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Issue 98: Japanese Encephalitis part 2: the JEV, MVE, WNV/KV, YFV and dengue flaviviruses

28 Mar 2022

Issue 98: Japanese Encephalitis part 2: the JEV, MVE, WNV/KV, YFV and dengue flaviviruses

While Japanese encephalitis virus (JEV) was implicated in six human clinical cases (including two deaths) from the Torres Strait islands and North Queensland in the 1990’s and ‘sentinel pigs’ were shown to have developed antibodies (an indication of prior infection, #20), the prevalence was such that no vaccination program was instituted and anything beyond routine surveillance was soon dropped. That’s not surprising, as there are always questions regarding the allocation of inevitably limited resources to rare threats.  Now, though, with the JEV suddenly appearing in human populations along the Murray Valley, the alarm bells are ringing and it seems likely that, with the related Murray Valley encephalitis (MVE) virus, JEV will be of continuing concern (#97).

Along with MVE and Kunjin virus (KV) – which we now recognise as being a variant of the the West Nile Virus (WNV) that suddenly emerged (1999) in the USA and continues to kill birds (especially corvids), horses (there is now a vaccine) and people – JEV adds to the list of flaviviruses that are clinically important in Australia. ‘Flavus’ is the latin word for ‘yellow’: the prototype is yellow fever virus (YFV) which, around 1906 for example, debilitated the 10,000 or more workers in the first (French) phase of the construction of the Panama Canal. Much more lethal than JEV, MVE or WNV, over 85 per cent were hospitalised, and half of the 15 per cent with severe disease died with bleeding, vomiting, kidney and liver damage.  The latter causes the skin and the whites of the eyes to ‘yellow’, the characteristic sign of jaundice caused by the failure to excrete the bile pigment bilirubin, a breakdown product from the haemoglobin in red blood cells that have passed their ‘use by’ date. By contrast, the incidence of clinical encephalitis is about one in 100 for JEV, and one in 800 for MVE and, though KV can be lethal in 20 to 40 per cent of infected horses, it hasn’t been implicated in a single human death.

While the clinically important ‘target organ’ – liver for YFV, the brain for JEV, MVE and WNV – may vary, what links all the flaviviruses and, indeed all arboviruses, is viremia and the presence of high virus titres in the blood. Unlike the respiratory spread of SARS-CoV-2 which, so far as we know multiplies only in mammals, the transmission of any arbovirus requires that some form of arthropod takes a blood meal from one individual (particularly in what we may think of as the amplifying/maintaining species) then further transmits the virus to a human subject. Of the flaviviruses that sporadically cause problems in Australia, only one (dengue virus, DV) is thought to involve humans as a key maintaining host. Clinical dengue (also called breakbone fever) is characterised by fever, rash, vomiting, muscle and joint pains. Dengue occurs periodically in northern Australia but, perhaps because human numbers are relatively low and there are no non-human primates to maintain a ‘sylvatic (forest) cycle’, it is an ‘occasional invader’ and has not so far become endemic. The fact that Australia has never had a problem with YFV may also reflect that absence of a non-human primate (monkey) reservoir.             

This new profile of JEV being detected as far south as the Murray Valley likely reflects that it is now endemic in maintaining host species in, at least, northern Australia. Despite the fact that evidence of JEV infection has been found in at least 70 ‘southern’ piggeries the likely scenario is that  – as the cooler months remove the mosquito ‘vector’ species (Culex annulirostris) – any ‘virus reservoir will only be maintained north of a tropical ‘mosquito-line’. If the latter is the case, how frequently, as with the long MVE experience, will we see periodic re-introductions for the southern summer season? This would likely involve the virus ‘hitching a ride’ in migrating birds (herons or egrets), then local mosquito transmission to pigs as an ‘amplifying host’.

Infected pigs might be expected to be viremic for, say, 5 to 7 days before they start making the antibodies that terminate the blood-borne phase (#20). The consequence is that, though a constant supply of new litters should provide immunologically naïve piglets, will there be enough mosquitos around to maintain transmission? Additionally, if the sow has been infected or vaccinated, it’s also possible that piglets will be protected for a couple of months by colostral antibodies supplied in the mother’s milk. We know from endemic areas that JEV can cause reproductive loss (stillborn piglets) in younger, previously uninfected sows, but local disease incidence profiles will no doubt tell us whether vaccination is justified here from the economic and/or public health perspective. Clearly, we would not be vaccinating feral pigs.

Time will also clarify whether it is important to vaccinate all piggery workers and, indeed, everyone who lives in potentially threatened locations. Perhaps those who vacation along the Murray in summer would also want to be added to that list. The available vaccines have been in use for a long time across the Pacific region, and they are known to be safe, effective and to confer durable (at least 10 years) protection. Also, unlike SARS-CoV-2, JEV is antigenically stable and does not change over the decades. We’ll discuss that further next week. To be continued…

Setting it Straight by Laureate Professor Peter Doherty Archive