Rationale:

• The risk of acquiring dengue varies according to the geographic region visited, type of accommodations (e.g., camping vs. air-conditioned hotel), duration of stay (e.g., business trip lasting less than 1 week vs. 3-month adventure travel), time of travel (high vs. low transmission season), and the altitude of the destination (less than 2000 m vs. higher).
• Age probably has a significant effect on the presentation of dengue. Young children often have asymptomatic infection and are at risk for more severe disease. Adults are unlikely to have asymptomatic infection.
• Previous infection puts individuals at risk for more severe disease. For persons from the U.S., this would mean either a previous trip to the tropics or immigration from the tropics.
• Another risk factor is poor knowledge of the extent and potential severity of dengue.

Evidence:

• Data from 107 Swedish patients in whom dengue fever was diagnosed after returning from travel in 1998 and 1999 were compared with data from a sample of all Swedish travelers to dengue-endemic countries in the same years. Risk factors for a diagnosis of dengue fever were travel to the Malay Peninsula (OR, 4.9), age 15 to 29 years (OR, 3.0), and travel for more than 25 days (OR, 8.8). Only 3 of the patients had received pretravel advice concerning dengue fever from their physicians (1).
• In a retrospective study including 323 German expatriate families after an average stay of 9.8 years in dengue-endemic areas, antibodies to dengue were detected in 4.3% of patients. Length of stay clearly correlated with seropositivity (2).
• Among 670 German aid workers who spent an average of 37.7 months overseas, 7.4% were dengue seropositive. Seroprevalence rates were highest in aid workers returning from Thailand (19.4%), Benin (14.8%), and Burkina Faso (9.2%) (3).
• In a study that included 232 successive patients admitted to a tertiary care hospital in Victoria, Australia, for management of a febrile illness acquired overseas, dengue fever was diagnosed in 8%. An itinerary that included Asia was associated with a 13-fold increased risk of dengue (4).
• The rate of self-reported dengue fever among Israeli travelers to Thailand in 1998 was 3.4 per 1000 travelers (5).
• A study of 104 long-term travelers (median 5.3-month stay abroad) from Israel to various dengue-endemic countries showed dengue seroconversion in 7 (6.7%). Three of the seven infections were asymptomatic (6).
• In a study that included 2259 German citizens after they returned from dengue-endemic countries from 1996 to 2004, serotype-specific dengue antibodies indicated acute dengue infections in 51 travelers (4.7%) with recent fever and 13 travelers (1.1%) with no recent fever. This finding depended largely on destination and epidemic activity in the countries visited (7).
• A study of Dutch short-term travelers (mean, 1 month of travel) with destinations in dengue-endemic areas of Asia found an incidence rate of probable dengue infection of 30 per 1000 person-months. The clinical/subclinical infection ratio was 1:3.3 (8).
• A review suggests that a rapid increase in urban populations brings greater numbers of people into contact with Aedes aegypti, a predominantly urban mosquito species, and, hence, increases the risk of dengue (9).
• A study investigated a 1999 outbreak of dengue that affected Nuevo Laredo in Mexico and Laredo, Texas. The incidence of recent cases was higher in Nuevo Laredo, Mexico, although the vector, A. aegypti, was more abundant in Laredo, Texas. Environmental factors that affect contact with mosquitoes, such as air conditioning and human behavior, appeared to account for this paradox (10).
• Dengue is less likely to be acquired during the dry season, when mosquito transmission is markedly reduced. Dengue epidemics mainly occur during warm, humid, rainy seasons. These conditions shorten the extrinsic incubation period and increase the mosquito population. Temperature-related variations in vector efficiency were seen when the effect of temperature variations on the ability of A. aegypti to transmit dengue viruses was studied. The extrinsic incubation period for this mosquito was reduced from 12 days at 30°C (86°F) to 7 days at 32°C (89.6°F) to 35°C (95°F). This could account for the annual cyclic pattern of dengue hemorrhagic fever epidemics in Bangkok, Thailand (11).
• The risk of acquiring dengue is minimal at altitudes higher than 2000 m. An outbreak of classic dengue fever occurred in the city of Taxco, Mexico, from March to August of 1988. This city is at an elevation of 1700 m above sea level and is the highest altitude at which an outbreak of dengue has been reported (12).
• Within the European Network on Surveillance of Imported Infectious Diseases, dengue hemorrhagic fever was reported in 2.7% of 483 cases of dengue (13).
• Based on data collected by the European Network on Surveillance of Imported Infectious Diseases and the German Surveillance Network on Imported Infectious Diseases between January 1999 and December 2002, the risk of dengue hemorrhagic fever was 4.3 times higher in immigrants and in persons visiting friends and relatives in areas where the disease is endemic than in general travelers (13).
• Between 1993 and 2000, two deaths were reported in a series of more than 200 cases of dengue imported to the U.S. (14; 15; 16; 17; 18).
• Reasons for the resurgence of dengue in the tropics and subtropics include unprecedented urbanization with substandard living conditions, lack of vector control, virus evolution, and international travel. Urbanization has probably had the most impact on the amplification of dengue within a given country, and travel has had the most impact on the spread of dengue from country to country and continent to continent (19).
• Mathematical modeling was used to estimate the risk of dengue-infected blood transfusions in Singapore in 2005. Assuming a ratio of asymptomatic to symptomatic infections of 2:1 to 10:1, the risk was 1.625 to 6 per 10,000 blood transfusions. The level of viremia required to cause clinical dengue was person dependent and unknown (20).

Comments:

• Up-to-date maps and information identifying dengue areas within countries can be found in the CDC's Traveler's Health: Yellow Book.
• The dengue virus strain and 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 dengue hemorrhagic fever. In Asia, where a high proportion of the population has experienced a dengue infection early in life, dengue hemorrhagic fever is observed most commonly in infants and children under age 15. In the Americas and the Pacific, where herd immunity is lower, dengue hemorrhagic fever is more commonly observed in older children and adults. International travelers from nonendemic areas are generally at low risk for dengue hemorrhagic fever. Although all four dengue viruses are able to produce dengue hemorrhagic fever, dengue-2 and dengue-3 viruses are more frequently associated with severe disease (9; 21).
• Immigrants returning home to visit relatives are at higher risk of developing dengue, often do not take precautionary measures because they are going home and do not consider dengue a serious disease, are often medically underserved and therefore less likely to seek pretravel advice, often travel with children or when pregnant, and do not know that a second infection could lead to severe disease.
• The inherited bacterial symbiont Wolbachia was successfully transferred into adult A. aegypti. Under laboratory conditions, this halved the adult life span and, hence, may be a viable strategy to reduce the transmission of dengue pathogens (22).