Clinical course
The characteristic symptoms of dengue are sudden-onset fever, headache (typically located behind the eyes), muscle and joint pains, and a rash. An alternative name for dengue, "breakbone fever", comes from the associated muscle and joint pains. The course of infection is divided into three phases: febrile, critical, and recovery.The febrile phase involves high fever, potentially over 40 °C (104 °F), and is associated with generalized pain and a headache; this usually lasts two to seven days. Nausea and vomiting may also occur. A rash occurs in 50–80% of those with symptoms 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. A rash described as "islands of white in a sea of red" has also been observed. 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, as may some mild bleeding from the mucous membranes of the mouth and nose. The fever itself is classically biphasic or saddleback in nature, breaking and then returning for one or two days.In some people, the disease proceeds to a critical phase as fever resolves. During this period, there is leakage of plasma from the blood vessels, typically lasting one to two days. This may result in fluid accumulation in the chest and abdominal cavity as well as depletion of fluid from the circulation and decreased blood supply to vital organs.
The white blood cells respond by producing several 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. Viral replication
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 cells endoplasmic reticulum, where the cells protein synthesis apparatus produces new viral proteins that replicate the viral RNA and begin to form viral particles.