The Pathophysiology of Dengue Hemorrhagic Fever

Dengue fever is an infection caused by any of four types of flavivirus (DENV 1, DENV 2, DENV 3, DENV 4) which are spread by mosquitoes in tropical and sub topical areas. Although dengue fever can cause serious symptoms such as muscle and joint pain, there is usually no permanent long term harm. And infection by one subtype gives lifelong immunity to it, though not to other subtypes.

In a small number cases complications arise. For example the virus can cause vascular permeability; the blood vessels can become leaky and there is bleeding from the gums, nose and other organs. There can also be problems with clotting, and if not treated dengue hemorrhagic fever has a high mortality rate.

In the first few days of infection the symptoms are indistinguishable from those of dengue fever, but after a few days a person can become restless, perspire excessively and enter a shock-like state. Other symptoms include vomiting, generalized rash, cold and clammy extremities, and bleeding which may appear as tiny spots on the skin or patches of blood under it. In addition there can be a low platelet count and an individual with DHF may bruise easily.

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This is because DHF is characterised by vascular permeability which is caused by the release of cytokines (immune system signalling molecules) from virus-infected white blood cells. So how does this happen?

When there is a secondary infection from a different type of dengue virus the immune system generates an antigen-antibody complex that somehow allows more virus particles to enter monocytes (white blood cells). These infected cells release more cytokines which cause DHF symptoms. This is known as antibody dependent enhancement where antibodies enhance entry of a virus into host cells.

Currently there are no known cures or vaccines for dengue hemorrhagic fever and so the only treatment is to manage the symptoms which can include: -

• Blood transfusion
• Intravenous fluids to rehydrate patent
• Intravanous electrolytes to restore electrolyte balance
• Oxygen therapy if blood oxygen levels are low

For patients who are treated the prognosis is good as most recover. However, about half of those who are not treated go into shock and do not survive.

Preventative measures include travelling during periods of low mosquito activity, mosquito repellents, netting, and clothing that covers the body.