Dengue and Dengue haemorrhagic fever

Dengue/ DHF in short

• a viral disease transmitted by mosquitoes
• endemic in more than 100 tropic and subtropic countries around the world
• global incidence is growing with about 2.5 billion people at risk
• no vaccine available
• without appropriate treatment, Dengue haemorrhagic fever – a severe complication of dengue – can reach fatality rates of 20% or more
• mosquito control can effectively prevent transmission of the virus and reduce incidence

Dengue/ DHF in detail

Pathogenic agent
Dengue is caused by four closely related viruses (Den-1 to Den-4) within the genus flavivirus. These are single-stranded RNA viruses with a size of approximately 40 to 50 nm. The RNA genome is associated with the "C"-protein to form a nucleocapsid. In the surrounding lipid membrane, two proteins named "M" and "E" are embedded. The four serotypes differ in the amino acid composition of their "E"-proteins.

Transmission/pathogenesis
The dengue viruses are spread by the bites of infected female Aedes mosquitoes. The most important vector species is Aedes aegypti. In recent years, however, a secondary dengue vector in Asia, Aedes albopictus, has spread into the Americas, parts of Europe and Africa, causing several dengue outbreaks.

Only female mosquitoes transmit the virus. When an infected female feeds on human blood, the virus is transmitted. While the virus circulates in the human blood (for 2 to 7 days), the infected individual experiences fever – the most prominent dengue symptom. During this time, other female Aedes mosquitoes biting the infected human can take up the virus and – after an incubation time of about 10 days – spread it on to other human hosts during subsequent blood meals. The viruses are also transferred vertically, i.e. from a female mosquito to her offspring via the eggs. Human to human transmission does not occur, but the virus can be transmitted by infected blood or blood products (platelets, plasma).

Symptoms
Dengue is a moderate to severe flu-like illness, with the severity of symptoms depending on the viral serotype and the age of the patients. In younger children, the course of disease is often milder than in older children or adults. The principal symptoms are high fever, severe headache, muscle and joint pain, nausea and vomiting, eye pain and rash.

A potentially fatal complication is Dengue haemorrhagic fever (DHF), which is characterized by high fever that last for 2 to 7 days and subsequent haemorrhagic manifestations, such as the tendency to bruise easily, bleeding of the nose or gums and internal bleeding. Without proper treatment, circulatory failure and shock may occur (Dengue shock syndrome, DSS). Fatality rates may exceed 20%, but with early and appropriate medical care, death rates can be reduced to less than 1%.

Infection with one viral serotype does not provide protective immunity against the other three viruses; quite the opposite, sequential infection with another serotype seems to develop more often into DHF.

Treatment
There is no specific treatment for dengue or DHF. In severe cases, fluid replacement therapy can effectively prevent death from DHF.

Prevention
Control of the mosquito vector remains critical in dengue/DHF prevention. Most importantly, breeding places for female Aedes mosquitoes need to be eliminated. Aedes aegypti mainly breeds in man-made containers for water storage and other items that collect water, such as used tires. In Africa, it also breeds extensively in natural habitats, e.g. in tree holes or leaves. In urban and semi-urban environments, the best method to prevent dengue transmission is to cover all water-catching items or to properly discard them.

Insecticides might also be used to prevent breeding in possible larval habitats and/or to kill eggs, larvae and adult mosquitoes.

Vaccination
There is currently no commercially available vaccine, but several candidates are being tested.

Epidemiology, incidence, mortality
Dengue is endemic in more than 100 countries with tropical or sub-tropical climate. According to the World Health Organization (WHO), global incidence has increased dramatically in recent decades. This is thought to be due to the expanding geographical distribution of the mosquitoes and different viral serotypes. The WHO estimates that as many as 50 million infections may occur annually, with 2.5 billion people worldwide at risk. In 2007, more than 890,000 cases were reported in the Americas alone, with 26,000 cases of DHF.

During epidemics, infection rates among people who have not been exposed previously are normally 40 to 50% but can even reach 80 to 90%. While dengue fever is lethal only in isolated cases, the lethality rates of DHF and DSS may reach 20% and 44%, respectively.

To know or not to know...
Aedes aegypti transmits not only Dengue viruses but also yellow fever, Chikungunya and several other viruses that cause infectious disease in humans and animals.

More information
- WHO: www.who.int/csr/disease/dengue/en/index.html
- Centers for Disease Control and Prevention: www.cdc.gov/ncidod/dvbid/dengue/index.htm

Literature
- WHO fact sheet Dengue/DHF: www.who.int/mediacentre/factsheets/fs117/en/index.html
- Centers for Disease Control and Prevention: www.cdc.gov/ncidod/dvbid/dengue/index.htm
- Robert Koch Institute (in german only): www.rki.de/nn_196658/DE/Content/InfAZ/D/Dengue/Dengue.html
- Molekulare Virologie, Susanne Modrow, Dietrich Falke, Spektrum Akademischer Verlag GmbH Heidelberg, 1997