BACKGROUND

Dengue – a new global public health concern

Dengue fever – colloquially also called breakbone fever [in german: Knochenbrecherfieber] – is a human disease caused by the dengue virus (DENV) and transmitted by certain species of mosquitoes. It mainly occurs in tropical and subtropical countries and can, in rare cases, be life-threatening. Dengue fever now is regarded as an emerging disease with major public health implications.

The symptoms of the Dengue disease are fever, headache (typically located behind the eyes), muscle pain, joint pain, and a skin rash reminiscent of measles. Most infected people (80%) are asymptomatic or have only mild symptoms such as uncomplicated fever. About five percent have a more severe illness and a small group of infected people develops the very serious dengue hemorrhagic fever (DHF), resulting in bleeding, low levels of platelets and blood plasma leakage, or the dengue shock syndrome (DSS) with dangerous low blood pressure. Both outcomes are life-threatening with approximately 25,000 deaths per year.

The Dengue virus is a RNA-containing Flavivirus. Other members of the same genus include yellow fever virus, West Nile virus, etc. Most of them are transmitted by arthropods (mosquitoes or ticks) and are therefore also referred to as “arboviruses” (arthropod-borne viruses). The Dengue virus genome contains about 11.000 nucleotides, which code for three different proteins (C, prM and E), which form the virus particle, and seven other proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5), which are only present in infected host cells and play a role in viral replication. There are four strains (serotypes) of the virus known, which are named DENV-1 to DENV-4. Infection with one type usually gives lifelong immunity to that type, but only short-term immunity to all the others. Subsequent infection with a different type increases the risk of severe complications. It is not entirely understood why secondary infection with a different strain of dengue virus places people at risk of dengue hemorrhagic fever or dengue shock syndrome. A hypothesis is that of antibody-dependent enhancement (ADE). The exact mechanism of ADE is unclear. It may be caused by poor binding of non-neutralizing antibodies and delivery into the wrong compartment of white blood cells that have ingested the virus for destruction. There is a suspicion that T-cells and soluble factors such as cytokines and the complement system may also play a role in the development of severe complications.

Aedes albopictus By James Gathany, CDC [Public domain], via Wikimedia Commons

Dengue can also be transmitted via infected blood products and organ transplantation. In countries, where dengue is endemic, for instance Singapore, the risk is estimated to be between 1.6 and 6 per 10,000 transfusions. Person-to-person transmission of Dengue viruses has been reported, but is rather unusual.

What is known about the disease mechanism in humans? When a mosquito carrying Dengue virus bites a person, the virus enters the skin with the saliva of the mosquito. It enters white blood cells and reproduces inside the cells while they move throughout the body. The white blood cells respond by producing a number of signaling proteins, such as cytokines and interferons, which are responsible for many of the symptoms, such as fever, cold-like symptoms and pains. In severe diseases, the virus production inside the body is greatly increased and more organs such as liver and bone marrow can be affected. Due to endothelial dysfunction, fluid from the blood stream leaks through the walls of small blood vessels into body cavities. As a result, less blood circulates in the blood vessels, and the blood pressure becomes very low and cannot supply sufficient blood to the organs. Furthermore, dysfunction of the bone marrow due to infection of stromal cells leads to a reduced number of platelets, which are necessary for effective blood clotting. This increases the risk of bleeding, the other major complication of Dengue fever.

Dengue shock syndrome and Dengue hemorrhagic fever occur in less than five percent of all cases of Dengue, however those who have previously been infected with other types of Dengue virus are at an increased risk. This critical phase is observed more often in children and young adults.

Most people with dengue recover without any problems. The mortality is one to five percent without treatment, and less than one percent with adequate treatment; however severe disease has a mortality of about 25 percent. Dengue is endemic in more than 110 countries and infects nearly 400 million people worldwide a year, leading to half a million hospitalizations and approximately 25,000 deaths.

Treatment of acute Dengue fever consists oral or intravenous rehydration for moderate diseases, and intravenous rehydration or blood transfusion for the severe forms of the disease.

In spite of great efforts there is no vaccine available at present and thus prevention is sought by reducing the habitat and the number of mosquitoes and by avoiding exposure to bites. Reducing or eliminating the mosquitoe's habitats is done by emptying water containers or by adding insecticides or biological control agents to these areas, although spraying with organophosphate or pyrethroid insecticides is not thought to be effective. Reducing open water collections through environmental modification is the preferred method of control, given the concerns of negative health effect from insecticides and logistical difficulties with control agents. Moreover, people can prevent mosquito bites by using clothes that fully cover the skin, using mosquito netting while resting, and/or the application of insect repellents, with DEET being the most effective.

The incidence of dengue fever has increased significantly since the 1960s, with around 400 million people infected yearly. Since World War II and the subsequent globalization, Dengue fever has become a global problem. In former times Dengue fever was regarded as a disease of topical and subtropical countries, because the transmitting mosquitoes live only between the latitudes of 35° North and 35° South. However - possibly due to climate changes - the mosquitoes (and the disease) now spread also to more temperate zones. Recently, there have been reports of Dengue fever cases in Southern France, Croatia, and the Portuguese Island Madeira. Dengue is now seen as an emerging disease in areas with moderate climate such as Middle Europe and the United States!

Current issues:

July 31, 2013: As reported on n-tv.de, the government of Honduras declared the national emergency for dengue fever. So far, 15,831 have been infected, of which 2003 are seriously ill and 16 have already died. In neighboring Nicaragua, the number of infected people meanwhile rose to 2005; there, five people died.

Süddeutsche Zeitung (Sept. 5, 2013): Mittelamerika im Griff des Dengue-Fiebers (in german): sz.de/1.1762972

Al Jazeera (Feb. 17, 2014): Malaysia seeks to control dengue fever: www.aljazeera.com/video/asia-pacific/2014/02/malaysia-seeks-control-dengue-fever-20142173710444493.html

Weblink:

DengueMap: Worldwide distribution of Dengue fever cases: www.healthmap.org/dengue/