to travellers

• Dengue is one of the most common vector-borne diseases contracted by travellers in tropical and sub-tropical countries.
• The use of repellents is recommended as well as the use of bed nets during siesta (these mosquitoes bite during the day).

References

• Gubler D. Dengue and dengue hemorrhagic fever: its history and resurgence as a global public health problem. In: Gubler D, Kuno G. Dengue and dengue hemorrhagic fever. Wallingford: Oxon, UK ; New York: CAB International; 1997. p. 478.
• La Ruche G et al, First two autochthonous dengue virus infections in metropolitan France, September 2010. Euro Surveill. 2010;15(39):pii=19676
• Reiter P. Oviposition, dispersal and survival in Aedes aegypti; implications for the efficacy of control strategies. Vector Borne Zoonotic Dis 2007: Summer;7(2):261-73
• Reiter P, Gubler DJ. Surveillance and control of urban dengue vectors. In: Gubler D, Kuno G. Dengue and dengue hemorrhagic fever. New York: CAB International 1997; p. 425–462.
• Reiter P. Yellow fever and dengue: a threat to Europe?. Euro Surveill. 2010;15(10):pii=19509
• Schmidt-Chanasit J et al (2010). « Dengue virus infection in a traveller returning from Croatia to Germany ». Euro Surveillance 2010;15(40):pii=19677.
• Shepard DS , Coudeville L, Halasa YA, Zambrano B, and Dayan GH. Economic Impact of Dengue Illness in the Americas. Am. J. Trop. Med. Hyg., 84(2), 2011, pp. 200–207
• Wilder-Smith A, Ooi EE, Vasudevan SG, Gubler DJ. Update on dengue: epidemiology, virus evolution, antiviral drugs, and vaccine development. Curr Infect Dis Rep. 2010 May;12(3):157-64
• Wilder-Smith A. Risk of Dengue in Travelers: Implications for Dengue Vaccination. Curr Infect Dis Rep. 2018 Oct 29;20(12):50

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