Japanese encephalitis (JE) is a potentially deadly viral infection spread by mosquitos that is endemic in 24 countries of the Asia-Pacific region, exposing an estimated 1.5 billion people to the risk of infection. Caused by a flavivirus, closely related to West Nile virus, JE is a devastating, emerging disease with a 20–30% case fatality rate that primarily affects children in poor, rural areas with minimal access to healthcare. JE leaves 30–50% of survivors suffering long-term disability.
JE virus is rarely detected in patients, with the poor accuracy of existing diagnostic tests a fundamental limitation in controlling JE. There is no means of detecting the disease in remote settings. A rapid diagnostic test to detect JE in less accessible areas is urgently needed.
A group of researchers from the Department of Biochemistry, University of Oxford, NDM’s Mahidol Oxford Tropical Medicine Research Unit, Target Discovery Institute, Centre for Medicines Discovery and other collaborating organizations analysed over 5,000 proteins associated with JE and other flavivirus infections extensively. In this study published in the Journal of Proteome Research, they found a nine-protein JE diagnostic signature in human cerebrospinal fluid that could discriminate between JE and other brain infections, including other endemic flavivirus infections such as dengue and West Nile virus.
The researchers say that future studies using antibody-based methods could narrow the nine proteins to 2-3 proteins that could then be used to develop an RDT that would allow JE to be diagnosed quickly and accurately in remote settings.
Professor Paul Newton, Professor of Tropical Medicine, Head of Medicine Quality Research Group and Head of Medicine Quality Research Group, Mahidol Oxford Tropical Medicine Research Unit said: ‘Although the host protein biomarkers need to be verified in different patient populations by an antibody-based method, this gives hope of a way towards a rapid diagnostic test for JE, to bring diagnostic tests to the many people living far from reference assays.’
Led by Dr Tehmina Bharucha, a DPhil Student in Professor Nicole Zitzmann’s laboratory at the Department of Biochemistry, University of Oxford, UK, the Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Laos, and Aix-Marseille Université, France, in collaboration with colleagues at NDM’s Target Discovery Institute, researchers performed untargeted proteomics analysis using liquid chromatography-mass spectrometry (LC-MS) of 163 patient cerebrospinal fluid (CSF) samples collected as part of the Laos Central Nervous System and South-East Asia encephalitis projects.