Dengue fever, a contagious disease transmitted by the Aedes aegypti mosquito, infects between 50 million and 100 million

people worldwide each year. Also known as breakbone or dandy fever, dengue fever is found in the tropical and subtropical regions of the world. Exposure to the flavivirus that causes dengue fever results in one of three pathophysiologies: dengue fever, the more severe dengue hemorrhagic fever (DHF) or dengue shock syndrome.

Transmission of Dengue Fever

1. Dengue fever is transmitted only through an infected mosquito or by contact with the blood of someone who is actively infected with one of the four viruses responsible for the fever. Infection with one of these viruses generally provides immunity from dengue fever for as much as a year after the illness. A small minority of cases of dengue fever develop into severe forms of the fever, DHF or dengue shock syndrome, which require hospitalization.

Symptoms of Dengue Fever

2. Early symptoms of dengue fever include headache, chills, backache, fever, nausea and joint pain. The initial fever may be as high as 104 degrees Fahrenheit at the onset of the illness and individuals may develop severe pain in the legs and behind the eyes. A rash consisting of patchy bright red spots may develop over the body after the first few days of illness.

Time Frame:Dengue Infection

3. After five to eight days of incubation, individuals infected with dengue fever develop symptoms abruptly. The initial symptoms of dengue fever last about six to seven days. The fever climbs rapidly in the first 48 to 96 hours of the illness and then may break for a day before elevating rapidly again. This second phase of the fever is often when a rash may appear on the limbs or chest.

Diagnosis of Dengue Fever

4. A diagnosis of dengue fever is typically not considered unless the individual has been in a tropical location where the virus is present such as Central America, South America, Africa or Asia. Clinically, individuals with dengue fever may develop a low white blood cell count by the second day of illness. This low white blood cell count, coupled with the "dengue triad" of fever, rash and headache, represent the most common diagnostic criteria for dengue fever.

Prevention of Dengue Fever

Read more: Pathophysiology of Dengue Hemorrhagic Fever | eHow.com

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Alternative Names -Hemorrhagic dengue; Dengue shock syndrome; Philippine hemorrhagic fever; Thai hemorrhagic fever; Singapore hemorrhagic fever Definition -Dengue hemorrhagic fever is a severe, potentially deadly infection spread by certain mosquitoes (Aedes aegypti ). Causes -Four different dengue viruses have been shown to cause dengue hemorrhagic fever. This condition occurs when a person catches a different dengue virus after being infected by another type sometime before. Prior immunity to a different dengue virus type plays an important role in this severe disease. Worldwide, more than 100 million cases of dengue fever occur every year. A small number of these develop into dengue hemorrhagic fever. Most infections in the United States are brought in from other countries. It is possible for a traveler who has returned to the United States to pass the infection to someone who has not traveled. Risk factors for dengue hemorrhagic fever include having antibodies to dengue virus from prior infection and being younger than 12, female, or Caucasian. Symptoms -Early symptoms of dengue hemorrhagic fever are similar to those of dengue fever, but after several days the patient becomes irritable, restless, and sweaty. These symptoms are followed by a shock-like state. Bleeding may appear as pinpoint spots of blood on the skin (petechiae) and larger patches of blood under the skin (ecchymoses). Bleeding may occur from minor injuries. Shock may cause death. If the patient survives, recovery begins after a one-day crisis period. Early symptoms include the following: Fever Headache Muscle aches Joint aches Malaise

Decreased appetite Vomiting Acute phase symptoms include the following: Shock-like state -Sweaty (diaphoretic) -Cold, clammy extremities Restlessness followed by: -Worsening of earlier symptoms -Petechiae -Ecchymosis -Generalized rash Exams and Tests Physical examination may reveal the following: -Low blood pressure -A weak, rapid pulse -Rash -Red eyes -Red throat -Swollen glands -Enlarged liver (hepatomegaly) Tests may include the following: -Hematocrit -Platelet count -Electrolytes -Coagulation studies -Liver enzymes -Blood gases -Tourniquet test (causes petechiae below the tourniquet) -X-ray of the chest (may demonstrate pleural effusion) -Serologic studies (demonstrate antibodies to Dengue viruses) -Serum studies from samples taken during acute illness and convalescence (increase in titer to Dengue antigen) Treatment Because Dengue hemorrhagic fever is caused by a virus for which there is no known cure or vaccine, the only treatment is to treat the symptoms.

-Rehydration with intravenous (IV) fluids is often necessary to treat dehydration. -IV fluids and electrolytes are also used to correct electrolyte imbalances. -A transfusion of fresh blood or platelets can correct bleeding problems. -Oxygen therapy may be needed to treat abnormally low blood oxygen. Outlook (Prognosis) -With early and aggressive care, most patients recover from dengue hemorrhagic fever. However, half of untreated patients who go into shock do not survive Possible Complications -Shock -Encephalopathy -Residual brain damage -Seizures -Liver damage When to Contact a Medical Professional -Call your health care provider if you have symptoms of dengue fever and have been in an area where dengue fever is known to occur. Prevention -There is no vaccine available to prevent dengue fever. Use personal protection such as full-coverage clothing, netting, mosquito repellent containing DEET, and if possible, travel during periods of minimal mosquito activity. Mosquito abatement programs can also reduce the risk of infection. Pathophysiology

Dengue infection is caused by 1 of 4 related, but antigenically distinct, viral serotypes: dengue virus 1 (DENV-1), dengue virus 2 (DENV-2), dengue virus 3 (DENV-3), and dengue virus 4 (DENV-4). Genetic studies of sylvatic strains suggest that the 4 viruses evolved from a common ancestor in primate populations approximately 1000 years ago and that all 4 viruses separately emerged into a human urban transmission cycle 500 years ago in either Asia or Africa.1,8 Albert Sabin speciated these viruses in 1944. Each serotype is known to have several different genotypes. Infection with one dengue serotype confers lifelong homotypic immunity and a very brief period of partial heterotypic immunity, but each individual can eventually be infected by all 4 serotypes. Several serotypes can be in circulation during an epidemic. Dengue viruses are transmitted by the bite of an infected Aedes (subgenus Stegomyia) mosquito. Globally, A aegypti is the predominant highly efficient mosquito vector for dengue infection, but

A albopictus and other Aedes species can also transmit dengue with varying degrees of efficiency. Aedes mosquito species have adapted well to human habitation, often breeding around dwellings in small amounts of stagnant water found in old tires or other small containers discarded by humans. Female Aedes mosquitoes are daytime feeders. They inflict an innocuous bite and are easily disturbed during a blood meal, causing them to move on to finish a meal on another individual, making them efficient vectors. Entire families who develop infection within a 24- to 36-hour period, presumably from the bites of a single infected vector, are not unusual. Humans serve as the primary reservoir for dengue; however, certain nonhuman primates in Africa and Asia also serve as hosts but do not develop dengue hemorrhagic fever. Mosquitoes acquire the virus when they feed on a carrier of the virus. The mosquito can transmit dengue if it immediately bites another host. In addition, transmission occurs after 8-12 days of viral replication in the mosquito's salivary glands (extrinsic incubation period). The mosquito remains infected for the remainder of its 15- to 65-day lifespan. Vertical transmission of dengue virus in mosquitoes has been documented.9 The eggs of Aedes mosquitoes withstand long periods of desiccation, reportedly as long as 1 year, but are killed by temperatures of less than 10C. Once inoculated into a human host, dengue has an incubation period of 3-14 days (average 4-7 d) while viral replication takes place in target dendritic cells. Infection of target cells, primarily those of the reticuloendothelial system, such as dendritic cells, hepatocytes, and endothelial cells,10,11,12,13 result in the production of immune mediators that serve to shape the quantity, type, and duration of cellular and humoral immune response to both the initial and subsequent virus infections.14,15,10,16,17,18,19 Following incubation, a 5- to 7-day acute febrile illness ensues. Recovery is usually complete by 7-10 days. Dengue hemorrhagic fever or dengue shock syndrome usually develops around the third to seventh day of illness, approximately at the time of defervescence. The major pathophysiological abnormalities caused by dengue hemorrhagic fever and dengue shock syndrome include the rapid onset of plasma leakage, altered hemostasis, and damage to the liver, resulting in severe fluid losses and bleeding. Plasma leakage is caused by increased capillary permeability and may manifest as hemoconcentration, as well as pleural effusion and ascites. Bleeding is caused by capillary fragility and thrombocytopenia and may manifest in various forms, ranging from petechial skin hemorrhages to life-threatening gastrointestinal bleeding. Liver damage manifests as increases in levels of alanine aminotransferase and aspartate aminotransferase, low albumin levels, and deranged coagulationparameters(PT,PTT).20,21 In persons with fatal dengue hepatitis, infection was demonstrated in more than 90% of hepatocytes and Kupffer cells with minimal cytokine response (tumor necrosis factor [TNF] alpha, interleukin [IL]2). This is similar to that seen with fatal yellow fever and Ebola infections.20 Most patients who develop dengue hemorrhagic fever or dengue shock syndrome have had prior infection with one or more dengue serotypes. In individuals with low levels of neutralizing antibodies, nonneutralizing antibodies to one dengue serotype, when bound by macrophage and

monocyte Fc receptors, have been proposed to result in increased viral entry and replication and increased cytokine production and complement activation. This phenomenon is called antibodydependent enhancement. Some researchers suggest T-cell immunopathology may play a role, with increased T-cell activation and apoptosis. Increased concentrations of interferon have been recorded 1-2 days following fever onset during symptomatic secondary dengue infections.22 The activation of cytokines, including TNF-alpha, TNF receptors, soluble CD8, and soluble IL-2 receptors, has been correlated with disease severity.10 Cuban studies have shown that stored serum sample analysis demonstrated progressive loss of cross-reactive neutralizing antibodies to DENV-2 as the interval since DENV-1 infection increased.17 In addition, certain dengue strains, particularly those of DENV-2, have been proposed to be more virulent, in part because more epidemics of dengue hemorrhagic fever have been associated with DENV-2 than with the other serotypes.
Frequency http://emedicine.medscape.com/article/215840-overview

Clinical
History

Fever in persons with symptomatic dengue fever may be as high as 41C. The fever typically begins on the third day and lasts 5-7 days, abating with the cessation of viremia. Fever is often preceded by chills, erythematous mottling of the skin, and facial flushing (a sensitive and specific indicator of dengue fever). Occasionally, and more commonly in children, the fever abates for a day and then returns, a pattern that has been called saddleback fever. Patients are at risk for development of dengue hemorrhagic fever or dengue shock syndrome at approximately the time of defervescence. In travelers, symptoms that begin more than 2 weeks after they depart from an endemic area and fever that lasts longer than 10 days are probably not due to dengue. Headache is usually generalized. Retroorbital pain is common and is often described as severe. Patients may report nausea and vomiting. Patients typically describe a maculopapular or macular confluent rash over the face, thorax, and flexor surfaces, with islands of skin sparing. The rash typically begins on day 3 and persists 2-3 days. Patients may have severe myalgias, particularly of the lower back, arms, and legs, and arthralgias, especially of the knees and shoulders. Hemorrhagic manifestations may range from small amounts of bleeding from the nose or gums to melena, menorrhagia, or hematemesis. Abdominal pain is reported; often, abdominal pain in conjunction with restlessness, change in mental status, hypothermia, and a drop in the platelet count presages the development of dengue hemorrhagic fever. Patients report fatigue and malaise. Patients may report conjunctival injection, sore throat, and cough.

Cardiomyopathy is reported, with tachycardia during the febrile period and bradycardia and conduction defect. Myocarditis and congestive heart failure are rare.

Physical

Fever is present. Rash is described as follows: o Up to half of patients with dengue fever develop a characteristic rash. o The rash is variable and may be maculopapular or macular. o Petechiae and purpura may develop as hemorrhagic manifestations. Conjunctival injection develops in approximately one third of patients with dengue hemorrhagic fever. Optic neuropathy has been reported and occasionally results in permanent and significant visual impairment.25 Pharyngeal injection develops in almost 97% of patients with dengue hemorrhagic fever. Generalized lymphadenopathy is observed. Hepatomegaly is present more often in dengue shock syndrome than in milder cases. Hepatic transaminase levels may be mildly elevated. Hemorrhagic manifestations include the following o Petechiae and bleeding at venipuncture sites are most common. o Results from a tourniquet test are often positive. This test is performed by inflating a blood pressure cuff on the upper arm to midway between diastolic and systolic blood pressures for 5 minutes. The results are considered positive if more than 20 petechiae per square inch are observed on the skin of the arm. o Other hemorrhagic manifestations include nasal or gingival bleeding, melena, hematemesis, and menorrhagia. Encephalopathy is a rare complication that may result from a combination of cerebral edema, intracranial hemorrhage, anoxia, hyponatremia, and hepatic injury. Dengue fever presents in a nonspecific manner and may not be distinguishable from other viral or bacterial illness. The PAHO has developed the following case definitions for the diagnosis of dengue fever and dengue hemorrhagic fever or dengue shock syndrome: o The clinical description of dengue fever is an acute febrile illness of 2-7 days duration associated with 2 or more of the following: Severe headache Retroorbital pain Severe myalgias Arthralgia Characteristic rash Hemorrhagic manifestations Leukopenia o Laboratory criteria for diagnosis include one or more of the following: Isolation of the dengue virus from serum, plasma, leukocytes, or autopsy samples Demonstration of a 4-fold or greater change in reciprocal immunoglobulin G (IgG) or immunoglobulin M (IgM) antibody

titers to one or more dengue virus antigens in paired serum samples Demonstration of dengue virus antigen in autopsy tissue via immunohistochemistry or immunofluorescence or in serum samples via enzyme immunoassay (EIA) Detection of viral genomic sequences in autopsy tissue, serum, or cerebral spinal fluid (CSF) samples via polymerase chain reaction (PCR) o Cases are classified as suspected if they are compatible with the clinical description. o Cases are classified as probable if they are compatible with the clinical definition and satisfy one or more of the following criteria: Supportive serology (reciprocal hemagglutination-inhibition antibody titer greater than 1280, comparable IgG EIA titers, or positive IgM antibody test in late acute or convalescent-phase serum specimen) Occurrence at the same location and time as other confirmed cases of dengue fever o A confirmed case is one that is compatible with the clinical definition and is confirmed by the laboratory. o Criteria for the diagnosis of dengue hemorrhagic fever include a probable or confirmed case of dengue infection and hemorrhagic tendencies as evidenced by one or more of the following: A positive result from the tourniquet test Petechiae, ecchymoses, or purpura Bleeding from the mucosa, gastrointestinal tract, injection sites, or other sites Hematemesis or melena and thrombocytopenia (<100,000 cells/L) and evidence of plasma leakage due to increased vascular permeability that manifests as one or more of the following: greater than 20% rise in average hematocrit level for age and sex, greater than 20% drop in hematocrit level following volume replacement compared to baseline, or signs of plasma leakage (eg, pleural effusion, ascites, hypoproteinemia) o Dengue shock syndrome is diagnosed in cases meeting all of the above criteria plus evidence of circulatory failure, such as the following: Rapid, weak pulse Narrow pulse pressure (<20 mm Hg), with increased peripheral vascular resistance (PVR) and elevated diastolic pressure Hypotension Cool, clammy skin Altered mental status, although the patient may initially remain alert o The onset of shock may be subtle, indicated by raised diastolic pressure and increased PVR in an alert patient. The WHO classification system was recently studied in Indonesian children and was found to have a sensitivity of 86% (95% CI, 76-94) for the detection of dengue shock syndrome.14 The clinical reliability of the WHO criteria was compared with those of several modified systems, which added the above early predictors of compensated shock and considered models using varying

combinations of evidence of hemorrhagic tendencies, thrombocytopenia, and hemoconcentration. These modified systems were found to yield higher sensitivities (88%-99%) for dengue diagnosis than the WHO classification system and were more in line with clinical determinations made by local expert physicians. A Belgian study examined predictors of diagnosis in 1962 febrile travelers and expatriates returning from the tropics. After malaria was ruled out, the main predictors of dengue infection included skin rash, thrombocytopenia, and leukopenia.26

Causes

Dengue infection is caused by 1 of the 4 dengue viruses (ie, DENV-1, DENV-2, DENV-3, DENV-4) and is transmitted to humans by the bite of an infected mosquito.
printable version Fact sheet N117 March 2009

Dengue and dengue haemorrhagic fever

Key facts

Dengue is a mosquito-borne infection that causes a severe flu-like illness, and sometimes a potentially lethal complication called dengue haemorrhagic fever. Global incidence of dengue has grown dramatically in recent decades. About two fifths of the world's population are now at risk. Dengue is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas. Dengue haemorrhagic fever is a leading cause of serious illness and death among children in some Asian countries. There is no specific treatment for dengue, but appropriate medical care frequently saves the lives of patients with the more serious dengue haemorrhagic fever. The only way to prevent dengue virus transmission is to combat the diseasecarrying mosquitoes.

Dengue is a mosquito-borne infection that in recent decades has become a major international public health concern. Dengue is found in tropical and sub-tropical regions around the world, predominantly in urban and semi-urban areas.

Dengue haemorrhagic fever (DHF), a potentially lethal complication, was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand. Today DHF affects most Asian countries and has become a leading cause of hospitalization and death among children in the region. There are four distinct, but closely related, viruses that cause dengue. Recovery from infection by one provides lifelong immunity against that virus but confers Related links only partial and transient protection against subsequent infection by the other three viruses. There is good evidence that sequential :: Dengue/dengue infection increases the risk of developing DHF. haemorrhagic fever
Global burden of dengue

The incidence of dengue has grown dramatically around the world in recent decades. Some 2.5 billion people two fifths of the world's population are now at risk from dengue. WHO currently estimates there may be 50 million dengue infections worldwide every year. In 2007 alone, there were more than 890 000 reported cases of dengue in the Americas, of which 26 000 cases were DHF.

:: Dengue haemorrhagic fever: diagnosis, treatment, prevention and control :: Dengue (Special Programme for Research and Training in Tropical Diseases, TDR)

The disease is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South-east Asia and the Western Pacific. South-east Asia and the Western Pacific are the most seriously affected. Before 1970 only nine countries had experienced DHF epidemics, a number that had increased more than four-fold by 1995. Not only is the number of cases increasing as the disease is spreading to new areas, but explosive outbreaks are occurring. In 2007, Venezuela reported over 80 000 cases, including more than 6 000 cases of DHF. Some other statistics:

During epidemics of dengue, infection rates among those who have not been previously exposed to the virus are often 40% to 50%, but can reach 80% to 90%. An estimated 500 000 people with DHF require hospitalization each year, a very large proportion of whom are children. About 2.5% of those affected die. Without proper treatment, DHF fatality rates can exceed 20%. Wider access to medical care from health providers with knowledge about DHF - physicians and nurses who recognize its symptoms and know how to treat its effects can reduce death rates to less than 1%.

The spread of dengue is attributed to expanding geographic distribution of the four dengue viruses and their mosquito vectors, the most important of which is the predominantly urban species Aedes aegypti. A rapid rise in urban mosquito populations is bringing ever greater numbers of people into contact with this vector, especially in areas that are favourable for

mosquito breeding, e.g. where household water storage is common and where solid waste disposal services are inadequate.
DengueNet: WHO surveillance Transmission

Dengue viruses are transmitted to humans through the bites of infective female Aedes mosquitoes. Mosquitoes generally acquire the virus while feeding on the blood of an infected person. After virus incubation for eight to 10 days, an infected mosquito is capable, during probing and blood feeding, of transmitting the virus for the rest of its life. Infected female mosquitoes may also transmit the virus to their offspring by transovarial (via the eggs) transmission, but the role of this in sustaining transmission of the virus to humans has not yet been defined.

WHO/TDR/Stammers

Infected humans are the main carriers and multipliers of the virus, serving as a source of the virus for uninfected mosquitoes. The virus circulates in the blood of infected humans for two to seven days, at approximately the same time that they have a fever; Aedes mosquitoes may acquire the virus when they feed on an individual during this period. Some studies have shown that monkeys in some parts of the world play a similar role in transmission.
Characteristics

Dengue fever is a severe, flu-like illness that affects infants, young children and adults, but seldom causes death. The clinical features of dengue fever vary according to the age of the patient. Infants and young children may have a fever with rash. Older children and adults may have either a mild fever or the classical incapacitating disease with abrupt onset and high fever, severe headache, pain behind the eyes, muscle and joint pains, and rash. Dengue haemorrhagic fever (DHF) is a potentially deadly complication that is characterized by high fever, often with enlargement of the liver, and in severe cases circulatory failure. The illness often begins with a sudden rise in temperature accompanied by facial flush and other flu-like symptoms. The fever usually continues for two to seven days and can be as high as 41C, possibly with convulsions and other complications. In moderate DHF cases, all signs and symptoms abate after the fever subsides. In severe cases, the patient's condition may suddenly deteriorate after a few days of fever; the temperature drops, followed by signs of circulatory failure, and the patient may rapidly go into a critical state of shock and die within 12 to 24 hours, or quickly recover following appropriate medical treatment (see below).