A Preliminary Randomized Double Blind Placebo-Controlled Trial of Intravenous Immunoglobulin for Japanese Encephalitis in Nepal

Rayamajhi, Ajit, Nightingale, Sam, Bhatta, Nisha Keshary, Singh, Rupa, Ledger, Elizabeth, Bista, Krishna Prasad, Lewthwaite, Penny, Mahaseth, Chandeshwar, Turtle, Lance, Robinson, Jaimie Sue, Galbraith, Sareen Elizabeth, Wnek, Malgorzata, Johnson, Barbara Wilmot, Faragher, Brian, Griffiths, Michael John and Solomon, Tom (2015) 'A Preliminary Randomized Double Blind Placebo-Controlled Trial of Intravenous Immunoglobulin for Japanese Encephalitis in Nepal'. PLoS ONE, Vol 10, Issue 4, e0122608.

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Abstract

Background

Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG’s anti-inflammatory properties may also be beneficial.

Methodology/Principal Findings

We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group.

Conclusions/Significance

A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Reference Works. General Immunology > QW 520 Research (General) QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies WB Practice of Medicine > Therapeutics > WB 330 Drug therapy WC Communicable Diseases > Virus Diseases > Viral Hemorrhagic Fevers. Other Virus Diseases > WC 542 Arbovirus encephalitis. Equine encephalomyelitis (in humans)
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pone.0122608
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	23 Jun 2015 09:04
Last Modified:	06 Feb 2018 13:10
URI:	https://archive.lstmed.ac.uk/id/eprint/5221

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