Dengue fever

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"Dengue Fever" redirects here. For the band of the same name, see Dengue Fever (band).
Dengue virus

A TEM micrograph showing

Dengue virus virions (the cluster of
dark dots near the center).
Virus classification
Group: Group IV
((+)ssRNA)
Family: Flaviviridae
Genus: Flavivirus
Species: Dengue virus
Dengue fever
Classification and external resources
ICD-10 A90.
ICD-9 061
DiseasesDB 3564
MedlinePlus 001374
eMedicine med/528
MeSH C02.782.417.214

Dengue fever (pronounced UK: /ˈdɛŋɡeɪ/, US: /ˈdɛŋɡiː/) and dengue hemorrhagic fever (DHF)
are acute febrile diseases, found in the tropics, 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 includes northern Australia, northern Argentina, and the entire Singapore,
Malaysia, Taiwan, Thailand, Cambodia, Vietnam, Indonesia, Honduras, Costa Rica, Panama,
Paraguay[2], Philippines, Pakistan, India, Sri Lanka, Bangladesh, Mexico, Suriname, Dominican
Republic, Puerto Rico, Jamaica, Bolivia[3], Brazil, Guyana, Venezuela, Barbados, Trinidad and
Samoa[4]. Unlike malaria, dengue is just as prevalent in the urban districts of its range as in rural
areas. 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 or more rarely the Aedes albopictus mosquito, which feed during the day.[5]

The WHO says some 2.5 billion people, two fifths of the world's population, are now at risk
from dengue and estimates that there may be 50 million cases of dengue infection worldwide
every year. The disease is now epidemic in more than 100 countries.[6]

Contents
[hide]

• 1 Signs and symptoms

• 2 Diagnosis
o 2.1 When to go for Dengue test
• 3 Etiology
• 4 Treatment
o 4.1 Traditional and emerging treatments
• 5 Epidemiology
• 6 Prevention
o 6.1 Vaccine development
o 6.2 Mosquito control
o 6.3 Potential antiviral approaches
• 7 Etymology
• 8 History
• 9 Use as a biological weapon
• 10 See also

• 11 References

[edit] Signs and symptoms

The disease manifests as a sudden onset of severe headache, muscle and joint pains (myalgias
and arthralgias—severe pain that gives it the nick-name break-bone fever or bonecrusher
disease), fever, and rash.[7] 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. DHF combined with a cirrhotic liver has been
suspected in rapid development of hepatocellular carcinoma (HCC). Given that the Dengue virus
(DEN) is related to the Hepatitis C virus, this is an avenue for further research as HCC is among
the top five cancerous causes of death outside Europe and North America. Normally HCC does
not occur in a cirrhotic liver for ten or more years after the cessation of the poisoning agent. DHF
patients can develop HCC within one year of cessation of poisoning agent.

[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 -
low platelet and white blood cell count. Care has to be taken as diagnosis of DHF can mask end
stage liver disease and vice versa.

1. Fever, bladder problem, constant headaches, eye pain, 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)
5. Encephalitic occurrences.

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.

A dependable immediate information of the Dengue diagnostics in the rural areas can be
performed by the introduction of Rapid Diagnostic Test kits which also differentiates between
primary and secondary dengue infections.[8] Serology and polymerase chain reaction (PCR)
studies are available to confirm the diagnosis of dengue if clinically indicated. Dengue can be a
life threatening fever.

[edit] When to go for Dengue test

If one has persistent fever for more that 2 days then one should go for CBC (Complete blood
check) checkup. If the platelet count and WBC count are below than their usual range one should
go for a Dengue Antigen test. If one has continuous fever for more than 2 days and/or constant
headaches one should go for CBC checkup. And one should decide whether to go for Dengue
Test depending on the result of CBC Counts.

[edit] Etiology
Dengue fever is caused by Dengue virus (DENV), a mosquito-borne flavivirus. DENV is a
ssRNA positive-strand virus of the family Flaviviridae; genus Flavivirus. There are four
serotypes of DENV. The virus has a genome of about 11000 bases that codes for three structural
proteins, C, prM, E; seven nonstructural proteins, NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5;
and short non-coding regions on both the 5' and 3' ends.[9]

[edit] Treatment
The mainstay of treatment is timely supportive therapy to tackle shock due to hemoconcentration
and bleeding. Close monitoring of vital signs in critical period (between day 2 to day 7 of fever)
is critical. 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.[10]

[edit] Traditional and 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.[11] In vivo studies, however, have not yet been done. Unlike HIV therapy, lack of
adequate global interest and funding greatly hampers the development of a treatment regime.

In Brazilian traditional medicine, dengue is treated with cat's claw herb, which is for
inflammation and does not prevent dengue.[12]

In Malaysia, dengue is treated by some using natural medicine. Mas Amirtha and Semalu
developed by the Alternative Medicine Research Institute, Center for Asia.[citation needed] The
treatment is speculated to be able to arrest and reverse the viral infection and prevent the disease
from advancing into a critical stage, though no evidence has yet shown effectiveness. In
Philippines dengue patients use tawa-tawa herbs and sweet potato tops juice to increase the
platelets counts and revived the patients.[citation needed]
[edit] Epidemiology

Worldwide dengue distribution, 2006. Red: Epidemic dengue. Blue: Aedes aegypti.

Dengue is transmitted by Aedes mosquitoes, particularly A. aegypti and A. albopictus. Dengue

may also be transmitted via infected blood products (blood transfusions, plasma, and platelets),
but the scale of this problem is unknown.[13]

Worldwide dengue distribution, 2000.

The first recognized Dengue epidemics occurred almost simultaneously in Asia, Africa, and
North America in the 1780s, shortly after the identification and naming of the disease in 1779. A
pandemic began in Southeast Asia in the 1950s, and by 1975 DHF had become a leading cause
of death among children in the 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, with around 40 million cases of dengue fever and several hundred
thousand cases of dengue hemorrhagic fever each year. Significant outbreaks of dengue fever
tend to occur every five or six months. The cyclical rise and fall in numbers of dengue cases is
thought to be the result of seasonal cycles interacting with a short-lived cross-immunity[clarification
needed]
for all four strains in people who have had dengue. When the cross-immunity wears off the
population is more susceptible to transmission whenever the next seasonal peak occurs. Thus
over time there remain large numbers of susceptible people in affected populations despite
previous outbreaks due to the four different serotypes of dengue virus and the presence of
unexposed individuals from 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 another
one of dengue fever's four serotypes. 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.[14] This process is also known as
superinfection.[15][16]

Reported cases of dengue are an under-representation of all cases when accounting for
subclinical cases and cases where the patient did not present for medical treatment.

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.[17] By April
3, 2008, the number of cases reported rose to 55,000 [18]

In Singapore, there are 4,000–5,000 reported cases of dengue fever or dengue haemorrhagic
fever every year. In the year 2004, there were seven deaths from dengue shock syndrome[19].

An epidemic broke out in Bolivia in early 2009, in which 18 people have died and 31,000
infected.

An outbreak of dengue fever was declared in Cairns, located in the tropical north of Queensland,
Australia on 1 December 2008. As at 3 March 2009 there were 503 confirmed cases of dengue
fever, in a residential population of 152,137. Outbreaks were subsequently declared the
neighbouring cities and towns of Townsville (outbreak declared 5 January 2009), Port Douglas
(6 February 2009), Yarrabah (19 February 2009), Injinoo (24 February 2009), Innisfail (27
February 2009) and Rockhampton (10 March 2009). There have been occurrences of dengue
types one, two, three and four in the region. March 4 2009, Queensland Health had confirmed an
elderly woman had died from dengue fever in Cairns, in the first fatality since the epidemic
began last year. The statement said that although the woman had other health problems, she
tested positive for dengue and the disease probably contributed to her death.

In 2009, in Argentina, a dengue outbreak was declared the northern provinces of Chaco,
Catamarca, Salta, Jujuy, and Corrientes, with over 9673 cases reported as of April 11, 2009 by
the Health Ministry [1]. Some travelers from the affected zones have spread the fever as far
south as Buenos Aires [2]. Major efforts to control the epidemic in Argentina are focused on
preventing its vector (the Aedes mosquitoes) from reproducing. This is addressed by asking
people to dry out all possible water reservoirs from where mosquitoes could proliferate (which
is, in other countries, known as "descacharrado"). There have also been information campaigns
concerning prevention of the dengue fever; and the government is fumigating with insecticide in
order to control the mosquito population.[20]
The first cases of dengue are currently being reported on the island of Mauritius, in the indian
ocean. One of the South Asian country still highly suffering from this problem is Sri Lanka.[21]

[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.[22] 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.[23] A number of other vaccine
candidates are entering phase I or II testing.[24]

[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, Aedes aegypti, from
southeast United States.

Primary prevention of dengue mainly resides in mosquito control. There are two primary
methods: larval control and adult mosquito control.[citation needed] In urban areas, Aedes mosquitos
breed on water collections in artificial containers such as plastic cups, used tires, broken bottles,
flower pots, etc. Periodic draining or removal of artificial containers is the most effective way of
reducing the breeding grounds for mosquitos.[citation needed] Larvicide treatment is another effective
way to control the vector larvae but the larvicide chosen should be long-lasting and preferably
have World Health Organization clearance for use in drinking water. There are some very
effective insect growth regulators (IGRs) available which are both safe and long-lasting (e.g.
pyriproxyfen). For reducing the adult mosquito load, fogging with insecticide is somewhat
effective.[citation needed]

Prevention of mosquito bites is another way of preventing disease. This can be achieved by using
insect repellent, mosquito traps or mosquito nets.

In 1998, scientists from the Queensland Institute of Medical Research (QIMR) in Australia and
Vietnam's Ministry of Health introduced a scheme that encouraged children to place a water bug,
the crustacean Mesocyclops, in water tanks and discarded containers where the Aedes aegypti
mosquito was known to thrive.[25] This method is viewed as being more cost-effective and more
environmentally friendly than pesticides, though not as effective, and requires the continuing
participation of the community.[26]

Even though this method of mosquito control was successful in rural provinces, not much is
known about how effective it could be if applied to cities and urban areas. The Mesocyclops can
survive and breed in large water containers, but would not be able to do so in small containers of
which most urban area have within their homes. Also, Mesocyclops are hosts for the guinea
worm, a pathogen that causes a parasite infection, and so this method of mosquito control cannot
be used in countries that are still susceptible to the guinea worm. The biggest dilemma with
Mesocyclops is that its success depends on the participation of the community. This idea of a
possible parasite bearing creature in household water containers dissuades people from
continuing the process of inoculation, and without the support and work of everyone living in the
city, this method would not be successful.[27]

In 2004, scientists from the Federal University of Minas Gerais, Brazil, discovered a fast way to
find and count mosquito population inside urban areas. The technology, named Intelligent
Monitoring of Dengue (in Portuguese), uses traps with kairomones that capture Aedes gravid
females, and upload insect counts with a combination of cell phone, GPS and internet
technology. The result is a complete map of the mosquitoes in urban areas, updated in real time
and accessible remotely, that can inform control methodologies.[28] The technology was
recognized with a Tech Museum Award in 2006.[29]

In 2009, scientists from the School of Integrative Biology at The University of Queensland
revealed that by infecting Aedes mosquitos with the bacterium Wolbachia, the adult lifespan was
reduced by half.[30] In the study, super-fine needles were used to inject 10,000 mosquito embryos
with the bacterium. Once an insect was infected, the bacterium would spread via its eggs to the
next generation. A pilot release of infected mosquitoes could begin in Vietnam within three
years. If no problems are discovered, a full-scale biological attack against the insects could be
launched within five years.[31]

[edit] Potential antiviral approaches

Dengue virus belongs to the family Flaviviridae, which includes the hepatitis C virus, West Nile
and Yellow fever viruses among others. Possible laboratory-based modification of the yellow
fever vaccine YF-17D to target the dengue virus via chimeric replacement has been discussed
extensively in scientific literature.[32] To date, however, no full scale studies have been
conducted.[33]

In 2006, a group of Argentine scientists discovered the molecular replication mechanism of the
virus, which could be specifically attacked by disrupting the viral RNA polymerase.[34] In cell
culture[35] and murine experiments,[36][37] morpholino antisense oligos have shown specific activity
against Dengue virus.
In 2007 scientists' attenuated virus replication by interfering with activity of the dengue viral
protease;[38] subsequently, a project to identify novel protease disruption mechanisms has been
launched.

[edit] Etymology
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.[39] The
Swahili word "dinga" may possibly have its origin in the Spanish word "dengue" meaning
fastidious or careful, which would describe the gait of a person suffering the bone pain of dengue
fever.[40] Alternatively, the use of the Spanish word may derive from the similar-sounding
Swahili.[41]

Also known as "Dandy Fever", slaves in the West Indies who contracted dengue were said to
have the posture and gait of a dandy.[42]

[edit] History
The first recorded potential case of dengue fever comes from a Chinese medical encyclopedia
from the Jin Dynasty (265–420 AD). The Chinese referred to a “water poison” associated with
flying insects.[41] 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.[43] The viral etiology and the transmission by mosquitoes were deciphered only in the
20th century. Population movements during World War II spread the disease globally. A
pandemic of dengue began in Southeast Asia after World War II and has spread around the globe
since then.[44]

[edit] Use as a biological weapon

Dengue fever was one of more than a dozen agents that the United States researched as potential
biological weapons before the nation suspended its biological weapons program.[45]