[IMJ On-Air] A tiger in the mallee: Victoria’s JEV cluster

[IMJ On-Air] A tiger in the mallee: Victoria’s JEV cluster
Date:
16 July 2023
Category:

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On the 28th of January 2022 a 75-year-old man was admitted to the regional Albury Wodonga Health Service with a high fever and Parkinsonian symptoms. The patient spent over a week in intensive care, but brain scans did not reveal an obvious aetiology and assays for a range of pathogens came up negative.

When serology eventually revealed the presence of antibodies against Japanese encephalitis virus this became only the second ever locally-acquired case on Australia’s mainland. Even more startling was the fact that the previous one had been way back in 1998 in Cape York, far north Queensland. 

The Victorian patient was the first what would become an outbreak of 43 symptomatic human cases that resulted in six deaths. The JE virus would be detected in all mainland states and retrospectively linked to another fatality in March 2021 from the Tiwi islands of the Northern Territory. In this podcast we hear about the confluence of factors that brought a classically tropical disease to the southern states. The story is told from the perspective of the treating clinicians, microbiology specialist and public health physician who started putting the puzzle together from four sentinel cases. 

Credits

Guests
Adjunct Associate Professor Ian Woolley FRACP (Monash Infectious Diseases; Monash University)
Dr Justin Jackson FRACP (Albury Wodonga Health)
Dr Sam Thorburn (Austin Health)
Dr Paul Kinsella (Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity)
Associate Professor Deborah Friedman FRACP (Victorian Department of Health; Deakin University)

Production
Produced by Mic Cavazzini DPhil. Music licenced from Epidemic Sound includes ‘Dusty Delta Day’ and ‘Hard Shoulder’ by Lennon Hutton. Image from Smith Collection/ Gado licenced from Getty Images. Editorial feedback kindly provided by Dr Aidan Tan.

Further Resources

Member access to Internal Medicine Journal, Journal of Paediatrics and Child Health and Occupational Medicine Journal
Japanese encephalitis clinical update: Changing diseases under a changing climate [Aust J Gen Pract. 2023]
Japanese encephalitis – Australia [WHO]

Transcript

JUSTIN JACKSON:             Meeting the first patient in what turned out to be this sentinel cluster is something I'll never forget. It was a Friday morning, January 28 2022 and he was in the resuscitation bay there of our emergency department at Albury-Wodonga Health. He was 75. The handover was that he had persistent rigors and that he'd had them for the last three days.

When I went and saw him what was reported as rigors were, in fact, really large amplitude myoclonic contractions of his upper limbs and there was increased tone globally. He was confused and drowsy. He had word-finding difficulty. I thought this was very unusual. I’d never, ever seen a patient presenting with persistent fever like this, and myoclonic jerks like that. So, this was already a first for me.

MIC CAVAZZINI:                 That’s Justin Jackson, consultant physician and infectious disease specialist at Albury-Wodonga Health. The regional base hospital sits on the Victoria-New South Wales border and serves a catchment of 280,000 people only a third of whom live in town. Dr Jackson is describing the first patient in a case series published in the May Edition of the Internal Medicine Journal. The journal, and this IMJ On-Air podcast are brought to you from the Royal Australasian College of Physicians.

I’m Mic Cavazzini but you won’t hear too much from me because the interview was hosted by Associate Professor Ian Woolley, who is the Infectious Diseases subeditor at the IMJ and Director of the HIV clinic at Monash Health. Just to frame the significance of these patients; after a battery of tests, it would be weeks before serology eventually revealed the presence of antibodies against Japanese encephalitis virus. This was startling because there had only every been one locally-acquired case on Australia’s mainland before, and that was way back in 1998 in Cape York, far north Queensland.

In fact, the Victorian patient was the first in what would become an outbreak of 43 symptomatic human cases that resulted in six deaths. The JE virus would be detected in all mainland states and retrospectively linked to another fatality in March 2021 from the Tiwi islands of the Northern Territory. In today’s podcast we’ll hear about the confluence of factors that brought a classically tropical disease to the southern states. The story is told from the perspective of the treating clinicians, microbiology specialist and public health physician who started putting the puzzle together from four sentinel cases. I’ll introduce the other authors as we go along, but for now I’ll hand over to Ian Woolley.

IAN WOOLLEY:  So, Justin, can you tell us what were your thoughts on that? What were you thinking was happening?

JUSTIN JACKSON:             Well, he'd actually been transferred across to us from a small hospital due to an altered conscious state and they'd found that point as well that he had gram positive cocci resembling Staph in his blood culture bottles. We really wanted to get some collateral history, so the first thing we did was contact his wife who was a great storyteller. And she told us that they had actually been out on the Murray River since the opening of the cod. And I didn't know about the opening of the cod, but that's something that happens on December 1 every year. And so they'd been fishing for the last two months. And she described how his dinghy had occasionally been absolutely covered in mosquitoes. And, you know, the favourite fishing spots they'd had to move on from because there were just so many mosquitoes.

The actual day of the illness, he'd been out on the river for seven hours straight and had very little to drink. And when he returned to camp, his wife noted that he was staring and vacant, and just not really connecting with the conversation at all. They had a caravan that was set up there on the Murray River and he woke at two—well, she woke actually, when he was kicking her in bed with these, what turned out to, be myoclonic. jerks, and speech disturbance. And so, at that point, she rushed him into the local hospital. And there, you know, he was looked after for the first three days before being transferred across to our facility, as I described.

IAN WOOLLEY:  What test results did you have at that time or shortly after?

JUSTIN JACKSON:             Yeah, we didn't have too much in the key investigations. But we did have his full blood count and his CRP, which were both almost plumb normal. There was just a mild thrombocytopenia on the full blood count. But the white cells and the neutrophils were—and the lymphocytes were—strikingly normal. So for someone that had had a fever for three days, you'd really expect some changes there. The other thing was that the CRP was plumb normal as well. So when we were thinking about the case, initially, I thought I was going to see someone with Staph aureus bacteraemia. That was that was really top of my list with septic emboli and confusion. But a normal CRP after three days made that much less likely. Shortly—well, it actually took a little while to get an MRI and a lumbar puncture, but the MRI was also completely normal, which again, struck me as pretty unusual. And the CSF wasn't—it wasn't normal, but it wasn't grossly abnormal. There were 20 lymphocytes, 7 polymorphs there and a slightly raised protein of 0.62. The only thing that sort of fitted was the CK, which was up about 2000. And that fitted with his rigidity and myoclonic jerks.

IAN WOOLLEY:  So, what was your differential diagnosis at that point?

JUSTIN JACKSON:             Yeah, well, as I said, initially, we were really thinking that it was going to turn out to be a Staph aureus bacteraemia. But when those blood culture results and the myoclonic jerks became more apparent, and the story of fishing on the Murray River and the heavy mosquito exposure, we really moved to thinking about a mosquito-borne viral encephalitis has been the most likely. As many of our listeners will recall, 2020, 2021, 2022 were all La Niña events with widespread flooding across you know, the Murray Darling Basin from Queensland, all the way down to Victoria. And we'd had—not acquired locally—but we've seen cases of Murray Valley encephalitis in the past at our hospital. And we thought that that was probably going to be the most likely diagnosis.

The other thought that we wondered about was Kunjin. So the previous La Niña event was in 2010, where we saw widespread Murray River encephalitis. But at that point, I was living up in the Northern Territory, and it was just amazing, actually. There were these huge flocks of budgerigars and the water holes were all full, the wildflowers were out. But yeah, Tim Gray, a colleague of mine, a registrar at that point, led a paper on a case report of Kunjin in an 80-year-old male, who presented almost identically to our patient with fever, confusion, and a movement disorder with myoclonus cogwheel rigidity and Parkinsonism. And I was privileged to be involved in providing details to the paper of other historical cases from around the Alice Springs area. So, I knew that Kunjin could go relatively far south. So, that was second on our list.

We'd had the mouse plague in New South Wales the year before. I don’t know if you recollect the images of hundreds of thousands of mice, and so there was the New South Wales colleagues had written up a case of lymphocytic choriomeningitis. I'd never seen a case of that before we sort of wondered about that. We covered for HSV. We covered for listeria, and yeah, I guess in the back of our minds, non-infectious causes are always possible, but that they were really the top differentials at that point.

IAN WOOLLEY:  And how did the patient progress and after that,

JUSTIN JACKSON:             Yeah, we were pretty concerned about him. He progressed to intubation on day five of his illness and the second day that he was there in hospital with us, he actually had a respiratory arrest while we were trying to get a CT-guided lumbar puncture, and so that was that was quite dramatic. Once he was intubated with a propofol and some Keppra his fever and his myoclonic jerks settled. Our initial results, including a pan-flavivirus PCR on blood, urine, and CSF were all unrevealing and at that point, we really weren't too sure. And that was a key learning point, for me, as we went back and looked at the literature; the PCR is not a great test, and perhaps Paul might comment a little bit further on this down the track.

We did wonder about an autoimmune encephalitis with some of those negative results. And perhaps, you know, an older gentleman with an underlying malignancy. So, we ended up pulsing him with three days of methylpred, and then put him on prednisolone. On day nine, he was able to be extubated. And then February 17, and I guess that's a key date that will lead us on to the next case, he was transferred to rehab. He was improving, but still not oriented to place or time and required assistance with all his care needs.

MIC CAVAZZINI: Let’s hear now from Sam Thorburn, who is the first author of the IMJ paper. He was a first-year advanced trainee in infectious diseases when he attended to another patient presenting with encephalitic syndrome.

SAM THORBURN:             Yeah, so the second case was admitted the following days. She was a 46-year-old woman who lived at home with her family, her husband and five kids and was previously very well. Again, like all of these cases, she reported a very bad- or collateral reported a very bad mosquito season with multiple bites in the lead up to her illness, and had presented with four days of headaches and lower back pain, followed by fevers and subsequent confusion that prompted her husband to bring her into hospital. She was also febrile when she presented but didn't have as marked focal neurological deficits. She was clearly confused and disorientated and was unable to follow instructions. She once again had quite benign inflammatory markers and normal microbiological investigations like blood cultures. In her case underwent a bit more of a prompt lumbar puncture, which once again showed a lymphocytic pleocytosis, this time a bit more marked with 400 white cells, the vast majority of which were mononuclear cells and raised protein. And again, underwent initial testing for more typical pathogens causing encephalitis like HSV, negative PCR and also again underwent flavivirus PCR at multiple sites, including blood and urine and CSF which were once again negative. She pleasingly had a bit more of a rapid recovery, and they spent a week in hospital. After three days or so she was able to follow two stage commands and was orientated again but with some ongoing cognitive slowing. By day seven, while still not quite herself, according to the collateral, went home with the support of her husband. We became a bit concerned during this admission, and as another patient was admitted, that there might be a cluster developing of cases for which a pathogen was not yet identified or clear.

IAN WOOLLEY:  So, after the second case went home, then almost immediately, there was a third case, is that right?

SAM THORBURN:             So, during her admission, on about day four of her admission, another patient was admitted, which was a 61 year old gentleman who lived in a town very close to our first case along the Murray, lived at home there with his wife. He again reported multiple mosquito bites in the leadup to his illness and had actually been swimming in the Murray River the week prior. And he presented with about three days of symptoms. So the development of headaches followed by widespread arthralgias and nausea and then a day of quite profound confusion, and was found by his wife in the evening unable to get out of his chair or move his left side. And on arrival in the emergency department, once again was febrile, but this time had quite a marked left sided facial droop and left sided upper limb and lower limb weakness. And again, confusion with word-finding difficulties. In his case, there was concern potentially for an acute stroke, given that unilaterality to the neurology, but nothing was found on an acute stroke protocol CT of his brain. Unfortunately, he had a more tumultuous course and required intubation on day two of his admission, at which point we were fairly concerned that there was a pathogen at play causing all of these illnesses.

IAN WOOLLEY:  So, that's why you called Deb in Melbourne. Now, what did you think when you got that phone call, Deb?

MIC CAVAZZINI: Deborah Friedman is an infectious diseases consultant with Barwon Health and a Deputy Chief Health Officer with the Victorian Department of Health. She’s also an Associate Professor with the Deakin University School of Medicine.

DEBORAH FRIEDMAN:   Yeah, I think one of my junior members of our team received that phone call about these unusual cases of encephalitis. And I guess we didn't know what to think. We had our suspicions about mosquito borne diseases. But of course, Murray Valley encephalitis hadn't been seen in 50 years and Japanese encephalitis had never been seen this far south in Australia before. But I think in mid-February of 2022 was really a perfect storm. There were stillbirths and weak piglets that were being investigated in a few different piggeries and these came to national attention when one area of Victoria realised that they were having the same reproductive losses some piggeries in New South Wales and Queensland. 

IAN WOOLLEY:  So which came first, the positive tests in the pigs of the positive tests in humans for Japanese encephalitis?

DEBORAH FRIEDMAN:   So interestingly, on the 25th of February we finally had a national meeting. And at that time, we had confirmation of Japanese encephalitis virus in a pig herd, and that was from northern Victoria, in the Campaspe local government area. And it was on the 11th of March, so nearly a few weeks later, that we had Japanese encephalitis virus detected in mosquitos in northern Victoria. So, it was in fact initially from a pig herd. And then obviously, we what we now know is that those Victorian clinical cases also confirmed as being caused by Japanese encephalitis virus.

IAN WOOLLEY:  So just to pivot a bit, Deb, can you tell us a bit about Japanese encephalitis, and how it relates to pigs?

DEBORAH FRIEDMAN:   Yes, so Japanese encephalitis is a flavivirus. It's in the same family as other types of flaviviruses that can cause encephalitis, and these include West Nile encephalitis, and also St Louis encephalitis virus and also Murray Valley encephalitis virus. And we know that the lifecycle of Japanese encephalitis includes the vector which is the mosquito that transmits infection, but there's also what we refer to as amplifying hosts and they are pigs, and also waterbirds. And what that means is when pigs and water birds get bitten by mosquitoes and develop an acute viremia, they develop actually, reasonably, high levels of viremia. And then we know that they're capable of transmitting infection either via mosquitoes or in the case of pigs, they can transmit infection directly to other pigs, and very rarely to humans. So, the pigs and the birds are part of the lifecycle of Japanese encephalitis virus and what we know is that humans, and also some other animals in particular horses are what we refer to as dead end hosts. So, we don't develop the same degree of viremia. And we don't transmit from person to person. And so, the infection ends with us when we become infected.

IAN WOOLLEY:  Does everyone who gets bitten by a mosquito with Japanese encephalitis disease.

DEBORAH FRIEDMAN:   So Japanese encephalitis virus is one of the interesting viruses in which the majority of people who become infected have no symptoms. And so probably for every 100 people who become infected with Japanese encephalitis 99, or more than 90 of them would have no symptoms, a few of them might have an acute febrile illness, and only about one in 100 would develop the brain inflammation known as encephalitis.

IAN WOOLLEY:  Sam, are there lots of piggeries in the in the Albury region.

SAM THORBURN:             So we were a little bit surprised, after finding out that this was Japanese encephalitis, exactly how many piggeries were in the region. Particularly with regard to cases one and three who live on opposite sides of the Murray River. The southern hemisphere’s largest piggery is about seven kilometres from there, about 100,000 pigs and a number of other piggeries are close to the other cases that were discussed in this paper. So certainly, a plethora of hosts nearby.

IAN WOOLLEY:  And is there any other sort of surveillance for those encephalitises that public health does Deb? I know that in other parts of Australia, they're a sentinel plot festival chickens to test for encephalitides these is that something on the Murray?

DEBORAH FRIEDMAN:   So, in Victoria, we'd actually retired our sentinel chicken flocks in the couple of years before this outbreak. And you know, there are still sentinel chicken flocks in other states, but not in Victoria. But what we do have is an extensive mosquito surveillance program which frequently throughout, not only the mosquito season, but often beginning before the mosquito season, starts doing surveillance and trapping mosquitoes in multiple different local government areas, looking for a couple of things, looking for both the species of mosquito and then also looking for some of the viral infections or other infections that can be carried by mosquitoes.

IAN WOOLLEY:  When you heard the news about the Japanese encephalitis being in in the piggeries, Justin, were you surprised? And how does that relate to previous human cases in Australia?

JUSTIN JACKSON:             Yeah, no, great question. I think for—and I speak, I’m sure, on behalf of others—it was really like walking through the Australian bush and instead of seeing a koala in a tree or a kangaroo in the scrub, seeing a monkey swinging from gumtree, or, you know a tiger lurking in the mallee. It was just completely out of place and foreign, completely alien. The story in retrospect makes sense, but no, it wasn't something that that we were looking for. There had been four cases in the outer Torres Strait between Australia and New Guinea back in 1995. The first case report on the mainland was from Cape York in 1998. Interestingly, all of these cases were genotype 2. It's turned out that that our cases from temperate Australia are genotype 4. And there's a fantastic paper by Vicki Krauss, Bart Currie and colleagues from Darwin, that was published in the New England Journal in 2020 of a case the previous year—so exactly 12 months before our cases—from the Tiwi Islands, which is just 80 kilometres north of Darwin. And this, this patient also had genotype 4 Japanese encephalitis viral infection. This genotype is recognized to occur in Indonesia as well as well, including Bali. How it got to Australia, I think, is still a matter of conjecture.

IAN WOOLLEY:  Paul, we haven't heard from you. When you got this information about the possibility of Japanese encephalitis, what sort of tests were you doing in the laboratory to look for it?

MIC CAVAZZINI: Dr Paul Kinsella is an advanced trainee with the Victorian Infectious Diseases Reference Laboratory and was a microbiology registrar at Albury Wodonga Health at the time of these presentations.

PAUL KINSELLA:                Yeah, thanks. I guess we, like everybody else didn't really have much experience with Japanese encephalitis in southern Australia. I think the first signal that we had that was a positive, at the time that all this was occurring, was a positive molecular test for Japanese encephalitis, which again, is something that we just weren't expecting to see. And as Justin described something that we had to go back to, again, to make sure that it really was genuine. I think extrapolating from other flaviruses that we were more familiar with, we were also surprised by the fact that PCRs were negative. And a lot of these diagnoses were made in retrospect, using serologic methods.

IAN WOOLLEY:  And what were there any other any other sites that we should be testing for other than the CSF? Or the blood?

PAUL KINSELLA:                Yeah, I guess, from our limited experience with Japanese encephalitis, we had a small number of cases previously, where flavivirus was detected in blood and urine. But I think what we've learned from this most recent outbreak is probably that case was an outlier. And actually, the majority of cases are negative at other sites by PCR. And so to make a diagnosis, really, the samples of choice, or the key specimens would be a CSF, a cerebrospinal fluid for flavirvirus virus PCR, recognizing that they're often negative, but when they're positive, they're extremely helpful and very specific. But the majority of our cases have been made using serology. With the downside to serology being that it can often be a retrospective diagnosis after we've got an acute and convalescent sample.

IAN WOOLLEY:  So, Deb, you have this information from the piggeries, at some stage confirmation of the tests from VIDRL, from the laboratory, to say that this was Japanese encephalitis. What were you thinking from a public health point of view?

DEBORAH FRIEDMAN:   So, our public health response from that point, first of all included really enhancing our mosquito surveillance across the state. So not only the number of traps, but also the location of traps, really trying to cover as much of northern Victoria as possible. We also coordinated a One Health approach with our agricultural colleagues in Agriculture Victoria, and we set up surveillance of piggeries across the state. And then really within the agricultural setting they made some important decisions at that point, including stopping the movement of pig herds from piggery to piggery, to prevent the spread of infections. And the veterinarians began a surveillance project looking at all agricultural animals that could become infected by Japanese encephalitis virus.

From the remainder of our public health response include a lot of education, so education of the public about the risk of mosquito-borne disease, education of clinicians about the fact that this flavivirus previously known to Asia, and the Torres Strait had now been found in southeast Australia, and indicating to them what the sorts of clinical scenarios would be in which they should test for Japanese encephalitis virus. We also put out more mosquito bite prevention messaging. And we embarked on some retrospective case finding, and we also asked all of our colleagues in hospitals around the state to do a lookback of cases of encephalitis, that did not have a microbiological diagnosis and if there was cerebrospinal fluid remaining, we could test it. Otherwise, we could perform serology on these patients to see whether or not we could detect any further cases retrospectively. And with all of that put together, that very large lookback by clinicians didn't actually find us any additional cases of Japanese encephalitis. Which probably indicates that hadn't been around for very long in Victoria. And then I guess the last thing to mention that we did was rapidly trying to procure some vaccine that was in reasonably short supply at the time.

IAN WOOLLEY:  You mentioned the mosquitoes, did you find anything different in the mosquito population?

DEBORAH FRIEDMAN:   So what we knew by looking at the mosquito population was that the species that we know is an appropriate species to transmit Japanese encephalitis virus was detected in numerous trapped mosquitoes, and that was Culex annulirostris. So we knew that we had the right mosquitoes in Victoria at that time and they were in enormous numbers. And overall through that mosquito season, or really the remainder of that mosquito season of 21-22 we had numerous detections of Japanese encephalitis in mosquitos from northern Victoria.

MIC CAVAZZINI:                In terms of tying all these species together, so the mosquito vector Culex annulirostris was already there. Maybe in larger numbers during the wet season. The pigs were already there. So what's the magic formula? I do we think that the virus just found the set of circumstances to progress a bit further south than it had but the background of pigs and mosquitoes was already there? Or was everything tweaked to make the conditions better?

DEBORAH FRIEDMAN:   And that's a that's an important point to make. We think that probably the bit to mention, in addition to what you just mentioned, is migratory waterbirds, moving south with extensive wet weather. And I think that was the thing that linked up having the appropriate mosquito vector and having already abundant pigs to actors amplifying hosts. So it was probably the weather patterns, the La Nina weather patterns causing extensive rain, especially in south-eastern Australia, which was probably the thing that brought all of these different factors together to enable the lifecycle of Japanese encephalitis virus to you to function that far southeast in Australia.

IAN WOOLLEY: Was there any consideration of feral pigs and what role they might be playing in this outbreak?

DEBORAH FRIEDMAN:   As you probably know, Australia has really abundant populations of feral pigs, especially in Queensland and Northern Territory, and the northern parts of Western Australia, a little bit less so down in the southeast and states of Australia. But we felt that feral pigs could certainly play a role and there certainly has been some retrospective testing done of feral pigs from late 2021 in the Northern Territory, where Japanese encephalitis virus had been detected. So we now know that that fits in very well from with the case from the Tiwi islands in 2021, and indicates that there probably was circulating Japanese encephalitis virus beginning in 2021, at least in northern Australia.

IAN WOOLLEY:  So, Sam, by this time, the fourth case presented to Albury hospital. Can you tell us about that case.

SAM THORBURN:             So the fourth case presented about 10 days after the third. He was a 30-year-old who lived in the same town as the third case, again about 500 meters from the Murray River, and once again, five kilometres from a very large piggery. He presented again with a pretty short prodrome, so four days of headache and quite prominent meningitic features with photophobia and neck stiffness. He had fevers when he presented to the emergency department, but had more subtle cognitive impairment, so had a degree of inattention and some word-finding difficulties, but was orientated and didn't have any other focal neurology.

He once again had a lumbar puncture that showed a lymphocytic pleocytosis this time about 83 leukocytes, the majority once again mononuclear cells and raised protein. And in this instance, had a normal MRI of his brain. He had a pretty quick resolution of symptoms. So once again was able to be discharged after a week in hospital, and we followed him over a number of months with pretty rapid resolution. The two-week follow up, he largely returned to normal and started to return to his normal activities of daily living. And so seemed to predominantly have a aseptic meningitis picture with some component of encephalitis, rather than the more fulminant cases we'd seen earlier.

IAN WOOLLEY:  So, each of these cases seem quite different in a way. Is there a broad spectrum of presentations described overseas?

SAM THORBURN:             There is, as Deb mentioned earlier, the vast majority of patients will be asymptomatic or minimally symptomatic with a nonspecific febrile illness, which did seem to be part of the prodrome in a lot of these cases. But a smaller proportion, and the exact rate varies a little bit between series and generally less or around one percent develop neuroinvasive disease. And that can have a real spectrum of manifestations which can be on the end of aseptic meningitis, as we saw in our fourth case, or much more fulminant encephalitis. And within that encephalitis subset the deficits can be pretty varied. So the most classic description historically has been Parkinsonism, as in our first case with very prominent extrapyramidal signs. And that probably occurs in about 25 percent of the neuroinvasive cases. A smaller proportion will have quite focal neurological deficits that may mimic stroke. And a smaller proportion, about 7 percent, will develop an acute flaccid paralysis, which we actually saw in our third case as he progressed, and it's associated with very poor neurological recovery. A lot of the cases have seizures, and it's very common in most case series throughout the world. And, you know, overall, the outcomes of these illnesses are very poor with about 30 percent mortality, and of those who survive a significant minority having long term neurological sequelae.

IAN WOOLLEY:  Thank you. So what evidence did you have that there was large numbers of people who might have been infected but had been asymptomatic? Were there any sort of serological surveys?

DEBORAH FRIEDMAN:   So, obviously, initially, we didn't know that, although we suspected that to be the case. And so we embarked on a serosurvey, later in 2022. And what we were trying to find out was what sort of numbers did we have for the 99 percent of people without encephalitis that were infected. So, there were two different types of serosurveys that were performed. One was performed through the Blood Bank looking at people who donated blood in many states in Australia. And then we did something else within Victoria, which was where people came in to pathology testing sites to have other blood tests done, we opportunistically recruited them to have Japanese encephalitis virus serology performed.

And so, through those two methods, we found out, starting with the Blood Bank, we found out overall, in different Australian states, about 2 percent of blood donors were found to be positive for Japanese encephalitis virus. And then once people who were born in countries where Japanese encephalitis virus is endemic, were excluded, this came about down to about 1.5 percent. In our testing through people presenting to pathology providers, we overall initially found that about 3.3 percent of people were positive for Japanese encephalitis virus. And then the third thing that we did was we looked at people who lived or worked on pig farms who were presenting for vaccination. And we recruited them to have their blood testing done before they were vaccinated. And of them, we found that about 6 percent were positive for Japanese encephalitis virus at that time. So that gave us a reasonable indication that there certainly was evidence of some infection, but obviously, it also meant that the majority of the population is still vulnerable to Japanese encephalitis virus. And there was some variable results in different states in Australia but around the 2 to 3 percent mark was the average in all of these different serosurveys.

IAN WOOLLEY:  Several of those endemic areas, there's routine vaccination for Japanese encephalitis. So can you tell us about the use of the vaccine here in Australia, the decisions that you made with the with the piggery workers, and what you see happening in the future with Japanese encephalitis vaccination?

DEBORAH FRIEDMAN:   As you mentioned, Japanese encephalitis vaccine is widely used in parts of Asia to protect the population, typically from childhood onwards. We procured some vaccine in March of 2022. And at that time, and these were through sort of Commonwealth decisions, the eligibility criteria were created for people who could get free Japanese encephalitis vaccine, and that included people who lived or worked on pig farms. We also included people above the age of 50 years, because people of older age tended to be overrepresented in our clinical cases of encephalitis. And we wanted it to be people who spent a lot of time outdoors because of their mandatory work or recreation.

Moving on from there, it took months to be able to establish a larger supply of Japanese encephalitis vaccine, and we were able to get some of the live vaccine, which is IMOJEV and also some of the Attenuated Vaccine, which is JE-SPECT, which we can use for people with lowered immunity, or pregnant women or children between the ages of two months and nine months of age. And so, since that time, we've rapidly expanded the eligibility criteria to include anyone above the age of two months living in any one of 19 different local government areas in northern Victoria, who might be at risk of Japanese encephalitis virus. So, we've got wide eligibility and we've so far vaccinated over 30,000 people.

There have been three more cases of Japanese encephalitis virus in the 2022 to 2023 mosquito season, one in Victoria, one in New South Wales, and one in South Australia. Interestingly, in all of our mosquito surveillance throughout that entire season, we did not detect any Japanese encephalitis virus in mosquitoes. Clearly there was some but the obviously there was just a low number of clinical infections detected. But of course, we subsequently know that we now have cases of Murray Valley encephalitis in this last season.

IAN WOOLLEY:  So, Paul from the laboratory point of view, how has this changed what you're going to do moving forward with, with cases of encephalitis?

PAUL KINSELLA: Yeah, thanks, Ian. I think it's really changed the aetiology of encephalitis, in Victoria. I guess now we'll be thinking more broadly of flaviviruses. In terms of testing, I guess we generally recommend testing for both or for any endemic flaviviruses present. So, in this case, both Japanese encephalitis and Murray Valley encephalitis as well. That's quite a tricky area, because differentiating the two infections using serology alone can be very difficult. So again, would still suggest that in those cases, a molecular diagnosis by PCR on a CSF really is the most specific and best way of differentiating whether it's Japanese encephalitis, or Murray Valley encephalitis. But serology testing is also helpful, in some cases that may be able to determine which of the flaviviruses is causing an infection. But in other cases, things are going to be a bit more difficult in teasing apart, which may be the inciting agent.

IAN WOOLLEY:  Thankyou. I think that's almost the end of the story of this cluster of cases. Justin, would you like to make some final comments?

JUSTIN JACKSON:             Thanks here. Yeah, I guess I just finished with a few learning lessons for me. And one of those is really that unusual weather patterns or other atypical events can lead to infectious diseases outbreaks really in divergent places where we wouldn't usually expect them. And I think in those instances, working very closely with laboratory services and public health really can provide the clues to link the data. In this case, it was linking the data from the animal cases, and then retrospectively finding the answer with the human cases.

I guess there are so many questions to be answered. It was really surprising to me not to see further cases of Japanese encephalitis here locally after this cluster last year so I would like to know the answers to the question, “Why?” What is it that made Japanese encephalitis more prominent in the first season in Murray Valley encephalitis in the next season when the when the mosquito vector appears to be the same. So, a lot of research questions and certainly some learning points.

MIC CAVAZZINI: Many thanks to Justin Jackson, Deborah Friedman, Sam Thorburn and Paul Kinsella for joining this episode of IMJ On-Air. The other co-authors were Dr Genevieve Martin from the Victorian Infectious Diseases Reference Laboratory, and its director and Professor Deborah Williamson. Also Dr John Burston, ID physician at Albury Wodonga Health. Dr Jackson would also like to acknowledge all team members from intensive care, general med, neurology and infectious diseases who looked after these patients, both at Albury Wodonga and the Alfred Hospital in Melbourne.

Finally, I want to thank Professor Ian Woolley for putting forward this interesting paper for the podcast. He already volunteers so much of his time to the Internal Medicine Journal, on top of his clinical and academic commitments. The Royal Australasian College of Physicians thrives as it does because of contributions like his. 

All members of the RACP can access the IMJ, the Journal of Paediatrics and Child Health, and the Occupational Medicine Journal via the link racp.edu.au/fellows/resources/journals. And at the College’s elearning page there are courses in microbiology and divisional exam readiness. These are just some of the resources developed to help you meet your training and CPD requirements and excel in your practice. If you don’t find what you’re after or have some feedback to help improve the show, please send an email to podcast@racp.edu.au.

I’m Mic Cavazzini, recording on the country of the Gadigal people of the Eora nation. I pay respect to their elders past and present, and their ongoing connection to land and sea. Thanks for listening.

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17 Jun 2024
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