ඩෙංගි උණ

Dengue fever
Classifications and external resources

ICD-10	A90.
ICD-9	061
DiseasesDB	3564
MedlinePlus	001374
eMedicine	med/528
MeSH	C02.782.417.214

ඩෙංගි උණ (සැකිල්ල:IPA2) and ඩෙංගි රක්තපාත උණ (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 Aedes aegypti (rarely Aedes albopictus) mosquito.This mosquito tends to bite just after dawn and just before sunset.

Etymology

The origins of the name are not clear but the most convincing explanation is that it is derived from the Swahili "dinga" (seizure, cramp) that describes the disease as being caused by an evil spirit.

රෝග ලක්ෂණ

This infectious disease is manifested by a sudden onset of fever, with severe headache, muscle and joint pains (myalgias and arthralgias — severe pain gives it the name break-bone fever or bonecrusher disease) 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 diarrhea.

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 been 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 show higher fever, haemorrhagic phenomena, thrombocytopenia and haemoconcentration. A small proportion of cases lead 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:

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 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, 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.

ප්‍රතිකාර

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. But the transfusion is recommendable on platelet count falling below 20,000 without hemorrhage / bleeding or approx 50,000 with hemorrhage/bleeding. Internal bleeding indicated by dark color of stools, other bleedings indicated at surface as red rashes all over or most of the body parts.

It is very important to avoid Aspirin and non-steroidal anti-inflammatory medications. These drugs are often used to treat pain and fever, but in this case, they may actually aggravate the bleeding tendency associated with some of these infections. If dengue is suspected, patients should receive instead acetaminophen preparations to deal with these symptoms [1].

Epidemiology

World-wide dengue distribution, 2005

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 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. 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 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. This process is also known as superinfection (Nowak and May 1994; Levin and Pimentel 1981).

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.

වැලැක්වීම

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 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.

Thai researchers, in phase III testing, have planned to test a dengue fever vaccine on 3,000-5,000 human volunteers within the next three years after having successfully conducted tests on animals and a small group of human volunteers.

A field technician looking for larvae in standing water containers during the 1965 Aedes Aegypti eradication program in Miami, Florida. In the 1960s, a major effort was made to eradicate the principal urban vector mosquito of dengue and yellow fever viruses, A. aegypti, from southeast United States.
Courtesy: Centers for Disease Control and Prevention Publich Health Image Library

Primary prevention of dengue mainly resides in eliminating or reducing the mosquito vector for dengue. Public spraying for mosquitoes is the most important aspect of this vector. Application of larvicides such as Abate® to standing water is more effective in the long term control of mosquitoes. 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 and mice Morpholino antisense oligos have shown specific activity against Dengue virus.

In 2002 the Swiss pharmaceutical 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.

In 2006, a group of Argentine scientists directed by Andrea Gamarnik discovered the molecular replication mechanism of the virus, which could be attacked by disruption of the polymerase's work.

Recent outbreaks

සැකිල්ල:2005 dengue outbreak tally During the first months of 2007 over 16,000 cases have been reported in Paraguay, of which around 100 have been detected as DHF cases. This new epidemic is expected to continue in Paraguay for several months, given the forecast of continuous rain all through the summer. Ten deaths have also been reported, including recently a high ranking member of the Ministry of Health. The epidemic has been the root of a scandal in the Paraguayan Department of Health, where one official has resigned because he had approved the use of expired batches of insecticide to control the mosquito vectors of dengue. The disease has propagated to Argentina (where it is not considered endemic), in almost all cases by people who recently arrived from Paraguay. In the Brazilian state of Mato Grosso do Sul, which borders on Paraguay, the number of cases in March 2007 is estimated to be more than 45,000. Epidemics in the states of Ceará, Pará, São Paulo, and Rio de Janeiro have taken the Brazilian national tally of cases this year to over 70,000, with upwards of 20 deaths. The proportion of cases registered as DHF is reported to be higher than in previous years.

Recent dengue outbreaks in America:

• Dominican Republic (August – October 2006) 4,968 cases with 44 dead.
• Media reports (dated September and October 2006) speculate on an outbreak in Cuba, although there is no official report.

Recent dengue outbreaks in Asia and Pacific:

• Cook Islands (October 2006-January 2007) 460 cases.
• Philippines (January - August 2006) 13,468 cases with 167 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 (2006) 15 March 2006, 2 Confirmed Cases at Gordon Vale, Cairns, Queensland.
• China September 2006, 70 cases since June in Guangzhou,Guangdong.

As of September 2005, Singapore reported a significant rise in the number of dengue cases - about 9000 in the year to date, 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.

• New Delhi, India (September 2006) More than 400 cases and 22 deaths were reported due to dengue fever in the Indian capital. By October 7, 2006, reports were of 3,331 cases of the mosquito-borne virus and a death toll of 49.
• 2006 dengue outbreak in Pakistan with number of cases have climbed to over to 3,230 with 50 deaths.
  • Karachi, Pakistan (October 2006) The number of infected patients rose to 1,836 by October 28, 2006, of which 30 had died.
  • Lahore, Pakistan (October 2006) The Infection shifted to Lahore on 23 October 2006 during Eid Holidays with the luggage of some people travelling to their homes to celebrate Eid. The number of infected patients is 400 by October 31, 2006, of which 4 had died.

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.

See also

• Tropical disease
• 2006 dengue outbreak in Pakistan
• 2005 dengue outbreak in Singapore
• 2006 dengue outbreak in India
• Chikungunya

References

• Manson's Tropical Diseases
• Mandell's Principles and Practices of Infection Diseases
• 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.

බාහිර යොමු

• CDC site on Dengue Fever.
• Dengueinfo.org - Resources & depository of Dengue Virus genomic sequences for biomedical researchers.