Factsheet about dengue fever

factsheet

Dengue fever is present in Asia, the Pacific, the Caribbean, the Americas and Africa. Humans are infected with dengue virus through bites of tiger (Aedes) mosquitoes. There are 4 different dengue types, and infection with one type gives little immune protection against the other types. After an incubation of 8-10 days, a mild and usually self-limited flu-like illness develops. Current scientific evidence shows that sequential infection increases the risk of a severe form of the infection with bleedings - dengue hemorrhagic fever.

In several Asian countries, dengue haemorrhagic fever has become an important cause of disease and death, mainly in children. No specific treatment or vaccine exists for dengue, and general intensive care is often needed.

Dengue fever

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. There is currently no vaccine available for dengue. 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.

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.
  • 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 fever 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.
  • 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 (see the VBORNET maps). The presence of Aedes aegypti in Madeira is a main concern.
  • The risk of transmission of dengue through blood donations is under investigation
  • Dengue illness in the Americas was estimated to cost $2.1 billion US dollars (1.55 billions Euros) per year on average from 2000 to 2007 (in 2010 US$). The cost did not include the vector control activities.
  • 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. As dengue is a “viral hemorrhagic fever”, it is a notifiable disease in the EU and information is collected through the Tessy system.
  • There is no specific case definition for dengue. The EU case definition for “viral hemorrhagic fevers” (VHF) - Commission decision of 28 April 2008 - is used:
     
    • Clinical Criteria : Any person with at least one of the following two:

– Fever
– Haemorrhagic manifestations in various forms that may lead to multi-organ failure

    • Laboratory Criteria : At least one of the following two:

– Isolation of specific virus from a clinical specimen
– Detection of specific virus nucleic acid in a clinical specimen and genotyping

    • Epidemiological Criteria : At least one of the following:

– Travel in the last 21 days to a region where VHF cases are known or believed to have occurred
– Exposure within the last 21 days to a probable or confirmed case of VHF whose onset of illness was within the last 6 months

    • Case classification

A. Possible case ; NA
B. Probable case : Any person meeting the clinical criteria and with an epidemiological link
C. Confirmed case : Any person meeting the clinical and the laboratory criteria

Public health control measures

  • No vaccine or prophylactic drug is available.
  • 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.
  • More information on mosquitoes can be found here:  Aedes albopictus and Aedes aegypti. 

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 long and especially during the hours of highest mosquito activity (mid-morning, late afternoon to twilight).
  • Personal protection measures to avoid mosquito bites should be applied when staying in risk areas by:
  • using repellents and wearing long-sleeved shirts and long pants especially during the hours of highest mosquito activity,
  • using long-lasting insecticidal treated mosquito bed nets which are essential in providing protection from mosquitos bites if the accommodations are not adequately screened or air conditioned,
  • removing mosquito breeding sites in close outdoor/indoor premises.
  • Repellent use must be strictly done in accordance with the instructions indicated on the product label. For newborn children under three months of age, repellents are not recommended.
  • 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).
  • No specific risk for pregnant women

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