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

被引：39

作者：

Rayamajhi, Ajit ^{[1
,2
,3
]}

Nightingale, Sam ^{[1
]}

Bhatta, Nisha Keshary ^{[4
]}

Singh, Rupa ^{[4
]}

Ledger, Elizabeth ^{[1
]}

Bista, Krishna Prasad ^{[3
]}

Lewthwaite, Penny ^{[1
]}

Mahaseth, Chandeshwar ^{[2
,3
]}

Turtle, Lance ^{[1
]}

Robinson, Jaimie Sue ^{[5
]}

Galbraith, Sareen Elizabeth ^{[6
]}

Wnek, Malgorzata ^{[1
]}

Johnson, Barbara Wilmot ^{[5
]}

Faragher, Brian ^{[7
]}

Griffiths, Michael John ^{[1
,8
]}

Solomon, Tom ^{[1
,9
,10
,11
]}

机构：

[1] Univ Liverpool, Inst Infect & Global Hlth, Liverpool L69 3BX, Merseyside, England

[2] Natl Acad Med Sci, Kathmandu, Nepal

[3] Kanti Childrens Hosp, Kathmandu, Nepal

[4] BP Koirala Inst Hlth Sci, Dharan, Nepal

[5] Ctr Dis Control & Prevent, Arbovirus Dis Branch, Diagnost & Reference Lab, Div Vector Borne Dis, Ft Collins, CO USA

[6] Leeds Metropolitan Univ, Inst Hlth & Wellbeing, Leeds LS1 3HE, W Yorkshire, England

[7] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England

[8] Alder Hey Childrens Natl Hlth Serv Fdn Trust, Liverpool, Merseyside, England

[9] Walton Ctr Natl Hlth Serv Fdn Trust, Liverpool, Merseyside, England

[10] Natl Consortium Zoonosis Res, Liverpool, Merseyside, England

[11] Natl Inst Hlth Res, Hlth Protect Res Unit Emerging & Zoonot Infect, Liverpool, Merseyside, England

来源：

PLOS ONE | 2015年 / 10卷 / 04期

关键词：

CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; NILE-VIRUS-INFECTION; MONOCLONAL-ANTIBODY; CYTOKINE PRODUCTION; NEUTRALIZING ANTIBODY; WEST; MICE; INTERLEUKIN-6; MODULATION;

D O I：

10.1371/journal.pone.0122608

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：21

共 79 条

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