#22 – Marburg Virus: Why This Infection Is So Dangerous

00:00:07: And it turned out that most people during the outbreak actually got infected directly by working with these monkeys or monkey tissues.

00:00:14: But there were also secondary cases, meaning human-to-human transmission.

00:00:46: Low and welcome to this episode of Virological!

00:00:50: This was recorded on January twenty fourth twenty twenty six in Vienna.

00:00:56: Today we're going to talk about Marburg virus, the cause of Marburg Virus disease which is a hemorrhagic fever basically meaning disease that comes with fever and with bleeding.

00:01:10: And it's actually pretty severe diseases as you'll see.

00:01:13: A little bit about marburg virus.

00:01:16: Marburg viruses belongs to the family of filoviruses.

00:01:19: It closely related to Ebola virus and Quavo virus.

00:01:24: Most people are familiar with Ebola virus, Quavo virus is basically a phyllovirus that was recently found in Europe.

00:01:31: Probably going to make an episode about this one at some point because it's interesting and the genus Marburg virus has two members which are relatively similar One actually called Marburg Virus.

00:01:46: The other one is called Raven Virus.

00:01:49: The disease that they are causing is basically the same.

00:01:52: One is more common than other, so Mabuk virus is much more prevalent and Raven virus.

00:01:57: but yeah...the only difference it's genetically a little bit different.

00:02:02: Both viruses are biosafety level four agents can be handled in Biosafety Level Four facilities which is basically highest biosafetety level.

00:02:13: The virus itself has negative sense RNA genome.

00:02:17: It only has one strand, so it's different from influenza viruses which have eight genomic segments.

00:02:23: for example in this case its just one genomic segment-one genome.

00:02:28: If you look at the virus itself we have a genome on the inside that is covered by a nucleoprotein.

00:02:39: this complex of nuclear protein and genome is also associated with polymerase, with a polymerase.

00:02:45: And then there's two more proteins VP-CERDI and VP-CERDI-FIVE.

00:02:50: VP in this case stands for viral protein so they're just called viral protein CERDI or viral protein CerDI-FI.

00:02:58: Then we have two matrix proteins one main one which is VP-FOURTY and then we have a lipid envelope, so it's an envelope virus.

00:03:12: And in this envelope you have spike protein which is called Gb which stands for glycoprotein.

00:03:20: The virus particles are filamentous.

00:03:23: I mean that the family name right filoviruses.

00:03:25: filamentous makes sense.

00:03:28: They're elongated.

00:03:30: they basically look like a night crawler There about eighty nanometers in diameter and about eight hundred nanometers long.

00:03:39: This is a little bit shorter than Ebola viruses, which are on average a little longer... ...and the virions when you look at them under their electron microscope they often have a U-shape or they're shaped like a six so basically with one end sticking out then other hand making a circle.

00:03:58: The virus has very interesting way of entering cells And it shares that wave as Ebola virus.

00:04:05: The virus attaches to the cells and then it's taking up into the cell in little vesicles that are called endosomes.

00:04:13: And, in these endosoms, the glycoprotein, the GP is partially digested by proteases.

00:04:21: Proteases basically enzymes that digest proteins... ...and the digested version of the glycobroteins binds to the actual receptor which is in the endosome and that's a protein called Niemann Big C-one.

00:04:36: And this then triggers fusion of these endosomal membrane, and the viral membrane.

00:04:42: so basically then the virus membrane fuses with the membrane of these vesicles can get into the cytoplasm, so basically really inside the cell and that's then where replication starts.

00:04:59: That is when the whole infection starts.

00:05:02: So how do you get infected?

00:05:04: There are two ways either via contact with infected animals or their excretions.

00:05:11: One important animal there is an Egyptian fruit bed which has a relatively large fruit bed can be found in many regions across Africa.

00:05:22: It's not everywhere in Africa, it needs certain environments and feeds on fruits so you won't find them in deserts but rainforest areas for example.

00:05:32: You'll also get infected by contact with non-human primates or by consumption of bushmeat.

00:05:42: And then there's a second way of getting infected, but it is more rare and that basically human-to-human transmission.

00:05:47: So you can get infected by contact with the person who already has the Marburg virus infection... ...and for this you need direct contact to bodily fluids, blood for example.. But also excretions including feces or urine.

00:06:07: milk can be a way of transmitting basically from mothers to babies.

00:06:13: And then, similar to Ebola virus this virus can hide in the body and certain sites that are in a way immunoprivileged meaning that immune system is not very active there.

00:06:24: That includes parts of our eyes but also testicles.

00:06:29: so for Ebola it was shown people who survive Ebola infections intertesticles basically for quite some time and they can actually transmit the virus on via sexual contacts.

00:06:45: And this hypothetically, it also happens with Marburg virus.

00:06:48: so that's something to keep in mind which is really interesting.

00:06:52: with these viruses The first cells that get infected in our body are cells of the innate immune system of macrophages monocytes dendritic cells.

00:07:06: Those are the cells that are supposed to be first line of defense and they're also very mobile, meaning that there's circulate in their body.

00:07:14: And when they're infected basically start to distribute the virus throughout the body.

00:07:19: later on other types of cells get infected too all kinds organs but initially it really is innate immune cells.

00:07:26: Incubation time of the viruses two to twenty-one days, but usually it's somewhere between five and nine days.

00:07:34: And infection progresses in different phases.

00:07:39: once you have symptoms there is a first phase which comes around day one through Day Five of symptomatic disease.

00:07:48: this associated initially with very high fever headaches chills fatigue nausea vomiting, diarrhea.

00:07:58: A lot of people develop a rash abdominal pain but also conjunctivitis or eye infection and just in general malaise.

00:08:06: People feel very sick.

00:08:09: Then there's the second phase that typically lasts from day five to day thirteen after infection.

00:08:16: Here we see these hemorrhagic symptoms.

00:08:18: so basically it is bleeding.

00:08:21: This bleeding that comes with hemorrhagic fever virus infections, it's not just the Marburg virus Ebola virus.

00:08:27: There are similar things but there is plenty of other viruses That also can cause hemorrhaegic fevers.

00:08:33: So what you see here?

00:08:34: often bloody stools Hematomas.

00:08:37: so basically you see blood under the skin or bleeding under the Skin bleeding from mucosal surfaces The gums for example nose from the eyes, often people are vomiting and the vomit is bloody.

00:08:52: Encephalitis can be a symptom in that phase.

00:08:54: so infection of brain inflammation of the brain edema or basically having swollen legs.

00:09:00: it's something you see during this face and often also have trouble breathing.

00:09:06: And then we have last phase which typically lasts from day thirteen to day twenty one.

00:09:13: There's a separation between people who will survive the infection and those that succumb to it.

00:09:21: Typically, people who start recovering still have muscle aches during this phase.

00:09:28: They might get hepatitis or basically liver inflammation, liver infections... they may get psychotic.

00:09:34: so there is certainly involvement of the central nervous system but these are usually signs for people having it.

00:09:40: finally survive the infection.

00:09:43: With fatal cases, usually it goes very fast.

00:09:46: in this phase people have shock they fall into a coma and to get multi-organ failure then die.

00:09:55: The case for delerty rate depends on their outbreak.

00:09:57: It's between twenty and hundred percent.

00:10:00: On average is around sixty percent.

00:10:02: So if you're infected your chance of surviving are less than fifty percent which is pretty bad.

00:10:07: A little bit about the history of Marburg virus.

00:10:11: The first outbreak occurred in nineteen sixty-seven, In Marburg under Laan in Germany and that's where name of the virus comes from.

00:10:22: but at this point there were also cases in Frankfurt in Germany or Belgrade in Yugoslavia.

00:10:28: back then it was Yugoslavia And total there are thirty two infections.

00:10:35: I believe seven people died.

00:10:37: They had five people who died in Frankfurt too and I don't think any of the people infected in Belgrade die.

00:10:45: There was, of course an investigation into the disease and what could cause it.

00:10:49: there was a team from University of Marburg working on this And that team from the Bernhard Nocht Institute in Hamburg Germany.

00:10:57: they basically isolated and characterized the virus but at the same time Anna Gilgitsch, Dwarlach Institute in Belgrade also isolated the virus and found cause of disease.

00:11:09: And investigation was done to find out where these infections came from.

00:11:16: so in Marburg they had the Behringwerke this is now I believe CSL Zekairis.

00:11:23: This was a facility that was producing syrup, but also vaccines.

00:11:29: And they used to get regular shipments of monkeys from Uganda.

00:11:36: in this case it was African green monkeys and there were used to basically harvest organs.

00:11:42: then from these organ cell cultures are made and the cell culture is very useful for vaccine production ,but also for vaccine safety testing.

00:11:52: These monkeys were infected with Marburg virus.

00:11:55: And the same shipment of monkeys from Uganda was split up and some of these monkeys went to Marburg, Some of them went to Frankfurt... ...and some of they went to Belgrade!

00:12:06: That's why this outbreak occurred.

00:12:09: It turned out that most people during that outbreak actually got infected directly by working with these monkey or monkey tissues but there also secondary cases meaning human-to-human transmission.

00:12:21: So three cases in Marburg were due to human-to-human transmission, it seems.

00:12:26: Two cases in Frankfurt and one case in Belgrade.

00:12:29: Then over the next years there are a number of smaller outbreaks basically In African countries And in nineteen eighty seven The first case with Ravan virus was identified.

00:12:43: This is in Kenya.

00:12:45: The infection occurred in a fifteen-year old Danish boy, teenager who was in Kenya on vacation and he was visiting caves.

00:12:54: And it seems that's where he got infected... ...and unfortunately has come to the infection.. ..and the virus is basically named after him.

00:13:01: I believe his first name was Raven.

00:13:04: What also interesting are cases in nineteen eighty eight and ninety ninety occurred at Vector Institute in Kotsvo, Novosibirsk in Russia.

00:13:15: Those were associated with work on Marburg virus I believe as bioweapons and one person got infected there unfortunately died And the second person I believe survived infection.

00:13:31: Back during that time of course There was research in the USSR on bio weapons And the good thing is that this has been now shut down to international treaties and nobody's doing stupid stuff like that anymore, hopefully.

00:13:47: There were outbreaks with Mabuk virus off-and on again in African countries.

00:13:53: usually smaller outbreak was only a few cases but there are some more notable outbreaks one in nineteen ninety eight from nineteen ninety two thousand in the Democratic Republic of Congo with a hundred fifty-four cases.

00:14:09: There's another bigger one that happened around two thousand four, two thousand five in Angola.

00:14:14: this two hundred and fifty-two cases.

00:14:16: And then more recently we had In twenty twenty three forty cases in Equatorial Guinea and Then also an outbreak in twenty twenty four With fifty eight cases in Rwanda.

00:14:29: and there were also more recent outbreaks But small outbreaks in Tanzania in Ghana and in Guinea.

00:14:36: And as I mentioned earlier, the case fidelity rate varies from outbreak to outbreak.

00:14:40: Usually some... As i said somewhere between twenty two hundred percent but on average around sixty percent.

00:14:46: so pretty bad infection.

00:14:50: Another interesting cases occurred in two thousand eight also in Uganda.

00:14:59: Basically what they have in Uganda.

00:15:02: In some areas this case in the Marama Gambo forest which is a A bark, they have caves where there are a lot of these beds.

00:15:13: A lot of the Egyptian food beds and you also have a lot snakes in this cave.

00:15:19: There's actually really cool videos online Where I can see the bats flying out of their cave night And snakes waiting outside catching the bats mid-air and feeding on them.

00:15:32: So tourists like to go there as tours.

00:15:35: You can visit those caves And in two thousand eight, a couple from the Netherlands went to one of these caves and then they went back home.

00:15:44: One of them had been infected with Marburg virus got symptoms in the Netherlands and unfortunately succumbed to infection.

00:15:54: Another tourist from the US has also been at that same cave and went back to the U S and got symptomatic.

00:16:03: disease was pretty bad, she was in the hospital.

00:16:07: She wasn't doing well but survived.

00:16:10: at that point of time nobody figured out her had a Marburg infection But later on I believe she heard about this case and got tested again And it turned out that she had lot's of antibodies to Marburg basically indicating that she has this infection when she visited this cave then returning back to US.

00:16:29: So thats pretty interesting.

00:16:33: Go on vacation to places like Uganda and you go do caves with bats.

00:16:38: You have to be very careful And so I also wanted to talk about this association, which is Egyptian fruit bats Which are actually called Rosettos egyptiacus.

00:16:48: That association was basically figured out between two thousand seven and two thousand nine.

00:16:53: I think there were suspicions before that But back then I think it was really proven that these bats are one of the reservoirs, potential reservoirs.

00:17:03: There might be other reservoirs out there as well and the bats may get infected from other sources.

00:17:08: but this is a very nice proof that the virus spreads between these bats in which many of them were infected.

00:17:15: so again Uganda another cave, Kitaka Cave.

00:17:22: People who work there, I think that they're looking or their mining gold in this cave and There was a small outbreak there in two thousand seven And people rushed here to investigate it.

00:17:35: Then wanted to see how these miners got infected.

00:17:40: They went into the cave to sample the bats.

00:17:46: It's kind of an interesting situation tight in terms of space.

00:17:53: In these caves I'm a little bit claustrophobic.

00:17:56: so for me the imagination.

00:17:59: going into a cave like that is terrible anyways and then you probably have the ceiling full with thousands and thousands of beds, they drop their feces or urine which might be full of virus.

00:18:13: but if you want to do that kind of research it basically has met suit what i've also heard a lot of snakes, right?

00:18:22: Bites but also cobras for example which feed on these bats.

00:18:26: And so the situation going into a cave like that full of bats infected with deadly virus it's hot you're claustrophobic and you have this snake around.

00:18:39: I'm afraid of snakes.

00:18:40: So then there is another factor i can't just not imagine doing something like that.

00:18:45: But this guy did.

00:18:46: that actually could show in his case.

00:18:50: many of these beds, this Egyptian full beds were infected with Marburg virus.

00:18:56: But again there might be other reservoirs for this virus in other species as well.

00:19:01: So what can we do about marburg virus infections?

00:19:05: That bad news is actually not much so.

00:19:08: There are no specific therapeutics.

00:19:11: you can try to treat people who have the infection In terms of their symptoms.

00:19:15: You know provide supportive therapy therapy, but there's no specific therapeutics that you could use.

00:19:23: There are also no vaccines.

00:19:25: so there is not way to prevent the infections.

00:19:28: The interesting part for Ebola.

00:19:30: we now have these things right?

00:19:31: There're two vaccines at least two different vaccines on market.

00:19:36: they more in development.

00:19:38: We've got therapeutics which based on monoclonal antibodies So if your infection already can do something about it and very similar technologies basically would work for Marburg virus as well.

00:19:51: So, vaccines have been tested in non-human primates and monkeys And they do work.

00:19:57: There's also monoclonal antibodies that neutralize marburg virus.

00:20:00: That in animal models also works.

00:20:03: But because there are usually small outbreaks... ...there is not much interest in marburg viruses As much significance there has for Ebola virus where you have larger outbreaks more frequent outbreak.

00:20:15: There's not a lot of investment into development these things.

00:20:19: And, it is also very hard to develop vaccines or therapeutics if you have only sporadic cases because you can't evaluate this thing properly in humans and that's needed in order to license them to bring them the market.

00:20:33: So its tough situation specifically in areas where we get infected with these viruses.

00:20:41: the hope is that these changes, vaccines will get licensed at some point and therapeutics become available to a point where they can be used as compassionate treatment for example.

00:20:54: Okay so very deadly virus no counter measures not good thing.

00:21:00: but I also wanted give you my opinion about potential of this virus cause larger outbreaks large epidemics or even pandemics.

00:21:12: The basic situation is that if you get infected with this virus, in contact with the virus.

00:21:19: That's bad right?

00:21:20: The chances of having an infection are probably lower than fifty percent.

00:21:26: There isn't much one can do once you're infected and If you go to areas where these viruses might be prevalent in bad populations there's no prevention either in terms of vaccines.

00:21:39: Of course, you can make sure that your wear proper safety gear or might not even want to go into a cave like this and then you cannot get infected but at least there is no vaccine that you take ahead of visiting right?

00:21:54: On the other side these viruses seem to be not very efficient in human-to-human transmission.

00:22:02: You need direct contact with bodily fluids to get infected or you need direct contacts with these bats and other species, but the virus is not good in jumping from humans into humans.

00:22:13: And that means risk –in my opinion– that this virus will ever cause a pandemic is very low because it's also easy to stop.

00:22:22: I think that's the good news!

00:22:24: Okay... That's for today from Virological.

00:22:27: As always, if you have comments or suggestions or questions please just write an email to Virological at podcastwerkstatt.com.

00:22:39: Thanks for listening in and talk with us next week!

00:23:18: Bye!