An Inside Look at The World’s Deadliest Viruses With Anita McElroy, MD, PhD

Dr. McElroy's research interests include studying the interactions that occur between the host immune system and emerging viral pathogens. To do this, animal model systems, clinical specimens from cases of human disease, and in vitro models are used. Previous work has focused on the Hantaviruses, Rift Valley fever virus (RVFV), Crimean-Congo hemorrhagic fever virus, and Ebola virus. Current studies are utilizing the mouse model to elucidate the role of T cells in immunity to RVFV.

Released: 9/10/19

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Steph Dewar: This podcast is for information and educational purposes only and is not to be considered medical advice for any particular patient. Clinicians must rely on their own informed clinical judgments when making recommendations for their patients. Patients in need of medical advice should consult their personal healthcare provider.

Hello and welcome to That's Pediatrics. I'm Steph Dewar, Vice Chair of Clinical Affairs and Program Director of Pediatric Residency Training Program here at UPMC Children's Hospital of Pittsburgh.

John Williams: I'm John Williams, Professor of Pediatrics and Chief of Pediatric Infectious Diseases here at the University of Pittsburgh and UPMC Children's Hospital of Pittsburgh. We are delighted to welcome our guest today, Dr. Anita McElroy. Dr. McElroy, MD, PhD, who is a specialist in pediatric infectious diseases and is a researcher. And in her lab, she studies some of the world's most deadly viruses. Anita, welcome to That's Pediatrics.

Dr. McElroy: Morning guys, great to be here.

Steph Dewar: So I am so very curious to hear about your interests, your work, and what sorts of viruses you're surrounded with.

Dr. McElroy: Sure. So, we study viruses that generally fall into a category known as hemorrhagic fever viruses, which of course sounds very scary. When people think of hemorrhagic fever, they think of people bleeding from orifices. It's not quite that dramatic in real life, but these are viruses that can cause very severe disease in people. We have a moniker in our lab, we've dubbed ourselves the Fab Lab, and that stands for FAB, which is filoviruses, arenaviruses, and bunyaviruses, which are the three families that we focus most of our efforts on.

Steph Dewar: So where would people encounter these types of viruses? Why are people well like you motivated to learn about them?

Dr. McElroy: Sure. Most of these viruses are found in the developing world, so areas of Africa, Southeast Asia has a few hemorrhagic fever viruses as well, Central and South America. We typically don't see these viruses in the developed world. We don't see them in Europe, we don't see them in the United States, we don't see them in Canada or North America. We're interested in studying these because they make people really, really sick to the extreme. For example, viruses like Ebola can have a case fatality rate ranging from 60 to 90%. And those numbers are astronomical and there is a lot of mimicking, I think, for hemorrhagic fever viruses to what we see in the developed world as sepsis.

We see patients coming into our pediatric intensive care unit here at UPMC Children's who are really sick and require blood pressure support and they require additional breathing support, and that sepsis like picture looks a lot like we see with some of these hemorrhagic fever viruses. So we think that by studying these viruses, we can not only learn about these pathogens that affect the developing world, but also develop new knowledge about how we might intervene in patients that come in just with plain old sepsis in our own ICUs.

John Williams: Now you have a really unusual research program, Anita, because you've done both research in humans infected with some of these viruses as well as in more traditional laboratory mouse models with these viruses, correct?

Dr. McElroy: That is correct. So as a physician scientist, my goal is to make my work as translational as possible. I like to when at all possible do studies using primarily derived humans specimen. So we have done a few studies looking at patient samples from patients who have Ebola virus disease. We've looked at samples from patients who have Lassa disease and we've also done some Rift Valley fever virus disease human work. I think it's really important to get this baseline information from the human studies because we can learn which pathways are perturbed in humans. We look at normal aspects of pathophysiology, things like endothelial function, coagulopathy, inflammatory responses.

We use that information from patients to then say, what questions can we now ask in our laboratory models to model this disease process because clearly you don't do experiments in people. We need to do much more hypothesis driven experiments using our in vitro and animal models, which is what we do in the laboratory here at the University of Pittsburgh.

Steph Dewar: It sounds to me in my somewhat simplified immunologic mind that you are working on treatment rather than prevention.

Dr. McElroy: That's correct. Certainly as a member of the Center for Vaccine Research, we're always thinking about development of new vaccines. We do have some projects ongoing for vaccine development. In fact, there was a recent call from an organization known as SEPI for a huge funding opportunity for human Rift Valley fever virus vaccine development, so that has now been awarded to two separate groups. There's another call coming out. We hope to to think about applying for that in the future. But there is now resource and motivation for development of human Rift vaccines, which has never existed in the past, so that's a really exciting prospect for the future.

But the work that we're doing in the laboratory focusing on immunology is not just how do vaccines protect, but also which aspects of the host immune response are beneficial and which aspects of the host immune response might be detrimental to someone when they have their primary infection with one of these viruses.

John Williams: So can you give us an example of something you've learned from, say, the human study of Rift Valley fever and then how you apply that in an animal model?

Dr. McElroy: Sure. There were two observations that were made in from our human Rift studies and that is individuals who survived their rift Valley fever virus disease have higher levels of a protein known as soluble CD40 ligand and a protein known as rantes, R-A-N-T-E-S. Really a long name for that that's not really relevant. These proteins both play an important role in adaptive immune responses. We're talking about B cells and T cells generating antibodies and T cell mediated immunity. So we've used our mouse model of Rift Valley fever virus here at Pittsburgh to try and understand how adaptive immunity is important in protecting from Rift Valley fever virus disease.

We've been able to show that CD4 T cells specifically are really important in preventing the encephalitis form of the disease. So, Rift causes two diseases in humans, either a fulminant severe hepatitis or a later onset encephalitis. From our work, it seems like the hepatitis can be prevented with a really good innate immune system, but you need adaptive immunity to protect you from encephalitis, which gets back a little bit to Dr. Dewar's comment about therapies for these pathogens. So the idea then would be if we can identify an individual who's destined to develop these late onset encephalitis issues, perhaps we could have a therapeutic monoclonal antibody or a therapeutic drug that could be given to those individuals to prevent that particular complication.

We're exploring all that in the mouse model.

Steph Dewar: Once again, you've jettisoned well beyond my grasp of immunology, which is brilliant to to know that there are people like you out there thinking about these issues and working on these issues. So my question is, how does someone like you come to this place? What was your path to end up in Peds ID and with these research interests?

Dr. McElroy: Yeah. This is always a fun question. So, I did it backwards from most people who are MD PhDs. I went to undergrad at university of Maryland college park and got a degree in microbiology because I loved studying viruses. I had some phenomenal mentors there and then I went to grad school at UC San Diego, worked for Debbie Spector studying human cytomegalovirus. Again, phenomenal mentor. But, I knew that the herpes viruses weren't really where my passion was. So then I did a post doctoral fellowship at the US Army Medical Research Institute for Infectious Diseases where I worked with Connie Schmaljohn studying emerging viruses like the ones I study now.

I did work on Rift there. I did work on Crimean-Congo hemorrhagic fever virus. I did some work on the Hanta viruses, which you may have heard of. We actually have those in the United States. Then I had an incident while I was there where I had a filter unit burst on me while I was working in the containment lab and Hanta virus, one called, the local one, Sin Nombre virus. It's the one we have in the United States, burst out of the filter and sprayed all over my chest. Now this is a virus that has a case fatality rate of about 30%, so it gave me an opportunity to do some introspection and think about where I had been and where I was going.

It was at that point that I decided I wanted to go back to school and get an MD. So, I went to George Washington University in DC and then realized that I could not take care of adults, that I must be a pediatrician and went to Emory where I did my pediatric training and then a pediatric ID fellowship. It sounds like a really long and involved story as I'm telling it, but stayed on at Emory as junior faculty. But while I was there, I had to do all of my work at the CDC, which is just down the street from Emory, conveniently located, because Emery didn't have containment facilities to do the kinds of work with the viruses I work with.

So, I had some great mentors at CDC, both Dr. Stewart Nickel and Christina [Spadopalu 00:09:40] really supportive of me over the years, but knew that in order to be an independent investigator, I needed to move on. And when I thought about where I could go, I could think of no better place than the University of Pittsburgh and Children's Hospital of Pittsburgh. That is because there's fantastic leadership here. John Williams, who happens to be in the room with us today is my division director, who's a pediatric infectious disease physician who is also a basic science virologist.

And guess what, so is our department chair, a pediatric ID physician who's a basic science virologist. Just as a bonus, the University of Pittsburgh happens to have a regional bio containment lab where the Center of Vaccine Research is housed down in Oakland, where we can work with pathogens that require VSL3 containment. So, it was a win, win, win for me with fantastic leadership and a great place to do science. It was kind of a no brainer for me to come to Pittsburgh when it was time to move on.

Steph Dewar: That is a great explanation and actually your experience with the military and that makes perfect sense to me that they would have a great interest in worldwide infections. That sort of helps to clarify your path in my mind, so thank you for that. So I'm just wondering what is it that we don't know about? What's the thing that you're excited about? What are you anticipating in the next five, 10, 15 years?

Dr. McElroy: I guess the thing I worry about the most is the thing that WHO calls disease X. It is the emerging viral pathogen that we don't yet know about. If you think about it, we didn't know about SARS until SARS showed up on the planet. We didn't know about MERS until all of a sudden camels from Saudi Arabia were giving MERS to people. We didn't really think much about Zika until all of a sudden Zika became a worldwide craze, so there is another pathogen on the horizon and we just don't know what it is yet. I think by studying the pathogens we do know about, we can have infrastructures and platforms in place to allow us to be ready when disease X arrives so that we can have the best shot at protecting people from it.

John Williams: If I could just, Anita, to get close to wrapping up. I have the advantage of working with Dr. McElroy, so I can say she is a terrific pediatrician, and you've highlighted the research you do in the Center for Vaccine Research. Podcast listeners will recall that we had the director of the Center for Vaccine Research, Paul Duprex as a guest on a measles podcast. Maybe you could tell us a little bit about what it's like balancing seeing patients in the hospital versus being a researcher in the lab dressed in one of those spacesuits to go into the high containment facility.

How do you balance all this?

Dr. McElroy: Not well is the answer. It's difficult to do a little bit of both, but I wouldn't change the way my life is at this point. I absolutely love working in the lab. I love doing the science. I love being the person holding the pipette and that's going to continue to fascinate me to be involved directly in the doing of the science. But I really value the time I have on clinical service. I spend six weeks a year seeing patients here at UPMC Children's on the infectious disease inpatient service, and that time allows me to reorder my priorities.

It allows me to sort of refocus my efforts on what's important to people and to patients and to say this is what really matters and it influences my science. It really helps me to see a patient in the ICU and to understand what's going wrong in that patient with sepsis to help influence the questions that I might ask in the laboratory. So the two experiences really inform an influence each other, and I really can't think of a better job than to to be an MD PhD.

Steph Dewar: Knowing what you know as a scientist and knowing what you know as a pediatrician, what advice would you give to people about travel, infections, prevention, that sort of thing?

Dr. McElroy: Yeah. I have a great anecdote for that. I had a patient when I was at Emory. I got called in three o'clock in the morning. I was on the clinical ID service and it was an eight month old who had just been brought back from a trip to Southeast Asia and a very astute mom had said to the ER physician, my child has measles. They called me and said, could this child have measles? And we talked about the story and it turns out that the child had been exposed to an uncle who had measles in that country and the child had not been vaccinated prior to travel and had come back to the US and thankfully because of that very astute mom, the patient was appropriately placed in precautions.

We sent off the appropriate testing. The child did have measles and the kid was managed appropriately in the hospital, given some vitamin A as we do for measles a and then did well. That was a success story of things done right, but things often are not done well and things can go wrong. So I think the best way for people to protect themselves, especially if they travel a lot, is to go to travel clinic. There are a whole series of vaccines that you can get before you go to a different part of the world and your local friendly travel doctor will know exactly which ones you need that will help protect you.

Interestingly, that child who was eight months old could have received a measles vaccine prior to travel. You can get that as early as six months, but that particular patient's pediatrician didn't know that that was an option. So it's really important that we get the word out to each other that there are lots of options, and the CDC has a great website to tell you which vaccines you can get. You can go to ACIP or you can go to the the travel site for CDC and figure out what anti-malarials you should take before you travel, which vaccines you should get before you travel.

And good advice no matter where you go in the world would be don't drink the water if you have questions about it, drink bottled water and take anti-malarials if they're indicated, and always, always, always wash your hands. That's the best advice that any ID doc can give to anyone. Hand washing is supreme.

Steph Dewar: Well, I'm so happy that you didn't recommend staying at home and keeping the doors and windows shut because I actually enjoy traveling and I agree that's excellent advice for travelers and also for us as pediatricians to know how to advocate for our patients and families when they are moving around this world, which is a very interesting place.

John Williams: Well, Dr. McElroy, I just want to thank you for being our guest today. This has been a terrific episode.

Steph Dewar: And thank you so much for joining us on That's pediatrics. You can find us on Google Play or iTunes. Please send us your feedback about other topics that you might want to hear about.