[Music] In July of 2022, because the outbreak was growing, the WHO declared a public health emergency of international concern. [Music] Biological with Florian Kramer. [Music] Hello and welcome to this episode of Biological. This was recorded on March 9th of 2026 in Helsinki in Finland. Today we're going to talk about an infection that was in the media quite a lot in the last few years. And that's "Impox". A little bit about the name. The disease was originally called monkeypox and we'll get back to why that was. And it was then renamed to "Impox" from monkeypox. And the virus that causes it is, I believe, still called monkeypox virus. But the abbreviation is also MPXV so, "Impox virus". It's becoming a really important petrochannel. And so that's why I wanted to make an episode about it. So, it's a bona fide box virus. It's related to varioolar virus, which is the virus that causes or used to cause box in humans. Of course, that's a disease that has been eradicated and boxed the original varioolar virus. Box virus is not around anymore. That has been eradicated. And this monkeypox virus is also related to vaccineia virus, which is the virus that we use. We use this vaccine against the box viruses. So, the relationship is very close. I think monkeypox virus and varioolar virus share about 96% of their genes, of their genome. And so, they're really closely related. Which will become important when we talk about vaccines. Okay, so this monkeypox or "Impox virus" is a double-stranded DNA virus. It has a large genome, but 200,000 base pairs that encode for approximately 190 proteins. The virus itself is brick-shaped. That's how it's described. And it's somewhere between 100 and 350 nanometers in diameter. It has, as I said, a lot of proteins. So, when I talk about destruction, I'm not going to go through the single proteins or separate proteins. But in terms of destruction, we basically have the genome on the inside. That's encapsulated by a nucleocapsid. That's then surrounded by a core wall. Then we have a lateral body and then we have a membrane. And depending on what type of virus particle we're talking about, there can be one membrane or there can be two membranes. So, basically, we have two forms of variants. One of them is the mature variant or MV, and that has one membrane. And that's the variant that is responsible for infection between humans or between animals. But so, basically, when the virus jumps from one individual to another, the idea is that it is caused by these mature variants. And then we have envelopeed variants or EVs. They have a double membrane. And the idea is that they are mostly responsible for a cell to cell spread of the virus within an infected person or within an infected animal. So, rather, they've become complicated life that these box viruses have. The virus binds to a receptor on the cell surface that's called acosamine, which I can. And it can typically enter the cell directly at the cell membrane or via the endosomes. So, I think it can use both pathways. And what's interesting about this box viruses is that most DNA viruses actually go to the nucleus to replicate their genome because they co-use DNA polymerases. That the cell already has. But that's not the case for box viruses. Box viruses replicate in the side of the plasma. They have their own polymerase. And they actually reshape an organelle in the side of the plasma. And the plasma dichotomym basically deform little virus factories where replication happens and where a lot of the virus assembly happens. Yeah, so relatively complicated virus with a lot of proteins, a lot of genes. A little bit about the history. It was discovered in 1958 in Maccachs in Copenhagen in Denmark. So, they had the re-keeping Maccachs there. And they got this disease. And the virus was isolated there. And that's why it's called monkey box because it was originally isolated from monkeys. The first documented human infection took place in the 1970 in the Democratic Republic of Congo, DRC. And I think in the same year there were also detections in humans in Liberia. And then from the 1970s to the 2000s, the virus was mostly endemic in rainforest regions of Central and West Africa. And the idea is that those infections that happened during the time were mostly, or a lot of them were so nodic, the idea is that different rodents like squirrels, the Gambian pouched red, dormice, and similar rodents carry the virus. And then it can either jump to monkeys and from there to humans or directly to humans. And there was actually a recent scientific paper recent study where soot and mango bees were studied. That's basically monkey species. And an outbreak happened in that monkey community. And it could be traced back to the consumption of fire-footed rope squirrels. So these monkeys snag on the squirrels. And unfortunately the squirrels carry the virus. And then the monkeys get infected and get sick. And so the idea is that the infection of humans happens during that time, mostly, or often during exposure to animals. Often because people hunt wild animals. And of course when they hunt them and they process the meat and so on and so forth, they get in contact with bodily fluids of these animals with blood and with the virus. And another issue is when meat is consumed that's not properly cooked, then you can also have transmission. A little bit about the disease, the incubation time is somewhere between three days to four weeks. But usually it's about one week. Then you get first symptoms of fever, muscle aches, a sore throat. And then after that a rash, first I guess red rash and then it's blisters and then it's caps. The rash can be pretty painful. People also get headaches, swollen lymph nodes and fatigue is also an issue with the infections. Typically the symptoms resolve within two to four weeks. Often there's also no most cars to the left behind by this rash. But in other cases there can be complications. One complication is secondary bacterial infections, sapsis, and syphilitis, brain infections, and also loss of vision because the virus can actually replicate in some cases in the eyes. It's problematic and those complications often happen in people who have a weakened immune system or in pregnant women or in children. Ascent of the medical infections have been recorded but they are not very common. Typically the case fatality rates of the mortality rate is somewhere between 0.2% and 10%, but that depends really on the outbreak and the virus that causes the infection, the different genotypes that will get to that. And also the setting depending on how much care you get and how good the care is, the case fatality rate changes quite a bit. And the idea is that after the infection you're having immunity against re-infection. So initially I talked about so notic infections but these viruses can also spread from humans to humans. Typically it's through physical contact, body fluids, sexual transmission is important in many outbreaks. But also through just clothes, then bathing for example, also shears dolls and so on and so forth that can lead to virus transmission. And how well the virus transmits from humans to humans depends against a little bit on the virus and the outbreak. So until 1986 there were about 340 recorded cases. The assumption is that about 30% of them were due to human transmission. And 95% of those cases were in the DRC in the Democratic Republic of Congo. And what was important was what was interesting.
that initially mostly young people were affected. And a little bit of background about this, until the late 1970s, people got vaccinated against smallpox. So the originalpox were the very olderpox virus. And then that stopped because the virus was eradicated. And so there was then a generation of young people without any immunity topox viruses. And I mentioned earlier that smallpox and also monkeypox virus and vaccineia virus and so on and so forth. They're very closely related. And so there's cross immunity. And so if you got vaccinated against smallpox, you also had immunity against monkeypox virus. But then people didn't get vaccinated anymore because it was necessary anymore. And that's when you started to see more of these inbox cases coming up. Starting in 1996, there was a reemergence. There were more cases again. And in this case, also older people were infected, probably because some immunity rained from the smallpox infections. But maybe, but also because now people who there was an older generation already didn't get vaccinated against smallpox. And after 2005, there were often more than 1,000 cases per year. Again, focused rural areas in rainforests, in central and west Africa, often younger men that were not vaccinated against smallpox. And it's likely that it was focused on biased towards young men because there were probably people who went hunting and then processed meat. Another example in the first 9 months of 2020, there were actually 4,500 cases and about 170 deaths. So, you know, these outbreaks can be pretty, pretty big and devastated. But I didn't mention earlier was that there's two genetic clades, clade 1, which is associated with the Congo basin. And that has a mortality rate of case-fatellar rate historically of about 10%, then clade 2, which is associated with west Africa, which has a lower case-fatellar rate of about 1%. Throughout the years, there were also every now and then cases exported to Europe. And sometimes there were small clusters where these patients then infected a health care personnel. But usually these clusters were relatively small. In 2003, there was a first outbreak in the US. And that's interesting because that was a sonotica outbreak. And it wasn't travel list that were infected, that brought the virus to the US. It was actually imported rodents from Africa, that were co-housed with prairie dogs, that people seemed to use spets as well, I don't know that. And so these prairie dogs were sold mostly in the Midwest. And there were 71 human infections. In one case, a child, for example, was beat by one of these pet prairie dogs, and then got infected. The good thing is there were no deaths of all people who got infected recovered. And so this was a sonotica outbreak, basically. What is interesting is that we can also have reverse sonosis with monkeypox. This has been described with monkeypox virus. This has been described where people were infected and then the virus jumped from humans to their pet dogs. So it's basically from rodents or non-human primates to humans and then from humans to dogs. And if something jumps back, something that was sonotic initially, jumps back from humans into animals, then we call this reverse sonosis. There were two more recent outbreaks that were bigger and more concerning. The first one started in May of 2022, with a class of cases in the UK. The first case was a traveler from Lagos in Nigeria. There was contact tracing done and it turned out that there were already a bunch of cases in the UK. But already in May cases were also reported from Portugal, Spain, the US, Canada, Israel, Sweden, Belgium, France, Australia, the Netherlands, and the United Arab Emirates. And this could be mostly traced back to RAFE festivals in Europe. It turned out that this outbreak was caused by a K2, more specifically K2B of monkey box virus. And the good thing is that K is typically more mild. It turned out that this virus was mostly spreading via physical contact and sexual contact, and mostly in a community of men who have sex with men. In July of 2022, because the outbreak was growing, the WHO declared the public health emergency of international concern. So this is one step before they would declare a pandemic. So it's a bigger outbreak that they were worried about. And it descended up to be a global outbreak that involved about 120 countries. It was about 100,000 documented cases and about 200 deaths. Basically, a case fatality rate of 0.2%, which is low for an inbox. And probably had to do with the K8, but also with mostly good medical care. Because a lot of these cases were in high income countries. The more severe cases were usually in people with suppressed immune system. And affected were mostly young men or middle aged men. The outbreak ended in May of 2023. That's when the WHO declared the end of the public health emergency of international concern. And the outbreak was stopped by sharing information about the symptoms, raising awareness in the community, but also vaccination will get to the vaccines in the end. So the good thing is that the case numbers dropped rapidly, and the outbreak got under control, even though there is still some circulation of K2 inbox or monkey box virus. Global. Also, as part of this outbreak, the name was changed in 2022. There were racist comments about monkeys and African continent and monkey box infections. And so the decision was made to change the name to inbox, which doesn't refer to monkeys, at least for the disease. As I said, I believe the virus itself is still called monkey box virus officially. There's also an ongoing outbreak right now that likely started in September of 2023, again in the dear scene, the Democratic Republic of Congo. This is unfortunately outbreak with CLATE 1, more specifically CLATE 1B. And because of that outbreak, the WHO also declared the public health emergency of international concern in August of 2024. So far, there have been about 50,000 cases reported within this outbreak. We said 2-3% case fatality rate. So that's essentially higher than what was seen in the previous outbreak, which was caused by a different CLATE. The most affected countries, the DRC, but there's also a number of other African countries with larger numbers of cases. They include Uganda, Burundi, Kenya, Rwanda, Tanzania, Sandvia and Malawi. There have been a number of exported cases as well here to the US, but also European countries, Germany, Austria for example. And there have been human-to-human transmission clusters in countries outside of Africa as well, including Sweden, Spain and Thailand. And so hopefully that outbreak can be stopped soon. I mentioned vaccines. And so, vaccines have been developed by Edward Chenna already against smallpox. Those vaccines were based on vaccine virus, which is a related virus that's not very severe in humans, but when you get this infection with vaccine virus, you mount cross-reactive immunity to smallpox virus. And it turns out you also mount cross-protective immunity to the M-boxer to monkeypox virus. And on that basis, smallpox vaccines, or vaccines that were originally designed against smallpox, some that were newer developments, are used against M-box. One of these vaccines is MVAPN, that's also known as Genios. MVAPN stands for modified vaccine virus, Ankara, Bavaria Nordic, so Bavaria Nordic is the company that makes it. And that vaccine is especially that's a newer development. It's replication deficient in humans, so that makes it super safe. That virus grows well in chicken cells, but doesn't grow in human cells, and so that can be used for a vaccination against M-box. What was also used is an older vaccine against smallpox, A-CAM2000, that can have more side effects, that's replication active, and then there's more two more vaccines, one that has been developed in Japan, LC-16, and then also order box-wack, which was developed in Russia, and licensed in Russian, 2022. So there's basically globally four vaccines that can be used against M-box. [Laughter]
They're all based on vaccine virus, the rivets and the rivets of vaccine virus. And again, vaccine virus was what Edward Chen already used for vaccination against small box back in the day. There's also medication that can be used. One of them is the Covary Med, which has been developed for small box. It has been tested against monkey box virus. It's not here that it works super well, specifically not when the infections are mild, but it can be used in severe cases for treatment. And there are also antibody-based treatments where antibody preparations are made from people who had been vaccinated against small box, and that can be used for treatment as well. I want to get back to this interesting finding that there is an increase in in-ampox cases since we stop vaccinating the whole population against small box. That's worth thinking about. So basically stopping the vaccination against small box was a good thing because small box wasn't around anymore, and so it's not necessary to vaccinate people and vaccines come with risks too. But of course, it leaves most of the global population vulnerable to box viruses in general. And we have seen in the last years that not just monkey box virus can again jump into humans at the high rate, but there's also other box viruses that have cost human infections in Alaska, for example, boreal box, cow box, camel box, have cost human cases. And the idea is that this will happen more often in the future because again, more and more of the population have no immunity to box viruses anymore. And of course, small box is eradicated, but there are still samples in the US and in Russia in high security labs that are government controlled, but you never know what happens in the future. So the good thing is we have vaccines that are safe, that work, and that could be rolled out in case any of these other box viruses causes a larger outbreak. Alright, so that's it for today about inbox and the monkey box virus. Very interesting virus, relatively complicated life cycle with many box viruses, concerning outbreaks in recent years, but you also have good countermeasures. As always, if you have questions, comments, suggestions, please write an email to
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