The current available vaccines in the UK are the Japanese Encephalitis Green Cross (GC) vaccine and the Ixiaro® Japanese B encephalitis vaccine, which has recently become available. Japanese Encephalitis-VAX was a formalin-inactivated vaccine derived from mouse brain against Japanese B Encephalitis (called Biken), it has now been discontinued.^1,2,3,4

The GC vaccine is not available on the NHS as it is unlicensed, but can be obtained on a named patient basis from MASTA (Medical Advisory Services for Travellers Abroad).

Previous inactivated vaccines have been costly e.g. Biken and thus a live attenuated vaccine has been used in children in China and India with some success.⁵ The other flava virus vaccine is yellow fever vaccine. There does not appear to be cross protection with other flava virus disease, although the risk of Dengue may be reduced.

The Ixiaro® vaccine is licensed for use in adults aged 18 years and older (for children aged 12 months or older, give the GC vaccine).

Efficacy

The older Biken vaccine was associated with a seroconversion rate of 100% following 3 doses.⁶ Efficacy was also good but not 100%.

At present data is neither available on the efficacy of the GC vaccine, nor on the Ixiaro® vaccine.²

Immunisation schedule

Green Cross vaccine

• The current schedule for those aged 1 year or older is 3 injections on days 0, 7, and 28.
• The last dose of vaccine should be given no less than 10 days before entering an endemic area (to watch for any delayed allergic reactions).
• Ideally the schedule should be completed a month before travel to allow immunity to develop.
• If there is a lack of time between the traveller's intended departure then a more rapid course can be given, e.g. over 14 days; however, the efficacy of this may be inadequate.¹

Ixiaro® vaccine

• There is lack of data regarding the correct timing of administration.
• The current advice is two doses of vaccine administered on days 0 and 28.²

Adverse reactions

The data on GC vaccine and Ixiaro® vaccine is limited but they have similarities to the discontinued Biken vaccine.¹ Thus the adverse reaction profile is likely to be similar.

• Mild adverse reactions are reported in as many as 20% of people.⁷ These include:
  • Local pain and redness
  • Fever
  • Gastrointestinal symptoms
  • Headache and myalgia
• The incidence of reactions usually decreases with each subsequent dose. In a study of over 14,000 US marines who received the vaccine, the rate of reactions for the 3 doses was around 16, 10 and 2 cases respectively per 10,000 doses.⁸
• Severe hypersensitivity, including angio-oedema or urticaria, occurs in 0.6% of patients.⁸
• 2.6 per 100,000 have a response severe enough to require admission to hospital.
• The hypersensitivity reaction may occur as late as 10 to14 days after the last dose. Hence, patients should have access to medical care for 10 days after the last dose.
• A history of allergies or urticaria may increase the risk for adverse reactions.⁸
• Adverse reactions tend to occur within 48 hours for the first dose but around 96 hours for the second.
• Cases of encephalitis and other potentially vaccine-related neurological symptoms have been reported. This association has not been definitively established and surveillance in the United States in the 1990s of more than 800,000 doses reported no neurological sequelae.

Candidates for immunisation

• The vaccine is recommended for people living in endemic and epidemic areas and for travellers planning extended trips to rural areas, e.g. rice fields and marshland. This is usually defined as in excess of 30 days.
• For an area with active epidemic Japanese encephalitis, vaccination should be considered for shorter stays.
• Vaccination, even for short stays, is recommended if the person expects unprotected nocturnal outdoor exposure in an endemic area.

Risks and benefits

The GC vaccine is effective but not without risks and the substantial risks of the disease and the risks of the vaccine have to be balanced,⁹ especially for stays of brief duration. As with malaria, prophylaxis must be supplemented by techniques to avoid being bitten by mosquitoes.

With regards to the Ixiaro® vaccine, studies on effectiveness are underway.

Document references

1. National Travel Health Network and Centre (NaTHNac); Travel Health Information Sheet - Japanese Encephalitis; July 2008.
2. NaTHNaC; Clinical update: Ixiaro® Japanese encephalitis vaccine, May 2009.
3. Specific Product Characteristics (SPC) IXIARO suspension for injection - Japanese encephalitis vaccine (inactivated, adsorbed); Novartis Vaccines; Apr 2009.
4. Department of Health; Immunisation against infectious disease - 'The Green Book' (various dates).
5. Gould EA, Solomon T; Pathogenic flaviviruses. Lancet. 2008 Feb 9;371(9611):500-9. [abstract]
6. Defraites RF, Gambel JM, Hoke CH Jr, et al; Japanese encephalitis vaccine (inactivated, BIKEN) in U.S. soldiers: immunogenicity and safety of vaccine administered in two dosing regimens. Am J Trop Med Hyg. 1999 Aug;61(2):288-93. [abstract]
7. Plesner AM; Allergic reactions to Japanese encephalitis vaccine. Immunol Allergy Clin North Am. 2003 Nov;23(4):665-97. [abstract]
8. Berg SW, Mitchell BS, Hanson RK, et al; Systemic reactions in U.S. Marine Corps personnel who received Japanese encephalitis vaccine. Clin Infect Dis. 1997 Feb;24(2):265-6. [abstract]
9. Shlim DR, Solomon T; Japanese encephalitis vaccine for travelers: exploring the limits of risk. Clin Infect Dis. 2002 Jul 15;35(2):183-8. Epub 2002 Jun 19. [abstract]

Internet and further reading

• Kallen AJ; Japanese Encephalitis. emedicine, June 2005.
• World Health Organsiation; Infectious diseases of potential risk for travellers

Acknowledgements