CDC Dengue Fever 2007

Description
Dengue fever and dengue hemorrhagic fever (DHF) are viral diseases transmitted by Aedes mosquitoes, usually Aedes
aegypti. The four dengue viruses (DEN-1 through DEN-4) are immunologically related, but do not provide crossprotective immunity against each other.

Occurrence
Dengue, a disease found in most tropical and subtropical areas of the world, has become the most common arboviral
disease of humans. More than 2.5 billion persons now live in areas where dengue infections can be locally acquired (1).
Reported attack rates for disease during epidemics range from 1 per hundred to 1 per thousand of the population (2).
However, because persons with milder illness may not seek medical attention and subsequently be reported, the actual
number of infections in a population may be 5 to 10 times greater than the number reported. Epidemics caused by all
four virus serotypes have become progressively more frequent and larger in the past 25 years. As of 2005, dengue
fever is endemic in most tropical countries of the South Pacific, Asia, the Caribbean, the Americas, and Africa (see
Maps 4-1, 4-2). Additionally, most tropical urban centers in these regions have multiple dengue virus serotypes cocirculating (hyperendemicity), which is associated with increased dengue transmission and the appearance of DHF.
Future dengue incidence in specific locales cannot be predicted accurately, but a high level of dengue transmission is
anticipated in all tropical areas of the world for the indefinite future. The incidence of the severe disease, DHF, has
increased dramatically in Southeast Asia, the South Pacific, and the American tropics in the past 25 years, with major
epidemics occurring in many countries every 3-5 years. The first major epidemic in the Americas occurred in Cuba in
1981, and a second occurred in Venezuela in 1989-1990 (3,4). Since then, outbreaks and rates of endemic, confirmed
DHF have occurred in most tropical American countries. After an absence of 35 years, several locally acquired cases of
dengue fever occurred in southern Texas in 1980 associated with epidemic dengue in adjacent states in Mexico (5). In
the last decade, such dengue cases have been identified in Texas every 1 to 5 years. The most recent cases in 2005
included the first locally acquired DHF case in the continental United States (6). After an absence of 56 years, a limited
outbreak of dengue fever occurred in Hawaii in 2001, associated with imported cases arriving from areas with epidemic
dengue in the South Pacific (7).

MAP 4-01 Distribution of dengue, Western Hemisphere.

Risk for Travelers

The principal mosquito vector, Ae. aegypti, is most frequently found in or near human habitations and prefers to feed on
humans during the daytime. It has two peak periods of biting activity: in the morning for several hours after daybreak
and in the late afternoon for several hours before dark. Nevertheless, the mosquito may feed at any time during the day,
especially indoors, in shady areas, or when it is overcast. Mosquito breeding sites include artificial water containers
such as discarded tires, uncovered water storage barrels, buckets, flower vases or pots, cans, and cisterns.
Cases of dengue fever and DHF are confirmed every year in travelers returning to the United States after visits to
tropical and subtropical areas (8). Studies of military and relief workers placed the estimated risk for travelers returning
from dengue-endemic areas near one illness per thousand travelers (9, 10). This estimate may overstate the danger for
tourists who may have less contact with the vector when they stay only a few days in air-conditioned hotels with wellkept grounds, or when they participate in outdoor recreational activities where the vector mosquito may be absent (such
as sunbathing or playing golf in the middle of the day). A recent study of tourists visiting Hawaii during a dengue
outbreak in 2001 failed to identify serologic evidence of dengue infection among over 3,000 travelers; however, this
study was limited by the fact that only persons sick enough to seek medical attention received dengue testing (11). As a
result, milder dengue infections that did not require medical attention might have been missed. Moreover, travelers who
stay in the homes of friends and relatives in locations with intense disease transmission may have a higher risk of
illness. Therefore, travelers to endemic and epidemic areas should take precautions to avoid mosquito bites (see
Chapter 2).
Current data suggest that co-circulation of all four dengue strains in the same geographic region, virus genotype, and
host factors such as immune status (i.e., having had a previous dengue infection), age, and genetic background are the
most important risk factors for developing DHF (12). In Asia, where a high proportion of the population has experienced
a dengue infection early in life, DHF is observed most commonly in infants and children younger than 15 years of age
who are experiencing a second dengue infection. In the Americas and the Pacific, where primary infection at a young
age is less common, DHF is typically observed in older children and adults. Therefore, international travelers from
nonendemic areas (such as the United States) are generally at low risk for DHF.
There is little information in published reports about the consequences of dengue infection for pregnant women. No
convincing evidence demonstrating an association between dengue infection during pregnancy and congenital
malformations has been reported. However, if the mother is ill with dengue at the time of delivery, the child can be born
with dengue infection or can acquire dengue through the delivery process itself, and then develop the manifestations of
dengue fever or DHF (13). Passive transplacental transfer of maternal anti-dengue antibodies acquired from a previous
maternal infection can also place infants at greater risk of DHF with their first dengue infection, but these maternal
antibodies are cleared by 9-12 months of age (14,15). Transfusion-related dengue infection is a theoretical possibility
(16).

MAP 4-02 Distribution of dengue, Eastern Hemisphere.

Clinical Presentation
Dengue fever is characterized by sudden onset after an incubation period of 3-14 days (most commonly 4-7 days) of
high fevers, severe frontal headache, and joint and muscle pain. Many patients have nausea, vomiting, and a
maculopapular rash, which appears 3-5 days after onset of fever and can spread from the torso to the arms, legs, and
face. The disease is usually self-limited, although convalescence can be prolonged. Most patients report a nonspecific
viral syndrome or a flu-like illness. Asymptomatic infections are also common. Although these patients do not
experience symptoms at the time of the acute infection, the immunity that results increases the risk for DHF during a
subsequent infection. Approximately 1% of patients with dengue infection progress to DHF. As the patients fever
resolves, usually 3-5 days following the onset of fever, patients may develop leaky capillaries, which allow serum
proteins and fluid to accumulate in the pleural and abdominal cavities. Thrombocytopenia and hemorrhagic
manifestations, which can range from microscopic hematuria or increased menstrual flow to hemetemesis, are part of
the syndrome. Neutropenia, elevated liver enzymes, and disseminated intravascular coagulation are also
common. The case-fatality ratio for DHF averages about 5% worldwide, but can be kept below 1% with proper clinical
management. Dengue shock syndrome is the progression of DHF to a hypotensive state. Despite the name, the
progression of DHF to DSS is primarily due to capillary leakage rather the hemorrhaging (12).
Physicians should consider dengue in the differential diagnosis of all patients who have fever and a history of travel to a
tropical area within 2 weeks of onset of symptoms. Commercial tests are available for serologic diagnosis, but their
results must be interpreted with care. Sensitivity and specificity of kits may vary among manufacturers, laboratories, and
over time. In combination with a compatible travel history and symptom profile, anti-dengue IgM positivity suggests a
recent dengue infection, but IgG positivity may only indicate infection at an indeterminate time in the past. Both antidengue IgM and IgG antibodies cross-react with anti-West Nile, -yellow fever, -Japanese encephalitis, and -other
flavivirus anti-bodies; therefore, prior infection or vaccination with another flavivirus may also result in positive antidengue antibody results. If testing at CDC is requested, acute- and convalescent-phase serum samples (collected 0-5
days and 6-30 days from fever onset, respectively) should be obtained and sent through state or territorial health
department laboratories to CDCs Dengue Branch, Division of Vector-Borne Infectious Diseases (DVBID), National
Center for Infectious Diseases, 1324 Calle Caada, San Juan, Puerto Rico 00920-3860. Serum samples should be
accompanied by clinical and epidemiologic information, including the date of disease onset, the date of collection of the
sample, and a detailed recent travel history. For additional information, the Dengue Branch can be contacted by
telephone 1-787-706-2399; fax 1-787-706-2496; e-mail hseda@cdc.gov; or the DVBID website at
http://www.cdc.gov/ncidod/dvbid/dengue/index.htm.

Prevention

No vaccine is available. Travelers should be advised that they can reduce their risk of acquiring dengue by remaining in
well-screened or air-conditioned areas when possible, wearing clothing that adequately covers the arms and legs, and
applying insect repellent to both skin and clothing. The most effective repellents are those containing N,Ndiethylmetatoluamide (DEET) (see Chapter 2).

Treatment
Acetaminophen products are recommended for managing fever. Acetylsalicyclic acid (aspirin) and nonsteroidal antiinflammatory agents (such as ibuprofen) should be avoided because of their anticoagulant properties. Salicylates (e.g.,
aspirin) should be especially avoided in children due to the association with Reye syndrome. Patients should be
encouraged to rest and take fluids. Warning signs of progression to severe disease include abrupt change from fever to
hypothermia, severe abdominal pain, prolonged vomiting, and altered mental status (e.g., irritability, confusion,
lethargy). Prompt treatment of DHF with intravenous fluid can improve patient outcomes. In such cases, hospitalization
with close monitoring of vital signs, fluid balance, and hematologic parameters is indicated, as well as additional
supportive measures (12).

References
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Gubler DJ. The global emergence/resurgence of arboviral diseases as public health problems. Arch Med Res.
2002;33:330-42.
Pan American Health Organization. 2005: Number of reported cases of dengue & dengue hemorrhagic fever
(DHF), Region of the Americas (by country and subregion). Available at:
http://www.paho.org/English/AD/DPC/CD/dengue-cases-2005.htm. Accessed 12 July 2006.
Kouri GP, Guzman MG, Bravo JR, Triana C. Dengue haemorrhagic fever/dengue shock syndrome: lessons
from the Cuban epidemic, 1981. Bull World Health Organ. 1989;67:375-80.
Pan American Health Organization. Dengue hemorrhagic fever in Venezuela. Epidemiol Bull. 1990;11:7-9.
CDC. DengueTexas. MMWR Morbid Mortal Wkly Rep. 1980;29:451.
Lacayo M, Taylor R, Duran H, Abell A, et al. Outbreak investigation of dengueTexas, 2005 (Late-breaker).
Presented at 54th Annual Meeting: American Society of Tropical Medicine and Hygiene. Washington, DC,
December 11-15, 2005.
Effler PV, Pang L, Kitsutani P, Vorndam V, Nakata M, Ayers T, et al., and Hawaii Dengue Outbreak
Investigation Team. Dengue Fever, Hawaii, 20012002. Emerg Infect Dis. 2005;11:5:742-749.
CDC. Travel-associated dengue United States, 2005. MMWR Morbid Mortal Wkly Rep. 2006;55:22:700-2.
Trofa AF, DeFraites RF, Smoak BL, Kanesathasan N, King AD, Burrous JM, et al. Dengue fever in US military
per-sonnel in Haiti. JAMA. 1997;277:1546-8.
OLeary DR, Rigau-Prez JG, Hayes EB, Vorndam AV, Clark GG, Gubler DJ. Assessment of Dengue risk in
relief workers in Puerto Rico after Hurricane Georges. Am J Trop Med Hyg. 2002;66:35-39.
Smith CE, Tom Tammy, Sasaki J, Ayers T, Effler PV. Dengue risk among visitors to Hawaii during an outbreak.
Emerg Infect Dis. 2005;11:750-66.
Rigau-Prez JG, Clark GC, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV. Dengue and dengue haemorrhagic
fever. Lancet. 1998;352:971-7.
Garca-Rivera EJ, Rigau-Prez JG. Dengue virus. In: Scott GB, Hutto SC, eds. Diagnosis of congenital and
perinatal infections: a concise guide. Totowa, NJ: Humana Press, 2005:189-99.
Kliks SC, Nimmanitya S, Nisalak A, Burke DS. Evidence that maternal dengue antibodies are important in the
development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg. 1988;38:4119.
Fernandez R, Rodriguez T, Borbonet F, Vasquez S, Guzman M, Kouri G. Estudio de la relacion dengueembarazo en un grupo de madres cubanas. Rev Cubana Med Trop. 1994;46:768.
Beatty ME, Biggerstaff B, Rigau J, Petersen L. Estimated risk of transmission of dengue virus through blood
transfusion in Puerto Rico (#126). At 5th International Conference on Emerging Infectious Diseases. Atlanta,
GA. March 19-22, 2006.

Outbreak Notice
Update: Dengue, Tropical and Subtropical Regions
This information is current as of today,

Updated: August 07, 2007

Dengue has become one of the most common viral diseases transmitted to humans by the bite of infected mosquitoes
(usually Aedes aegypti); it is the most common cause of fever in travelers returned from the Caribbean, Central
America, and South Central Asia.* Symptoms of dengue include fever, severe headache, retro-orbital eye pain (pain
behind the eye), joint and muscle pain, and rash. Dengue can produce a range of illness from mild to severe, as well as
fatal hemorrhagic fever. Travelers are at risk for dengue infection if they travel to or reside in areas where dengue virus
is transmitted; the preventive measures outlined below can reduce their risk.

Dengue Risk Areas

The range of areas where dengue is located has rapidly expanded in recent years. Today it includes many tropical
countries in Southeast Asia, the Indian Subcontinent, the South Pacific, the Caribbean, South and Central America,
northeastern Australia, and Africa. See the Distribution of dengue maps for areas where it is present most of the time.
Risk of infection is related to mosquito exposure, which can vary with the season. The mosquitoes that transmit dengue
breed in man-made and natural containers, which are especially common in and around houses; therefore, dengue is
common where many houses are clustered.
Currently, an outbreak of dengue is being reported in French Polynesia and Palau in the South Pacific. Singapore is
also experiencing an increase in dengue cases this year. As of June 30, 2007, the outbreak of dengue in Paraguay was
reported to be subsiding. Other areas in South and Central America and the Caribbean, such as Brazil, Mexico,
Nicaragua, and Puerto Rico, are experiencing an increase in dengue cases in 2007.

Prevention Measures for Travelers

No vaccine is available to prevent dengue, and there is no specific treatment other than therapeutic support. Travelers
can reduce their risk by protecting themselves from mosquito bites:

Use insect repellent containing DEET or Picaridin on exposed skin. DEET concentrations of 30% to 50% are
effective for several hours. Picaridin, available in 7% and 15% concentrations, must be applied more
frequently. When using sunscreen, apply it before insect repellent.
o DEET formulations as high as 50% are recommended for both adults and children over 2 months of
age. Protect infants less than 2 months of age by using a carrier draped with mosquito netting with an
elastic edge for a tight fit.
Wear loose, long pants and long-sleeved shirts when outdoors.
Indoors, spray insecticide where the Aedes mosquito likes to linger: closets, behind curtains, and under beds.
If practical, empty or cover containers containing water.
Air conditioned, screened rooms furnished with mosquito nets provide further protection.
Empty or cover containers that can collect water (e.g., uncovered barrels, flower vases, or cisterns), because
mosquitoes that transmit dengue breed in standing water.

Aedes mosquitoes, the principal mosquito vector, usually are active at dusk and dawn, but may feed at any time during
the day, especially indoors, in shady areas, or when the weather is cloudy. Unlike malaria, dengue is often transmitted
in urban as well as in rural areas.

Additional Information
Proper diagnosis of dengue is important; many other diseases may mimic dengue and health-care providers should
consider dengue, malaria, and (in South Asia and countries bordering the Indian Ocean), chikungunya in the differential
diagnosis of patients who have fever and a history of travel to tropical areas during the 2 weeks before symptom onset.
See Dengue and Dengue Hemorrhagic Fever: Information for Health-Care Practitioners for information regarding
reporting dengue cases and instructions for specimen shipping. Serum samples obtained for viral identification and
serologic diagnosis can be sent through state or territorial health departments to CDC's Dengue Branch, Division of
Vector-Borne Infectious Diseases, National Center for Zoonotic, Vector-Borne and Enteric Diseases, 1324 Calle
Caada, San Juan, Puerto Rico 00920-3860; telephone, 787-706-2399; fax, 787-706-2496.
For more information about dengue and protection measures, see the following links:

Dengue Fever in CDC Health Information for International Travel 2008

Insect and Arthropod Protection
Questions and Answers: Insect Repellent Use and Safety
Overview of dengue from CDC Division of Vector-Borne Infectious Diseases

For more information about dengue in travelers, see

Travel-Associated DengueUnited States, 2005 [MMWR 2006, 55 (25)].

Travel-Associated Dengue InfectionsUnited States, 2001-2004 [MMWR 2005, 54 (22)]

For more information about recent dengue outbreaks, see

Pan American Health Organization http://www.paho.org/english/ad/dpc/cd/dengue.htm

South East Asia-Region/WHO (SEARO) http://www.searo.who.int/EN/Section10/Section332_1098.htm

* Freedman DO, Weld LH, Kozarsky PE, Fisk T, Robins R, von Sonnenburg F, et al.; for the GeoSentinel Surveillance
Network. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med
2006;354:119-130