Vaccines for preventing Japanese encephalitis.
BACKGROUND
Vaccination is recognized as the only practical measure for preventing Japanese encephalitis. Production shortage, costs, and issues of licensure impair vaccination programmes in many affected countries. Concerns over vaccine effectiveness and safety also have a negative impact on acceptance and uptake.


OBJECTIVE
To evaluate vaccines for preventing Japanese encephalitis in terms of effectiveness, adverse events, and immunogenicity.


METHODS
In March 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 1), MEDLINE, EMBASE, LILACS, BIOSIS, and reference lists. We also attempted to contact corresponding authors and vaccine companies.


METHODS
Randomized controlled trials (RCTs), including cluster-RCTs, comparing Japanese encephalitis vaccines with placebo (inert agent or unrelated vaccine), no intervention, or alternative Japanese encephalitis vaccine.


METHODS
Authors independently extracted data and assessed methodological quality. Dichotomous data were compared with relative risks and a 95% confidence interval (CI), and converted into percentage vaccine efficacy.


RESULTS
Eight RCTs involving 358,750 participants were included. These trials investigated two available and three pre-licensure vaccines. Two RCTs assessing efficacy of the commercially available inactivated Nakayama vaccine were identified. A two-dose schedule of the licensed vaccine provided significant protection of 95% (95% CI 10% to 100%) for one year only, while two doses of an unpurified precursor vaccine protected children by 81% (95% CI 45% to 94%) in year one and by 59% (95% CI 2% to 83%) in year two. Serious adverse events were not observed. Mild and moderate episodes of injection site soreness, fever, headache, and nausea were reported in less than 6% of children receiving inactivated vaccine compared to 0.6% of unvaccinated controls. One cluster-RCT compared the live-attenuated SA14-14-2 vaccine (widely used in China) with no intervention measuring adverse events. Fever was reported in 2.7% of vaccinees compared to 3.1% of controls, while 0.1% of both groups suffered diarrhoea or seizures. Four small pre-licensure RCTs assessing a genetically engineered vaccine and two cell culture-derived inactivated vaccines revealed high immunogenicity and relative safety.


CONCLUSIONS
Only one of the three currently used vaccines has been assessed for efficacy in a RCT. Other RCTs have assessed their safety, however, and they appear to cause only occasional mild or moderate adverse events. Further trials of effectiveness and safety are needed for the currently used vaccines, especially concerning dose levels and schedules. Trials investigating several new vaccines are planned or in progress.
Schiøler
K L
KL
Liverpool School of Tropical Medicine, C/O Cochrane Infectious Diseases Group, Pembroke Place, Liverpool, UK, L3 5QA. klschioler@gmail.com
Samuel
M
M
Wai
K L
KL
D004672:Encephalitis, Japanese / Q000517:prevention & control*; D006801:Humans; D022321:Japanese Encephalitis Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use
D022321:Japanese Encephalitis Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated