Dengue has acquired the dubious honour of being the world’s most important mosquito-borne viral disease, rendering about 2.5 million people in 100 countries at risk. An estimated 60 million cases occur annually, a significant fraction of whom require hospitalisation for haemorrhagic and hypotensive complications, culminating in 30,000 fatalities. Epidemics of dengue fever have been reported regularly, particularly in crowded urbanised areas in tropical and subtropical regions, including Southeast Asia and recently in India. In addition to population expansion, urbanisation, poverty, lifestyle changes and widespread travel, changing climate patterns have been blamed for the worldwide upsurge of dengue outbreaks.

Dengue Fever has been recognised for at least several hundred years Since Benjamin Rush from Philadelphia first described it as ‘breakbone fever’ in 1780. Dengue virus, first isolated in 1943, is morphologically indistinguishable from the agent causing yellow fever. Dengue fever is caused by one of four closely related, but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3 and DEN-4), of the genus Flavivirus. Infection with one of these serotypes does not provide cross-protective immunity, so persons living in a dengue-endemic area can have four dengue infections during their lifetime. The viruses that cause dengue are maintained in a cycle that involved humans and Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans. Transmission of dengue virus is often seasonal, with rates increasing during hot, humid months. The vector A.aegypti breeds in peridomestic fresh water as might be stored in natural and artificial containers in and around human dwellings (e.g. flowerpots, water storage containers).

Dengue virus infections may be asymptomatic or lead to a range of clinical presentations, even death. The incubation period is 4-7 days (range 3-14). Typically Dengue fever is an acute febrile illness characterized by frontal headache, retroocular pain, muscle and joint pain, nausea, vomiting and rash. The febrile, painful period of Dengue fever lasts 5-7 days, and may leave the patient feeling tired for several more days. The vast majority of infections especially in children under age 15 years are asymptomatic or minimally symptomatic. Infants and young children may have an undifferentiated febrile disease with a maculopapular rash. Older children and adults may have either a mild febrile syndrome or the classical and even incapacitating disease. Leukopenia and mild thrombocytopenia are frequent.

DHF is defined as an acute febrile illness with minor or major bleeding. Thrombocytopenia (£ 105/ml) and evidence of plasma leakage documented by haemoconcentration, pleural or other effusions, or hypoalbuminaemia or hypoproteinamia. The major pathological change that determines the severity of disease in DHF and differentiates if from dengue fever is the leakage of plasma. DHF commonly begins with a sudden rise in temperature and other symptoms resembling dengue fever. DHF usually develop around the third to seventh day of illness.

DSS is defined as DHF with signs of circulatory failure including narrow pulse pressure (£ 20 mmg Hg), hypotension, or frank shock. The four warning signs for impending shock are intense, sustained abdominal pain, persistent vomiting, restlessness or lethargy and a sudden change from fever to hypothermia with sweating and prostration. The development of any of these signs or any suggestion of hypotension are indications for hospital admission and management to prevent shock.

They include severe haemorrhage, hepatic damage, cardiomyopathy and encephalopathy. Neurological manifestations such as altered consciousness, convulsions and coma have been ascribed to an encephalopathy secondary to prolonged DHF/DSS, resulting from the leakage of plasma into serious spaces, haemorrhage, shock, and metabolic disturbances. However, invasion of the central nervous system (viral encephalitis) is a recently documented possibility.
Vertical transmission of dengue virus has been recorded in a small number of cases, leading to neonatal DF or even DSS.

Laboratory findings include leukopenia, thrombocytopenia and in many cases, serum aminotransferase elevations. The majority of suspected dengue patients are most rapidly diagnosed by serology, the method of choice being IgM capture ELISA. As an adjunct technique, amplification of viral nucleic acid by the polymerase chain reaction (PCR) facilitates the early detection of dengue virus in the serum during viraemia which correlates with the febrile phase.

Patients with Dengue Fever require rest, oral fluids to compensate for losses via diarrhoea or vomiting, analgesics, and antipyretics for high fever (paracetamol but not aspirin, so that platelet function will not be impaired). Steroids in DSS are not helpful. With the earliest suspicion of threatened severe illness, an intravenous line should be placed so that fluids can be provided. Monitoring of blood pressure, haematocrit, platelet count, haemorrhagic manifestations, urinary output, and level of consciousness is important. Because patients have loss of plasma they must be given isotonic solutions and plasma expanders, such as Ringer’s acetate or Ringer’s lactate, plasma protein fraction, and dextran 40. Vital signs should be measured every 30-60 min and haematocrit every 2-4 h, then less frequently as the patient’s condition stabilizes.

Monitoring should be continued for at least a day after defervescence. Once the patient begins to recover, extravasated fluid is rapidly reabsorbed, causing a drop in haematocrit. Before discharge, the patient should meet the following criteria: absence of fever for 24 h (without antipyretics) and a return of appetite; improvement in the clinical picture; hospital care for at least 3 days after recovery from shock; no respiratory distress from pleural effusion or ascites; stable haematocrit; and platelet count greater than 50,000/mL.

Vaccine development

An effective vaccine will have to be tetravalent because pre-existing heterotypic dengue antibody is a risk factor for DHF. Candidate attenuated vaccine viruses have been evaluated in phase I and II trials in Thailand.

At present, dengue transmission can only be reduced by mosquito control.

Effective and sustainable prevention of dengue outbreaks must include the individual community’s participation in dengue control; government participation for the elimination of mosquito production sites when legal or large-scale action is necessary; and some, though limited, use of larvicides and adulticides.