Japanese encephalitis vaccine for travelers: risk-benefit reconsidered

Résumé fourni par la source

A number of years ago, an article on the risk of Japanese encephalitis (JE) in travelers by Shlim and Solomon quoted a popular movie at the time, ‘Chicken Run’, describing in a jocular fashion the one in a million chance of the imprisoned chickens mounting a successful escape. Rather than be deterred by this low probability, one of the protagonist chickens instead exhibited hope saying, ‘Then there is still a chance!’.1 While past estimates suggest that the risk for a traveler to Asia of contracting JE was one in a million,2 today there remains a risk of exposure to the JE virus and symptomatic disease, and the incidence of JE may be on the rise throughout Asia. Consequently, it is imperative that travel medicine practitioners provide risk prevention and awareness advice to those travelers at greatest risk. What we have learned about JE since the publication of this article should change the minds of the travel medicine community, and should also serve as a lesson to the traveling public. Let’s start with the oft quoted figure of risk being <1 case per million travelers.2 Is this for all travelers to Asia, all travelers to at-risk or endemic areas for JE or a calculation using some other numerator and denominator? Fact is, these data are >10 years old, travel to Asia has markedly increased and because underreporting of JE may occur, we do not know precisely how many individuals travel to JE virus endemic regions, nor do we know how many actually acquire JE virus infection during travel. Consequently, we cannot be certain that we have accurate numerator and denominator data.3 In endemic areas of Asia, it has been estimated that ~70 000 JE cases occur annually, despite implementation of vaccination programs in some of these endemic areas.3 Thus, the 70 000 incidence likely underestimates the true risk of disease for the non-immune traveler as returning travelers with signs and symptoms compatible with JE may be misdiagnosed as suffering from other viral illnesses, even if severe, and therefore go largely unreported to public health authorities. A combination of low levels of clinical suspicion, especially in the face of a non-specific febrile illness, as well as infrequent use of reliable laboratory testing even if illness is suspected, makes the diagnosis difficult. Over 50 years ago in a seminal work on JE infections, Scott Halstead cited the risk of clinical disease occurrence as being 1 in 25 if a naïve host (a traveler) is bitten by an infected mosquito in an endemic area.4 Though the epidemiology of infection is dynamic, this information should be considered in the pre-travel risk assessment. Most individuals with JE infection are asymptomatic or have only mild flu-like symptoms (fever, headache), but ~1 in 250 infections result in more severe systemic illness characterized by high fever, neurologic symptoms and ultimately death.5 In reviewing reports from the GeoSentinel Surveillance Network database in ill-returning travelers from JE endemic areas, there are a large number of cases of ‘viral syndromes’ without a definitive diagnosis, with many lasting >3 weeks, and 48 cases of acute encephalitis reported without an etiologic diagnosis between 2009 and 2018. Many travelers returning from trips are seen by emergency doctors, primary care providers, hospitalists and others where JE may not be in their differential diagnosis. In the risk assessment, we also should consider whether JE virus could, like other arboviruses, represent a serious threat during pregnancy, both to the mother and fetus. As data accumulate about the sexual transmission of Zika virus, acquisition during pregnancy, and the disease’s sequelae, as well as problems associated with chikungunya infection during pregnancy, we wonder whether there are similar risks associated with JE virus. In fact, there is evidence that JE virus is found in aborted fetal tissue.6 Blood and blood product transfusion during viremia may also carry risk. What is also missing from current recommendations is an appreciation of the changing epidemiology of JE infection.7 In the absence of reliable incidence data, sero-epidemiologic methods are used to measure exposure and make inferences about endemicity. A recent study documented serologic evidence of JE virus in children living in urban and peri-urban areas of Indonesia, Malaysia, the Philippines and Vietnam.8 While there is a possibility that these children were infected in a rural area before moving to an urban location, it is unlikely that all participants would have had rural exposures. Breeding grounds for mosquitos that transmit JE virus are not only areas of rice culture and pig farming rural areas, but also include areas close to major cities, and often in the ‘backyards’ of residential and commercial areas. Peri-urban transmission occurs and travelers need to be aware that in some Asian cities just a few meters outside their hotel are vague city boundaries where one may encounter rice paddies or standing water that may serve as breeding sites for mosquitoes. Mosquito surveillance is not adequate and results may be misleading.9 Defining time spent in rural activities as the highest risk may be inaccurate as rapid changes in urbanization and increased development of pig farming to meet food demands are occurring in places that have never before experienced JE transmission.10 We also know that travelers who report that they will only be traveling to urban areas are either unaware of the true surroundings of their upcoming trip or frequently decide, while traveling, to take side trips into more rural environments. What then are the obstacles to JE vaccination in the travel clinic? When the JE vaccine was first introduced in the United States in January 1993, the vaccine was recommended in rare instances, not only because the disease was presumed rare, but because the available mouse-brain–derived vaccine was believed to carry a risk for significant adverse events such as high fever, vomiting and urticaria. This resulted in its indication for those traveling >30 days during the transmission season in an endemic area.11 In virtually every other case of vaccine-preventable disease, language that equates length of stay with risk has been eliminated, such as typhoid and rabies, because of the realization that exposure may occur on any day of travel, including on day 1. Now that the original mouse-brain–derived vaccine has been replaced by the current inactivated (Vero cell culture derived) vaccine that has a lower probability of severe local adverse events,12 and the original cumbersome vaccination schedule was superseded by a recently approved more convenient schedule (days 0 and 7), providers should be re-thinking JE vaccination and allotting ample time during the consultation to discuss the potential risk with the traveler. Although cost remains a consideration, in a disease where the case-fatality rate among those with encephalitis is as high as 30%, and 30–50% of those who survive suffer serious neurologic sequelae, the vaccine may be indicated for a greater number of travelers. Careful consideration needs to be made for vaccinating pregnant women as no studies have been done in this group. The Centers for Disease Control and Prevention states that administration of this vaccine to pregnant women usually should be deferred. However, pregnant women who must travel to an area where risk for infection is high should be vaccinated when the theoretical risk of immunization is outweighed by the risk of infection.13 We believe the time has come for a thoughtful and accurate discussion of the risk of this vaccine-preventable disease with all travelers to all Asian areas where JE is endemic and JE-infected reservoir hosts (wild birds, e.g. egrets, herons; and pigs) are likely to be present in the local environment. To address some of these issues, the US Advisory Committee on Immunization Practices (ACIP) recently updated its policy recommendation for US t

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.