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Background: The mainstay of diagnostic confirmation of acute Japanese encephalitis (JE) involves detection of anti-JEV IgM by ELISA. Limitations in the specificity of this test are increasingly apparent with the introduction of JEV vaccinations and the endemicity of other cross-reactive flaviviruses. Virus neutralisation testing (VNT) is considered the gold standard but is challenging to implement and interpret. We performed a pilot study to assess IgG depletion prior to VNT for detection of anti-JEV IgM neutralising antibodies, 'IgM-VNT' as compared to standard VNT. Methods: We evaluated IgM-VNT in paired sera from anti-JEV IgM ELISA positive patients (JE n=35) and negative controls of healthy flavivirus naïve (n=10) as well as confirmed dengue (n=12) and Zika virus (n=4) patient sera. IgM-VNT was subsequently performed on single sera from additional JE patients (n=76). Results: Anti-JEV IgG was detectable in admission serum of 58% of JE patients. The positive, negative and overall percentage agreement (PPA, NPA, OPA) of IgM-VNT was 100%. 12/14 (86%) patient samples unclassified by VNT, and with sufficient sample available for IgG depletion and IgG ELISA confirming depletion were classified by IgM-VNT. IgM-VNT enabled JE case classification in 72/76 (95%) of the patients for whom only a single sample was available. Conclusions: The novel approach has been readily adapted for high-throughput testing of single patient samples, and it holds promise for incorporation into algorithms for use in reference centres.

Type

Journal

Transactions of The Royal Society of Tropical Medicine and Hygiene

Publisher

Oxford University Press

Publication Date

28/03/2022

Keywords

FFR