Hantavirus outbreak: cruising for a biological bruising

0:01Amesh Adalja:All engines running. Absolute genius. Get this.

0:04Colin Crump:Welcome.

0:05Amesh Adalja:Welcome. This is the show where we bring you science. What that essentially means is discovery is advances. Research. Technology. Unbelievable. Without further ado, this is the Naked Scientist. Hello, welcome to the Naked Scientist podcast, the show that brings you the biggest breakthroughs and talks to the major movers and shakers in the worlds of science, technology and medicine. I'm Chris Smith and today, Hantavirus aboard the MV Hondias. We're exploring how the outbreak of this viral disease could have occurred on this cruise, what happens to the people who've been affected and how the international community is responding.

0:49Amesh Adalja:On the 1st of April, the MV Hondias cruise ship set sail from Argentina. Just over a week later, one passenger suddenly became ill and died. At the time, natural causes were suspected, but in the days following, more people fell ill, including some who'd already disembarked and were en route home internationally. At this point, it was recognised that the cause was an unusual and thankfully relatively rare disease with a high mortality rate called Hantavirus. And specifically, it was a form of Hantavirus called the Andes virus, specific to the Americas and usually carried by rodents. So far, of the roughly 150 people who set sail from Argentina, at least nine have since been confirmed with the infection and two more symptomatic individuals are suspected of having contracted the virus.

1:43Amesh Adalja:Well, here's shortly how the international community guided by the World Health Organization are managing the situation and what risk is posed from exposed travellers who've been returning to their home countries. But first, let's hear about the cause of the problem itself, the Hantavirus. Here's Colin Crump, who's a virologist and a fellow of Robinson College in Cambridge. Hantaviruses are RNA viruses, so they have a genome of a single-stranded RNA, and actually their genome is made up of three different segments, so it's a segmented virus, a little bit like influenza. Very small, they're about 100-120 nanometres in diameter.

2:17Amesh Adalja:That's about one ten-thousandth of a millimetre, isn't it? That's correct, yes. They live naturally in rodents, and generally their thoughts are not causing any disease in their normal hosts. But they can spread sometimes into humans and other species and cause disease. Where are they found? They're found throughout the world. So there's a lot of hantavirus spread throughout Europe and Asia and Africa. And then there's also some other ones in the Americas. They tend to be classed as New World and Old World. So the New World are the ones found in the Americas, and the Old World are the ones found in Asia and Europe.

2:46Amesh Adalja:When we say hantavirus, it sounds like one single thing. but from what you're saying it's a suite of viruses. Yeah, it's a whole family of viruses. So the original name of the virus family comes from the first one that was isolated in Korea back in the 70s near a river called the Hantan River, hence the name Hantavirus. But within that family there's maybe 60 or more different viruses spread across the world and I'm sure there's plenty more to find. And how many of those jump into us? Off the top of my head there's maybe half a dozen or more that we know of that can cause disease at least. So there may be many that jump into humans that don't cause disease that we don't know of.

3:19Amesh Adalja:But there are certainly a few well-known ones that do cause disease in humans. There's the Hantan virus I mentioned and the Sol virus, which can cause disease around Asia and China. There's also a few in Europe. There's Pumala virus and there's Dubrava virus. And then also in North America, there's Sinombre virus and there's Andes virus, which you may have heard of in the news. now when you say they live in rodents they don't make the rodents ill because what the virus has evolved to live with the rodent the rodent has evolved to live with the virus so they're they're better bedfellows yeah that's that's the the general consensus so these viruses are natural sort of uh infection in the rodents and they've evolved over the millennia to be in sort of a reasonable balance so that the viruses don't tend to evolve to kill their own natural hosts um so they tend to more cause disease when they get into an unnatural host that they don't normally live in.

4:08Amesh Adalja:And that's where we come in? Exactly, yes. So when they do spread, and this is quite rare fortunately, when they do spread into humans they can cause some quite severe disease. And there's two main types, generally associated with the old world and new world, handoviruses. So the old world ones tend to cause more of a sort of renal disease as well as a hemorrhagic fever type disease, whereas the new world ones tend to be more associated with cardio and pulmonary complications. Do they mutate? Because when we had the COVID pandemic, that was a coronavirus, obviously a very different virus entirely but we noticed that it was changing it was evolving and people became very familiar with people talking about this variant and this variant and high risk and lower risk variants do these ones do the same from what we understand at the moment not a lot no i think because they live naturally in the rodent host there's no sort of pressure for them to change if they were to sort of continue spreading in their non-natural hosts like humans then there may be more pressure to evolve but fortunately the transmission from human to human is very, very rare and only happens for like one or maybe two viruses that we know of.

5:09Amesh Adalja:A lot's been made of that, hasn't it, where people have said and made reassuring noises, these viruses don't spread efficiently in people. It seems a bit paradoxical that something can be bad enough to kill you but not infect another person from you, by and large. It all depends on how it spreads and where it's released from and how much is released. So from what we know with these viruses, it's quite difficult for them to transmit from the natural reservoir, other rodents to humans it tends to be associated with exposure to mouse urine and faeces and dust that's caused from there when sort of working in the field or working in the environment clearing up sort of you know mass droppings and things like that tend to be associated with disease and contraction and there's very little limited evidence of it ever transmitting from human to human so maybe there's just not excretion into the fluids of the human which is enough to get into another human unless you've got really really close contact they don't cause you to sneeze or cough that can spread the virus further.

6:02Amesh Adalja:But a case is being made that this Andes variant, which is the South American form at the heart of this present outbreak centred on the cruise ship, people are arguing that that one does have a track record of spreading between people. So what would be different about it that would enable it to do that then? As far as I understand this, the only real hantavirus that has shown some evidence has spread from human to human. Very small localised events like, you know, 15, 30 people in a few outbreaks in South America. It's probably down again to the biology of the virus or how it replicates when it gets into the human.

6:34Amesh Adalja:If it replicates just a little bit more or can excrete just a little bit more into bodily fluids, then it's got slightly more chance of spreading to somebody else if there's enough close contact. Do you think there's a risk, because we're thinking of it as a one-way street, that rodents have this, they give it to us, we might occasionally give it to each other. But say there's a population of rats or mice on the ship at the centre of this. And there's now a virus on the boat that does appear to spread between people. Could the people give their virus back to the mice and rats on the boat? And then we end up with a kind of a new zoonosis, which is actually quite good at spreading among people and is being carried by that population.

7:16Amesh Adalja:I guess in theory anything's possible, but that seems very unlikely. You'd think there would need to be very close contact between the human and the rodents for that transmission to go back again. So that seems not to be a likely scenario. treatments what can we do about it when someone catches these things are there any drugs are there any molecules is anyone looking at that do we have any vaccines that might be useful against these things in the future there's not a lot there has been a couple of vaccines made in china for the viruses that circulate there so the hantan virus and solvirus and are showing perhaps some promise but i think it's early days in terms of antiviral drugs there's nothing really out there specific i think there's been a few tests with some general rna virus inhibitors like ribavirin the evidence i've seen they slightly lessen the disease symptoms if they're given really early but beyond the first few days that they have no effect so there's not really much out there i think at the moment most of it is just about sort of fluid care management and the clinical setting colin trump at robinson college cambridge so let's explore the clinical impact of hantavirus infection in a bit more detail now if someone's unlucky enough to become infected which we think most likely happens when a person breathes in viral particles shed into the environment by rodent carriers of the disease or as we're learning with this present outbreak potentially through close contact with an infectious human they develop a systemic infection which can affect a number of different organs so what happens to them why and how are they diagnosed and treated as people are being returned home provision for care is being organized in specialist isolation units most countries have a number of these and they're set up to allow health care workers to look after patients while minimising the risk of an infectious agent being able to spread.

8:55Amesh Adalja:Some US patients who have tested positive for the Hantavirus are being monitored by authorities in Georgia, where experts at Emory University, Atlanta, are part of the response team. Bahuma Tatangi is an infectious diseases physician at Emory, and she's among them, and I've been speaking with her about how the virus causes disease and what they can do about it.

9:15Boghuma Titanji:One of the things that has been very well characterised, particularly in the case of the strains of hantavirus found in the Americas is that the virus has the ability to really affect the lining of blood vessels called the endothelial lining. And what it does is that it renders this cellular lining of the blood vessels leaky. You then have fluid that could potentially leak into the lungs, leading to what we call a cardiopulmonary syndrome in the most extreme cases. So that is why you probably have heard described that individuals may have difficulty with breathing, requiring advanced respiratory support from mechanical ventilation, all the way to something we call extracorporeal membrane oxygenation, which is just a system that allows the blood to be oxygenated outside the body and provide the highest level of support while someone is not able to use their own lungs for that oxygen exchange.

10:16Boghuma Titanji:The good thing, though, is that this acute and very severe phase, which is what causes lethal infection in a lot of cases of the severe infection, only lasts about two to four days. And if you're able to provide that very high level of intensive care unit support, most individuals would go on to recover because that endothelial lining also repairs itself relatively quickly once this acute phase has passed.

10:44Amesh Adalja:Do patients get any warning? Do they feel off colour for a period of time before those very dramatic respiratory and cardiopulmonary effects kick in?

10:53Boghuma Titanji:Yes, something we call the prodromal phase can last up to two to seven days and precedes this acute crash into the cardiopulmonary symptom. And that particular prodrome is characterized by Very nonspecific symptoms that you could get with any other viral infection, such as fever, severe muscle aches, a headache, chills have been described, as well as gastrointestinal syndromes or symptoms going from nausea, vomiting, diarrhea, and abdominal pain, and also just a general sense of fatigue. And this can be deceptive because some people may just assume that they have another viral infection that's going to quickly resolve.

11:35Boghuma Titanji:But then ultimately after that phase, if they progress to the more severe form with this cardiopulmonary syndrome, this can happen pretty quickly. which is why when someone has a known exposure and you're worried that they have the potential to have an Andes virus infection, when they're in that prodromal phase, it's very important to be able to test and confirm if that is indeed what is causing their symptoms and also have them in a facility that is capable of providing a high level of respiratory support and care should they progress to the more severe form.

12:13Amesh Adalja:And what's the nature of that testing? How do you confirm a person with that constellation of symptoms and the right history of contact has or hasn't got hantavirus?

12:24Boghuma Titanji:Testing for the virus in the patient's blood or you could also collect swabs from the respiratory tract. Additionally, besides these PCR testing, there are also ELISA tests that exist to test for antibodies, But these tend to be positive a little bit later than the PCR. So you can test for early antibodies that will appear in the acute phase of illness known as IgM antibodies. And these tend to be positive about a week into that whole prodromal phase that I was describing and could also help guide in making a diagnosis.

13:03Amesh Adalja:Are there any drugs that can be used to help turn the corner or is a person entirely on their own? They've obviously given supportive management, but it's down to their own immune system to try and sort this out.

13:15Boghuma Titanji:Unfortunately, there are no antiviral drugs that have been shown to be effective against the Andes strain of hantaviruses. And so we do not have any antiviral treatments that we can offer these individuals. The treatment really relies on what we call supportive care, which in the case of patients who are presenting with very severe pulmonary symptoms, constitutes of ensuring that we're providing ventilatory support. If they have low blood pressure, we're providing vasopressor support to ensure that they don't go into shock. And we are also just providing general support for all their body systems to function properly and support them through that phase of acute illness until they get to the point of recovery.

14:05Amesh Adalja:The incubation period is quite long, isn't it? In some cases, it's been documented to be two months. So the current guidance, the World Health Organization and other policymakers in different countries are adopting a sort of stance of six weeks of waiting after a person's last contact in the present outbreak. So what will happen to those people? They're being repatriated to their home countries. Some are coming here to the UK. I know you've got some coming to your neighbourhood in the US. What's going to happen to those patients? Are they going to be locked up? or kept at home? How will they be managed?

14:37Boghuma Titanji:For now, most countries are having the approach that individuals who qualify as high risk, who were in close contact with a probable or confirmed case, will be taken to facilities where they can be monitored for clinical symptoms, tested and potentially also confined and quarantined throughout that period where they remain at a high risk for developing symptoms up to six weeks from their last contact or exposure contact. Now, in terms of the individuals who are in the lower tier of exposure, who don't have a very strong exposure history, I'm taking, for example, someone who may have been on a flight with an individual who was on the Hondis and flew on that flight, but wasn't necessarily in close proximity with that individual, they will most likely just have to be passively monitored.

15:32Boghuma Titanji:This would involve monitoring themselves at home for symptoms, being connected to their health department and checking in regularly, and also notifying health authorities should they develop symptoms. So the monitoring really depends on where the risk of exposure is classified, whether it's a high risk exposure or low risk exposure. Because as you would imagine, if you try to contact trace and you end up with a thousand people who qualify as contacts, it then becomes really unreasonable to imagine a situation where you're having to quarantine a thousand people in terms of resources and just the practical logistics of making that operational.

16:18Boghuma Titanji:So we have to approach this in a manner that is guided by public health principles and logic and also in a way that still keeps the public safe.

16:29Amesh Adalja:Emory University's Behuma Titangi. The Naked Scientist podcast is produced in association with Spitfire, cost-effective voice, internet and IP engineering services for UK businesses. Find out how Spitfire can empower your company at spitfire.co.uk. Music in the programme is sponsored by Epidemic Sound, perfect music for audio and video productions. This is the Naked Scientist podcast with me Chris Smith and this week we're taking a closer look at hantavirus including the outbreak on the MV Hondias and the response from the World Health Organisation. Now the World Health Organisation have been emphatic that this is not the start of another pandemic and the UN health body added that cases are most likely linked to a bird watching trip in South America.

17:20Amesh Adalja:That's how it all started because it included visits to sites where a species of rat known to carry the disease is present. But what exactly is known about how this virus passes into humans in the first place? And what factors play a role in increasing the odds of this happening, including with other viruses jumping the species barrier? Amesh Adalja is from the Johns Hopkins University Centre for Health Security.

17:42Colin Crump:The biggest factor is a human coming into contact with that rodent. And it can happen in various different ways. It could be rodents are living in a shed that might be in somebody's backyard, living in someone's attic, and there's cleaning going on, and the rodent droppings aerosolize, and that person then develops exposure to hantavirus and then develops the symptoms later on. The other way that this can happen is that there are just more rodents around. And that could happen because of increasing rainfall patterns, for example, that increase the food supplies of rodents, which leads to a boom in their population.

18:19Colin Crump:And I think that's interesting because that's something that goes back in old Navajo legends, that when there were bountiful seasons, hantavirus soon followed in the southwest of the United States.

18:32Amesh Adalja:That's hantaviruses, but can there be other viruses following the same sort of pattern. Presumably, if you've got these sorts of things happening, the same mechanism could drive the emergence of a whole raft of different infections.

18:43Colin Crump:Exactly, not just viruses, even bacteria. So you think about in the United States, we are endemic, or we have so much Lyme disease in certain parts of the country, and that's that same cycle. So if you have high rodent populations, there are more rodents for the ticks to feed on, and then those ticks are more likely to come into contact with humans. So yes, anything that changes kind of the balance of what the reservoir is, where the pathogen, where it normally resides, anything that changes that population dynamic so that people are more likely to come into contact with it, that's going to lead to more infections.

19:17Amesh Adalja:This is therefore a human nature conflict issue, presumably.

19:21Colin Crump:It's a human-animal interface issue that leads to infectious diseases. And many of our infectious diseases, if you look back far enough, all originate from animal species.

19:30Amesh Adalja:So what sorts of factors are the big players then? You've mentioned that the weather and climate can do it you've mentioned that the rodent population which might lie downstream of us making a mess and attracting them with rubbish dumps as well it might be our activity that's doing it but what are the other big factors that will be big drivers or things we need to consider when looking mechanistically or why this sort of thing happens i think it has to do with what activities a human

19:53Colin Crump:does because you just don't always come into contact with these rodents in everyday life so if you look at this outbreak that's occurred on the ship the first patient was somebody who was bird watching and going to places like garbage dumps and places like that to look for birds, that activity, that human activity, what that person was doing had an increased risk. And that's not just for hantavirus, it's for any infectious diseases. So for example, if someone likes to explore caves, that's a human factor that increases their risk of infectious diseases. So these things are always there. Those populations are going to be fluxing based on all kinds of different variables.

20:29Colin Crump:But one thing we can control as humans is what we do. and when you're doing things that are sort of the tip of the spear literally going into places where you're more likely to come into contact with these types of animals and their viruses and

20:43Amesh Adalja:their bacteria that's a major factor and therefore the more of us there are the more rolls of the dice for this to happen the human population is going up not down it's up a third in the last couple of decades so that must be increasing the odds of this sort of thing happening the more

20:57Colin Crump:humans there are the more rodents there are the more opportunity for interaction there's going to be between the two species. But I would also argue the more humans there are, the more human brains there are, which means the more vaccines and drugs and diagnostic tests and understanding that we get as well.