Dengue and severe dengue

Fact sheet N117

Updated March 2014

Key facts

Dengue is a mosquito-borne viral infection.

The infection causes flu-like illness, and occasionally develops into a potentially lethal
complication called severe dengue.

The global incidence of dengue has grown dramatically in recent decades.

About half of the world's population is now at risk.

Dengue is found in tropical and sub-tropical climates worldwide, mostly in urban and
semi-urban areas.

Severe dengue is a leading cause of serious illness and death among children in some
Asian and Latin American countries.

There is no specific treatment for dengue/ severe dengue, but early detection and access
to proper medical care lowers fatality rates below 1%.

Dengue prevention and control solely depends on effective vector control measures.

Dengue is a mosquito-borne infection found in tropical and sub-tropical regions around the
world. In recent years, transmission has increased predominantly in urban and semi-urban areas
and has become a major international public health concern.
Severe dengue (also known as Dengue Haemorrhagic Fever) was first recognized in the 1950s
during dengue epidemics in the Philippines and Thailand. Today, severe dengue affects most
Asian and Latin American countries and has become a leading cause of hospitalization and death
among children in these regions.
There are four distinct, but closely related, serotypes of the virus that cause dengue (DEN-1,
DEN-2, DEN-3 and DEN-4). Recovery from infection by one provides lifelong immunity against
that particular serotype. However, cross-immunity to the other serotypes after recovery is only

partial and temporary. Subsequent infections by other serotypes increase the risk of developing
severe dengue.
Global burden of dengue
The incidence of dengue has grown dramatically around the world in recent decades. Over 2.5
billion people over 40% of the world's population are now at risk from dengue. WHO
currently estimates there may be 50100 million dengue infections worldwide every year.
Before 1970, only nine countries had experienced severe dengue epidemics. The disease is now
endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, Southeast Asia and the Western Pacific. The American, South-east Asia and the Western Pacific
regions are the most seriously affected.
Cases across the Americas, South-east Asia and Western Pacific have exceeded 1.2 million cases
in 2008 and over 2.3 million in 2010 (based on official data submitted by Member States).
Recently the number of reported cases has continued to increase. In 2013, 2.35 million cases of
dengue were reported in the Americas alone, of which 37 687 cases were severe dengue.
Not only is the number of cases increasing as the disease spreads to new areas, but explosive
outbreaks are occurring. The threat of a possible outbreak of dengue fever now exists in Europe
and local transmission of dengue was reported for the first time in France and Croatia in 2010
and imported cases were detected in three other European countries. In 2012, an outbreak of
dengue on Madeira islands of Portugal resulted in over 2000 cases and imported cases were
detected in 10 other countries in Europe apart from mainland Portugal.
In 2013, cases have occurred in Florida (United States of America) and Yunnan province of
China. Dengue also continues to affect several south American countries notably Honduras,
Costa Rica and Mexico. In Asia, Singapore has reported an increase in cases after a lapse of
several years and outbreaks have also been reported in Laos. In 2014, trends indicate increases in
the number of cases in the Cook Islands, Malaysia, Fiji and Vanuatu, with Dengue Type 3 (DEN
3) affecting the Pacific Island countries after a lapse of over 10 years.
An estimated 500 000 people with severe dengue require hospitalization each year, a large
proportion of whom are children. About 2.5% of those affected die.
Transmission

WHO/TDR/Stammers

The Aedes aegypti mosquito is the primary vector of dengue. The virus is transmitted to humans
through the bites of infected female mosquitoes. After virus incubation for 410 days, an infected
mosquito is capable of transmitting the virus for the rest of its life.
Infected humans are the main carriers and multipliers of the virus, serving as a source of the
virus for uninfected mosquitoes. Patients who are already infected with the dengue virus can
transmit the infection (for 45 days; maximum 12) via Aedes mosquitoes after their first
symptoms appear.
The Aedes aegypti mosquito lives in urban habitats and breeds mostly in man-made containers.
Unlike other mosquitoes Ae. aegypti is a daytime feeder; its peak biting periods are early in the
morning and in the evening before dusk. Female Ae. aegypti bites multiple people during each
feeding period.
Aedes albopictus, a secondary dengue vector in Asia, has spread to North America and Europe
largely due to the international trade in used tyres (a breeding habitat) and other goods (e.g.
lucky bamboo). Ae. albopictus is highly adaptive and therefore can survive in cooler temperate
regions of Europe. Its spread is due to its tolerance to temperatures below freezing, hibernation,
and ability to shelter in microhabitats.
Characteristics
Dengue fever is a severe, flu-like illness that affects infants, young children and adults, but
seldom causes death.
Dengue should be suspected when a high fever (40C/ 104F) is accompanied by two of the
following symptoms: severe headache, pain behind the eyes, muscle and joint pains, nausea,
vomiting, swollen glands or rash. Symptoms usually last for 27 days, after an incubation period
of 410 days after the bite from an infected mosquito.
Severe dengue is a potentially deadly complication due to plasma leaking, fluid accumulation,
respiratory distress, severe bleeding, or organ impairment. Warning signs occur 37 days after
the first symptoms in conjunction with a decrease in temperature (below 38C/ 100F) and
include: severe abdominal pain, persistent vomiting, rapid breathing, bleeding gums, fatigue,
restlessness, blood in vomit. The next 2448 hours of the critical stage can be lethal; proper
medical care is needed to avoid complications and risk of death.
Treatment
There is no specific treatment for dengue fever.
For severe dengue, medical care by physicians and nurses experienced with the effects and
progression of the disease can save lives decreasing mortality rates from more than 20% to less
than 1%. Maintenance of the patient's body fluid volume is critical to severe dengue care.
Immunization

There is no vaccine to protect against dengue. Developing a vaccine against dengue/severe

dengue has been challenging although there has been recent progress in vaccine development.
WHO provides technical advice and guidance to countries and private partners to support
vaccine research and evaluation. Several candidate vaccines are in various phases of trials.
Prevention and control

WHO/TDR/Crump
At present, the only method to control or prevent the transmission of dengue virus is to combat
vector mosquitoes through:

preventing mosquitoes from accessing egg-laying habitats by environmental management

and modification;

disposing of solid waste properly and removing artificial man-made habitats;

covering, emptying and cleaning of domestic water storage containers on a weekly basis;

applying appropriate insecticides to water storage outdoor containers;

using of personal household protection such as window screens, long-sleeved clothes,

insecticide treated materials, coils and vaporizers;

improving community participation and mobilization for sustained vector control;

applying insecticides as space spraying during outbreaks as one of the emergency vector
control measures;

active monitoring and surveillance of vectors should be carried out to determine

effectiveness of control interventions.

WHO response
WHO responds to dengue in the following ways:

supports countries in the confirmation of outbreaks through its collaborating network of

laboratories;

provides technical support and guidance to countries for the effective management of
dengue outbreaks;

supports countries to improve their reporting systems and capture the true burden of the
disease;

provides training on clinical management, diagnosis and vector control at the regional
level with some of its collaborating centres;

formulates evidence-based strategies and policies;

develops new tools, including insecticide products and application technologies;

gathers official records of dengue and severe dengue from over 100 Member States;

publishes guidelines and handbooks for case management, dengue prevention and control
for Member States.

Southeast Asian J Trop Med Public Health. 1987 Sep;18(3):398-406.

Dengue haemorrhagic fever with unusual

manifestations.
Nimmannitya S1, Thisyakorn U, Hemsrichart V.

Author information
Abstract
A retrospective study on 18 cases of DHF presented with jaundice and neurological signs which
were considered unusual manifestation of DHF reveals that the causes or contributing factors are
multifactorial. Most commonly found associated conditions were prolonged shock with
metabolic acidosis and severe DIC that lead to hypoxia/ischaemia and resulted in both hepatic
and brain dysfunction. Gross haemorrhage in the brain was noted in 6 of the 10 fatal cases while
brain oedema was noted in 3 cases. Electrolyte disturbance such as hyponatremia could be
another cause of brain oedema. It is certain from this study that there is no pathological evidence
of encephalitis. Hepatic dysfunction found in associated with jaundice and encephalopathy is
possibly caused by toxic substances, drugs and/or associated with underlying liver conditions.
Reye's or Reye's-like syndrome was postulated in one case.
PMID:

3433170
[PubMed - indexed for MEDLINE]

Dengue hemorrhagic fever

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Dengue hemorrhagic fever is a severe, potentially deadly infection spread by mosquitos, mainly
the species Aedes aegypti.

Causes
Four different dengue viruses are known to cause dengue hemorrhagic fever. Dengue
hemorrhagic fever occurs when a person is bitten by a mosquito that is infected with the virus.
There are more than 100 million new cases of dengue fever every year throughout the world. A
small number of these develop into dengue hemorrhagic fever. Most infections in the United
States are brought in from other countries. Risk factors for dengue hemorrhagic fever include
having antibodies to dengue virus from an earlier infection and being younger than 12, female, or
Caucasian.

Symptoms
Early symptoms of dengue hemorrhagic fever are similar to those of dengue fever. But after
several days the patient becomes irritable, restless, and sweaty. These symptoms are followed by
a shock-like state.
Bleeding appears as tiny spots of blood on the skin (petechiae) and larger patches of blood under
the skin (ecchymoses). Minor injuries can cause bleeding.
Shock can lead to death. If the patient survives, recovery begins after a one-day crisis period.
Early symptoms include:

Decreased appetite

Fever

Headache

Joint or muscle aches

Malaise

Vomiting

Acute phase symptoms include:

Restlessness followed by:

o

Ecchymosis

Generalized rash

Petechiae

Worsening of earlier symptoms

Shock-like state
o

Cold, clammy extremities

Sweating

Exams and Tests

A physical examination may reveal:

Enlarged liver (hepatomegaly)

Low blood pressure

Rash

Red eyes

Red throat

Swollen glands

Weak, rapid pulse

Tests may include:

Arterial blood gases

Blood tests (find signs of the virus in the blood)

Coagulation studies

Electrolytes

Hematocrit

Liver enzymes

Platelet count

Serum studies from samples taken during acute illness and convalescence
(increase in titer to Dengue antigen)

Tourniquet test (causes petechiae to form below the tourniquet)

X-ray of the chest (may demonstrate pleural effusion)

Treatment
Because Dengue hemorrhagic fever is caused by a virus for which there is no known cure or
vaccine, the only treatment is to treat the symptoms.

A transfusion of fresh blood or platelets can correct bleeding problems

Intravenous (IV) fluids and electrolytes are also used to correct electrolyte
imbalances

Oxygen therapy may be needed to treat abnormally low blood oxygen

Rehydration with intravenous (IV) fluids is often necessary to treat

dehydration

Supportive care in an intensive care unit/environment

Outlook (Prognosis)
With early and aggressive care, most patients recover from dengue hemorrhagic fever. However,
half of untreated patients who go into shock do not survive.

Possible Complications

Encephalopathy

Liver damage

Residual brain damage

Seizures

Shock

When to Contact a Medical Professional

See your health care provider right away if you have symptoms of dengue fever and have been in
an area where dengue fever occurs, and especially if you have had dengue fever before.

Prevention
There is no vaccine to prevent dengue fever. Use personal protection such as full-coverage
clothing, mosquito nets, mosquito repellent containing DEET. If possible, travel during times of
the day when mosquitos are not so active. Mosquito abatement (control) programs can also
reduce the risk of infection.

Alternative Names
Hemorrhagic dengue; Dengue shock syndrome; Philippine hemorrhagic fever; Thai hemorrhagic
fever; Singapore hemorrhagic fever

References
Haile-Mariam T, Polis MA. Viral illnesses. In: Marx JA, Hockberger RS, Walls RM, et al, eds.
Rosens Emergency Medicine: Concepts and Clinical Practice. 7th ed. Philadelphia, PA: Elsevier
Mosby; 2009:chap 128.
Lupi O. Mosquito-borne hemorrhagic fevers. Dermatologic Clinics. 2011;29:33-38.
Vaughn DW, Barrett A, Solomon T. Flaviviruses (Yellow Fever, Dengue, Dengue Hemorrhagic
Fever, Japanese Encephalitis, West Nile Encephalitis, St. Louis Encephalitis, Tick-Borne
Encephalitis). In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's
Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Elsevier ChurchillLivingstone; 2009:chap 153.

Update Date: 11/10/2012

Updated by: Jatin M. Vyas, MD, PhD, Assistant Professor in Medicine, Harvard Medical School;
Assistant in Medicine, Division of Infectious Disease, Department of Medicine, Massachusetts
General Hospital, Boston, MA. Also reviewed by A.D.A.M. Health Solutions, Ebix, Inc.,
Editorial Team: David Zieve, MD, MHA, David R. Eltz, Stephanie Slon, and Nissi Wang.

Chapter 3Infectious Diseases Related To Travel

Chapter 3 - Cysticercosis

Chapter 3 - Diphtheria

Dengue
Kay M. Tomashek, Harold S. Margolis
INFECTIOUS AGENT

Dengue is caused by infection with any 1 of 4 related positive-strand RNA viruses of the genus
Flavivirus, dengue viruses (DENV) 1, 2, 3, or 4.
TRANSMISSION

Transmission occurs through the bite of an infected Aedes mosquito, primarily Aedes aegypti and
Ae. albopictus. Humans are the main host and the primary source of virus for female mosquitoes,
which become infective after an extrinsic incubation period of 812 days and can then transmit
DENV for the rest of their approximately 1-month lifespan.
Because of the approximately 7-day viremia in humans, bloodborne transmission is possible
through exposure to infected blood, organs, or other tissues (such as bone marrow). In addition,

perinatal DENV transmission occurs, and the highest risk appears to be among infants whose
mothers are acutely ill around the time of delivery. It is not known if DENV is transmitted
through breast milk.
EPIDEMIOLOGY

Dengue is endemic throughout the tropics and subtropics and is a leading cause of febrile illness
among travelers returning from the Caribbean, South America, and South and Southeast Asia,
according to an analysis of data collected by the GeoSentinel Surveillance Network. Dengue
occurs in >100 countries worldwide (Maps 3-01, 3-02, and 3-03), including Puerto Rico, the US
Virgin Islands, and US-affiliated Pacific Islands. Sporadic outbreaks with local transmission have
occurred in Florida, Hawaii, and along the Texas-Mexico border. Although the geographic
distribution of dengue is similar to that of malaria, dengue is more of a risk in urban and
residential areas than is malaria. The DengueMap (www.healthmap.org/dengue/index.php
) shows areas of ongoing transmission.

Map 3-01. Distribution of dengue in the Americas and the Caribbean

View Larger Map PDF Version (printable)

Map 3-02. Distribution of dengue in Africa and the Middle East

View Larger Map PDF Version (printable)

Map 3-03. Distribution of dengue in Asia and Oceania

View Larger Map PDF Version (printable)

CLINICAL PRESENTATION

About 75% of all DENV infections are asymptomatic. Symptomatic infection (dengue) most
commonly presents as a mild to moderate, nonspecific, acute, febrile illness. However, as many
as 5% of all dengue patients develop severe, life-threatening disease. Early clinical findings are
nonspecific but require a high index of suspicion, because recognizing early signs of shock and
promptly initiating intensive supportive therapy can reduce risk of death among patients with
severe dengue from 10% to <1%. See Box 3-01 for information regarding the new World Health
Organization (WHO) guidelines for classifying dengue.

Dengue begins abruptly after an incubation period of 47 days (range, 314 days), and the
course follows 3 phases: febrile, critical, and convalescent. Fever typically lasts 27 days and
can be biphasic. Other signs and symptoms may include severe headache; retroorbital pain;
muscle, joint and bone pain; macular or maculopapular rash; and minor hemorrhagic
manifestations, including petechiae, ecchymosis, purpura, epistaxis, bleeding gums, hematuria,
or a positive tourniquet test result. Some patients have injected oropharynx and facial erythema
in the first 2448 hours after onset. Warning signs of progression to severe dengue occur in the
late febrile phase around the time of defervescence and include persistent vomiting, severe
abdominal pain, mucosal bleeding, difficulty breathing, signs of hypovolemic shock, and rapid
decline in platelet count with an increase in hematocrit (hemoconcentration).
The critical phase of dengue begins at defervescence and typically lasts 2448 hours. Most
patients clinically improve during this phase, but those with substantial plasma leakage develop
severe disease as a result of a marked increase in vascular permeability. Initially, physiologic
compensatory mechanisms maintain adequate circulation, which narrows pulse pressure as
diastolic blood pressure increases. Patients with severe plasma leakage have pleural effusions or
ascites, hypoproteinemia, and hemoconcentration. Patients may appear to be well despite early
signs of shock. However, once hypotension develops, systolic blood pressure rapidly declines,
and irreversible shock and death may ensue despite resuscitation. Patients can also develop
hemorrhagic manifestations, including hematemesis, bloody stool, melena, or menorrhagia,
especially if they have prolonged shock. Dengue patients can have atypical manifestations,
including hepatitis, myocarditis, pancreatitis, and encephalitis.
As the plasma leakage subsides, the patient enters the convalescent phase and begins to reabsorb
extravasated intravenous fluids and pleural and abdominal effusions. As a patients well-being
improves, hemodynamic status stabilizes (although he or she may manifest bradycardia), and
diuresis ensues. The patients hematocrit stabilizes or may fall because of the dilutional effect of
the reabsorbed fluid, and the white cell count usually starts to rise, followed by a slow recovery
of platelet count. The convalescent-phase rash may desquamate and be pruritic.
Laboratory findings commonly include leucopenia, thrombocytopenia, hyponatremia, elevated
aspartate aminotransferase and alanine aminotransferase, and a normal erythrocyte sedimentation
rate.
Data are limited on health outcomes of dengue in pregnancy and effects of maternal DENV
infection on the developing fetus. Perinatal DENV transmission can occur, and peripartum
maternal infection may increase the likelihood of symptomatic disease in the newborn. Of the 34
perinatal transmission cases described in the literature, all developed thrombocytopenia and all
but 1 had fever in the first 2 weeks after birth. Nearly 40% had a hemorrhagic manifestation, and
one-fourth had hypotension. Transplacental transfer of maternal IgG anti-DENV (from a
previous maternal infection) may increase risk for severe dengue among infants infected at 612
months of age.
Box 3-01. New guidelines for classifying dengue

In November 2009, World Health Organization (WHO) issued a new guideline that classifies
symptomatic cases as dengue or severe dengue.

Dengue is defined by a combination of 2 clinical findings in a febrile person who traveled to or

lives in a dengue-endemic area. Clinical findings include nausea, vomiting, rash, aches and
pains, a positive tourniquet test, leukopenia, and the following warning signs: abdominal pain or
tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy,
restlessness, and liver enlargement. The presence of a warning sign may predict severe dengue in
a patient.
Severe dengue is classified as dengue with any of the following: severe plasma leakage leading
to shock or fluid accumulation with respiratory distress; severe bleeding; or severe organ
impairment such as elevated transaminases 1,000 IU/L, impaired consciousness, or heart
impairment.
From 1975 through 2009, symptomatic dengue virus infections were classified according to the
WHO guidelines as dengue fever, dengue hemorrhagic fever (DHF), and dengue shock
syndrome (DSS, the most severe form of DHF). The case definition was changed to the 2009
clinical classification after reports that the case definition of DHF was both too difficult to apply
in resource-limited settings and too specific, as it failed to identify a substantial proportion of
severe dengue cases, including cases of hepatic failure and encephalitis. Many dengue experts
felt that the original case definitions, which were developed based on data from pediatric cases in
Southeast Asia, were not applicable to other regions and populations. The 2009 clinical
classification has been criticized because it is felt to be overly inclusive, as it allows several
different ways to qualify for severe dengue, and nonspecific warning signs are used as diagnostic
criteria for dengue. Last, the new guidelines have been criticized because they do not define the
clinical criteria for establishing severe dengue (with the exception of providing laboratory cutoff
values for transaminase levels), thereby leaving severity determination up to individual clinical
judgment.
DIAGNOSIS

Clinicians should consider dengue in a patient who was in an endemic area within 2 weeks
before symptom onset. All suspected cases should be reported to the local health department,
because dengue is a nationally reportable disease. Laboratory confirmation can be made from a
single acute-phase serum specimen obtained early (5 days after fever onset) in the illness by
detecting DENV genomic sequences with RT-PCR or DENV nonstructural protein 1 (NS1)
antigen by immunoassay. Later in the illness (4 days after fever onset), IgM anti-DENV can be
detected with ELISA. For patients presenting during the first week after fever onset, diagnostic
testing should include a test for DENV (PCR or NS1) and IgM anti-DENV. For patients
presenting >1 week after fever onset, IgM anti-DENV is most useful, although NS1 has been
reported positive up to 12 days after fever onset.
Presence of DENV by PCR or NS1 antigen in a single diagnostic specimen is considered
laboratory confirmation in patients with a compatible clinical and travel history. IgM anti-DENV
in a single serum sample suggests a probable, recent DENV infection. IgM anti-DENV
seroconversion in acute- and convalescent-phase serum specimens is considered laboratory
confirmation of dengue.

IgG anti-DENV by ELISA in a single serum sample is not useful for diagnostic testing, because
it remains elevated for life after any DENV infection and can be falsely positive in people with
antibodies to other flaviviruses (such as West Nile, yellow fever, Japanese encephalitis).
Dengue diagnostic testing (molecular and immunoassay) is available from several commercial
reference diagnostic laboratories, state public health laboratories, and CDC
(www.cdc.gov/Dengue/clinicalLab/index.html). Consultation on dengue diagnostic testing can
be obtained from CDC at 787-706-2399.
TREATMENT

No specific antiviral agents exist for dengue. Patients should be advised to stay well hydrated
and to avoid aspirin (acetylsalicylic acid), aspirin-containing drugs, and other nonsteroidal antiinflammatory drugs (such as ibuprofen) because of their anticoagulant properties. Fever should
be controlled with acetaminophen and tepid sponge baths. Febrile patients should avoid
mosquito bites to reduce risk of further transmission. For those who develop severe dengue,
close observation and frequent monitoring in an intensive care unit setting may be required.
Prophylactic platelet transfusions in dengue patients are not beneficial and may contribute to
fluid overload.
PREVENTION

No vaccine is available, although several are in clinical trials; no chemoprophylaxis is available

to prevent dengue. Travelers to dengue-endemic areas are at risk of getting dengue; risk increases
with longer duration of travel and disease incidence in the travel destination (such as during
dengue season and during epidemics). Travelers should be advised to avoid mosquito bites by
taking the following preventive measures:

Select accommodations with well-screened windows and doors or air

conditioning when possible. Aedes mosquitoes typically live indoors and are
often found in dark, cool places, such as in closets, under beds, behind
curtains, and in bathrooms. Travelers should be advised to use insecticides to
get rid of mosquitoes in these areas.

Wear clothing that adequately covers the arms and legs, especially during
the early morning and late afternoon, when risk of being bitten is the highest.

Use insect repellent (see Chapter 2, Protection against Mosquitoes, Ticks, &
Other Insects & Arthropods).

For long-term travelers, empty and clean or cover any standing water that
can be mosquito-breeding sites in the local residence (such as water storage
tanks or flowerpot trays).

CDC website: www.cdc.gov/dengue

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