Dengue

 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 Puerto Rico, Singapore, Malaysia, Taiwan, Thailand,
Indonesia, Philippines, India, Brazil and Venezuela. 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]

Dengue virus
A TEM micrograph showing dengue virus
Virus classification
Group: Group IV ((+)ssRNA)
Family: Flaviviridae
Genus: Flavivirus
Species: Dengue virus

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 n 2007 replication mechanism of the virus was interrupted by interception
of the viral protease , 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.

Dengue fever 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.The geographical spread
is similar to malaria, but unlike malaria, dengue is often found in urban areas of tropical
nations, including Puerto Rico, Singapore, Malaysia, Taiwan, Thailand, 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.

Pathophysiology of dengue
 Dengue (DF) and dengue hemorrhagic fever (DHF) are caused by one of four closely
related, but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of
 the genus Flavivirus. Infection with one of these serotypes provides immunity to only that
serotype for life, so persons living in a dengue-endemic area can have more than one
dengue infection during their lifetime. DF and DHF are primarily diseases of tropical and
sub tropical areas, and the four different dengue serotypes are maintained in a cycle that
involves humans and the Aedes mosquito. However, Aedes aegypti, a domestic, day-biting
mosquito that prefers to feed on humans, is the most common Aedes species. Infections
produce a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe
and fatal hemorrhagic disease. Important risk factors for DHF include the strain of the
infecting virus, as well as the age, and especially the prior dengue infection history of the
patient.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 deciphered only 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 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;
 chills;
 constant headaches;
 bleeding from nose, mouth or gums;
 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.

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]
 Fever, bladder problem, constant headaches, severe dizziness and loss of appetite.
 Hemorrhagic tendency (positive tourniquet test, spontaneous bruising, bleeding from
mucosa, gingiva, injection sites, etc.; vomiting blood, or bloody diarrhea)
 Thrombocytopenia (<100,000 platelets per mm³ or estimated as less than 3 platelets per
high power field)
 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.

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.
 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.[4]

Emerging Treatment
 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.
 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]

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 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 months. 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]

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.[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]
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. Courtesy: Centers for Disease Control and
Prevention Public Health Image Library
 Primary prevention of dengue mainly resides in mosquito control. There are two primary
methods: larval control and adult mosquito control. In urban areas, Aedes mosquitos
breed on water collections in artificial containers such as plastic cups, used tires, broken
bottles, flower pots, etc. Continued and sustained artificial container reduction or periodic
draining of artificial containers is the most effective way of reducing the larva and thereby
the aedes mosquito load in the community. Larvicide treatment is another effective way of
 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 (IGR`s) available which are both safe and long alasting
e.g. pyriproxyfen. For reducing the adult mosquito load, fogging with insecticide is
somewhat effective.
 Prevention of mosquito bites is another way of preventing disease. This can be achieved
either by personal protection or by using mosquito nets. In 1998, scientists from the
Queensland Institute of Research 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. This method is viewed as being more cost-effective and more environmentally
friendly than pesticides, though not as effective, and requires the ongoing participation of
the community.
 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 vaccine for 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.

Recent outbreaks
 A public service ad teaching people how to prevent dengue and yellow fever in
Encarnación, Paraguay (2007)
 CountryCasesDeathsDate of InformationSourcesCambodia20,00038Sep.[1]Costa
Rica19,00017 Sep.India, (West Bengal)90,0001,500Sep.[3]Indonesia80,8371,099Jan.
2006[4]Malaysia32,950831 Nov.[5]Martinique6,000226 Sep.[6]Philippines21,5372802 Oct.
[7]Singapore12,7001922 Oct.[8]Sri Lanka3,000-16 Sep.[9]Thailand31,00058Sep.
[10]Trinidad and Tobago25,000108Sep.[11]Vietnam20,000284 Oct.[12]Pakistan4,8005011
Dec 2006.[13]Total†232,72416,673——†For listed countries only. World Health
Organization estimates that there may be 50 million cases of dengue infection worldwide
each year. [14]
 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.
 The disease has propagated to Argentina (where it is not considered endemic) 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 to over 70,000, with upwards of 80 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 [not in citation given(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
 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 1. An
outbreak of Dengue in the first seven months of 2007 reported more than 438,000 cases
of dengue fever, with 97 deaths.
 Mexico: As of October 2007 there is a serious problem in Monterrey, Nuevo Leon almost
reaching epidemic proportions.

Asia Pacific
 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; 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.