CLINICAL MANIFESTATION Since the recognition of DHF in the 1950s investigators have sought to define the clinical differences

between severe and mild forms of dengue. Mild hemorrhagic manifestations, such as epistaxis, petechiae, gingival bleeding and menorrhagia, are accepted as part of the clinical picture of classic dengue.(28) Manifestations of severe dengue include severe hemorrhage leading to shock through blood loss, (29) sudden increased vascular permeability leading to shock with or without hemorrhage (26,53) and severe encephalopathy with hepatitis.(54-56) The classification of severe dengue has been complicated by the variety of these clinical pictures, for which the underlying pathophysiology may be different. (29,35,57) Two to 15 days after the bite of an infective mosquito, the patient typically suffers sudden onset of headache, fever, retroorbital pain, backache, bone and joint pain, weakness, depression and malaise. Some patients have an evanescent rash over the thorax and joint flexures. There may be flushing of the face and conjunctivitis as well as taste aberrations, anorexia, nausea, vomiting and abdominal pain. Lymphadenopathy and hepatomegaly may occur but splenomegaly is infrequent. Patients may complain of sore throat, cough, groin pain, hyperesthesia, dizziness, photophobia, eye pain and, rarely, a "yellow flamelike" color to objects. Fever and associated symptoms may subside after 3 or 4 days and the patient may recover completely. Alternatively the decline in fever may be followed 1 to 3 days later by a resurgence of fever and symptoms, giving a "saddleback" appearance to the temperature curve. A second rash, varying in form from scarlatiniform and maculopapular to petechial and occasionally purpuric, may appear with the initial decline of the fever. Severe itching, especially of the hands and feet, may accompany this rash, which is sometimes followed by desquamation. The symptoms persist for 1 to 3 days more and then subside with the fever. During the course of the illness there is often a relative or paradoxical bradycardia in the face of increased temperature. Patients may have hemor- rhagic manifestations such as epistaxis or menorrhagia. Jaundice is rare. Convulsions may occur with the onset of fever. The spinal fluid is almost always clear with no elevation of cell count but the pressure may be increased. Depression, weakness and blurred vision may resolve slowly during convalescence. Patients may take several weeks to recover completely. Although these symptoms characterize "classical" dengue fever, dengue virus infection may also manifest as a nonspecific febrile illness which can be confused with influenza, measles or any nonspecific vital syndrome. The lack of a clear clinical pattern for dengue makes laboratory diagnosis a necessary part of any definitive evaluation of the disease.(58) Patients who develop DHF or other severe manifestations of dengue generally have an onset of illness similar to that seen in "classical" or nonhemorrhagic dengue. (59) The course usually begins with the sudden onset of fever, headache, nausea, vomiting, abdominal pain, pharyngitis, lymphadenopathy and sometimes a rash, which may be petechial or even ecchymotic early in the course. (59,60)

The liver may become enlarged and pleural effusions may develop, usually beginning on the right side.(59,60) As the fever begins to drop around Day 3 to 5, circulatory instability may develop with signs of decreased peripheral perfusion. Profound shock may follow. (59,60) Disseminated intravascular coagulation and severe gastrointestinal hemorrhage have been described.(29) The descriptions of such patients led to the following WHO case definitions for DHF: (1) fever; (2) hemorrhagic manifestations, including at least a positive tourniquet test (except in shock cases), and either major or minor bleeding phenomena; (3) thrombocytopenia (platelet count less than or equal to 100 000/ mm3); and (4) hemoconcentration (hematocrit increased by 20% or more relative to baseline values, or objective evidence of increased capillary permeability).(28) In addition to this pattern of DHF, cases of severe dengue with massive gastrointestinal hemorrhage preceding the onset of shock, and without evidence of increased vascular permeability, have been described.(29) Many of these fatal hemorrhagic cases did not meet the WHO case definition for DHF. Severe encephalopathy with convulsions and/or coma has also been described with dengue infection.(29,54-56) Increased spinal fluid white blood cell counts (up to 27/ mm(3)) were found in one series(29) and normal spinal fluid was seen in another.(56) Significant thrombocytopenia may occur in both DHF and "classical" dengue.(47,61,63) A fall in platelet count associated with a rising hematocrit may suggest the development of DHF.(59) Results of coagulation tests may be abnormal; prolonged partial thromboplastin and thrombin times are noted more frequently than prolonged prothrombin times.(59) Elevated concentrations of serum aspartate amino- transferase have been noted in several studies.(56,59,62,64) Hyponatremia is commonly found in DHF patients with shock and may be a cause of convulsions.(56) Results of urinalysis are usually normal,(20) but hematuria, trace amounts of albumin and urinary casts have been reported. (47,60,65) ________________________________________ DIAGNOSIS Classical dengue fever may be confused with a variety of febrile ill- nesses, including influenza, measles, typhoid fever and malaria. DHF may be confused with sepsis, toxic shock and any of the viral hemorrhagic fevers including yellow fever. Diseases with specific treatments, such as bacterial meningitis, sepsis, malaria and Lassa fever, should be ruled out. Specific diagnosis of dengue infection is made by isolating the virus from the patient's blood. Acute serum samples are inoculated into tissue cultures of mosquito cells or directly into live Toxorhynchites or Aedes mosquitoes. Isolates can be identified from 2 to 7 days after inoculation depending on the actual technique used.( Viruses are most likely to be isolated from acute serum samples obtained within 5 days after the onset of illness.(34,35) Specific dengue serotypes can be identified by the indirect fluorescent antibody test, with the use of type-specific monoclonal antibodies on the isolated virus

Immunodiagnostic methods for determining dengue infection include detection of anti-dengue IgM and IgG by enzyme-linked immunosorbent assay (ELISA) and detection of hemagglutination inhibition antibody. Dengue-induced hemagglutination inhibition antibody cross-reacts broadly with other flaviviruses such as yellow fever and St. Louis encephalitis viruses.(35) Complement fixation and neutralization antibody tests are more specific than hemagglutination inhibition.(35) Most serologic screening for dengue infection is now done with an IgM ELISA.(35,68) With appropriately timed samples, the sensitivity and specificity of this test in diagnosing dengue infection appear to be high. In a review of 131 patients from whom dengue virus was isolated at the Centers for Disease Control, Dengue Branch, 96% of the 76 samples drawn between 7 and 20 days after the onset of illness were positive by IgM capture ELISA (DJ Gubler, G Kuno, I Gomez, et al. unpublished data). A study of the performance of IgM ELISA in Thailand showed the sensitivity of this test in convalescent samples to be 97%, and none of the samples from the 2 groups of noninfected controls (98 soldiers and 39 schoolchildren) were positive.(69) The pattern of HI response has been used to classify dengue infections as primary or secondary, based on the concept that initial, or primary dengue infections tend to elicit lower HI titers than do secondary infections (subsequent infections with a different dengue serotype or antigenically related flavivirus).(28) IgM:IgG ratios as determined by ELISA may be an alternative method of distinguishing primary from secondary infections. (69,70) The rise in neutralizing antibody in primary infection is believed to be relatively type-specific and can be used to determine the infecting serotype.(35) In secondary infections, because the immunologic cross- reactivity to different flaviviruses and anamnestic responses may result in heterologous titer elevations, the only reliable method for determining the infecting serotype is virus isolation.(35) In summary diagnosis of dengue infection is best accomplished by obtaining an acute serum sample within 5 days after the onset of illness for virus isolation and antibody testing and a convalescent serum sample 14 to 21 days after illness onset for detecting IgG antibody titer rise and/or the presence of antidengue IgM. ________________________________________ TREATMENT Treatment for classic dengue fever is supportive. Patients should be encouraged to drink plenty of fluids. Acetaminophen may be taken to control fever and aching if necessary. Aspirin is contraindicated both because of its anticoagulant effects and the increased risk of developing Reye syndrome. (56,71,72) Patients or parents should be carefully instructed of the need to seek medical attention immediately if major or ongoing hemorrhage, signs of impending shock or any change in mental status should occur. The onset of cardiovascular collapse in patients who develop DHF may be sudden.(28) Patients with significant hemorrhage or signs of increased capillary permeability such as hemoconcentration, effusions, edema or low serum albumin, as well as patients with mental status changes or with abnormal fluid and electrolyte balance, should be hospitalized and may require admission to an intensive care unit. Isolation is not necessary in mosquito- free environments. Usual precautions handling blood specimens should be observed.

Intravenous fluid therapy is the mainstay of treatment for patients with DHF.(28,59) Patients with dehydration and hemoconcentration may require intravenous fluids similar in volume and composition to regimens used to treat dehydration due to diarrheal illness.(25) Patients in shock should be given fluids and other therapy according to accepted regimens for shock. (28,73) The administration of heparin may need to be considered in patients who develop DIC.(28,59) There is some controversy over the role of steroids in treatment of severe dengue.(74) Studies by Sumarmo et al.(74,75) showed no benefit, over fluid therapy alone, of hydrocortisone injection given either 30 mg/kg/day or 50 mg/kg in a single dose. The potential effect of high dose methylprednisolone in certain severe cases may need further evaluation. (74,76) ________________________________________ PATHOGENESIS The site of viral replication during dengue infection remains uncertain. Mononuclear phagocytes may be the most likely site,(57) but infection of megakaryocytes in the bone marrow has also been proposed.(61) Viral particles or antigen have been detected in monocytes in kidney, skin tissue, liver, spleen, thymus and lung.(57) Dengue virus has been isolated from peripheral blood leukocytes, as well as from autopsy tissue from liver, spleen, lymph node, bone marrow, thymus, heart, kidney, stomach and lung (DJ Gubler, unpublished).(57) Several hypotheses have emerged to explain why DHF occurs in some individuals who are infected with dengue viruses. These include (1) changes or differences in viral virulence between serotypes and/or between strains within serotypes, (22,35,77-79) (2) interactions of dengue viruses with other environmental or infectious agents, (22) (3) differences in genetic susceptibility or other host factors, (35,50,56) and (4) the immunologic enhancement of dengue infection by antibody acquired from a previous infection with a different dengue serotype.(45) The theory of immune enhancement, developed extensively by Halstead, (80) predicts that individuals who have been immunologically sensitized to one dengue virus serotype may develop nonneutralizing antibodies that actually enhance the entry of different serotype dengue viruses into mononuclear phagocytes, resulting in the increased activation of complement and kinins, and the release of mediators of vascular permeability. (57) This proposed mechanism has been supported by laboratory investigation, (57) and several studies have shown that during outbreaks a large majority of DHF patients show secondary immune response patterns.(17,81,82) However, cases of DHF have been described in patients with primary dengue infection, (34,35,78,79,83) and the denominators for estimating proportions of primary and secondary infections that result in DHF have been difficult to evaluate with certainty.(78) Carefully designed epidemiologic studies are needed to further evaluate this theory and to study the possible interaction of immune enhancement with other risk factors. The recognition of various forms of severe or fatal dengue that are different from DHF as defined by WHO may require revisions or additions to the case definitions required for such studies.(29)

The liver is responsible for breaking down glucose and making proteins. Unfortunately, an enlarged liver, medically known as hepatomegaly, can be a sign of an underlying medical problem. Typically, a physician discovers this upon physical examination when he feels the stomach for any abnormalities. Enlarged liver causes have specific treatments.

Read more: http://www.livestrong.com/article/87407-enlarged-liver-causes/#ixzz1VtAImO70 Overview Dengue fever is caused by four viruses that are very similar to one another. The viruses are spread through the bite of the Aedes Aegypti mosquito. The disease is prevalent in tropical and sub-tropical areas, including South and Central America, sub-Saharan Africa, Indonesia and Southeast Asia. Although most dengue fever is not life-threatening, a deadly strain may develop if an individual is re-infected, a condition called dengue hemorrhagic fever. Dengue hemorrhagic fever is life-threatening because it interferes with blood clotting, which causes internal bleeding. Disease Time Frame Symptoms of infection begin about three to seven days after an individual is bitten by an infected mosquito, according to the Centers for Disease Control and Prevention. Dengue hemorrhagic fever, which usually occurs during a second infection by any of the four viruses, is characterized by a fever that lasts between two to seven days. When the fever goes away, blood clotting fails over the next two days, and internal bleeding occurs. Complications Dengue hemorrhagic fever has many complications and some may be life-threatening, according to the National Institute of Health. The disease prevents clotting of blood, which causes fluid to accumulate around the stomach and lungs. The body may go into shock and coma. Prevention of clotting also leads to bruising, bleeding from the gums and nose, and internal bleeding. Symptoms Symptoms of initial dengue fever include severe head and back aches, nausea and vomiting, a fever up to 105 degrees Fahrenheit, a recurrent rash over the entire body, severe joint and muscle pain, and pain behind the eyes.

Dengue hemorrhagic fever symptoms include a decrease in blood clotting cells called platelets, bleeding from the nose and mouth, damage to blood and lymph vessels, bleeding under the skin, and eventual death.

A third condition called dengue shock syndrome has symptoms that include heavy bleeding, disorientation, severe abdominal pain, sudden drop in blood pressure or shock, leaking of fluid Dengue Fever Symptoms in Children Dengue fever is caused by a flavivirus, which is a class of viruses transmitted to people primarily through the bite of an infected tick or mosquito. For dengue fever, the carrier insect is the female Aedes aegypti mosquito. This mosquito is active during the daytime and most active during the two hours after sunrise and a few hours before sunset. There are four serotypes of dengue virus fever, known as DENV-1, DENV2, DENV-3 and DENV-4. Infection with one type could result in a nonlethal infection that will give the person immunity to that serotype but not the others. Any single person can catch dengue fever up to four times, once for each serotype. There are three associated diseases with varying levels of severity: dengue fever, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue Fever Symptoms Dengue fever is characterized by a sudden onset of fever for up to a week. Other symptoms may include a severe headache, muscle and joint pain, nausea and vomiting. Older children may experience severe back pain. A rash may appear about the same time that the fever subsides. The rash may not be visible in darker-skinned people. There may also be minor bleeding, including bleeding of the gums. Localized outbreaks of dengue fever are frequent, but fatalities are few with proper medical care. There is no vaccine for dengue fever. Medical treatment is to ease the symptoms until the worst of the infection passes. Dengue Hemorrhagic Fever Symptoms Dengue hemorrhagic fever (DHF) is a much more severe manifestation of dengue fever. This complication of dengue fever is endemic in southeastern Asia, Africa and Latin America. Symptoms include high fever of up to 105.8F (41C) and a tendency for spontaneous abnormal bleeding and blood clotting. Fevers in this very high range can lead to convulsions. Gastrointestinal hemorrhage and liver damage are also signs that dengue fever has become DHF. Treatment includes replacement of fluids lost and transfusion if bleeding is sever. If untreated, dengue hemorrhagic fever is often fatal in children. Dengue Shock Syndrome Symptoms Dengue shock syndrome (DSS) occurs after dengue fever has progressed to dengue hemorrhagic fever (DHF) and fluid replenishment and bleeding control have not been established. Because it starts as dengue fever, DSS is preceded by the typical very or very high fever lasting up to a week, hemorrhagic bleeding that is characteristic of DHF, a decrease in circulating platelet counts and evidence of plasma leakage. Dengue shock syndrome causes a rapid, weak pulse, a very narrow blood pressure, restlessness and a cold, clammy skin, plus signs of shock. When shock sets in, the fatality rate can be as high as 50 percent. With appropriate fluid replacement therapy and bleeding controls in place, mortality decreases. Two-thirds of all DSS fatalities are children. BLOOD COMPONENTS

The immune system includes certain types of white blood cells. It also includes chemicals and proteins in the blood, such as antibodies, complement proteins, and interferon. Some of these directly attack foreign substances in the body, and others work together to help the immune system cells. Lymphocytes are white blood cells, which includes B cells and T cells. B cells produce antibodies. Antibodies attach to a specific antigen and make it easier for the immune cells to destroy the antigen. T cells attack antigens directly and help control of the immune response. They also release chemicals, known as interleukins, which control the entire immune response. As lymphocytes develop, they normally learn to tell the difference between your own body tissues and substances that are not normally found in your body. Once B cells and T cells are formed, a few of those cells will multiply and provide "memory" for the immune system. This allows the immune system to respond faster and more efficiently the next time you are exposed to the same antigen, and in many cases will prevent you from getting sick. For example, an individual who has had chickenpox or has been immunized against chickenpox is immune from getting chickenpox again. INFLAMMATION The inflammatory response (inflammation) occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause. The damaged tissue releases chemicals including histamine, bradykinin, and serotonin. These chemicals cause blood vessels to leak fluid into the tissues, causing swelling. This helps isolate the foreign substance from further contact with body tissues. The chemicals also attract white blood cells called phagocytes that "eat" microorganisms and dead or damaged cells. This process is called phagocytosis. Phagocytes eventually die. Pus is formed from a collection of dead tissue, dead bacteria, and live and dead phagocytes. The fever is caused by mosquito bites. Mosquito acts as a carrier of the Dengue Virus. The virus's main effect is on the PLATELET production. Normally a platelet in our body lasts for about 5 to 10...