Dengue Fever

Description

Dengue fever and dengue hemorrhagic fever (DHF) are viral diseases transmitted by Aedes mosquitoes, usually Ae. 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 rapidly expanding disease in most tropical and subtropical areas of the world, has become the most important arboviral disease of humans. More than 2.5 billion persons now live in areas at risk of infection, and attack rates for reported disease in epidemics are in the range of 1 per thousand to 1 per hundred of the population. Infection rates (that is, proportion of the population that is infected, including persons who do not get severe symptoms or are not reported) can be five- to ten-fold greater. The case-fatality ratio for DHF averages about 5% worldwide, but can be kept below 1% with proper clinical management. Epidemics caused by all four virus serotypes have become progressively more frequent and larger in the past 25 years. As of 2004, dengue fever is endemic in most tropical countries of the South Pacific, Asia, the Caribbean, the Americas, and Africa. Additionally, most tropical urban centers in these regions have multiple dengue virus serotypes co-circulating (hyperendemicity), which increases dengue transmission and the risk 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 major epidemic of DHF occurred in Venezuela in 1989-1990. Since then, outbreaks, sporadic cases, or both, of confirmed DHF have occurred in most tropical American countries. After an absence of 35 years, several autochthonous cases of dengue fever occurred in southern Texas in 1980, 1986, 1995, 1997, 1998 and 1999, associated with imported cases and epidemic dengue in adjacent states in Mexico. After an absence of 56 years, a limited outbreak of dengue fever occurred in Hawaii in 2001, associated with imported cases and epidemic dengue in the South Pacific.

Risk for Travelers

The principal vector mosquito, 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. The mosquito may feed at any time during the day, however, especially indoors, in shady areas, or when it is overcast. Mosquito breeding sites include artificial water containers such as discarded tires, uncovered barrels, buckets, flower vases or pots, cans, and cisterns.

Estimates derived from studies of military and relief workers allow for an estimate of risk near one illness per thousand travelers. This estimate may overstate the danger for tourists who will have less contact with the vector, who stay only a few days in air-conditioned hotels with well-kept grounds, and who participate in outdoor recreational activities where the vector mosquito may be absent (such as sunbathing or playing golf in the middle of the day). Travelers who stay at other types of accommodations or with friends and relatives in locations with intense disease transmission may have a higher risk of illness. Cases of dengue are confirmed every year in travelers returning to the United States after visits to tropical and subtropical areas. Travelers to endemic and epidemic areas, therefore, should take precautions to avoid mosquito bites.

Current data suggest that virus strain, the immune status (i.e., having had a previous dengue infection), age, and genetic background of the human host are the most important risk factors for developing DHF. 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 <15 years of age who are experiencing a second dengue infection. In the Americas and the Pacific, where herd immunity is lower, DHF is more commonly observed in older children and adults. 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. In spite of many epidemics, no increase in congenital malformations has been noted after dengue epidemics. A small number of recently reported cases suggests that 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.

Clinical Presentation

Dengue fever is characterized by sudden onset after an incubation period of 3-14 days (most commonly 4-7 days), high fevers, severe frontal headache, and joint and muscle pain. Many patients have nausea, vomiting, and rash. The rash 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. Many cases of nonspecific viral syndrome or even subclinical infection occur, but dengue can also present as a severe, sometimes fatal disease characterized by hemorrhagic manifestations and hypotension (DHF/ dengue shock syndrome).

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. IgM positivity indicates a recent dengue infection, but IgG positivity may only indicate infection at an indeterminate time in the past. In addition, either IgM or IgG positivity may result from cross-reactivity with anti-West Nile, yellow fever, Japanese encephalitis, and other flavivirus antibodies, so the possibility of exposure to other flaviviruses must be considered. If testing at CDC is requested, acute- and convalescent-phase serum samples 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 at telephone 1-787-706-2399; fax 1-787-706-2496; e-mail This e-mail address is being protected from spambots. You need JavaScript enabled to view it '; document.write( '' ); document.write( addy_text48104 ); document.write( '<\/a>' ); //--> This e-mail address is being protected from spambots. You need JavaScript enabled to view it ; 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 Protection against Mosquitoes and Other Arthropods.)

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. Patients should be encouraged to rest and take abundant fluids. In severe cases, the prompt infusion of intravenous fluids is necessary to maintain adequate blood pressure. Because shock may develop suddenly, vital signs must be monitored frequently. Hypotension is a more frequent complication of DHF than severe hemorrhage.

Bibliography

• CDC. Imported dengue —United States, 1999 and 2000. MMWR Morbid Mortal Wkly Rep 2002; 5:281-3.
• Ellerin T, Hurtado R, Lockman S, Baden L. Fever in a returned traveler: an "off the cuff" diagnosis. Clin Infect Dis 2003; 36:1004-5, 10-74-75.
• García-Rivera EJ, Rigau-Pérez JG. Dengue severity in the elderly in Puerto Rico. Rev Panam Salud Pública/ Pan Am J Public Health 2003; 13:362-8.
• Gubler DJ. Cities spawn epidemic dengue viruses. Nature Med 2004; 10:129-30.
• Harris E, Pérez L, Phares CR, Pérez MA, Idiaquez W, Rocha J, et al. Fluid intake and decreased risk of hospitalization. Emerg Infect Dis 2003; 9:1003-6.
• Kroeger A, Nathan M, Hombach J. Disease Watch: Dengue — Nature Reviews. Microbiology 2004; 2:360-1.
• Rigau-Pérez JG, Gubler DJ, Vorndam AV, Clark GG. Dengue: A literature review and case study of travelers from the United States, 1986-1994. J Travel Med 1997; 4:65-71.

-José G. Rigau-Pérez, Duane J. Gubler, Gary G. Clark