Dengue Hemorrhagic Fever (DHF)

Dengue fever and dengue hemorrhagic fever (DHF) are acute febrile diseases, found in the tropics, with a geographical spread similar to malaria. Caused by one of four closely related virus serotypes of the genus Flavivirus, family Flaviviridae, each serotype is sufficiently different that there is no cross-protection and epidemics caused by multiple serotypes (hyperendemicity) can occur. Dengue is found in tropical and sub-tropical regions around the world, predominantly in urban and semi-urban areas.

Alternative names are Hemorrhagic dengue, Dengue shock syndrome, Philippine hemorrhagic fever, Thai hemorrhagic fever, Singapore hemorrhagic fever.

Dengue is transmitted to humans by the mosquito Aedes aegypti (rarely Aedes albopictus).

Dengue haemorrhagic fever (DHF), a potentially lethal complication, was first recognized in the 1950s during the dengue epidemics in the Philippines and Thailand, but today DHF affects most Asian countries and has become a leading cause of hospitalisation and death among children in several of them.

There are four distinct, but closely related, viruses that cause dengue. Recovery from infection by one provides lifelong immunity against that serotype but confers only partial and transient protection against subsequent infection by the other three. There is good evidence that sequential infection increases the risk of more serious disease resulting in DHF.

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.

There exists a WHO definition of dengue haemorrhagic fever that has been in use since 1975; all four criteria must be fulfilled:

1. Fever
2. Haemorrhagic tendency (positive tourniquet test, spontaneous bruising, bleeding from mucosa, gingiva, injection sites, etc.; vomiting blood, or bloody diarrhea)
3. Thrombocytopaenia (<100,000>
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, hypoproteinaemia)

Dengue shock syndrome is defined as dengue haemorrhagic fever plus

• Weak rapid pulse,
• Narrow pulse pressure (less than 20 mm Hg)

or,

• Hypotension for age;
• Cold, clammy skin and restlessness.

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

Epidemiology

The term "dengue" is a Spanish attempt at the (Swahili language)phrase "ki denga pepo", meaning "cramp-like seizure caused by an evil spirit". It emerged during a Caribbean outbreak in 1827-1828.

Outbreaks resembling dengue fever have been reported throughout history. The first case report dates back from 1789 and is attributed to Benjamin Rush, who coined the term "breakbone fever" (because of the symptoms of myalgia and arthralgia). The viral etiology and the transmission by mosquitoes were only deciphered in the 20th century. The socioeconomic impact of World War II resulted in increased spread globally.

The global prevalence of dengue has grown dramatically in recent decades. 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 most seriously affected. Before 1970 only nine countries had experienced DHF epidemics, a number that had increased more than four-fold by 1995.

The first epidemics occurred almost simultaneously, in Asia, Africa, and North America in the 1780s. The disease was identified and named in 1779. A global pandemic began in Southeast Asia in the 1950s and by 1975 DHF had become a leading cause of death among 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. In February 2002 there was a serious outbreak in Rio de Janeiro, affecting around one million people but only killing sixteen.

Significant outbreaks of dengue fever tend to occur every five or six 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. This is due to a process 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 phenomena, 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.

Some 2500 million people -- two fifths of the world's population -- are now at risk from dengue. WHO currently estimates there may be 50 million cases of dengue infection worldwide every year.

In 2001 alone, there were more than 609 000 reported cases of dengue in the Americas, of which 15 000 cases were DHF. This is greater than double the number of dengue cases which were recorded in the same region in 1995.

Not only is the number of cases increasing as the disease is spreading to new areas, but explosive outbreaks are occurring. In 2001, Brazil reported over 390 000 cases including more than 670 cases of DHF.

Some other statistics:

• During epidemics of dengue, attack rates among susceptibles are often 40 -- 50%, but may reach 80 -- 90%.
• An estimated 500 000 cases of DHF require hospitalisation each year, of whom a very large proportion are children. At least 2.5% of cases die, although case fatality could be twice as high.
• Without proper treatment, DHF case fatality rates can exceed 20%. With modern intensive supportive therapy, such rates can be reduced to less than 1%.

The spread of dengue is attributed to expanding geographic distribution of the four dengue viruses and of their mosquito vectors, the most important of which is the predominantly urban species Aedes aegypti. A rapid rise in urban 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.

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 6 deaths from dengue shock syndrome. 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.

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