Dengue fever is caused by a flavivirus, transmitted by the Aedes aegypti mosquito (hence an arbovirus). Aedes albopictus also transmits it, but less effectively. It is an enveloped RNA virus. There are 4 well characterised serotypes of dengue virus. A fifth serotype may exist.
EpidemiologyDengue fever has become a global pandemic over recent decades. Each year, an estimated 100 million cases of dengue fever and several hundred thousand cases of dengue haemorrhagic fever occur (depending on epidemics). Widespread in tropical regions, particularly of Asia & Americas, not so much in Africa. Travellers to Dengue affected regions are at risk and Dengue should be considered in returning travellers with the appropriate clinical picture. Associated with global warming, from 2010 onwards there were significant outbreaks in southern Europe, although North America has had this issue for many years
The Dengue fever virus is probably the most important of the arboviruses in terms of cases and deaths. The vector is the Aedes mosquito, which has spread globally due to its ability to breed in domestic habitats eg small water containers, and increased urbanization. Transmission can also occur my mechanisms such as needle stick injury. Breast milk or sexual transmission has not been reported unlike with similar viruses, although might be theoretically possible given viral shredding studies.
Dengue can present with anything from a minor febrile illness to fatal haemorrhagic disease. The presentation is not related to the serotype. It can be related to human genotype, and multiple polymorphisms are now known to modify susceptibility. In endemic areas, infection usually produces a mild disease especially in children. Classic Dengue fever usually affects older children and adults, and causes sudden onset fever, headache, muscle pains. Incubation period is typically 4-7 days and never more than 14 days. A rash may be present, which may develop into petechiae, and eventually desquamates.
Haemorrhagic manifestations e.g. epistaxis, purpura, GI haemorrhage may be seen, but the illness is usually self-limiting and rarely fatal. A vascular leak syndrome may occur between the 4th and 6th day of the illness.
Dengue haemorrhagic fever (DHF) primarily affects children. Initial presentation is similar to that of classic dengue fever, but at the time of defervescence (or shortly before) vascular leak develops causing shock (often with abdominal pain) then haemorrhage in skin, GI tract and at venepuncture sites. Besides thrombocytopenia and haemoconcentration, a tourniquet test (demonstrating capillary fragility) may help diagnosis. If shock is appropriately managed and the patient survives the first 24 hours then recovery is usually quick and uneventful.
Other features are neutropenia, atypical lymphocytosis, thrombocytopenia and mild elevations of transaminases (this last a constant feature). The neutropenia can be severe, even if the illness is not. Clotting derangement is possible and so is low albumin. Acute kidney injury is rare.
DHF is an antibody-dependent enhancement phenomenon. The patient must first have antibodies to Dengue, through previous exposure. On second exposure, but with a different serotype, antigen-antibody complexes form that are taken up by macrophages, but that are not effectively neutralized; instead, replication continues and inflammatory mediators are produced causing vascular leak etc.
FBC, LFTS, Dengue serology.
- Before day 5 - virus isolation or RNA identification(RT-PCR) or detection viral antigens (eg NS1)
- After day 5 viral antigens, IgM (from day 4). IgG from day 10 and can last for life.
The twin tests for NS1 and IgM by point of care testing has revolutionised diagnosis.
Supportive - usually with crystalloid +/- colloid resuscitation. The morbidity and mortality associated with DHF is significant, especially where patients do not have access to ITU/HDU facilities.
The development of a vaccine was a priority, but faced the potential problem of increasing the risk of DHF through immune enhancement. A tetravalent vaccine is required. Clinical trials established as of 2014 that one such vaccine:
- Reduces severe haemorrhagic disease by 80% and provides over 50% protection to all but serotype 2
- Appears to only really work in those already primed by arbovirus exposure. This excludes young children which are a high risk group and travellers from areas where arbovirus infection rare
CYD-TDV was licensed in 2015. It is now recommended only for sero postive patients (ie to prevent DHF) as in seronegative patients it does increase risk of severe Dengue fever. Second generation vaccines are in clinical trials as of 2019.
Notifiable in the UK.
- ↑ Valerio L, de Balanzó X, Jiménez O, Pedro-Bolet ML. Haemorrhagic exanthema due to dengue virus induced by acetylsalicylic acid.. Anales del sistema sanitario de Navarra. 2006 Sep-Dec; 29(3):439-42.
- ↑ Kho LK, Wulur H, Himawan T. Dipyridamole in the treatment of dengue haemorrhagic fever. The Southeast Asian journal of tropical medicine and public health. 1979 Sep; 10(3):385-8.
- ↑ Guzman MG, Harris E. Dengue. Lancet. 2014 Sep 12.(Epub ahead of print) (Link to article – subscription may be required.)
- ↑ da Silva Voorham JM. A possible fifth dengue virus serotype. Nederlands tijdschrift voor geneeskunde. 2014; 158:A7946.
- ↑ Gubler DJ. Dengue and dengue hemorrhagic fever. Clinical microbiology reviews. 1998 Jul; 11(3):480-96.
- ↑ de Alwis R, Williams KL, Schmid MA, Lai CY, Patel B, Smith SA, Crowe JE, Wang WK, Harris E, de Silva AM. Dengue viruses are enhanced by distinct populations of serotype cross-reactive antibodies in human immune sera. PLoS pathogens. 2014 Oct; 10(10):e1004386.(Epub) (Link to article – subscription may be required.)
- ↑ Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F, Greenfield M, Durkan M, Leong YS, Dong Y, Cook H, Axford J, Callahan AG, Kenny N, Omodei C, McGraw EA, Ryan PA, Ritchie SA, Turelli M, O'Neill SL. Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature. 2011 Aug 25; 476(7361):454-7.(Epub) (Link to article – subscription may be required.)
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