The 55 travel-associated JE cases identified over the 36-year period from 1973 through 2008 represent an average of 1.5 published cases per year. Although there was a small increase in case frequency over time, this may reflect the increase in overall tourist numbers during the same period, or possibly clinicians more frequently considering the diagnosis of JE. The majority of cases occurred among expatriates or tourists who visited JE-endemic countries for at least one month.
The risk of JE for travelers is clearly low, although the precise risk is unknown. Among U.S. citizens, only 15 travel-associated JE cases were identified during 1973–2008. The annual number of entries of U.S. citizens to Asia was approximately 2–3 million earlier in this period and increased to approximately 5.5 million entries in 2004.12,49
On the basis of these data, the approximate risk estimate was < 0.2 cases/1 million U.S. travelers. However, this figure does not differentiate between the lower risk for short-term travelers with low-risk itineraries and the greater risk for expatriates, travelers on long trips, or short-term travelers with high-risk itineraries. In addition, the JE vaccine licensed in the United States in 1992 undoubtedly has prevented cases. However, a recent survey in the United States found that only 47 (11%) of 415 travelers to JE-endemic countries with at-risk itineraries were vaccinated with ≥ 1 dose of JE vaccine (Duffy M and others, unpublished data). Despite this low rate of vaccination, only four cases have been reported in U.S. travelers since 1992, reinforcing the fact that the overall risk of JE in travelers is low.
The percentage of the total number of JE travel-associated cases that these 55 published cases represent is unknown. Some indication is given by using available national data. In Australia, for example, JE has been a nationally notifiable disease since 2001. During 2001–2008, three JE cases were reported nationally; case reports were published for two of the cases and the third patient had a mild, self-limiting illness (Marich A, New South Wales Department of Health, unpublished data).30,31,50
A recent review suggested that among Scandinavian patients, 7 (54%) of 13 cases that occurred during 1994–2008 were reported in the literature.15
Documents from health departments in the United Kingdom and Canada in 2008 indicated that all known cases that had occurred in their travelers had been published.51,52
These data suggest that at least 50%, and perhaps a higher percentage, of travel-associated JE cases that are diagnosed are published. It is likely that some travel-associated cases are never diagnosed as JE. Nevertheless, on the basis of the risk estimate calculated above of < 0.2 cases per 1 million travelers, and despite some degree of under-diagnosis and under-reporting, it is unlikely that the overall JE risk for travelers is > 1 case/1 million travelers.
The age groups represented among the reported cases ranged from young children to elderly adults. Before implementation of JE immunization programs in JE-endemic countries, the majority of cases characteristically occur in children less than 15 years of age because most of the older population has developed immunity from previous subclinical infection.6
However, unvaccinated travelers who enter JE-endemic areas are usually immunologically naive with respect to JEV. As a result, travelers of all ages are susceptible to infection as clearly demonstrated in this review.
Cases among two particular subgroups of tourists, VFRs and students on study-abroad programs, were noted. Both groups are important in relation to risk of travel-associated JE because they frequently spend several months in JE-endemic countries, often in rural or remote locations. Despite potentially high risk itineraries, many may not seek pre-travel advice. It is well-recognized that the perception of risk among VFRs is often low, particularly in those traveling back to their country of birth.53
Students may not always seek travel-related preventive medical advice, or receive appropriate interventions, for financial or other reasons.54
Organized travel programs, including study-abroad programs, should ensure that their clients receive appropriate preventive health information.
Cases of JE were reported in travelers to countries where there is no ongoing surveillance for JE, including Papua New Guinea, Myanmar, and the Philippines. In countries where JE cases among the local population are not routinely recognized or reported, a tourist may act as a sentinel for the presence of JEV transmission. In the late 1980s and early 1990s, it was the reporting of JE in tourists to Bali that accelerated recognition by the Indonesian government that JE was a public health problem.38,39,43,55
The lack of recognition and reporting of JE locally should not affect the decision to vaccinate tourists planning travel to areas considered to be JE-endemic.
Although many of the persons who visited countries with recognized peak JEV transmission seasons were infected during these periods, some travelers to Thailand and Vietnam acquired infection at other times of the year. Thailand has year-round JEV transmission in much of the country with a seasonal peak during May–October, mainly in the northern part of the country.56,57
Vietnam has seasonal transmission in its northern region but year-round transmission in the southern region.3,58
Because of prominent seasonal peaks in some areas of these countries, the year-round disease risk in many parts of both countries is often under-appreciated. Travel medicine providers should review each traveler's itinerary in detail to provide the most appropriate preventive recommendations for JE.
The U.S. Advisory Committee on Immunization Practices recommends JE vaccine for travelers who plan to spend a month or longer in JE-endemic areas during the JEV transmission season. Japanese encephalitis vaccine should be considered for short-term travelers (< 1 month) to JE-endemic areas during the transmission season if their activities will increase the risk of JEV exposure. Japanese encephalitis vaccine is not recommended for short-term travelers whose visit will be restricted to urban areas or times outside of a well-defined JEV transmission season.59
Although no minimum duration of travel eliminates a traveler's risk for JE, a longer itinerary increases the likelihood that a traveler will spend time in an area with active JEV transmission. Although a recent survey suggested that longer-term travelers comprise approximately 20% of U.S. travelers to JE-endemic countries (Duffy M and others, unpublished data), 65% of the cases included in this review were in expatriates and longer-term travelers, highlighting the increased JE risk in this group and need for protection by vaccination.
Among the 35% of case-patients who acquired infection during stays < 1 month, their itineraries, activities, or accommodations likely contributed to their risk of JEV exposure, despite their shorter lengths of stay. These cases demonstrate the complexity for both travelers and providers in assessing the risk presented by a specific travel itinerary. Decisions regarding the use of JE vaccine must weigh several factors. JE is a severe disease, no specific treatment is available, and disease outcome is often poor. Conversely, the overall risk of travel-associated JE disease is low, vaccination is costly, and there are potential side effects associated with vaccination.60
Because shorter-term travelers represent a much higher proportion of travelers overall, consideration of risk in this group is important. Among JE cases in our review with travel duration < 1 month, Thailand and Indonesia (Bali) were the two commonest destinations. On average, 4.5 million tourists from non JE-endemic countries visited Thailand each year during 2000–2008.61
On the basis of survey data from U.S. travelers to Asia, which indicated 80% of all travelers have short-term (< 1 month) itineraries (Duffy M and others, unpublished data), and a conservative assumption that twice as many travel-associated JE cases occurred than were published, the JE risk was approximately 1 case/3.3 million short-term travelers since 1996, when the first case was reported. In 1988, the first reported JE case in a short-term tourist to Bali occurred; since then three additional such case reports have been published. The most recent case occurred in 2000 in a tourist who traveled to Java and Bali but likely acquired his JEV infection in Bali. On average, approximately 620,000 tourists from non–JE-endemic countries have visited Bali annually during the past decade.62
Using conservative assumptions that annual tourists visits were half this amount in the 11 years before this decade, twice the number of cases occurred than were published, and 80% of Bali-visiting tourists had short-term itineraries, the JE risk in the 21-year period since 1988 was approximately 1 case/1.0 million short-term travelers.
The limitations of this review include that the 55 cases reported here cannot be considered a complete or representative sample of all travel-associated JE cases. Details of a case diagnosed and treated abroad may not be available in the person's home country. A case report is not published for every patient that is diagnosed, and the diagnosis may be missed. The reported cases may not be representative of all travel-associated JE cases, either diagnosed or undiagnosed. For example, publication may have been more likely if a case had a unique or more severe clinical presentation, unusual travel destination, or another noteworthy epidemiologic feature such as JEV infection associated with short-term travel. Our search strategy may not have detected all cases. Furthermore, we were unable to include 18 (33%) of the 55 cases in the detailed risk analysis because risk factor information was unavailable. Finally, we were able to conduct only a fairly simple, mostly qualitative description of possible risk factors for travel-associated JE. A more quantitative risk-factor study (e.g., a case–control study) would require a suitable comparison group of adequate size and composed of otherwise similar travelers who did not acquire JEV infection. Because constructing such a control group would be logistically extremely difficult, no analytic studies of this type have ever been published.
When consulted by a traveler planning to visit a JE-endemic country, travel medicine providers should perform a careful assessment of each traveler's itinerary, including destinations, duration and season of travel, and potential activities. All travelers should be advised of the risks of JE and the importance of personal protective measures to reduce the risk of mosquito bites. For some travelers who will be in a high-risk setting based on travel destination, duration, season, and activities, JE vaccine can further reduce the risk of infection.