Dengue fever

"Dengue Fever" redirects here. For the band of the same

name, see Dengue Fever (band).
Dengue virus

A TEM micrograph
showing dengue virus
Virus classification
Grou Group IV
p: ((+)ssRNA)
Famil Flaviviridae
y:
Genu Flavivirus
s:
Speci Dengue
es: virus
Dengue fever
Classification & external
resources
ICD-10 A90.
ICD-9 061
Disease
3564
sDB
Medline
001374
Plus
eMedici
med/528
ne
C02.782.417.2
MeSH
14

Dengue fever (IPA: /ˈdɛŋgeɪ/) and dengue hemorrhagic fever (DHF) are acute
febrile diseases, found in the tropics and Africa, with a geographical spread similar to
malaria. One major difference, however, is that malaria is often eradicated in major
cities, whereas dengue is often found in urban areas of developed tropical nations,
including Singapore, Taiwan and Brazil. 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, which feeds during the day.

Contents
 1 History
 2 Signs and symptoms
 3 Diagnosis
 4 Treatment
o 4.1 Emerging
treatments
 5 Epidemiology
 6 Prevention
o 6.1 Vaccine
development
o 6.2 Mosquito control
o 6.3 Personal protection
o 6.4 Potential antiviral
approaches
 7 Recent outbreaks
o 7.1 Americas

o 7.2 Asia Pacific

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. 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 or, alternatively, the Spanish word may derive from
the Swahili. 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. 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.

Signs and symptoms

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 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.
 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:

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,
 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. 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 acetaminophen
preparations to deal with these symptoms if dengue is
suspected.

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. In vivo studies,
however, have not yet been done.

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.

Significant outbreaks of dengue fever tend to occur every

five or six years. There tends 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.[6] 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.

Prevention
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.[7] 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. A number
of other vaccine candidates are entering phase I or II
testing.[9]

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, i.e. 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.

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.[10]

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.

Potential antiviral approaches

In cell culture experiments and mice Morpholino antisense
oligos have shown specific activity against Dengue virus.

The yellow fever vaccine (YF-17D) is a related Flavivirus,

thus the chimeric replacement of yellow fever vaccine with
dengue has been often suggested but no full scale studies
have been conducted to date.

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.[14]

Recent outbreaks
A public service ad teaching people how to prevent dengue
and yellow fever in Encarnación, Paraguay (2007)

2005 dengue
outbreak (edit)

Dat S
D
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at
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Ca
mb [1
- 38 Sep.
odi ]
a

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Ric Sep. ]
00
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Ind 80 1, Jan. [4
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sia 37 9 6

Mal 32 1
[5
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]
a 50 .

Mar 6,
26 [6
tini 00 2
Sep. ]
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Phili 21
28 2 [7
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0 Oct. ]
nes 37

Sin 12
22 [8
gap ,7 19
Oct. ]
ore 00

Sri 3,
16 [9
Lan 00 -
Sep. ]
ka 0

Tha 31
[1
ilan ,0 58 Sep.
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d 00

Viet 20
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Oct. 1]
m 00

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Paki 4,
Dec [1
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6.

1
23
6,
Tot 2,
6 — —
al† 72
7
4
3
†
For listed
countries only.
World Health
 Organization
estimates that
there may be 50
million cases of
dengue infection
worldwide each
year.

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. 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. [15][16]
The disease has propagated to Argentina (where it is not
considered endemic) by people who recently arrived from
Paraguay.[17] 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 to over
70,000, with upwards of 20 deaths. Larvae have also been
found in Parana state. The proportion of cases registered as
DHF is reported to be higher than in previous years.

Americas
 Puerto Rico: (August 2007) 2,343 confirmed cases of
dengue in 2007.
 Dominican Republic: (August – October 2006) 4,968
cases with 44 dead
 Cuba: Media reports (dated September and October
2006) speculate on an outbreak although there is no
official report

Asia Pacific

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.
 Cook Islands: (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. By October 7, 2006, reports were of 3,331 cases
of the mosquito-borne virus and a death toll of 49.
 Indonesia: 2004 80,000 infected with 800 deaths.
 Malaysia: January 2005 33,203 cases.
 Pakistan: 2006 Over 3230 cases, 50 deaths.
o Karachi 2006 October, the number of infected
patients rose to 1836 of which 30 had died.
o 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: (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 9460
cases. 2003, 4788 cases.
 Thailand: May 2005, 7200 infected. At least 12 dead.