A need to raise the bar — A systematic review of temporal trends in diagnostics for Japanese encephalitis virus infection, and perspectives for future research

Highlights

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  Japanese encephalitis virus (JEV) remains a leading cause of neurological infection in Asia.

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  A systematic review identified 20,212 published human cases of laboratory-confirmed JEV infections from 205 studies.

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  15,167 (75%) of cases were confirmed with the lowest confidence diagnostic test, i.e., level 3 or 4, or level 4.

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  Only 109 (53%) of the studies reported contemporaneous testing for dengue-specific antibodies.

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  A fundamental pre-requisite for the control of JE is lacking — that of a simple and specific diagnostic procedure that can be adapted for point-of-care tests and readily used throughout JE endemic regions of the world.

Abstract

Objective

Japanese encephalitis virus infection (JE) remains a leading cause of neurological disease in Asia, mainly involving individuals living in remote areas with limited access to treatment centers and diagnostic facilities. Laboratory confirmation is fundamental for the justification and implementation of vaccination programs. We reviewed the literature on historical developments and current diagnostic capability worldwide, to identify knowledge gaps and instill urgency to address them.

Methods

Searches were performed in Web of Science and PubMed using the term 'Japanese encephalitis' up to 13th October 2019. Studies reporting laboratory-confirmed symptomatic JE cases in humans were included, and data on details of diagnostic tests were extracted. A JE case was classified according to confirmatory levels (Fischer et al., 2008; Campbell et al., 2011; Pearce et al., 2018; Heffelfinger et al., 2017), where level 1 represented the highest level of confidence.

Findings

20,212 published JE cases were identified from 205 studies. 15,167 (75%) of these positive cases were confirmed with the lowest-confidence diagnostic tests (level 3 or 4, or level 4). Only 109 (53%) of the studies reported contemporaneous testing for dengue-specific antibodies.

Conclusion

A fundamental pre-requisite for the control of JEV is lacking — that of a simple and specific diagnostic procedure that can be adapted for point-of-care tests and readily used throughout JE-endemic regions of the world.