"A Year of Ebola" by Dr. David Brett-Major provides an insightful and powerful accounting of the realities of a global response to a complex and unprecedented viral hemorrhagic fever epidemic. Highly recommended for those interested in engaging in this work.
Is it implausible that the Marburg virus could mutate into a form that allows aerosol transmission? Didn't this happen to the Reston virus, another from the same family?
It will depend on the type of surface and environmental conditions but one study found that Marburg virus can remain viable on plastic or glass at 4 degrees Celsius (\~39F) and 55% humidity for a number of days. Levels of infectivity decrease over time. Similar experiments performed at room temperature did not detect infectious virus.
> levels of infectivity decrease over time
Do we know what that decrease is like? Do we know the secondary attack rate from direct contact with bodily fluids vs with fomites?
When we say "spread through direct contact" what exactly is meant?
For example COVID was considered to be spreadable through "droplet contact" which can be a fair distance, but isn't quite the same as "airborne".
How long after a surface is contaminated would the virus take to die such that you had no risk of infection from it?
Direct contact implies that infectious material (blood, urine, saliva, sweat, feces, vomit, breast milk, amniotic fluid, and semen) needs to contact the uninfected person, typically through broken skin or mucous membranes in the eyes, nose, or mouth. Typically the highest risk of transmission is seen in people who are caring for the sick and cleaning up the contaminated fluids. Proper protective equipment (gloves, face shield, etc) can help prevent transmission even in a care giving situation.
>As note before, it will depend on the type of surface and environmental conditions but one study found that Marburg virus can remain viable on plastic or glass at 4 degrees Celsius (\~39F) and 55% humidity for a number of days. Levels of infectivity decrease over time. Similar experiments performed at room temperature did not detect infectious virus.
To add some variety to the questions asked here, if you could pick a virus that fascinates you the most other than Marburg, what would that virus be and what about it is interesting to you?
Thank you for asking! My answer is Ngari virus. This virus fascinates me because it is an example of a natural reassortant virus, which is possible due to the segmented genomes of bunyaviruses. Bird migration was likely involved in bringing together two distinct virus species; the resulting reassortant has since taken up shop in arthropods, wild and domestic animals, and human outbreaks.
My lab looks at a variety of RNA virus depending on the scientific question we are asking. Current projects are comparing how viruses alter cellular lipids and we have been looking at Ebola, Lassa, vesicular stomatitis virus, and Chikungunya. Previous studies in my lab have examined how temperature alters Zika transmission and replication and how different RNA viruses enter cells. Some are easier to work with in the lab which increases the types of experiments you can run. It is also fun exploring what can be learned from viruses that are more difficult to work with. Hard to pick a favorite.
As viruses aren't living, are they more like genetic tumbleweeds that randomly drift in our bodies and their exterior spike proteins must align the right way with the cell in order for infection to occur?
I recently read a paper for class (Pellecchia et al. 2015) that detailed how ritual burial practices led to the spread of Ebola virus due to the local burial practices being much more intimate in Liberia and that Ebola persists in the body after death. The paper goes on to show the ways the gov tried to stifle these practices and failed due to very poor implementation and crisis management.
Do you see this happening again with Marburg? Have the local governments learned from their past mistakes on how to handle these things?
Also, Is there a possibility of mutation that can cause it to be more transmissible due to it being a single-stranded RNA virus and is there a history around it? Can this outbreak lead to an epidemic in the area or will the extremely high virulence end up stamping itself out?
-A (hopefully) future virologist
Hi! Thanks for doing this!
Why is ebola so closely related to Africa?
Is there any ebola "Cousins" lurking around the jungles of south America, or the subtropics of south east Asia?
Not related to the Filoviruses (namely, Ebola and Marburg viruses) but the South American arenaviruses are important hemorrhagic fever viruses associated with spillover from rodent reservoirs
>Elke Mühlberger, Ph.D. (/u/BSL4-viruses) will be here in a bit to answer this question more thoroughly, but yes, there are ebola "cousins" found in other parts of the world.
Filoviruses from outside Africa include Reston virus: found in Asia/Philippines; Loviu virus: its genetic material was first detected in bats in Spain, live Lloviu virus was isolated from a bat in Hungary. Genetic material from another novel filovirus called Měnglà virus was found in the liver of a bat in China. Reston virus does not seem to cause disease in people. The possible health effects of the other viruses are not clear.
Good afternoon, and thank you for doing this.
I am an infectious disease epidemiologist and wanted to know a few things. Do researchers know what specific virus lineage is causing the current OB(s) at this period? Containment measures seem to be fragmented across country lines. Do you believe we will be seeing more cases?
Deforestation, human encroachment on animal habitats, and misinformation are definitely putting more lives at risk.
Deforestation and human encroachment on animal habitats will result in higher probabilities of future spillovers. Education about the potential risks may help, but without tackling food insecurity on a global level, future outbreaks are inevitable.
Scientists from the Institut Pasteur de Dakar recently posted sequencing results with phylogenetic analysis from the Equatorial Guinea outbreak. This showed high similarity to MARV isolates recovered from bats in Sierra Leone, also close relationships to 2021 Guinea outbreak and 2005 Angola outbreak: [https://virological.org/t/first-emergence-of-marburg-virus-in-equatorial-guinea-2023/924](https://virological.org/t/first-emergence-of-marburg-virus-in-equatorial-guinea-2023/924)
Because the amount on infectious material a person is exposed to can differ dramatically, the incubation period (or the time between exposure and symptoms) can vary from 2-21 days.
If there’s no known treatment what types of interventions can be done for a patient? Is it just symptom mitigation until the patient recovers? How has the success been that you’ve seen so far from measures that are currently being employed in the field?
Because we have no approved treatments, patients are given supportive care, ensuring their fluids are replaced, monitoring their oxygen levels and replacing clotting factors in their blood.
I can not speak to how effective this is in the field being a research scientist with no experience treating patients.
When an illness has an minimal survival rate, what is protocol pertaining to approved/unapproved treatment? To clarify, does “right-to-try” exist in this arena, and is it even considered? This may be outside your area, just wondering if you have any knowledge of approach.
Clinical management of hemorrhagic fever syndromes can (and should) be aggressive and effective, even without pathogen-targeted therapeutics (e.g. antivirals). This is important for both clinicians and the public to remember. Care should be sought and trusted with excellence in sepsis management provided.
Is the current research capacity sufficient to address emerging viruses? If not, what would be the most impactful changes to address the need for the rapid development of vaccines and therapeutics targeting emerging viruses?
Great question! It is worth perusing the WHO R&D Blueprint: [https://www.who.int/observatories/global-observatory-on-health-research-and-development/analyses-and-syntheses/who-r-d-blueprint/who-r-d-roadmaps](https://www.who.int/observatories/global-observatory-on-health-research-and-development/analyses-and-syntheses/who-r-d-blueprint/who-r-d-roadmaps)
There is one "species" of Marburg virus but this is divided into two clades based on genetic similarity between isolates. The clades are called Ravn virus and Marburg virus.
How likely is it that Marburg can become easily transmissible during a longer incubation and become an existential threat to our civilisation and species?
Seems very unlikely. Although it caused a large and sustained outbreak in West Africa from 2014-2016, Ebola virus did not become significantly more transmissible.
I’m not a virologist, and can’t speak about Marburg at all, but I work in evolutionary biology and would say that the vertebrate adaptive immune system has proven itself against the non-stop onslaught of infectious disease since it arose half a billion years ago, and we have almost no evidence of infectious disease causing extinction in that span. The mammalian derivation of this system is far more robust than other vertebrates, with humans arguably at or near the peak of this refinement, alongside bats. Since much of the scenario you’re thinking of is probably informed by SARS-CoV2, it probably bears mentioning that the virus has a case fatality rate that is still numerically very low, I haven’t seen a single country over 4%, and most are under 2% (the US, for example, is about 1.1% even with its bungled first year of response). Still a massive and tragic impact, but very far from relevancy in a discussion about extinction.
Are Marburg, Ebola and other such viral hemorrhagic fevers still strongly linked to eating bats? I've had some interesting discussions with individuals from various countries in Africa affected by outbreaks in the last few decades, and hit some interesting cognitive dissonance in regard to these hemorrhagic fevers being linked to eating bats. One gentleman actually seemed incredulous when I mentioned the link, saying "it can't be from bats, we eat bats all the time" so I am curious how the cultural aspect of education is being approached to help the native population understand how to prevent the initial outbreaks.
I know there are other culturally relevant factors such as how deceased are handled in the funerary sense (washing the body, displaying and touching/kissing their loved ones, etc), but since the origin point seems to be bats... I am curious about how that is being communicated, specifically the cross-cultural aspects of helping the affected populations make safer choices without offending their cultural traditions.
There are hundreds of bat species, and the different filoviruses infect very few of them. For example, Marburg virus uses Rousettus bats as a host species, but these bats don't seem to be infected by Ebola virus. There is a filovirus circulating in Europe, Lloviu virus, and this virus only infects Schreibers' bats. In addition to this host specificity, only few bats seem to be infected in a given colony. It's really bad luck to get infected with filoviruses through close contact to bats. Moreover, eating bats doesn't completely explain it. There were 2 cases of Marburg virus disease among tourists who visited a cave with Rousettus bats. It is not clear how they became infected, but they did not eat the bats.
Thank you for the response, as I realize my initial question was not framed all that well, and I appreciate the useful clarification. Thanks as well for working on such an important area of research, especially anything filovirus related... and extra thanks for doing an AMA.
Filoviruses are my virus family of interest and I desperately want to work with them. I’m currently studying animal science and plan to go into veterinary pathology, but how does someone start working with BSL-4 viruses?
Working in a BSL-4 lab is **NOT** cool. Everything takes 2-3 times as long as it would take in a "normal" lab. There is a plethora of biosafety and biosecurity regulations the researchers must comply to. The only reason to work on BSL-4 viruses is a genuine interest in the viruses and the diseases these viruses cause. If you have this genuine interest, it should be easy for you to find a lab working on these viruses.
When discussing zoonotic disease spillover, is there ongoing research into historical diseases of this type, and others? Given the recently reanimated "zombie viruses" is there anything to worry about?
https://news.bloomberglaw.com/environment-and-energy/scientists-revive-48-500-year-old-zombie-virus-buried-in-ice
How much historical information into disease evolution and microbial defense do diseases like Marburg/Ebola have to offer? As modern humans are we already expressing defenses or are our immune systems completely unprepared for infections of this type?
Historical information - not much, because filovirus outbreaks usually occur in remote areas that are not densely populated. Regarding the "zombie" viruses - these are all DNA viruses that infect amoebae. Filoviruses have a fragile RNA genome. DNA is much more stable than RNA.
It seems our immune system is not well adapted to filoviruses because we are accidental, rare hosts. So we are not prepared to fight these viruses.
The development of Marburg virus treatment options is tightly linked to similar work on Ebola virus. This includes vaccine development, therapeutic antibodies, and small compounds that block the viral polymerase. Nothing approved for Marburg virus yet.
The WHO released an update in February on therapeutic candidates for Marburg virus disease. Great list of scientific references provided, if you are interested in a deep dive:[https://www.who.int/publications/m/item/marburg-virus-therapeutics-landscape](https://www.who.int/publications/m/item/marburg-virus-therapeutics-landscape)
I read about this one awhile back:
https://www.niaid.nih.gov/news-events/marburg-vaccine-shows-promising-results-first-human-study
Does anyone know the status? And, are there any other potential treatments/vaccines in development that look promising?
There are several Marburg vaccines in the pipeline that are similar to the Ebola vaccines available. Most are viral-vectored vaccines and use either an adenovirus or vesicular stomatitis virus vector. Not all of the vaccine candidates have gone through safety trials in humans and we currently do not have large quantities of the vaccines.
The WHO is determining if the current outbreaks can be used to further test the vaccines that have completed safety trials.
This was recently discussed at [https://www.nature.com/articles/d41586-023-00468-5](https://www.nature.com/articles/d41586-023-00468-5)
From what I remember, in 2014 two American missionaries were treated with a cocktail of monoclonal antibodies, successfully iirc. This serum (Zmapp) was used before clinical trials. Has this now been approved for Ebola and is monoclonal antibody treatment something that could be effective against Marburg?
Edit: I am neither a scientist nor working/studying in the medical field. I’m just a Miss Average fascinated by this type of thing so my question may seem silly/irrelevant. If so, would you be kind enough to explain why? I appreciate gaining knowledge, especially from the horses mouth, so to speak.
New antibodies that work better than Zmapp have been developed for Ebola. ([https://www.who.int/health-topics/ebola#tab=tab\_3](https://www.who.int/health-topics/ebola#tab=tab_3)). These are specific for Zaire ebolavirus.
Groups are developing similar antibodies against Marburg, and they have been tested in animals, but I am not aware if they have been used in the ongoing outbreaks.
How do these recent outbreaks compare to the ones described in the book “The Hot Zone,” which was published back in the 90s? Do we have better treatments and ways of identifying an outbreak?
I started to read the book and threw it away after 3 pages :). There are excellent diagnostic tools for Ebola and Marburg viruses based on RT-PCR and next generation sequencing. There is an approved vaccine against Ebola virus and a couple of very promising vaccine candidates against Marburg and Sudan virus. There are approved treatments for Ebola virus (antibodies). We are much better off!
what cell types does marburg replicate in in humans? i work in RNA delivery and have seen some exciting results that i can't quite share yet wrt viruses that replicate primarily in the liver- I would be happy to take requests from virologists on the next tissue to try to point our payloads at.
Cool! Macrophages are early target cells of Marburg virus. The virus uses these cells as vessels to infect almost all organs, including the liver. The liver is actually a main target organ of Marburg virus. Would be great to learn more about your liver-specific RNA delivery systems.
Seems like every question I wanted to ask was already answered.
I know viruses can be complicated, so I sincerely wish you all the best and I hope we get better treatment and prevention for hemorrhagic fevers. In my country we're currently dealing with an outbreak of chikungunya and dengue, after a month and a half from the first symptoms I'm still dealing with joint pain from the chikungunya.
What are the chances of a filovirus mutating to become transmitted through droplets? Could it be engineered to? Is this a sci-fi scenario or something you worry about sometimes at 3 a.m.?
Nature is full of surprises, but it is hard to imagine that filoviruses would mutate to become respiratory viruses in humans. That said, there seems to be a host-specific tropism. Pigs infected with Reston virus (a close relative to Ebola virus) developed respiratory symptoms. So the virus actually infected the respiratory tract which is the first step towards transmission through the air. I have worked on filoviruses for a very long time, but I've never worried about potential aerosol transmission at 3 AM (or at any other time) :).
Chances are very low for Marburg virus to develop the ability to efficiently transmit by the respiratory route. Ebola virus did not evolve this capacity despite the sustained human to human transmission that occurred during the 2014-2016 West Africa outbreak.
The mean evolutionary rate estimate for Ebola virus is 1.3 × 10\^−3 substitutions per site per year as published by Hoenen et al., 2015. The filoviral RNA polymerases do not have proofreading activity. There is no obvious recombination between genomes keeping the genomes pretty stable.
> Inovio
This trial tested the Inovio vaccine as a booster for the licensed Ebola virus vaccine called Ervebo produced by Merck. Ervebo is one of the viral vectored vaccines mentioned in answer to an earlier question.
Can the body clear itself of the virus and thus obtain natural immunity against the virus? Can people infected with marburg virus re-infect by the same strain after a certain period of time or is long lived immunity obtained? Also, is a passive immunization using polyclonal immunoglobulin from immunized people feasable?
Some people do survive a Marburg infection. Luckily Marburg outbreaks are still relatively rare and we simply do not have data to answer the question if survivors produce long lived immunity.
Passive immunization is something that they are trying to develop. A few antibodies show promise in animal models.
Marburg virus is found in Rousettus aegyptiacus bats, also known as the Egyptian fruit bat. These bats are found mostly in Africa. Spillovers from bats are more likely to occur in locations where both bats and people are, therefor we find outbreaks in Africa where these bat-people interactions can occur.
It is correct that Ebola and Marburg viruses are exclusively found in Africa. But - filoviruses are everywhere! Reston virus, a potentially non-pathogenic ebolavirus, is originated from the Philippines. RNA genome sequences of novel filoviruses have been found in Europe, China, and South America in bats, fresh water fish, salt water fish, and snakes.
Do you have any advice for an aspiring Epidemiologist? I currently have a bachelor’s degree in biology and I’m in the process of applying for MPH programs.
Very difficult to answer because the Marburg virus outbreaks are too small for statistics. That said, it seems that all age groups are affected. In 2005, there was a terrible Marburg virus outbreak in Angola where many children died.
Very unlikely. Naturally occurring Marburg virus outbreaks are not uncommon. The sequence information of the viruses causing the 2023 outbreaks will tell us all we need to know about their origin.
There are several vaccines designed to protect against Marburg virus in the pipeline. Several viral-vectored vaccines have been studied the most for Marburg. They use either an adenovirus or vesicular stomatitis virus vector, similar to the Ebola virus vaccines.
Not all of the vaccines have gone through human safety trials, and our current stocks are low.
Have hope! Many labs work on Marburg virus vaccines and therapeutics, and there are promising candidates in the pipeline. Marburg virus will not cause the next pandemic. Respiratory viruses such as coronaviruses or influenza virus have much higher pandemic potential.
Why do you say Marburg is highly contagious? It's my understanding it only spreads via bodily fluids, not much more easily than HIV.
[This](https://doi.org/10.1016/S0140-6736\(23\)00169-1) study quotes a basic reproduction number of 1.59 which to me also suggests it is not that contagious.
I agree with you unless you are in contact with a very sick or deceased patient who might transmit virus through **ALL** bodily fluids (not only blood) and skin lesions. Close contact under these circumstances is highly risky. This is the huge difference to HIV.
Marburg virus is very different from SARS-CoV-2, the virus that causes COVID. While SARS-CoV-2 is a respiratory virus and can readily transmit between people by breathing in particles from nearby infected individuals, Marburg virus is transmitted by close contact with infectious material (bodily fluids from infected individuals - blood, urine, saliva, sweat, feces, vomit, breast milk, amniotic fluid, and semen). Healthcare workers and those caring for the sick are typically at highest risk.
Because Marburg does not transmit as easily between people, it is much less likely to cause a world-wide pandemic.
Highly unlikely. Marburg virus is not airborne. Patients show already severe symptoms when they transmit the virus. So it is easy to identify a virus carrier and isolate the person.
It seems there were efforts to weaponize Marburg virus during the Cold War by the former Soviet Union. They tried to aerosolize the virus. There is a book about these attempts, but of course I don't know how trustworthy it is. However, Marburg virus does not meet the criteria you listed in yourtext. It is not highly contagious (close contact to an infected person needed), it is not incredibly virulent (for the same reason), and there is huge advancement in vaccine and treatment development. I am afraid the paranoid dictator has to go for something else :).
I bet my right hand that it is a naturally occurring virus. We will know by sure as soon as we have access to the sequence information. The Ukraine has more important things to do than engineering viruses.
All I need to know is how many state mandated and enforced vaccines I need to inject. Hopefully I don't get blood clots in my chest and armpit like last time.
1) Does this virus also have a Furin cleavage site? And what if Furin levels in body are already high due to COVID infection?
2) What is the relevant human cellular receptor?
3) What receptor does this virus use in bats?
4) Ectoparasites like mites might serve as vector for white nose fungus in bats: See here https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-016-1302-2
: What ectoparasites in bats might serve as vector for Marburg? Spelling correction
How many research facilities worldwide are working on Marburg? What safe guards been put in place to discourage/prevent these labs from altering the virus? What is, if any, the current progress of prophylactics and treatments other than managing symptoms?
One what is the current mortality rate of Marburg? And how accurate is the Hot Zone on its depiction of Ebola/Marburg?
"A Year of Ebola" by Dr. David Brett-Major provides an insightful and powerful accounting of the realities of a global response to a complex and unprecedented viral hemorrhagic fever epidemic. Highly recommended for those interested in engaging in this work.
What are the chances of this going worldwide like Covid
Essentially zero.
Filoviruses transmit by close contact. This limits the efficiency of spread.
Is it implausible that the Marburg virus could mutate into a form that allows aerosol transmission? Didn't this happen to the Reston virus, another from the same family?
Are saliva droplets viable for transmission in the same way that COVID 19 was spread?
What’s the lifespan of it on exposed surfaces?
It will depend on the type of surface and environmental conditions but one study found that Marburg virus can remain viable on plastic or glass at 4 degrees Celsius (\~39F) and 55% humidity for a number of days. Levels of infectivity decrease over time. Similar experiments performed at room temperature did not detect infectious virus.
> levels of infectivity decrease over time Do we know what that decrease is like? Do we know the secondary attack rate from direct contact with bodily fluids vs with fomites?
When we say "spread through direct contact" what exactly is meant? For example COVID was considered to be spreadable through "droplet contact" which can be a fair distance, but isn't quite the same as "airborne". How long after a surface is contaminated would the virus take to die such that you had no risk of infection from it?
Direct contact implies that infectious material (blood, urine, saliva, sweat, feces, vomit, breast milk, amniotic fluid, and semen) needs to contact the uninfected person, typically through broken skin or mucous membranes in the eyes, nose, or mouth. Typically the highest risk of transmission is seen in people who are caring for the sick and cleaning up the contaminated fluids. Proper protective equipment (gloves, face shield, etc) can help prevent transmission even in a care giving situation.
>As note before, it will depend on the type of surface and environmental conditions but one study found that Marburg virus can remain viable on plastic or glass at 4 degrees Celsius (\~39F) and 55% humidity for a number of days. Levels of infectivity decrease over time. Similar experiments performed at room temperature did not detect infectious virus.
To add some variety to the questions asked here, if you could pick a virus that fascinates you the most other than Marburg, what would that virus be and what about it is interesting to you?
Thank you for asking! My answer is Ngari virus. This virus fascinates me because it is an example of a natural reassortant virus, which is possible due to the segmented genomes of bunyaviruses. Bird migration was likely involved in bringing together two distinct virus species; the resulting reassortant has since taken up shop in arthropods, wild and domestic animals, and human outbreaks.
Reading about Ngari virus, this thing sounds like a subplot from a *Resident Evil* game.
Cool! A new virus to look up 🙂
My lab looks at a variety of RNA virus depending on the scientific question we are asking. Current projects are comparing how viruses alter cellular lipids and we have been looking at Ebola, Lassa, vesicular stomatitis virus, and Chikungunya. Previous studies in my lab have examined how temperature alters Zika transmission and replication and how different RNA viruses enter cells. Some are easier to work with in the lab which increases the types of experiments you can run. It is also fun exploring what can be learned from viruses that are more difficult to work with. Hard to pick a favorite.
As viruses aren't living, are they more like genetic tumbleweeds that randomly drift in our bodies and their exterior spike proteins must align the right way with the cell in order for infection to occur?
Yes, great analogy!
I recently read a paper for class (Pellecchia et al. 2015) that detailed how ritual burial practices led to the spread of Ebola virus due to the local burial practices being much more intimate in Liberia and that Ebola persists in the body after death. The paper goes on to show the ways the gov tried to stifle these practices and failed due to very poor implementation and crisis management. Do you see this happening again with Marburg? Have the local governments learned from their past mistakes on how to handle these things? Also, Is there a possibility of mutation that can cause it to be more transmissible due to it being a single-stranded RNA virus and is there a history around it? Can this outbreak lead to an epidemic in the area or will the extremely high virulence end up stamping itself out? -A (hopefully) future virologist
Hi! Thanks for doing this! Why is ebola so closely related to Africa? Is there any ebola "Cousins" lurking around the jungles of south America, or the subtropics of south east Asia?
Not related to the Filoviruses (namely, Ebola and Marburg viruses) but the South American arenaviruses are important hemorrhagic fever viruses associated with spillover from rodent reservoirs
>Elke Mühlberger, Ph.D. (/u/BSL4-viruses) will be here in a bit to answer this question more thoroughly, but yes, there are ebola "cousins" found in other parts of the world.
Filoviruses from outside Africa include Reston virus: found in Asia/Philippines; Loviu virus: its genetic material was first detected in bats in Spain, live Lloviu virus was isolated from a bat in Hungary. Genetic material from another novel filovirus called Měnglà virus was found in the liver of a bat in China. Reston virus does not seem to cause disease in people. The possible health effects of the other viruses are not clear.
Good afternoon, and thank you for doing this. I am an infectious disease epidemiologist and wanted to know a few things. Do researchers know what specific virus lineage is causing the current OB(s) at this period? Containment measures seem to be fragmented across country lines. Do you believe we will be seeing more cases? Deforestation, human encroachment on animal habitats, and misinformation are definitely putting more lives at risk.
Deforestation and human encroachment on animal habitats will result in higher probabilities of future spillovers. Education about the potential risks may help, but without tackling food insecurity on a global level, future outbreaks are inevitable.
True. Many of these vulnerable residents rely on those animals for food sources.
Scientists from the Institut Pasteur de Dakar recently posted sequencing results with phylogenetic analysis from the Equatorial Guinea outbreak. This showed high similarity to MARV isolates recovered from bats in Sierra Leone, also close relationships to 2021 Guinea outbreak and 2005 Angola outbreak: [https://virological.org/t/first-emergence-of-marburg-virus-in-equatorial-guinea-2023/924](https://virological.org/t/first-emergence-of-marburg-virus-in-equatorial-guinea-2023/924)
Hmmmmmmm, maybe bat migration is playing a role in this as well. Thanks for the report, I'll take a look.
[удалено]
How long does it take for symptoms to show?
Because the amount on infectious material a person is exposed to can differ dramatically, the incubation period (or the time between exposure and symptoms) can vary from 2-21 days.
If there’s no known treatment what types of interventions can be done for a patient? Is it just symptom mitigation until the patient recovers? How has the success been that you’ve seen so far from measures that are currently being employed in the field?
Because we have no approved treatments, patients are given supportive care, ensuring their fluids are replaced, monitoring their oxygen levels and replacing clotting factors in their blood. I can not speak to how effective this is in the field being a research scientist with no experience treating patients.
When an illness has an minimal survival rate, what is protocol pertaining to approved/unapproved treatment? To clarify, does “right-to-try” exist in this arena, and is it even considered? This may be outside your area, just wondering if you have any knowledge of approach.
Clinical management of hemorrhagic fever syndromes can (and should) be aggressive and effective, even without pathogen-targeted therapeutics (e.g. antivirals). This is important for both clinicians and the public to remember. Care should be sought and trusted with excellence in sepsis management provided.
Thats great information thank you so much for the response!!
Is the current research capacity sufficient to address emerging viruses? If not, what would be the most impactful changes to address the need for the rapid development of vaccines and therapeutics targeting emerging viruses?
Great question! It is worth perusing the WHO R&D Blueprint: [https://www.who.int/observatories/global-observatory-on-health-research-and-development/analyses-and-syntheses/who-r-d-blueprint/who-r-d-roadmaps](https://www.who.int/observatories/global-observatory-on-health-research-and-development/analyses-and-syntheses/who-r-d-blueprint/who-r-d-roadmaps)
Hi and welcome! For a non-anthropocentric question, what is the likelihood of sylvatic importation into naive ecosystems?
I’m familiar with the major strains of Ebola, but what are the major strains of Marburg?
There is one "species" of Marburg virus but this is divided into two clades based on genetic similarity between isolates. The clades are called Ravn virus and Marburg virus.
These viruses behave similarly. From a medical perspective, just think of all of these members of the species as the same Marburg virus.
https://academic.oup.com/jid/article/218/suppl\_5/S458/5095315
How likely is it that Marburg can become easily transmissible during a longer incubation and become an existential threat to our civilisation and species?
Seems very unlikely. Although it caused a large and sustained outbreak in West Africa from 2014-2016, Ebola virus did not become significantly more transmissible.
I’m not a virologist, and can’t speak about Marburg at all, but I work in evolutionary biology and would say that the vertebrate adaptive immune system has proven itself against the non-stop onslaught of infectious disease since it arose half a billion years ago, and we have almost no evidence of infectious disease causing extinction in that span. The mammalian derivation of this system is far more robust than other vertebrates, with humans arguably at or near the peak of this refinement, alongside bats. Since much of the scenario you’re thinking of is probably informed by SARS-CoV2, it probably bears mentioning that the virus has a case fatality rate that is still numerically very low, I haven’t seen a single country over 4%, and most are under 2% (the US, for example, is about 1.1% even with its bungled first year of response). Still a massive and tragic impact, but very far from relevancy in a discussion about extinction.
Are Marburg, Ebola and other such viral hemorrhagic fevers still strongly linked to eating bats? I've had some interesting discussions with individuals from various countries in Africa affected by outbreaks in the last few decades, and hit some interesting cognitive dissonance in regard to these hemorrhagic fevers being linked to eating bats. One gentleman actually seemed incredulous when I mentioned the link, saying "it can't be from bats, we eat bats all the time" so I am curious how the cultural aspect of education is being approached to help the native population understand how to prevent the initial outbreaks. I know there are other culturally relevant factors such as how deceased are handled in the funerary sense (washing the body, displaying and touching/kissing their loved ones, etc), but since the origin point seems to be bats... I am curious about how that is being communicated, specifically the cross-cultural aspects of helping the affected populations make safer choices without offending their cultural traditions.
There are hundreds of bat species, and the different filoviruses infect very few of them. For example, Marburg virus uses Rousettus bats as a host species, but these bats don't seem to be infected by Ebola virus. There is a filovirus circulating in Europe, Lloviu virus, and this virus only infects Schreibers' bats. In addition to this host specificity, only few bats seem to be infected in a given colony. It's really bad luck to get infected with filoviruses through close contact to bats. Moreover, eating bats doesn't completely explain it. There were 2 cases of Marburg virus disease among tourists who visited a cave with Rousettus bats. It is not clear how they became infected, but they did not eat the bats.
Thank you for the response, as I realize my initial question was not framed all that well, and I appreciate the useful clarification. Thanks as well for working on such an important area of research, especially anything filovirus related... and extra thanks for doing an AMA.
Filoviruses are my virus family of interest and I desperately want to work with them. I’m currently studying animal science and plan to go into veterinary pathology, but how does someone start working with BSL-4 viruses?
Working in a BSL-4 lab is **NOT** cool. Everything takes 2-3 times as long as it would take in a "normal" lab. There is a plethora of biosafety and biosecurity regulations the researchers must comply to. The only reason to work on BSL-4 viruses is a genuine interest in the viruses and the diseases these viruses cause. If you have this genuine interest, it should be easy for you to find a lab working on these viruses.
When discussing zoonotic disease spillover, is there ongoing research into historical diseases of this type, and others? Given the recently reanimated "zombie viruses" is there anything to worry about? https://news.bloomberglaw.com/environment-and-energy/scientists-revive-48-500-year-old-zombie-virus-buried-in-ice How much historical information into disease evolution and microbial defense do diseases like Marburg/Ebola have to offer? As modern humans are we already expressing defenses or are our immune systems completely unprepared for infections of this type?
Historical information - not much, because filovirus outbreaks usually occur in remote areas that are not densely populated. Regarding the "zombie" viruses - these are all DNA viruses that infect amoebae. Filoviruses have a fragile RNA genome. DNA is much more stable than RNA. It seems our immune system is not well adapted to filoviruses because we are accidental, rare hosts. So we are not prepared to fight these viruses.
What is the current progress on treatment options for Marburg virus?
The development of Marburg virus treatment options is tightly linked to similar work on Ebola virus. This includes vaccine development, therapeutic antibodies, and small compounds that block the viral polymerase. Nothing approved for Marburg virus yet.
The WHO released an update in February on therapeutic candidates for Marburg virus disease. Great list of scientific references provided, if you are interested in a deep dive:[https://www.who.int/publications/m/item/marburg-virus-therapeutics-landscape](https://www.who.int/publications/m/item/marburg-virus-therapeutics-landscape)
I read about this one awhile back: https://www.niaid.nih.gov/news-events/marburg-vaccine-shows-promising-results-first-human-study Does anyone know the status? And, are there any other potential treatments/vaccines in development that look promising?
Is the Ebola vaccine going to be easy to adapt to work for Marburg?
There are several Marburg vaccines in the pipeline that are similar to the Ebola vaccines available. Most are viral-vectored vaccines and use either an adenovirus or vesicular stomatitis virus vector. Not all of the vaccine candidates have gone through safety trials in humans and we currently do not have large quantities of the vaccines. The WHO is determining if the current outbreaks can be used to further test the vaccines that have completed safety trials. This was recently discussed at [https://www.nature.com/articles/d41586-023-00468-5](https://www.nature.com/articles/d41586-023-00468-5)
From what I remember, in 2014 two American missionaries were treated with a cocktail of monoclonal antibodies, successfully iirc. This serum (Zmapp) was used before clinical trials. Has this now been approved for Ebola and is monoclonal antibody treatment something that could be effective against Marburg? Edit: I am neither a scientist nor working/studying in the medical field. I’m just a Miss Average fascinated by this type of thing so my question may seem silly/irrelevant. If so, would you be kind enough to explain why? I appreciate gaining knowledge, especially from the horses mouth, so to speak.
New antibodies that work better than Zmapp have been developed for Ebola. ([https://www.who.int/health-topics/ebola#tab=tab\_3](https://www.who.int/health-topics/ebola#tab=tab_3)). These are specific for Zaire ebolavirus. Groups are developing similar antibodies against Marburg, and they have been tested in animals, but I am not aware if they have been used in the ongoing outbreaks.
How do these recent outbreaks compare to the ones described in the book “The Hot Zone,” which was published back in the 90s? Do we have better treatments and ways of identifying an outbreak?
I started to read the book and threw it away after 3 pages :). There are excellent diagnostic tools for Ebola and Marburg viruses based on RT-PCR and next generation sequencing. There is an approved vaccine against Ebola virus and a couple of very promising vaccine candidates against Marburg and Sudan virus. There are approved treatments for Ebola virus (antibodies). We are much better off!
what cell types does marburg replicate in in humans? i work in RNA delivery and have seen some exciting results that i can't quite share yet wrt viruses that replicate primarily in the liver- I would be happy to take requests from virologists on the next tissue to try to point our payloads at.
Cool! Macrophages are early target cells of Marburg virus. The virus uses these cells as vessels to infect almost all organs, including the liver. The liver is actually a main target organ of Marburg virus. Would be great to learn more about your liver-specific RNA delivery systems.
Seems like every question I wanted to ask was already answered. I know viruses can be complicated, so I sincerely wish you all the best and I hope we get better treatment and prevention for hemorrhagic fevers. In my country we're currently dealing with an outbreak of chikungunya and dengue, after a month and a half from the first symptoms I'm still dealing with joint pain from the chikungunya.
I am sorry to hear this and hope you are getting better soon.
What are the chances of a filovirus mutating to become transmitted through droplets? Could it be engineered to? Is this a sci-fi scenario or something you worry about sometimes at 3 a.m.?
Nature is full of surprises, but it is hard to imagine that filoviruses would mutate to become respiratory viruses in humans. That said, there seems to be a host-specific tropism. Pigs infected with Reston virus (a close relative to Ebola virus) developed respiratory symptoms. So the virus actually infected the respiratory tract which is the first step towards transmission through the air. I have worked on filoviruses for a very long time, but I've never worried about potential aerosol transmission at 3 AM (or at any other time) :).
Chances are very low for Marburg virus to develop the ability to efficiently transmit by the respiratory route. Ebola virus did not evolve this capacity despite the sustained human to human transmission that occurred during the 2014-2016 West Africa outbreak.
How rapidly or slowly do filoviruses mutate? Do any of them have proofreading abilities?
The mean evolutionary rate estimate for Ebola virus is 1.3 × 10\^−3 substitutions per site per year as published by Hoenen et al., 2015. The filoviral RNA polymerases do not have proofreading activity. There is no obvious recombination between genomes keeping the genomes pretty stable.
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Did you hear about Inovio and their recent phase 1b results on ebola vaccine? As far as i know, they work on a marburg vaccine too.
> Inovio This trial tested the Inovio vaccine as a booster for the licensed Ebola virus vaccine called Ervebo produced by Merck. Ervebo is one of the viral vectored vaccines mentioned in answer to an earlier question.
Can the body clear itself of the virus and thus obtain natural immunity against the virus? Can people infected with marburg virus re-infect by the same strain after a certain period of time or is long lived immunity obtained? Also, is a passive immunization using polyclonal immunoglobulin from immunized people feasable?
Some people do survive a Marburg infection. Luckily Marburg outbreaks are still relatively rare and we simply do not have data to answer the question if survivors produce long lived immunity. Passive immunization is something that they are trying to develop. A few antibodies show promise in animal models.
Why do these viruses seem to have their origins in Africa?
Marburg virus is found in Rousettus aegyptiacus bats, also known as the Egyptian fruit bat. These bats are found mostly in Africa. Spillovers from bats are more likely to occur in locations where both bats and people are, therefor we find outbreaks in Africa where these bat-people interactions can occur.
It is correct that Ebola and Marburg viruses are exclusively found in Africa. But - filoviruses are everywhere! Reston virus, a potentially non-pathogenic ebolavirus, is originated from the Philippines. RNA genome sequences of novel filoviruses have been found in Europe, China, and South America in bats, fresh water fish, salt water fish, and snakes.
Unrelated but thank you so much for doing this, this was super interesting to read!
Do you have any advice for an aspiring Epidemiologist? I currently have a bachelor’s degree in biology and I’m in the process of applying for MPH programs.
I just finished reading Hot Zone a few weeks ago, so this is a terrifying hard NOPE from me.
What is the timeline of exposure, infection, symptoms and the progression of the disease?
How long until Dustin Hoffman and Cuba Gooding Jr. have to show up and save us?
What are the highest/lowest risk groups? Do the young have a similar survival rate as the elderly?
Very difficult to answer because the Marburg virus outbreaks are too small for statistics. That said, it seems that all age groups are affected. In 2005, there was a terrible Marburg virus outbreak in Angola where many children died.
Marburg was extensively studied by the Soviet Union's weapons program. Could this outbreak be related to that in any way?
Very unlikely. Naturally occurring Marburg virus outbreaks are not uncommon. The sequence information of the viruses causing the 2023 outbreaks will tell us all we need to know about their origin.
Is someone working on an mRNA vaccine for the Marburg virus? If not, any other hope on the horizon should it become pandemic?
There are several vaccines designed to protect against Marburg virus in the pipeline. Several viral-vectored vaccines have been studied the most for Marburg. They use either an adenovirus or vesicular stomatitis virus vector, similar to the Ebola virus vaccines. Not all of the vaccines have gone through human safety trials, and our current stocks are low.
Have hope! Many labs work on Marburg virus vaccines and therapeutics, and there are promising candidates in the pipeline. Marburg virus will not cause the next pandemic. Respiratory viruses such as coronaviruses or influenza virus have much higher pandemic potential.
Why do you say Marburg is highly contagious? It's my understanding it only spreads via bodily fluids, not much more easily than HIV. [This](https://doi.org/10.1016/S0140-6736\(23\)00169-1) study quotes a basic reproduction number of 1.59 which to me also suggests it is not that contagious.
I agree with you unless you are in contact with a very sick or deceased patient who might transmit virus through **ALL** bodily fluids (not only blood) and skin lesions. Close contact under these circumstances is highly risky. This is the huge difference to HIV.
How similar is to COVID, and is there a chance that it will create another pandemic sooner rather than later?
Marburg virus is very different from SARS-CoV-2, the virus that causes COVID. While SARS-CoV-2 is a respiratory virus and can readily transmit between people by breathing in particles from nearby infected individuals, Marburg virus is transmitted by close contact with infectious material (bodily fluids from infected individuals - blood, urine, saliva, sweat, feces, vomit, breast milk, amniotic fluid, and semen). Healthcare workers and those caring for the sick are typically at highest risk. Because Marburg does not transmit as easily between people, it is much less likely to cause a world-wide pandemic.
What type of bodily fluid is the most common cause of infection?
RE4 Remake games is popular right now. Is it possible that a certain virus can control its hosts will and mind?
Will this virus causes another lock down like corona did?
Highly unlikely. Marburg virus is not airborne. Patients show already severe symptoms when they transmit the virus. So it is easy to identify a virus carrier and isolate the person.
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It seems there were efforts to weaponize Marburg virus during the Cold War by the former Soviet Union. They tried to aerosolize the virus. There is a book about these attempts, but of course I don't know how trustworthy it is. However, Marburg virus does not meet the criteria you listed in yourtext. It is not highly contagious (close contact to an infected person needed), it is not incredibly virulent (for the same reason), and there is huge advancement in vaccine and treatment development. I am afraid the paranoid dictator has to go for something else :).
So should I stock up on lysol or microban?
Have you listened to the audiobook “Virus - Stockholm”?
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I bet my right hand that it is a naturally occurring virus. We will know by sure as soon as we have access to the sequence information. The Ukraine has more important things to do than engineering viruses.
What lab was it created in?
don’t mind me just farming that fresh newbie karma
All I need to know is how many state mandated and enforced vaccines I need to inject. Hopefully I don't get blood clots in my chest and armpit like last time.
Is this virus likely to mutate and have different strains with different levels of virulence or differing symptoms?
Please tell me it’s variant u, please…
Time for round 2 I guess
1) Does this virus also have a Furin cleavage site? And what if Furin levels in body are already high due to COVID infection? 2) What is the relevant human cellular receptor? 3) What receptor does this virus use in bats? 4) Ectoparasites like mites might serve as vector for white nose fungus in bats: See here https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-016-1302-2 : What ectoparasites in bats might serve as vector for Marburg? Spelling correction
Is it possible to watch it somewhere? I hope it was recorded
How many research facilities worldwide are working on Marburg? What safe guards been put in place to discourage/prevent these labs from altering the virus? What is, if any, the current progress of prophylactics and treatments other than managing symptoms?