Emerging Viruses: Monkeypox on the up

This week there were alarming reports of polio virus, which can cause paralysis, circulating in London. The detection was made by sampling sewage from Becton. This is worrying because, for 20 years, the UK has enjoyed “polio elimination” status, meaning the disease does not circulate here.But, what’s actually been detected is the genetic signature of polio vaccine, rather than the wild-type disease itself. Nevertheless, this is concerning because we don’t use live polio vaccines here any more, so this must have come in from abroad; and the sustained presence of the agent over many months, which is what’s been found, suggests that it’s found a toe-hold in the community, arguing that not enough people have been vaccinated to stop polio spreading. And if the spreading, weakened vaccine strain mutates into a nastier form, which can happen, we could have a problem. Virologist Wendy Barclay…

Wendy - We've had this announcement from the UK health security agency that some poliovirus has been picked up in sewage samples. So we do this routine surveillance where we look to see what viruses are out there in the water, and it can indicate what viruses might be circulating in a community in a certain place. Whereas we normally pick up very few of these polio viruses. There've now been some reports all the way through from February, till May. There is some vaccine derived polio virus in the sewage samples that have been collected in North and East London. This has caused some alarm because there's more of it than usual and over a longer period than usual, which suggests that there could well be some level of circulation in the community there.

Chris - If it's a vaccine, why are we bothered?

Wendy - The fact that it's a vaccine is interesting in several ways. First of all, we don't use the live oral vaccine against polio virus at all in the UK. We use what's called the inactivated polio virus vaccine. So that tells us that this virus which is circulating has been introduced from somewhere outside of the UK. The fact that it's circulating again is not unheard of, but the fact that it's circulating suggests that actually there are a group of people in whom it's circulating who are not immune to polio, and that's a bad way to be. We don't want there to be groups of people in the UK who aren't immune to polio.

Chris - So we've got really two headaches here in the sense that we've got admittedly vaccine derived polio virus circulating, so it's not just a one off pickup from one person shedding it. The fact that it's been there for months shows that it must be circulating among a group of people. And this shows that there's enough people who are not immune to polio in the immediate area this is happening, that it is clearly transmitting among those people.

Wendy - Yes, that's right. And then the third thing to worry about is that although the live attenuated polio virus vaccine that we have used orally in the UK in the past and is still used in a few places in the world is a good vaccine, it is attenuated as with all viruses, it can mutate. And if it reverts to being fully virulent, what that means is that it's a vaccine derived virus, but it's no longer necessarily completely attenuated and could cause serious illness.

Chris - So what will the public health practitioners who have sounded the alarm now be doing?

Wendy - So what public health agencies will be encouraging people to do is to come forward and get a polio vaccine. They will be offered the inactivated polio virus vaccine, which is widely available in the UK, and that will protect them against any serious consequences of picking up this particular vaccine derived polio virus.

“We sometimes encounter people, even perfect strangers, who begin to interest us at first sight, somehow suddenly, all at once, before a word has been spoken.” - the words of Fyodor Dostoevsky in his novel “Crime and Punishment.” It might have been written in 1866, but it’s still absolutely true today: there are people with whom we feel an instant bond when we meet them. But rather than it being down just - as Dostoevsky suggested - to what they look like, what they smell like might be a hidden part of the formula. A new study has shown that people with the same body odour profiles are much more likely to “click” instantly and become friends. It was an idea hatched by Inbal Ravreby, at the Weizmann Institute in Israel. She works with Noam Sobel, who joined Chris to talk about the work, but from a slightly unusual venue, because Israel’s got strikes going on, just like we have…

Noam - I'm actually hiding behind some building in a pool with my children running around here somewhere because there's a teacher's strike in Israel today. So life has been turned upside down a bit.

Chris - So we've got trains on strike. You've got teachers on strike, but science prevails. We're gonna try and converse all the same and you're hiding behind this cafe. I hope they don't mind. Tell us about this study. The people that you're there at the pool with, do they smell like you?

诺姆-我认为氯可能是敲门。Everybody's smell out here, but this study is about the fact that people are smelling each other and they're probably making decisions based on that. And so this particular study is decisions of the type of who you would like to befriend or become friends with. Basically it built on two observations. So one is we know for a long time that people are constantly sniffing and smelling themselves. If you just observe people, whether I do that now at the pool or you at, at your radio station or wherever people are constantly smelling themselves. Of course, if you wanna take this to the extreme, in our lab, we call this the "Lev Effect" named after German football coach, Joachim Low - or "lef" depends how you wanna pronounce it - and to those of you who have a spare minute - and this is not for the faint of heart - you can go into YouTube and perform the search "Joachim Low sniff", and you will be amazed! But that aside, we all do this. So, people are constantly sniffing themselves. We also sniff strangers, but we tend to do this in a covert manner. For example, a study from our group demonstrated that often after we shake hands with individuals, the hand that shook then comes to our nose. And the question is, what does this serve? Why do we do this? And what Inbal, the lead author, hypothesised is that we're comparing - at some subconscious level - we're comparing our own odour to other people's odour. And if the odors are the same, then that promotes social interaction. That's good for connecting. So we become friends with people who look like us, with people who have similar values to ours, even with people who have similar patterns of brain activity to ours. So similarity promotes friendship. Maybe similarity promotes friendship in body odour as well!

Chris - So how did you test that then?

Noam - Inbal concentrated on a very particular type of social setting? What she refers to as "click friends". Now, this is something we're all really familiar with from our life. Do you have any person you ever met and, you know, the minute you met, you clicked? Everybody's familiar with this phenomenon, but how did that happen? What was it there that made you click? And Inbal hypothesised that this would be chemistry. So she recruited from around Israel pairs of click friends. And once she identified a cohort of both male and female click friends, she then sampled their body odours.

Chris - But how do you actually smell that, and work out what the smells are that are on the odour profile?

Noam - Right then Inbal carried out two types of experiments. In one, she used the device we call an electronic nose. Now this is a bit deceiving because it's not really a nose, but it's a set of chemical sensors that are supposed to act like a nose. And so she smelled these pairs of body odours with an electronic nose, and then she smelled also just random pairs of people. And she asked whether the electronic nose finds the body odour of click friends to be more similar to each other than just random people. And the answer was a resounding yes, click friends smell more similar than just random pairs of individuals.

Chris - What about if you go the next step and say, "I'm now gonna ask a human to do it."

Noam - And so Inbal did exactly that, and she had cohorts of smellers smell these body odours and rate their similarity. And once again, consistent with the e-nose results, she found that smellers find that click friends - these pairs of people who are friends - smell more similar to each other than just random pairs of people.

Chris - Have you gone a step further, which is to make someone smell different?

Noam - Ah, have you been spying?

Chris - Well, maybe. I've been hanging around your swimming pool! Because, if you could take someone who, you know shouldn't be friends and subvert the smell system by making them smell better, could you do that? Or have you tried that?

Noam - So you, you know, so that's a superb question and, you know, in science jargon, what that means, if a scientist tells you that your question is superb, that means that's just what they're working on now. So yes, we're doing exactly that right now. We found a way to engineer people's body odour. And so we have now formed groups of people that we've engineered to have body odour X and other groups of people that we've engineered to have body odour Y. And we're seeing if the Xs get along together with themselves better than they get along with the Ys!

Chris - Does it work?

Noam - I don't know yet. We're also doing part of it while conducting functional magnetic resonance imaging, or brain imaging. So in other words, we're measuring the brain response while all this is happening, because we also want to identify the mechanism that's underlying all this. But we're doing exactly what you suggested we do. Namely, see if we can engineer a social interaction by engineering body odour.

Chris - Do we sort of do that as a race anyway, because when I get out the shower, I reach for the deodorant tin or I reach for the aftershave or whatever. We all do it. We all distort our natural smell profile a bit don't we?

Noam - I, you know, that's, that's a good question that, that actually we haven't yet really systematically addressed. We don't know. I'll just say one word on that. There's an interesting set of studies from about 20 years ago or 15 years ago. And what they found is that people actually select perfumes that are in a way of function of their own genetic makeup. So even your selection of perfumes is not a random act. It's something that reflects your body chemistry in some way!

In mid-May, alarm bells began to ring among public health practitioners in a number of countries when they noticed a sudden spike in cases of the rare disease monkeypox. Caused by a close relative of the smallpox virus, it’s normally found only in a handful of African countries where it’s naturally an infection of small mammals like rats and squirrels. In this respect, monkeypox is a misnomer: monkeys are only an accidental victim, like we occasionally are.People who catch the disease, usually after contact with an infected animal, often present with a high fever, swollen glands, muscle aches and weakness, and a pustular blistering rash. So why are lots of cases abruptly cropping up among men in western countries with no travel history to parts of the world where the disease is endemic? What’s changed? So far 2000 cases have been found across 40 countries, and one person has died. Michael Head is a global health researcher at the University of Southampton..

Michael - So, this Monkeypox outbreak is not like any Monkeypox outbreak we've seen before. Usually, they've been quite small in number and have been restricted to the parts of Sub-Saharan Africa that you mentioned, particularly Nigeria and Ghana, or sometimes the Democratic Republic of Congo. Here, the index case, that first case of this outbreak, will almost certainly have had a travel history with those parts of the world. We may or may not have detected the index case here and maybe it went under the radar, but it's almost certain that it will have come from that part of the world and that it will have brought the Monkeypox infection with them. With these cases that have been reported over the last few weeks, they are almost all, if not actually all, linked to these sexual networks amongst men who have sex with men and the transmission has taken place within those networks. We know that Monkeypox spreads predominantly via skin to skin contact. Well, it's very, very close contact. So, it's presumably the case that the rashes and the blisters that we see typically present with Monkeypox, as they appear on the skin, that will have been the mode of transmission from one person to another. So far, the wider community has not been impacted. So it's very, very different to, for example, Covid, which of course is a respiratory infection where everyone is at risk around an infectious person. But with Monkeypox, you do need that close contact. And within these sexual networks, there has been that close contact enough to transmit it initially, and then to sustain transmission across a few countries.

朱莉a - So we're seeing these cases of Monkeypox increasing, but we've had imported cases in the past before. So why is it now that these cases are taking hold?

Michael - So there will be a combination of several different factors that are combining here to create an outbreak that appears to be sustaining for at least a little while. One of that is population mixing as a result of restrictions being lifted from the pandemic that we've seen over the last two years. Populations are starting to mix in greater numbers. And if you introduce one infection into that community, you then provide opportunities to transmit further. As we have seen within these sexual networks, specifically with Monkeypox, we know that the smallpox vaccine does provide some level of protection against Monkeypox. Now, the smallpox vaccine was used routinely in decades previous across the globe, but it's not been used routinely for many years now. So it might well be that we're seeing a reduction in population levels of immunity against smallpox, which is therefore translating into reduced immunity to Monkeypox as well. And if there are, again, encounters between humans and animals to create that initial infection, then the population mixing might mean further cases beyond the index case. So there's a few factors like that that are combining to create outbreaks. Like we're seeing here with Monkeypox.

朱莉a - Now we've been seeing this increased transmission, what is being done to contain it?

Michael - So the key aspect of this will be the contact tracing by the public health teams to find contacts of cases and people who might be at high risk of infection. And that is a little bit of a tricky job here, because we do want to highlight the problem to those high risk populations, who are these gay sexual networks, but also we don't wish to stigmatize them. So it does pose a little bit of a problem for the public health teams. And of course the media and people who have to report on it, but we do want people to come forward. The sexual health teams who are dealing with this are extremely expert at doing so. So, actually, within this particular population, with a population that's probably used to being contacted about possible outbreaks, and certainly a public health level of expertise is used to addressing these problems as well. So that contact tracing will be crucial to reduce the number of new cases, to highlight the transmission, and where the risk areas are, and ultimately to slow down the outbreak and eventually bring it to a close.

朱莉a - And now that we're seeing these cases here, do we think that Monkeypox could become endemic in other countries like the UK? So if it got into these small mammals that normally carry the disease, could it then just become a disease that's in the background here in the UK?

Michael - That is a concern, yes. We certainly don't know if that will happen, or even if it's likely to happen. But it's something that the public health teams, the global health teams, will need to keep a very close eye on, to see if it does become endemic in our rodent populations, for example, or in any other small animals. It could happen. It may or may not happen. There's a lot we don't know about Monkeypox because there's been so few cases, generally speaking, across the world, and certainly few cases in Europe or North America, or other westernised parts of the world. So, again, a bit like Covid, it's a crash course in learning about an infectious disease as the outbreak happens. So only time will tell on that.

Of course, the most relevant example of an emerging viral infection at the moment is Covid-19, which has cost trillions. This means it’s also served as a wake-up call and also as a learning opportunity to put in place better safeguards to try to reduce the risks of this happening again. So what shape should those measures take? With us is virologist Vincent Racaniello, from Columbia University...

文森特——在我看来,有一个主要结论d that is we were caught totally unprepared and we need to do better surveillance to know what viruses are out there, poised to be the next pandemic. We just can't afford to be surprised like we were with Covid. Covid Itself tells us that we can do this surveillance; we are surveilling humans, we are surveilling sewage, we are surveilling all sorts of animals so we can know exactly when and where the new variants are. We do a great job doing surveillance for influenza virus as you just heard. We can do that for other viruses, but we barely do it. Take the polio detection in sewage in the UK - we don't even look in sewers in the US for polio virus. And so the threat is out there in animals. It's mainly in mammals because the viruses of mammals are the ones most likely to infect us. The most numerous mammals are bats and rodents, and our surveillance of them is minimal. We need to know what's out there. First of all, we need to know all the viruses that are in those animals in bats and in rodents. We need to know where they are. And then we need to do a surveillance program akin to the ones we do for influenza viruses and COVID. And we need to know what's out there. We need to know at the interface of these animals and people what viruses are circulating. And we have to look in people as well. We have to have some kind of surveillance programme where we look at, say, people who are at the interface with bats in the countryside, people who are at the interface with rodents, and we need to know what travel is doing to these viruses. We have nothing of this sort. And that's really the lesson I hope we learned from the COVID pandemic.

朱莉a - And we're seeing these increased numbers of cases of monkeypox now. So if we were more widely surveying different viruses and different animals, do you think these cases we're seeing now could have been prevented?

Vincent - It depends on how extensive the surveillance is. Right at the moment, our surveillance of monkeypox is really nonexistent. And we're only looking now because we have cases, but we don't even know which rodents are harbouring this. There's very little wildlife sampling for monkeypox and we need to do that. There's no routine sampling at travel locations. So if we could do that, we would've known, "Oh, look, suddenly there's circulation of monkeypox virus and maybe we should look out for it before we have the first cases." So, the answer is, if it's done properly then yes, we could have anticipated this particular outbreak.

朱莉a - And this goes beyond just surveying these different viruses. There's also problems accessing data in different countries. So are the ways that we can solve some of the political problems that also contribute to new viral infections emerging?

Vincent - Well, that's the big problem, right? Because politics supplies the money to do all of this research. And so the data that we generate has to be shared by everyone. It would help to have laboratories in many countries generating this data instead of sending samples, say, from Central Africa to the UK and the US. Make laboratories in those locations. Immediately put the data on servers so that everyone could access it. The money to do this is the problem, right? This is going to cost a lot of money and inevitably politicians will say, well, what really is the risk of the next pandemic? And do I have to spend 10 billion a year to find that out? I don't know how to get around the political issues because I'm a scientist and that's all I know.

茱莉亚-最后一个问题,一个罗t of these infections arise in countries with less resource. So is there a way that we can equip these countries to be better at surveillance?

Vincent - Yes, I do think so. The lesson comes from the Ebola outbreak in West Africa in 2015, where many individuals set up the technology locally in order to do viral genome sequences, rather than shipping out the samples elsewhere, they set up laboratories, they taught local individuals how to do the work, and they generated the data and they made the local people able to do it. That's what we need. We need to bring the technology elsewhere. We don't want to parachute in and out. We want to bring the technology to them. So I think it can be done. And that outbreak showed that it could be done.