Japanese encephalitis primary prevention
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The control of Japanese encephalitis is based essentially on three interventions: mosquito control, avoiding human exposure to mosquitoes and immunization. Mosquito control has been very difficult to achieve in rural settings and avoidance of exposure is difficult as Culex mosquitoes bite during day time. Immunization is the only effective method for sustainable control. Routine immunization of school-age children is currently in use in Korea, Japan, China, Thailand and Taiwan. The introduction of the JE vaccine into the Expanded Program of Immunization has helped curb the disease in countries like Thailand, Vietnam, Sri Lanka and China[1].
Primary Prevention
- Use insect repellent and wear long pants and sleeves
- Sleep in air-conditioned or well-screened rooms or use bednets
- A vaccine against JE virus is available.
Vaccine
Among the currently available vaccines is a formalin-inactivated vaccine derived from mouse brain-grown JEV strain Nakayama[2][3] , which still is produced by manufacturers in Korea, Thailand and Vietnam. The vaccine is relatively expensive, requires three doses on days 0, 7 and 30, followed by a booster at 1 year and thereafter at intervals of 3 years. The vaccine can often generate neurological adverse reactions. In addition to local and systemic side effects, individual cases of generalized urticaria and angioedema were reported in about 1 case per 1000 vaccinees after vaccination of travelers from western countries.
Another formalin-inactivated JE vaccine is prepared in China using the JEV P3 strain propagated in primary hamster kidney-cell cultures. The vaccine appears to be more immunogenic than that based on the Nakayama strain and can be integrated into the routine childhood immunization schedule but is not distributed outside of China. It is now largely being replaced by the live attenuated vaccine.
Several attempts are in progress to prepare inactivated JEV vaccines starting from virus grown in controlled cell line cultures. Several manufacturers are developing Vero cell-derived purified inactivated JE vaccines, either using the virulent Nakayama strain, as done by Japanese manufacturers, or starting from the attenuated SA14-14-2 JEV strain, as done by the Austrian biotech company Intercell. Phase I and Phase II clinical trials have shown that the vaccine was safe and immunogenic[4] and a Phase III trial was recently completed[5] . The Japanese vaccine candidates have been recently licensed in Japan, while the Intercell vaccine, Ixiaro, was licensed by the US FDA for adults. A two-dose rapid immunization schedule has been worked up for administration to travelers. Most people immunized with the Intercell vaccine developed protective neutralizing antibody levels that lasted for at least one year[6][7] and the vaccine was well tolerated [83] [84] . The company pursues a separate clinical development for pediatric indication for endemic countries in a joint venture with Biological E, an Indian manufacturer. A large pediatric Phase IIb trial is currently taking place in endemic settings in India. Similarly, a Vero cell inactivated vaccine is now being produced in China by the Beijing Institute of Biological Products.
Infection with Japanese encephalitis virus confers life-long immunity. All current vaccines are based on the genotype III virus. A formalin-inactivated mouse-brain derived vaccine was first produced in Japan in the 1930s and was validated for use in Taiwan in the 1960s and in Thailand in the 1980s. The widespread use of vaccine and urbanisation has led to control of the disease in Japan, Korea, Taiwan and Singapore. The high cost of the vaccine, which is grown in live mice, means that poorer countries have not been able to afford to give it as part of a routine immunization programme.
In the UK, the two vaccines used (but which are unlicensed) are JE-Vax® and Green Cross. Three doses are given at 0, 7–14 and 28–30 days. The dose is 1ml for children and adult, and 0.5ml for infants under 36 months of age.
The most common adverse effects are redness and pain at the injection site. Uncommonly, an urticarial reaction can develop about four days after injection. Because the vaccine is produced from mouse brain, there is a risk of autoimmune neurological complications of around 1 per million vaccinations.
Neutralising antibody persists in the circulation for at least two to three years, and perhaps longer.[8][9] The total duration of protection is unknown, but because there is no firm evidence for protection beyond three years, boosters are recommended every two years for people who remain at risk.
- U.S. Expatriates: Japanese encephalitis vaccine is recommended for persons who plan to reside in areas where Japanese encephalitis is endemic or epidemic (residence during a transmission season). Risk for acquiring Japanese encephalitis is highly variable within the endemic regions. The incidence of Japanese encephalitis in the location of intended residence, the conditions of housing, nature of activities, and the possibility of unexpected travel to high-risk areas are factors that should be considered in the decision to seek vaccination.
- Travelers: JE vaccine is recommended for travelers who plan to spend at least 1 month in endemic areas during the JE virus transmission season. Vaccine should also be considered for the following:
- Short-term (less than 1 month) travelers to endemic areas during the transmission season, if they plan to travel outside an urban area and their activities will increase the risk of exposure. Higher-risk activities include participating in extensive outdoor activities (such as camping, hiking, trekking, biking, fishing, hunting, or farming) and staying in accommodations without air conditioning, screens, or bed nets.
- Travelers to an area with an ongoing outbreak.
- Travelers to endemic areas who are uncertain of specific travel destinations, activities, or duration.
References
- ↑ Tauber E, Dewasthaly S (2008). "Japanese encephalitis vaccines--needs, flaws and achievements". Biol Chem. 389 (5): 547–50. PMID 18953721.
- ↑ Chambers TJ, Tsai TF, Pervikov Y, Monath TP (1997). "Vaccine development against dengue and Japanese encephalitis: report of a World Health Organization meeting". Vaccine. 15 (14): 1494–502. PMID 9330458.
- ↑ Monath TP (2002). "Japanese encephalitis vaccines: current vaccines and future prospects". Curr Top Microbiol Immunol. 267: 105–38. PMID 12082985.
- ↑ Sugawara K, Nishiyama K, Ishikawa Y, Abe M, Sonoda K, Komatsu K; et al. (2002). "Development of Vero cell-derived inactivated Japanese encephalitis vaccine". Biologicals. 30 (4): 303–14. PMID 12421588.
- ↑ Schuller E, Klade CS, Wölfl G, Kaltenböck A, Dewasthaly S, Tauber E (2009). "Comparison of a single, high-dose vaccination regimen to the standard regimen for the investigational Japanese encephalitis vaccine, IC51: a randomized, observer-blind, controlled Phase 3 study". Vaccine. 27 (15): 2188–93. doi:10.1016/j.vaccine.2008.12.062. PMID 19200452.
- ↑ Lyons A, Kanesa-thasan N, Kuschner RA, Eckels KH, Putnak R, Sun W; et al. (2007). "A Phase 2 study of a purified, inactivated virus vaccine to prevent Japanese encephalitis". Vaccine. 25 (17): 3445–53. doi:10.1016/j.vaccine.2006.12.046. PMID 17241714.
- ↑ Schuller E, Jilma B, Voicu V, Golor G, Kollaritsch H, Kaltenböck A; et al. (2008). "Long-term immunogenicity of the new Vero cell-derived, inactivated Japanese encephalitis virus vaccine IC51 Six and 12 month results of a multicenter follow-up phase 3 study". Vaccine. 26 (34): 4382–6. doi:10.1016/j.vaccine.2008.05.081. PMID 18599165.
- ↑ Gambel JM, DeFraites R, Hoke C; et al. (1995). "Japanese encephalitis vaccine: persistence of antibody up to 3 years after a three-dose primary series (letter)". J Infect Dis. 171: 1074.
- ↑ Kurane I, Takashi T (2000). "Immunogenicity and protective efficacy of the current inactivated Japanese encephalitis vaccine against different Japanese encephalitis virus strains". Vaccine. 18 Suppl: 33&ndash, 5.