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

18m 19s

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

Lassa virus, discovered in 1969 in Nigeria, is an arenavirus that causes Lassa hemorrhagic fever, a severe disease classified as biosafety level 4. It has an ambisense RNA genome with two segments: the L segment encodes polymerase and matrix protein, and the S segment encodes the spike glycoprotein and nucleoprotein. The virus is primarily zoonotic, transmitted from the multimammate mouse (*Mastomys natalensis*) to humans via aerosolized excreta, contaminated food, or consumption of rodents. Human-to-human transmission occurs through bodily fluids, including sexual contact, and post-mortem handling. Incubation is 7–21 days, with symptoms starting as flu-like (fever, sore throat, muscle aches) and progressing to hemorrhagic manifestations, neurological issues, and multi-organ failure. The overall case fatality rate is about 1%, but it rises to 15–20% in hospitalized cases and up to 80% in pregnant women and 75% in newborns. Long-term effects include hearing loss and chronic fatigue. Currently, no specific treatments or licensed vaccines exist; only supportive care (hydration) is available. Vaccine development is hindered by the flexible spike protein, which evades neutralizing antibodies. A promising VSV-vectored vaccine, similar to the Ebola vaccine, is in phase 2 trials. Other approaches (measles, DNA, adenovirus, rabies vectors) are in early stages. The virus is genetically diverse, with 17 lineages circulating in West Africa, and causes an estimated 300,000–500,000 cases annually, with 5,000 deaths.

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Unfortunately, there are not a lot of treatment options for elasa. Basically, you can only treat the symptoms and make sure that the patient stays hydrated, but there's not much more that can be done once the infection occurs. Virological with Florian Kramer Welcome to this week's episode of Virological. This was recorded on February 28th of 2026 in New York. This episode is about lassa virus, which is the cause of lassa hemorrhagic fever. That's a pretty severe disease, and that's also why one of the reasons why this virus is classified as biosafety level 4 virus, similar to maubwork or Ebola virus. Lassa viruses and arena viruses, arena viruses are a group of viruses that can cause relatively severe infections. They're prevalent in South America, but also in Africa, and then there is one member lymphocytic coriomanagitis virus, or LCMV that actually exists globally in the house, mouse population, and can also cause severe disease. Maybe we'll have an episode about that one at some point. So arena viruses are single-stranded RNA viruses. They have genomic segments, so they have two RNA segments. That's similar to what we have for influenza viruses, where we have each genomic segments, but here it's just two. One of them is called the ALE segment, that stands for large, and that encodes a polymerase and the matrix protein. And then we have the second segment, which is called S segment, and that stands for small, and that encodes for the spike protein, which for arena viruses we call glycoprotein complex and the nuclear protein. And the interesting thing is usually I mentioned if a virus is negative sense or positive sense, in this case it's ambi sense. So always one of the proteins on each of the segments is encoded in negative strength orientation and the second one in positive strength orientation. So that's pretty interesting. In terms of the virus structure, on the inside we have these RNA segments, they are covered by nuclear protein and associated with polymerase. And then we have the matrix protein, which is called set protein here, that stabilizes the lipid envelope from the inside. And in this lipid envelope, we have the spike protein, this GPC protein. The viruses are bleomorphic in general, they're round, but they some of them are elongated, some of them are small, some of them are bigger. They can actually range from 50 to 300 nanometers in diameter, or the most of them are about 100 to 120 nanometers in diameter. If you look at them under the electron microscope, they seem to have sometimes dark spots on the inside. And that's actually where the name comes from. When people looked at the virus initially, they kind of basically found that these dark spots look like sand, and arena is the Latin word for sand, and that's where the name comes from. The idea is that these dark spots are ribosomes from the wholesale that are packaged into the virus, but it's not really clear if that's that's really the case. And I also want to dimension that the virus binds to our cells via a receptor on the cell surface, which is called alpha-destructlychan, in the case of lasavirus. Other renavirus use different receptors. Lasavirus are genetically diverse. There's so far 17 autofocus, they're prevalent in West Africa. In the animal reservoir, you find all 17 autofocus in countries like Nigeria, Mali, Sierra Deon, Guinea, Dogo, and Cotihuah. Human infections are so far not all of these genotypes have been found in human infections, but it might be that all of them can cause human infections. The virus itself was discovered in 1969 when nurse, an American nurse, Laura Vine, got infected in Nigeria in a little village that's called Lassa. I don't think it's that little anymore. I think it grew quite a bit, but back then it was a village, and that's in the east of of Nigeria in the Borno province that's on the border to Cameroon. So she got sick and she was then transported to Yos, which was a bigger down. Unfortunately, she died there and I was a little relatively quickly after she arrived. She infected two more nurses, Charlotte Shaw and Lily Pineo. Charlotte Shaw actually died of the infection, but Lily Pineo was flown out to New York City, so she was originally from upstate New York, I think from Rochester. She was flown to New York, and was in hospitalized at Columbia Presbyterian Hospital, and she fell in a coma for quite some time, but she survived the infection and recovered. It's actually interesting to read how she was transported to the US. It was basically just a regular commercial flight, and she was just on that flight without a lot of safety precautions, which is nowadays something that you would never do. You would fly her out on a special plane and under containment and so on and so forth, but back then this safety precautions were not in place. So samples were taken from her and brought to Yale, and their two-varrologists actually identified the virus that had infected her. One of them, Yodica Salis, is actually known for discovering a number of viruses. I think you also described C.Ca virus for the first time, and the second person involved in the discovery of last of us, Sonia Bakke. Actually, Yodica Salis got infected with the virus when he was working with it, and a technician in the laboratory Juan Roman also got infected. Yodica Salis survived the infection, and he actually got treated with convalescent plasma from Lily Pineo, but unfortunately Juan Roman died of the virus infection. And of course, when that happened, everybody was alarmed, and the virus samples were moved from Yale to the CDC and work on these viruses on the continued and the high containment. And if you're interested in these events from 1969, there's actually a book about it that's called Fever, with an exclamation mark afterwards, that was published in 1974 by John Fola. It's a super interesting book that details what happened in this discovery of the virus. I don't think it's in print anymore, but you can get it second hand online. I can highly recommend it. In 1972, the animal reservoir for last-a-virus was discovered, and the main reservoir seems to be mastomas natalenses, the multi-memetrade or multi-memetmouse. It's called like that because it has a lot of nipples, actually 18 to 24, which also indicates that this rodent has a relatively high reproduction capacity and can multiply relatively quickly. These rodents are present basically everywhere in Africa, south of the Sahara, down to South Africa. So they're pretty prevalent, but it seems that they only carry the virus in West Africa. So these mice get infected with the virus, and then they carry it lifelong. They typically don't have symptoms, so it doesn't seem to bother the mice much, but they excrete the virus via urine and feces. The problem is that these mice actually like to live close to humans. They like to invade homes. They like to feed on food that is around in these homes, and unfortunately they leave their droppings and they're urine, this material dries and then can get aerosolized, and then people inhale it, and that's one way of getting infected. The other way is that they're their droppings and they urine basically stay behind on food, and then when that food is eaten, you can also get infected. And another way of getting infected is by eating the rodents. So in some areas, these mice are actually hunted and eaten, and that is also a way of getting infected. Most of these infections, most of these epidemics with sonotic lacer virus happen in the dry season, and I should also mention that most of these infections, the sonotic infections and epidemics with lacer happen in the dry season. The virus can infect a large number of different cells, but it can also infect immune cells like macrophages and the tridic cells, and that's a problem because those cells are supposed to fight the infection, but the problem is if they get infected, they're not activated, so they can't fight the infection, and they're mobile in the body, they move around, and the problem is that they basically distribute the virus in the body. The incubation time is about seven to twenty one days, and the symptoms then start with flu-like symptoms, often with a stores road, fever, people are tired, they get headaches, muscle aches. Later on also problems, people might have problems breathing so the lung is affected. The GI tract can be affected, people can develop their rear and often people start to bleed from their gums for example, from other membranes and that's why this is hemorrhagic fever. So hemorrhagic fever means fever resplaining. The problem here is that the virus infects cells in the vascular system and then it becomes leaky and that's why blood can basically come out. Other symptoms are myocarditis, often the face of the infected person gets swollen and blood pressure can drop significantly. If the infection becomes more severe, it often includes neurological symptoms and then multi-organ failure and if that happens usually people die that's often happening about 14 days after onset of the initial symptoms. There's also long-term issues when people survive the infection, about 30% of people who survive have hearing loss, chronic fatigue is also often a problem and depression so there could be long-term neurological symptoms as well. The estimate is that there are about 300,000 to 500,000 cases every year in the West African region with about 5,000 deaths so that's a case fatality rate of about 1%. That doesn't seem high when compared to viruses like Ebola and Marburg but still it is pretty high and pretty concerning. When people get the infection severe enough to get hospitalized, the case fatality rate increases about 15 to 20% of the hospitalized cases die of the infection but in general the case fatality rate is also dependent on the specific outbreak while on average it's about 1% it can be as high as 50% in some outbreaks. The infection is also very problematic for pregnant women in the third trimester. There the case fatality rate is about 80% and unfortunately the virus also spreads to the fetus and even if the mother survives often the fetus unfortunately dies and last infections are also a big problem in newborn babies where the case fatality rate is about 75% and here the symptoms include swelling of the legs and swelling of the stomach and then also bleeding and that's often described as swollen babies in terms of it's pretty terrible disease in babies. While most of these infections are acquired through contact with these multi-memid mice and their their droppings human to human transmission is possible that's typically through relatively intense contact the virus is transmitted through bodily fluids but also through through sexual contacts and the virus can be detected in semen of survivors up to three months after they recovered. So that's certainly also something that needs to be kept in mind with lasavarus. There's also post-mortem transmission so there is plenty of cases where people get infected by handling the body of a lasavictim. This partially has to do with with certain certain practices, burial practices in the region but post-mortem transmission for lasav has also been recorded for example in Germany. Unfortunately there are not a lot of treatment options for a lasso. Basically you can only treat the symptoms and make sure that the patients stay hydrated but there's not much more than can be that can be done once the infection occurs. What also needs to be mentioned is that the immune response to the infection is often not that great. Very often immune response is relatively low. There's often very low titers of neutralizing antibodies and it often takes a long time after recovery until neutralizing antibodies show up. People typically lifelong protected from secondary infection once they had one infection but still the immune response is not that good and the hypothesis is that the immune system really has problems attacking this spike protein, this chai-crop protein complex because it seems for a lasso virus, this protein is very flexible and that makes it hard for for B cells to form proper antibodies against it. This is very different compared to many other viruses where the chai-crop proteins are relatively rigid and it's relatively easy for the immune system to make antibodies but for a lasso virus that's a problem and that is also a problem for vaccine development. But if you're interested in in these lasso infections how they are treated in the situation and for these lasso infected patients in West Africa, I have another book recommendation. The book is called the lasso word and it was written by Ross Donaldson who is an MD and he spent time as a medical student in Sierra Leone in a lasso word and describes his experience there. I can also highly recommend that book. All right, as I said, there is not much that can be done in terms of treatment for for lasso infections and so far we also don't have a vaccine that can be used. Most of these vaccines are actually in early clinical development. Some of them have already been abandoned because they didn't seem to work well and that might have to do with this again flexibility of the spike protein and so it's not so easy to design vaccines that give you good immune responses but one vaccine is currently in phase two clinical trials and that looks promising. That's a vaccine that's based on a vesicular stomatitis vector that expresses the glycoprotein and that's the same strategy that was used for Ebola and successfully used for Ebola. So a Bola vaccine based on the same platform has actually been licensed and is in use. A number of technologies have been tested for for a loss for development of lasso vaccines including using a measles vaccine vector, using DNA vaccines, using adenovirus vectors and there's even a platform that uses rabies virus that then expresses, recombinantly, lasso versus glycoprotein and is then inactivated and used as inactivated vaccine or tested as inactivated vaccine. But as I said, most of them are in phase one trials. Some of them have been abandoned because they didn't work but of course it would be very important to develop a lasso vaccine and get it licensed also because there's actually a large number of people affected by these virus in West Africa and it would be good to have something to protect the population there. So the summarized lasso virus is an interesting arena virus that causes severe infections in West Africa. It's transmitted to humans from a rodent, from the multi-memet mouse and can spread from humans to human to human in some cases as well. Unfortunately we don't have any treatment options and currently we don't have any licensed vaccines against it either. So that's it for today. As always if you have any comments, questions or suggestions please write an email to [email protected] and if you liked the podcast you can support it by a steady. Thanks for listening in and until next time, bye. Podcast app.

Podcast Summary

Key Points:

  1. Lassa virus, a biosafety level 4 pathogen, causes Lassa hemorrhagic fever, a severe disease endemic in West Africa.
  2. The virus is an arenavirus with an ambisense RNA genome, transmitted primarily via the multimammate mouse (*Mastomys natalensis*) through urine, feces, or consumption.
  3. Human-to-human transmission occurs via bodily fluids, including sexual contact and post-mortem handling.
  4. Symptoms range from flu-like illness to bleeding, neurological issues, and multi-organ failure; case fatality rate is ~1% overall but up to 80% in pregnant women and 75% in newborns.
  5. No specific treatments or licensed vaccines exist; supportive care (hydration) is the only option.
  6. Vaccine development is challenging due to the flexible spike protein, though a VSV-vectored vaccine is in phase 2 trials.

Summary:

Lassa virus, discovered in 1969 in Nigeria, is an arenavirus that causes Lassa hemorrhagic fever, a severe disease classified as biosafety level 4. It has an ambisense RNA genome with two segments: the L segment encodes polymerase and matrix protein, and the S segment encodes the spike glycoprotein and nucleoprotein. The virus is primarily zoonotic, transmitted from the multimammate mouse (*Mastomys natalensis*) to humans via aerosolized excreta, contaminated food, or consumption of rodents.

Human-to-human transmission occurs through bodily fluids, including sexual contact, and post-mortem handling. Incubation is 7–21 days, with symptoms starting as flu-like (fever, sore throat, muscle aches) and progressing to hemorrhagic manifestations, neurological issues, and multi-organ failure. The overall case fatality rate is about 1%, but it rises to 15–20% in hospitalized cases and up to 80% in pregnant women and 75% in newborns.

Long-term effects include hearing loss and chronic fatigue. Currently, no specific treatments or licensed vaccines exist; only supportive care (hydration) is available. Vaccine development is hindered by the flexible spike protein, which evades neutralizing antibodies.

A promising VSV-vectored vaccine, similar to the Ebola vaccine, is in phase 2 trials. Other approaches (measles, DNA, adenovirus, rabies vectors) are in early stages. The virus is genetically diverse, with 17 lineages circulating in West Africa, and causes an estimated 300,000–500,000 cases annually, with 5,000 deaths.

FAQs

Lassa virus is an arenavirus that causes Lassa hemorrhagic fever, a severe disease classified as biosafety level 4. It is prevalent in West Africa and transmitted primarily from rodents to humans.

Transmission occurs through inhalation of aerosolized virus from rodent urine or feces, ingestion of contaminated food, or eating infected rodents. Human-to-human transmission is possible via bodily fluids, sexual contact, and handling of deceased victims.

Symptoms start with flu-like signs such as fever, headache, and muscle aches, progressing to breathing problems, GI issues, bleeding, and neurological symptoms. Severe cases can lead to multi-organ failure and death, typically around 14 days after onset.

The overall case fatality rate is about 1%, but it can reach 15-20% in hospitalized patients and up to 50% in some outbreaks. For pregnant women in the third trimester, it is about 80%, and for newborns, about 75%.

Currently, there are no specific treatments or licensed vaccines. Care focuses on symptom management and hydration. One vaccine using a vesicular stomatitis vector is in phase two clinical trials and looks promising.

The main reservoir is the multimammate mouse (Mastomys natalensis), which carries the virus lifelong without symptoms. It excretes the virus in urine and feces, often near human homes.

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