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Dengue pathogenesis: a disease driven by the host response

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Dengue viruses cause mild disease in the majority of infected individuals. In most cases, the disease is characterised by fever, headache, pain behind the eyes, muscle ache, joint pains, vomiting and diarrhoea. In a low percentage of patients, bleeding and loss of plasma (haemorrhage and plasma leakage) may occur. The hyper-permeability syndrome results in plasma leakage and, if the compensatory mechanisms of the body fail to control the plasma leakage or if medical intervention is late, shock may set in. Profound shock will subsequently lead to acidic blood (metabolic acidosis) and development of disseminated intravascular coagulation (DIC). During DIC multiple micro thromboses occur, leading to organ failure. The mechanisms governing pathogenesis of these forms of severe disease are not clear. High amounts of virus in the blood are believed to cause vascular fragility which, together with infection of endothelial cells and high levels of cytokines and other soluble mediators, may result in bleeding. In the absence of a correlation between the amount of virus in the blood and disease severity, it is likely that response to infection is an important cause of disease. The aberrant immune response to infection is believed to result in a cytokine storm, defined as an imbalance between cytokines driving an inflammation (pro-inflammatory) and those silencing an inflammation (anti-inflammatory). Several lines of evidence indicate that displacement of viral genotype and host genetic background are key factors driving the production of a cytokine storm. Several cytokines are known to induce apoptosis, a form of cell suicide (cause of haemorrhage), and/or affect adherens junctions (cause permeability) in vitro. Whether these cytokines may have such effects in vivo remains to be established.
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Keywords: CYTOKINE STORM; DENGUE PATHOGENESIS; GENOTYPE; HOST RESPONSE; SEVERE DISEASE

Document Type: Review Article

Publication date: 01 September 2014

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    Cover image: Plastic debris washed-up on a river bank. The manufacture and use of different types of plastic, and the effects of pollution by these materials are discussed in the article on pages 207–260. Credit: By igorstevanovic/Shutterstock.com.

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