Update on the Novel Influenza A H1N1 Virus and New Findings Published

Glen Nowak: Thank you, and my apologies to all the reporters who tried to call in, and ran into a dead line, as I understand it.

We've been working with our phone services to fix that problem, and I think we have managed to get it solved, so, again, I apologize for that inconvenience in getting this call started today. Today's update, we're going to focus on two things. Dr. Anne Schuchat, director of CDC's national center for immunization and respiratory diseases is going to give an update on the novel H1N1 in the United States, and we are also joined today by Nancy Cox, Dr. Nancy Cox, that's C-O-X, who is director of CDC's influenza division, and she'll be talking about a paper that's been published today in "Science" that looks at the origins of this novel H1N1 swine influenza virus. So, I will turn it over first to Dr. Anne Schuchat for an update.

Anne Schuchat: Good afternoon, everyone. You know, this is -- we're heading into Memorial Day weekend now, and it's a time to reflect on sacrifice and service, and of course, observance of this holiday often also involves travel and other outdoor activities that involve crowds. I hope people will remember to be safe this weekend and to think about personal protection and personal responsibility in the context of the current outbreak of Novel H1N1 virus. This is no time for us to relax on the important reminders people have been taking to wash their hands, cover their coughs and to avoid traveling if they're sick or their children are sick. But we do hope people will be able to enjoy the weekend. The new virus continues to circulate in the U.S., and while it still is a very new virus, it appears to be behaving a lot like seasonal flu, except, of course, it's circulating so late in the spring. We also know that even the seasonal flu viruses cause much illness and harm each year in the U.S., and we are continuing to take this new virus very seriously. While we're seeing activity decline in some areas, we should expect to see more cases, more hospitalizations, and perhaps, more deaths over the weeks ahead and possibly into the summer. Today, the situation in the New York City area and a few other parts of the country have led to more school closings. We believe that there are 60 schools around the country that have dismissed students and that about 42,000 students are out of school because of this virus. Local authorities are dismissing students from school when school has been disrupted from excess absenteeism of students or staff and when it's just not feasible to keep the school open. Of course, some schools and universities are finishing up for the year, and so, I want to say happy graduation to my niece, Dora. Today's update, for those who are actually following the call, we have officially 6,552 probable and confirmed cases here in the U.S., but we remind you, these are just the tip of the iceberg. We're estimating more than 100,000 people probably have this virus now in the United States. The U.S. count for fatalities is at 9 and there are over 300 known hospitalizations. There are, as I mentioned, some outbreaks of influenza-like illness in schools that are leading to those dismissals, consistent with our guidance on this of having the local authorities decide about those matters. I want to say a few words about vaccine before I turn things over to Dr. Cox. Today's CDC received from one institution a candidate vaccine virus. This was created by combining the genes of the novel H1N1 virus that are responsible for eliciting protection to influenza with other parts from other viruses that are needed for high growth in eggs. That process is called reassortment. Also, CDC and FDA have created a candidate virus using reverse genetics. Here at CDC, we're performing analysis of the egg-derived and reverse genetics-derived candidate vaccine viruses to make sure that they are able to stimulate optimal immune responses or that their ability to do that remains intact. And after that work is done, suitable viruses will be sent out to manufacturers. We expect by the end of May that will happen so that they can begin work on developing candidate vaccine seed for production of pilot loss of vaccine. You may have heard that today Secretary Sebelius announced that she's directing about $1 billion for clinical studies of vaccine pilot laws and for commercial production of potential ingredients for a pre-pandemic influenza stockpile. So, these are pretty big developments, but I think today's big news is really a report in the journal "Science" that I think represents a big breakthrough from global scientific collaboration, and Nancy Cox, who's the director of our influenza division, is going to describe that briefly.

Nancy Cox: Thanks very much, Anne, and good afternoon, everyone. I'm very pleased to have this opportunity to discuss some of the key findings published today in the article in "Science." The publication is entitled "Antigenic and Genetic Characteristics of the Early Isolates of Swine Origin Development H1N1 Virus Circulating in Humans," a fairly complex title, and I'll try to explain the analyses that we did in a simple way. This publication really represents an excellent collaboration within public health partners in the United States, with our Mexican counterparts, and with our long-term collaborators at Cambridge University. This work could not have been done without rapid sharing of specimens and information about the emergence and spread of the 2009 H1N1 viruses, both with our Mexican colleagues and with our public health partners in the United States. And without this collaboration, our understanding of these H1N1 viruses, their epidemiology and other aspects of the disease and so on would not have been possible. When any new pathogen emerges in humans and begins to spread globally, it is critically important to try to understand the origin of the pathogen to potentially stop its re-emergence. We also need to determine the most important characteristics of the emerging pathogen and concentrate here at CDC specifically on those properties of the pathogen that have relevance for prevention and control efforts. To do this, we and our colleagues collected specimens from ill people, diagnosed the disease and then sequenced the genomes of more than 70 samples of the novel influenza H1N1 viruses that were first identified in April 2009 in the United States and Mexico. Our paper describes for the first time in detail the antigenic and genetic characteristics of these H1N1 viruses and explains the history and evolution of human and swine influenza viruses in North America and other areas of the world. From our analysis, we have confirmed that the novel H1N1 virus likely originated from pigs based on data that each of the genetic components of this virus are most closely related to corresponding influenza virus genes identified from swine influenza viruses. We found that the new H1N1 viruses are antigenically similar to each other, that is, they react to antibodies in a similar way. They're rather homogenous. However, they're antigenically very different from human influenza H1N1 viruses. As you know, this indicates that seasonal influenza H1 vaccines may not protect people from infection with this novel virus. This study reinforces the fact that swine are an important reservoir of influenza viruses with the potential to cause significant respiratory outbreaks or even a possible pandemic in humans, and the results of the study show the global need for more systemic surveillance of influenza viruses in pigs. So, I'll talk just little bit more now about, give you little bit more detailed remarks about the genetic and antigenic analysis of these viruses. So, we had full or partial genome sequences from more than 70 novel H1 viruses, including 17 viruses isolated in Mexico and 59 viruses from 12 states in the United States. As stated in previous press briefings, our analysis showed that the novel virus contains a combination of gene segments that previously had not been reported among swine or human influenza viruses in the United States or elsewhere. And the novel aspect was that two of the genes, a matrix protein gene, and the nerve gene segments appear to be derived from Eurasian swine viruses previously not detected outside Eurasia. Now, if we go back in time, we can actually determine where each of the genes of the H1N1 viruses originated. And I think that what I would like to do rather than to have very, very extensive comments, just to hit on some of the highlights. So, we have this unique gene combination within the 2009 H1N1 viruses, and while our analysis shows that all gene segments are derived from swine influenza viruses, at this time, we do not know if the virus entered the human population directly from swine or via an intermediate host, nor do we know for certain the exact host that the viruses might previously have circulated in to obtain its current properties. We do know that our veterinary colleagues at USDA and elsewhere in the world are now looking very carefully to see if they have in their freezers samples from pigs or other animals that might provide the missing links and information about intermediate viruses that could help narrow down the times and place of emergence of this novel influenza virus. Now, to really focus in on the public health aspects of our analysis, we wanted to look very carefully to see if these viruses were homogenous and if it might be easy to derive a vaccine candidate virus that would cover all of the novel H1 viruses that are circulating in different countries around the world. And so, we did what is called antigenic analysis, and what we found is that these viruses are very homogenous in their antigenic properties, that is, the way they interact with antibodies, as well as in their genetic properties that we can see from sequenced data. This makes our job of coming up with a reference candidate vaccine virus much, much easier. We see much less variation among these new H1N1 viruses than we do for typical, seasonal influenza viruses. In addition, we have been monitoring these viruses, these H1N1 viruses, very, very closely for their resistance patterns to the antiviral drugs that are licensed for use in many countries around the world. And I want to just reiterate that the novel viruses that have been tested up to this point are sensitive to the neuraminidase inhibitors, but resistant to the M2 blockers or rimantidine and amantadine. So, these findings from this paper, out lined in this paper and mentioned on earlier press briefings are really critically important for our global public health response. So, I think I'll close now with my comments and we will both be available for questions. Thank you.

Glen Nowak: Operator, this is Glen. We'll take the first question.

Operator: The first is from Steve Sternberg from "USA Today." Your line is open.

Steve Sternberg: Hi, thank you for this explanation. I wonder if -- you did a very good job of boiling this down, but I wonder if you could try and take it to one greater step of simplicity. Is the goal here primarily to figure out where the virus emerged or is that the primary goal? Is the primary goal to determine, you know, our capability to combat it with a vaccine?

Anne Schuchat: Our primary goal is really to respond to the emergence of this novel virus. And so, our primary responsibility is to respond. And so, our analysis attempts to do two things, two inform our public health response, that is by helping us understand how we can make a vaccine and make the most effective vaccine possible, to inform our recommendations on use of antivirals for treatment and prophylaxis, but it's very important also to understand the origin of these viruses, because if we can determine the origin, we also then can take measures to make sure that the virus doesn't re-emerge in a slightly different form, and so, our first goal is to prepare for response, but understanding the origin is a part of that response, but it's a secondary part.

You can also think about the new tools that we have at our disposal in the scientific community. With the type of genetic and antigenic characterization that the scientists did, they can look backwards in history and try to understand where these parts of the virus emerged from, and that can help us really try to prevent those types of reassortments or emergences in the future. And so, this is little bit like medical or sort of scientific detective work, understanding the sources of this virus through the genetic characterization but also looking forward, preventive, so that the more we understand how these new strains come into human populations, the easier it will be for us to counter them in the future.

Glen Nowak: Thank you. Operator, we'll take the next question.

Operator: The next is from Donald McNeil, "The New York Times." Your line is open.

Donald McNeil: Hi, thank you. This is in part a call for more surveillance of swine influenza. I know that the chicken industry stepped forward very quickly a couple of years ago when there was a need for more surveillance of Avian influenza. Does this mean that the pork industry needs to step forward and pig farmers around the world need to, or submit more samples, or what needs to be done now that this problem has emerged?

Anne Schuchat: Yeah, you know, I think that this really hits home how important it is for animal and human health to cooperate and collaborate. We're pleased with the improved collaboration of the two disciplines, but for many infectious diseases that have emerged over the past few decades, we see that what happens is that the animal-human interface is very important. And so, part of our strategies now involve joint investigations and shared information. And I think this does point to the need for that going forward.

Glen Nowak: Next question, operator?

Operator: Thank you. Again, if you'd like to ask a question, please press Star 1. The next is from David Brown, "Washington Post." Your line is open.

David Brown: Yes, thanks a lot. Dr. Cox, I just -- I'm trying to make sure that I understand the possible sequence of events. There was a triple reassortment that occurred, you know, a number of years ago, and this new emergent strain, my understanding, is a triple reassortment that took place on top of that might have occurred in one event but is more likely to have occurred in two events, and you're now looking for the intermediate, you know, the product of the first event, because we have the product of the second event, which is the new strain. Is that correct? And my sort of related question is, can you talk a little bit about the survey -- surveys that have been done in North America and maybe elsewhere of existing swine herds to see, do we have anything that looks like this that has been actually out in pigs any time recently? How thorough has that canvas been and where has it occurred?

Nancy Cox: Okay, David, those are very good questions, and I hope I can simplify my answer as much as possible to the first question. As you know, a triple reassortment virus that contained genes that had originated in -- of course, let me preface this remark by saying that all influenza viruses are present in the Avian reservoir. And so, the ultimate origin of all influenza viruses is from birds. And so, what had happened was in swine, there had been introduction of the 1918 virus, and that virus evolved and continued to circulate in pigs without interruption, as far as we can tell, between 1918 and the current time.In addition, human influenza viruses have been introduced into pigs because pigs are susceptible to human influenza viruses. In addition, another Avian influenza virus was introduced into pigs in North America. These viruses interacted in such a way as to reassort, essentially, swap genes, and thus, we had a triple reassortment virus that's been circulating fairly widely in pigs in the United States and occasionally causing human infections. So, we were very well aware of this triple reassortment, both because it caused infections in pigs and because it caused occasional sporadic infections in humans. This triple reassortant virus, which had originated in North America, was then later detected in pigs in Europe and Asia. And this triple reassortant virus that originated in North America co-circulated with Eurasian swine viruses. Now, those Eurasian swine viruses, as I mentioned, originated in birds, the ultimate source of all influenza viruses.But once they enter a new host, they evolve in a way that you can distinguish the genes from those from the original Avian source. So, the reassortant event that occurred was between this triple reassortant and the Eurasian swine influenza virus. Now, if you look very closely at the gene sequences that are present in the databases that exist, such as GenBank, you will see that reassortants between the North American viruses that have been very well described in the literature and the Eurasian swine lineage viruses have been detected in people and in pigs. However, the exact gene combination that we've seen for the viruses that are spreading in humans had not been detected previously either in North America or in Asia. So, we know that the reassortment had occurred and there were reassortants, but they didn't have exactly the same gene constellation. In the United States, surveillance in pigs for influenza viruses does occur when there is an outbreak that causes disease and it comes to the attention of veterinary authorities, but the surveillance is not very systemic. Sometimes farmers don't report that they have outbreaks in pigs. Often these outbreaks don't cause serious disease and so on. And while we have some surveillance in the United States, the surveillance in other parts of the world is much more limited than that that we have in the United States. And I think that's where we can see the greatest gaps in surveillance in pigs. I hope that's answered part of your question.

Glen Nowak: Operator, we'll take another question.

Operator: The next is from Maggie Fox, Reuters. Your line is now open.

Maggie Fox: Hi. I want to ask about the homogeneity of the antigens and what that says to you. I also want to ask what the intermediate host might be if it's not pigs. And thirdly, I want to ask if there's any elements that you saw genetically that were different from what we had seen before in the triple reassortant virus and the Eurasian swine virus that combined to make this one.

Glen Nowak: I will start by turning it over to Dr. Cox.

Nancy Cox: Okay, so, the homogeneity that we're seeing in these viruses, both with respect to the genetic characteristics and the antigenic characteristics indicate that this virus may have been introduced into humans in sort of a single event, or possibly an alternative hypothesis is that there were multiple events where this virus was introduced into humans, but the introductions were of very similar viruses infecting humans. So, it really looks like a very, almost a clonal introduction of this virus into humans, if you will. Once the virus begins to circulate in humans, then there's a bit more genetic diversity that occurs. Now, in terms of alternative hosts, we really don't have a hypothesis for an alternative host based on what we know today. And I must say that we don't know a lot about circulation of influenza viruses in other hosts. You know, we found out that H5N1 viruses could infect feline species, including tigers, leopards and cats, and we didn't know this before. So, for each different combination of genes in an influenza virus, you might have slightly different host species that can be infected. So, there's a lot that we don't know, but what we can say is that the closest gene for each of the eight segments were circulating in swine.

Glen Nowak: Next question, operator?

Operator: Karen Kaplan, "L.A. Times," your line is open.

Karen Kaplan: Hi. Before this paper, when I was talking to scientists, they all would say that this strain was the first time that they had seen the North American and Eurasian swine viruses mixed together, but you referenced this lineage from Thailand in 2005, and I want to make sure I'm understanding this correctly. So, we have previously seen cases of North American swine and Eurasian swine viruses getting together?

Nancy Cox: That's correct, but not in North America. And this particular gene constellation has never been described anywhere in the world. So, just to be very clear, if you look at the gene sequences in GenBank, you can see that reassortment had occurred in the past between the two different lineages and that viruses representing reassortment between these two lineages had been detected in Asia, but those viruses did not have this particular gene constellation.

Glen Nowak: Next question, please?

Operator: The next is from Jennifer Peifer, CNN. Your line is open.

Jennifer Peifer: Hi. Thanks for taking my call. Just clarification on a couple points. At one point, you said it's estimated we may have more than 100,000 cases in the United States. Can you -- I just want to make sure I got that number right, because I was --

Glen Nowak: Dr. Schuchat can answer that.

Anne Schuchat: We know that many people with influenza-like illness are not tested for a laboratory diagnosis, and in fact, don't think that everyone who has that condition right now needs to get a diagnostic test. We do some estimation around what we have confirmed in the laboratory and what we're seeing in terms of the monitoring of influenza-like illness, and we are currently estimating that, perhaps, 1 in 20 of the reported cases -- or that the reported cases may represent about 1 in 20 of the actual illness due to this. We think, perhaps, the hospitalization reporting is a little bit more complete than the total reports, but we know that most years, influenza circulates very widely, and it's the minority of cases that we actually count individually. So, what we're trying to convey is that the numbers are going up each day by a couple hundred, for instance, but that the actual infections out there are a lot more common. What's important, though, is to say that nationally, influenza-like illness seems to be falling. In a couple areas, it's continuing to rise or is still causing a lot of illness. And so, we do know that there are several states that have widespread disease, and there are a few parts of the country that are having outbreaks of influenza-like illness in schools and they're dismissing students because of the high level of absentee rates. So, while on the national level, the picture is looking better, there's some places where it's still very, very active, and we don't want people to think that they're out of the woods yet. We also need people to remember that this is a new virus, and it could keep circulating during the summer, even though usual seasonal influenza viruses become very rare in the summer. It's also a new virus that could come back in a worse way in the fall. So, those are important cautions about what's going on today and what may be coming in the next weeks or months.

Glen Nowak: Thank you. Operator, next question?

Operator: The next is from Richard Knox, National Public Radio. Your line is now open.

Richard Knox: Hi, thanks very much again. I wonder if the picture you're presenting in the "Science" paper, a lot of stability over a long time of the swine H1N1 compared to the higher immunability, you know, greater among human H1N1 during the time period, number one. And second, the stability so far you're seeing in the 2001 H1N1 circulating in humans, does that imply to you at all that this new virus is likely to be more stable, less variable in the future than the seasonal virus? And I have a second question, if I may.

Glen Nowak: Turn it over to Dr. Cox.

Nancy Cox: That's a very good question. What we've learned over time by looking at swine influenza viruses and human influenza viruses is that influenza viruses in swine just inherently mutate at a slower rate. We believe this may be because there's less antibody pressure because the animals simply don't live so long and have subsequent infections. We do expect that now that these viruses have been introduced into humans that they will evolve at about the same rate that other human influenza viruses, seasonal influenza viruses mutate. We'll be looking at that very carefully over the coming months and years.

Glen Nowak: You had a second question?

Richard Knox: Yes, please. How much concern do you currently have as the new H1N1 gets established throughout the world, and maybe especially in Asia and perhaps in places like Egypt, where H5N1 is still circulating that there could be another reassortment event between H1N1, the new H1N1 and H5N1, and how good do you think we'll be picking that up?

Nancy Cox: That's another very good question. Influenza viruses, because of their ability to reassort, do pose a particular challenge to us. And so, we're concerned first and foremost about reassortment between seasonal influenza viruses and the currently circulating seasonal influenza viruses and this new H1N1 virus. And we feel that this is a much more likely reassortment event to occur simply because there's so many more human infections with seasonal influenza viruses.Nevertheless, we are somewhat concerned about the possibility that the new H1N1 virus could reassort with H5N1 viruses if they co-infected humans. But the frequency of infection of humans by H5N1 virus is just very low. It's a relatively rare infection. And so, that's not where our biggest concern is for reassortment. Thank you.

Glen Nowak: Operator, time for two more questions. Take the next question.

Operator: The next is from Mike Stobbe, "Associated Press." Your line is open.

Mike Stobbe: Hi. Thanks for taking the call. Two questions. First, following up David Brown's question about surveillance in pigs. We've seen numbers for surveillance in humans, but could you give us some numbers for surveillance in pigs, a little more detail about how many pigs in the United States and the other countries have been tested? And then I have a second question.

Glen Nowak: I'll have Anne answer that first one.

Anne Schuchat: We don't actually have that kind of information, but the USDA would be a good source for you to follow up with.

Glen Nowak: Your next question?

Mike Stobbe: Okay. It appears that there's a little difference between what the W.H.O. is saying and what the CDC is saying in terms of whether the new swine flu virus is more infectious than the seasonal flu. Could you help clarify that? Is it or is it not more infectious than seasonal flu?

Anne Schuchat: Right now, we're learning all that we can about the behavior of this virus, and we are working with infectious disease modelers to estimate the transmissibility of the virus. We have studies going on with households and in some other settings, and we think some of the parameters of this virus look similar to seasonal influenza and some of them look a little bit different. So, I think it's one of those things where we're going to have to just hold our breath a while until we really have solid numbers. Some of the estimates so far are based on relatively small numbers, but we're trying to really update those models and get more solid estimates for people.

Glen Nowak: Next question, operator?

Operator: Next is from Denise Grady, "The New York Times." Your line is open.

Denise Grady: Thank you very much. When you talk about learning about the origins of these viruses and hoping to prevent their re-emergence, could you give us some idea what you mean when you talk about preventing a re-emergence? How could -- what would that entail? What would you have to do? What does that mean?

Anne Schuchat: You know, I think when you think about infections in animal populations, there are controls like good agricultural and good farming practices that can lead to recognition when there are ill animals, and of course, taking care of the animals in ways that reduce the chances that viruses will persist or swap around. There are also ways that people and animals can interface that are safer than others. You know, we can think back to the SARS situation and those wet markets where many different species were in close quarters together, and that was just a recipe for disaster in terms of emerging infections. So, we really think that there's a lot that can be done in the animal arena. In addition, there are animal vaccines that are often developed to try to control infectious diseases in the animal population and prevent their spread across the animal populations and then, perhaps, into humans.

Glen Nowak: Thank you all for your interest and attendance, and if you have additional questions, please contact CDC's Division of Media Relations. So, thank you and have a good weekend.