Dengue and severe dengueFact sheet N°117Updated 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 50–100 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, South-east 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 4–10 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 4–5 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 (40°C/ 104°F) 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 2–7 days, after an incubation period of 4–10 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 3–7 days after the first symptoms in conjunction with a decrease in temperature (below 38°C/ 100°F) and include: severe abdominal pain, persistent vomiting, rapid breathing, bleeding gums, fatigue, restlessness, blood in vomit. The next 24–48 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 feverShare on facebook Share on twitter Bookmark & Share Printer-friendly version

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 Ecchymosiso Generalized rasho Petechiaeo Worsening of earlier symptoms

Shock-like state o Cold, clammy extremitieso 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. Rosen’s 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 Churchill-Livingstone; 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 8–12 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 4–7 days (range, 3–14 days), and the course follows 3 phases: febrile, critical, and convalescent. Fever typically lasts 2–7 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 24–48 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 24–48 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 patient’s well-being improves, hemodynamic status stabilizes (although he or she may manifest bradycardia), and diuresis ensues. The patient’s 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 6–12 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 anti-inflammatory 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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