Dengue fever (IPA: /ˈdɛŋgeɪ/) 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] The geographical spread is similar to malaria, but
unlike malaria, dengue is often found in urban areas of tropical nations, including Singapore,
Taiwan, Indonesia, Philippines, India and Brazil. 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.[2]

Contents
[hide]
• 1 Signs and symptoms
• 2 Diagnosis
• 3 Treatment
○ 3.1 Emerging treatments
• 4 Epidemiology
• 5 Prevention
○ 5.1 Vaccine development
○ 5.2 Mosquito control
○ 5.3 Personal protection
○ 5.4 Potential antiviral approaches
• 6 Recent outbreaks
○ 6.1 Americas
○ 6.2 Asia Pacific
• 7 History
• 8 See also
• 9 Footnotes
• 10 References
• 11 External links

[edit] Signs and symptoms

This article or section is missing citations or needs footnotes.
Using inline citations helps guard against copyright violations and factual inaccuracies. (April 2008)

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 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.
Other symptoms include:
• fever;
• bladder problems;
• constant headaches;
• severe dizziness; and,
• loss of appetite.
Some cases develop much milder symptoms which can, when no rash is present, be
misdiagnosed as influenza 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 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, 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:[3]
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) or,
• 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 supportive therapy. 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.
It is very important to avoid aspirin and non-steroidal anti-inflammatory drugs; these drugs may
aggravate the bleeding tendency associated with some of these infections. Patients should receive
instead paracetamol preparations to deal with these symptoms if dengue is suspected.[4]
[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.[5] In vivo studies, however, have not yet been done. It is recommended that
patients consume warm tomato juice to reduce the fever.
[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 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. 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. [6] By April 3, 2008, the number of cases
reported rose to 55,000 [7]
Significant outbreaks of dengue fever tend to occur every five or six years. 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.[8] 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 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.[citation needed]
[edit] Prevention
[edit] Vaccine development
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.[9] Thai researchers are
testing a dengue fever vaccine on 3,000–5,000 human volunteers after having successfully
conducted tests on animals and a small group of human volunteers.[10] A number of other vaccine
candidates are entering phase I or II testing.[11]
[edit] Mosquito control

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 Public Health Image Library
Primary prevention of dengue mainly resides in mosquito control Mosquito control can be
achieved by mainly two methods, first and foremost is larval control and second one is adult
mosquito control. Aedes mosquito breeds mainly on water collections in artificial containers, like
plastic cups, used tyres,broken bottles, flower pots etc. Continued and sustained artificial
container reduction or periodic draining of artificial containers is the most effective way i n
reducing the larval and thereby the aedes mosquito load in the community. For reducing the adult
mosquito load, either fogging with insecticide is some what effective. Prevention of mosquito
bites is another way of preventing disease. this can be achieved either by personnel protection or
by using mosquito nets. In 1998, scientists from the Queensland Institute of Research in
Australia and Vietnam's Ministry of Health had introduced a scheme that encouraged children to
place a water bug, a crustacean called Mesocyclops, in water tanks and discarded containers
where the mosquito, Aedes aegypti, was known to thrive. It is viewed as being more cost-
effective and more environmentally friendly than pesticides, though not as effective, and
required the ongoing participation of the community.[12]
[edit] Personal protection
Personal prevention consists of the use of mosquito nets, repellents containing NNDB or DEET,
covering exposed skin, use of DEET-impregnated bednets, and avoiding endemic areas.
[edit] Potential antiviral approaches
In cell culture experiments[13] and mice [14] Morpholino antisense oligos have shown specific
activity against Dengue virus.
The yellow fever vaccine (YF-17D) is a related Flavivirus,[clarify] thus the chimeric replacement of
yellow fever vaccine with dengue has been often suggested[clarify] but no full scale studies have
been conducted to date.[15]
In 2006, a group of Argentine scientists discovered the molecular replication mechanism of the
virus, which could be attacked by disruption of the polymerase's work.[16]
[edit] Recent outbreaks
A public service ad teaching people how to prevent dengue and yellow fever in Encarnación,
Paraguay (2007)
2005 dengue outbreak (edit)
D Date of S
Count C
eat Inform ourc
ry ases
hs ation es
Camb 20,0
38 Sep. [1]
odia 00
Costa 19,0
1 7 Sep. [2]
Rica 00
India,
(West 90,0 1,50
Sep. [3]
Benga 00 0
l)
Indon 80,8 1,09 Jan. [4]
esia 37 9 2006
Malay 32,9 1
83 [5]
sia 50 Nov.
Marti 6,00 26
2 [6]
nique 0 Sep.
Philip 21,5
280 2 Oct. [7]
pines 37
Singa 12,7 22
19 [8]
pore 00 Oct.
Sri 3,00 16
- [9]
Lanka 0 Sep.
Thaila 31,0
58 Sep. [10]
nd 00
Vietna 20,0
28 4 Oct. [11]
m 00
11
Pakist 4,80
50 Dec [12]
an 0
2006.
232, 16,6
Total† — —
724 73
†
For listed countries only.
World Health Organization
estimates that there may be
 50 million cases of dengue
infection worldwide each
year. [13]
During the first months of 2007, over 16,000 cases have been reported in Paraguay and in the
end of the year, more than 100.000, of which around 300 or 400 have been detected as DHF
cases. Ten deaths have also been reported, including a high ranking member of the Ministry of
Health. One Department of Health official resigned because he had approved the use of expired
batches of insecticide to control the mosquito vectors of dengue.[17][18] The disease has propagated
to Argentina (where it is not considered endemic) by people who recently arrived from
Paraguay.[19] 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.[18] Epidemics in the states of
Ceará, Pará, São Paulo, and Rio de Janeiro have taken the Brazilian national tally of cases to
over 70,000, with upwards of 80 deaths.[20] Larvae have also been found in Parana state. The
proportion of cases registered as DHF is reported to be higher than in previous years.[citation needed]
[edit] Americas
• Puerto Rico: [21](August 2007) 2,343 confirmed cases of dengue in 2007.
• Dominican Republic:[not in citation given][22](August – October 2006) 4,968 cases with 44 dead
• Cuba: Media reports [23][24][25][26] (dated September and October 2006) speculate on an
outbreak although there is no official report
• Brazil: 2008 Health officials say an outbreak of dengue fever has infected more than
110,000 people in Rio de Janeiro state and claimed at least 95 lives since January 1st. An
outbreak of Dengue in the first seven months of 2007 reported more than 438,000 cases
of dengue fever, with 97 deaths.[27]
• Mexico: As of October 2007 there is a serious problem in Monterrey, Nuevo Leon almost
reaching epidemic proportions.[citation needed]
[edit] Asia Pacific
See also: 2006 dengue outbreak in Pakistan, 2005 dengue outbreak in Singapore, and
2006 dengue outbreak in India
• Australia: 2006 March 15, 2 confirmed cases at Gordonvale, Cairns, Queensland.
• China: September 2006, 70 cases since June in Guangzhou,Guangdong.[28]
• Cook Islands: [29](October 2006 – January 2007) 460 cases.
• India: 2006 September, more than 400 cases and 22 deaths were reported due to dengue
fever in New Delhi.[30] By October 7, 2006, reports were of 3,331 cases of the mosquito-
borne virus and a death toll of 49.[31]
• Indonesia: 2004 80,000 infected with 800 deaths.
• Malaysia: January 2005 33,203 cases.
• Pakistan: 2006 Over 3,230 cases, 50 deaths.
○ Karachi 2006 October, the number of infected patients rose to 1,836 of which 30
had died.
 ○ Lahore, 2006 October 23, the disease shifted to Lahore during the holidays with
the luggage of some people travelling to their homes to celebrate Eid. The number
of infected patients is 400 by October 31, of which 4 had died.
• Philippines: [32](January – August 2006) 13,468 cases with 167 dead.
• Singapore: 2007 more than 4029 cases, 8 deaths at 29 September 2005 at least 13 deaths.
2004 9,460 cases. 2003, 4,788 cases.
• Thailand: May 2005 , 7,200 infected. At least 12 dead.

[edit] History
The origins of the word dengue are not clear, but one theory is that it is derived from the Swahili
phrase "Ka-dinga pepo", which describes the disease as being caused by an evil spirit.[33] The
Swahili word "dinga" may possibly have its origin in the Spanish word "dengue" (fastidious or
careful), describing the gait of a person suffering dengue fever[34] or, alternatively, the Spanish
word may derive from the Swahili.[35] It may also be attributed to the phrase meaning "Break
bone fever", referencing the fact that pain in the bones is a common symptom.
Outbreaks resembling dengue fever have been reported throughout history.[36] The first definitive
case report dates 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. Population movements
during World War II spread the disease globally.
In 2007 replication mechanism of the virus was interrupted by tnterception of the viral protease
[14], and currently a project to identify new protease interception mechanisms of the whole
familly of the virus has been launched (Dengue virus belong to the familly Flaviviridae, which
includes among others HCV, West Nile and Yellow fever viruses). The software and information
about the project can be found at the World Community Grid web site.[15]
[edit] See also
• Tropical disease
• Chikungunya
• Joseph Franklin Siler

[edit] Footnotes
1. ^ Chapter 4, Prevention of Specific Infectious Diseases. CDC Traveler's Health: Yellow
Book. Retrieved on 2007-05-20.
2. ^ Dengue Fever – Information Sheet. World Health Organization, October 9, 2006.
Retrieved on 2007-11-30.
3. ^ Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. 2nd edition.
World Health Organization. Retrieved on 2007-11-30.
4. ^ Dengue and Dengue Hemorrhagic Fever: Information for Health Care Practitioners.
Center for Disease Control. October 22, 2007 Retrieved on 2007-11-30.
5. ^ Takhampunya R, Ubol S, Houng HS, Cameron CE, Padmanabhan R (2006). "Inhibition
of dengue virus replication by mycophenolic acid and ribavirin". J. Gen. Virol. 87 (Pt 7):
1947–52. doi:10.1099/vir.0.81655-0. PMID 16760396.
6. ^ Fernanda Pontes (20 March 2008), "Secretário estadual de Saúde Sérgio Côrtes
admite que estado vive epidemia de dengue", O Globo Online,
<http://oglobo.globo.com/rio/mat/2008/03/20/secretario_estadual_de_saude_sergio_cor
tes_admite_que_estado_vive_epidemia_de_dengue-426368388.asp>.
7. ^ CNN (3 April 2008), "Thousands hit by Brazil outbreak of dengue", CNN,
<http://www.cnn.com/2008/HEALTH/conditions/04/03/brazil.dengue/index.html>.
8. ^ Rothman AL (2004). "Dengue: defining protective versus pathologic immunity". J.
Clin. Invest. 113 (7): 946–51. doi:10.1172/JCI200421512. PMID 15057297.
9. ^ Pediatric Dengue Vaccine Initiative website. International Vaccine Institute. Retrieved
on 2007-11-30.
10. ^ Thailand to test Mahidol-developed dengue vaccine prototype. People's Daily Online
(2005-09-05). Retrieved on 2006-10-08.
11. ^ Edelman R (2007). "Dengue vaccines approach the finish line". Clin. Infect. Dis. 45
Suppl 1: S56–60. doi:10.1086/518148. PMID 17582571.
12. ^ "Water bug aids dengue fever fight", BBC News, February 11, 2005. Retrieved on
2007-11-30.
13. ^ Kinney RM, Huang CY, Rose BC, et al (2005). "Inhibition of dengue virus serotypes 1
to 4 in vero cell cultures with morpholino oligomers". J. Virol. 79 (8): 5116–28.
doi:10.1128/JVI.79.8.5116-5128.2005. PMID 15795296.
14. ^ Burrer R, Neuman BW, Ting JP, et al (2007). "Antiviral effects of antisense morpholino
oligomers in murine coronavirus infection models". J. Virol. 81 (11): 5637–48.
doi:10.1128/JVI.02360-06. PMID 17344287.
15. ^ Querec T, Bennouna S, Alkan S, et al (2006). "Yellow fever vaccine YF-17D activates
multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity".
J. Exp. Med. 203 (2): 413–24. doi:10.1084/jem.20051720. PMID 16461338.
16. ^ Filomatori CV, Lodeiro MF, Alvarez DE, Samsa MM, Pietrasanta L, Gamarnik AV
(2006). "A 5' RNA element promotes dengue virus RNA synthesis on a circular genome".
Genes Dev. 20 (16): 2238–49. doi:10.1101/gad.1444206. PMID 16882970.
17. ^ Dengue sparks Paraguay emergency. BBC News (2 March 2007). Retrieved on 2007-
06-19.
18. ^ a b Paraguay dengue official sacked. BBC News (6 March 2007). Retrieved on 2007-06-
19.
19. ^ (Spanish) "Hay 93 casos de dengue", Clarín, 22 February 2007.
20. ^ (Spanish) "Dengue Outbreak Sweeps Through Rio", New York Times, 15 April 2008.
21. ^ "Dengue fever surging in Puerto Rico", MSNBC, Telemundo, August 08, 2007.
Retrieved on 2007-13009.
22. ^ (Spanish) Batista, L.; A Santiago Díaz. "Más de 4,968 afectados por dengue", Diario
Libre. Retrieved on 2006-10-19.
23. ^ "Protecting the Revolution", Strategypage.com, September 17, 2006. Retrieved on
2006-10-07.
 24. ^ Acosta, Dalia. "War on Mosquitoes Continues During Global Summit", Inter Press
Service, 2006-09-12. Retrieved on 2006-10-07.
25. ^ "Cuba wages war on tiny enemy", Independent Online, South Africa, September 25,
2006. Retrieved on 2006-10-07.
26. ^ "Cuba waging war against dengue fever", Miami Herald, October 7, 2006. Retrieved on
2006-10-07.
27. ^ State secretary of Health
http://www.saude.rj.gov.br/Docs/Acoes/Dengue/Relat%F3rio%20de%20Casos%20de%2
0Dengue%20(25-04-2008%20-%2019h10m).pdf
28. ^ China, Dengue Fever Cases Jump. Taipei Times, 29 August, 2006.
29. ^ "460 people in Cook Islands affected by Dengue Fever outbreak", Radio New Zealand
International, 15 January 2007. Retrieved on 2007-01-15.
30. ^ "Dengue fever kills 14 in India, affects more than 400", International Herald Tribune,
Associated Press News, October 2, 2006. Retrieved on 2006-10-02].
31. ^ India says dengue outbreak serious as death toll rises Pratap Chakravarty,
news.yahoo.com, 7 October 2006. Retrieved 8 October 2006.
32. ^ Santos, Tina. "DOH names dengue-hit areas in metropolis", Philippine Daily Inquirer,
September 10, 2006. Retrieved on 2006-10-07.
33. ^ Dengue fever: Essential data. Chemical and Biological Warfare Agents. Retrieved on
2007-11-30
34. ^ Dengue. Online Etymology Dictionary. Retrieved on 2007-11-30
35. ^ "etymologia: dengue" (PDF) (2006). Emerging Infectious Diseases 12: 893.
36. ^ Gubler DJ (1998). "Dengue and dengue hemorrhagic fever". Clin. Microbiol. Rev. 11
(3): 480–96. PMID 9665979.
[edit] 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.