Encephalitis

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus that is closely related to the West Nile and St. Louis encephalitis viruses endemic to North America. JE virus is a leading cause of viral encephalitis in Asia (1) but is rarely reported among travelers to countries where JE is endemic (2). This report describes a case of an unvaccinated Washington resident who had JE after traveling to northern Thailand. The Advisory Committee on Immunization Practices (ACIP) recommends JE vaccine for travelers to JE-endemic areas of Asia during the transmission season, especially those spending [greater than or equal to]1 month in those areas and whose travel itineraries include rural settings (2). JE vaccine should also be considered for travelers visiting areas with epidemic transmission or those engaging in extensive outdoor activity in rural settings in areas where JE is endemic, regardless of the duration of their visit. In addition, health-care providers and organized international travel programs should ensure that travelers obtain appropriate preventive health guidance before travel.

Case Report

In late June 2004, a previously healthy woman aged 22 years was admitted to a Seattle hospital within hours of returning from a 32-day visit to Thailand. She had become ill 2 days earlier with fever (101.5[degrees]F [38.6[degrees]C]), nausea, headache, photophobia, and stiff neck that had worsened over time. A lumbar puncture was performed; her cerebrospinal fluid (CSF) revealed a white blood cell count of 47 cells/[micro]L (97% polymorphonuclear leukocytes), glucose 60 mg/dL, and protein 37 mg/dL. The patient was presumptively treated for herpes encephalitis with acyclovir and for cerebral malaria with quinidine and corticosteroids.

Two days later, the patient had dysarthria, dysphagia, profound lethargy, and fever (104.0[degrees]F [40.0[degrees]C]); as a result, she was sedated and endotracheally intubated. A nonenhanced magnetic resonance image revealed edema in the hypothalamus. Polymerase chain reaction studies of CSF for herpes simplex virus and enteroviruses were negative, and peripheral blood smears were negative for plasmodia. The patient improved clinically and was extubated after 2 days but had onset of Bell's palsy on hospital day 11. After 14 days of hospitalization, she was discharged and underwent outpatient rehabilitation for 6 weeks. The patient had no apparent neurologic sequelae. CSF and serum collected 4 days after illness onset and serum collected 21 days after illness onset had JE virus--specific IgM antibodies and neutralizing antibodies confirming a recent JE viral infection.

In May 2004, the patient had traveled with 21 other students to Chiang Mai City, Thailand, on a university-affiliated study-abroad program. Although the program did not require students to consult a health-care provider before travel, the patient consulted her primary-care physician. She did not receive any vaccinations or malaria prophylaxis. During her month-long stay, the patient slept in a dormitory, where her room did not have screened windows or bed nets. She also spent one night in a poorly screened cabin in the rural Chiang Mai Valley. The patient reported receiving mosquito bites in both the dormitory and cabin.

Cohort Survey

Approximately 6 weeks after hospital admission, a telephone survey of the patient's travel cohort was performed. Of 22 students, 20 (91%) participated in the survey; none had a similar illness. Mean age of respondents was 22 years (range: 19-30 years), and the median time spent in Asia during the study-abroad program was 6.5 weeks (range: 4.5-16.0 weeks). In preparation for the trip, five (25%) students consulted a travel medicine specialist, seven (35%) consulted a primarycare provider or a parent in the health-care field, and eight (40%) did not consult a health-care provider. One student was vaccinated against JE. All students participated in outdoor activities in Thailand, and 19 (95%) reported receiving mosquito bites. Three (1 5%) students reported having screens or bed nets at the dormitory; however, 15 (75%) reported "sometimes" or "always" using insect repellent while in Chiang Mai City.

On the basis of the cohort survey results, the Washington State Department of Health recommended that the university study-abroad program 1) require all students traveling to areas outside of North America or Western Europe to consult a knowledgeable health-care provider for advice on appropriate vaccinations, malaria prophylaxis, and other health precautions before travel, and 2) develop a formal curriculum oil travelers' health topics to be presented during predeparture orientation.

Editorial Note: JE virus is a leading cause of viral encephalitis in Asia; JE has a case-fatality rate of approximately 30% (1,3). No virus-specific treatment exists, and survivors commonly have neurologic sequelae (1,3). Although JE is a substantial public health problem in Asian countries, transmission to short-term travelers to JE-endemic countries rarely has been reported (2,4). This report describes the first reported case in a U.S. traveler since 1992.

Less than 1% of JE virus--infected persons have onset of encephalitis (3); however, because an effective JE vaccine is available, vaccination should be considered for use in travelers to Asia. Although the risk for infection among travelers is low overall, risk varies substantially by season (e.g., risk is highest in the rainy season), geographic location, duration of travel, outbreak presence, and activities of the traveler (2,5). Risk estimates based on JE incidence among residents of countries where the disease is endemic are often inaccurate because JE surveillance is not conducted in many Asian countries. In countries with childhood vaccination programs or where the majority of persons aged < 15 years have developed immunity after a natural, asymptomatic JE viral infection, the low incidence among residents can be misleading. Despite a history of JE outbreaks in rural Chiang Mai Valley (6,7) and [greater than or equal to]1 month's stay for all 22 travelers described in this report, 40% received no pre-travel medical advice from a health-care provider, and only one was vaccinated against JE.

The specific ecologic setting in which the patient described in this report was infected is unknown. Swine production and flood-irrigated rice farming provide a hospitable environment for both the proliferation of the principal mosquito vector, Culex tritaeniorhynchus, and amplification of JE virus in swine. Mosquito infection rates can be as high as 10% in areas where virus transmission to vertebrates is high (8). The virus can also be transmitted in urban and other ecologic settings, although the intensity of transmission is often much less than in endemic, rice-producing areas. JE cases have been reported among urban residents and travelers to Asian cities who had little or no rural exposure and were likely infected by urban Culex species (2). In addition, because wading birds (e.g., egrets) and large mammals other than swine can serve as amplifying hosts, JE virus transmission can occur in areas where swine are not raised. JE virus infected persons do not have high-titer viremia and are therefore considered "dead-end" hosts.

A single, formalin-inactivated, mouse brain--derived, JE vaccine is licensed for use in the United States in persons aged [greater than or equal to]1 year. The preferred primary vaccination series consists of 3 doses administered at 0, 7, and 30 days, but an accelerated schedule consisting of 3 doses administered at 0, 7, and 14 days can be used when the longer schedule is impractical or inconvenient because of time constraints. With either schedule, the primary series should be completed at least 10 days before travel to allow an adequate immune response and monitoring of adverse events (AE) after vaccination; therefore, JE vaccination should begin at least 24 days before travel abroad. In addition to a moderate rate of local side effects (2), rare and more serious neurologic (e.g., encephalitis) and allergic AE (e.g., urticaria or angioedema) have been reported (9).

JE vaccine is not recommended for all travelers to Asia. For each traveler, careful consideration of the potential risks and benefits of vaccination should be made by a health-care prorider familiar with the person's itinerary, the vaccine, and current CDC recommendations for its use (2). In general, vaccine should be offered to persons spending [greater than or equal to]1 month in JE-endemic areas during the transmission season, especially if travel will include rural areas. Under specific circumstances, vaccine should be considered for persons spending < 1 month in JE-endemic areas (e.g., travelers to areas experiencing epidemic transmission and persons whose activities, such as extensive outdoor activities in rural areas, place them at high risk for exposure). In all instances, travelers should be advised to take personal precautions to reduce exposure to mosquito bites (e.g., avoidance of mosquitoes and use of repellents and protective clothing).

To determine a traveler's need for vaccination and prophylaxis, health-care providers and travelers can review regularly updated CDC travel recommendations for JE, malaria, other vector-borne diseases, and endemic infectious diseases at http:/www.cdc.gov/travel. In addition, health-care providers can call the CDC Division of Vector-Borne Infectious Diseases, telephone 970-221-6400, or Division of Global Migration and Quarantine, telephone 404-498-1600. Finally, organized international travel programs should ensure that their clients obtain appropriate preventive health guidance before travel.

References

(1.) Halstead SB, Tsai TF. Japanese encephalitis vaccines. In: Plotkin SA, Orenstein WA, eds. Vaccines. 4th ed. Philadelphia, PA: WB Saunders; 2004:919-58.

(2.) CDC. Inactivated Japanese encephalitis virus vaccine. Recommendations of the Advisory Committee on lmmnnization Practices (ACIP). MMWR 1993;42(No. RR-1):1-15.

(3.) Solomon T. Flavivirus encephalitis. N Engl J Med 2004;351:370-80.

(4.) Geraghty CM, McCarthy JS. Japanese encephalitis vaccine: is it being sufficiently used in travelers? Med J Aust 2004;181:269-70.

(5.) Shlim DR, Solomon T. Japanese encephalitis vaccine for travelers: exploring the limits of risk. Clin Infect Dis 2002;35:183-8.

(6.) Grossman RA, Edelman R, Willhight M, et al. Study of Japanese encephalitis virus in Chiang Mai Valley, Thailand. Am J Epidemiol 1973;98:133-49.

(7.) CDC. Health information for international travel 2003-2004. Atlanta, GA: US Department of Health and Human Services, Public Health Service; 2003.

(8.) Maeda O, Karaki T, Kuroda A, et al. Epidemiological studies on Japanese encephalitis in Kyoto City area, Japan. III. Seasonal prevalence of virus infections in several pig populations shown by virus recovery from engorged Culex tritaeniorhynchus summorosus. Jpn J Med Sci Biol 1978;31:277-90.

(9.) Plesner AM. Allergic reactions to Japanese encephalitis vaccine, Immunol Allergy Clin North Am 2003;23:665-97.

P Hashisaki, MD, Overlake Hospital Medical Center, Bellevue; V Hsu, MD, M Granjean, C DeBolt, MPH, J Duchin, MD, Public Health-Seattle and King County, Seattle; L Kidoguchi. MPH, M Leslie, DVM, J Hofmann, MD, Washington State Dept of Health. A Marfin, MD, G Campbell, MD, Div of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, CDC.

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