Side Effects of Japanese Encephalitis Vaccination
Japanese encephalitis vaccination is generally well-tolerated with predominantly mild local and systemic reactions, and serious adverse events are rare, occurring in approximately 1% of vaccinees. 1
Common Local Reactions
In adults, the most frequent local reactions after JE-VC (Vero cell-derived vaccine) are: 1
- Pain at injection site: 28% after first dose, 18% after second dose
- Tenderness: 29% after first dose, 23% after second dose
- Severe local reactions occur in only 3% of recipients 1
In children, local reactions vary by age: 1
- Ages 2 months to <3 years: Redness is most common
- Ages 3-17 years: Pain and tenderness predominate
- Ages 2 months-17 years: Injection-site tenderness in 50% receiving 0.5-mL dose 1
Common Systemic Reactions
In adults, the most frequent systemic reactions include: 1
- Headache: 22% after first dose, 13% after second dose
- Myalgia: 13% after first dose, 6% after second dose
- Influenza-like illness: 13%
- Fatigue: 13%
In children, the most commonly reported systemic reaction is: 1
- Fever (most frequent across all pediatric age groups)
- Muscle pain in 31% of children receiving 0.5-mL dose 1
Important Pattern: Reactions Decrease After Second Dose
Systemic adverse events are reported by a lower percentage of participants after the second dose compared with the first dose, which is reassuring for vaccine completion. 1
Serious Adverse Events
Serious adverse events are uncommon, occurring in approximately 1% of JE-VC recipients in pooled analyses of over 3,558 vaccinees. 1
No serious neurologic events were identified in the pivotal safety study of nearly 2,000 adults. 1
Serious allergic reactions did not occur in any study group during prelicensure trials comparing JE-VC to placebo or older mouse brain-derived vaccine. 1
Allergic/Hypersensitivity Reactions
Urticaria and angioedema represent the most concerning allergic pattern, though rare with modern JE-VC: 1
- In pivotal trials, only 2 cases of urticaria occurred among 2,650 participants
- One case of generalized urticaria occurred 8 days after second JE-VC dose, was moderate in severity, resolved in 3 days with antihistamine treatment, and angioedema was not observed 1
Historical context with older mouse brain-derived vaccine (JE-MB): 1
- Since 1989, a pattern of hypersensitivity reactions (urticaria and/or angioedema) was reported primarily in travelers from Australia, Europe, and North America
- Reactions occurred after a median of 12 hours following first dose (88% within 3 days)
- After second dose, reactions had longer median interval of 3 days
- Past history of urticaria was associated with increased risk (relative risk 9.1) 1
The modern JE-VC vaccine has a significantly better safety profile than the older mouse brain-derived vaccine, with severe local reactions occurring in only 3% versus 6% with JE-MB. 1
Neurological Concerns
No serious neurologic events were identified in the pivotal JE-VC safety study. 1
Historical surveillance data from older vaccines in Japan (1965-1973) disclosed neurologic events (encephalitis, encephalopathy, seizures, peripheral neuropathy) at rates of 1 to 2.3 per million vaccinees, though causality was never established. 1
With modern JE-VC, postlicensure surveillance covering >1 million doses distributed in the U.S. (2009-2016) showed: 1
- Overall adverse event rate: 14.8-15.2 per 100,000 doses
- Serious adverse event rate: 1.1-1.8 per 100,000 doses
- No patterns of serious hypersensitivity, neurologic, or other serious adverse events considered vaccine-related were identified 1
Booster Dose Safety
Booster doses are well-tolerated with similar or lower reaction rates: 1
In adults receiving booster at 15 months: 1
- Tenderness: 19%
- Pain: 13%
- Headache: 11%
- Fatigue: 10%
- No serious adverse events reported within 28 days
In children receiving booster: 1
- Local adverse events: 8%
- Systemic adverse events: 14%
Concomitant Vaccination Considerations
Co-administration with hepatitis A vaccine: 1
- Increased reports of pain, redness, and swelling at injection site
- No other safety differences compared to either vaccine alone
Co-administration with rabies vaccine: 1
- Higher rates of both local (75%) and systemic (60%) reactions when given together
- Compared to 63% local and 54% systemic when JE-VC given alone
Key Clinical Pitfalls to Avoid
Do not withhold second dose due to mild reactions after first dose - reactions typically decrease with subsequent doses 1
Monitor for delayed hypersensitivity reactions - while rare with JE-VC, reactions can occur up to 2 weeks after vaccination, particularly after second dose 1
Consider patient history of urticaria - historically associated with increased reaction risk, though data primarily from older vaccine formulations 1
Reassure patients about neurological safety - modern JE-VC has excellent neurological safety profile with no identified patterns of serious neurologic events in over 1 million distributed doses 1