SciCafe Special Event: Zika - What You Need To Know

SciCafe Special Event: Zika - What You Need to Know - Transcript

Susan Perkins (Curator, Division of Invertebrate Zoology, American Museum of Natural History):

Hi, everybody. Welcome to this very special edition of SciCafe called Zika: What You Need to Know. My name is Susan Perkins, and I'm the curator of microbial genomics here at the museum. And I'm going to be moderating tonight's panel. I'm also the curator of our current exhibit that's going on called The Secret World Inside You, which is all about your microbiome. And if you haven't seen it, don't delay because the show will close in mid-August and move on.

So, tonight we're thrilled to have three scientists joining us this evening to talk about the latest news on the Zika virus outbreak and answer questions. So, I'm going to begin by asking a series of questions that are general about the virus, its transmission and the risks, and then we'll open up the floor to your questions. And as always, we encourage you to tweet and use the hashtag amnhscicafe. And, finally, before I introduce our panelists I want to thank the Science Education Partnership Award or SEPA program of the National Institutes of Health for their generous support of tonight's program.

Our first panelist is Dr. Ian Lipkin. He is the John Snow professor and director of the Center for Infection and Immunity at Columbia University. He is world renown for his methods of viral discoveries in epidemiology of pathogenic research. Ian, please come up to the stage and tell us about your research for a couple minutes.

Ian Lipkin (Director, Center for Infection and Immunity, Columbia University):

People who come to visit us say that their visit's like an episode of CSI microbiology. So, what we do is we discover bacteria viruses, and we try to figure out their roles in health and disease. And you've already talked about the—I guess, the exhibit that you now have, which is closing in August. We have some footage in that particular exhibit. It was a lot of fun to help participate in that exhibit.

I was brought here to New York in 1999 shortly after our group discovered West Nile virus here. At that point, I was in California. That's the last mosquito-borne outbreak that was severe that hit the New York City area. So, in addition to studying viruses that cause diseases that you would recognize as being due to infection like pneumonia or hemorrhagic fevers or diarrhea or skin infections that you can readily see, we also study the role of viruses in autism and cancer and diabetes, a whole range of interesting conditions that you wouldn't think of as necessarily being due to infection.

Perkins:

Great. Thank you. Our next panelist is Dr. Catherine Spong. She's the acting director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health. And she's an expert on maternal and fetal health. Cathy, please tell us a little bit more about the work that you do.

Catherine Spong (Acting Director, National Institutes of Child Health and Human Development):

Thank you so much. So, the National Institutes of Health supports research that includes the whole gamut, from basic science through translational research through clinical research. Specific to Zika virus, we've just recently launched a large multi-country cohort study to follow 10,000 women beginning early in pregnancy and monitoring them throughout pregnancy those who symptomatically get Zika, those without symptoms who get Zika and those who do not get Zika.

And we'll be following them through their pregnancies and the women for at least six weeks, and the children for at least a year, to try to understand best what is the risk of Zika in pregnancy and how can we counsel women and their families. I'm also—as you mentioned—an obstetrician-gynecologist. I do see patients in Washington D.C. at Inova Alexandria Hospital. And I do get patients who have traveled or their families have traveled to Brazil and have lots of questions. So, I look forward to the discussion today.

Perkins:

Yeah, we'll hear more about that soon. Yeah. And, finally, is Dr. Jay Varma. He's the deputy commissioner for disease control at the New York City Department of Health and Mental Hygiene. And prior to joining us here in New York, he was with the Centers for Disease Control and had posed in both China and Thailand. Jay, would you please share a summary of your current work?

Jay Varma (Deputy Commissioner for Disease Control, New York City Department of Health):

Great. Thank you, Susan. So, as Susan mentioned most of my career has actually been spent working overseas for the U.S. government working on emerging infectious diseases in Asia. And I moved to New York City a little over five years ago to take my current position where I oversee all of the infectious disease programs at the New York City Health Department.

So, one of the things that's great about New York City is that because we are a global city, everything that happens around the world has a potential impact here. So, I've had a great experience to work on not just diseases that are already endemic here in New York City and of big importance like HIV, sexually transmitted diseases and vaccine preventable diseases, but also when we have emerging epidemics like Zika I am the lead for the health department to marshal our response. And some of that includes helping to get information out. Some of it includes helping to get tests available. And a lot of it really is about coordination and trying to make sure that every part of the city has a role in trying to prevent and control these infections.

Perkins:

Great. And we'll ask you some more details of that soon. So, Ian, I'd like you to take on this first question, which is really the most basic one. What is Zika virus? Where did it come from?

Lipkin:

Well, first of all, what is a virus?

Perkins:

Yeah, let's start there.

Lipkin:

A virus is a piece of genetic material that's wrapped up in a coat of protein. It may have another shell in addition to that. And it has differences from bacteria that we can treat with antibiotics that may not be familiar to many of you. Viruses can really only reproduce themselves inside of cells. So, what they do is once they enter your body, they latch on to cells where they have the capacity to grow, entering through something which sits on the surface of a cell that's known as a receptor. And if it finds that receptor, it assumes—if you can attribute intelligence to the virus—that this is a place where it's going to be able to reproduce itself. Once inside that cell, it reproduces itself thousands and thousands of times, breaks the cell apart and releases many, many more particles.

So, it's not truly alive, but it certainly does a lot of damage as though it were alive. Now, one of the questions that people frequently ask is whether or not all viruses are bad. And the answer to that is no. There's some that are quite useful, but I don't have time to go into that. You can ask later if you wish.

Perkins:

So, what about Zika virus? What is it? What's it related to? And can you tell us a little bit about the history of it?

Lipkin:

Oh, I'm sorry. You want to know about the Zika virus specifically. So, Zika virus is what's known as a flavivirus, which is a descriptive term. It's related to West Nile virus and Dengue virus. And these are viruses that are typically mosquito-borne, which means that they're transmitted when a mosquito bites you and you're infected or an animal's infected. It takes that blood meal, it flies to another human or animal, and then transmits that infection.

It's called Zika virus because it was isolated first in the Zika Forest in Uganda. And it was fairly quiet, and then in the late 1940s it began to appear sporadically around the world. We became aware of the first real outbreaks in Micronesia in an island known as Yap, which is a very, very small island not too far from Guam where the majority of people who are on the island actually became infected.

And thereafter it began to spread. And, ultimately as you've seen now, it's in the Caribbean and in South America. Now, there are many cases as well in Africa. I mention it's related to Dengue virus. This is extremely important because the areas where Dengue virus is found we're also now beginning to find Zika. And I mentioned to you the ways in which viruses enter cells, find a receptor, latch on, enter and begin to reproduce themselves.

Well, if you've been previously exposed to a related virus like Dengue, you may have what's known as a cross-reactive immunological response. What this means is that an antibody will bind to the Zika virus particle, and the antibody itself, which has a little tag that sticks out of the end, which is called Fc for the aficionados, will bind to other cells just through that Fc receptor. It can actually accelerate the rate at which this virus can replicate inside your bodies.

So, when we talk about vaccines later on, we'll have to talk about cross-reactivity and the importance of thinking about that in vaccine design.

Perkins:

Definitely. All right, I want to skip over to Jay for a minute and have him tell us a little bit about the main mode of transmission that we know about. And we'll talk about other modes of transmission shortly, but the main mode of transmission is—as Ian just mentioned—by mosquito bites, primarily of the Aedes aegypti mosquito. And if you want, we've brought down—we've dusted off a model that's almost 100 years old of Aedes aegypti that used to be on display here. So, it's back on the floor, and you can check it out in the back. Jay, can you tell us a little bit about the history of the mosquitoes? Are they here in the New York City area? Is this the same kind of mosquito that transmits West Nile?

Varma:

Yeah. So, if you want to be truly horrified, go look at that case back there.

Perkins:

It's larger than life.

Varma:

Exactly. It's quite large in fact. So, I think to understand a little bit—to understand the differences between the viruses and the mosquitoes that carry them, you need to know that there are thousands of different types of mosquitoes. There's probably over 3,000 different types of mosquitoes that can be found anywhere in the world. And just like humans, they behave differently depending on where they are.

In the United States, there're probably a few hundred different types of mosquitoes. And, again, some of them—the only harm they may cause is to annoy you, but some of them can actually have a virus in them that can then be transmitted from one human to another human. So, as Ian mentioned before, the last big mosquito-borne outbreak that we had in the United States that was worrisome was in 1999, and that was here in New York City where we had the West Nile virus.

The mosquito that transmits that virus is known as the Culex mosquito. And just so you understand what happens when there is a human that has the infection in them and the virus is circulating in their blood and the mosquito bites, it is taking a very, very small amount of blood into its mouth, and then into its gut. And some of these 3,000 mosquitoes in the world have the ability after they take that blood to have the virus go not just through its gut, but back through its circulatory system and go back into its saliva, so that when it bites another human—somebody who's never been infected—it can transmit that infection.

The mosquitoes that transmit West Nile virus behave differently, however, than the Aedes type of mosquitoes. Here in New York City, that horrifying mosquito you see over there, the Aedes aegypti mosquito, doesn't actually live in our climates. It really likes warm, tropical climates. So, it does exist in parts of the United States like Texas and Florida that have that type of climate, but it doesn't really extend this far north.

Now, that may change over time. As we know, our climate is changing, and that could change for the future. What's concerning for us is that there is a relative of that mosquito—of the Aedes aegypti mosquito called Aedes albopictus. That mosquito is here in New York City. And as we'll talk about, I think, at the end, even though the risk of transmission is probably low with this mosquito—it's not quite as efficient or effective at transmitting infection—it is something that we need to be on the watch for and control for.

Perkins:

Great, thanks. So, Cathy, without a doubt the thing that's really capturing a lot of attention and causing a sense of panic in many people with respect to this current outbreak of Zika are these frightening developmental complications when pregnant women get infected. And so would you please tell us what do we currently know about the lengths between Zika virus and birth defects like microcephaly and other neurological and developmental problems?

Spong:

Right. The reason why this has become a public health emergency really is because of the complications for women who are pregnant and the complications for the fetus. We've seen in Brazil really came to light these complications of microcephaly where the baby's head is very small. And as we've been learning more about this, we've realized that in fact it's much more than just microcephaly itself.

The impact of having Zika during pregnancy affects many aspects of the fetus. And part of this includes—much of what we know right now is really just when a women is symptomatic with Zika virus infection. And many of the studies that are out there have looked at symptomatic women and found that there are higher risks of fetal loss or still birth or miscarriage, fetal growth abnormalities where the baby's small, these brain abnormalities, the microcephaly, the ventriculomegoly where the ventricles inside of the baby's brain are enlarged, calcifications inside the baby's brain, as well as abnormal structures or loss of structures within the brain itself.

And then there are other complications as well: neurodevelopmental complications, motor complications and neurobehavioral complications, as well as eye lesions. Much of what we know for the child really has been, again, looking only at the babies with microcephaly and following those children. But in fact we really need to study all children who are exposed to Zika virus during pregnancy.

And there have been some case reports coming out showing that in fact even children who don't have microcephaly have complications. And I think it's going to take some time for us to really understand the long-term implications of this. It's not something you can just determine at birth. We really need to take the time to follow these children and see what happens in the long term. We know that when someone is pregnant and gets a viral infection, there can be complications that can be long term. Even something as simple as influenza during pregnancy can result in higher rates of autism or schizophrenia later in life.

So, there's a lot for us to learn. In addition, not only to understanding what happens for these children with or without microcephaly or small heads, but also looking at the women who are symptomatic, which is about 20 percent of people who get Zika virus during—Zika virus at all have some type of symptom, which is a pretty mild symptom; maybe a headache, a fever, a rash. But about 80 percent of people don't even know that they have Zika. And it's really important for us to be able to do studies to capture all of that.

Perkins:

Yeah. Wow, it's very sobering. And speaking of sobering, one of the things that has made Zika a little different from some of the other arboviruses like Dengue and West Nile is this evidence that the virus can also be transmitted sexually between two people. And so, Ian, would you tell us a little bit about how this second mode of transmission, in addition to the traditional or typical mosquito-borne transmission, how is this effecting the epidemiology of the disease?

Lipkin:

Well, I think as Jay as said, the major route of transmission is still the mosquito. But recently we've learned that there are a wide range of viral infections that can be transmitted via the sex route. A year ago we were concerned about Ebola, and what we've learned, for example, is some viruses have the capacity to lurk in seminal secretions for weeks, maybe even months. We don't really know yet the full extent of that period of time. But what it does mean is that it's not enough to tell a woman that you need to avoid going to an area where you may become infected, but if you have a partner who travels to this area, we need to make certain that individual is not carrying a virus home, so that you can become infected secondarily.

Now, there are tests that can be used to examine whether or not semen has this virus in it. You can do this by culture. You can use genetic tests, and I'm sure that these are things that we'll be hearing much more about. In addition, there's going to be a concern, of course, that it's going to be in the blood supply. And with West Nile virus, we didn't really worry about that for a couple of years. And then suddenly there were cases that were associated with blood transfusion, organ donation. And I would anticipate that this is something that people may become concerned about as well.

Perkins:

Yeah. So, Jay, would you follow up on that in a more specific sense? So, how does the sexual transmission complicate the city's ability to control Zika? And then maybe continue on from there and tell us about what's the potential for local infection from people who have traveled away, whether by other mosquitoes or by person-to-person transmission?

Varma:

Good, yeah. So, I just wanted to add on to what Ian just mentioned. I think one of the most important messages we're trying to get to New Yorkers is the importance of understanding your risk of getting infected. If you are a woman of reproductive age that is planning to travel to Mexico, Central America, the Caribbean, you need to be using a durable form of birth control and you need to be using condoms when you're there. The risk is real.

Transmission probably does not occur very often. Again, mosquitoes are the way you get epidemics of this, but we know that the consequences of infection can be very severe. So, we are advising any woman of reproductive age to be very careful about durable forms of birth control and the use of condoms. And even more important, if you are a woman that's pregnant, you really shouldn't be going south this time of the year. You really should be considering a vacation somewhere else until the epidemic is changed.

And so how it's directly impacting New York is, again, the transmission that occurs via the sexual route is probably not very common. Again, if the hundreds of cases that have been diagnosed in the United States that have been imported, only a handful have been through sexual transmission. The remainder—the vast majority are all through mosquitoes. But the concern is that the way you get this infection in a community is you have humans that have this virus in their blood, and then you have a group of mosquitoes that are affective at biting those humans and having that infection spread to their saliva, and then transmitting it.

So, for us the concern is about, one, making sure New Yorkers get all of these messages, which are complicated about all the different ways you could get infected, all the ways you can prevent yourself. And, secondarily, there is always the concern that this could increase the total number of people with this virus in their blood and, therefore, in the presence of the right mosquitoes you could get transmission here in New York or some other setting.

Perkins:

Great. And, Cathy, I was hoping you could follow up with some more specifics. So, Jay talked about these general travelers advice. But maybe more specifically how does one know they have it? You mentioned many people don't have symptoms. How do you get tested? What are the questions you need to ask? Any other advice that you might give for people traveling to these countries, and then specifically men and women who might be involved in making family choices in the near future?

Spong:

Right. So, for a woman who's pregnant or who's interested in becoming pregnant or a family unit who's interested in becoming pregnant or is pregnant, I think the first message is not to travel to some place where there is active Zika transmission. And if you are going to travel there, understanding what those risks are to take the precautions that you need in order to try to minimize your risk of getting Zika. So, this is a mosquito that bites during the day, so it's not one that you can say, okay, well, it's during the day. I'm not so worried about it. So, other things that you should do are to encourage people to be in air-conditioned places, to be in places where there are screens, to use repellants that are approved, to wear long sleeves and long pants to try to avoid that type of transmission.

Now, for someone who is perhaps not traveling, but they have a partner who is traveling to a place where there is active Zika transmission, again, because of the risk of sexual transmission there is a concern. And so as an example I had a patient in my clinic who she had come back from Brazil. She was pregnant. And this was right at the beginning. This was the day actually that the WHO declared it a public health emergency. So, it's February 1. It's the last patient of the day, and she comes in and she's there for an anatomy scan—just a regular scan—and handwritten on the front of the note was traveled to Brazil over the holidays. Is interested in what her risks are. And so they're very concerned. They've heard about this. The WHO just declared this an emergency. What are the risks to me, and then what should I do? How do I protect myself?

And our discussion went along the lines of probably to avoid going back to Brazil unless she really needed to. And she was comfortable with that and said, "I'm not planning on going back. I understand there's that risk." And then we talked a little bit more, and at that point there'd only been one case of sexual transmission. And I said your partner probably doesn't want to travel either, or if they do travel you will need to take precautions if you want to try to avoid that route of transmission. So, either abstinence or using condoms or some other methods, so as to avoid that risk of sexual transmission.

And I think these are things that we need to talk with our patients about. If someone has—if a male has had Zika virus they should—because of the risk of it staying in the semen for a prolonged period of time—in fact, there was a case report published where a man had active Zika and 41 days later transmitted it sexually to his partner. So, there is that concern. And the recommendation then is to wait six months before having unprotected intercourse to try to prevent sexual transmission in order to try to capture as much duration as we can. For women or men who travel some place where there is active transmission and they are not pregnant, but are thinking about becoming pregnant, the recommendation is for them to wait eight weeks after coming back before trying to become pregnant.

Perkins:

And what kinds of questions—like this woman that you mentioned and others, I mean, this is one of the more common things I've heard, is people have gone on a honeymoon to the Caribbean or maybe to Brazil, and then they find out they're pregnant and so they're worried about the length of time. How are we training doctors to monitor these things? And what should they be asking their doctor to test for or look for?

Spong:

Right. So, if someone has come back and they are pregnant and they were at a place where they had active Zika transmission, she should be tested for Zika virus. And there's a whole system out there for how that is done. If she tests back positive, she's going to need to be followed throughout her pregnancy to determine whether or not there are any sequela for the fetus. So, this will require serial ultrasounds and monitoring throughout the pregnancy.

Perkins:

But if she tests negative, can she relax?

Spong:

So, part of the difficulty—and I know we're going to talk a little bit about this diagnostics and the cross-reactivity is, as Ian mentioned, with Dengue. And so the difficulty is that if she has come from somewhere where she could have had Dengue as well, it's difficult to know for certain whether or not they had Zika or Dengue. If she's never had Dengue virus, then you can feel more comfortable that in fact she has not been infected with Zika.

Perkins:

Okay, thank you. So, Ian, in the last couple days there were some splash in the news about maybe we're on the hot trail of some vaccines. So, at least in a mouse system, in a monkey system, it looked like there were some promise in terms of offering protection against Zika virus. Can you tell us about these developments, your cautionary note about these developments and also talk about how even if we found a really good vaccine, how that has to translate in terms of controlling this outbreak?

Lipkin:

Well, there's several challenges with vaccines. So, this is clearly the least expensive approach that we have, and it's the only one that we can really implement for the millions of people who are going to be at risk for infection with this and other viruses. Now, what we try to do is we find some region of the virus that's capable of inducing what we call protective immunity because there are many different types of immunity. Some will result in what we call neutralizing antibodies that will bind to a virus or bind to a bacterium and prevent it from entering a cell or from causing disease or from releasing some sort of a toxin that has a deleterious effect.

One of the problems that we frequently have, however, is that some of these vaccines may not work as well as we planned, so we try to test them in animals first. And we want to make sure that they can protect those animals. Now, we have many drugs that work beautifully in mice that don't work so well in humans. So, we try to go to other models as well. The best, of course, are non-human primates and we want to demonstrate that they're protected. And what we want to do is to replicate all of the various circumstances that might pertain with a human infection. So, if you're talking about someone who's going from New York City who's at risk for going to some area in the world where there's yellow fever and they've never seen a yellow fever-related virus, you give them the yellow-fever vaccine and as long as it's safe and you get reasonable protection, you're happy.

If, on the other hand, you're talking about vaccinating people in a part of the world where there are related viruses, you have to be concerned that the cross-reactive immunity against one virus doesn't aggravate the disease that might occur if they see the second one. So, with Dengue virus, there are four different types in a majority sense of Dengue viruses. And you want to make certain that any vaccine you develop for Dengue virus protects against all four. Otherwise, you have to worry about the fact that the vaccine response, which is excellent for two of the types of Dengue virus might make subsequent infection with the other two worse.

The same thing pertains here with Zika. So, the first thing we try to do is we demonstrate efficacy in an animal model. Our preference is to have a second animal model that's closer to humans to prove that it's effective there. Then we test it for safety in humans, and then there's this last concern, which I haven't mentioned at all, which came up with the Lyme vaccine, which was quite unfortunate because, frankly, it was a great vaccine.

But we don't use it anymore because people were concerned that making an immune response to the Lyme vaccine was going to actually result in autoimmune disease. The evidence in favor of that is so weak that I wasn't worried about it, but the companies that manufacture the vaccine decided that the risk to them was too great to proceed with this as a trial. So, vaccines are tricky. Now, you mentioned diagnostics. We are going to get back to diagnostics, or not?

Perkins:

I would love if you would tell us a little bit about it. Yeah.

Lipkin:

Okay. So, Cathy was talking about the ways in which she counsels patients and the kinds of things you can do. We have two broad types of diagnostic tests. And Jay supervises a huge group that employs these tests in the city Department of Health. But they basically boil down to those that detect genetic footprints of the virus and those that detect antibodies to the virus.

Now, the first test that's going to be positive with an infection is going to be the one that's genetic because you're actually detecting the virus in the body, whether it's in the seminal fluid or it's in the blood or it's in the tissue or amniotic fluid. That's where you're finding the virus itself. The antibody response doesn't appear until about a week to two later, and it tends to come up, gets very high, and then it slowly begins to drop off. So, if a woman came into her clinic and said I'm concerned about it and I was there a month ago, would you do the genetic test? Probably not. You might do it anyway, but if it was negative it wouldn't provide any real reassurance.

It might be useful if you tested the seminal fluid on her partner, but there she needs to look for the antibody test. And one of the things that's been quite sobering was a report that came out of Columbia suggesting that the greatest risk they found was in women who actually didn't recall having an infection at all. So, if you don't have any sort of experience that's consistent with the Zika virus infection, it doesn't mean you're safe. You have to have the additional laboratory tests. And the laboratory tests are, frankly, not very good. The genetic test is great, and we can distinguish Zika and Dengue and everything else.

But the serology is tough because there is this problem of cross-reactivity and we can't be absolutely certain—even with the gold standard neutralization test, which everyone uses as the second line—that in fact we can be certain that it was Zika and not Dengue. Because there is this problem with cross-neutralization. Now, we are trying to, in fact, work with Jay and some of his colleagues in trying to find very small peptides, very short fragments of protein, that can distinguish between antibodies to Zika and antibodies to Dengue. So, stay tuned for that.

Perkins:

Great. And even if we found this vaccine against Zika, it's not on the shelves tomorrow, right? I mean, I think that's one thing people have to appreciate, that it takes time not only to go through the safety trials, but to roll it out, and then getting it out to the people that need it is a huge challenge. So, we're about to turn it over to your questions, but I want to ask one final one to Jay here. And that is to be very specific about New York City.

So, what is your department doing to continue to monitor this, the plans for responding to it? And I would love it if you would maybe put this into some kind of context with other health risks. So, influenza kills hundreds of thousands of people a year. Many people get malaria locally. How does Zika fit into this scheme of things in terms of what are day-to-day things we need to be worried about? So, maybe the L train, getting Zika. Put that into perspective.

Varma:

No, I know. I think this is—I think what we're really challenge with here is a lot of uncertainty. And I think that's what worries us. And, of course, even more important it worries all of the people who are potentially at risk or have already been exposed. When we think about risk in public health, we think about two things. We think about what is the likelihood of the event occurring, and then what are the consequences if that event occurs.

So, we in public health are often times concerned about events that occur very commonly. And even if the consequence of them isn't great every time, the fact that they occur so often is a real concern. So, the flu is a perfect example. A lot of people get the flu every year. Very few people who get the flu die from it, but because you have so many people infected it still adds up to thousands and thousands of deaths every year in the United States.

Now, Zika presents a unique challenge because for the average New Yorker who stays in New York and doesn't go anywhere else, the risk is incredibly low of you contracting Zika. Not just because of the work we're doing, but just simply because of the climate that we have here in New York. But we know that one of the things that's great about New York is you've got flights everywhere in the world. We get to interact with people from all over the world. So, the risk is not zero and it's not even close to zero. It's a lot higher than that of that event occurring.

And then you have the other issue, which is the consequences of the event. And I think what's always been most concerning to me about Zika and what's really truly worrisome about it is that it doesn't hurt the person who gets infected, but it hurts your ability to reproduce. And as a species, that is a dangerous thing. If you really wanted to cause harm in the world, you'd stop people from passing on their genetic material to the next generation.

So, we think that the risk for the average New Yorker is very low, but because the consequences are high and because of travel, it's something that we're doing a lot about. What are we working on? All of you have these yellow cards there. One of our biggest and most important things that we do is we educate the public. We want to get facts into your hands, so you can make informed decisions that are right for you and that are right for your families. So, you'll see these ads on the subway. You'll see information there. You can go to our website. We have lots of information, not just for all of you, but if you're a medical doctor and you need that information.

We're working very actively with the medical community. It's a huge challenge, as Cathy can say from the OB perspective. This isn't something an OB/GYN doctor is usually worried about. We usually work with ER doctors or infectious disease doctors. But they're having to come up with an entirely new workflow for how do you screen women, ask them the right questions, make sure they get tested. There's a lot of uncertainty with these diagnostic tests, so we're spending a lot of time working on this.

We have over 230 cases that have been diagnosed in New York City since January. Twenty-four pregnant women. In addition to those women who are confirmed, there are a number of women who have these indeterminate tests where they're not really truly infected, but we can't tell them for sure that you're out of the woods. And this presents a lot of challenges.

So, we're doing a lot of work with them. And then as it relates to mosquito control, the strategy that we've taken in general is that when we can do an intervention, even if the risk is low, if we can do an intervention that's safe to bring that risk even closer to zero as possible we're going to do it. So, even though we know that the Aedes mosquito that we have here in New York City is not very effective at transmitting it, we've adapted our mosquito control program. So, in the past to control West Nile virus we sprayed primarily at night time. We sampled mosquitoes when they're positive for West Nile. We do mosquito control in those neighborhoods.

We've taken that infrastructure and changed it a little bit. Now, because these mosquitoes are very aggressive at biting during the day, because they can breed in very small amounts of water, we're pushing a message out there—and this is a message that you can take home and act on, which is that if there is water anywhere that's standing and stagnant—and it can be as little as—we're not talking about having a backyard pool that isn't clean. We're talking about even small amounts of water. You can address that in your homes. Empty out flower pots. Don't have even soda cans that are sitting around that have water because those mosquitoes can lay their eggs in them. If you see standing bodies of water elsewhere, you can call 311.

We're advertising this a lot, and our calls are vastly exceeding what we've had in previous years. Collecting standing water, we put something into that standing water in large, marshy areas called larvicide, which kills off the eggs of those mosquitoes. And we're going to sample in a lot more areas to look for the density of these Aedes mosquitoes. We haven't needed to spray to kill off the adult mosquitoes; what's called adulticiding, but we're prepared to do that if these efforts at controlling standing water and killing off the eggs doesn't work.

Perkins:

Great. All right, I'm going to open up the floor. We've got some mics to go around, so if you'd like to ask one of our panelists a question, raise your hand and Kira or somebody will bring a mic around to you.

Question:

Hi. Thank you for that wonderful talk. I had a question from a public health standpoint, and I was wondering if any of you wanted to offer an opinion on the current situation with the Rio Olympics coming up very quickly because as you were discussing, transmissibility is a really, really important factor to consider in these kinds of epidemic situations.

And part of the reason why we're worried in New York is because we're so connected with the rest of the world. And I was particular interested to know if you guys think there will be a great impact on the spread of Zika that results from the amount of international traffic that's now headed to Brazil, which from my understanding has a very specific strain of Zika that is either more transmissible or more virulent somehow. So, I was hoping I could get your opinion on that.

Varma:

Yeah. I'll answer the question about New York, and if everybody else wants to weigh in on the global situation. From our perspective, again, what makes New York City great is our connectedness to the rest of the world. We have over five million arrivals every year from Zika-affected regions into the area airports. And so travel to and from the Olympics for us is really just a drop in the bucket, I think, compared to all of that.

So, from our perspective, specifically looking at travel to and from the Olympics, to New York, it's not a huge concern for us. We're already concerned about the fact that we have—the vast majority of the cases that have occurred in New York City are people who have traveled to the Dominican Republic. That's not because the Dominican Republic is more dangerous than anywhere else. It's because we have over a million travelers to and from the Dominican Republic every year; people visiting family, people going on holiday.

So, from our narrow perspective just looking at the city, it's not as big a concern. And I don't know if Cathy wants to talk about the global perspective and introduction into other places.

Spong:

Yeah, I agree with you. I think that's been the take-home message that the amount of travel that we get to and from the Olympics is going to also be offset by people not traveling because of the Olympics there. So, it's not going to really make a big difference.

Varma:

The other thing—and this is sort of a glass half empty way of looking at it—is that their climate is the reverse of where we are here. So, they're heading into winter, which is not the peak season. So, in fact there may be a reduction in mosquito burden. That said, I would not advise my daughter, were she pregnant, to go participate in the Olympics, but that's probably for two reasons.

Question:

Hi. So, let's say that a female does travel and does contract the Zika virus and her male partner does not have it, and then plus eight weeks later they want to have a child, is there any risk of it still being birth defects? Or are there proven cases where they're fine?

Spong:

So, the information that we have is for someone who contracts Zika while they are pregnant. And so that's why the recommendation is if someone has Zika virus to wait a period of time to allow the virus to go away and to allow enough time—so eight weeks to before they were to try to become pregnant. For a man, the recommendation is longer simply because it stays in the semen for a longer period of time. We don't have additional information to look at a subsequent pregnancy that there are complications. We don't have any information that there is a complication there.

Ian Lipkin

But to take that one step further, the question might also be whether or not there's evidence of female to male transmission, which would then set the stage for subsequent infection. And the answer to that one is I have absolutely no idea. I've not heard it reported, but we do know it the other direction.

Spong:

That's correct.

Question:

Hi. So, you've mentioned that Zika's been around for quite a while. I was wondering if you could comment on any research, if there is any research, on potentially finding a wildlife reservoir, if you could comment on that.

Ian Lipkin

Yeah. So, the question—and I should have addressed this in the introduction to Zika virus. I got too excited talking about viruses in general. It was first identified in a monkey. So, we know that monkeys are capable of sustaining Zika virus infection. And it would not surprise me if there were wildlife reservoirs. But right now the best reservoir seems to be humans.

Question:

I was just going to ask if people need to worry about their dogs [unintelligible 44:22]?

Varma:

Not that I—you're looking at me. I don't know. I don't think so. We don't know. I mean, the reality is like a lot of things we don't actually know. But as Ian mentioned and from what we know already, it's non-human primates and humans that are the primarily reservoirs, but stay tuned.

Question:

Hi, thank you. It seems it's very clear that women infected during the first trimester have a great risk. And you mentioned that waiting eight weeks might decrease the risk. How effective is the testing right now both for women and for men? So, say a woman is exposed, you wait the eight weeks, can you test the man at that point? Or how much can we trust those tests at this point?

Spong:

So, there was a lot so questions in your question. And so we'll start with some, and I'll let Ian take over for some of the testing as well. Related to the timing in pregnancy—and you brought up that in the first trimester there's associated risk—one of the biggest questions we have is what really is that risk. What is the degree of that risk, and how can we counsel women about it?

In fact, there was a study that looked at 88 women who had symptoms consistent with Zika in Brazil and what were their outcomes. And they followed subsequently with ultrasounds a little over half of these women. And what they found was in these symptomatic women, 29 percent had complications in the fetus. And these complications ranged from things like microcephaly to fetal loss or still birth.

Now, this is only in symptomatic women. And this included infections in the first trimester, the second trimester and the third trimester, which is very concerning. In fact, that to me was the most concerning part of the report. That even an infection in the third trimester had so many complications. As an obstetrician, typically we think about risk and think, well, if you haven't an infection in the first trimester or an insult of any type in the first trimester, that's when you're going to have the most harm. Because that first trimester is when all the organs are initially forming.

Then, again, in fact in the second and third trimester, those organs are continuing to form. I mean, in fact if you look at a developing brain across gestation, it's remarkable how much brain structure and formation is still occurring in the second and third trimesters. Since this virus is so neurotrophic—it really seems to go after neural tissue, it might suggest why we see even significant complications in the second and—with infections in the second and third trimester.

One of the problems I have is I don't have a lot of information about how to quantify that risk for patients. And I don't have any information about asymptomatic infection. In fact, I only have occasional case reports where a woman never knew she had Zika, but clearly the child has the sequela associated with Zika virus. So, it's likely that even without symptoms, many of these complications can still occur. So, for a woman—your second question asked about diagnostics. And Ian did a really nice job kind of walking through the different diagnostic tests.

If someone has the symptoms of Zika you can test using PCR testing—the genetic-type testing—and really know does the person have Zika or not. Those are really easy tests that are very strong for us to be able to tell someone whether or not they have the infection. If in fact you've passed that period—it's a couple of weeks out—you're going to be looking at that antibody response. And that's where the diagnostics aren't as strong. I think in the future—and Ian's working on this and others are working on this—we're going to have some really solid diagnostic tests for Zika virus. But right now we don't have those.

Varma:

Just for those of you who are New York City residents, if you are exposed or you have a family member that's exposed and you need to get tested, you go to your doctor. Your doctor has a number that they can call at the Health Department. It's wildly available. Just call our—you can even just call 311 and they'll connect you to us. What we do is we have the doctor—we have him call us. We make sure it's appropriate for you to get tested because you really were exposed. You'll provide two tubes of blood and one sample of urine. And that will go to our public health laboratory.

The first test that we'll do is this PCR test on both the blood sample and the urine sample to test to see if you have the genetic fragments of this. And then the second test that we'll do—if it's appropriate and for women who are pregnant it's done on all of them—is this test to look at antibodies. And I think really the big challenge we have is that this genetic test is great for people who have had symptoms and it's positive. Then we know for sure that you had it. It's making for sure that you didn't have it that still remains a problem.

Question:

Mine isn't related to pregnancy. Mine is a concern with the Columbia reports of Guillain-Barre syndrome. And Columbia had more of those reports than Brazil did. I live in Brooklyn, which has a fairly large Caribbean/West Indian population. Most have had Dengue as a child or when they visited home. And that seems to increase the complications of Zika. Or am I misreading the current literature?

Lipkin:

So, the question, first of all, is whether this particular disorder Guillain-Barre syndrome, which for those of you who don't know what this is, I'll describe it. It's essentially an immune attack on the insulating substance around peripheral nerves. And as a result of this attack on the insulating substance, you lose your ability to walk, to control your fingers. And, in some instances, if it progresses far enough you can actually lose your ability to breathe. And as the attack recedes and the immune response recedes, you get the restoration of the insulating material, and then hopefully you recover. But some people take months or even years to recover, and some people never recover fully.

Now, the evidence linking Zika to Guillain-Barre is less strong than the evidence linking it to the microcephaly that Cathy's been talking about. There are reports every few years of another virus or another bacterium that is linked to Guillain-Barre syndrome. But just accepting for a moment the argument that there is a relationship—and I'm not persuaded yet, though, it's highly plausible. The question then would be does the infection with Dengue increase the risk that if you get exposed to Zika you will have this additional complication of Guillain-Barre? And the answer is it's biologically plausible, but it hasn't been proven. Would not surprise me, though.

Question:

Hi. It was stated that it's harder to have a test showing that you don't have the disease. Is that because there's no way to definitively know how long it lays dormant? Is that correct?

Lipkin:

No. Let me just follow through the diagnostic testing paradigm because what Jay was describing for you was the way in which patients would screen through physicians. And there are ways to be absolutely, unequivocally certain. You do the genetic test first. First, you have to look for evidence that somebody could have bene infected. If you don't find the genetic fragments—I'm referring now to a woman, not to a man because we've already talked about differences in the compartments that might be positive.

And as he said, you've tested the blood and you've tested the urine, and that's negative. You then do an antibody test. And forgetting about the cross-reactivity issue, if it's stone-cold negative at that point you still need to do another test a few weeks later because you might have been in this eclipse window when the genetic test is negative and the antibody test hasn't yet come up.

But if you do the genetic test and it's negative, and you do the antibody test and it's negative, and four weeks later you have a negative antibody test, then you haven't been exposed. At least you haven't been infected. You might have been bitten by a mosquito with Zika, but the infection didn't take off. Now, all bets are off if you're someone who's immunosuppressed or in high doses of steroids for any reason or you have some sort of unusual medical condition, which prevents you from mounting an immune response. So, we're talking about the average healthy person.

Question:

Thank you. I'd like to get a comment on the lysogenic state. You mentioned something about the lytic state, but you didn't say anything about the lysogenic state. And also its mutation rate if you know anything about that. And the last one is you mentioned calcium deposits in the brain, and I was wondering if you could say something about the cognitive skills of these. And that's it.

Spong:

I'll let you start, and then I'll finish up.

Lipkin:

So, mutation rates—viruses come in many different flavors. And some viruses are made of DNA, which is a very stable molecule for the most part, particularly if there are two copies of it and they ride side-by-side. And as the virus makes more of itself, there's a proofreading. It checks—on this one says, no, we screwed up here and it backtracks. And then it makes the appropriate substitution.

RNA viruses, in contrast, are continually evolving and mutating. Now, we don't yet know, in contrast to some other viral infections that I won't talk about right now—but in contrast to some of the ones we already have identified, specific mutations that make them more dangerous. We don't have anything yet to suggest that has occurred with Zika.

But the concerns that Jay was raising about the fact that we have other strains of this Aedes mosquito that might not be the best vector for carrying this virus, it might evolve to become better adapted to that particular mosquito strain. In which case, it could be more effective. Or God help us it adapts to a Culex, which we have in abundance in New York City. So, the answer is we have to continually track these viruses. We have to figure out how they behave as we replicate them in culture systems and in animal models to figure out whether or not they are in fact becoming more dangerous.

Spong:

So, you asked a question about the calcifications in the brain and the cognitive outcome. And those are two different things actually, or they could be. Because the fetus, as it's affected, depending on the timing of that infection and what happens in pregnancy you can get calcifications in the brain where you have areas that you can see white spots on an ultrasound or on an MRI scan or a CT scan. And depending on where those are might affect different parts of the brain. So, if they're in one part of the brain that controls a motor function, you might have an abnormality there. If those spots are in a place where you have a vision function, it might impair the child's vision.

Now, that said, Zika has been shown to have many different malformations in the brain, including not only microcephaly where you can have a small brain, that brain can also be abnormal. There have been case reports showing where there have been absence of specific structures in the brain and where there have been very large ventricles in the brain.

Depending on which of these outcomes has occurred and the timing of when that occurred is going to impact what happens to this child. Now, we don't have good information to know what is the long-term impact, but it is clear from other infections and complications in pregnancy when you see some of these abnormalities that these children will have complications, whether it affects their motor or their IQ long term in life.

And one of the biggest concerns is to best understand how should we evaluate, monitor and manage these children for the long term? And we don't have good information on that. We will be having a workshop at the NIH in the end of September to really try to address the child to say given what we know—these brain malformations, these eye malformations, these growth abnormalities—how should we evaluate these children? How should we monitor then, and then how should we treat them?

And the way that we can do that is to take what we know from other infections and other complications that result in this same outcome and say how do we treat those, how are those similar or different to Zika, and then what recommendations could we come up with? What is the best evidence we have on how to evaluate these children and manage them? And then based on that, the professional societies and organizations can come up with a plan for how we care for these children. And I think that is one of the big impacts that we need to be able to address.

Question:

Hi, thank you. For women not trying to get pregnant—actively trying not to get pregnant, but with children who are girls, who are also not getting pregnant, is this a real concern? I feel like this is very specific population, which we are rightly concerned about, but for everybody else apart from the fact that if you have it in your blood you can then infect a mosquito, which can then infect another person, this feels not something to worry about. Is that accurate?

Varma:

Yeah. I mean, basically what we are focused on is women of reproductive age who are at risk of getting pregnant or trying to get pregnant. I mean, without question if you have to pick any group that we're focused on most, it's that group right there. So, you're absolutely correct. If you are an otherwise healthy adult or child that is traveling to those areas, you're not trying to get pregnant, you're not at risk of getting pregnant because of your age or your birth control status, the odds of having something bad happen are pretty low. This is a very—the vast majority of people get no symptoms at all.

That 20 percent of people that do get symptoms, the symptoms tend to be fairly mild. So, yes, it is very reassuring in that regard. I think what gives us pause and the reason we are here in New York City and at the national level and in the academic community and focused so much on it is this level of uncertainty about complications. But you're absolutely correct. From everything we know right now, everybody who gets this illness—if they're not a pregnant woman—the outcomes are very mild, except for these unusual neurological manifestations, which can occur with other infections as well.

Lipkin:

Except, again, if you're immunocompromised it's a very different story. So many of these virus infections or bacterial infections that are otherwise innocuous can become devastating.

Question:

It's related to the last question actually. So, for people that's not planning to get pregnant I heard that having Dengue increase your chance of getting Zika. Does it work the other way around? So, I'm not trying—I'm not planning on getting pregnant, but I do travel to Singapore quite regularly. So, meaning that if I get Zika, does it increase my chance of getting Dengue there?

Varma:

I don't think we know the answer. I think it's the [unintelligible 61:51] unfortunate thing.

Spong:

Right. I think the one piece that I would come back to is a question that we have about the risk in pregnancy that what is making it more severe in some women. And there is the thought that perhaps by having an exposure to another infection such as Dengue may potentiate the risk of Zika itself. We don't know that answer, but that is something that we need to study and we need to understand. So, we're doing this large study, and one of the things that we will be collecting and trying to look at is this either prior exposure or co-exposure with another infection and whether that has any effect on the risk of Zika in pregnancy.

Lipkin:

So, what we do know is that at least three scientific groups independently have looked at the impact of antibodies to Dengue on infectivity with Zika in tissue culture, if you know what I mean by that; cultured cells. And two of them have done this in animal models as well. And what's been shown consistently by these three groups is that there's some antibodies which will in fact increase the rate at which a virus can get into certain types of cells and increases the amount of virus that is produced by those cells.

Analysis using structural biology has shown that there are other regions within some of these viruses—and this is the most promising vaccine work that I've seen in terms of design [unintelligible 63:41] Pasteur—suggesting that there's a region where you can make antibodies that will neutralize not only all types of Dengue viruses that are known, but also Zika. So, as people begin to try to develop vaccines using these sorts of tools, you can make predictions about which designs are most likely to be effective.

Question:

Back in August of 2003 I had a stem cell transplant as a cure for leukemia, and my wife and I are planning to travel to the Dominican Republic. Should I be concerned? In August we're planning to travel to the DR.

Lipkin:

What's your immunological status now?

Varma:

We are not—we don't currently have a recommendation that's focused on people with immune-compromised conditions. And I think that's because we just simply don't know enough. Our focus has been primarily on, as we said, women of reproductive age.

Spong:

That would be really important for you to talk with your physician about what is your status and how much of a risk is it for you. I think it's difficult without having all that information to really be able to provide you guidance, but I think you're right on target to be asking those critical questions.

Varma:

Yeah. And the reality is the risk of these other—Dengue is a very serious and very severe illness. Chikungunya is, as well, too. So, it's not—

Spong:

It's not just Zika.

Varma:

It's not just Zika. There's a lot of mosquito-borne infections in this world.

Question:

Since you can remain unsymptomatic, but still have the virus, if a couple together travels to the Caribbean and comes back symptom free, but does want to get pregnant, I understood that you said a woman should wait eight weeks and the male longer. Did you say six months for the male?

Spong:

So, if both are asymptomatic—they had no symptoms at all—it's eight weeks. If a man is symptomatic or a man is known to have had Zika—a positive test for it—six months.

Question:

Okay. Minus the testing, though, they could still both be infected without having symptoms. So, will people be tested just because they traveled and want to get pregnant?

Varma:

We're not currently testing people who—we're advising them to follow this guidance. And the challenge with—as Ian mentioned, it is possible in certain laboratory settings to test, for example, the semen. And we get request like that. Well, I want to be tested to make sure that I'm clean. The danger with that and the challenge with that is you can't be sure that a negative test really means that they don't actually have it. It may be that shedding is intermittent. In other words, it doesn't occur all the time. And so that's one concern that you have on top of whether the test actually performs well.

The other challenge is even if you do detect it, what you may be detecting is just the remnants of this virus having been in your body, as opposed to a virus that truly has the ability to infect other people. And so in addition to the fact the test isn't widely available in any reproducible form, that's the other reason we don't reliably test people, say, their semen, for example.

Perkins:

And we're just going to take a few more questions.

Question:

Do we know enough about Zika to worry that it might evolve rapidly like influenza virus and produce new strains in a very short period of time?

Spong:

That's Ian.

Lipkin:

If I had a crystal ball like that I'd retire. We don't know.

Question:

Hi. Thank you for this. I'm reacting to the recommendation of not leaving the can of Diet Coke out because of the breeding possibilities in such small amounts of water. And I have a toddler, and the majority of the parks that he goes to are sprinkler water parks. And he's too young, at least according to the pediatrician, to start using DEET and other strong repellents. So, I was wondering what thoughts are with very young children who spend all of their time over the summer in sprinkler parks.

Varma:

I would say, first of all, the sprinkler park itself doesn't necessarily represent a standing water risk unless for some reason that water sits there outside for long periods after that because there's a pothole or something else like that. So, that exposure isn't that much of a concern. And then the second is that there are mosquito repellents that are quite safe at all ages. And so you can check both on our website, on the EPA website, for recommendations about which ones to use.

Perkins:

Last one in the front.

Question:

[Unintelligible 68:54].

Varma:

Correct. The mosquito that's causing these wide epidemics throughout the Caribbean and Latin America does not exist in New York City. We've tested over a million mosquitoes in New York City in the past 10 years. We've never once found this type of mosquito. It's in a cage.

Spong:

Except in the case in the back.

Varma:

Exactly. We keep it in a cage here in case we ever want to let it go.

Spong:

It's a little magnified.

Varma:

Exactly, yeah. It's like smallpox. It's only in one lab.

Question:

Back to the question about children's exposure risk, isn't it not a problem if your child gets Zika virus? I mean, your young child isn't going to have a baby, so it doesn't matter. Correct?

Varma:

I mean, again, as we're saying, for the vast majority of people, whether you're a child or whether you're an adult or somebody else, this is not a concern. It's the concern is really focused on, unfortunately, women of reproductive age. I mean, I think just to emphasize for people, we want to reassure people about the work that we do here in New York City, the ways we try to control it, about being realistic about what the actual risks are.

From a public health level and the reason people like me are spending a lot of time at all levels who's doing it is something like 40 percent of pregnancies in the United States are unintended. So, we have to operate under the assumption that any woman of reproductive age is potentially at risk of having a pregnancy. And because this infection is potentially very devastating, we have to plan for those circumstances.

Perkins

All right. I want to take just one last minute to thank our panelists Ian Lipkin, Catherine Spong and Jay Varma. Thank you so much for being here with us.

[Applause

[End of audio]