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It's confusing. You hear that Ebola victim Thomas Eric Duncan was so contagious that two Dallas nurses in protective gear caught the virus. But then you hear, in more recent days, that apparently nobody else did, including the inner circle who lived with him and cared for him. The CDC announced today that all of Mr. Duncan's "community contacts" have completed their 21-day monitoring period without developing Ebola.
How to understand that? And how to address alarmists' claims that for the nurses and so many West Africans to have caught Ebola, it must have gone "airborne"?
I turned to Dr. Elke Muhlberger, an Ebola expert long intimate with the virus — through more than 20 years of Ebola research that included two pregnancies. (I must say I find this the ultimate antidote for the fear generated by the nurses' infections: A researcher so confident in the power of taking the right precautions that she had no fear — and rightly so, it turned out — for her babies-to-be.)
Dr. Muhlberger is an associate professor of micriobiology at Boston University and director of the Biomolecule Production Core at the National Emerging Infectious Diseases Laboratories (widely referred to as the NEIDL, pronounced "needle") at Boston University. Our conversation, lightly edited:
Is it really true you worked on Ebola through two pregnancies?
Yes, but in the proper protective gear. That makes a huge difference, if you're protected, if you know how to protect yourself, and that is the case in a Biosafety Level 4 lab, of course. If you compare the protective gear we're wearing in a Biosafety Level 4 lab and the gear they're wearing in West Africa now treating patients, it's like comparing a stainless steel vault to a cardboard box.
But on the other hand, if you look at the nurses in Dallas, you say, 'How did they get infected?' It makes you worry that maybe protective gear isn't good enough — but you're proof of the opposite.
A Biosafety Level 4 lab is such a high-end lab, it is not possible to use protective gear like that in every hospital in the U.S.
Could you please lay out a brief primer on the biology of how Ebola is transmitted?
We know from previous outbreaks, and also from the current outbreak, that Ebola is transmitted by having very close contact to infected patients. So we know that it is transmitted by bodily fluids, which include blood, first of all — because the amount of virus in the blood is very, very high, especially at late stages of infection — but it’s also spread by vomit, by sputum, by feces, by urine and by other bodily fluids.
The reason for that is that at late stages of infection, the Ebola virus affects almost all our organs — it causes a systemic infection. One main organ targeted by Ebola virus is the liver, and that could be one of the reasons that we see these very high concentrations of viral particles in the blood. But I would like to emphasize that that occurs late in infection.
Early infection is the other way around. The primary targets — the first cells that come in contact with Ebola virus and get infected — are cells that are part of our immune system. And these cells most likely spread the virus throughout our body. But there are not so many cells infected at the very beginning of the infection, which might be the reason why Ebola virus patients do not spread virus at the very beginning of infection. And that's why it’s safe to have contact with these patients, because the viral titers in their blood are so low that we cannot even detect them with methods like PCR, which is one of the methods we use to diagnose Ebola virus.
Is a virus only contagious when it reaches a certain level of "titer" or load?
That’s very difficult to answer because we know that for some viral infections most likely one viral particle is enough to infect somebody. So then the answer would be no. But we also know that some viruses are not really good spreaders, so you do need a certain amount of viruses to transmit this virus to another person.
Is that true for Ebola?
For Ebola virus, it seems to be true, because from experience, we know that this virus is not transmitted early in infection. If the viral titers are very low, if you’re not able to detect free viruses in the blood, then it seems Ebola virus is not transmitted to other people. Which is very good because, theoretically, that makes it really easy to control Ebola virus infection. And the reason why we have such a disaster right now, with almost 10,000 infected in West Africa and more than 4,000 already dead, is not so much the transmissibility of Ebola but rather the lack of infrastructure in these countries.
Some people are claiming that to infect so many people, the virus must have moved from just bodily fluids to "airborne"...
I think there's some confusion here. We know that some viruses — like influenza virus, and measles — are transmitted before the patient shows symptoms. Especially the measles virus, which is the winner in terms of being contagious. What these viruses do is infect the respiratory tract — that is their first target organ. That’s how they start the infection, and then they replicate or amplify themselves in cells of the upper respiratory tract. And then when we breathe, we release these viruses because they're part of our 'breathing air.' There are tiny, tiny, tiny little droplets, and these droplets contain the virus. They can stretch pretty far, like a couple of feet. And that is what we call an airborne infection. If we breathe and then we shed virus with our breath.
So you don’t even need visible droplets, it’s just air?
They’re tiny little droplets in our breath. And these viral particles are part of it. This is completely different from Ebola virus. First of all, Ebola virus does not begin an infection by infecting our upper respiratory tract. The route of infection starts with little lesions in our skin, and then the virus gets in our skin, and then in our blood system, and then in these immune cells I mentioned before, which are the primary target cells. It’s also able to get into our eyes and mucosal membranes, but it does not infect the cells which we need to get infected to have an infection be airborne. Late in the infection, when the Ebola virus patients have very high viral loads, they are really really ill, way too ill to get on a train and sit there.
So you’re saying that when they’re so ill that it could be in the respiratory system, they're super-ill, not able to go anywhere?
Exactly. The cells in the lung can be infected by Ebola virus but really late in the infection. That's very important. As far as we know, the infection starts with the immune cells — for those who know a little more about the immune system, it’s dendritic cells and macrophages. Then it goes to lymph nodes. Then very quickly to the liver, and there it goes crazy. The liver is very crucial in Ebola virus infections because it is so heavily affected. Ebola virus also spreads to the spleen, to other organs, and then later in infection it tends to infect the cells that coat the blood vessels, and of course we have these cells in the lung as well.
So when we are infected with Ebola virus and we are really sick, then we spread the virus through all our body fluids, which includes blood, sputum, feces urine, breast milk and semen. Again, then we have Ebola virus in little droplets, which is the reason we talk about infection via droplets, but these droplets are much bigger — though they are tiny, of course — but these are much bigger than the droplets which cause aerosol-borne disease. So it’s a matter of size. And if they are bigger they cannot be transmitted over a large distance.
So if they’re bigger they can’t just float in your breath? But you could perhaps project them?
Of course you have them in your sputum — as you speak, you kind of shed virus — but then the droplets drop to the ground pretty quickly because they are heavier. It's really a matter of size and weight.
The CDC recently tweeted an answer to a common Ebola question: It said yes, if someone with Ebola sneezes on you and the droplets land in your eyes or mouth, then conceivably you could catch Ebola. But that doesn't count as airborne?
Exactly, and it’s all about timing. When someone is infected with measles and then sneezes or coughs, and is not sick at this point, they can transmit the virus to others and you're not even aware that someone with the disease is contacting you. That’s the big difference with Ebola virus and these bigger droplets — but nevertheless droplets, of course. When Ebola virus patients start to transmit the virus, they have already developed a fever and are obviously sick.
So that helps explains why more people haven’t been infected in the U.S.?
Exactly. It's very unfortunate, what happened in Dallas — that's already the worst-case scenario for the U.S. It already happened to us. First, the patient came into the country without being identified as infected. That could happen again, just because of travel activity. Also, if the outbreak in West Africa is not controlled, more and more people will become infected. This makes it likely that infected patients will get into other countries. So that was the first thing that happened, which most likely is not easy to avoid.
Second — and this is something that could have been avoided — is that the infected person was not quarantined immediately, though we knew he had already gotten sick. He had contact with other persons who were not protected during his illness.
Finally, the nurses, who contracted the virus from the patient and eventually became ill, were not immediately quarantined and could have infected more people. And that is the worst-case scenario we can think of with Ebola virus.
Although what's interesting is that, at least so far, aside from the two nurses, none of the people around Thomas Eric Duncan or the nurses has caught it.
Exactly. And that's exactly what we know about Ebola virus: You really need close contact, especially contact with those who are severely ill, and that is because of of this special mode of transmission. Even early in infection it is not so contagious. Those who are at risk to get infected are those who take care of the ill patients — health care workers or relatives at home — and then the second group who got really hard hit by Ebola virus infections is those who care for the deceased, like relatives who washed the deceased, which is not really our funeral rites. So that is not a real risk for us, especially if you know someone died of Ebola virus.
Speculating, what do you think happened with the two nurses?
It's a very interesting question. Since we know how to avoid Ebola virus infection, my assumption — but it's really just an assumption — is that they did not wear the correct protective gear or, most likely, they were not trained to wear the protective gear correctly. Because you have to make sure that you protect every little bit of your skin, that's so important. We talked about these droplets — if tiny little parts of your skin are not covered, and the patient is bleeding, and you get these droplets somewhere on your skin and then you have a tiny, tiny little scratch --
That maybe you can't even see —
Exactly. And we all have little scratches, or your eyes are not properly protected. Even a little bit of unprotected skin — because of these little lesions we have in our skin — is enough to get infected. And it’s also important to think about how you take off your protective gear, because if you’re covered in the bodily fluids of the patient and then you have to take it off, how do you do that without touching your skin at one point?
So we are in a very fortunate position in the Biosafety Level 4 labs because we have chemical showers — and this is exactly why we have the chemical showers, to make sure that every part of us is somehow wetted with disinfectant, that we have contact with disinfectant everywhere. In the field, it’s very difficult to do that because you obviously don’t have chemical showers. Taking off the protective gear is something that needs a lot of training and very importantly, it needs a buddy system, you need somebody to help you to take off your protective gear. I don't know if that happened in Dallas but that's something that's very, very important. That is really the most dangerous part of it: even if you wear this protective gear, at one point you have to take it off, and how do you do that without touching somewhere on your skin?
In some ways, Ebola transmission seems reminiscent of HIV. Could you please compare the two?
Comparing Ebola to HIV is like comparing a a bulldozer to a high-end intelligent robot. Because Ebola is not at all adapted to us, so it just infects us, it kills us pretty quickly or at least causes severe disease, and then when we are done, the virus is done as well because if the host is dead, the virus is dead as well. Ebola virus causes what we call an acute infection: It lasts about two weeks and then it’s over one way or the other.
HIV is completely different. HIV manages to get its little tiny genome into our genome in the cells, and some of these cells survive forever, and that's the big issue with HIV. It becomes part of our own genomic equipment and so if these cells, which carry these little fragments, little HIV genomes, if they get activated, it really is not important how, then HIV starts to replicate its own genome and the infection starts again. That's what we call a persistent infection, which is much, much harder to fight. With the Ebola virus, my guess is it’s much simpler to fight the infection.
And in terms of transmission?
I already mentioned that Ebola virus causes a systemic infection, so the entire body is affected by the infection. HIV is much more picky about the cells it would like to infect; it only infects a special subset of our immune cells — T cells — and it stays in these cells forever; until the cells die, it's there. And since it is only in this special subset of blood cells, it’s only transmitted by blood and fluids, but not by sputum, for example, not by feces, not by saliva. The highest risk with HIV is sexual intercourse — it’s almost the only risk, and contact with blood, of course. And that makes it so different.
But nevertheless, because HIV lasts in our body forever once we are infected, that’s the reason why if you are infected with HIV and you don’t get treatment that helps you get the viral concentration down, then you theoretically can spread the virus as long as you live. And that is different from Ebola virus because Ebola is cleared after two weeks. You’re virus free and maybe even protected from a new Ebola virus infection. There’s a lot of speculation about that — we don't know for sure if Ebola patients are protected going forward.
The news lately has been that in Dallas, people are coming off of quarantine after 21 days — that's solid, that after 21 days you're clear?
We know for Ebola virus the longest incubation period --- the time from when you get infected to the time you show symptoms, that’s the incubation period — we ever heard about is 21 days. So if you're healthy for 21 days, you do not have the infection.
And that's different from having the infection and clearing it?
Then you have to do tests with these patients — you have to look at their blood and see if there’s still virus. Once you see there’s no virus in the blood — and you should repeat that at least two or three times to make sure there’s really no virus anymore — if this is the case then the patients are cleared and safe. With one exception — semen. That is a little bit strange, but it is as it is — it seems that Ebola virus can last in the body a little bit longer, because there are reports that it has been transmitted by sexual intercourse after seven weeks or so. But patients, if they know about that, they can easily take care of it.
Do we have any idea why that would be, biologically?
Sorry, no! it’s very weird, it was completely unexpected but it happened, unfortunately.
Was it a single case report? Or more?
I know about one report of a very similar virus — Marburg virus — so that was a very well-controlled outbreak in 1967 in Germany, in Marburg, and exactly that happened. And one of the patients who survived the infection then infected his wife, and that’s why we know about that. There have also been reports of detection of Ebola virus in semen almost three months after the infection.
As you’ve watched media coverage and public reaction, any other scientific corrections you've especially wanted to make, or additions to public understanding of how Ebola is transmitted?
I think we really should focus on the outbreak in Africa. To make it crystal clear, we do not have an Ebola virus outbreak in the U.S. We do have an Ebola virus outbreak in West Africa. We have to do all we can do to stop this outbreak for our own good because we do not want to have a similar situation as the Dallas patient.
I also want to make clear that this virus is not transmitted by the air, and this virus will not be transmitted by the air. In virology, we are not aware of a single virus which changed its transmission route so dramatically. I've asked a lot of my colleagues: Are you aware of any virus which changed its transmission route? Any virus which went from blood-borne or transmitted by bodily fluids to airborne? And nobody knew of any virus.
Ever. In 100 years of virology. I would be glad to learn if that happened but I talked to a number of people and nobody could tell me a single example of that. It’s nature, you never know, a scientist never says never, but it’s very, very, very, very, very unlikely.
And I also want to mention, because we have cases not only here in the U.S. but I also heard about incidents in Europe — that there was somebody sitting on the train, throwing up, and people surrounded this person — a black person, which gives it some racist element too — and completely freaked out and called 911, 'It’s Ebola, it’s Ebola!' And that won’t happen because Ebola virus patients are really sick, and that’s also something you should keep in mind. They do not walk around happily and all of a sudden they start to throw up, that is not the case. It's a deadly disease, and deadly means deadly, so you are ill and you won’t be able to walk around and infect people so easily.
You can’t really get out of bed by the time your fluids would be contagious?
Are there people who have been basically immune to Ebola virus?
That’s a very interesting question. There’s a very nice study by a French and African group, published in 2000, in which they identified what they called asymptomatic Ebola virus patients. There were people who had very close contact to Ebola virus patients but they did not become ill. They looked more closely at these people and they found that they had a very effective and well-regulated immune response to Ebola virus infection. They developed antibodies and they did not show any signs of infection. Obviously they were infected because they developed antibodies, but they were able to clear the infection.
So there are people like that...
Yes, but we don't know why that is the case. One possibility could be that there are genetic differences, of course. Another possibility could be that they were infected with only very very tiny little amounts of virus and the immune system was able to clear the infection before the concentration goes up like crazy. But we don't know the mechanism, not at all. That’s something that's very important to learn: Why do some people get infected but not develop the disease?
Most media coverage says clearly that Ebola is not airborne, but there was one piece in the Los Angeles Times with the headline, "Some Ebola experts worry virus may spread more easily than assumed." It referred to a monkey study in which monkeys that caught Ebola from each other were in close quarters and raised the question of whether it might be airborne.
If it’s the paper I think it is, there were no controlled conditions. It's not really clear how the virus was transmitted. That's scary. But we don't know how that happened.
There is another study that was published more recently, with Ebola virus Zaire, by Gary Kobinger in Winnipeg: His team infected pigs with Ebola virus Zaire and then monkeys in the same room as the pigs got infected. They obviously transmitted the virus but pigs are not the most clean and neat animals and they were in the same room.
What is really important is then they did exactly the same study with monkeys only: They infected monkeys with Ebola virus and they had another set of monkeys in the same room in another cage. In this case, the monkeys were not infected with the Ebola virus. So it was pig to monkey but not monkey to monkey, with Ebola virus Zaire.
I feel so much better...
You should get your flu vaccine, that’s much more important. That’s my last message to everybody: Please get your flu vaccine.
Readers, lingering questions?
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