Investigation of Japanese encephalitis virus as a cause of acute encephalitis in southern Pakistan, April 2015-January 2018

PLoS One. 2020 Jun 12;15(6):e0234584. doi: 10.1371/journal.pone.0234584. eCollection 2020.

Abstract

Background: Japanese encephalitis (JE) occurs in fewer than 1% of JE virus (JEV) infections, often with catastrophic sequelae including death and neuropsychiatric disability. JEV transmission in Pakistan was documented in 1980s and 1990s, but recent evidence is lacking. Our objective was to investigate JEV as a cause of acute encephalitis in Pakistan.

Methods: Persons aged ≥1 month with possible JE admitted to two acute care hospitals in Karachi, Pakistan from April 2015 to January 2018 were enrolled. Cerebrospinal fluid (CSF) or serum samples were tested for JEV immunoglobulin M (IgM) using the InBios JE DetectTM assay. Positive or equivocal samples had confirmatory testing using plaque reduction neutralization tests.

Results: Among 227 patients, testing was performed on CSF in 174 (77%) and on serum in 53 (23%) patients. Six of eight patient samples positive or equivocal for JEV IgM had sufficient volume for confirmatory testing. One patient had evidence of recent West Nile virus (WNV) neurologic infection based on CSF testing. One patient each had recent dengue virus (DENV) infection and WNV infection based on serum results. Recent flavivirus infections were identified in two persons, one each based on CSF and serum results. Specific flaviviruses could not be identified due to serologic cross-reactivity. For the sixth person, JEV neutralizing antibodies were confirmed in CSF but there was insufficient volume for further testing.

Conclusions: Hospital-based JE surveillance in Karachi, Pakistan could not confirm or exclude local JEV transmission. Nonetheless, Pakistan remains at risk for JE due to presence of the mosquito vector, amplifying hosts, and rice irrigation. Laboratory surveillance for JE should continue among persons with acute encephalitis. However, in view of serological cross-reactivity, confirmatory testing of JE IgM positive samples at a reference laboratory is essential.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / immunology
  • Child
  • Child, Preschool
  • Cross Reactions
  • Encephalitis Virus, Japanese / immunology
  • Encephalitis Virus, Japanese / pathogenicity*
  • Encephalitis, Viral / diagnosis
  • Encephalitis, Viral / etiology
  • Encephalitis, Viral / virology*
  • Humans
  • Immunoglobulin M / blood
  • Immunoglobulin M / cerebrospinal fluid
  • Infant
  • Male
  • Middle Aged
  • Pakistan / epidemiology
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin M

Grants and funding

This research was supported in part by Bill & Melinda Gates Foundation grant #OPP1115522 to PATH (to AAM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.