Nine travelers (9/33; 27%) with influenza having cross-hemispheric (n = 12) or out-of-season departures (n = 21) to tropical regions received a pre-travel encounter where influenza vaccine could have been administered had it been available. There was vaccine mismatch of the respective A or B strains between the hemispheres for three (3/12; 25%) of those with cross-hemispheric influenza acquisition. Analysis of 10

years of surveillance data in >37,000 ill-returned travelers has enabled identification of travel patterns among those who acquired influenza. While cross-hemispheric travel into reciprocal hemispheres during influenza season occurred in only five travelers, cross-hemispheric travel of any kind was more likely to be associated with hospital-based care than intra-hemispheric or tropical travel and acquisition of influenza. Travelers with influenza Apitolisib were not at extremes of age where risk of complicated influenza infection is higher. That 71% of travelers with

influenza A traveled to the ESEACN (Figure 1) parallels known contributions of this network to the global burden of influenza A in any given season.9,10 The ESEACN is particularly relevant to travel and influenza due to the 6.6% annual growth in tourist FK866 chemical structure arrivals to Asia and the Pacific since 1990, with arrivals to East Asia expected to reach 397 million by 2020.11 Travel to the ESEACN conferred an approximate 7-fold and 3.6-fold higher proportionate morbidity estimate for influenza

A and B, respectively, than travel outside the network. Thirty-seven percent of travelers with influenza in this analysis engaged in multicountry itineraries during their most recent travel, which would have likely increased the contact time in airports and on airplanes. A small but measurable risk of influenza acquisition aboard commercial aircraft has been well documented,12 with long haul flights conferring the highest risk of infection.13 Thus, transit-related conditions may affect risk of influenza. This analysis has several limitations. First, heterogeneity in laboratory diagnostics performed at each GeoSentinel site, including variable performance characteristics such as sensitivity NADPH-cytochrome-c2 reductase and specificity, may have influenced the number of cases represented in the database. An acknowledged limitation is the lack of information regarding specific diagnostic tests used at individual GeoSentinel sites. That biological confirmation of infection may have occurred by one or more of antigen detection, cell culture, or PCR would necessarily influence the number of cases identified due to varying test performance. Second, the cohort represents only those ill-returned travelers who presented to GeoSentinel clinics, thus, our conclusions may not extend to all ill-returned travelers.