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

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 Detect TM 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.

Uncovering the mosaic of emerging infections: The threat of Japanese encephalitis virus in Pakistan

“…The presence of the mosquito vector, amplifying hosts, and rice irrigation in Pakistan continue to pose a risk for the transmission of JEV. 2 Although there is no ongoing active surveillance program for JEV in the country, evidence of JEV presence has been reported in Pakistan particularly in Sindh. [2][3][4] A recent sero-survey in Karachi, investigating patients with acute undifferentiated febrile illness, provided additional confirmation of the presence of JEV in the country when antibodies against the virus were detected in 50 out of 115 samples.…”

“…2 Although there is no ongoing active surveillance program for JEV in the country, evidence of JEV presence has been reported in Pakistan particularly in Sindh. [2][3][4] A recent sero-survey in Karachi, investigating patients with acute undifferentiated febrile illness, provided additional confirmation of the presence of JEV in the country when antibodies against the virus were detected in 50 out of 115 samples. 4 Additionally, among 360 healthy blood donors screened by Khan et al, one sample was found to have antibodies against JEV, with an overall donor seropositivity for arboviruses being 7.2%.…”

“…3 Furthermore, testing of 227 blood samples for seropositivity against JEV revealed eight samples to be positive or equivocal for JEV IgM. 2 While the primary mode of transmission of JEV is through the bite of infected mosquitoes, continuous transmission of the virus is facilitated by factors such as the presence of new susceptible hosts, and suitable breeding sites. 5 In addition to this, there is also evidence regarding the potential for transmission through alternative routes, including transmission associated with blood transfusions.…”

“…3 Furthermore, testing of 227 blood samples for seropositivity against JEV revealed eight samples to be positive or equivocal for JEV IgM. 2…”

Global magnitude of encephalitis burden and its evolving pattern over the past 30 years

“…South Asia, Central Asia, and Southeast Asia were the top three GBD regions with the highest ASMRs in 2019 (more than 1. 25), where all the ASMRs of encephalitis declined significantly over the past 30 years (Table S2). The lowest ASMR was found in Australasia (0.06), followed by Oceania, and Southern Sub-Saharan Africa.…”