#6 – MPOX: What We Know About The Recent Outbreaks

00:00:06: in July of twenty-twenty two because the outbreak was growing.

00:00:10: The WHO declared a public health emergency with international concern.

00:00:28: Viralogical, with Florian Kramer.

00:00:41: Hello and welcome to this episode of Virological!

00:00:45: This was recorded on March ninth of twenty twenty six in Helsinki in Finland.

00:00:52: Today we're going talk about an infection that has been in media quite a lot over these last few years and that's M-Box.

00:01:00: A little bit about the name, The disease was originally called Monkey Box we'll get back to why it was and then renamed to M-box from Monkey Box.

00:01:12: And the virus that causes is I believe still called monkey box virus but the abbreviation also MBXV so M-Box Virus.

00:01:23: It's becoming a really important pathogen and so that is why I wanted to make an episode about it.

00:01:30: So, its a bona fide box virus.

00:01:34: Its related to variole virus which is the virus that causes or used to cause bugs in humans.

00:01:42: Of course thats disease has been eradicated and the original variola virus is not around anymore.

00:01:51: that has been eradicated.

00:01:53: and this monkeypox virus is also related to the vaccine virus which we use as a vaccine against the box viruses.

00:02:04: So, their relationship is very close.

00:02:07: I think monkeypox-virus and mariolla virus share about ninety six percent of their genes after genome so they're really closely become important when we talk about vaccines.

00:02:22: Okay, so this monkey box or M-box virus is a double-stranded DNA virus that has large genome.

00:02:29: it's about two hundred thousand base pairs that encode for approximately one hundred ninety proteins.

00:02:35: the virus itself is brick shaped That how its described and it's somewhere between hundred and three hundred fifty nanometers in diameter.

00:02:45: It has, as I said a lot of proteins.

00:02:47: So when they talk about destruction not going to go through the single proteins or separate proteins but in terms of this structure we basically have the genome on the inside.

00:02:58: that's encapsulated by a nucleocapsid That stands surrounded by a core wall.

00:03:05: then We have a lateral body and Then we have a membrane And depending on what type of virus particle we are talking about, there can be one membrane or two membranes.

00:03:17: So basically you have two forms of virions.

00:03:20: One is the mature virion or MV and that has one membrane.

00:03:26: That's the virion responsible for infection between humans or animals.

00:03:34: so when the virus jumps from individual to another the idea is that it's caused by this mature variant.

00:03:42: And then we have enveloped variants or EVs, they are a double membrane and their ideas there mostly responsible for cell-to-cell spread of the virus within an infected person or in an infected animal.

00:03:58: so relatively complicated life.

00:04:00: these box viruses has.

00:04:03: The virus binds to receptor on the cell surface called ecosaminoglycan and it can typically enter the cell directly at the cell membrane or via the endosomes, so I think you could use both pathways.

00:04:18: And what's interesting about these box viruses is that most DNA viruses actually go to the nucleus to replicate their genome because they co-use host DNA polymerases that this already has.

00:04:34: but that's not the case for box viruses.

00:04:37: Box viruses replicate in the cytoplasm, they have their own polymerase and actually reshape an organelle on the cytoplasm to endoplasmatic reticulum basically to form little virus factories where replication happens a lot of the virus assembly happens.

00:04:55: yeah so relatively complicated virus with alot proteins, lots genes.

00:05:00: A bit about history.

00:05:03: It was discovered in nineteen fifty-eight in Macauks, in Copenhagen and Denmark.

00:05:09: So they were keeping Macaukes there And then got this disease.

00:05:13: the virus is isolated here.

00:05:15: That's why it called monkey box because originally it was isolated from monkeys.

00:05:20: The first documented human infection took place in the nineteen seventies In the Democratic Republic of Congo at year C And I think in the same year, there were also detections of humans in Liberia.

00:05:36: Then from the nineteen seventies to the two thousands... ...the virus was mostly endemic in rainforest regions of Central and West Africa.

00:05:48: The idea is that those infections happened during that time where a lot of them are zoonotic.

00:05:55: The idea is that different rodents like squirrels, the Gambian-pouched rat, dormice and similar rodents carry the virus.

00:06:05: And then it can either jump to monkeys from there to humans or directly to humans.

00:06:12: There was actually a recent scientific study where Suti mangubis were studied as basically monkey species.

00:06:24: an outbreak happened in that monkey community and it could be traced back to the consumption of fire-footed rope squirrels.

00:06:34: So these monkeys snagged on the squirrel's, unfortunately they carry the virus.

00:06:39: then the monkeys get infected... ...and get sick!

00:06:44: The idea is that the infection happens during that time mostly or often during exposure to animals often because people hunt wild animals and of course when they hunt them, they process the meat etc.

00:07:03: They get in contact with bodily fluids of these animals with blood and with the virus.

00:07:10: And another issue is that when a meat is consumed it's not properly cooked.

00:07:15: then you can also have transmission.

00:07:17: A little bit about disease.

00:07:18: The incubation time is somewhere between three days to four weeks but usually its one week.

00:07:25: Then you get first symptoms of fever, muscle aches and sore throat.

00:07:32: And then after that a rash... First I guess it's red rash with blisters or caps.

00:07:41: The rash can be pretty painful.

00:07:44: People also have headaches, small lymph nodes and fatigue is an issue for the infection.

00:07:52: Typically, the symptoms resolve within two to four weeks.

00:07:56: Often there's also no scars that are left behind by this rash.

00:08:02: but in other cases they can be complications.

00:08:06: one complication is secondary bacterial infections sepsis encephalitis brain infections and loss of vision because the virus actually replicating some cases in Y-eyes.

00:08:19: And those complications often happen in people who have a weakened immune system, or in pregnant women and children.

00:08:31: Asymptomatic infections are recorded but they're not very common.

00:08:36: Typically the case fidelity rate is somewhere between zero point two percent to ten percent But that depends really on their outbreak and virus that causes infection.

00:08:49: different genotypes.

00:08:50: we'll get to that.

00:08:51: And also the setting, depending on how much care you get and how good their care is... ...the case for Delta rate changes by a bit.

00:09:00: The idea it's after infection your have immunity against reinfection.

00:09:05: Initially I talked about zoonotic infections but this virus can spread from humans to humans.

00:09:11: Typically through physical contact body fluids sexual transmission is important in many outbreaks but also through just you know clothes, then batting for example.

00:09:26: Also sheer dolls and so on.

00:09:28: that can lead to virus transmission.

00:09:31: And how well the virus transmits from humans to humans depends again a little bit on the virus in their outbreak.

00:09:38: So until nineteen eighty six there were about three hundred forty recorded cases.

00:09:43: The assumption is that about thirty percent of them are due human-to-human transmission And ninety-five percent of those cases were in the DRC and the Democratic Republic, after Congo.

00:09:59: What was interesting?

00:10:00: that initially mostly young people are affected... ...and a little bit background about this.

00:10:07: until late nineteen seventies People got vaccinated against smallpox So the original box or the Bariola Box virus because the virus was eradicated.

00:10:20: And so there's, there wasn't a generation of young people without any immunity to box viruses.

00:10:26: and I mentioned earlier that smallpox and also monkeyboxvirus and vaccinia virus and so on and so forth.

00:10:34: they're very closely related.

00:10:36: So there is cross-immunity.

00:10:38: And so if you got vaccinated against smallpox, You also had immunity against the monkey box virus.

00:10:43: But then people didn't get vaccinated anymore because it was necessary any more.

00:10:47: and that's when you started to see more of these inbox cases coming up.

00:10:52: starting in nineteen ninety six there were re-emergence.

00:10:55: There are more cases again.

00:10:57: In this case all other people were infected probably Because some immunity went from the smallbox infections but maybe but also because now people who there was an older generation already didn't get vaccinated against smallpox and after two thousand five, they were often more than a thousand cases per year again focused rural areas in rainforests.

00:11:24: In Central and West Africa are often younger men that we're not vaccinated against.

00:11:31: It's likely that it was focused on Biastards young men because they were probably people who went hunting and then processed meat.

00:11:39: Another example in the first nine months of twenty-twenty there are actually four thousand five hundred cases, about one hundred seventy deaths.

00:11:46: so you know these outbreaks can be pretty big and devastating.

00:11:51: What I didn't mention earlier is two genetic clades.

00:11:55: Clade One which is associated with the Congo basin and that has a mortality rate or case fidelity rate historically of about ten percent, then K-II which is associated with West Africa.

00:12:08: Which has lower case fidelity rates at one per cent.

00:12:13: Throughout the years there were also every now and then cases exported to Europe And sometimes they are small clusters where these patients then infected a health care personnel, but usually this clusters were relatively small.

00:12:32: In two thousand three there was the first outbreak in the US and that's interesting because it wasn't so Nordic outbreak.

00:12:40: It wasn't travelers who were infected.

00:12:42: they brought the virus to the

00:12:43: U.S.,

00:12:44: which actually imported rodents from Africa That were co-housed with prairie dogs.

00:12:50: people seemed use spats as well I did not know.

00:12:54: And so these prairie dogs were sold mostly in the Midwest and there are seventy-one human infections.

00:13:02: In one case a child for example was bit by one of this pet prairie dog's, then got infected.

00:13:09: The good thing is that no deaths or people who get infected recovered.

00:13:14: This was a zoonotic outbreak.

00:13:16: basically What interesting about it.

00:13:18: we can also have reverse zoonosis with monkeypox with monkeypox virus, this has been described where people were infected and then the virus jumped from humans to their pet dogs.

00:13:33: So it's basically from rodents or non-human primates to humans and then from human to dog.

00:13:40: And if something jumps back that was zoonotic initially jumps back from humans into animals.

00:13:47: than we call these reverse zoonosis.

00:13:50: There were two more recent outbreaks that are bigger and more concerning.

00:13:56: The first one started in May of twenty-twenty-two with a cluster cases in the UK, the First case was a traveler from Lagos in Nigeria.

00:14:07: there was contact tracing done And it turned out to be already a bunch of cases In the UK but already may cases we're also reported from Portugal Spain the US Canada, Israel, Sweden Belgium France Australia the Netherlands and United Arab Emirates.

00:14:28: And this could be mostly traced back to two rave festivals in Europe.

00:14:36: it turned out that this outbreak was caused by K-II more specifically K- IIB of monkey box virus.

00:14:49: It turned out that this virus was mostly spreading via physical contact and sexual contact, And most in a community of men who have sex with man.

00:15:01: In July of twenty-twenty two because the outbreak is growing The WHO declared about the health emergency of international concern.

00:15:09: So it's one step before they would declare pandemic.

00:15:13: so bigger outbreak than worried.

00:15:15: And this ended up to be a global outbreak that involved about hundred twenty countries with about hundreds thousand documented cases and about two hundred deaths.

00:15:27: Basically, case fidelity rate of zero point two percent which is low for M-Box and probably had to do with the clade but also was mostly good medical care because lot of these cases were in high income countries.

00:15:44: More severe cases were usually in people with a suppressed immune system and the fact that we're mostly young men or middle-aged man.

00:15:54: The outbreak ended May of twenty, twenty three.

00:15:57: That's when the WHO declared to end public health emergency of international concern And the outbreak was stopped by sharing information about symptoms raising awareness but also a vaccination.

00:16:13: we'll get to the vaccines in end.

00:16:16: So, good thing is that case numbers dropped rapidly and outbreak got under control even though there's still some circulation of K-II inbox or monkey box virus globally.

00:16:30: Also as part this outbreak name was changed.

00:16:34: In twenty twenty two.

00:16:35: there were racist comments about monkeys on African continent monkey box infections and so the decision was made to change the name to mbox which doesn't refer to monkeys at least for the disease.

00:16:50: As I said, i believe that virus itself is still called monkey box virus officially.

00:16:57: there's also an ongoing outbreak right now that likely started in september of twenty-twenty three again in the drc in the democratic republic.

00:17:07: This is unfortunately an outbreak with Clade I, more specifically Clade IB.

00:17:11: And because of that outbreak the WHO also declared about a health emergency of international concern in August of twenty-twenty four.

00:17:20: so far there have been about fifty thousand cases reported within this outbreak.

00:17:26: we said two to three percent case fidelity rate.

00:17:29: So that's substantially higher than than what was seen in the previous outbreak which was caused by a different clade.

00:17:37: The most affected countries, the DRC.

00:17:39: but there's also number of other African countries with larger numbers of cases.

00:17:45: that include Uganda Burundi Kenya Rwanda Tanzania Zambia and Malawi.

00:17:52: There have been a number of exported cases as well here to the US But also European Countries Germany, Austria for example.

00:18:01: and there have been human-to-human transmission clusters in countries outside of Africa as well including Sweden Spain and Thailand.

00:18:10: And so hopefully that outbreak can be stocked soon.

00:18:14: I mentioned vaccines and so vaccines has been developed by Edward Jenner already against smallpox.

00:18:21: 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 vaccinia virus.

00:18:30: You mount cross-reactive immunity to smallpox virus and it turns out you also mount cross protective immunity to Mbox or the monkey box virus.

00:18:43: And on that basis some vaccines were originally designed against smallpox.

00:18:52: newer developments are used against MBOX.

00:18:56: One of these vaccines is MVAPN, that's also known as GENIOS.

00:19:02: MVAPn stands for Modified Vaccinia Virus Anchora Bavaria Nordic so Bavarian Nordics the company makes it.

00:19:10: and that vaccine especially a newer development its replication deficient in humans.

00:19:20: that virus grows well in chicken cells but doesn't grow in human cells and so, it can be used for vaccination against M-box.

00:19:28: What was also used is an older vaccine against smallpox ACAM-II That can have more side effects, that's replication active.

00:19:40: And then there are two vaccines.

00:19:43: one has been developed in Japan LC-XVI and then also orthobox WAC which was developed in Russia, licensed in Russia in two thousand twenty-two.

00:19:54: So there's basically globally four vaccines that can be used against the MBOX And they're all based on vaccinia virus Derivate and derivates of vacciniavirus.

00:20:07: and again vacciniaVIRUS was what Edward Chen already use for vaccination against smallpox back in day.

00:20:14: There's also medication that can be used.

00:20:16: One of them is the Covirimat which has been developed for smallpox, it has been tested against monkeypox virus.

00:20:24: It's not clear that it works super well specifically when the infections are mild but it Can be used in severe cases For treatment.

00:20:35: and there're also antibody-based treatments where antibody preparations Are made from people who had being vaccinated against smallpox and that can be used for treatment as well.

00:20:47: I want to get back into this interesting finding, there is an increase in inbox cases since we stopped vaccinating the whole population against smallpox.

00:20:58: That's worth thinking about.

00:21:02: So basically stopping vaccination against smallbox was a good thing because smallpox wasn't around anymore and so it's not necessary to vaccinate people, and vaccines come with risks too.

00:21:15: But of course that leaves most of the global population vulnerable to box viruses in general And we have seen In last years Not just monkey pox virus can again jump into humans at a higher rate.

00:21:32: But there's also other box viruses that have caused human infections.

00:21:36: in Alaska, for example Boreal Box, Cow Box, Camel Box... ...have caused human cases and the idea is this will happen more often in future because even more of population has no immunity to box viruses anymore.

00:21:54: And of course, small box is eradicated but there are still samples in the US and then Russia.

00:22:01: In high security labs that our government controlled.

00:22:04: But you never know what happens in the future.

00:22:07: so The good thing is we have vaccines That are safe, they work... ...and it could be rolled out if any of these other box viruses Causes a larger outbreak.

00:22:19: Alright!

00:22:19: So thats for today about M-Box And the monkey box virus, very interesting virus.

00:22:28: Relatively complicated life cycle as with many box viruses concerning outbreaks in recent years.

00:22:35: but we also have good countermeasures.

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