Dengue: A reemerging concern for travelers

Why do primary care physicians in nontropical parts of the world need to be on the lookout for tropical diseases such as dengue?

First, more people are traveling than ever before, and second, more people are traveling to parts of the world where dengue and other tropical diseases are endemic. Thus, dengue should now be included in the differential diagnosis of fever in anyone returning from travel to a part of the world where dengue is endemic (Table 1).¹

The number of cases of dengue in returning US travelers has been increasing steadily over the past 25 years.^2,3 Dengue is a more common cause of febrile illness than malaria in US travelers returning from all tropical and subtropical regions except Africa.⁴

Moreover, dengue may be gaining a permanent foothold in the United States, and in areas of the country where mosquitoes that can transmit the virus are found, primary care physicians are the first line of defense in public health. Specifically, to prevent the virus from becoming established locally, primary care physicians need to quickly identify and report cases to public health authorities, who can promptly follow up and initiate prevention measures.⁵

Underscoring the importance of dengue, this infection was added in 2009 to the list of nationally notifiable infectious diseases in the United States.⁶

A COMMON INFECTION WORLDWIDE

Dengue causes up to 100 million new infections, 500,000 hospitalizations, and 25,000 deaths every year in the 2.5 billion people who live in subtropical and tropical areas of the world.⁷ It is transmitted by mosquitoes of the genus Aedes (which, unlike most other mosquitoes, often bite in the daytime), and it is the most common arboviral infection (ie, transmitted mainly by arthropods) worldwide.

The dengue virus belongs to the family of flaviviruses, which includes West Nile virus, St. Louis encephalitis, and yellow fever. It has four closely related but antigenically distinct serotypes, designated DENV-1, DENV-2, DENV-3, and DENV-4. Infection with one serotype induces lifetime homotypic immunity but only short-lived heterotypic immunity to the other dengue serotypes.⁸ Hence, a person can be infected over time with each of the four serotypes. The first infection is termed the primary infection; subsequent infection with any of the remaining three serotypes is termed a secondary infection.

Source: US Centers for Disease Control and Prevention.

Dengue virus transmission has been expanding since the end of World War II in Asia and since the 1980s in the Americas following the end of many regional vector-control programs.⁹ Although dengue is known to occur in tropical Africa, its epidemiology is less well defined on that continent (Figure 1).¹⁰

Explosive epidemics of dengue occur when there are enough mosquitoes and a susceptible population across a broad age range, ie, both children and adults.^11,12 Transmission can be halted with vigorous vector-control programs, or it slows and stops when the pool of susceptible people is exhausted.^13–15

On the other hand, hyperendemic transmission occurs in areas in which multiple virus serotypes continuously circulate in a large pool of susceptible people. In these areas, dengue seroprevalence increases with age, and most adults are immune.

Anyone of any age who travels from a nonendemic area to an epidemic or hyperendemic area is at risk of infection.¹⁶

DENGUE IN THE UNITED STATES

Reported cases of dengue in South and Central America, the Caribbean, and Mexico, common destinations for US travelers, have increased more than fourfold since the 1980s. There were a total of approximately 1 million cases in the 10-year period ending in 1989, compared with more than 4.5 million in the 8-year period from 2000 to 2007.¹¹

The geographic proximity of these areas to the continental United States and the large numbers of US residents travelling to these areas have raised concern that dengue could emerge in the continental United States in areas where potential vectors exist (see below).¹⁷ Furthermore, several US territories and former territories where tourism is an economic mainstay, including the Commonwealth of Puerto Rico,¹⁸ the US Virgin Islands,¹⁹ American Samoa, and other smaller Pacific island jurisdictions such as Palau,²⁰ have reported dengue virus circulation.

Arbonet database, maintained by the US Centers for Disease Control and Prevention.

Adding to the concern that dengue could gain a persistent foothold in the United States, competent dengue vectors are found here. Two mosquito vectors, Aedes aegypti21 and Aedes albopictus,^22,23 live in some areas of the southwestern and southeastern United States (Figure 2), with Aedes aegypti being the more competent transmitter. Both vectors may be abundant in warmer months. This raises a concern that a returning dengue-infected traveler could initiate an outbreak of autochthonous transmission.²⁴

Notably, endemic dengue transmission has occurred in the past in the United States, and the virus is circulating here again at low levels. From 1946 to 1980, no cases of dengue were acquired in the continental United States. However, since 1980 there have been seven outbreaks of laboratory-confirmed, locally acquired dengue along the Texas-Mexico border.^25–27 More recently, local transmission emerged in Key West, Florida,^28,29 the first outbreak since 1945 of dengue in the continental United States not to occur near the Texas-Mexico border. And in early 2011, nonsustained but locally acquired transmission was confirmed in Hawaii after a transmission-free decade.³⁰