Japanese encephalitis — the prospects for new treatments

Key Points

  • Japanese encephalitis is a severe disease caused by Japanese encephalitis virus, genus Flavivirus, family Flaviviridae, which is endemic to most of rural Asia and for which no specific treatment exists.

  • Japanese encephalitis causes loss of more disability-adjusted life years than any other arthropod-borne virus owing to the frequent neurological sequelae of the condition.

  • Pathogenesis studies indicate that inhibition of viral replication, viral spread and the host response are needed in combination for optimal therapy.

  • Animal models and in vitro experiments highlight a number of compounds that are potentially suitable for treatment of Japanese encephalitis in humans that could be tested without delay.

  • The minimum clinically significant treatment effect has probably been underestimated, and previous clinical trials of Japanese encephalitis have been too small; larger, pragmatic trials are needed.


Japanese encephalitis is a mosquito-borne disease that occurs in Asia and is caused by Japanese encephalitis virus (JEV), a member of the genus Flavivirus. Although many flaviviruses can cause encephalitis, JEV causes particularly severe neurological manifestations. The virus causes loss of more disability-adjusted life years than any other arthropod-borne virus owing to the frequent neurological sequelae of the condition. Despite substantial advances in our understanding of Japanese encephalitis from in vitro studies and animal models, studies of pathogenesis and treatment in humans are lagging behind. Few mechanistic studies have been conducted in humans, and only four clinical trials of therapies for Japanese encephalitis have taken place in the past 10 years despite an estimated incidence of 69,000 cases per year. Previous trials for Japanese encephalitis might have been too small to detect important benefits of potential treatments. Many potential treatment targets exist for Japanese encephalitis, and pathogenesis and virological studies have uncovered mechanisms by which these drugs could work. In this Review, we summarize the epidemiology, clinical features, prevention and treatment of Japanese encephalitis and focus on potential new therapeutic strategies, based on repurposing existing compounds that are already suitable for human use and could be trialled without delay. We use our newly improved understanding of Japanese encephalitis pathogenesis to posit potential treatments and outline some of the many challenges that remain in tackling the disease in humans.

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Figure 1: JEV structure.
Figure 2: Features of Japanese encephalitis.
Figure 3: Clinical outcome of Japanese encephalitis.
Figure 4: Origin and genotype spread of JEV in Southeast Asia.
Figure 5: Overview of the pathogenesis of Japanese encephalitis.
Figure 6: CD4+ T cell responses in patients recovered from Japanese encephalitis.


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L.T. is a Wellcome clinical career development fellow supported by grant number 205228/Z/16/Z. T.S. is a UK National Institute for Health Research (NIHR) senior investigator and member of the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England. This work was conducted independently of influence from the NIHR. T.S. and L.T. are also supported by the European Union's Horizon 2020 Research and Innovation programme under grant agreement 734584 and the Zika Pan Latin American Network (ZikaPLAN).

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Both authors contributed substantially to the discussion of content for the article, wrote the article and reviewed and edited the article before submission. L.T. researched data for the article.

Correspondence to Lance Turtle.

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Turtle, L., Solomon, T. Japanese encephalitis — the prospects for new treatments. Nat Rev Neurol 14, 298–313 (2018) doi:10.1038/nrneurol.2018.30

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