The Science of Ebola -- Questions Answered by Anthony Fauci, MD

Readers Have Questions on Ebola

Susan B. Yox, RN, EdD: Hello. I'm Susan Yox, Infectious Diseases and Public Health editor of Medscape. Our readers, primarily physicians and nurses, continue to have many science-related questions about Ebola. We want to find the best answers for them, so today we're talking to the expert. I'm joined by Dr Anthony Fauci of the National Institutes of Health's National Institute of Allergy and Infectious Diseases, who has graciously agreed to answer some of Medscape readers' most common questions. Hello, Dr Fauci.

Anthony S. Fauci, MD: Hello.

Dr Yox: Let's begin by talking about some potential misunderstandings of the terminology used around Ebola and modes of transmission. The first question from our readers is: "Experts keep saying that Ebola is not an airborne virus, yet airborne-level precautions are often recommended when professionals care for patients with Ebola (eg, powered air-purifying respirators [PAPRs], negative-pressure rooms, and talk about increased protection during aerosol-generating procedures)." Can you explain what seems to some of our readers to be a contradiction—how Ebola is spread and the recommendations for personal precautions? Are clinicians perhaps confusing aerosol-generating with airborne?

Dr Fauci: Correct. I think you just said it correctly. There is some confusion. When you classically think of a virus that's transmitted by the respiratory aerosol route, you're thinking of a typical influenza-like situation where someone who's within a few feet of you can cough or sneeze. You don't see anything. You don't see any visible spray, and then the person [who was coughed or sneezed upon] winds up getting infected. That's not the situation when you're dealing with somebody with Ebola who is walking around, feeling reasonably well, but is infected.

However, when you consider someone who is in the advanced stage of [Ebola virus] disease in a hospital setting, there are situations where the virus can be replicating in the lung, when there are large amounts of sputum, or when a patient is ill in an intensive care setting. For example, if a clinician needs to intubate someone, which is conceivable for someone who is so critically ill, the splashing of sputum or saliva when you have advanced disease with a very high titer of virus—that is when you need the PAPR or the face mask and all the other personal protective equipment (PPE).

I had the personal opportunity to take care of a patient who had Ebola, Nina Pham, when she was in our unit. [In that situation], our PPE completely covered everything; no skin was left exposed and we used a PAPR. [Using that level of equipment] doesn't mean that Ebola is a respiratory-borne virus. The protection provided by that level of PPE really protects against the splashing of droplets. The misunderstanding results when you fail to put that in the context of the potential for aerosol spread from someone out in the community feeling fairly well, versus aerosol spread when someone is very, very sick. [In the latter situation] there are high levels of virus in the lung and therefore in the sputum and possibly in the saliva.

Dr Yox: So Ebola is definitely not airborne, then, by the traditional definition.

Dr Fauci: Again, you have to be careful when you use the word airborne. Let's say—and I don't want to be too graphic about it in the sense of being facetious—but let's say that someone is in bed and they are dreadfully ill, and they have high titers of virus, including virus in their lung. They are having difficulty breathing and they cough out droplets. The droplet goes from the patient onto my protective equipment. Is that airborne? Well, yes, it is. I didn't directly touch the person but it came in via air.

You've got to be careful [with terminology] because when we classically think of airborne, we tend to think of an aerosolized approach where you barely see the material and you get it from essentially talking. The vapor that comes out looks almost like a mist, which is typical of influenza and other respiratory-borne viruses. Classically, Ebola is not a respiratory-borne virus, but when someone has advanced disease, where the virus titer is high, anything that comes out of the lung is going to be infected. However, at that point the patient is so sick that it is extremely unlikely, if not impossible, that they are going to be walking around the street, coughing on people.

Does the Ebola Virus Mutate?

Dr Yox: Thank you. I think that does help a great deal. The next question has to do with the scientific evidence and what it says about the mutagenic potential of Ebola. Our readers keep asking, "Why are the experts so convinced that Ebola will not mutate?"

Dr Fauci: First of all, Ebola does mutate. It mutates all the time. It's an RNA virus, and like influenza and HIV, it mutates because RNA viruses don't have good proofreading mechanisms when they make mistakes (and by "mistakes" we mean mutations). What we're saying is that the overwhelming majority of mutations are not relevant to the function of the virus. They're called synonymous mutations.

Nonsynonymous mutations occur less frequently and are associated with some sort of functional change. We know from years and years of experience with many, many viruses that viruses can mutate and have some modest change in function. Some become a little bit more virulent or, even more likely, a little bit less virulent as they continue to replicate and mutate. Sometimes a virus is spread a bit more efficiently or a bit less efficiently, but it is essentially unprecedented that a virus will mutate to the point where it completely changes the modality of its transmission.

Is that impossible? No. Nothing is impossible when you're dealing with these types of situations, but is it likely? No. It's extraordinarily unlikely, based on a lot of past experiences with viruses that mutate a lot but that don't fundamentally change the way they're transmitted. That's what we're talking about. No one is denying at all that Ebola mutates. It definitely does mutate; there are well-documented mutations.

Questions About the Transmission of Ebola

Dr Yox: A number of readers have detailed questions on transmission. Here's the first one. A reader asks, "What does the evidence show about how long Ebola can survive on dried surfaces and still infect another person?"

Dr Fauci: Again, there aren't definitive data where a lot of experiments have been done. But some have been done, and it really depends on so many things: the light in the room, the moisture of the room. But if you have Ebola virus that's not in a proteinaceous material like blood, sputum, diarrhea, or vomitus, but instead just dry virus on an inanimate object, [the length of time it can survive] is likely measured in minutes. However, if the Ebola virus is in material that's proteinaceous, like blood, diarrhea, or vomit, it can last for a considerable period of time, measured even in days.

We know that this happens because people get infected at funerals when they touch a body, or when they try to minister to a body, even if someone has been dead for a couple of days. We do know from the considerable experience with transmissibility from corpses of people who have died from Ebola that the virus can last. But when you're talking about something that you don't see—not something like a bloody doorknob or a bloody table or a bloody utensil—if something looks clean but there's a virus on there and it's dry, it is very unlikely that it lasts more than just a few minutes.

Dr Yox: Here is a related question. People have asked about Ebola being defined as "hard to catch," and they ask how much exposure, then, in terms of volume, is required to become infected. One reader asks, "Is just a drop enough?"

Dr Fauci: It is probably very little [volume needed] when you're dealing with a very sick patient in which the titer of the virus is very, very high. We know that with the healthcare workers who have gotten infected, some of them likely have gotten infected when they were taking off (doffing) their PPE. Sometimes you get material on the PPE that you might not even notice, and as you doff you brush it against your skin and then maybe touch your nose or your eye. It is impossible to quantify how much material is going to be required for transmission. It's related much more to what the titer of the virus is in that material.

Dr Yox: What about the evidence that only symptomatic Ebola patients can spread the disease? One of our readers asked, "Are there patients with antibodies to the disease who are perhaps never symptomatic? Could some people still be infectious if they were never symptomatic?"

Dr Fauci: First of all, there are reports of asymptomatic infection but those reports are really kind of weak in many respects. There's no evidence that those people can actually transmit infection, but let's get away from that because that's an outlier, and instead get to the core of the question that people do ask: someone who you know is infected, and that person will ultimately get sick. Let's not imagine that rare, rare person who has been reported who would remain asymptomatic, but a classic patient who gets infected.

From the time an Ebola patient gets infected, the overwhelming majority of data indicate that these persons don't transmit disease when they are without symptoms. In fact, in a recent paper published in the New England Journal of Medicine^[1] by individuals who were in West Africa in the current outbreak, they found that they could not trace a [single] person who has gotten infected from someone who is asymptomatic. Every one of the infections was traced to being in contact with someone who was clearly sick. There were no cases where someone said, "I never came into contact with someone who wasn't sick at all."

So the data are pretty strong. However, when you're dealing with biology it's never 100%. You can never say that something is impossible, but the large volume of data strongly suggests that a person who is without fever and has no symptoms does not transmit the infection to someone else.

Dr Yox: A couple of other detailed transmission questions. "Do Ebola viral particles have to be exposed to mucous membranes or can exposure to intact skin potentially result in infection?"

Dr Fauci: Again, the experiment [to answer this question] has not been preemptively done, for obvious ethical reasons. You don't take Ebola and put it on someone's intact skin. What you think is intact skin may not be. You could do a lot of animal studies to show that, but there are clearly microscopic rents in skin that you don't notice, that don't bleed. Skin may not be completely intact skin.

Dr Yox: That makes sense. The 21 days from exposure to possible infection was another question—is this incubation period of 2 to 21 days known to be the absolute limit for Ebola or is it a general observation?

Dr Fauci: Again, you've got to be careful when you talk about absolutes. Will there be people who clearly got sick more than 21 days after they were exposed? I'm sure that's the case, but when you look at the overwhelming majority of people, the incubation period is within that framework of 2 to 21 days. In fact, the overwhelming majority get sick in the 8- to 10-day period from the time they get exposed to the time they get sick. Some go out further, but in the multiple studies that have been reported, [the incubation period] has not gone beyond 21 days. However, there are some reports saying that it looked like a person was exposed at a certain time and did not get infected until beyond 21 days. Those are outliers, and then you could say, "Well, then, when is it?" It's tough to say, but the data strongly indicate that 2 to 21 days captures almost all of the people.

Dr Yox: Thank you. Next question: "Is there a ban on sex after recovery from Ebola infection, and how long should sex be avoided?" Are there any data on this?

Dr Fauci: Certainly there have been some data (primarily PCR and an occasional culture) identifying Ebola in seminal fluid beyond the time that a person was asymptomatic and did not have Ebola identified in their blood. [The time has been variable]—60 days, 70 days, 80 days—and that is the reason why the CDC makes a recommendation that if you are a male recovering from Ebola, or a female having sex with someone who's recovered from Ebola, that you practice safe sex with a condom for at least a few months following the complete recovery from Ebola.

Ebola and the Future: Lab Tests, Vaccines

Dr Yox: The last question relates to the (hopefully) near future. Clinicians ask, "When might we expect better laboratory tests to diagnose Ebola?" Clinicians are asking for tests that are quicker with results and positive earlier in the course of disease, perhaps before the person with Ebola is symptomatic.

Dr Fauci: There are two aspects to your question. There's a point-of-care diagnostic where someone comes in, is starting to feel some symptoms and maybe is febrile, and you would get a positive test if you took it, drew the blood, and sent it to a lab. However, you wouldn't get the results until a few hours later or you'd have to put the specimen in a truck to get to the lab, and maybe many, many hours would go by before you get the result. Then you also need a confirmatory test from the CDC or a CDC-approved lab.

Alternatively, a point-of-care diagnostic for someone who is having symptoms is one in which you draw the blood and within 20 minutes or so, you can get your answer. That's as important as, or even more important than, getting a test on an asymptomatic person, where you can get a positive result before they have symptoms. That would be a tough test to get because we know that the titer of virus is so low even when a person starts to get symptoms; it's only when they really become sick do you get a high enough titer to make a diagnosis. That is when the sensitivity of your assay clearly gives you a positive test. Although we hope we can get a diagnostic test that would be positive before a person had any symptoms, that would be more difficult than getting a point-of-care test for someone who is symptomatic.

Dr Yox: Are either of those tests at all close or are they way off in the future?

Dr Fauci: I wouldn't say that they are "way off." There are different biotech companies and different researchers working on both aspects of improved testing.

Dr Yox: I am wondering whether you have any final comments. Clinical readers are always interested in the vaccine trials, how they're coming along, or any other developments in closing that you may want to tell everyone about.

Dr Fauci: In closing, I could say that the vaccine phase 1 trial that was started in September 2014, with the hope of showing that [this vaccine] is safe and induces an appropriate immune response, [was] published in the New England Journal of Medicine on Thanksgiving day, so readers can take a look at that online. And now the next step would be to move into a phase 2/3 trial in West Africa.

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Cite this: The Science of Ebola -- Questions Answered by Anthony Fauci, MD - Medscape - Dec 03, 2014.