Japanese Encephalitis Virus: The Emergence of Genotype IV in Australia and Its Potential Endemicity

Abstract

A fatal case of Japanese encephalitis (JE) occurred in northern Australia in early 2021. Sequence studies showed that the virus belonged to genotype IV (GIV), a genotype previously believed to be restricted to the Indonesian archipelago. This was the first locally acquired case of Japanese encephalitis virus (JEV) GIV to occur outside Indonesia, and the second confirmed fatal human case caused by a GIV virus. A closely related GIV JEV strain subsequently caused a widespread outbreak in eastern Australia in 2022 that was first detected by fetal death and abnormalities in commercial piggeries. Forty-two human cases also occurred with seven fatalities. This has been the first major outbreak of JEV in mainland Australia, and geographically the largest virgin soil outbreak recorded for JEV. This outbreak provides an opportunity to discuss and document the factors involved in the virus' spread and its ecology in a novel ecological milieu in which other flaviviruses, including members of the JE serological complex, also occur. The probable vertebrate hosts and mosquito vectors are discussed with respect to virus spread and its possible endemicity in Australia, and the need to develop a One Health approach to develop improved surveillance methods to rapidly detect future outbreak activity across a large geographical area containing a sparse human population. Understanding the spread of JEV in a novel ecological environment is relevant to the possible threat that JEV may pose in the future to other receptive geographic areas, such as the west coast of the United States, southern Europe or Africa.

Keywords: Culex sp. mosquitoes; JEV genotype IV; Japanese Encephalitis Virus; Murray Valley encephalitis virus; ardeid birds; feral pigs; flavivirus.

Figure 2

Map of Northern Australia and southern Papua New Guinea with the islands of the Torres Strait showing the areas referred to in the text of JEV incursions between 1995–2004. Reproduced from van den Hurk et al. [43].

Figure 1

Geographical distribution of Japanese encephalitis virus prior to 2021. Map reproduced from van den Hurk et al. [6].

Figure 3

Map of Australia showing the Tiwi Islands and the States and Territories affected by JEV in 2021–2022 (orange shading). Human cases of Japanese encephalitis were reported from Northern Territory, Queensland, New South Wales, Victoria and South Australia; infected piggeries were reported from Queensland, New South Wales, Victoria and South Australia; infected feral pigs were reported from Queensland, South Australia and the Northern Territory; and isolations of JEV were obtained from mosquitoes trapped in Queensland, New South Wales and Victoria.

Figure 4

Phylogenetic tree showing the first JEV genome sequenced from an aborted fetus from a Queensland piggery in 2022 (green circle, inset) and its relationship to other available genotype IV whole genome sequences available from GenBank. The broader phylogenetic relationships of genotype IV with other JEV genotypes can be seen in the larger tree. The phylogenetic tree was estimated using the maximum likelihood method and a TN model with gamma rate heterogeneity, selected by IQ-TREE v.2.0.6. The results from 1000 bootstrap replicates are shown on the nodes and the scale represents the number of nucleotide substitutions per site.

Figure 5

Map of Australia showing the occurrence, distribution and abundance of feral pigs (Sus scrofa) in Australia. Map generously provided by Invasive Animals Ltd. (Canberra Bruce, Australia)/Centre for Invasive Species Solutions.