#10 - Lassa Virus: Why This Infection Is Hard to Control

00:00:06: Unfortunately, there are not a lot of treatment options for atlasa.

00:00:09: Basically you can only treat the symptoms and make sure that the patient stays hydrated but there's not much more to be done once the infection occurs.

00:00:46: Welcome to this week episode of Virological!

00:00:49: This was recorded on February twenty-eighth of twenty-twenty six in New York.

00:00:55: This episode is about Lassa virus, which is the cause of Lassa hemorrhagic fever.

00:01:01: That's a pretty severe disease and that also one reason why this virus is classified as biosafety level four virus similar to Marburg or Ebola virus.

00:01:13: Lassa Virus isn't an arena virus.

00:01:15: Arena viruses are group of viruses that can cause relatively severe infections.

00:01:21: they're prevalent in South America, but also Africa.

00:01:24: And then there's one member lymphocytic coriomaniacitis virus or LCMV that actually exists globally and the house mouse population can cause severe disease.

00:01:35: maybe we'll have an episode about it at some point.

00:01:39: So arena viruses are single-stranded RNA viruses.

00:01:44: They've genomic segments.

00:01:46: so two RNA segments.

00:01:48: That's similar to what we have for influenza viruses, where you have H genomic segments but here it is just two.

00:01:55: One of them called the L segment that stands for large and encodes a polymerase in matrix protein.

00:02:02: And then we have second segment which is called S-segment and that stands small and that encodes for spike protein Which for arena virus we call glycoprotein complex and nuclear protein.

00:02:15: The interesting thing usually I mention if a virus is negative sense or positive sense.

00:02:21: In this case, it's ambi-sense.

00:02:23: so always one of the proteins on each of these segments is encoded in negative strength orientation and second one in positive strength orientation.

00:02:34: So that's pretty interesting!

00:02:36: In terms of the virus structure On the inside we have these RNA segments.

00:02:40: They are covered by nuclear protein And associated with polymerase.

00:02:45: and then we have the matrix protein, which is called Z-protein here that stabilizes the lipid envelope from inside.

00:02:52: And in this lipid envelopes you get the spike proteins GPC protein.

00:02:57: The viruses are bleomorphic.

00:03:00: In general they're round but some of them are elongated Some of them smaller or bigger.

00:03:07: They can actually range between fifty to three hundred nanometers in diameter although most of these are about one hundred two hundred twenty nanometers in diameter.

00:03:16: If you look at them under the electron microscope, they seem to have sometimes dark spots on their inside and that's actually where the name comes from.

00:03:25: when people looked at the virus initially They kind of basically found out these dark spots looks like sand and arena is the Latin word for sand And thats were the names come form.

00:03:38: The idea was this dark spot are ribosomes into the virus, but it's not really clear if that is a case.

00:03:48: And I also wanted to mention that the virus binds to our cells via receptor on the cell surface which is called alpha distroglycan in the case of LASA virus.

00:03:58: other arena viruses use different receptors.

00:04:01: Lasaviruses are genetically diverse.

00:04:03: There's so far seven genotypes, they're prevalent in West Africa.

00:04:09: In the animal reservoir you find all seven Genotypes and countries like Nigeria Mali Sierra Leone Guinea Dogo and Cote d'Ivoire Human infections.

00:04:20: So far not all of these genotypes have been found in human infections But might be that all them can cause human infections.

00:04:29: The virus itself was discovered in nineteen sixty nine when nurse, an American nurse Laura Wein got infected.

00:04:38: In Nigeria and a little village that's called Lhasa.

00:04:44: I don't think it is that little anymore.

00:04:45: i think grew quite bit but back then there were villages on the east of Nigeria in the Borno province thats at the border to Cameroon.

00:04:55: So she got sick and she was then transported to Yaws, which is a bigger down.

00:05:03: And unfortunately she died there in the hospital relatively quickly after she arrived... ...and she infected two more nurses, Charlotte Shaw & Lily Pineo.

00:05:14: Charlotte Shaw actually died of the infection but Lily Pignea was flown out to New York City so she originally from upstate New York I think from Rochester.

00:05:24: So she was flown to New York and was then hospitalized at Columbia Presbyterian Hospital.

00:05:31: And she fell in a coma for quite some time, but she survived the infection and recovered.

00:05:38: it's actually interesting how she was transported to US basically just regular commercial flight on that flight without lot of safety precautions which is nowadays something you know... You would never do, you'd fly her out on a special plane and under containment but back then these safety precautions were not in place.

00:06:02: So samples we're taking from here are brought to Yale And their two virologists actually identified the virus that had infected her.

00:06:11: One of them Eureka Sals is known for discovering a number of viruses.

00:06:17: I think he also described Zika virus for the first time and second person involved in the discovery of Lassa was Sonia Bacchi.

00:06:25: Actually, Jordi Casals got infected with the virus when he worked on it and a technician at the laboratory Juan Roman also got infected.

00:06:35: Jordi casals survived infection but actually got treated by convalescent plasma from Lilipineo.

00:06:42: But unfortunately Juan Roman died of the virus infection And of course when that happened everybody was alarmed and the virus samples were removed from Yale to the CDC.

00:06:57: Work on this virus only continued under high containment, if you're interested in these events from nineteen sixty nine there's actually a book about it called Fever with an exclamation mark afterwards.

00:07:09: that was published in nineteen seventy-four by John Fuller.

00:07:14: It's a super interesting book, it details what happened to this discovery of the virus.

00:07:20: I don't think its imprint anymore but you can get second hand online.

00:07:25: i can highly recommend it.

00:07:26: In nineteen seventy two animal reservoir for lassovirus were discovered and main reservoir seems to be Mastomis natalensis the multi-memored red or multi-memed mouse.

00:07:40: It's called like that because it has a lot of nipples, actually eighteen to twenty four which also indicates this rodent has relatively high reproduction capacity and can multiply relatively quickly.

00:07:56: these rodents are present basically everywhere in Africa south of the Sahara down to South Africa.

00:08:04: So they're pretty prevalent, but it seems that the only carry the virus in West Africa.

00:08:09: These mice get infected with the virus and then they carry life long.

00:08:15: They typically don't have symptoms so doesn't seem to bother them much But they excrete a virus via urine and feces.

00:08:24: The problem is these mice actually like live close to humans.

00:08:28: They like to invade homes feet on food that is around in these homes and unfortunately they leave their droppings, the urine this material dries then can get aerosolized.

00:08:42: people inhale it.

00:08:43: That's one way of getting infected.

00:08:46: The other ways are that their droppings and urine basically stay behind on foods And when your food gets eaten you also get infected.

00:08:56: Another way of getting infected is by eating the rodents.

00:08:59: So in some areas this mice are actually hunted and eaten, that's also a way to get infected.

00:09:07: Most of these infections or epidemics with Sonotic Lassa virus happen during the tri-season And I should mention most of these infectious, Sonotic Infections and Epidemics with Lassa happens during the Tri-Season.

00:09:22: The virus can infect a large number of different cells, but it can also infect immune cells like macrophages and the dredic cells.

00:09:31: And that's a problem because those cells are supposed to fight infection But if they get infected then they're not activated so they can't fight the infection.

00:09:42: They move around in their body and basically distribute the virus.

00:09:47: The incubation time is about seven to twenty-one days and the symptoms then start with flu like symptoms, often with a sore throat fever.

00:10:00: People are tired.

00:10:03: they get headaches.

00:10:04: muscle aches later on also problem.

00:10:08: people might have problems breathing so the lung is affected the GI tract can be effected And often people start to bleed from their gums, for example.

00:10:22: From other membranes and that's why this is haemorrhagic fever.

00:10:27: so hemorrhage fever means fever with bleeding.

00:10:31: The problem here the virus in fact cells into vascular system.

00:10:35: then it becomes leaky.

00:10:36: That way blood can basically come out.

00:10:39: Other symptoms are myocarditis, often the face of infected person gets swollen and blood pressure can drop significantly.

00:10:48: If the infection becomes more severe it often includes neurological symptoms then multi-organ failure And if that happens usually people die.

00:10:58: That's often happening about fourteen days after onset of initial symptoms.

00:11:03: There is also long term Issues when people survive the infection, about thirty percent of people who survived have hearing loss.

00:11:14: Chronic fatigue is also often a problem and depression.

00:11:17: so there can be long-term neurological symptoms as well.

00:11:21: The estimate is that there are about three hundred thousand to five hundred thousand cases every year in the West African region with about five thousand deaths.

00:11:30: So thats case fatality rate at one per cent.

00:11:35: That doesn't seem high when compared to viruses like Ebola and Marburg, but still it is pretty high.

00:11:41: And really concerning When people get the infection severe enough to get hospitalized The case fatality rate increases.

00:11:51: about fifteen to twenty percent of their hospitalized cases die off the infection But in general that case fatalities also dependent on a specific outbreak while On average, it's about one percent.

00:12:04: It can be as high as fifty percent in some outbreaks.

00:12:09: The infection is also very problematic for pregnant women In the third trimester.

00:12:14: their case fertility rate is about eighty percent and unfortunately the virus also spreads to the fetus.

00:12:21: And even if the mother survives often that the fetuses unfortunately dies.

00:12:26: and last infections are also big problem in newborn babies where the case fatality rate is about seventy-five percent.

00:12:33: And here, their symptoms include swelling of the legs and swelling of stomach then also bleeding.

00:12:39: that's often described as swollen baby syndrome so it's pretty terrible disease in babies.

00:12:45: while most of these infections are acquired through contact with this multi mammoth mice and their droppings human to human transmission is possible.

00:12:56: That's typically through relatively intense contact.

00:13:00: The virus is transmitted to bodily fluids, but also through sexual contacts and the virus can be detected in semen of survivors upto three months after they recovered.

00:13:14: so that certainly something needs to be kept in mind.

00:13:17: with lassovirus There's also post-mortem transmission, so there is plenty of cases where people get infected by handling the body of a LASA victim.

00:13:29: This partially has to do with certain practices, burial practices in the region but post mortem transmission for LASa have been recorded as well

00:13:39: e.g.,

00:13:40: Germany.

00:13:40: Unfortunately they are not a lot treatment options.

00:13:44: basically you can only treat symptoms and make sure that The patient stays hydrated, but there's not much more that can be done once the infection occurs.

00:13:56: What also needs to be mentioned is that the immune response of the infection often isn't great and very often it is relatively low.

00:14:06: There are often very low titers for neutralizing antibodies which takes a long time after recovery until they show up Typically life-long protected from a secondary infection, once they had one infection.

00:14:25: But still the immune response is not that good and their hypothesis is that the immune system really has problems attacking this spike protein, this glycoprotein complex because it seems for a lesser virus.

00:14:37: these proteins are very flexible and that makes it hard for B-cells to form proper antibodies against them.

00:14:45: This is very different compared with many other viruses where the glycoproteins are relatively rigid, which means it's easy for the immune system to make antibodies.

00:14:54: but for a LASA virus this is also a problem of vaccine development.

00:14:59: But if you're interested in these LAS infections how they are treated for these lasso-infected patients in West Africa.

00:15:08: I have another book recommendation, the book is called The Lasso Ward and it was written by Ross Donaldson who's an MD And he spent time as a medical student In Sierra Leone at Lasso ward and describes his experience.

00:15:23: there can also highly recommend that book.

00:15:25: All right As i said There isn't much That Can be done in terms of treatment For lasso infections And so far we also don't have a vaccine that can be used.

00:15:35: Most of these vaccines are actually in early clinical development, some of them had already been abandoned because they didn't seem to work well.

00:15:42: and it might have to do with this again flexibility on the spike protein.

00:15:47: So its not easy.

00:15:49: design vaccines which give you good immune responses but one vaccine is currently in phase two clinical trials And that looks promising.

00:15:58: That's a vaccine based on the vesicular stomatitis vector, which expresses the glycoprotein and is used for Ebola successfully.

00:16:09: so an Ebola vaccine based in the same platform has actually been licensed.

00:16:15: A number of technologies have been tested for LASA, development of LASa vaccines including using measles vaccine vector.

00:16:25: Using DNA vaccines and using adenovirus vectors.

00:16:28: there's even a platform that uses rabies virus expresses recombinantly Lassa virus glycoprotein and is then inactivated, used as an inactivate vaccine or tested as an activated vaccine.

00:16:41: But most of them are in phase one trials.

00:16:44: some have been abandoned because they didn't work but it would be very important to develop a Lassa vaccine and get it licensed also.

00:16:54: there's actually large number people affected by this virus in West Africa and it would be good to have something to protect the population there.

00:17:03: So, the summarized lasso virus is an interesting arinovirus that causes severe infections in West Africa.

00:17:09: It's transmitted to humans from a rodent—from the multi-mammate mouse —and can spread human–to-human as well.

00:17:19: Unfortunately we don't have any treatment options... ...and currently we do not have any licensed vaccines against either.

00:17:26: That's all for today!

00:17:27: As always, if you have any comments questions or suggestions please write an email to Virological at podcastwerkstatt.com and If you like the podcast You can support it via steady.

00:17:40: Thanks for listening in until next time

00:18:18: Bye!