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 cross-protective 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 co-circulating (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).

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 well-kept 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).

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 patient’s 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 anti-dengue 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 anti-dengue 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 CDC’s Dengue Branch, Division of Vector-Borne Infectious Diseases (DVBID), National Center for Infectious Diseases, 1324 Calle Cañada, 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,N-diethylmetatoluamide (DEET) (see Chapter 2).

Treatment

Acetaminophen products are recommended for managing fever. Acetylsalicyclic acid (aspirin) and nonsteroidal anti-inflammatory 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

1. Gubler DJ. The global emergence/resurgence of arboviral diseases as public health problems. Arch Med Res. 2002;33:330-42.
2. 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.
3. 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.
4. Pan American Health Organization. Dengue hemorrhagic fever in Venezuela. Epidemiol Bull. 1990;11:7-9.
5. CDC. Dengue–Texas. MMWR Morbid Mortal Wkly Rep. 1980;29:451.
6. Lacayo M, Taylor R, Duran H, Abell A, et al. Outbreak investigation of dengue—Texas, 2005 (Late-breaker). Presented at 54th Annual Meeting: American Society of Tropical Medicine and Hygiene. Washington, DC, December 11-15, 2005.
7. Effler PV, Pang L, Kitsutani P, Vorndam V, Nakata M, Ayers T, et al., and Hawaii Dengue Outbreak Investigation Team. Dengue Fever, Hawaii, 2001–2002. Emerg Infect Dis. 2005;11:5:742-749.
8. CDC. Travel-associated dengue —United States, 2005. MMWR Morbid Mortal Wkly Rep. 2006;55:22:700-2.
9. 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.
10. O’Leary DR, Rigau-Pérez 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.
11. 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.
12. Rigau-Pérez JG, Clark GC, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV. Dengue and dengue haemorrhagic fever. Lancet. 1998;352:971-7.
13. García-Rivera EJ, Rigau-Pérez 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.
14. 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;38:411–9.
15. Fernandez R, Rodriguez T, Borbonet F, Vasquez S, Guzman M, Kouri G. Estudio de la relacion dengue-embarazo en un grupo de madres cubanas. Rev Cubana Med Trop. 1994;46:76–8.
16. 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.