Correspondence

Japanese Encephalitis in Australia — A Sentinel Case

To the Editor:

On March 4, 2022, Japanese encephalitis was identified as a “communicable disease incident of national significance” in Australia. This notification followed the detection of Japanese encephalitis virus (JEV) in mummified, stillborn, and weak newborn piglets from multiple commercial piggeries across four temperate southern Australian states, with concomitant recognition of human cases of Japanese encephalitis. As of August 1, 2022, a total of 40 cases of infection that had led to 5 deaths had been reported.1

In 1995 and 1998, in the tropical far north of Australia in Queensland, 5 cases of Japanese encephalitis (and 2 deaths) caused by genotype 2 were identified. It was hypothesized that this outbreak resulted from the incursion of cyclonic-wind–transported JEV-infected mosquitoes from Papua New Guinea.2 Since 1998, no further endemic cases of Japanese encephalitis had been detected in Australia until a case in February 2021 that resulted in death. This case appeared to be a sentinel human case of the current outbreak that was identified a year later at a location that was more than 3000 km to the south.

Magnetic Resonance Imaging and Histologic Analysis in the Sentinel Patient.

Panel A shows bilateral symmetric thalamic T2 hyperintensity and restricted diffusion in a 45-year-old resident of the Tiwi Islands who was treated for progressive neurologic deterioration caused by Japanese encephalitis in February 2021. The patient is now considered to be a sentinel human case of the 2022 outbreak of Japanese encephalitis in Australia. Panel B shows the results of postmortem histologic analysis of a midbrain sample from the patient indicating dense lymphocytic perivascular cuffing.

In the sentinel case, a 45-year-old resident of the Tiwi Islands (located 80 km north of Darwin on the Northern Territory coast) presented with a 2-day history of acute confusion and fever. The patient was admitted to Royal Darwin Hospital with progressive neurologic deterioration. Despite receiving mechanical ventilation in the intensive care unit, the patient died 15 days after admission. Analysis of the cerebrospinal fluid (CSF) revealed 11 million erythrocytes and 88 million lymphocytes per liter, a glucose level of 5.5 mmol per liter, and a protein level of 1.05 g per liter (reference range, 0.15 to 0.45). Magnetic resonance imaging showed changes with T2 hyperintensity in both thalami, in the right cerebellar hemisphere, and in the brain stem (Figure 1A). Results of polymerase-chain-reaction assay for flavivirus RNA were negative on initial analysis of serum and CSF. Serum indirect fluorescent antibody testing was negative on admission but positive on day 13 for JEV IgM and IgG and was equivocal for IgM for the closely related Murray Valley encephalitis (MVE) virus, which is endemic in northern Australia. Postmortem histologic analysis of the brain was consistent with viral panencephalitis (Figure 1B). Most affected were the thalami, brain stem, and upper cervical spinal cord, findings that were consistent with those seen in JEV, MVE, and West Nile virus (WNV) infection.3 A complete JEV genome sequence that was obtained from thalamus tissue (NCBI GenBank accession number, OM867669) indicated that the virus belonged to genotype 4 and was closely related to the 2022 Southeast Australian outbreak strains (>99.7% nucleotide identity) in samples obtained from pigs, humans, and mosquitoes.

Genotype 4 JEV has been recognized in Indonesia, including in Bali.4 Possibilities for this introduction into Australia include entry of JEV-infected mosquitoes, either wind-blown or harboring on planes or vessels, or transmission to local mosquitoes from a JEV-infected migratory bird. Subsequent dissemination to southern Australia is likely to have been facilitated by JEV-infected water birds, followed by virus amplification in commercial, domestic, and feral pigs. Ongoing surveillance of commercial piggeries and sampling of mosquitoes and feral pigs will determine the extent to which JEV persists over the current winter and reemerges next summer, with implications for the planning of a possible national rollout of JEV vaccination. The identification of JEV in Australia has many analogies to the introduction and dissemination of WNV in the United States,5 and it is worrisome that JEV may become endemic in Australia.

Claire Waller, F.R.A.C.P.
Marianne Tiemensma, F.R.C.P.A.
Northern Territory Department of Health, Darwin, NT, Australia

Bart J. Currie, F.R.A.C.P.
Menzies School of Health Research at Charles Darwin University, Darwin, NT, Australia

David T. Williams, Ph.D.
Australian Centre for Disease Preparedness, Geelong, VIC, Australia

Robert W. Baird, F.R.C.P.A.
Vicki L. Krause, M.D.
Northern Territory Department of Health, Darwin, NT, Australia

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

  1. 1. Australian Government Department of Health and Aged Care. Japanese encephalitis virus (JEV). August 1, 2022 (https://www.health.gov.au/health-alerts/japanese-encephalitis-virus-jev/about#current-status).

  2. 2. van den Hurk AF, Pyke AT, Mackenzie JS, Hall-Mendelin S, Ritchie SA. Japanese encephalitis virus in Australia: from known known to known unknown. Trop Med Infect Dis 2019;4:38-38.

  3. 3. Chong HY, Leow CY, Abdul Majeed AB, Leow CH. Flavivirus infection — a review of immunopathogenesis, immunological response, and immunodiagnosis. Virus Res 2019;274:197770-197770.

  4. 4. Kuwata R, Torii S, Shimoda H, et al. Distribution of Japanese encephalitis virus, Japan and Southeast Asia, 2016–2018. Emerg Infect Dis 2020;26:125-128.

  5. 5. Snyder RE, Cooksey GS, Kramer V, Jain S, Vugia DJ. West Nile virus-associated hospitalizations, California, 2004–2017. Clin Infect Dis 2021;73:441-447.

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