Fatal outcomes of imported dengue fever in adult travelers from non-endemic areas are associated with primary infections

Background: The case-fatality rate of dengue in travelers is low. Secondary dengue virus (DENV) infections are considered a risk factor for fatal outcome in endemic populations; however, the impact of secondary infections on mortality in travelers has not been studied systematically. We performed a descriptive analysis of case reports of dengue fatalities in travelers. Methods: We searched Medline for clinical case reports, using the free terms and MeSH headings: 'Dengue' OR 'Severe Dengue' AND 'Travel-Related Illness' OR 'travel' AND 'Mortality' OR 'Fatal Outcome'. We analyzed case reports of fatal dengue in returning travelers published from 1995 to 2020, with the objective to detail risk factors for dengue mortality in this population. We verified the authors' classifications of primary or secondary dengue infections; infections were considered as primary by absence of anti-DENV immunoglobulin (Ig)G or by IgM-To-IgG ratios greater than or equal to 1.8 in the first 7 days post symptom onset. Results: We identified nine detailed reports of dengue with fatal outcome among travelers from non-endemic countries. Eight fatalities were female. The median age was 32 years (range 21-63). Out of nine fatal cases, seven travelers had a primary DENV infection, one had a secondary infection and, in one, these data were not reported. The infecting DENV serotypes were DENV-1 (n = 2), DENV-2 (n = 2) and DENV-3 (n = 3); DENV-1 or 2 (n = 1) and in one case, the serotype could not be determined. Conclusions: Dengue-related deaths in travelers are rare. Most dengue cases in travelers are primary infections. Contrary to prevailing conceptions, we found that fatal outcomes of dengue in travelers from non-endemic countries were reported mainly with primary DENV infections. We alert health care providers that primary DENV infections are not always harmless and that in adult travelers from non-endemic countries, primary infections may contribute more to dengue-related mortality than secondary infections.