Background

Dengue, a Spanish alteration of the Swahili word Ki-dinga, is the most common mosquito-borne viral illness in humans. The earliest known documentation of denguelike symptoms was recorded in the Chinese Encyclopedia of Symptoms during the Chin Dynasty (AD 265-420). The illness was called "the water poison" and was associated with flying insects near water. Today, dengue is known to be caused by a single-stranded RNA virus (approximately 11 kilobases long) with an icosahedral nucleocapsid and covered by a lipid envelope. The virus is in the family Flaviviridae (of the genus Flavivirus), and the type-specific virus is yellow fever. The dengue virus has 4 closely related but distinct serotypes, DEN1-DEN4.[1]It maintains an infection cycle that uses mosquitoes, mostly the Aedes aegypti mosquito[2] and rarely the Asian tiger mosquito (Aedes albopictus), as vectors to human hosts, who also serve as sources of viral amplification. A aegypti is a small, highly domesticated, black-and-white tropical insect that prefers to feed on humans (favoring ankles and the back of the neck). See the images below.

Drawing of Aedes aegypti mosquito. Picture from the Centers for Disease Control and Prevention (CDC) Web

site.

Aedes aegypti mosquito. Picture from the Centers for Disease Control and Prevention (CDC) Web site.

Aedes albopictus From CDC Public Domain

The insect typically lays its eggs in artificial containers that contain water, and, as a consequence, dengue is frequently an urbanacquired disease. In 1779-1780, the first reported outbreak of dengue fever (DF) occurred almost simultaneously in Asia, North America, and Africa. This indicates that the virus and its vector have a worldwide distribution in the tropical regions of the world (see the images below).

Worldwide distribution of dengue in 2000. Picture from the Centers for Disease Control and Prevention (CDC)

Web site.

Worldwide distribution of dengue in 2003. Picture from the Centers for Disease Control and

Prevention (CDC) Web site. Control and Prevention (CDC) Web site

Worldwide distribution of dengue in 2005. Picture from the Centers for Disease

The clinical presentation of dengue infection involves a wide spectrum of findings, from asymptomatic or mild self-limiting infection of dengue fever to potentially fatal hemorrhage and shock (dengue hemorrhagic fever [DHF], dengue shock syndrome [DSS]).

http://emedicine.medscape.com/article/963213-overview
Pathophysiology
The pathologic process of dengue infection starts with an intimate relationship between the host and the vector that carries the virus. Humans become infected with the virus after an infected mosquito feeds or probes on the susceptible human host (see the image below).

Dengue transmission cycle. Illustration from the Centers for Disease Control and Prevention (CDC) Web site.

Rare reports of human-to-human transmission via needlestick injuries have also been published.[3] Infection with dengue virus manifests a wide spectrum of clinical presentations. In most cases, especially in children younger than 15 years, the patient is asymptomatic or has a mild undifferentiated febrile illness. Typical dengue fever is a self-limiting, acute, febrile illness, which occurs after an incubation period of 4-7 days. In younger children, it may be accompanied by a maculopapular rash. In older patients, the disease may also be mild or it may be more incapacitating, with rapid onset of high fever, headache, retroorbital pain, diffuse body pain (both muscle and bone), weakness, vomiting, sore throat, altered taste sensation, and a centrifugal maculopapular rash, among others. This painful "breakbone" and febrile phase lasts 2-7 days and, afterward, most patients slowly improve. Dengue virus disappears from the bloodstream at approximately the same time that the fever dissipates.

Leukopenia and thrombocytopenia are common findings in dengue fever and are believed to be caused by direct destructive actions of the virus on bone marrow precursor cells. The resulting active viral replication and cellular destruction in the bone marrow are believed to cause the bone pain. Approximately one third of patients with dengue fever may have mild hemorrhagic symptoms, including petechiae, gingival bleeding, and a positive tourniquet test (>20 petechiae in an area of 2.5 cm X 2.5 cm). Dengue fever is rarely fatal. Dengue hemorrhagic fever occurs less frequently than dengue fever but has a more dramatic clinical presentation. In Asia, where it first was described, dengue hemorrhagic fever is primarily a disease of children. However, in the Americas, dengue hemorrhagic fever has an equal distribution in all ages. The critical feature of dengue hemorrhagic fever is plasma leakage. This results from endothelial gaps in the peripheral vascular bed without necrotic or inflammatory changes in the endothelium. Dengue hemorrhagic fever typically begins with the initial manifestations of dengue fever. The acute febrile illness (temperatures 40C), like that of dengue fever, lasts approximately 2-7 days. However, in persons with dengue hemorrhagic fever, the fever reappears, giving a biphasic or "saddleback" fever curve that is not observed in individuals with dengue fever. Along with this biphasic fever, patients with dengue hemorrhagic fever have progressive thrombocytopenia, increasing hematocrit (20% absolute rise from baseline) that leads to hemoconcentration, more obvious hemorrhagic manifestations (>50% of patients have a positive tourniquet test), and progressive effusions (pleural or peritoneal). Accompanying the hemorrhagic phenomena, patients with dengue hemorrhagic fever may have circulatory failure and hepatomegaly. The major pathologic difference between dengue fever and dengue hemorrhagic fever is that the marked vascular leakage, with resultant hemoconcentration and serous effusions, can lead to circulatory collapse (ie, dengue shock syndrome). The progression of dengue hemorrhagic fever to dengue shock syndrome can be prevented by close observation of clinical changes and the use of isotonic intravenous fluids. As the term implies, dengue shock syndrome is essentially dengue hemorrhagic fever with progression into circulatory failure, with ensuing hypotension, narrow pulse pressure (< 20 mm Hg), and, ultimately, shock and death if untreated. Death may occur 8-24 hours after onset of signs of circulatory failure. The most common clinical findings in impending shock include hypothermia, abdominal pain, vomiting, and restlessness. The mechanism of progression from dengue fever to dengue hemorrhagic fever is not clearly understood. However, immune enhancement is the most commonly accepted current explanation. This hypothesis states that individuals who have had a prior infection (ie, primary infection) with 1 of the 4 dengue virus serotypes have circulating nonneutralizing antiviral antibodies. When an individual is infected with another serotype (ie, secondary infection), these nonneutralizing antibodies recognize the dengue virus but do not neutralize or inhibit virus replication. Instead, the virus and antibody form an antigen-antibody complex. This complex is recognized by receptors on macrophages, which then internalize the immune complex and allow the virus to replicate unchecked (ie, immune enhancement). The affected macrophages release vasoactive mediators that increase vascular permeability, leading to vascular leakage, hypovolemia, and shock. Recent research demonstrated that this mechanism, along with individual host and viral genome variations, plays an active role in pathogenesis.

http://emedicine.medscape.com/article/963213-overview#a0104
The presence of a growth factor called thrombopoietin (TPO), generally is needed beforeplatelet production can occur. TPOs mostly are made by the liver and the kidneys when levels of platelets in the blood are low. This in turn stimulates the bone marrow to produce megakaryocytes which are responsible in platelet production. Platelets technically then are released when megakaryocytes undergo fragmentation. Thrombocytes, commonly known as platelets, are important blood components that mostly are needed to control bleeding. They are tiny cells that contain neither a nucleus nor have a definite shape. Each platelet has a lifespan of approximately 12 days in the blood circulation from the time they were released from the megakaryocytes. Platelets contain many granules that usually are utilized during clot formation. When injury occurs in the blood vessels, platelets often adhere to the injured site and gather together to form what generally is known as a platelet plug. Then other important processes, such as the coagulation cascade, take place which technically lead to a stable blood clot. Ads by Google Problems usually arise when there are abnormal levels of platelets in the blood. Low plateletcount, or thrombocytopenia, occurs when there are disorders of platelet production as seen in some viral infections and after exposure to chemicals and radiation. Platelet production also can be affected by Vitamin B12 deficiency, folate deficiency, and diseases affecting the bonemarrow. Another factor which often causes thrombocytopenia is increased platelet destruction. This destruction could occur after exposure to snake venom, in the presence of acquired immune deficiency syndrome (AIDS), with disseminated lupus erythematosus, or after a reaction to a blood transfusion. A few inherited genetic diseases that can cause platelets to perform inadequately arehemophilia A and B, and von Willebrand disease. Platelet clotting factors often are missing or have very low levels in the blood since birth. Individuals with hemophilia and von Willebrand disease generally have higher tendencies to bleed from cuts and from tooth extraction. Some may even suffer from internal bleeding. Platelet treatment in the form of platelet transfusion is recommended at times for some hemophiliacs.

Thrombocytosis, or high platelet count, is seen in increased platelet production that occurs in many conditions. Examples include polycythemia vera, chronic myelogenous leukemia, essential thrombocytosis, hepatic cirrhosis, and inflammatory bowel diseases. A high plateletcount often may not show signs and symptoms, but it sometimes can promote thrombosis or clot formation inside the blood vessels. Increased risk for bleeding can occur with the use of drugs. Some prescription drugs and over-the-counter drugs that can affect platelet function are aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), antibiotics, diuretics, antihistamines, and anticoagulants. Drugs affectingplatelet production include chloramphenicol and many drugs used in the treatment of cancer.

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