Japanese encephalitis primary prevention: Difference between revisions

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__NOTOC__
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{{Japanese encephalitis}}
{{Japanese encephalitis}}
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{{CMG}}; {{AE}} {{AG}}


==Overview==
==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<ref name="pmid18953721">{{cite journal| author=Tauber E, Dewasthaly S| title=Japanese encephalitis vaccines--needs, flaws and achievements. | journal=Biol Chem | year= 2008 | volume= 389 | issue= 5 | pages= 547-50 | pmid=18953721 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18953721  }} </ref>.
Effective measures for the primary prevention of Japanese encephalitis include mosquito population control, avoidance of mosquitos, and [[immunization]]. Mosquito control has been difficult to achieve in rural settings. Avoidance of exposure is also difficult, as ''Culex'' mosquitos are active during day hours. 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 Japanese encephalitis vaccine into the [[Expanded Program on Immunization (Philippines)|Expanded Program of Immunization]] has helped curb the disease in countries like Thailand, Vietnam, Sri Lanka, and China.<ref name="pmid18953721">{{cite journal| author=Tauber E, Dewasthaly S| title=Japanese encephalitis vaccines--needs, flaws and achievements. | journal=Biol Chem | year= 2008 | volume= 389 | issue= 5 | pages= 547-50 | pmid=18953721 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18953721  }} </ref>


==Primary Prevention==
==Primary Prevention==
*Use insect repellent and wear long pants and sleeves
Primary prevention strategies for Japanese encephalitis include:
*Sleep in air-conditioned or well-screened rooms or use bednets
*Removal of [[standing water]]
*A [[vaccine]] against JE [[virus]] is available.
*Screens on doors and windows
*When outdoors, wearing:
**Insect repellent containing [[DEET]]
**Long sleeves, pants; tucking in pants into high socks
*[[Vaccination]]


===Vaccine===
===Vaccine===
Among the currently available [[vaccines]] is a [[formalin]]-inactivated vaccine derived from mouse brain-grown JEV [[strain]] Nakayama<ref name="pmid9330458">{{cite journal| author=Chambers TJ, Tsai TF, Pervikov Y, Monath TP| title=Vaccine development against dengue and Japanese encephalitis: report of a World Health Organization meeting. | journal=Vaccine | year= 1997 | volume= 15 | issue= 14 | pages= 1494-502 | pmid=9330458 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9330458  }} </ref><ref name="pmid12082985">{{cite journal| author=Monath TP| title=Japanese encephalitis vaccines: current vaccines and future prospects. | journal=Curr Top Microbiol Immunol | year= 2002 | volume= 267 | issue=  | pages= 105-38 | pmid=12082985 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12082985  }} </ref> , 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 drug reaction|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.
[[Infection]] with Japanese encephalitis virus confers life-long [[immunity]]. All current vaccines are based on the [[genotype]] III virus. Among the currently available [[vaccines]] is a [[formalin]]-inactivated vaccine derived from mouse brain-grown Japanese encephalitis virus [[strain]] Nakayama, which still is produced by manufacturers in Korea, Thailand, and Vietnam.<ref name="pmid9330458">{{cite journal| author=Chambers TJ, Tsai TF, Pervikov Y, Monath TP| title=Vaccine development against dengue and Japanese encephalitis: report of a World Health Organization meeting. | journal=Vaccine | year= 1997 | volume= 15 | issue= 14 | pages= 1494-502 | pmid=9330458 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9330458  }} </ref><ref name="pmid12082985">{{cite journal| author=Monath TP| title=Japanese encephalitis vaccines: current vaccines and future prospects. | journal=Curr Top Microbiol Immunol | year= 2002 | volume= 267 | issue=  | pages= 105-38 | pmid=12082985 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12082985  }} </ref> It 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 urbanization 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 struggled to administer it as part of a routine [[immunization]] program. The vaccine requires three doses on days 0, 7, and 30, a booster at 1 year, and thereafter at intervals of 3 years. The vaccine can often generate [[neurological]] [[adverse drug reaction|adverse reactions]]. In addition to local and [[systemic]] [[side effects]], individual cases of generalized [[urticaria]] and [[angioedema]] were reported in about 1 per 1000 vaccinees after [[vaccination]] of travelers from western countries.
 
====Inactivated Vaccines====
====Inactivated Vaccines====
Another [[formalin]]-inactivated JE vaccine is prepared in China using the JEV P3 [[strain (biology)|strain]] propagated in primary hamster [[kidney]] [[cell culture]]s. The vaccine appears to be more [[immunogenicity|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 virus|attenuated]] vaccine.
Another [[formalin]]-inactivated Japanese encephalitis vaccine is prepared in China using the Japanese encephalitis virus-P3 [[strain (biology)|strain]] propagated in primary hamster [[kidney]] [[cell culture]]s. The vaccine appears to be more [[immunogenicity|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 virus|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 trial|Phase I]] and [[Phase II clinical trial]]s have shown that the vaccine was safe and [[immunogenicity|immunogenic]]<ref name="pmid12421588">{{cite journal| author=Sugawara K, Nishiyama K, Ishikawa Y, Abe M, Sonoda K, Komatsu K et al.| title=Development of Vero cell-derived inactivated Japanese encephalitis vaccine. | journal=Biologicals | year= 2002 | volume= 30 | issue= 4 | pages= 303-14 | pmid=12421588 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12421588  }} </ref> and a [[Phase III trials|Phase III trial]] was recently completed<ref name="pmid19200452">{{cite journal| author=Schuller E, Klade CS, Wölfl G, Kaltenböck A, Dewasthaly S, Tauber E| title=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. | journal=Vaccine | year= 2009 | volume= 27 | issue= 15 | pages= 2188-93 | pmid=19200452 | doi=10.1016/j.vaccine.2008.12.062 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19200452  }} </ref> . 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 [[neutralisation|neutralizing]] [[antibody]] levels that lasted for at least one year<ref name="pmid17241714">{{cite journal| author=Lyons A, Kanesa-thasan N, Kuschner RA, Eckels KH, Putnak R, Sun W et al.| title=A Phase 2 study of a purified, inactivated virus vaccine to prevent Japanese encephalitis. | journal=Vaccine | year= 2007 | volume= 25 | issue= 17 | pages= 3445-53 | pmid=17241714 | doi=10.1016/j.vaccine.2006.12.046 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17241714 }} </ref><ref name="pmid18599165">{{cite journal| author=Schuller E, Jilma B, Voicu V, Golor G, Kollaritsch H, Kaltenböck A et al.| title=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. | journal=Vaccine | year= 2008 | volume= 26 | issue= 34 | pages= 4382-6 | pmid=18599165 | doi=10.1016/j.vaccine.2008.05.081 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18599165 }} </ref> and the vaccine was well tolerated <ref name="pmid18061060">{{cite journal| author=Tauber E, Kollaritsch H, Korinek M, Rendi-Wagner P, Jilma B, Firbas C et al.| title=Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial. | journal=Lancet | year= 2007 | volume= 370 | issue= 9602 | pages= 1847-53 | pmid=18061060 | doi=10.1016/S0140-6736(07)61780-2 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18061060  }} </ref> <ref name="pmid18588481">{{cite journal| author=Tauber E, Kollaritsch H, von Sonnenburg F, Lademann M, Jilma B, Firbas C et al.| title=Randomized, double-blind, placebo-controlled phase 3 trial of the safety and tolerability of IC51, an inactivated Japanese encephalitis vaccine. | journal=J Infect Dis | year= 2008 | volume= 198 | issue= 4 | pages= 493-9 | pmid=18588481 | doi=10.1086/590116 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18588481  }} </ref>. 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.
Several attempts are in progress to prepare inactivated Japanese encephalitis virus vaccines starting from virus grown in controlled cell line cultures. Several manufacturers are developing [[Vero cell]]-derived purified inactivated Japanese encephalitis vaccines, either using the [[virulent]] Nakayama strain, or starting from the attenuated SA14-14-2 JEV strain. [[Phase I trial|Phase I]] and [[Phase II clinical trial]]s have shown that the vaccine was safe and [[immunogenicity|immunogenic]]; [[Phase III trials]] were recently completed.<ref name="pmid12421588">{{cite journal| author=Sugawara K, Nishiyama K, Ishikawa Y, Abe M, Sonoda K, Komatsu K et al.| title=Development of Vero cell-derived inactivated Japanese encephalitis vaccine. | journal=Biologicals | year= 2002 | volume= 30 | issue= 4 | pages= 303-14 | pmid=12421588 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12421588  }} </ref><ref name="pmid19200452">{{cite journal| author=Schuller E, Klade CS, Wölfl G, Kaltenböck A, Dewasthaly S, Tauber E| title=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. | journal=Vaccine | year= 2009 | volume= 27 | issue= 15 | pages= 2188-93 | pmid=19200452 | doi=10.1016/j.vaccine.2008.12.062 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19200452  }} </ref> The most common [[adverse effect (medicine)|adverse effects]] are redness and [[pain]] at the [[injection]] siteUncommonly, an [[urticaria]]l reaction can develop about four days after injectionBecause the vaccine is produced from mouse brain, there is a risk of [[autoimmune]] [[neurological]] [[complication]]s of around 1 per million [[vaccination]]s.


====Live Attenuated Vaccines====
====Live Attenuated Vaccines====
The live attenuated JE vaccine strain, SA14-14-2, which was obtained after 11 passages in weaning mice followed by 100 passages in primary hamster kidney cells, has been developed and used in China since 1988. The vaccine, which is produced by the Chengdu Institute of Biological Products in China, was licensed in recent years in several Asian countries and was extensively used from 2006 to 2008 in mass [[immunization]] campaigns in India. Although the product is not WHO prequalified at this time, much investment and efforts have been made to bring the production and quality control to international standards. The vaccine is produced on primary hamster kidney cells, [[lyophilized]], and administered to children at one year of age and again at two years, in annual spring campaigns<ref name="pmid1569999">{{cite journal| author=Woods DL| title=Resuscitation of the newborn infant. | journal=Nurs RSA | year= 1992 | volume= 7 | issue= 1 | pages= 21-3, 26 | pmid=1569999 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1569999  }} </ref> . Initial observational studies in southern China involving more than 200,000 children had demonstrated the vaccine safety, [[immunogenicity]] (99-100% [[seroconversion]] rate in nonimmune subjects) and protective [[efficacy]] over 5 years<ref name="pmid12082985">{{cite journal| author=Monath TP| title=Japanese encephalitis vaccines: current vaccines and future prospects. | journal=Curr Top Microbiol Immunol | year= 2002 | volume= 267 | issue=  | pages= 105-38 | pmid=12082985 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12082985  }} </ref>. The short-term effectiveness of a single dose of SA14-2-14 was demonstrated in 2001 in a [[case control study]] on Nepalese children where an [[efficacy]] of 99.3% was reported<ref name="pmid16226615">{{cite journal| author=Ohrr H, Tandan JB, Sohn YM, Shin SH, Pradhan DP, Halstead SB| title=Effect of single dose of SA 14-14-2 vaccine 1 year after immunisation in Nepalese children with Japanese encephalitis: a case-control study. | journal=Lancet | year= 2005 | volume= 366 | issue= 9494 | pages= 1375-8 | pmid=16226615 | doi=10.1016/S0140-6736(05)67567-8 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16226615  }} </ref> . A five year follow-up study found the single-dose efficacy was maintained at 96.2%<ref name="pmid17521781">{{cite journal| author=Tandan JB, Ohrr H, Sohn YM, Yoksan S, Ji M, Nam CM et al.| title=Single dose of SA 14-14-2 vaccine provides long-term protection against Japanese encephalitis: a case-control study in Nepalese children 5 years after immunization. drjbtandan@yahoo.com. | journal=Vaccine | year= 2007 | volume= 25 | issue= 27 | pages= 5041-5 | pmid=17521781 | doi=10.1016/j.vaccine.2007.04.052 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17521781  }} </ref> . Another five-year follow up study showed that neutralizing antibody persistence was close to 90% at 4 years and 64% at 5 years after a single-dose of the vaccine in adult volunteers<ref name="pmid18294743">{{cite journal| author=Sohn YM, Tandan JB, Yoksan S, Ji M, Ohrr H| title=A 5-year follow-up of antibody response in children vaccinated with single dose of live attenuated SA14-14-2 Japanese encephalitis vaccine: immunogenicity and anamnestic responses. | journal=Vaccine | year= 2008 | volume= 26 | issue= 13 | pages= 1638-43 | pmid=18294743 | doi=10.1016/j.vaccine.2008.01.021 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18294743  }} </ref>. Recent studies in the Philippines have demonstrated the safety and [[efficacy]] of the vaccine even when co-administered with [[measles]] vaccine at 9 months of age. Similar studies in Sri Lanka and Indonesia will help confirm these findings in other Asian settings.
The live attenuated Japanese encephalitis vaccine strain, SA14-14-2, which was obtained after 11 passages in weaning mice followed by 100 passages in primary hamster kidney cells, has been developed and used in China since 1988. The vaccine, which is produced by the Chengdu Institute of Biological Products in China, was licensed in recent years in several Asian countries and was extensively used from 2006 to 2008 in mass [[immunization]] campaigns in India. The vaccine is administered to children at one year of age and again at two years, in annual spring campaigns.<ref name="pmid1569999">{{cite journal| author=Woods DL| title=Resuscitation of the newborn infant. | journal=Nurs RSA | year= 1992 | volume= 7 | issue= 1 | pages= 21-3, 26 | pmid=1569999 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1569999  }} </ref> Initial observational studies in southern China involving more than 200,000 children had demonstrated the vaccine safety, [[immunogenicity]] (99-100% [[seroconversion]] rate in nonimmune subjects), and protective [[efficacy]] over 5 years.<ref name="pmid12082985">{{cite journal| author=Monath TP| title=Japanese encephalitis vaccines: current vaccines and future prospects. | journal=Curr Top Microbiol Immunol | year= 2002 | volume= 267 | issue=  | pages= 105-38 | pmid=12082985 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12082985  }} </ref> The short-term effectiveness of a single dose of SA14-2-14 was demonstrated in 2001 in a [[case control study]] on Nepalese children, where an [[efficacy]] of 99.3% was reported.<ref name="pmid16226615">{{cite journal| author=Ohrr H, Tandan JB, Sohn YM, Shin SH, Pradhan DP, Halstead SB| title=Effect of single dose of SA 14-14-2 vaccine 1 year after immunisation in Nepalese children with Japanese encephalitis: a case-control study. | journal=Lancet | year= 2005 | volume= 366 | issue= 9494 | pages= 1375-8 | pmid=16226615 | doi=10.1016/S0140-6736(05)67567-8 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16226615  }} </ref> A five year follow-up study found the single-dose efficacy was maintained at 96.2%.<ref name="pmid17521781">{{cite journal| author=Tandan JB, Ohrr H, Sohn YM, Yoksan S, Ji M, Nam CM et al.| title=Single dose of SA 14-14-2 vaccine provides long-term protection against Japanese encephalitis: a case-control study in Nepalese children 5 years after immunization. drjbtandan@yahoo.com. | journal=Vaccine | year= 2007 | volume= 25 | issue= 27 | pages= 5041-5 | pmid=17521781 | doi=10.1016/j.vaccine.2007.04.052 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17521781  }} </ref> Another five-year follow up study showed that neutralizing antibody persistence was close to 90% at 4 years and 64% at 5 years after a single-dose of the vaccine in adult volunteers.<ref name="pmid18294743">{{cite journal| author=Sohn YM, Tandan JB, Yoksan S, Ji M, Ohrr H| title=A 5-year follow-up of antibody response in children vaccinated with single dose of live attenuated SA14-14-2 Japanese encephalitis vaccine: immunogenicity and anamnestic responses. | journal=Vaccine | year= 2008 | volume= 26 | issue= 13 | pages= 1638-43 | pmid=18294743 | doi=10.1016/j.vaccine.2008.01.021 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18294743  }} </ref> Recent studies in the Philippines have demonstrated the safety and [[efficacy]] of the vaccine even when co-administered with [[measles]] vaccine at 9 months of age.  


Currently, more than 30 million doses of the live SA14-2-14 vaccine are distributed annually in southern and western China and exported to Nepal, India and Korea. Starting in May 2006, the SA14-2-14 live attenuated vaccine was used in India to vaccinate 9.3 million children in 11 districts scattered among 4 states where JE was considered as highly [[endemic]]. More than 500 adverse events were reported during the campaign, including 66 severe AE, of which 22 were fatal. These cases were reviewed by an expert committee which concluded that none of the deaths were attributable to the vaccine. The severe [[Adverse Drug Event|adverse events]] and critical press coverage nevertheless had a deep negative impact on vaccine acceptance in the rest of the country, highlighting the need for proper safety monitoring and case investigations.
Currently, more than 30 million doses of the live SA14-2-14 vaccine are distributed annually in southern and western China, and are exported to Nepal, India, and Korea. Starting in May 2006, the SA14-2-14 live attenuated vaccine was used in India to vaccinate 9.3 million children in 11 districts scattered among 4 states where Japanese encephalitis was considered as highly [[endemic]]. More than 500 adverse events were reported during the campaign, including 66 severe adverse events, of which 22 were fatal. These cases were reviewed by an expert committee which concluded that none of the deaths were attributable to the vaccine. The severe [[Adverse Drug Event|adverse events]] and critical press coverage nevertheless had a deep negative impact on vaccine acceptance in the rest of the country, highlighting the need for proper safety monitoring and case investigations.


====Chimeric Vaccines====
====Chimeric Vaccines====
A promising approach for a future JE vaccine has been the construction of a YF-JE [[chimera (genetics)|chimera]] based on the attenuated 17D YF virus [[genome]], in which the YFV sequences encoding viral [[structural classification of proteins|structural proteins]] prM and E were replaced by the corresponding prM and E sequences from JEV strain SA14-2-14. The resulting YF-JE chimeric virus, ChimeriVax-JETM, developed by Acambis and now licensed to Sanofi Pasteur, was grown on Vero cells and shown to elicit JEV neutralizing [[antibodies]] as well as protection against [[nasal]] and [[cerebrum|intracerebral]] [[virus]] challenge in [[Rhesus Monkeys|rhesus monkeys]]<ref name="pmid112032">{{cite journal| author=Wienker TF, von Reutern GM, Ropers HH| title=Progressive myoclonus epilepsy. A variant with probable X-linked inheritance. | journal=Hum Genet | year= 1979 | volume= 49 | issue= 1 | pages= 83-9 | pmid=112032 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=112032  }} </ref> <ref name="pmid10217584">{{cite journal| author=Monath TP, Soike K, Levenbook I, Zhang ZX, Arroyo J, Delagrave S et al.| title=Recombinant, chimaeric live, attenuated vaccine (ChimeriVax) incorporating the envelope genes of Japanese encephalitis (SA14-14-2) virus and the capsid and nonstructural genes of yellow fever (17D) virus is safe, immunogenic and protective in non-human primates. | journal=Vaccine | year= 1999 | volume= 17 | issue= 15-16 | pages= 1869-82 | pmid=10217584 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10217584  }} </ref><ref name="pmid15315852">{{cite journal| author=Beasley DW, Li L, Suderman MT, Guirakhoo F, Trent DW, Monath TP et al.| title=Protection against Japanese encephalitis virus strains representing four genotypes by passive transfer of sera raised against ChimeriVax-JE experimental vaccine. | journal=Vaccine | year= 2004 | volume= 22 | issue= 27-28 | pages= 3722-6 | pmid=15315852 | doi=10.1016/j.vaccine.2004.03.027 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15315852  }} </ref>. The vaccine was tested in human adult volunteers in the USA, showing good safety and [[immunogenicity]], with 94% of the vaccinees in the [[phase II clinical trial|Phase II trial]] developing protective neutralizing antibody levels after a single dose<ref name="pmid14551893">{{cite journal| author=Monath TP, Guirakhoo F, Nichols R, Yoksan S, Schrader R, Murphy C et al.| title=Chimeric live, attenuated vaccine against Japanese encephalitis (ChimeriVax-JE): phase 2 clinical trials for safety and immunogenicity, effect of vaccine dose and schedule, and memory response to challenge with inactivated Japanese encephalitis antigen. | journal=J Infect Dis | year= 2003 | volume= 188 | issue= 8 | pages= 1213-30 | pmid=14551893 | doi=10.1086/378356 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14551893  }} </ref> . The chimeric virus was shown not to replicate in mosquitoes which were fed the Chimerivax-JE vaccine<ref name="pmid17038690">{{cite journal| author=Reid M, Mackenzie D, Baron A, Lehmann N, Lowry K, Aaskov J et al.| title=Experimental infection of Culex annulirostris, Culex gelidus, and Aedes vigilax with a yellow fever/Japanese encephalitis virus vaccine chimera (ChimeriVax-JE). | journal=Am J Trop Med Hyg | year= 2006 | volume= 75 | issue= 4 | pages= 659-63 | pmid=17038690 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17038690  }} </ref>, a further proof of attenuation. The vaccine has been undergoing [[Phase III clinical trial]]s in the USA and Australia for adult indication, whereas a parallel [[pediatric]] development program has been launched in Thailand by SanofiPasteur.
A promising approach for a future Japanese encephalitis vaccine has been the construction of a YF-JE [[chimera (genetics)|chimera]] based on the attenuated 17D YF virus [[genome]], in which the YFV sequences encoding viral [[Structural Classification of Proteins|structural proteins]] prM and E were replaced by the corresponding prM and E sequences from JEV strain SA14-2-14. The vaccine was tested in human adult volunteers in the United States, demonstrating good safety and [[immunogenicity]], with 94% of the vaccinees in the [[phase II clinical trial|Phase II trial]] developing protective neutralizing antibody levels after a single dose.<ref name="pmid14551893">{{cite journal| author=Monath TP, Guirakhoo F, Nichols R, Yoksan S, Schrader R, Murphy C et al.| title=Chimeric live, attenuated vaccine against Japanese encephalitis (ChimeriVax-JE): phase 2 clinical trials for safety and immunogenicity, effect of vaccine dose and schedule, and memory response to challenge with inactivated Japanese encephalitis antigen. | journal=J Infect Dis | year= 2003 | volume= 188 | issue= 8 | pages= 1213-30 | pmid=14551893 | doi=10.1086/378356 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14551893  }} </ref> The chimeric virus was shown not to replicate in mosquitos which were fed the Chimerivax-JE vaccine, a further proof of attenuation.<ref name="pmid17038690">{{cite journal| author=Reid M, Mackenzie D, Baron A, Lehmann N, Lowry K, Aaskov J et al.| title=Experimental infection of Culex annulirostris, Culex gelidus, and Aedes vigilax with a yellow fever/Japanese encephalitis virus vaccine chimera (ChimeriVax-JE). | journal=Am J Trop Med Hyg | year= 2006 | volume= 75 | issue= 4 | pages= 659-63 | pmid=17038690 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17038690  }} </ref>


====Live Recombinant JEV Vaccines====
====Live Recombinant JEV Vaccines====
[[Viral replication|Replication]]-defective canarypox (ALVAC) and the highly attenuated [[vaccinia]] virus strain NYVAC were used as [[vector]]s to express the pr-M, E, NS1 and NS2a [[gene]] from JEV. The vaccine candidates were found to be well tolerated but their [[immunogenicity]] was too weak, especially in non-vaccinia immune volunteers, to warrant further development<ref name="pmid11027812">{{cite journal| author=Kanesa-thasan N, Smucny JJ, Hoke CH, Marks DH, Konishi E, Kurane I et al.| title=Safety and immunogenicity of NYVAC-JEV and ALVAC-JEV attenuated recombinant Japanese encephalitis virus--poxvirus vaccines in vaccinia-nonimmune and vaccinia-immune humans. | journal=Vaccine | year= 2000 | volume= 19 | issue= 4-5 | pages= 483-91 | pmid=11027812 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11027812  }} </ref>.
[[Viral replication|Replication]]-defective canarypox (ALVAC) and the highly attenuated [[vaccinia]] virus strain NYVAC were used as [[vector]]s to express the pr-M, E, NS1 and NS2a [[gene]] from Japanese encephalitis virus. The vaccine candidates were found to be well tolerated but their [[immunogenicity]] was too weak, especially in non-vaccinia immune volunteers, to warrant further development.<ref name="pmid11027812">{{cite journal| author=Kanesa-thasan N, Smucny JJ, Hoke CH, Marks DH, Konishi E, Kurane I et al.| title=Safety and immunogenicity of NYVAC-JEV and ALVAC-JEV attenuated recombinant Japanese encephalitis virus--poxvirus vaccines in vaccinia-nonimmune and vaccinia-immune humans. | journal=Vaccine | year= 2000 | volume= 19 | issue= 4-5 | pages= 483-91 | pmid=11027812 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11027812  }} </ref>


[[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.
====Vaccination in Population at Risk====
[[Neutralisation|Neutralizing]] [[antibody]] persists in the [[circulation]] for at least two to three years, and perhaps longer.<ref>{{cite journal | author=Gambel JM, DeFraites R, Hoke C, ''et al.'' | year=1995 | title=Japanese encephalitis vaccine: persistence of antibody up to 3 years after a three-dose primary series (letter) | journal=J Infect Dis | volume=171 | pages=1074 }}</ref><ref>{{cite journal | author=Kurane I, Takashi T | year=2000 | title=Immunogenicity and protective efficacy of the current inactivated Japanese encephalitis vaccine against different Japanese encephalitis virus strains | journal=Vaccine | volume=18 Suppl | pages=33&ndash;5 }}</ref> 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.


In the UK, the two vaccines used (but which are unlicensed) are JE-Vax&reg; and Green Cross.  Three [[dose]]s are given at 0, 7&ndash;14 and 28&ndash;30 days. The dose is 1ml for children and adult, and 0.5ml for [[infant]]s under 36 months of age.
For US 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.


The most common [[adverse effect (medicine)|adverse effects]] are redness and [[pain]] at the [[injection]] site.  Uncommonly, an [[urticaria]]l reaction can develop about four days after injection.  Because the vaccine is produced from mouse brain, there is a risk of [[autoimmune]] [[neurological]] [[complication]]s of around 1 per million vaccinations.
For travelers, Japanese encephalitis is recommended for those who plan to spend at least 1 month in endemic areas during the Japanese encephalitis virus [[transmission]] season, or if high-risk activities are being performed during shorter periods of travel.  


[[Neutralisation|Neutralising]] [[antibody]] persists in the [[circulation]] for at least two to three years, and perhaps longer.<ref>{{cite journal | author=Gambel JM, DeFraites R, Hoke C, ''et al.'' | year=1995 | title=Japanese encephalitis vaccine: persistence of antibody up to 3 years after a three-dose primary series (letter) | journal=J Infect Dis | volume=171 | pages=1074 }}</ref><ref>{{cite journal | author=Kurane I, Takashi T | year=2000 | title=Immunogenicity and protective efficacy of the current inactivated Japanese encephalitis vaccine against different Japanese encephalitis virus strains | journal=Vaccine | volume=18 Suppl | pages=33&ndash;5 }}</ref>  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.
==Risk for travellers==
The risk of japanese encephalitis is very low for most travellers to Asia, particularly for short-term visitors to urban areas. However, the risk varies according to season, destination, duration of travel and activities.
*Vaccination is recommended for travellers with extensive outdoor exposure (such as camping, hiking and working) during the transmission season, particularly in endemic countries or areas where farming involves flooding irrigation.
*Prevention is by avoidance of mosquito bites and by vaccination.
==Vaccine==
Inactivated Vero cell-derived, live attenuated and live recombinant vaccines are available. Vaccination against japanese encephalitis is recommended for travellers to endemic areas who will have extensive outdoor exposure during the transmission season.
==Summary of vaccine data==
{| class="wikitable"
! colspan="2" |Considerations
|-
| rowspan="4" |Type of vaccine and schedules
|Japanese encephalitis vaccines fall into 3 classes:
|-
|Inactivated Vero cell-derived vaccines:
*It requires 2 intramuscular doses administered 4 weeks apart. The recommended age for the first dose varies.


*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.
*The dose for children aged <3 years is 0.25 ml, and for those aged ≥3 years 0.5 ml.


*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:
*Travellers aged ≥17 years who have received primary immunization more than one year previously may be given a booster dose if continued or repeated exposure to Japanese encephalitis virus is expected.
**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.
|Live attenuated vaccines:
**Travelers to endemic areas who are uncertain of specific travel destinations, activities, or duration.
*In China, the first dose is given subcutaneously at age 8 months, followed by a booster dose at 2 years of age.
 
*In Australia, the first dose is administered to persons aged ≥ 9 months, and no booster is required for persons aged ≥18 years when receiving the primary dose.
 
*In some areas and countries, an additional booster is offered at 6–7 years of age.
|-
|Live recombinant (chimeric) vaccines:
*Primary immunization is with 1 dose given subcutaneously at 9 months of age or older.
 
*A booster dose is recommended 12–24 months later for those <18 years of age. Currently, there is no booster recommendation for adults.
|-
|Adverse reactions
|Occasional mild local or systemic reactions.
|-
|Contraindications and precautions
|
*A hypersensitivity reaction to a previous dose is a contraindication.
 
*In principle, the live attenuated vaccine should not be given to pregnant women unless there is a high risk of exposure to the infection.
|}


==References==
==References==
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[[Category:Neurology]]
 
 
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[[Category:Infectious disease]]
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[[Category:Needs overview]]

Latest revision as of 18:06, 18 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

Overview

Effective measures for the primary prevention of Japanese encephalitis include mosquito population control, avoidance of mosquitos, and immunization. Mosquito control has been difficult to achieve in rural settings. Avoidance of exposure is also difficult, as Culex mosquitos are active during day hours. 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 Japanese encephalitis vaccine into the Expanded Program of Immunization has helped curb the disease in countries like Thailand, Vietnam, Sri Lanka, and China.[1]

Primary Prevention

Primary prevention strategies for Japanese encephalitis include:

  • Removal of standing water
  • Screens on doors and windows
  • When outdoors, wearing:
    • Insect repellent containing DEET
    • Long sleeves, pants; tucking in pants into high socks
  • Vaccination

Vaccine

Infection with Japanese encephalitis virus confers life-long immunity. All current vaccines are based on the genotype III virus. Among the currently available vaccines is a formalin-inactivated vaccine derived from mouse brain-grown Japanese encephalitis virus strain Nakayama, which still is produced by manufacturers in Korea, Thailand, and Vietnam.[2][3] It 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 urbanization 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 struggled to administer it as part of a routine immunization program. The vaccine requires three doses on days 0, 7, and 30, 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 per 1000 vaccinees after vaccination of travelers from western countries.

Inactivated Vaccines

Another formalin-inactivated Japanese encephalitis vaccine is prepared in China using the Japanese encephalitis virus-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 Japanese encephalitis virus vaccines starting from virus grown in controlled cell line cultures. Several manufacturers are developing Vero cell-derived purified inactivated Japanese encephalitis vaccines, either using the virulent Nakayama strain, or starting from the attenuated SA14-14-2 JEV strain. Phase I and Phase II clinical trials have shown that the vaccine was safe and immunogenic; Phase III trials were recently completed.[4][5] 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.

Live Attenuated Vaccines

The live attenuated Japanese encephalitis vaccine strain, SA14-14-2, which was obtained after 11 passages in weaning mice followed by 100 passages in primary hamster kidney cells, has been developed and used in China since 1988. The vaccine, which is produced by the Chengdu Institute of Biological Products in China, was licensed in recent years in several Asian countries and was extensively used from 2006 to 2008 in mass immunization campaigns in India. The vaccine is administered to children at one year of age and again at two years, in annual spring campaigns.[6] Initial observational studies in southern China involving more than 200,000 children had demonstrated the vaccine safety, immunogenicity (99-100% seroconversion rate in nonimmune subjects), and protective efficacy over 5 years.[3] The short-term effectiveness of a single dose of SA14-2-14 was demonstrated in 2001 in a case control study on Nepalese children, where an efficacy of 99.3% was reported.[7] A five year follow-up study found the single-dose efficacy was maintained at 96.2%.[8] Another five-year follow up study showed that neutralizing antibody persistence was close to 90% at 4 years and 64% at 5 years after a single-dose of the vaccine in adult volunteers.[9] Recent studies in the Philippines have demonstrated the safety and efficacy of the vaccine even when co-administered with measles vaccine at 9 months of age.

Currently, more than 30 million doses of the live SA14-2-14 vaccine are distributed annually in southern and western China, and are exported to Nepal, India, and Korea. Starting in May 2006, the SA14-2-14 live attenuated vaccine was used in India to vaccinate 9.3 million children in 11 districts scattered among 4 states where Japanese encephalitis was considered as highly endemic. More than 500 adverse events were reported during the campaign, including 66 severe adverse events, of which 22 were fatal. These cases were reviewed by an expert committee which concluded that none of the deaths were attributable to the vaccine. The severe adverse events and critical press coverage nevertheless had a deep negative impact on vaccine acceptance in the rest of the country, highlighting the need for proper safety monitoring and case investigations.

Chimeric Vaccines

A promising approach for a future Japanese encephalitis vaccine has been the construction of a YF-JE chimera based on the attenuated 17D YF virus genome, in which the YFV sequences encoding viral structural proteins prM and E were replaced by the corresponding prM and E sequences from JEV strain SA14-2-14. The vaccine was tested in human adult volunteers in the United States, demonstrating good safety and immunogenicity, with 94% of the vaccinees in the Phase II trial developing protective neutralizing antibody levels after a single dose.[10] The chimeric virus was shown not to replicate in mosquitos which were fed the Chimerivax-JE vaccine, a further proof of attenuation.[11]

Live Recombinant JEV Vaccines

Replication-defective canarypox (ALVAC) and the highly attenuated vaccinia virus strain NYVAC were used as vectors to express the pr-M, E, NS1 and NS2a gene from Japanese encephalitis virus. The vaccine candidates were found to be well tolerated but their immunogenicity was too weak, especially in non-vaccinia immune volunteers, to warrant further development.[12]

Vaccination in Population at Risk

Neutralizing antibody persists in the circulation for at least two to three years, and perhaps longer.[13][14] 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.

For US 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.

For travelers, Japanese encephalitis is recommended for those who plan to spend at least 1 month in endemic areas during the Japanese encephalitis virus transmission season, or if high-risk activities are being performed during shorter periods of travel.

Risk for travellers

The risk of japanese encephalitis is very low for most travellers to Asia, particularly for short-term visitors to urban areas. However, the risk varies according to season, destination, duration of travel and activities.

  • Vaccination is recommended for travellers with extensive outdoor exposure (such as camping, hiking and working) during the transmission season, particularly in endemic countries or areas where farming involves flooding irrigation.
  • Prevention is by avoidance of mosquito bites and by vaccination.

Vaccine

Inactivated Vero cell-derived, live attenuated and live recombinant vaccines are available. Vaccination against japanese encephalitis is recommended for travellers to endemic areas who will have extensive outdoor exposure during the transmission season.

Summary of vaccine data

Considerations
Type of vaccine and schedules Japanese encephalitis vaccines fall into 3 classes:
Inactivated Vero cell-derived vaccines:
  • It requires 2 intramuscular doses administered 4 weeks apart. The recommended age for the first dose varies.
  • The dose for children aged <3 years is 0.25 ml, and for those aged ≥3 years 0.5 ml.
  • Travellers aged ≥17 years who have received primary immunization more than one year previously may be given a booster dose if continued or repeated exposure to Japanese encephalitis virus is expected.
Live attenuated vaccines:
  • In China, the first dose is given subcutaneously at age 8 months, followed by a booster dose at 2 years of age.
  • In Australia, the first dose is administered to persons aged ≥ 9 months, and no booster is required for persons aged ≥18 years when receiving the primary dose.
  • In some areas and countries, an additional booster is offered at 6–7 years of age.
Live recombinant (chimeric) vaccines:
  • Primary immunization is with 1 dose given subcutaneously at 9 months of age or older.
  • A booster dose is recommended 12–24 months later for those <18 years of age. Currently, there is no booster recommendation for adults.
Adverse reactions Occasional mild local or systemic reactions.
Contraindications and precautions
  • A hypersensitivity reaction to a previous dose is a contraindication.
  • In principle, the live attenuated vaccine should not be given to pregnant women unless there is a high risk of exposure to the infection.

References

  1. Tauber E, Dewasthaly S (2008). "Japanese encephalitis vaccines--needs, flaws and achievements". Biol Chem. 389 (5): 547–50. PMID 18953721.
  2. 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.
  3. 3.0 3.1 Monath TP (2002). "Japanese encephalitis vaccines: current vaccines and future prospects". Curr Top Microbiol Immunol. 267: 105–38. PMID 12082985.
  4. 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.
  5. 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.
  6. Woods DL (1992). "Resuscitation of the newborn infant". Nurs RSA. 7 (1): 21–3, 26. PMID 1569999.
  7. Ohrr H, Tandan JB, Sohn YM, Shin SH, Pradhan DP, Halstead SB (2005). "Effect of single dose of SA 14-14-2 vaccine 1 year after immunisation in Nepalese children with Japanese encephalitis: a case-control study". Lancet. 366 (9494): 1375–8. doi:10.1016/S0140-6736(05)67567-8. PMID 16226615.
  8. Tandan JB, Ohrr H, Sohn YM, Yoksan S, Ji M, Nam CM; et al. (2007). "Single dose of SA 14-14-2 vaccine provides long-term protection against Japanese encephalitis: a case-control study in Nepalese children 5 years after immunization. drjbtandan@yahoo.com". Vaccine. 25 (27): 5041–5. doi:10.1016/j.vaccine.2007.04.052. PMID 17521781.
  9. Sohn YM, Tandan JB, Yoksan S, Ji M, Ohrr H (2008). "A 5-year follow-up of antibody response in children vaccinated with single dose of live attenuated SA14-14-2 Japanese encephalitis vaccine: immunogenicity and anamnestic responses". Vaccine. 26 (13): 1638–43. doi:10.1016/j.vaccine.2008.01.021. PMID 18294743.
  10. Monath TP, Guirakhoo F, Nichols R, Yoksan S, Schrader R, Murphy C; et al. (2003). "Chimeric live, attenuated vaccine against Japanese encephalitis (ChimeriVax-JE): phase 2 clinical trials for safety and immunogenicity, effect of vaccine dose and schedule, and memory response to challenge with inactivated Japanese encephalitis antigen". J Infect Dis. 188 (8): 1213–30. doi:10.1086/378356. PMID 14551893.
  11. Reid M, Mackenzie D, Baron A, Lehmann N, Lowry K, Aaskov J; et al. (2006). "Experimental infection of Culex annulirostris, Culex gelidus, and Aedes vigilax with a yellow fever/Japanese encephalitis virus vaccine chimera (ChimeriVax-JE)". Am J Trop Med Hyg. 75 (4): 659–63. PMID 17038690.
  12. Kanesa-thasan N, Smucny JJ, Hoke CH, Marks DH, Konishi E, Kurane I; et al. (2000). "Safety and immunogenicity of NYVAC-JEV and ALVAC-JEV attenuated recombinant Japanese encephalitis virus--poxvirus vaccines in vaccinia-nonimmune and vaccinia-immune humans". Vaccine. 19 (4–5): 483–91. PMID 11027812.
  13. 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.
  14. 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.


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