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Recent modeling and consensus building efforts among experts have estimated the global dengue burden to be as high as 390 million dengue infections,[1] much higher than the estimated 50 to 100 million cases as reported by the World Health Organization (WHO).[2] In the past 50 years, the incidence of dengue has increased 30-fold.[2] The marked increase of dengue over the past decades is in tandem with increasing reports of international travelers acquiring dengue while traveling to tropical and sub-tropical countries.[3] With forecasts of international tourist arrivals predicted to reach 1.8 billion by 2030, [4] travelers will increasingly be affected by this mosquito-borne disease.

The article by the Boston Area Travel Medicine Network in this month's edition of the Journal of Travel Medicine showed that 6.9% travelers from nonendemic countries who had traveled to dengue-endemic countries for more than 2 weeks but less than 1 year are dengue IgG positive.[5] This number is relatively high, higher than that reported in Dutch travelers[6] but similar to that reported in Israeli travelers.[7] It is also higher than the numbers based on mathematical modeling for travelers to Singapore[8] and to Thailand.[9] However, because of the retrospective nature of seroprevalence studies, this high figure observed by the Boston Area Travel Medicine Network can also be explained by the effect of cumulative travel in the past. Furthermore, this group only included travelers with relatively long travel duration. An overestimation may also have occurred because of the cross-reactivity of dengue IgG with yellow fever vaccination or other flavivirus infections,[10] and the results (where available) based on plaque reduction neutralization test (PRNT) were consistently lower as shown by the same group.

The Boston Area Travel Medicine Network also showed a high dengue seroprevalence rate in travelers who were born or had lived in a dengue-endemic country for more than 1 year (51 and 40%, respectively). This is in keeping with the high seroprevalence rates reported in dengue-endemic countries: for example 45% in Singapore,[11] 71% in Thailand,[12] between 74 and 91% in Brazil,[13] and 92% in Puerto Rico.[14]

Obviously, the main question that arises from such high dengue seroprevalence rates is whether travelers with prior exposure to dengue are at increased risk of more severe disease with repeated travel to dengue-endemic countries, and thus increased risk of secondary infections. This question appears to be the “holy grail” question for travel medicine providers dealing with dengue. More severe or fatal disease is generally less frequently reported in travelers when compared with persons from endemic areas.[15] The pathophysiology of severe disease is still poorly understood and thought to be multifactorial: age, host factors, virus strain, and interval between infections are all contributing factors,[16] in addition to the often-quoted secondary infections. Because of the overall low case fatality rate of severe disease (<0.1% in centers with expertise in the management of severe dengue), and because of the overall low frequency of severe disease even after secondary infection, there are currently no evidence-based risk assessments for dengue-positive travelers who engage in repeated travel to dengue-endemic countries. Hence, there are also no guidelines.

The overall high attack rate of dengue in travelers—comparably higher than that of other “traditional” travel-related vaccine-preventable diseases such as hepatitis A or typhoid fever—highlights the urgent need for a dengue vaccine for travelers.[17] The Boston Area Travel Medicine Network also conducted a study on the acceptability of hypothetical dengue vaccines among travelers, published in this issue.[18] Four dengue vaccines with hypothetical variations of different combinations of efficacy and adverse event profiles were studied with regards to their acceptability among travelers. Not unsurprisingly, acceptance of the four hypothetical vaccines was high; it ranged from 54% for the vaccine with lower efficacy and serious adverse event risk to 95% for the vaccine with higher efficacy and minor adverse event risk. As a better measure of true acceptability, however, the authors could have included a question on “willingness to pay.”

“Vaccine candidates are being studied aggressively and may be ready for licensure soon,” the authors write.[18] Indeed, many dengue vaccine candidates are currently at different stages of development, with the chimeric dengue vaccine developed by Sanofi Pasteur being the leading candidate.[17] This vaccine showed promising results with high immunogenicity and a good safety profile for all four serotypes.[19] However, the recent results of the efficacy studies in Thailand have thrown a spanner in the works: despite documented high immunogenicity, the clinical protective efficacy was disappointingly low, only around 30% for all serotypes combined.[20] The grim reality is that a dengue vaccine remains elusive for the time being.

Without a dengue vaccine, travelers will continue to be at individual risk of acquiring dengue during their vacation or business trips in the tropics and subtropics—and the recent update by GeoSentinel underlines this high risk.[21]

Furthermore, travelers will also continue to import dengue to currently nonendemic countries. The recent dengue outbreak in Angola highlights this risk: within a matter of 6 weeks, travelers from Angola exported dengue to four continents.[22] Dengue: quo vadis? Where will it go next? What is the risk of introduction and establishment of dengue into currently nonendemic countries? Such a risk depends on the ecological and climate suitability for the vector, the importation rate of both the vector and of viremic travelers, and national preparedness and vector control capabilities. Many research gaps exist to quantify such a risk. The DengueTools consortium, a consortium of 14 partners from around the world, has set out to address this research priority.[23] The autochthonous cases in Southern France[24] and Croatia in 2010,[25] and the major dengue outbreak in Madeira off Portugal in 2012[26] certainly should serve as a wake-up call to all currently nonendemic countries.

The review article on dengue in international travelers in this month's edition[27] provides a comprehensive summary of all the issues of dengue in international travelers, and makes an excellent read.

Declaration of Interests

  1. Top of page
  2. Declaration of Interests
  3. References

The author states she has no conflicts of interest to declare.

References

  1. Top of page
  2. Declaration of Interests
  3. References
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