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 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 (RDT) to detect JE in less accessible areas is urgently needed.
After an extensive analysis of over 5,000 proteins associated with JE and other flavivirus infections, University of Oxford researchers reported in a study published in the Journal of Proteome Research that they had found a nine-protein JE diagnostic signature in human cerebrospinal fluid (CSF) 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.
“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,” said Prof Paul Newton, University of Oxford, and Head of Medicine Quality Research Group (MQRG), Mahidol Oxford Tropical Medicine Research Unit (MORU).
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 Oxford’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.
Dr Tehmina Bharucha, firstname.lastname@example.org
Deep Proteomics Network and Machine Learning Analysis of Human Cerebrospinal Fluid in Japanese Encephalitis Virus Infection. Bharucha T, Gangadharan B, Kumar A, Myall AC, Ayhan N, Pastorino B, Chanthongthip A, Vongsouvath M, Mayxay M, Sengvilaipaseuth O, Phonemixay O, Rattanavong S, O'Brien DP, Vendrell I, Fischer R, Kessler B, Turtle L, de Lamballerie X, Dubot-Pérès A, Newton PN, Zitzmann N, SEAe Consortium. J Proteome Res. 2023 Jun 2;22(6):1614-1629. doi: 10.1021/acs.jproteome.2c00563. Epub 2023 May 23. PMID: 37219084; PMCID: PMC10246887.
Laos Central Nervous System infection
Management of Central Nervous System Infections, Vientiane, Laos, 2003-2011. Dubot-Pérès A, Mayxay M, Phetsouvanh R, Lee SJ, Rattanavong S, Vongsouvath M, Davong V, Chansamouth V, Phommasone K, Moore C, Dittrich S, Lattana O, Sirisouk J, Phoumin P, Panyanivong P, Sengduangphachanh A, Sibounheuang B, Chanthongthip A, Simmalavong M, Sengdatka D, Seubsanith A, Keoluangkot V, Phimmasone P, Sisout K, Detleuxay K, Luangxay K, Phouangsouvanh I, Craig SB, Tulsiani SM, Burns MA, Dance DAB, Blacksell SD, de Lamballerie X, Newton PN. Emerg Infect Dis. 2019 May;25(5):898-910. doi: 10.3201/eid2505.180914. PMID: 31002063; PMCID: PMC6478220.
South-East Asia encephalitis projects
Childhood encephalitis in the Greater Mekong region (the SouthEast Asia Encephalitis Project): a multicentre prospective study. Pommier JD, Gorman C, Crabol Y, Bleakley K, Sothy H, Santy K, Tran HTT, Nguyen LV, Bunnakea E, Hlaing CS, Aye AMM, Cappelle J, Herrant M, Piola P, Rosset B, Chevalier V, Tarantola A, Channa M, Honnorat J, Pinto AL, Rattanavong S, Vongsouvath M, Mayxay M, Phangmanixay S, Phongsavath K, Tin OS, Kyaw LL, Tin HH, Linn K, Tran TMH, Pérot P, Thuy NTT, Hien N, Phan PH, Buchy P, Dussart P, Laurent D, Eloit M, Dubot-Pérès A, Lortholary O, de Lamballerie X, Newton PN, Lecuit M; SEAe Consortium. Lancet Glob Health. 2022 Jul;10(7):e989-e1002. doi: 10.1016/S2214-109X(22)00174-7. PMID: 35714649; PMCID: PMC9210261.
Estimating the cost of illness of acute Japanese encephalitis and sequelae care in Vietnam and Laos: A cross-sectional study. Nguyen ALT, Slavkovsky R, Phan HT, Nguyen HTT, Vannachone S, Le DH, Dubot-Pérès A, Vongsouvath M, Dinh ST, Marfin AA, Letson GW, Vu HM, Tham DC, Mayxay M, Ashley EA, Pham TQ, Pecenka C. PLOS Glob Public Health. 2023 Jun 13;3(6):e0001873. doi: 10.1371/journal.pgph.0001873. PMID: 37310946; PMCID: PMC10263309.