A Case of Imported JE Acquired During Short Travel in Vietnam. Are Current Recommendations About Vaccination Broader?

Japanese encephalitis (JE) virus is the most common cause of viral encephalitis in eastern and southern Asia, with 30,000 to 50,000 cases reported annually. 1 Clinical disease ranges from a flulike fever to a severe and deadly meningoencephalitis with parkinsonian syndrome. Mortality is high (25%–30%), and neuropsychiatric sequelae occur in 50% of survivors. 1 The symptomatic to asymptomatic ratio is about 1:250. The incubation period is 5 to 15 days. No specific treatment is available. The chance of a traveler contracting symptomatic JE is estimated to be 1:1,000,000. 2 A previously healthy 49‐year‐old Italian man was admitted to hospital immediately after arriving in Italy after a 3‐week trip to Vietnam (April 25 to May 16). Most of the trip took place in a rural area in North Vietnam (details are shown in Figure 1). The accommodation was hotel based. No mosquito bites were noticed. On his way back, the patient complained of fatigue, fever, and altered mental status. He was admitted the day after and found to be stuporose, disoriented, and febrile (39.5°C), with mild meningismus. A parkinsonian syndrome with orofacial dyskinesiasis and intentional tremors developed in the following days. Diffuse theta–delta activity and generalized slow waves were shown by electroencephalography. Lesions at the right lentiform nucleus and bilateral thalamus (T1‐weighted hypointense and T2‐weighted hyperintense, without contrast enhancement) were observed by magnetic resonance imaging (Figure 2). JE virus infection was confirmed by serology (immunofluorescence) with increasing titers on subsequent samples on serum and cerebrospinal fluid (detailed in Table 1). Due to worsening clinical status, a 5‐day treatment course of intravenous immunoglobulin (IVIG) (400 mg/kg) was administered. This is the first case reported of IVIG use in JE but is the standard management for certain infectious diseases with a strong hyperinflammatory component (acute disseminated encefalomielitis). 3 Detailed treatment discussion is available elsewhere. 4 The patient recovered and was discharged. Only a slight deficit in recent memory was recorded 1 month after discharge. Travel details: destinations and periods of sojourn are listed. Incubation period for Japanese encephalitis is usually estimated to be 5 to 15 days and in this case extends from May 1 to May 11. Magnetic resonance imaging shows T2‐weighted lesions of (a) right lentiform nucleus (b) and left thalamus. Complete serological examination and the evolution of antibody titers CSF = cerebrospinal fluid; IgG = immunoglobulin G; IgM = immunoglobulin M. Complete serological examination and the evolution of antibody titers CSF = cerebrospinal fluid; IgG = immunoglobulin G; IgM = immunoglobulin M. JE is a deadly and invalidating but preventable disease for which no specific treatment is available; the risk of acquiring the disease during traveling may be underestimated. 5 Centers for Disease Control and Prevention recommend JE vaccination to travelers spending more than 30 days in an endemic environment or less than 30 days in areas with epidemic transmission. 6 However, the use of an arbitrary cutoff cannot protect all travelers. Advance knowledge of trip details, accommodation and purpose as well as local geography, is warranted to give adequate advice. JE is described as a rural disease: the vector, Culex tritaeniorhynchus, breeds in rice paddies and pigs behave both as an amplifying host and as a bridge to human infections. 1 However, many factors could increase risk exposure even in an urban setting. First, in Asia, the proximity to animals is greater than in the West, animals are often transported in open trucks and carts through the city, and wet markets are still widespread. Second, the vector can disperse over long distances (up to 250–500 km) carried by the wind, and infestation of towns is an expected phenomenon. 7 Third, recently a change in Culex’s resting behavior was reported in India with indoor preferred to outdoor resting during daytime. 8 In Vietnam, two epidemiological patterns of transmission coexist: an endemic pattern in the South with a broad seasonal peak after the start of the rainy season and an epidemic pattern in the more temperate areas in the North with a precise summer season (May to October). 7 In 2005, the number of children hospitalized for JE in North Vietnam increased by 20% to 30% compared with 2004. 9 While the estimated risk of acquiring JE is 1:1,000,000 in tourists, the risk for travelers to rural destinations during the rainy season could increase up to 1:5,000 case per month. 2 Usually, the recommendations for vaccination derive from the balance of the risk of acquiring the infection and the risk of developing a vaccine‐related reaction (around 15 events per 100,000 doses with the available formalin‐inactivated mouse brain–derived vaccine). 5 In the patient described, no vaccination was suggested, as the general recommendations were applied. However, we think that the exposure risk was underestimated: the trip was due to take place in an epidemic area in full epidemic period; local transport, visits to rural areas, and natural parks were planned. Between 1978 and 1992, 24 cases of JE among travelers or expatriates were reported: among them just 1 or 2 were tourists. 5 Since that report, five more tourists acquired JE in Bali (two cases in 1994 and 1995), Thailand, Indonesia, and China (one case from each country in 2005). 2,10,11 Two cases of five were fatal. In Israel, JE virus vaccination is recommended prior to travel to Thailand, after a single Israeli traveler acquired the disease in Thailand. 2 However, we think that general recommendations may not be able to protect all travelers. JE is a rare, vaccine‐preventable infection with potentially devastating outcome. Travel medicine services should personalize advice through a detailed pretravel interview to identify travelers with a higher risk profile (destination, rural setting, accommodation, season) or greater willingness to be vaccinated, while time of permanence could not be so important in determining the choice. Moreover, recommendations should be constantly updated on the ground of epidemic outbreaks or notified imported cases. This case outlines the importance of constant surveillance of imported diseases throughout a network of integrated systems (Promedmail, TropNet Europe, Geosentinel) to improve risk estimation and address prophylaxis indications for travelers. 9 The availability of newer and safer vaccines (ie, new live attenuated vaccine obtained on Vero cells culture, at the moment on phase II testing) may broaden the indications of JE vaccination for tourists, to include all travelers judged as at risk, by means of a thoroughly pretravel interview. 12,13 The authors state that they have no conflicts of interest.