Dengue fever

       Dengue Fever

What is Dengue fever:-

Dengue fever also known as breakbone fever, is an infectious tropical disease caused by the dengue virus.  And this virus is transmitted by mosquitoes.

Dengue goes by other names, including "breakbone" or "dandy fever."

 Dengue (pronounced DENgee) fever is a painful, debilitating mosquito-borne disease caused by any one of four closely related dengue viruses. These viruses are related to the viruses that cause West Nile infection and  yellow fever.

Dengue virus has been recognised since the latter part of the 18th century ascausing epidemics in tropical and subtropical parts throughout the world.Dengue was first recognised in Townsville late in the 19th century and early in the 20th century. Outbreaks occurred in an area from the coast of Western Australia to the Northern Territory and down through high rainfall areas of Queensland and New South Wales. At that time Aedes aegypti mosquitoes were widely distributed in northern Australia and occurred as far south as the Victorian border in eastern Australia and south of Perth in Western Australia. By the 1970s Aedes aegypti were restricted to a small area of northern Queensland. Epidemic dengue returned to north Queensland in 1981–82. Other outbreaks occurred there in the 1990s, a time when Aedes aegypti mosquitoes were spreading westwards from Queensland to the Northern Territory border and towards the New South Wales border.

Dengue fever virus (DENV) is an RNA VIRUS of the family Flaviviridae; genus Flavivirus. Other members of the same genus include yellow fever virus, West Nile virus, St. Louis encephalitis virus, Japanese encephalitis virus, tick-borne encephalitis virus, Kyasanur forest disease virus, and Omsk hemorrhagic fever virus.Most are transmitted by arthropods(mosquitoes or ticks), and are therefore also referred to as arboviruses (arthropod-borne viruses).

The dengue virus genome (genetic material) contains about 11,000 nucleotide bases, which code for the three different types of protein molecules (C, prM and E) that form the virus particle and seven other types of protein molecules (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5) that are only found in infected host cells and are required for replication of the virus.There are five strains of the virus, called serotypes, of which the first four are referred to as DENV-1, DENV-2, DENV-3 and DENV-4. The distinctions between the serotypes is based on the their antigenicity.

Each year, an estimated 100 million cases of dengue fever occur worldwide. Most of these are in tropical areas of the world, with the greatest risk occurring in:

·         The Indian subcontinent

·         Southeast Asia

·         Southern China

·         Taiwan

·         The Pacific Islands

·         The Caribbean (except Cuba and the Cayman Islands)

·         Mexico

·         Africa

·         Central and South America (except Chile, Paraguay, and Argentina)

Ø Method of Transmission:-

Dengue virus is primarily transmitted by Aedes mosquitoes, particularly A. aegypti These mosquitoes usually live between the latitudes of 35° North and 35° South below an elevation of 1,000 metres (3,300 ft). They typically bite during the day, particularly in the early morning and in the evening, but they are able to bite and thus spread infection at any time of day all during the year Other Aedes species that transmit the disease include A. albopictus, A. polynesiensis and A. scutellaris.Humans are the primary host of the virus but it also circulates in nonhuman primates An infection can be acquired via a single bite. A female mosquito that takes a blood meal from a person infected with dengue fever, during the initial 2–10 day febrile period, becomes itself infected with the virus in the cells lining its gut. About 8–10 days later, the virus spreads to other tissues including the mosquito's salivary glands and is subsequently released into its saliva. The virus seems to have no detrimental effect on the mosquito, which remains infected for life. Aedes aegypti prefers to lay its eggs in artificial water containers, to live in close proximity to humans, and to feed on people rather than other vertebrates.

Dengue can also be transmitted via infected blood products and through organ donation. In countries such as Singapore, where dengue is endemic, the risk is estimated to be between 1.6 and 6 per 10,000 transfusions. Vertical transmission (from mother to child) during pregnancy or at birth has been reported. Other person-to-person modes of transmission have also been reported, but are very unusual. The genetic variation in dengue viruses is region specific, suggestive that establishment into new territories is relatively infrequent, despite dengue emerging in new regions in recent decades.

Ø Mechanism:-

When a mosquito carrying dengue virus bites a person, the virus enters the skin together with the mosquito's saliva. It binds to and 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 the fever, the flu-like symptoms and the severe pains. In severe infection, the virus production inside the body is greatly increased, and many more organs (such as the liver and the bone marrow) can be affected. Fluid from the bloodstream leaks through the wall of small blood vessels into body cavities due to capillary permeability. As a result, less blood circulates in the blood vessels, and the blood pressure becomes so low that it cannot supply sufficient blood to vital organs. Furthermore, dysfunction of the bone marrow due to infection of the stromal cells leads to reduced numbers of platelets, which are necessary for effective blood clotting; this increases the risk of bleeding, the other major complication of dengue fever

Once inside the skin, dengue virus binds to Langerhans cells (a population of dendritic cells in the skin that identifies pathogens)^]The virus enters the cells through binding between viral proteins and membrane proteins on the Langerhans cell, specifically the C-type lectins called DC-SIGN, mannose receptor and CLEC5A DC-SIGN, a non-specific receptor for foreign material on dendritic cells, seems to be the main point of entry. The dendritic cell moves to the nearest lymph node. Meanwhile, the virus genome is translated in membrane-bound vesicles on the cell's endoplasmic reticulum, where the cell's protein synthesis apparatus produces new viral proteins that replicate the viral RNA and begin to form viral particles. Immature virus particles are transported to the Golgi apparatus, the part of the cell where some of the proteins receive necessary sugar chains (glycoproteins). The now mature new viruses bud on the surface of the infected cell and are released by exocytosis. They are then able to enter other white blood cells, such as monocytes and macrophages.

The initial reaction of infected cells is to produce interferon, a cytokine that raises a number of defenses against viral infection through the innate immune system by augmenting the production of a large group of proteins mediated by the JAK-STAT pathway. Some serotypes of dengue virus appear to have mechanisms to slow down this process. Interferon also activates the adaptive immune system, which leads to the generation of antibodies against the virus as well as T cells that directly attack any cell infected with the virus.Various antibodies are generated; some bind closely to the viral proteins and target them for phagocytosis (ingestion byspecialized cells and destruction), but some bind the virus less well and appear instead to deliver the virus into a part of the phagocytes where it is not destroyed but is able to replicate further

Ø Clinical Features:-

·       Dengue fever (break bone fever)

Dengue fever classically presents as an acute febrile illness of sudden onset. It is extremely debilitating with fever lasting three to five days, myalgia (particularly backache), arthralgia, retro-orbital pain,anorexia, gastrointestinal disturbance,rash and increased vascular permeability.There is a high subclinical rate of milder disease in children compared to adults and a low fatality rate. Recovery from infection with one serotype of the dengue virus results in homologous immunity but does not provide protection against infection with other serotypes.

·       Dengue haemorrhagic fever

                    Dengue haemorrhagic fever (DHF) is a severe complication of dengue virus infection.

                    It occurs mainly in children and is characterised by abrupt onset of fever,

                    Haemorrhagic phenomena and thrombocytopaenia.

                    In its severest form it may result in shock   (dengue shock syndrome [DSS]),

                    which has a high fatality rate.

                    The rate of death from DHF without DSS is usually quoted at 1–5%.

                    This is believed to be caused by immune enhancement when a person with

                    dengue antibodies due to a previous infection is subsequently infected by a

dengue virus of a different serotype.

Ø Sign and Symtoms:-

Symptoms, which usually begin four to six days after infection and last for up to 10 days, may include

·         Sudden, high fever

·         Severe headaches

·         Pain behind the eyes

·         Severe joint and muscle pain

·         Nausea

·         Vomiting

·         Skin rash, which appears three to four days after the onset of fever

·         Mild bleeding (such a nose bleed, bleeding gums, or easy bruising)

Sometimes symptoms are mild and can be mistaken for those of the flu or anotherviral infection. Younger children and people who have never had the infection before tend to have milder cases than older children and adults. However, serious problems can develop. These include dengue hemorrhagic fever, a rare complication characterized by high fever, damage to lymph and blood vessels, bleeding from the nose and gums, enlargement of the liver, and failure of the circulatory system. The symptoms may progress to massive bleeding, shock, and death. This is called dengue shock syndrome (DSS).

People with weakened immune systems as well as those with a second or subsequent dengue infection are believed to be at greater risk for developing dengue hemorrhagic fever.

Ø Method of Diagnosis:-

Dengue virus infection is diagnosed by a significant rise in antibodies to the dengue virus serotype.

Laboratory evidence requires one of the following:

• isolation of dengue virus from clinical material

• detection of dengue viral RNA in clinical material

• a significant rise in the level of dengue virus specific IgG proven by neutralisation or another specific test

• dengue virus specific IgM in the CSF in the absence of IgM to Murray Valley encephalitis, Kunjin or Japanese encephalitis viruses

• dengue virus specific IgM in serum,except in north Queensland. In north Queensland dengue virus specific IgM in serum is acceptable evidence only when this occurs during a proven outbreak.Confirmation of laboratory results by a second arbovirus reference laboratory is required if the case occurs in previously unaffected areas of Australia. North Queensland is currently the only area

with the potential for indigenous (epidemic) dengue fever in Australia.

Ø Incubation Period:-

The incubation period is usually short but varies from three to fourteen days.

Ø Important measures to preventing fever:-

The best way to prevent the disease is to prevent bites by infected mosquitoes, particularly if you are living in or traveling to a tropical area. This involves protecting yourself and making efforts to keep the mosquito population down.To protect yourself:

·         Stay away from heavily populated residential areas, if possible.

·         Use mosquito repellents, even indoors.

·         When outdoors, wear long-sleeved shirts and long pants tucked into socks.

·         When indoors, use air conditioning if available.

·         Make sure window and door screens are secure and free of holes. If sleeping areas are not screened or air conditioned, use mosquito nets.

·         If you have symptoms of dengue, speak to your doctor.

To reduce the mosquito population, get rid of places where mosquitoes can breed. These include old tires, cans, or flower pots that collect rain. Regularly change the water in outdoor bird baths and pets' water dishes.

If someone in your home gets dengue fever, be especially vigilant about efforts to protect yourself and other family members from mosquitoes. Mosquitoes that bite the infected family member could spread the infection to others in your home.

Ø Treatment or Management:-

Because dengue fever is caused by a virus, there is no specific medicine or antibiotic to treat it. For typical dengue, the treatment is purely concerned with relief of the symptoms. Rest and fluid intake for adequate hydration is important. Aspirin and nonsteroidal anti-inflammatory drugs should only be taken under a doctor's supervision because of the possibility of worsening bleeding complications. Acetaminophen(Tylenol) and codeine may be given for severe headache and for joint and muscle pain (myalgia).

 Paracetamol (acetaminophen) is used for fever and discomfort while NSAIDs such as ibuprofen and aspirin are avoided as they might aggravate the risk of bleeding.