Severe Dengue Virus Infection in Travelers
Dengue has become one of the most important emerging disease problems among international travelers. This comes as no surprise, because dengue is now the most common arboviral disease in the tropics and subtropics—areas that have become popular tourist destinations. In some case series, dengue is the second most frequent cause of hospitalization (after malaria) among travelers returning from the tropics. GeoSentinel is a global provider‐based surveillance network of travel medicine providers; in its most recent update, dengue was the most frequent cause of systemic febrile illness in travelers to Asia.
The World Health Organization (WHO) classifies symptomatic dengue virus infections into 3 categories: undifferentiated fever, classic dengue fever, and dengue hemorrhagic fever (DHF). Dengue fever is defined clinically as an acute febrile illness with 2 manifestations (headache, retroorbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, or leukopenia). DHF is defined by 4 criteria: fever or history of fever lasting 2–7 days, a hemorrhagic tendency shown by a positive tourniquet test or spontaneous bleeding, thrombocytopenia (platelet count 100×109 cells/L), and evidence of plasma leakage shown either by hemoconcentration with substantial changes in serial measurements of packed‐cell volume (hematocrit) or by the development of pleural effusions or ascites; or both. Hemorrhagic manifestations without capillary leakage do not constitute DHF. The term “dengue shock syndrome” (DSS) refers to a condition in which shock is present as well as all 4 DHF‐defining criteria.
Solely on the basis of on this classification, however, it would be wrong to conclude that “classic dengue fever” is a mild disease. Hemorrhagic manifestations such as gum bleeding, epistaxis, menorrhagia, and gastrointestinal hemorrhage may be associated with dengue fever, as well as rare complications such as myocarditis, fulminant hepatitis, encephalopathy, and neuropathies. Classic dengue fever in travelers, although mostly self‐limiting and rarely fatal, can be incapacitating, may halt travel, and may require hospitalization and even evacuation and a return home.
Wichmann et al., in this issue of the Journal, report the results of an intensified surveillance of dengue in travelers within the European Network on Surveillance of Imported Infectious Diseases. Such networks are important in quantifying the risk of severe dengue in travelers. On the basis of strict WHO criteria, only 0.9% of the 219 travelers had DHF in this case series. The low incidence of DHF in these travelers, compared with 2%–6% in populations in which dengue is endemic, is most likely because most travelers do not have preexisting antibodies to dengue, given their lack of previous exposure. Secondary infection is thought to be one of the risk factors for DHF because of postulated antibody‐enhanced infection. However, although only 0.9% met the criteria for DHF, 11% of travelers had severe clinical manifestations (internal hemorrhage, plasma leakage, shock, or marked thrombocytopenia). The authors correctly point out that severe dengue is not uniformly defined and may be missed if the WHO classification is strictly applied. Indeed, the WHO classification of dengue is increasingly being criticized for several reasons. First, as clinicians who treat dengue know, the disease exists as a continuous spectrum rather than as distinct clinical entities listed in the WHO classification. There is considerable overlap among the 3 conditions.