PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Synonyms: breakbone fever, dengue haemorrhagic fever, dengue shock syndrome, dandy fever, seven-day fever, duengero, ki denga pepo (Swahili, meaning 'sudden overtaking by a spirit')
See also separate article Viral Haemorrhagic Fevers.
The dengue virus is caused by an arthropod-borne flavivirus. The main vector is the mosquito Aedes aegypti. There are four distinct serotypes of dengue virus (DEN1-4), which can all cause a spectrum of disease, ranging from asymptomatic infection to the most severe form of the disease - dengue haemorrhagic fever (DHF).
"Dengue is one disease entity with different clinical presentations and often with unpredictable clinical evolution and outcome".
They have suggested that a new classification of dengue and severe dengue be used. The non-severe dengue would be divided into two subgroups, depending on the presence or absence of specific warning signs. However, the classification of dengue into dengue fever, dengue haemorrhagic fever and dengue shock syndrome is still widely used.WHO case definition of DHF
All of the following are required:
- Current or recent fever lasting for 2-7 days.
- Thrombocytopenia with platelet count of ≤100 000/mm3.
- Haemorrhagic tendencies - such as a positive tourniquet test, petechiae, bruising, and bleeding from mucosa, gastrointestinal tract, injection sites, or other areas.
- Evidence of plasma leakage caused by increased vascular permeability:
- Elevated haematocrit (≥20% over baseline or a similar drop after intravenous fluid replacement).
- Pleural or other effusion - eg, ascites.
- Low protein.
Dengue virus is transmitted by the bite of an infected Aedes mosquito and is endemic in tropical and subtropical regions throughout the world. The female Ae. aegypti (the most important vector) mosquito is semi-domesticated, preferring to lay its eggs in man-made water containers, resting indoors and feeding in the early morning or late afternoon (unlike the malaria mosquito). Anti-malarial measures are largely ineffective against dengue. Aedes mosquitoes are easily disturbed during feeding (and infected mosquitoes are slower feeders) but will return to the same subject or others to complete a meal, thus potentially infecting several people during one feed. Transmission may occur transovarially (passage from maternal body into ova), potentially acting as a reservoir between epidemics.
- Dengue virus is an endemic disease in the tropics and subtropics and is found in the Caribbean, South and Central America, Mexico, Africa, the Pacific Islands, Southeast Asia, the Indian sub-continent, Hawaii, and Australia.
- During the eighteenth and nineteenth centuries, epidemic dengue outbreaks would occur, mainly centred on seaports, with mosquitoes introducing the virus or bringing novel serotypes by boat. During the twentieth century, increasing urbanisation and air transportation has allowed the disease to gather pandemic status with 40% of the global population currently living at risk of the disease.
- WHO recognises dengue virus as a major and emergent concern due both to its expanding distribution and also to an increased frequency of epidemics.
- It is the most common of the flaviviruses with an estimated 50-100 million cases of dengue fever and 0.5 million of DHF worldwide annually.
- 90% of DHF cases occur in children aged <15 years and DHF is a leading cause of death and serious illness in children in some Asian countries.
- Infection provides lifelong immunity but only against the infecting viral serotype. There is evidence that secondary infection with another serotype increases the risk of developing DHF. Pandemics in 1998 and 2001 are thought to have been due to the emergence of a new subtype of the DEN-3 virus.
- Travellers can also become infected. In 2012 and 2013 the Public Health England Rare and Imported Pathogens Laboratory (RIPL) reported an increase in imported cases of dengue fever in England, Wales and Northern Ireland. An increase in cases from Thailand and Barbados was noted. There was also a cluster of cases from Sri Lanka, Brazil and Jamaica. Cases were also reported in residents of the Autonomous Region of Madeira, Portugal. 
For contracting dengue virus:
- High population density
- Urban living
- Poor public hygiene
- Exposure to mosquitoes in endemic areas
For developing severe DHF:
- Age - 95% of DHF/dengue shock syndrome (DSS) occurs in the those aged under 15 years and physiological changes in capillary permeability may be important.
- Repeated dengue infections - infection with a secondary serotype is thought to be important in the development of severe haemorrhagic disease. Memory T cells may inappropriately activate when exposed to a different serotype of the disease.
- Genetic factors - disease severity and outcome unsurprisingly appear to be associated with allelic variation at multiple gene loci involved in acquired and innate immune response
- Viral genotypes - some strains may be more virulent and produce higher rates of DHF.
- Nutritional status - malnourished children are less likely to develop DHF than well nourished children, due to impaired cellular immunity but, where they do, the disease is more likely to be severe.
Patients become infected once bitten by mosquitoes. The virus passes to lymph nodes and replicates, which is followed by spread to the circulation and other tissues. Incubation period is 2-7 days. Take a full travel history, including stop-overs, and always consider the diagnosis in a febrile patient returning from the tropics or subtropics. Although worldwide the majority of dengue infections will be self-limiting, any fever in a traveller returning to the UK will merit further investigation.
The features of dengue fever and DHF are likely to be very similar at the start of the illness. It is the development of abnormal capillary permeability that characterises DHF. This usually occurs as the fever subsides and will result in fluid shift from the intravascular to extravascular space. There may be haemorrhage and thrombocytopenia in dengue fever but they are more common and severe in DHF.
- Haemorrhagic fever syndromes begin with abrupt onset of fever and myalgia.
- Fever is associated with frontal or retro-orbital headache accompanied by onset of a generalised rash.
- Symptoms regress for a day or two but may recur, although fever is rarely as high as at the onset.
- Dengue fever cases experience severe bony and myalgic pain in legs, joints and lower back which may last for weeks (hence, breakbone fever).
- Nausea, vomiting, cutaneous hyperaesthesia, taste disturbance and anorexia are common.
- Abdominal pain may occur and, if severe, suggests possible DHF.
- High fever - usually between 39.5-41°C - persisting for 1-7 days only. Fever is often biphasic with two peaks. Sudden disappearance of fever can be a warning signal of DHF.
- Cardiovascular signs include hypotension and narrow pulse pressure, poor capillary refill and relative bradycardia.
- Rash is initially generalised, macular and blanching and fades after 1-2 days; it may then reappear as a maculopapular, morbilliform rash with sparing of palms and soles. Desquamation may follow.
- Tender muscles on palpation.
- There may be hepatomegaly and lymphadenopathy.
- Positive tourniquet test. This can be performed by inflating a blood pressure cuff on the upper arm to a pressure midway between the systolic and diastolic pressures for five minutes. A test is considered positive when ≥20 petechiae per 2.5 cm2 are seen. It can be negative or just mildly positive during profound shock.
- Other haemorrhagic manifestations include spontaneous petechiae (best visualised in the axillae), purpura, epistaxis, gum bleeding, gastrointestinal haemorrhage and menorrhagia.
- With DHF, there may be pleural effusion, ascites and pericarditis due to plasma leakage.
- Periorbital oedema and proteinuria may be present.
- Maculopathy and retinal haemorrhages may also occur.
- DSS occurs with the development of profound hypotensive shock.
- Central nervous system involvement - eg, encephalopathy, coma, convulsions.
- Typhoid fever
- HIV seroconversion
- Infectious mononucleosis
- Coxsackie and other enteroviruses
- Rickettsial infections
- Parvovirus B19
- Weil's disease (leptospirosis)
- Scrub typhus
- Chikungunya viral infections
Dengue haemorrhagic fever
- Weil's disease (leptospirosis)
- Chikungunya viral infections
- Kawasaki disease
- Yellow fever
- Hantavirus and other viral haemorrhagic infections
- Meningococcal septicaemia
- Encephalitic viruses - eg, West Nile virus
Dengue shock syndrome
As DHF, plus any cause of shock, particularly septic shock and toxic shock syndrome caused by occult staphylococcal infection (check for tampon use).
- FBC may show high packed cell volume if haemoconcentrated and low platelets. There may be a paradoxical lymphocytosis (>15% circulating white cells) in context of overall leukopenia.
- Clotting studies can reveal prolongation of APTT and PT. Fibrin degradation products may be elevated.
- U&E may show electrolyte disturbance and LFTs can be elevated - especially AST.
- Severe cases may show reduced venous bicarbonate due to acidosis.
- Infection may be confirmed by isolation of virus in serum and detection of IgM and IgG antibodies by ELISA, monoclonal antibody or haemagglutination. PCR-based techniques are increasingly being used.
- X-rays are often used to exclude other sources of sepsis/assess complications, although in dengue infection the CXR may show abnormalities, such as pleural effusion, in the first week.
- Blood cultures and repeated malaria films should be checked in the traveller returning with a high fever.
The patient with dengue fever can quickly become severely unwell and close monitoring of clinical signs and laboratory measurements is the cornerstone of good clinical management. Whilst there is no specific treatment for dengue fever, medical care by teams experienced with the effects and progression of severe dengue fever frequently saves lives:
- Fever control with paracetamol, tepid sponging and fans.
- Intravenous fluid resuscitation with close monitoring, remembering the risk of increased capillary permeability. Monitor CVP and urine output and pay close attention to electrolytes, packed cell volume, platelets and LFTs. High volume and aggressive colloid/crystalloid infusion under expert guidance may be needed. Inotropes may also be required, as may renal support.
- Secondary bacterial infections may occur and require treatment.
- Haemorrhage and shock will require FFP and platelets.
- Those with DHF/DSS are likely to require intensive care, where available.
- Severe infections probably only account for 2-4% of cases.
- The vast majority have no serious sequelae and the return of appetite is a good marker of recovery. However, recovery can be associated with prolonged fatigue and depression.
- Background mortality rate in treated cases in Asia is about 0.5-3%.
- If severe and untreated or with complications, as listed below, then mortality is high - up to 50%.
- Any potential vaccine must be protective against all the subtypes of the disease. A number of different candidate vaccines are under development. A live attenuated tetravalent vaccine is at Phase 2 clinical testing. There are safety concerns including the potential of live vaccines to undergo recombination with flaviviruses.
- Anti-mosquito public health measures, such as reducing breeding sites, good sewage management, house design and use of insecticides, may help. Effective mosquito control is virtually non-existent in most endemic countries.
- Mosquito nets are unhelpful as the Aedes mosquito is day-biting.
- Repellents may reduce the risk by reducing the overall number of bites, especially those containing N,N-diethyl-3-methylbenzamide (DEET - use during the day).
- Unlike the other viral haemorrhagic fevers, dengue cannot be aerosolised and thus is an unattractive potential agent of bioterrorism.
- Dr Benjamin Rush (a signatory of the American Declaration of Independence) in Philadelphia coined the name 'breakbone fever' in 1780. This was the first clear description of dengue fever in English. This was during the first simultaneous reported epidemics in Asia, Africa, and North America of 1779-1780.
- Ashburn and Craig showed that the agent responsible was ultramicroscopic and non-filterable, and confirmed in 1906 that it could be transmitted by mosquito.
- The first epidemic in Europe was thought to have occurred in 1928 in Greece.
- Hotta and Kimura isolated the DEN-1 virus in 1943 in Japan, and independently, due to World War II, Sabin (of polio vaccine fame) and Schlesinger the DEN-1 a few months later, and DEN-2 shortly afterwards.
- In 1956, Philippine and Thai haemorrhagic fevers were shown to be caused by dengue viruses, by Dr Bill Hammond, who later isolated DEN-3 and DEN-4.
Further reading & references
- Piggot DC; CBRNE - Viral Hemorrhagic Fevers, Medscape, Apr 2011
- Teixeira MG, Barreto ML; Diagnosis and management of dengue. BMJ. 2009 Nov 18;339:b4338. doi: 10.1136/bmj.b4338.
- Dengue: guidelines for diagnosis, treatment, prevention and control -- New edition; World Health Organization. 2009.
- Senanayake S; Dengue fever and dengue haemorrhagic fever--a diagnostic challenge. Aust Fam Physician. 2006 Aug;35(8):609-12.
- Deen JL, Harris E, Wills B, et al; The WHO dengue classification and case definitions: time for a reassessment. Lancet. 2006 Jul 8;368(9530):170-3.
- Gibbons RV, Vaughn DW; Dengue: an escalating problem. BMJ. 2002 Jun 29;324(7353):1563-6.
- Dengue fever epidemiology; National Travel Health Network and Centre (NaTHNaC)
- Wilder-Smith A, Schwartz E; Dengue in travelers. N Engl J Med. 2005 Sep 1;353(9):924-32.
- Malavige GN, Fernando S, Fernando DJ, et al; Dengue viral infections. Postgrad Med J. 2004 Oct;80(948):588-601.
- Increase in imported dengue fever: England, Wales and Northern Ireland; Public Health England, May 2013
- Dengue fever in Autonomous Region of Madeira, Portugal; Public Health England, Oct 2012
- Rothman AL; Cellular immunology of sequential dengue virus infection and its role in disease pathogenesis. Curr Top Microbiol Immunol. 2010;338:83-98.
- Stephens HA; HLA and Other Gene Associations with Dengue Disease Severity. Curr Top Microbiol Immunol. 2010;338:99-114.
- John TJ; Dengue fever and dengue haemorrhagic fever. Lancet. 2003 Jan 11;361(9352):181-2.
- Ooi ET, Ganesananthan S, Anil R, et al; Gastrointestinal manifestations of dengue infection in adults. Med J Malaysia. 2008 Dec;63(5):401-5.
- Bacsal KE, Chee SP, Cheng CL, et al; Dengue-associated maculopathy. Arch Ophthalmol. 2007 Apr;125(4):501-10.
- Wang CC, Wu CC, Liu JW, et al; Chest radiographic presentation in patients with dengue hemorrhagic Fever. Am J Trop Med Hyg. 2007 Aug;77(2):291-6.
- Durbin AP, Whitehead SS; Dengue vaccine candidates in development. Curr Top Microbiol Immunol. 2010;338:129-43.
- Seligman SJ, Gould EA; Live flavivirus vaccines: reasons for caution. Lancet. 2004 Jun 19;363(9426):2073-5.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Gurvinder Rull
Dr Euan Lawson
Dr Helen Huins