Dengue fever

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

Signs and symptoms

This infectious disease is manifested by a sudden onset of fever, with severe headache, joint and muscular pains (myalgias and arthralgias — severe pain gives it the name break-bone fever) and rashes; the dengue rash is characteristically bright red petechia 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 diarrhoea.

Some cases develop much milder symptoms, which can, when no rash is present, be misdiagnosed as a flu or other viral infection. Thus, travelers from tropical areas may inadvertently pass on dengue in their home countries, having not being properly diagnosed at the height of their illness. Patients with dengue can only pass on the infection through mosquitoes or blood products 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 fever (the so-called "biphasic pattern"). Clinically, the platelet count will drop until the patient's temperature is normal.

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

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:

fever
haemorrhagic tendency (positive tourniquet test, spontaneous bruising, bleeding from mucosa, gingiva, injection sites, etc.; vomiting blood, or bloody diarrhoea)
thrombocytopaenia (<100 platelets per mm³ or estimated as less than 3 platelets per high power field)
evidence of plasma leakage (haematocrit 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, and
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.

Treatment

The mainstay of treatment is supportive therapy. The patient is encouraged to keep up oral intake, especially of oral fluids. If the patient is unable to maintain oral intake, supplementation with intravenous fluids may be necessary to prevent dehydration and significant hemoconcentration. A platelet transfusion is rarely indicated if the platelet level drops significantly or if there is significant bleeding.

Epidemiology

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 viral 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 - in a process known as antibody-dependent enhancement (ADE).

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.

Prevention

There is no commercially available vaccine for the dengue flavivirus. However, one of the many ongoing vaccine development programs is the Pediatric Dengue Vaccine Initiative (PDVI ^*) which was set up in 2003 with the aim of accelerating the development and introduction of dengue vaccine(s) that are affordable and accessible to poor children in endemic countries.

Primary prevention of dengue mainly resides in eliminating or reducing the mosquito vector for dengue. Initiatives to eradicate pools of standing water (such as in flowerpots) have proven useful in controlling mosquito borne diseases. Promising new techniques have been recently reported from Oxford University on rendering the Aedes mosquito pest sterile.

Personal prevention consists of the use of mosquito nets, repellents, cover exposed skin, use DEET-impregnated bednets, and avoiding endemic areas. This is also important for malaria prevention.

Potential antiviral approaches

In cell culture experiments Morpholino antisense oligos have shown specific activity against Dengue virus ^* .

In 2002 the Swiss pharma company Novartis and the Singapore Economic Development board created the Novartis Institute for Tropical Diseases (NITD). NITD is a public-private partnership that researches neglected tropical disease. NITD's dengue unit is researching anti-viral drug discovery to treat or prevent dengue fever.

Recent outbreaks

Recent dengue outbreaks in South East Asia:

Philippines ( January - October 2005) 21,537 cases with 280 dead.
Thailand (May 2005) 7200 infected. At least 12 dead.
Indonesia (2004) 80,000 infected with 800 deaths.
Malaysia (January 2005), 33,203 cases.
Singapore (2005), At least 13 deaths, (2004), 9460 cases, (2003), 4788 cases.
Australia ^* 15 March 2006, 2 Confirmed Cases at Gordon Vale, Cairns, Queensland.

As of September 2005, Singapore reported a significant rise in the number of dengue cases - about 9000 in the year to date so far, about double the rate for the same period in 2004. It is even possible to have more than 500 cases per week. The large increase in dengue cases has caused hospitals to cancel some elective surgery due to the need to allocate more beds for dengue patients.

History

The term "dengue" is a Spanish attempt at the Swahili 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.

References

Manson's Tropical Diseases
Mandell's Principles and Practices of Infection Diseases or *this site
Cecil Textbook of Medicine
The Oxford Textbook of Medicine
Harrison's Principles of Internal Medicine
Theiler, Max and Downs, W. G. 1973. The Arthropod-Borne Viruses of Vertebrates: An Account of The Rockefeller Foundation Virus Program 1951-1970. Yale University Press.
Downs, Wilbur H., et al. 1965. Virus diseases in the West Indies. Special edition of the Caribbean Medical Journal, Vol. XXVI, Nos. 1-4, 1965.
Earle, k. Vigors. 1965. "Notes on the Dengue epidemic at Point Fortin." The Caribbean Medical Journal, Vol. XXVI, Nos. 1-4, pp. 157-164.
Hill, A. Edward. 1965. "Isolation of Dengue Virus from a Human Being in Trinidad." Virus diseases in the West Indies. The Caribbean Medical Journal, Vol. XXVI, Nos. 1-4, pp. 83-84; "Dengue and Related Fevers in Trinidad and Tobago." Ibid, pp. 91-96.

External links

CNN report on dengue fever.
CDC site on Dengue Fever.
Dengueinfo.org - Resources & depository of Dengue Virus genomic sequences for biomedical researchers.
eMedicine® resource on dengue

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