Bharucha, T

Dubot-Pérès, A

Newton, P

Turtle, L

Zitzmann, N

Oxford University Research Archive

To the Editor,  Journal of Immunoassay and Immunochemistry 21st January 2022  Re: Sero-evidence of silent Japanese Encephalitis Virus infection among inhabitants of Ilorin, North-central Nigeria: a call for active surveillance https://www.tandfonline.com/doi/abs/10.1080/15321819.2021.1993897   We read with interest the recent article published in the Journal of Immunoassay and Immunochemistry reporting Japanese encephalitis virus (JEV) serological testing in Nigeria. There is no doubt that there are ongoing changes in the geographical distribution of flaviviruses (1), and surveillance for the relevant disease syndromes would be helpful. To our knowledge, serological testing of this kind has not been performed in Nigeria. JEV RNA was apparently detected in a patient with confirmed yellow fever in Angola; however, acute JEV infection was not corroborated by conventional IgM ELISA or seroneutralisation (2). As the authors discuss in the article, there is high cross-reactivity of flaviviruses, and very significant false positives with ELISA tests (3). We urge caution in the interpretation of the results. Anti-JEV IgG results cannot be interpreted alone, they require to be reported alongside testing for other endemic flaviviruses, most importantly anti-dengue and yellow fever virus IgG (4), and flavivirus vaccination history. Yellow fever is reported in Nigeria, and yellow fever vaccine is widely used. There are minimal data on the use of anti-JEV IgG, particularly the cited Diagnostic Automation assay, and the authors do not report any in-house validation. The optimal approach for detection of previous exposure or vaccination is a seroneutralisation assay involving contemporaneous testing to other flaviviruses (5). We understand that seroneutralisation requires considerable resources and technical expertise, but we would suggest that the authors consider verifying the anti-JEV IgG results by sending the samples to a reference laboratory for seroneutralisation testing. There is unequivocal evidence for the hyperendemicity of dengue virus and yellow fever vaccine use in Nigeria. In the absence of further testing, these results may be explained entirely by cross-reactivity with other flaviviruses, and do not represent any evidence of JEV circulation in Nigeria.   Kind regards,  Tehmina Bharucha, Department of Biochemistry, University of Oxford, U.K. and Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Lao PDR Nicole Zitzmann, Department of Biochemistry, University of Oxford, U.K. Paul Newton, Centre for Tropical Medicine & Global Health, University of Oxford, Oxford, UK and Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Lao PDR Audrey Dubot-Pérès, Unité des Virus Émergents - (UVE), Aix-Marseille Université - IRD_190 - Inserm_1207, France, and Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Lao PDR, and Centre for Tropical Medicine & Global Health, University of Oxford, Oxford, UK. Lance Turtle, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, U.K. and Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust (member of Liverpool Health Partners, Liverpool, U.K.   1. Pierson TC, Diamond MS. The continued threat of emerging flaviviruses. Nature microbiology. 2020;5(6):796-812. 2. Simon-Loriere E, Faye O, Prot M, Casademont I, Fall G, Fernandez-Garcia MD, et al. Autochthonous Japanese Encephalitis with Yellow Fever Coinfection in Africa. The New England journal of medicine. 2017;376(15):1483-5. 3. Endale A, Medhin G, Darfiro K, Kebede N, Legesse M. Magnitude of Antibody Cross-Reactivity in Medically Important Mosquito-Borne Flaviviruses: A Systematic Review. Infect Drug Resist. 2021;14:4291-9. 4. Klein RS. Encephalitic Arboviruses of Africa: Emergence, Clinical Presentation and Neuropathogenesis. Frontiers in Immunology. 2021;12. 5. Bharucha T, Shearer FM, Vongsouvath M, Mayxay M, de Lamballerie X, Newton PN, et al. A need to raise the bar - A systematic review of temporal trends in diagnostics for Japanese encephalitis virus infection, and perspectives for future research. Int J Infect Dis. 2020.  

Flavivirus cross-reactivity would explain the apparent findings of Japanese encephalitis virus infection in Nigeria

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