Background Japanese encephalitis virus (JEV) causes 35 000–50 000 cases and 10 000 deaths every year and is the most important cause of encephalitis worldwide. There is no known antiviral treatment for any flavivirus.

Methods We performed a randomised double-blind placebo-controlled trial of IVIG in 22 Nepalese children with suspected Japanese encephalitis, 13 of whom had serologically confirmed infection. IVIG obtained from areas endemic for JEV had 50% plaque reduction neutralisation test (PRNT50) against wild type JEV, and the IVIG with the highest titre was selected for treatment. Blood was collected pre, mid and post-treatment. Outcome was assessed at discharge and 3–6 month follow-up.

Results IVIG prepared from a JEV endemic population has detectable anti-JEV antibodies. There was evidence of passive transfer of anti-JEV antibody in JEV negative children. Intriguingly JEV positive children treated with IVIG had 3–4 fold higher PRNT50 titres than placebo (p=0.08), more than can be explained by passive transfer alone, suggesting an immune augmenting effect. IL-4 and IL-6 were also higher in the IVIG group. There were no significant differences in outcome.

Conclusion IVIG with neutralising antibody may be an effective treatment for Japanese encephalitis and other flaviviral encephalitis due to anti-inflammatory effects, immune augmentation and JEV neutralisation.