In a recent New York Times OpEd entitled What We’re Afraid to Say About Ebola, Michael Osterholm wonders whether Ebola virus could go airborne:
You can now get Ebola only through direct contact with bodily fluids. If certain mutations occurred, it would mean that just breathing would put one at risk of contracting Ebola. Infections could spread quickly to every part of the globe, as the H1N1 influenza virus did in 2009, after its birth in Mexico.
Is there any truth to what Osterholm is saying?
Let’s start with his discussion of Ebola virus mutation:
But viruses like Ebola are notoriously sloppy in replicating, meaning the virus entering one person may be genetically different from the virus entering the next. The current Ebola virus’s hyper-evolution is unprecedented; there has been more human-to-human transmission in the past four months than most likely occurred in the last 500 to 1,000 years.
When viruses enter a cell, they make copies of their genetic information to assemble new virus particles. Viruses such as Ebola virus, which have genetic information in the form of RNA (not DNA as in other organisms), are notoriously bad at copying their genome. The viral enzyme that copies the RNA makes many errors, perhaps as many as one or two each time the viral genome is reproduced. There is no question that RNA viruses are the masters of mutation. This fact is in part why we need a new influenza virus vaccine every few years.
The more hosts infected by a virus, the more mutations will arise. Not all of these mutations will find their way into infectious virus particles because they cause lethal defects. But Osterholm’s statement that the evolution of Ebola virus is ‘unprecedented’ is simply not correct. It is only what we know. The virus was only discovered to infect humans in 1976, but it surely infected humans long before that. Furthermore, the virus has been replicating, probably for millions of years, in an animal reservoir, possibly bats. There has been ample opportunity for the virus to undergo mutation.
More problematic is Osterholm’s assumption that mutation of Ebola virus will give rise to viruses that can transmit via the airborne route:
If certain mutations occurred, it would mean that just breathing would put one at risk of contracting Ebola. Infections could spread quickly to every part of the globe, as the H1N1 influenza virus did in 2009, after its birth in Mexico.
The key phrase here is ‘certain mutations’. We simply don’t know how many mutations, in which viral genes, would be necessary to enable airborne transmission of Ebola virus, or if such mutations would even be compatible with the ability of the virus to propagate. What allows a virus to be transmitted through the air has until recently been unknown. We can’t simply compare viruses that do transmit via aerosols (e.g. influenza virus) with viruses that do not (e.g. HIV-1) because they are too different to allow meaningful conclusions.
One approach to this conundrum would be to take a virus that does not transmit among mammals by aerosols – such as avian influenza H5N1 virus – and endow it with that property. This experiment was done by Fouchier and Kawaoka several years ago, and revealed that multiple amino acid changes are required to allow airborne transmission of H5N1 virus among ferrets. These experiments were met with a storm of protest from individuals – among them Michael Osterholm – who thought they were too dangerous. Do you want us to think about airborne transmission, and do experiments to understand it – or not?
The other important message from the Fouchier-Kawaoka ferret experiments is that the H5N1 virus that could transmit through the air had lost its ability to kill. The message is clear: gain of function (airborne transmission) is accompanied by loss of function (virulence).
When it comes to viruses, it is always difficult to predict what they can or cannot do. It is instructive, however, to see what viruses have done in the past, and use that information to guide our thinking. Therefore we can ask: has any human virus ever changed its mode of transmission?
The answer is no. We have been studying viruses for over 100 years, and we’ve never seen a human virus change the way it is transmitted.
HIV-1 has infected millions of humans since the early 1900s. It is still transmitted among humans by introduction of the virus into the body by sex, contaminated needles, or during childbirth.
Hepatitis C virus has infected millions of humans since its discovery in the 1980s. It is still transmitted among humans by introduction of the virus into the body by contaminated needles, blood, and during birth.
There is no reason to believe that Ebola virus is any different from any of the viruses that infect humans and have not changed the way that they are spread.
I am fully aware that we can never rule out what a virus might or might not do. But the likelihood that Ebola virus will go airborne is so remote that we should not use it to frighten people. We need to focus on stopping the epidemic, which in itself is a huge job.
This is really a fantastic article. People often forget the cost/benefit ratio when considering whether mutations will be adaptive or not. I really hope enough people share and see this article. You should write to the New York Times with this. I really feel that Osterholm’s piece had negative impacts on peoples’ understanding of virology, and I additionally think that the “we’re afraid to talk about” part would only make people think that scientists are hiding something. A rebuttal like this needs to be out in the mainstream media to show the public that we aren’t afraid to talk about this subject and that the opinions by Osterholm are unfounded and ultimately not supported by many virologists.
I enjoyed reading this article, and I had also read Osterholm’s article as well. I am honestly on the fence about this ebola virus and cannot get a grasp if its merely an endemic hell for the African people or truly a global catastrophe. I give the Osterholm article its due just because I know he is a key player in the world of viruses. Contrary to what has been reported, Ebola has been active in this area of Africa for at least a decade, mistaken for the Lassa virus, and interestingly this particular virus is now transmitted by exclusively humans as opposed to monkeys or rodents. Furthermore, the amount of U.S. involvement shows that the WHO and CDC know more than they are telling. There is a small chance in my opinion this may be “the big one” and if it is we all are in for a wild ride. There is definitely something fishy going on with this outbreak I cannot put my finger on, because I am terrified to ponder much further.
I’m wondering whether filamentous viruses don’t transmit so well by the respiratory route.
If I were a virus in a droplet I would minimize my surface and avoid contact with evil molecules and heat.
> Do you want us to think about airborne transmission, and do experiments to understand it – or not?
the question is not whether or not, but how much, of course.
And how much safety you would require and what you would publish.
> gain of function (airborne transmission) is accompanied by loss of function (virulence).
maybe often, or usually. But not always. See 1918.
Do similarities exist between rhabdoviruses and ebolavirus (othan than belonging to the same order, the Mononegavirales)? Some rhabdoviruses could – under certain circumstances – transmit airborne (very limited), especially in laboratory environment. My question is: are there functional constraints that impede these viruses to become fully airborne? And, filoviruses may be able to do the same? Rhabdo & Filoviruses surely are ancient organisms and both had a lot of opportunities to change, evolve during instances of animal-to-human spillovers. Is Replication of filoviruses in the airway epithelium cells viable?
Interestingly, H1N1pdm09 initally had a filamentous aspect, rather than the more usual globular particle presentation of seasonal flu viruses.
In Sénégal – so far – the imported case did not produce an explosive number of secondary cases. Actually, not a single confirmed secondary case has been confirmed in Senegal. Is it an indication of a change in epidemiology of ebov? That CDC knows something we don’t? Imported cases are a good occasion to see how the viruses work, if they changed, because overcome the need to rely on authoritative sources of the main epidemic centres.
The problem with some of these scientists who write on Big Media Outlets is that they are also ”think-tanks”: their role is to build a public opinion, to address it and sometimes to manipulate it, in order to achieve the goals of the interests groups they serve. It is a legitimate activity, it may be useful and respectable. But we have to recognize that they are doing something that may not be directly related to science or research or advancement of knowledge. Some former WHO officers went to private companies, other performed the inverse way. Interests criss-crossed and the scenario becomes less clear.
but was it filamentous inside the droplets that transmit ?
flu is pleomorphic (why ?)
“The message is clear: gain of function (airborne transmission) is accompanied by loss of function (virulence).”
IN THIS CASE. ONLY. NOT what happened in 1918!
In the case of Ebola, there is the nagging possibility that Ebola Reston was airborne: it spread between monkeys in cages in separate rooms, and the unfiltered air circulation was implicated. While this virus appears to only have caused subliminal infections in the human handlers, it COULD have been very different. While Ebolavirus Zaire may not evolve in that direction, there is no assurance that one of the others will NOT.
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In any case, to corroborate Osterholm suspicions we should have at least:
1) The full Clinical picture, from onset to Death;
2) Anatomo-pathological findings (gross changes in internal organs, lung tissues, co-infections presence, suggestive of changed pathogenesis, tissue tropism, portal of entry, dissemination and viral titers in airway epithelium…)
3) epidemiological findings suggestive of a sustained h2h transmission without close contacts or body fluids contacts;
4) microbiological examination, functional experiments with recent isolates in non-human primates.
Have we some of these data ready? And what do these findings suggest?
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I propose to make a Ebola vaccine based on my blood e-mail:riszhat@gmail.com I have immunity against many infectious diseases treatment of Ebola
Look at another member of Mononegavirales, VSV. This virus has been shown to be incredibly stable, with respect to its genomic sequence. It is believed that the virus is incredibly sensitive to mutations, and many of them are lethal mutations. I would not be surprised if this is also the case for Ebola.
In Philippines there were indication of RESTON subclinical infections in humans: http://www.who.int/csr/don/2009_02_03/en/ – Clearly, the two species (ZEBOV & RESTON) belong to distinct evolutionary lineages and possible the pathogenesis in pigs may be quite different to that in humans.
The 1918 and Reston stories actually support the notion of gain vs. loss of function and the limitations of host-jumping. 1918 flu came into humans as an airborne, highly pathogenic virus, and it stayed that way. Reston appears to be transmitted through the air between monkeys and probably to humans, but it’s harmless to us, and has stayed that way. If we force a non-airborne virus to become airborne in a particular host (H5N1), the available evidence suggests that it loses something in the process – in that case, pathogenicity.
So back to the questions: has any virus naturally changed its mode of transmission after entering humans? Can any virus do so without losing some other characteristic, such as pathogenicity? All the data we have suggest that the answer to both questions is “no.”
but 1918-flu combined other flu-segments by reassortment and the result
was more pathogenic and transmissable in humans than both(or more) parents.
We had other such examples in this blog, e.g. the multi-reassortment studies
last year. While most reassortants lost function, some gained.
—————————————
Avian (mallard) flu viruses that occasionally enter poultry or mammals
(usually only in parts by reassortment, though)
generally change their dominant way of transmission
from waterborne to respiratory
It may matter a tad less than we think. Even though the evidence for respiratory infection of Ebola has been minimal, this outbreak apparently commonly includes bleeding gums / nasal passages and bloody vomit symptoms. Therefore coughs & sneezes can induce blood contaminated droplet transmission. These droplets clearly have potential greater distance infectivity than the absurd ‘3 feet rule’ promulgated by the CDC & others, as indicated by numerous studies.
I find it counterproductive that normally intelligent people consider it OK to use the prior-in-use term “airborne” meaning ‘carried by air’ in a specialized manner that can only cause confusion and misinformation as a result. Ebola is “airborne” infective in the sense that blood containing droplets probably are infective out to considerable distances. And THAT is how people without knowledge of the specialized usage will misinterpret the real-world-false meme that Ebola is not airborne-transmitted. Use another word please.
Well said. If this viral lineage has already mutated into a form with likely aerosol transmission, it demonstrates non-zero probability of future replication. It is also obvious from what little information is available on the prior scale of outbreaks, that the current West-African outbreak represents a first-time wide area large scale infection with all of the possible results of adaptive radiation from thousands of passages through humans. Not only do we have the possibility of aerosol transmission capability, we have so many possibilities like new insect vectors, new reservoir-hosts, and so on. Can you predict the future ?
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Thanks for this post Vincent – you put across a lot of relevant points that will help me answer questions that a lot of students are asking this semester.
By the way, do we know the mode of transmission of ZEBOV in its natural host species?
OTOH, can one really say that pathogenicity was lost when airborne transmission was gained in the Fouchier-Kawaoka experiments? I seem to recall that the starting H5N1 strain that was highly pathogenic in humans did not cause pathology in the ferrets. Am I “misremembering” that point?
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Dr. Osterholm does all of us a disfavor by dangling such a provocative, and scientifically dubious, statement that Ebola virus “might” become airborne. The lay audiences are very anxious about this, and I agree with Vincent and others in TWIV that such a mutation is extremely unlikely. However, I also do not view this as justification for Gain of Function experiments, as GOF are useless without extensive field surveillance. Once a virus mutates in nature to change its pathogenicity or transmissibility, we find out about it through human disease….GOF does nothing to help us prevent such events from happening.
Vincent is quoted in this news article, and he is very clear about why a mutation of the Ebola filovirus is not feasible! Good job! http://www.vox.com/2014/9/19/6543157/ebola-is-unlikely-to-go-airborne
Someone should note that this disease arose in the 3 poorest countries in Africa. One of the symptoms is severe bleeding. Ring a bell anyone? Sound an alarm anyone? Poor diet, bleeding skin and internal bleeding? – “Cutaneous haemorrhage, ranging from petechial to massive extravasation is almost constantly found at autopsy in adults with vitamin C deficiency. The larger haemorrhages correspond to areas of trauma. Haemorrhage into muscles or along fascial planes is seen particularly at points of mechanical stress. Bleeding occurs from capillaries, presumably because of rupture of the loosened epithelial cells. In infants with vitamin C deficiency, massive sub periosteal haemorrhage is almost always present, especially in the legs.”
This quote is from a textbook of pathology in the 1970’s, published by Mosby.
Poorest countries in the world. Diet ? Nutrition? Disease?
My colleagues at the University of Illinois School of Public Health published this article that addresses droplet transmission, with their recommendations for personal protective equipment. I don’t think this level of PPE is achievable in a tropical environment, but they make a sound argument about droplet transmission.
“The current paradigm also assumes that only “small” particles (less than
5 micrometers [mcm]) can be inhaled and deposited in the respiratory
tract. This is not true. Particles as large as 100 mcm (and perhaps even
larger) can be inhaled into the mouth and nose. Larger particles are
deposited in the nasal passages, pharynx, and upper regions of the
lungs, while smaller particles are more likely to deposit in the lower,
alveolar regions. And for many pathogens, infection is possible
regardless of the particle size or deposition site.” http://www.cidrap.umn.edu/news-perspective/2014/09/commentary-health-workers-need-optimal-respiratory-protection-ebola
Severe bleeding is actually a relatively rare symptom. In some outbreaks less than half of patients have bled at all, and it wasn’t necessarily correlated with outcome.
Aside from the lack of experimental evidence for aerosol transmission of Ebola virus between primates, there is also no epidemiological evidence. Everything so far is fully consistent with uncontrolled contact transmission, Yes, droplets at close range included.
Even with Reston, I think it’s still an open question as to how well, if at all really it transmits by aerosol. But either way, as you note, it’s quote different from (Zaire) Ebola virus, which hasn’t transmitted between primates by aerosol even under ideal lab conditions.
my argument against Osterholm here would be that Ebola mutates 100 times slower than flu and
does not reassort and there are much less human Ebola cases than swineflu cases so you
can’t compare it with H1N1 in 2009.
But the mode of transmission change – I’m not so sure. How often have we heard recently
that “it does not transmit by respiratory droplets” and then it was changed to “efficiently transmit”.
What was with SARS,MERS,Measles,avian flu… ?
Almost everything in biology is “non-zero possibility” so stating this doesn’t tell us much new. Reston virus has actually been put into insects and completed failed to replicate, even when introduced directly into the midgut. The establishment of a reservoir host may often take thousands, perhaps millions of years unless the new host is genetically similar to the original one. ie. the appearance of a primate reservoir is vanishingly unlikely. Bats will be the issue from now until long after we are all gone.
Steve – less than half have bleeding you say? What about the others. I am not suggesting it is the only symptom, but an “interesting” one at least. It is clues I am looking for. Clues for a positive solution that does not involve billions of dollars.
Steve, I repeat. Less than half have bled? What about the other half? That’s a lot.
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There isn’t much evidence for Ebola transmission by any mechanism. Not too many people perform experiments with pathogens requiring level 4 containment for good reason.
Considering over 300 SNPs were observed on THIS virus several months ago, I would guess mutation IS feasible and reality. Perhaps you should rephrase your comment above to say what you actually mean ? Another pub indicated a rate of something like 7×10-3 per loci per annum as the derived mutation rate based on observations about those SNPs. I will take empirical observation over bloviation any day.
Thanks very much for the link; there is much interesting discussion in there. I think it is important to raise the awareness level of the potential for droplet transmission and the importance of avoiding the misuse & associated misunderstanding of the term ‘airborne’.
Please… you merely show your ignorance of how short a period a new genetic based adaption would take to spread through an insect population. Lab experiments have repeatedly demonstrated that pesticide resistance can spread through a local tropical mosquito population in as little as 2 – 4 years. The known Ebola reservoir(s) has(have) not been positively identified but instead has merely been assumed / suggested. Now we have a situation where a large suite of human associated species are newly exposed to the virus. Non-symptomatic infections of some of these animals & humans have been observed. We assume transmission is not associated with dogs, rats, etc. but we do not know very much at this point. What we do know is dwarfed by what we don’t know, what is possible, and what may already be reality.
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You’re a danger to people. This is disgusting and your email should be deleted immediately.
Then what of this? http://globalpoliticalawakening.blogspot.com/2014/09/airborne-ebola-clear-and-present-danger.html?utm_source=GlobalPoliticalAwakening&utm_medium=twitter&utm_campaign=Feed:+GlobalPoliticalAwakening+(GLOBAL+POLITICAL+AWAKENING)&m=1
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yeah, because Vox has a track record of knowing what they’re talking about
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The current “version” of ebola is that it is a bat virus, optimized for spreading between bats (which is its reservoir, I presume). The more it spreads between humans, the more evolution will change the bat virus to become a human virus, now optimized to spread in human populations without needing a bat reservoir to (re)infect humans.
The observation above is so obvious that it is banal. If ebola keeps on spreading in human populations, it *will* become a human virus, optimized for infecting and spreading in human populations. This is just evolution. As the virus adapts to a human host, it will (1) become more infectious (efficient at transmitting from human to human), and (2) less deadly (kill a smaller percentage of people it infects).
(2) happens because a live host is better than a dead host at spreading infection, (1) happens for obvious reasons.
Note that (2) is cold comfort — a virus which kills 80% of people it infects but only infects 0.001% of a population is certainly deadly to the people it infects, but almost without consequence to the larger population. In contrast a virus which kill 1% of people it infects but infects 20% of the population is catastrophic as it will kill millions of people.
Good article, I think jumping to airborne transmission at this stage (and given the remoteness of that possibility) is only to scare people. We should focus on stopping the epidermic for now.
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