Date Published: June 20, 2018
Publisher: Public Library of Science
Author(s): Baoyin Yuan, Hiroshi Nishiura, Nguyen Tien Huy.
Frequent international travel facilitates the global spread of dengue fever. Japan has experienced an increasing number of imported case notifications of dengue virus (DENV) infection, mostly arising from Japanese travelers visiting South and Southeast Asian countries. This has led an autochthonous dengue outbreak in 2014 in Japan. The present study aimed to infer the risk of DENV infection among Japanese travelers to Asian countries, thereby obtaining an actual estimate of the number of DENV infections among travelers.
For eight destination countries (Indonesia, Philippines, Thailand, India, Malaysia, Vietnam, Sri Lanka, and Singapore), we collected age-dependent seroepidemiological data. We also retrieved the number of imported cases, who were notified to the Japanese government, as well as the total number of travelers to each destination. Using a mathematical model, we estimated the force of infection in each destination country with seroepidemiological data while jointly inferring the reporting coverage of DENV infections among Japanese travelers from datasets of imported cases and travelers. Assuming that travelers had a risk of infection that was identical to that of the local population during travel, the reporting coverage of dengue appeared to range from 0.6% to 4.3%. The risk of infection per journey ranged from 0.02% to 0.44%.
We found that the actual number of imported cases of DENV infection among Japanese travelers could be more than 20 times the notified number of imported cases. This finding may be attributed to the substantial proportion of asymptomatic and under-ascertained infections.
Dengue fever is one of the most common mosquito-borne infectious diseases worldwide. The World Health Organization (WHO) estimates that 3.9 billion people in a total of 128 countries are at risk of dengue virus (DENV) infection [1,2]. Of these, more than 100 countries are endemic, extending to the Americas, Eastern Mediterranean, Southeast Asia, and Western Pacific regions [1,2]. Aedes aegypti and Aedes albopictus are known as the major vector species of DENV. The virus comprises four different serotypes, i.e., DENV-1, DENV-2, DENV-3 and DENV-4, belonging to the genus Flavivirus, family Flaviviridae. Of the total infections, 80% remain asymptomatic [1,3]. The spectrum of clinical symptoms range from moderate to acute and are sometimes even life-threatening [3,4]. The time from exposure to illness onset (i.e., the incubation period) ranges from 3 to 14 days (most commonly 4–7 days) . Thus, infected travelers can asymptomatically or pre-symptomatically return to Japan from endemic countries without recognizing an infection, thereby potentially increasing the risk of imported dengue outbreaks.
From 2006 to 2016, there were a total of 2026 imported cases of DENV infection from 63 different countries that could potentially act as the source of exportation (Online Supplementary Material). Of these, 176 patients visited multiple countries and their place of infection was not determined. Of the remainder (1850 patients), South and Southeast Asian countries accounted for the majority of cases. In descending order of incidence, imported cases came from Indonesia, Philippines, Thailand, India, Malaysia, Vietnam, Cambodia, Myanmar, Sri Lanka, Bangladesh, and Singapore. Owing to unavailability of seroepidemiological survey data, Cambodia, Myanmar, and Bangladesh were excluded and the remaining eight countries were included for further analyses (Fig 2). Imported cases from the eight selected countries accounted for 83.5% of the total notifications.
In the present study, we statistically inferred the risk of DENV infection among Japanese travelers to Asian countries, as the importation is recognized as increasing over time . To accomplish this task, we used multiple pieces of data as a trick to estimate asymptomatically infected fraction, including seroprevalence data of travelers’ destination country such that the force of infection could be explicitly estimated. Integrating the force of infection into the process of importation and assuming that travelers experienced a force of infection identical to that of local people during their travel, the reporting coverage of dengue was estimated to range from 0.6% to 4.3%. This finding implies that the actual importation of DENV infection among Japanese travelers may be more than 20 times the notified number of imported cases. Moreover, the risk of infection per travel ranged from 0.02% to 0.44%.