Última actualización:
February 09, 2021
Años publicados: 1988, 1989, 1995, 1999, 2000, 2001, 2009, 2021
NORD gratefully acknowledges Sarah Amirali, MDCM Candidate, McGill University School of Medicine and Gabriela Paz-Bailey, MD, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, for assistance in the preparation of this report.
Summary
Dengue fever is a virus transmitted by the bite of a female Aedes mosquito (Aedes aegypti and Aedes albopictus) carrying dengue virus. The infection is caused by one of four dengue viruses (DENV 1-4).These mosquitos also spread Zika, chikungunya and other viruses. More than half of the world population is at risk of dengue. Dengue outbreaks are occurring in many countries of the world including Latin America, the Caribbean and Southeast Asia. Asia accounts for 75% of the dengue disease burden, followed by Latin America and Africa. Each year, about 58 million people get sick from a dengue infection and 13,500 die from it.
Dengue fever is an acute viral infection characterized by fever and flu-like symptoms. Presentation varies ranging from no symptoms to a mild fever to a life-threatening shock and/or hemorrhage syndrome. Approximately 75% of individuals infected do not show any symptoms. Those who do show symptoms most commonly present with a mild to moderate, nonspecific fever 3-10 days after the bite of the infected mosquito. Other common symptoms along with the fever include a skin rash, severe headache, pain behind the eyes, in the muscles and joints. For many affected individuals, the disease is self-limited, ending with full recovery after symptoms resolve in 5-7 days.
Up to 5% of all dengue affected individuals develop severe, life-threatening disease. Warning signs of progression to severe dengue include persistent vomiting, severe abdominal pain, rapid breathing, extreme fatigue, bleeding gums and a drop in blood pressure with position change.
There are no specific medications for dengue and affected individuals are advised to stay well hydrated and control their fever with acetaminophen and tepid sponge baths. There are no medications to prevent dengue and travelers in endemic areas (high risk areas) are advised to avoid mosquito bites by staying indoors, wearing long clothing that cover their arm and legs, using bed nets and insect repellants.
From 1975 to 2009, symptomatic dengue virus infections were classified according to the World Health Organization (WHO) guidelines as dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (the most severe form of DHF). In 2009, the WHO issued a new guideline that classified cases as:
Introduction
Dengue infection is caused by one of four dengue viruses (DENV 1-4). Being infected from one dengue virus does not protect a person from the others. A primary dengue infection is when an individual is infected with the virus for the first time; a secondary infection is when the same individual is infected a second time with a different dengue virus. If the secondary dengue infection is more than 2 years after the primary infection, there is a higher risk of developing severe symptoms.
Individuals with suspected dengue should seek help from a healthcare provider for early recognition of warning signs and prompt initiation of aggressive therapy when necessary.
Severe dengue (previously known as dengue hemorrhagic fever) was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand. Today it affects over a hundred countries and has become one of the leading causes of hospitalization among individuals in these regions.
Dengue has a wide clinical spectrum with some individuals showing no symptoms, while others show mild symptoms to severe symptoms. The incubation period is a period between being infected with the virus to appearance of the first symptoms and for dengue it lasts 3-10 days. Approximately 25% experience a self-limited febrile illness, accompanied by mild-to-moderate haematological and biochemical abnormalities. Clinically relevant complications develop in a small proportion of these patients, including a systemic vascular leak syndrome, coagulation abnormalities that can be associated with bleeding, and organ involvement, typically hepatic or neurological. However, although these severe complications are infrequent the spectrum of clinical manifestations is broad. The most important risk factor for severe dengue is a prior dengue infection. The risk of developing severe dengue is greatest after a secondary infection with a different infecting type of dengue virus.
The three classifications recommended by WHO are (1) dengue without warning signs, (2) dengue with warning signs and (3) severe dengue
For many affected individuals, the disease is self-limited, ending with full recovery after symptoms resolves in 5-7 days.
When these warning signs are seen, the affected individual should be rushed to the emergency room or to the closest health care provider.
Transmission
Dengue fever is a virus transmitted by the bite of a female Aedes mosquito (Aedes aegypti and Aedes albopictus) carrying dengue virus. The infection is caused by one of four dengue viruses (DENV 1-4). These mosquitos also spread Zika, chikungunya and other viruses.
Once an individual is bit by an infected mosquito, the mosquito transmits the virus to that individual. The individual then becomes a carrier of the virus and the virus multiplies inside them. The virus circulates inside the blood of the infected person for 2-7 days during which time they become a source of the virus for uninfected mosquitos and can transmit the infection to another individual via Aedes mosquitos.
When an individual recovers from the infection by one dengue virus, they become immune against that particular type of virus but can be infected by any of the other dengue virus types.
There is a high risk of contracting dengue throughout the tropics and subtropics and it is the leading cause of fever among travelers returning from Latin America, the Caribbean and Southeast Asia. Sporadic outbreaks with local transmission have also been seen in Florida, Hawaii and Texas along the border with Mexico. The geographic distribution of dengue is similar to that of malaria; however the risk for dengue is higher in urban and residential areas versus malaria which is found in rural areas.
Dengue can be suspected in an individual showing the symptoms listed above and if they reside in or have traveled within the past 2 weeks to an endemic area. Early clinical presentation of dengue is similar to other viral infections such as Zika and Chikungunya; therefore laboratory tests are useful in such cases.
During the incubation period after the mosquito bites, the infected individual presents with no symptoms, however during this period the virus replicates, and an antibody response is developed.
Clinical Testing and Work-Up
A blood test can be done to detect particles of the genetic material of the virus or it can indirectly detect the increase in antibody to fight off the virus. Depending on the duration of the illness and when the patient presents for the evaluation, the health care professional will decide which test is more appropriate.
Performing a molecular and IgM antibody test can detect more cases than performing just one test during the first week after symptom onset.
If an individual has symptoms of dengue and resides in or has traveled to an endemic area, they should seek help from a healthcare professional. During the initial evaluation, the healthcare provider will review the individual’s past medical history, recent travel history and vaccination record to determine the likelihood that the illness is due to dengue.
If the infected individual presents to the healthcare provider within the first week of symptom onset, performing both a molecular test and an IgM antibody is preferred rather than one test.
If the infected individual presents more than seven days after symptom onset, antibody testing is preferred.
Dengue virus testing is not recommended for individuals who do not show symptoms after the incubation period.
Treatment
There is no treatment for the virus that causes dengue, but the symptoms can be managed and treated. Management is largely supportive and maintaining adequate fluid volume in the blood vessels by keeping the patient hydrated. Infected individuals with mild symptoms in the absence of warning signs may be told by their doctor to stay home. In these cases, the individual should rest and drink plenty of fluids and watch for signs of dehydration (decreased urination, dry mouth or lips, cold hands or feet). Acetaminophen (Tylenol) can also be taken to relieve fever and aches. It is not recommended to take aspirin or NSAIDS (such as ibuprofen – Advil, Motrin) or Naproxen (Aleve) as they can increase the risk of bleeding. These individuals should also be aware of the warning signs of severe dengue infection and present to the hospital if warning signs are present or symptoms get worse.
If the infected individual’s symptoms are more severe and presents with warning signs of severe infection, the doctor may decide to admit them to the hospital. Treatments in the hospital may include getting fluids through IV. Some individuals are at higher risk of developing severe dengue such as pregnant women, infants, elderly and individuals with asthma, obesity, diabetes, kidney failure or certain blood diseases.
Prevention
The best way to prevent dengue is to stay away from mosquitos that carry it. This can be done by
Vaccination
CYD-TDV (Dengvaxia) is a vaccine that was approved in Europe in 2018 and by the US Food and Drug Administration (FDA) in 2019 for use in dengue endemic territories and only in children ages 9-16 years of age with evidence of a previous dengue infection. It is approved in other countries for people aged 9-45 years of age. It is not yet approved for travelers visiting dengue endemic areas and is not commercially available in the United States or Europe. The main approach to avoid dengue in travelers is to avoid mosquitos carrying the dengue virus.
The World Health Organization (WHO), European Union and the Unites States regulatory agencies recommend the use of this vaccine only for individuals with laboratory evidence of previous dengue infection as a secondary infection can be more severe. Dengue vaccines are not 100% effective, however, and immunized individuals may present with a milder infection. The vaccine does not provide protection to people who have not had a dengue infection and should not be administered to seronegative persons.
A tetravalent dengue vaccine candidate is currently being studied in a clinical trial in Asia and Latin America by Takeda to determine the efficacy of 2 doses of this vaccine in preventing symptomatic dengue fever of any severity due to any of the four dengue virus serotypes in 4-16-year-olds. Another promising vaccine candidate developed by the National Institute of Allergy and Infectious Diseases is being studied in Brazil in people 2-50 years of age. This vaccine is only one dose.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
BOOKS
Handbook for clinical management of dengue. Geneva, Switzerland: World Health Organization; 2012. https://apps.who.int/iris/bitstream/handle/10665/76887/9789241504713_eng.pdf?sequence=1&isAllowed=y
Dengue Guidelines for Diagnosis Treatment Prevention and Control: New Edition. Geneva, Switzerland: World Health Organization; 2009. https://apps.who.int/iris/bitstream/handle/10665/44188/9789241547871_eng.pdf?sequence=1.
JOURNAL ARTICLES
Messina JP Brady OJ, Golding N, et al. The current and future global distribution and population at risk of dengue, Nat Microbiol. 2019;4:1508–1515. https://doi.org/10.1038/s41564-019-0476-8.
Wilder-Smith A, Ooi EE, Horstick O, Wills B. Dengue. Lancet. 2019 Jan 26;393(10169):350-363. doi: 10.1016/S0140-6736(18)32560-1.
Katzelnick LC, Gresh L, Halloran ME, Mercado JC, Kuan G, Gordon A, et al. Antibody399 dependent enhancement of severe dengue disease in humans. Science (New York, NY). 2017;358(6365):929-32.
Stanaway JD, Shepard DS, Undurraga EA, et al. The global burden of dengue: an analysis from the Global Burden of Disease Study 2013. Lancet Infect Dis. 2016: Jun;16(6):712-723.
doi: 10.1016/S1473-3099(16)00026-8. Epub 2016 Feb 10.
Bhatt, PW Gething, OJ Brady, et al. The global distribution and burden of dengue.Nature 2013;496:504-507.
Nujum ZT, Thomas A, Vijayakumar K, et al. Comparative performance of the probable case definitions of dengue by WHO (2009) and the WHO-SEAR expert group (2011). Pathog Glob Health. 2014;108(2):103-110. doi:10.1179/2047773214Y.0000000131. Published March 2014.
Anders KL, Hay SI. Lessons from malaria control to help meet the rising challenge of dengue. Lancet Infect Dis. 2012;12(12):977-984. doi:10.1016/S1473-3099(12)70246-3.
INTERNET
Dengue. Center for Disease Control and Prevention. Updated July 14, 2020. https://www.cdc.gov/dengue/index.html. Accessed Feb 9, 2021.
Dengue – Testing Guidance. Center for Disease Control and Prevention. Updated January 24, 2020 https://www.cdc.gov/dengue/healthcare-providers/testing/testing-guidance.html.. Accessed Feb 9, 2021.
Thomas SJ, Rothman AL, Srikiatkhachorn A and Kalayanarooj S. Dengue virus infection: prevention and treatment. UpToDate. Updated: Oct 27, 2020. https://www.uptodate.com/contents/dengue-virus-infection-prevention-and-treatment. Accessed Feb 9, 2021.
Zika Virus. Center for Disease Control and Prevention. Updated November 20, 2019. https://www.cdc.gov/zika/index.html. Accessed Feb 9, 2021.
Dengue Vaccine. Center for Disease Control and Prevention. Updated September 23, 2019. https://www.cdc.gov/dengue/prevention/dengue-vaccine.html. Accessed Feb 9, 2021.
Chikungunya Virus. Center for Disease Control and Prevention. Updated September 19, 2019. https://www.cdc.gov/chikungunya/index.html. Accessed Feb 9, 2021.
Thomas SJ, Rothman AL, Srikiatkhachorn A and Kalayanarooj S. Dengue virus infection: clinical manifestations and diagnosis. UpToDate Updated: Nov 25, 2019. https://www.uptodate.com/contents/dengue-virus-infection-clinical-manifestations-and-diagnosis#:~:text=Infection%20may%20be%20asymptomatic%20or,%2C%20disease%2C%20and%20disease%20severity. Accessed Feb 9, 2021.
Zika Virus. World Health Organization. Updated July 20, 2018. https://www.who.int/news-room/fact-sheets/detail/zika-virus. Accessed Feb 9, 2021.
Viral Hemorrhagic Fevers (VHFs). Center for Disease Control and Prevention. Updated January 29, 2014. https://www.cdc.gov/vhf/index.html. Accessed Feb 9, 2021.
Promoting dengue vector surveillance and control. World Health Organization. https://www.who.int/denguecontrol/disease/en/. Accessed Feb 9, 2021.
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