DENGUE FEVER (DEMAM BERDARAH)

Dengue fever

Dengue fever (pronounced /ˈdɛŋgeɪ/ (BrE), /ˈdɛŋgiː/ (AmE)) and dengue hemorrhagic fever (DHF) are acute febrile diseases, found in the tropics and Africa, and caused by four closely related virus serotypes of the genus Flavivirus, family Flaviviridae.[1] It is also known as breakbone fever. The geographical spread is similar to malaria, but unlike malaria, dengue is often found in urban areas of tropical nations, including Puerto Rico, Singapore, Malaysia, Taiwan, Thailand, Indonesia, Philippines, Pakistan, India, Brazil, Vietnam, Guyana, Venezuela and Bangladesh. Each serotype is sufficiently different that there is no cross-protection and epidemics caused by multiple serotypes (hyperendemicity) can occur. Dengue is transmitted to humans by the Aedes aegypti (rarely Aedes albopictus) mosquito, which feeds during the day.


Signs and symptoms

This is manifested by a sudden onset of severe headache, muscle and joint pains (myalgias and arthralgias—severe pain gives it the name break-bone fever or bonecrusher disease), fever, and rash.[3] The dengue rash is characteristically bright red petechiae and usually appears first on the lower limbs and the chest; in some patients, it spreads to cover most of the body. There may also be gastritis with some combination of associated abdominal pain, nausea, vomiting, or diarrhea.

Some cases develop much milder symptoms which can be misdiagnosed as influenza or other viral infection when no rash is present. Thus travelers from tropical areas may pass on dengue in their home countries inadvertently, having not been properly diagnosed at the height of their illness. Patients with dengue can pass on the infection only through mosquitoes or blood products and only while they are still febrile.

The classic dengue fever lasts about six to seven days, with a smaller peak of fever at the trailing end of the disease (the so-called biphasic pattern). Clinically, the platelet count will drop until the patient's temperature is normal.

Cases of DHF also show higher fever, variable haemorrhagic phenomena, thrombocytopenia, and haemoconcentration. A small proportion of cases lead to dengue shock syndrome (DSS) which has a high mortality rate.

[edit] Diagnosis

The diagnosis of dengue is usually made clinically. The classic picture is high fever with no localising source of infection, a petechial rash with thrombocytopenia and relative leukopenia.

The WHO definition of dengue haemorrhagic fever has been in use since 1975; all four criteria must be fulfilled:[4]

1. Fever, bladder problem, constant headaches, severe dizziness and loss of appetite.
2. Hemorrhagic tendency (positive tourniquet test, spontaneous bruising, bleeding from mucosa, gingiva, injection sites, etc.; vomiting blood, or bloody diarrhea)
3. Thrombocytopenia (<100,000 platelets per mm³ or estimated as less than 3 platelets per high power field)
4. Evidence of plasma leakage (hematocrit more than 20% higher than expected, or drop in haematocrit of 20% or more from baseline following IV fluid, pleural effusion, ascites, hypoproteinemia)

Dengue shock syndrome is defined as dengue hemorrhagic fever plus:

* Weak rapid pulse,
* Narrow pulse pressure (less than 20 mm Hg)
* Cold, clammy skin and restlessness.

Serology and polymerase chain reaction (PCR) studies are available to confirm the diagnosis of dengue if clinically indicated.

[edit] Treatment

The mainstay of treatment is timely supportive therapy to tackle shock due to haemoconcentration and bleeding. Close monitoring of vital signs in critical period (between day 2 to day 7 of fever) is vital. Increased oral fluid intake is recommended to prevent dehydration. Supplementation with intravenous fluids may be necessary to prevent dehydration and significant concentration of the blood if the patient is unable to maintain oral intake. A platelet transfusion is indicated in rare cases if the platelet level drops significantly (below 20,000) or if there is significant bleeding. The presence of melena may indicate internal gastrointestinal bleeding requiring platelet and/or red blood cell transfusion.

Aspirin and non-steroidal anti-inflammatory drugs should be avoided as these drugs may worsen the bleeding tendency associated with some of these infections. Patients may receive paracetamol preparations to deal with these symptoms if dengue is suspected.[5]

[edit] Emerging treatments

Emerging evidence suggests that mycophenolic acid and ribavirin inhibit dengue replication. Initial experiments showed a fivefold increase in defective viral RNA production by cells treated with each drug.[6] In vivo studies, however, have not yet been done. Unlike HIV therapy, lack of adequate global interest and funding greatly hampers the development of treatment regime.

[edit] Epidemiology
World-wide dengue distribution, 2006. Red: Epidemic dengue. Blue: Aedes aegypti.
World-wide dengue distribution, 2000.

The first epidemics occurred almost simultaneously in Asia, Africa, and North America in the 1780s. The disease was identified and named (see #History below) in 1779. A global pandemic began in Southeast Asia in the 1950s and by 1975 DHF had become a leading cause of death among many children in many countries in that region. Epidemic dengue has become more common since the 1980s. By the late 1990s, dengue was the most important mosquito-borne disease affecting humans after malaria, there being around 40 million cases of dengue fever and several hundred thousand cases of dengue hemorrhagic fever each year. There was a serious outbreak in Rio de Janeiro in February 2002 affecting around one million people and killing sixteen.

On March 20, 2008, the secretary of health of the state of Rio de Janeiro, Sérgio Côrtes, announced that 23,555 cases of dengue, including 30 deaths, had been recorded in the state in less than three months. Côrtes said, "I am treating this as an epidemic because the number of cases is extremely high." Federal Minister of Health José Gomes Temporão also announced that he was forming a panel to respond to the situation. Cesar Maia, mayor of the city of Rio de Janeiro, denied that there was serious cause for concern, saying that the incidence of cases was in fact declining from a peak at the beginning of February. [7] By April 3, 2008, the number of cases reported rose to 55,000 [8]

Significant outbreaks of dengue fever tend to occur every five or six months. The cyclicity in numbers of dengue cases is thought to be the result of seasonal cycles interacting with a short-lived cross-immunity for all four strains, in people who have had dengue (Wearing and Rohani 2006). When the cross-immunity wears off, the population is then more susceptible to transmission whenever the next seasonal peak occurs. Thus in the longer term of several years, there tend to remain large numbers of susceptible people in the population despite previous outbreaks because there are four different strains of the dengue virus and because of new susceptible individuals entering the target population, either through childbirth or immigration.

There is significant evidence, originally suggested by S.B. Halstead in the 1970s, that dengue hemorrhagic fever is more likely to occur in patients who have secondary infections by serotypes different from the primary infection. One model to explain this process is known as antibody-dependent enhancement (ADE), which allows for increased uptake and virion replication during a secondary infection with a different strain. Through an immunological phenomenon, known as original antigenic sin, the immune system is not able to adequately respond to the stronger infection, and the secondary infection becomes far more serious.[9] This process is also known as superinfection.[10][11]

In Singapore, there are about 4,000–5,000 reported cases of dengue fever or dengue haemorrhagic fever every year. In the year 2003, there were six deaths from dengue shock syndrome.[citation needed] It is believed that the reported cases of dengue are an underrepresentation of all the cases of dengue as it would ignore subclinical cases and cases where the patient did not present for medical treatment. With proper medical treatment, the mortality rate for dengue can therefore be brought down to less than 1 in 1000