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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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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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Clinical course

The characteristic symptoms of dengue are sudden-onset fever, headache (typically located behind the eyes), muscle and joint pains, and a rash. The alternative name for dengue, "break-bone fever", comes from the associated muscle and joint pains.[1][7] The course of infection is divided into three phases: febrile, critical, and recovery.[8] The febrile phase involves high fever, often over 40 °C (104 °F), and is associated with generalized pain and a headache; this usually lasts two to seven days.[7][8] At this stage, a rash occurs in approximately 50–80% of those with symptoms.[7][9] It occurs in the first or second day of symptoms as flushed skin, or later in the course of illness (days 4–7), as a measles-like rash.[9][10] Some petechiae (small red spots that do not disappear when the skin is pressed, which are caused by broken capillaries) can appear at this point,[8] as may some mild bleeding from the mucous membranes of the mouth and nose.[5][7] The fever itself is cl...
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