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Severe disease


It is not entirely clear why secondary infection with a different strain of dengue virus places people at risk of dengue hemorrhagic fever and dengue shock syndrome. The most widely accepted hypothesis is that of antibody-dependent enhancement (ADE). The exact mechanism behind 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.[12][13] There is a suspicion that ADE is not the only mechanism underlying severe dengue-related complications,[1] and various lines of research have implied a role for T cells and soluble factors such as cytokines and the complement system.[22]

Severe disease is marked by two problems: dysfunction of endothelium (the cells that line blood vessels) and disordered blood clotting.[6] Endothelial dysfunction leads to the leakage of fluid from the blood vessels into the chest and abdominal cavities, while coagulation disorder is responsible for the bleeding complications. Higher viral load in the blood and involvement of other organs (such as the bone marrow and the liver) are associated with more severe disease. Cells in the affected organs die, leading to the release of cytokines and activation of both coagulation and fibrinolysis (the opposing systems of blood clotting and clot degradation). These alterations together lead to both endothelial dysfunction and coagulation disorder.

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Diagnosis

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Research

Research efforts to prevent and treat dengue include various means of vector control,[43] vaccine development, and antiviral drugs.[27] With regards to vector control, a number of novel methods have been used to reduce mosquito numbers with some success including the placement of the guppy (Poecilia reticulata) or copepods in standing water to eat the mosquito larvae.[43] There are ongoing programs working on a dengue vaccine to cover all four serotypes.[27] One of the concerns is that a vaccine could increase the risk of severe disease through antibody-dependent enhancement.[44] The ideal vaccine is safe, effective after one or two injections, covers all serotypes, does not contribute to ADE, is easily transported and stored, and is both affordable and cost-effective.[44] As of 2009, a number of vaccines were undergoing testing.[13][33][44] It is hoped that the first products will be commercially available by 2015.[27] Apart from attempts to control the spread of the Aedes mosq...
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Viral reproduction

Once inside the skin, dengue virus binds to Langerhans cells (a population of dendritic cells in the skin that identifies pathogens).[22] 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.[12] DC-SIGN, a non-specific receptor for foreign material on dendritic cells, seems to be the main point of entry.[13] The dendritic cell moves to the nearest lymph node. Meanwhile, the virus genome is replicated in membrane-bound vesicles on the cell's endoplasmic reticulum, where the cell's protein synthesis apparatus produces new viral proteins, and the viral RNA is copied. 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 en...
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