Date Published: February 7, 2018
Publisher: Public Library of Science
Author(s): Femke W. Overbosch, Janke Schinkel, Ineke G. Stolte, Maria Prins, Gerard J. B. Sonder, Richard Paul.
Dengue is increasing rapidly in endemic regions. Data on incidence among travelers to these areas are limited. Five prospective studies have been performed thus far, mainly among short-term travelers.
To obtain the attack and incidence rate (AR, IR) of dengue virus (DENV) infection among long-term travelers and identify associated risk factors.
A prospective study was performed among long-term travelers (12–52 weeks) attending the Public Health Service in Amsterdam. Clients planning to travel to (sub)tropical countries were invited to participate. Participants kept a travel diary, recording itinerary, symptoms, and physician visits. Pre- and post-travel blood samples were serologically tested for the presence of Anti-DENV IgG antibodies. Seroconversion was considered suggestive of a primary DENV infection. Anti-DENV IgG present in both corresponding samples in combination with a post-/pre-travel ratio of ≥4:1 was suggestive of a secondary infection. Risk factors for a DENV infection were studied using poisson regression.
In total, 600 participants were included; median age was 25 years (IQR: 23–29), 35.5% were male, and median travel duration was 20 weeks (IQR: 15–25). In 39 of 600 participants (AR: 6.5%; 95% CI 4.5–8.5%) anti-DENV IgG test results were suggestive of a recent infection, yielding an IR of 13.9 per 1,000 person-months traveling (95%CI: 9.9–19.1). No secondary infections were found. IR for Asia, Africa, and America were comparable and 13.5, 15.8, and 13.6 per 1,000 person-months respectively. Of participants with a recent DENV infection, 51% did not report dengue-like illness (DLI) or fever, but 10% were hospitalized. In multivariable analysis, travelers who seroconverted were significantly more likely to be vaccinated with ≥2 flavivirus vaccines for the current trip or to have reported DLI in >1 consecutive weeks.
Long-term travelers are at substantial risk of DENV infection. Half of those with a DENV infection reported no symptoms, but 10% were hospitalized, demonstrating the importance of advising anti-mosquito measures during travel.
Dengue is an arthropod-borne viral disease found in (sub)tropical regions and is endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South East Asia, and the Western Pacific. The disease is transmitted by Aedes mosquitoes, and caused by four serotypes of dengue virus (DENV-1, -2, -3, and -4) . An estimated 3.9 billion people worldwide are at risk . Infection with a particular serotype provides lifelong immunity against that serotype after recovery, but cross-immunity to the other serotypes is only partial and temporary . Infection is often asymptomatic or subclinical, but can produce a wide range of illness in which symptoms vary from a mild febrile self-limiting illness to a severe disease . An estimated 390 million infections occur per year . Individual risk factors determine the severity of disease and include age (such as infants with a primary infection born to dengue-immune mothers or children with a secondary dengue infection), ethnicity (white individuals), certain chronic diseases, and secondary DENV infection with a different serotype . No specific curative treatment is available and although DENV vaccines have been developed, they are not yet available for travelers .
In this prospective study of long-term travelers to (sub)tropical countries we found a substantial AR and IR for DENV infection during travel. Our estimated AR ranged from 6.0% to 6.5% and is higher than found in previous prospective studies among short-term travelers in which ARs ranged between 1% and 2.9% [7–10]. The only other prospective study among long-term travelers (3–6 months) found a comparable AR of 6.7% . As expected, the duration of travel influences the AR, while it does not influence the incidence rate. Hence, unlike the AR, the DENV incidence observed in our study was comparable to those reported in other prospective studies, which varied from 6.7 to 30 per 1000 person-months among the predominantly short-term travelers, and was 11 per 1000 person-months among the long-term travelers [7–11]. Comparison of results between different prospective studies should, however, be interpreted with caution. The risk for travel-related DENV infection depends not only on endemicity, but also on outbreaks in a particular country during a particular time of travel. As the journeys of the participants were scattered over countries and over time, the influence of possible rain seasons or outbreaks in this cohort of long-term travelers could not be studied. Also, comparison of prospective studies with studies based on surveillance data of travelers returning ill should be done with greatest caution: increased awareness of dengue in hospitals and improvements in diagnostic procedures could also have influenced the increase of diagnosed DENV infections in surveillance data .
This is the second prospective study investigating DENV infection among long-term travelers. It confirms that the incidence rate of DENV infection among long-term travelers is substantial. As expected, the attack rate was higher among long-term than among previously investigated short-term travelers. Half of the travelers with a recent DENV infection reported no symptoms of dengue-like illness, suggesting they had asymptomatic infections, but almost all DENV-infected travelers who reported DLI symptoms in >1 consecutive weeks were hospitalized.