Influenza Viruses and Pandemics

Stanford University we're very glad this is not a World Series night if anyone cares so let me let me just ask one question is there anybody here in the room tonight who has a cough or a fever because we're violating one of the most important rules of infection control we're gathering together in this place so let's hope will sustain ourselves I hope you'll all be here next week now I must say that in December over the winter break when I put together the course program and all the titles as Cathy Gilliam will remember for for this program and the ones that will follow I did not at that point anticipate that we would be focusing tonight in part on h1n1 because that was December and the whole issue about h1n1 really didn't happen until March or April of this year and that really speaks to one of the dramatic changes that we're seeing which is the emergence of global infections in fact some years ago the Institute of Medicine of the National Academy of Sciences put forward a study that said that there could be a change in longevity in the United States and indeed worldwide for two reasons one obesity and all the consequences related thereto and the second the emergence of global infections and we are as you know at a time when organisms emerging in one part of the world and this is particularly true of flu which does it every year um can migrate to others and so this is a important saga when we think about epidemics we of course think about flu and we think about 1918 but there are many other epidemics that have taken place than I mentioned cholera to you last week and you can think about plague and so many other factors as well but tonight we're gonna focus on pandemics with a viral twist last week we focused on bacteria and our speaker tonight interestingly Lucie Thompkins is a world expert on bacterial infections in fact her research focuses on a GI organism that Julie thereö Theriault did not speak about last week which is an organism called HeLa bacter pylori which is a very fascinating organism because it is associated with cancer and this is one of the interplays between microorganisms and a risk for cancer but despite the fact that she is an expert in this area she's gonna put on another hat I'm tonight she actually wears his several here at Stanford in that she has been until recently the head of infectious diseases in the department of medicine she is an associate dean of academic affairs in the School of Medicine tonight shall not be talking about faculty challenges in behavior but she's also the director of hospital epidemiology and that puts her right at the epicenter of influenza and other hospital or community related infections and she was there from the very beginning of this event I remember communicating with her over the weekend when the first description of the h1n1 took place in Mexico just to check in and see what was going on and she was quite clear that they had been working all weekend on this problem dr. Thompkins is someone who's well poised to deal with these problems she's on both an MD and a PhD her MD comes from Dartmouth her PhD from Georgetown she's focus as I mentioned on bacterial pathogenesis I've had the privilege of knowing her way before I came to Stanford because she has been a national and international figure and Infectious Diseases for quite a long time and we had that privilege for one short period to serve together on the board of directors of the infectious disease Society of America a testament to her leadership as well so I'm really pleased tonight to welcome dr. Thompkins to take us through the journey of pandemic influenza in this century and the last and beyond well Phil there's one thing you don't have to worry about and that's the obesity problem flu could get us but well I'm not a virologist as Phil said but I've been fascinated by influenza for a long time and I actually want to find other jobs in the past was to serve on the National Advisory Committee on Immunization z-- for the Centers for Disease Control where I finally got immersed in what it takes to produce a vaccine and how we should recommend vaccines for our citizens and as an infectious diseases person one cannot ignore influenza and this is the perfect year to be talking about pandemics so here we go now I just have to give you a brief overview about a virus first of all viruses are parasites and they really require a host cell in order to multiply so they're somewhere in between a completely inert organic particle and another kind of life form they don't have any of their own cellular machinery but they do have a nucleic acid at their core and they all have a protein coat many viruses also have a membrane that surrounds them now the nucleic acid can be composed of either DNA molecules or RNA molecules and in order for viruses to do thing first of all they have to be able to enter cells and they do this very uniquely through some kind of attachment mechanism and then enter the host cell where they then co-opt the cellular machinery to make more copies of the nucleic acid as well as the protein code then to be successful all viruses have to somehow get out of the cell and then finally being transmitted to a susceptible host and so this is just a generic description of a virus I'm going quickly I realized that but I don't really want to focus on the nitty-gritty of viruses I really want to talk about influenza virus so this is just a very simplified overview of the lifecycle of influenza virus as you can see on the left the you see if I can get the pointer to show up here you can see that the virus has to attach and then it gets taken up and then the viral particles which in the case of flu virus are RNA genes then have to be copied and at the same time the proteins that are encoded by these genes have to be made and they use the host machinery to do that and then ultimately they have to be enclosed in another membrane in order to exit the cell now I have a video that I want to show you that I got off the internet just recently I think it's very helpful to sort of understand this lifecycle this about three and a half minutes a virus is a small infectious particle that hijacks the machinery and metabolism of our cells to grow and reproduce each viral particle or virion consists of nucleic acid either DNA or RNA in single or a double-stranded form enclosed by a capsid in most viruses the nucleo capsid is enclosed by an outer envelope influenza type A and envelope two single-stranded RNA virus has been widely studied and serves here to illustrate the lifecycle of one common virus scientists believe that influenza virus is spread from person to person through exposure to large respiratory droplets direct contact or airborne dispersal infection takes place mainly in the respiratory tract infection begins with attachment of virus proteins to a receptor on the surface of the host cell the virus is then taken in the cell by receptor mediated endocytosis as the virus enters the cell the virus is internalized in a membrane bound capture vesicle that carries the viral core the vesicle is transported on microtubules inside the cell by host proteins called kinesins during transport the membrane of the vesicle fuses with the membrane of the virus and the capsid undergoes on coding the viral core RNA and proteins are then released into the cytoplasm where they are guided by host proteins to the nucleus of the host cell at the nuclear membrane the viral core uses host protein channels to enter inside the nucleus cell machinery is utilized by the virus to replicate the viral genome and make messenger RNA M RNA some viral mRNA exits the nucleus to exploit cellular ribosomes to direct synthesis of viral proteins viral proteins go back to the nucleus to associate with viral RNA these nucleo proteins again leave the nucleus and use cellular processes to travel to the cell surface viral surface proteins are made and processed in the cytoplasm and also travel to the cell surface where they combine with encapsulated nucleo proteins to form progeny viruses which depart from the cell by budding the virion now goes on to infect other cells at present vaccines to stimulate the production of antibodies against the virus and stimulate host cellular responses to ingest the virus remain the best strategy for controlling certain viral diseases but they are of limited effectiveness against rapidly mutating viruses and are ineffective against viruses that cause the common cold and AIDS okay now there are two really important things to say about influenza virus that I hope will explain why we're having a pandemic the first one is that there are two very important proteins on the surface of this membrane of the influenza virus a one is called the hemagglutinin and this protein is essential for the attachment to a host cell receptor called sialic acid the other important protein is this neuraminidase which is actually an enzyme that actually is critical for releasing the viral particles from the host cell once it's but it out and this is another little schematic that I thought was helpful in and it's showing that as the RNA and the proteins near the surface of the host cell they actually make these hemagglutinin and neuraminidase proteins which are studded on the side of the host cell and then the whole thing buds off and into a viral particle but it's got to get released from this sciatic acid receptor that's still on the host cell and so that's what it uses the neuraminidase for it the neuraminidase enzyme actually cuts this bond here so that the particles are free now our drug Tamiflu oseltamivir and the other neuraminidase inhibitor drugs work by actually inhibiting the activity of the of the neuraminidase enzyme on the virus so there they keep the virus from spreading to other cells that's that's an important feature of Tamiflu sort of explains why it doesn't necessarily prevent infection but it does attenuate the infection now the wave of our influenza viruses are named by type such as type A as you see here or type B we're going to talk about a today because they are the most complex and they're also the causes of pandemics the second thing here is the city for which the initial isolate was made from which the initialized that was made the date that it was obtained and then the having trouble with the pointer but then the types of the hemagglutinin protein in this case it's an h1 and the type of neuraminidase it's an n1 that's the convention and as I said they're they're really three types of influenza viruses but C is really not much of a pathogen in humans and B doesn't undergo the changes that a does and B doesn't give rise to pandemics and so we're going to talk about a exclusively now it turns out that there are at least I believe somewhere between 11 and 15 different hemagglutinin proteins which all differ by a substantial amount when it comes down to the amino acid composition there are five neuraminidase proteins that are found in nature and in humans in the last hundred years we have really only experienced infection by three different H types and two different end types now the other critical feature about the influenza virus that this slide shows again is the fact that it's an RNA virus not a DNA virus and the problem with RNA viruses in general especially with influenza virus is that the copying machinery of this cell isn't very faithful at copying the RNA molecules and so mistakes are made and different nucleotide bases are inserted as mutants or mutations and the second feature that's very important to understand is that the genes of the influenza virus are separated so there are eight different strands of RNA that are inside each viral particle it's called a segmented genome on like the bacteria that Julie talked about last week which have essentially a single chromosome where all the genes are linked together well what does this mean well it explains I think the two phenomenon that we deal with with influenza first of all as you can see on this slide we're trying to talk about antigenic drift and and what that means is that because the virus the virus continues to evolve continuously in nature in its animal hosts and mistakes are made regularly in in all of these genes in the copying mechanisms but for instance if mistakes are made in the hemagglutinin gene where's my pointer darn nice my computer is so sensitive see if we can get this to work better okay then it's possible to change some components say the hemagglutinin gene such that it's slightly different not very different but they not different that if we look at the original hemagglutinin protein if one injected this this strain into into a human you would make antibodies that would be very specific and might block the attachment right here but I don't know why my computer is doing that and but on the other hand a slight change would essentially could essentially disrupt this binding and that's the reason why we have a new vaccine essentially every year because this process of antigenic drift takes place continuously and the strains that are circulating in the community like our seasonal flu strains that we had three types of this last year are continuously changing a little bit such that the vaccine won't be as protective as it was the year before and so we have to keep up with it that's why you need to get an annual flu shot one of the only reasons now it also turns out that if the give up on this thing thank you welcome if the if a cell happens to be infected with a virus from a human and a completely different influenza virus from a duck let's say and they're in the same cell the fact that this these are all independent genes they're segments they're independent of one another and if they're all mixed up in the same cell it's possible to have a reassortment and for this basically human virus to pick up say a completely new gene from the duck and let's say it's the hemagglutinin gene well if it's a duck hemagglutinin and none of the antibodies that would work before against the binding of the hemagglutinin will work now because this protein is entirely new and this is the substrate for a pendant the evolution of a pandemic strain and this is essentially what has happened in 2009 and I'll get back to that much later so antigenic drift is really a process of minor mutations in the RNA that code for either the hemagglutinin or the neuraminidase and these two proteins are really critical because they are what we use to vaccinate people with these are the major outer proteins that cause an immune response and are protective you had a question the question was what's the difference between h1n1 and the seasonal flu viruses could I get back to that because I I really do hope to explain that that that is the crux of what I'm gonna try to say I think thank you for asking though and then antigenic shift is when we see a whole scale new virus evolved that has either a new hemagglutinin protein of a different type or a new narrow amenities or both and over the last 100 years we've actually now had four new hemagglutinin and three new neuraminidase antigens that we have seen and I must add even if it's called H one not all H ones are the same actually there there are variations between the different H ones as well they're not as substantial beats as between an h1 and h2 protein but they are significant enough that for instance the h1 of the seasonal flu virus which we did have circulating for the last 40 years is really very different from the new H one that has evolved in California and Mexico so the other important thing to talk about is the natural reservoir for influenza viruses and in fact all of those different combinations of Ages and ends actually occur in migratory waterbirds so they are the natural reservoir for influenza viruses in nature and but they can infect domestic fowl especially ducks with their viruses now you'll also notice here that and those ducks can infect domestic poultry and that is essentially what happened in Asia actually starting in the 90s but now in 2005 and so forth with h5n1 that presumably the h5n1 evolved from water birds into domestic ducks and then into chickens and other poultry that are in Southeast Asia predominantly but you'll also notice that pigs and humans can share influenza viruses very readily they're very similar as far as the virus is concerned so that a human virus can infect pigs and vice versa and also the pig serves as a nice missing vessel for poultry viruses that are in the poultry any questions no we're going to keep going yes one questions right the hemagglutinin is used to bind itself well the the antibodies are things that we make to protect ourselves from being invaded but the question is if the if the hemagglutinin still has has been changed and our antibodies don't react to it why does it still actually work perfectly well to get the virus into the cell and that has to do with the nature of the receptor and so the receptor is more forgiving if you will and so the hemagglutinin isn't that changed and it also depends on where the receptors are and I think that gets into a more complex question that we shouldn't talk about right now but your honor the physical chemistry actually a receptor binding and I can't discuss it now symptoms of influenza how many of you have had flu in the course of your lives just to bet everybody so how is it different from the common cold well usually there's a high fever that's associated with influenza usually there are muscle aches and certainly cough is a predominant feature whereas the common cold you know is more upper respiratory tract and if you've had flu you remember your joints ache and the current strain is actually causing a significant amount of GI upset both diarrhea and vomiting not only in kids but in a significant proportion of adults but these are the symptoms and the transmission is shown in the video one major the transmission is through these droplets that are expelled when people sneeze or cough and so if there's anybody with a coffee here I hope you will leave if you're in the infectious period and then we inhale these droplets and they'll and predominantly in the back of the nose called the nasal pharynx and the throat the other mode of transmission is essentially these droplets land on environmental services but they also land on your hands if you happen to have the virus and therefore washing hands is a very helpful thing to prevent inoculation so basically the mucous membranes of our respiratory tract are not-- our mouths our noses and our eyes are all susceptible to entry of the virus into the system so hand washing hand gel are very important so let me talk about pandemics for a minute because this word is used very loosely and I think it's confusing or it has been confusing to a lot of people and there is no perfect definition but as an infectious diseases person and epidemiologist mainly what we mean by a pandemic and especially as it regards regards influenza is that it's a widespread epidemic that basically goes to multiple regions in the world and the World Health Organization had this very complex system of calling it a pandemic when it got to so many regions in the world but the fact is influenza is global and and if it's a widespread epidemic of a brand new strain that becomes global which it will that's a pandemic the other critical feature of influenza pandemics is that it means the majority of the population doesn't have any immunity so for our seasonal flu vaccine over the course of years the a greater and greater number of people develop some immunity to the seasonal flu virus but then if a brand-new virus enters the population of the world and 95 percent of the people in the world don't have any immunity then it leads to a pandemic and usually these move very quickly almost explosively and in the case of influenza we're talking about the ability to go from human to human so the bird is really not part of this cycle at all after it gets started now just film wanted me just to differentiate you know we've also caused talked about cholera pandemics and this is another organism that can eventually move around the world or to many parts of the world and let the plague essentially was pandemic in Europe in the 14th century and and and other times in history but influenza is a human to human transmission these others either require an environmental reservoir like the cholera organism or they're spread by inset vectors like the flea in the case of plague flu basically doesn't have any social stigma attached to it at least not seasonal flu or pandemic flu but we can point to several examples where having tuberculosis in the late 20th century certainly was stigmatizing in the early part of the 20th century and certainly HIV was very stigmatizing so these are other pandemic organisms if you will but the consequences are different in our society the first actually well-documented influenza pandemic occurred in 1580 of course we didn't have any we don't have any virus from that period of time but the symptoms and the historians have I think clearly shown that this is probably a very ancient disease and our last pandemic until this year was 1968 now I just want to get back to this point about the immunity in the role of immunity in the pandemic if we look at the left part of the slide which is the disease incidents and the yellow curve let's say it's 2009 we're gonna have an explosive outbreak of flu which we are to which none of the population is essentially immune that's the blue line but over the course of years to answer your question what we expect is that this will play out exactly the same way as our other pandemics have which is there will have epic s-- but as time goes by the amount of antibody if you will or immunity that's in the population will continue to grow as a result of more and more exposure and these epidemics will be smaller and smaller and smaller and at some point in time which is very hard to predict although at one time it was thought to be fairly predictable I don't think it is this is a perfect opportunity for a brand new virus to be very successful because of brand-new virus there won't be any immunity in the population and so it'll be to the advantage of a virus like that to emerge when most the population is is actually has antibodies to the preceding virus and then they then the whole thing starts all over again so it does depend on the level of immunity and this if you will the fitness of the virus as it as it continues throughout the ages and I think it would be impossible to say okay we're going to have another pandemic in 20 years or 40 years we don't know yeah doctor Pisa wanted me to comment about the effect of different ages of the population as as I will talk about a little bit later for instance we know right now that in this brand new strain the h1n1 the swine h1n1 that's circulating now people who are over the age of 60 appear to be relatively immune and that's probably because they have seen a similar virus 60 years ago or more that the rest of population hasn't seen and it does illustrate this point thank you for bringing that out so in the twentieth century we have had three pandemics and I'm going to concentrate on the 1918 pandemic because I think there are lessons to be learned for the contemporary pandemic and then I'm going to talk about 1976 when we didn't have a pandemic but we thought we were going to but just take a quick look at the mortality rates and I think you can see why the 1918 has been fascinating just from the fact that it's estimated between 50 and 100 million people in the world died of influenza in those year in that year and the population of the globe was 1.6 billion people as compared to 6 billion people now so you could multi the multiplication and in the United States at least 550,000 people died from influence of that year the subsequent next two strains and this is the one that's been predominantly circulating for the last 40 years were much milder so they didn't have the same degree of virulence I also want to point out right now is that we had no idea what caused the influenza pandemic of 1918 we didn't have the ability to culture the virus at that time and there were a lot of questions about whether this was a bacterial infection or it could be a filterable age as it was called at the time so on to 1918 first of all in 1918 is when the yes you have a question so how did if we couldn't culture it how did we know and I'll tell you how we know in a minute it's a great question yes and another yeah let me ask your second question was how did the drug companies know what vaccine to make and the drug company first of all although you may have a few mutant viruses that came out of you when you sneeze let's say just in the course of having had flu most of those might have other mistakes made that make them not able to cause any infections so and because there's a balance between your immune system and the virus and so forth and I'm talking at a global level not at an individual person level the virus tends to remain relatively the same it'll have the same hemagglutinin types in the same neuraminidase types over a prolonged period of time until there's some one of these episodes that occurs with this big shift and but to get to the point about how we make the vaccine I was going to talk about that a little bit later but I can say right now that what happens is that the World Health Organization has a meeting every year usually in February where in the meantime there have been many many Sentinel laboratories all around the world including the Centers for Disease Control here in Atlanta Georgia that contribute their strains to this huge strain collection and they continually keep track of what viruses are what influenza viruses are circulating around the world and from that collection the World Health Organization and this group of people who meet there make a decision about what the new VEX the seasonal flu vaccine will contain it always contains one influenza B virus which really they don't really change that much so beads that stays B it doesn't have all these different hemagglutinin and so forth and usually two types of influenza A and they'll be named by the city from whence they were derived and that is what all the vac vaccine manufacturers will get those strains from the w-h-o and they will all make the same seasonal vaccine essentially every once in a while a new virus or a new variant usually a new variant might evolve and that actually happened just about 2006 I believe we kind of missed the boat on a strain that came up after this decision was made and if you've been looking at all the news reports about how we're making the vaccine it takes months and months to make it because it's made in eggs it's a very old technology so once the commitment is made to make the vaccine there's really no going back and so it may be may may occur that a variant occurs that the vaccine is not going to be as protective against as you would like and so people might still get the flu or an attenuated case of the flu because the vaccine doesn't quite cover the latest variant that's arrived yes and the question is are different parts of the world having different strains yes and no there is a predictable travel of influenza viruses around the world generally they start first in China and move to the northern hemisphere through Europe and then to North America South America and you know as the world turns if you will so generally this covers the entire globe what's happening in China eventually will happen in California and it's very seasonal as well and I'd like to talk about that a little bit later Thanks so back to 1918 well 1918 some of you might know none of you will remember 1918 honey you and I will remember 1918 but my mother got the flu in 1918 was the year that the u.s. entered World War one the Great War and Woodrow Wilson who was the president was bound and determined for the u.s. to help win the war at all costs and I just wanted to read you one quote from Wilson he was actually talking about the Liberty loan campaign the Liberty loan campaign was a way to raise some funds to support the American involvement in World War one and basically if you were patriotic you needed to buy bonds which were used to support the war effort and there were many acts past that were I seem to be highly unethical and illegal these days but one was the decision act if you were not patriotic enough or you spoke out against the US joining the the effort you could be put in jail in fact you could go to jail for years for just speaking your mind the Sedition Act was resurrected essentially it is essentially the same as the what Lincoln had to do with rescinding habeas corpus so lots and there was a commission that was designed to keep track of who was patriotic and who wasn't and so forth and including the patriotism your evidence of patriotism was to sell these bonds and so he said is to open a Liberty loan drive Wilson demanded force forced to the utmost force without stinner limit the righteous and triumphant force which will make right the law of the world and cast every selfish Dominion down in the dust does this guy sound like a preacher or what so he was he had an incredibly religious zeal about this and in order for the for the for the u.s. to help win the war we had to mobilize he intended to mobilize hundreds of thousands of recruits to the Armed Forces and to and and therefore to do this they hundreds of cantonments were built to house thousands of men either on their way over to the front or on their way home from the front and these were built very hastily and extremely crowded there were thousands sometimes ten thousand men in a single cantonment all these were basically bases that were outside major cities and for the most part and they were the perfect breeding ground for a human human transmitted virus like influenza this is an example of the sleeping quarters in the San Francisco Naval Training station and you can see the only thing they did here to try to prevent spread of a infectious virus was they put them head to toe but if you can imagine a thousand people sleeping in the same room that that's what was going on and he was given advice by Gorgas who was then the Surgeon General of the United States and by dr. Welsh and other experts that you know this was these facilities were inadequate in improper and we're we're you know a catastrophe waiting to happen but it didn't matter because we're going to win the war at all costs this is an example of the Liberty loan parade that took place in Philadelphia right at the height of influenza in 1918 and you can see all the thousands of people who were gathered here to participate in the parade there is that here's a cop who's wearing a mask a lot of good that did but you can see he's got his his stop sign also has by Liberty Bonds so policemen were expected to do their patriotic bit as well so flu erupted actually began in the spring it went to Europe probably from the United States that's the best guess it affected the troops in Europe massively the Germans and the French for instance fighting on the Western Front and it probably finally put the kibosh on the German offensive to try to win the war in June of 1918 in that so many troops were ill with flu that they simply couldn't do it this is an example of one of these containments that's now been made into a hospital for the thousands of recruits who were ill with influenza and it's pretty amazing if you think about what it would take to take care of these people when we had really nothing specific I believe these are ill patients but there were attempts to try to stop the spread of influenza or whatever was the cause by masks mostly they were gauze masks which we know wouldn't really prevent droplets from being inhaled and and in some places they they used curtains now Philadelphia was the heart basically I think the hardest hit city in the United States essentially flu came back with a vengeance from Europe through the troops probably moving back and debarking at the port of Boston Boston was very hard hit but shortly thereafter with the troop movements the the cantonments outside of Philadelphia became infected and then the population of Philadelphia became affected they had so many deaths in such a short period of time in Philadelphia that they had sure they had a shortage of coffins they had a shortage of Undertaker's and they essentially had to go to burying people in mass graves eventually they had to use back hoes to dig the graves because they didn't have enough people to dig them and the morgue in Philadelphia is shown at the bottom here that bodies were just stacked up like cordwood in fact in Philadelphia there were bodies outside the morgue on the street and in other parts of Philadelphia as well as other cities there were people who were found dead in their homes I met a who'd been dead for days and I I met someone on a plane recently who told me he was an orphan hit both his parents died in the 1918 pandemic when he was about 2 he was adopted by his aunt he didn't know he was adopted turns out he grew up in the same city where his brothers and sisters lived and he only found out last year that he had brothers and sisters this is not a rare story we ran out of hospital beds we didn't have narrowly enough hospital beds to take care of the civilian population so this is that this is a hospital outside of Lawrence mass which we use tents to take care of the civilians we also did a tremendous shortage of physicians as well as nurses but predominantly physicians because they were all called up to take care of the soldiers and the Red Cross provided the nurses as many as there as they could find and they were really much more important than the physicians since there were really no specific remedies and the nursing care was really the most important thing for resolution in Philadelphia they asked the medical students from the medical colleges there to essentially start taking care of patients as nurses and so this is just a group of medical students all wearing masks or waiting to be assigned to their duties as I said you know they didn't really know what the cause was but spittoons were rampant in society then spitting was very common and so would they attempt they thought that spitting would probably not be a good thing and so there were signs everywhere and they took spittoons away I think that was the beginning of the end of spittoons except in Congress where they still had them in the 40s and there was some thought that clean fresh air would be helpful probably not a bad idea but probably didn't really work and even the street sweepers wore masks now this is this is the kind of data that we now see every year that's produced by the CDC and it looks at the pneumonia and the influenza mortalities across the United States for every week of the year and for purposes of epidemiologic statistics it's defined that there's a seasonal predictability to when we have flu and that there's a baseline expected number of cases of flu depending on which week of the year it is this is the winter month and the jagged line are the actual cases and so when the jagged line goes above what's predicted it's considered to be an epidemic of flu that's just the definition of an epidemic so you can see here's the epidemic period and it's 8% of all deaths or new to pneumonia and influenza this is what it looked like for 1918 there are actually two curves here I know you can't see this but this talk ERV are all deaths that occurred over this very short period of time I think this is a matter of days and this peak our deaths just due to influenza so this is a massive explosive epidemic with a massive number of deaths over a very short period of time two pictures tell it all these are the death records for the United States in 1918 and 1919 and they're about five times as thick up to five to ten times as thick is the average death record for a year would be there was something else very strange besides the fact that so many people died many more than what would normally occur in a usual year of influenza ten times at least ten times as many people in the United States the death rate may have been overall ten times as great as it wouldn't ordinarily be but there was something funny also about the age range of the people who died and these are data from 1911 and 1917 in this line and this is the typical this is what we see virtually every year of who dies with influenza it's very young people and very elderly people or somewhat elderly people I'm not using the word elderly anymore when you forget it when you hit a certain age but look at what happened in 1918 again the young people it's a much higher rate but but then there's this big peak right here between essentially 20 and 40 or 15 and 45 in fact in the United States 50 percent of the people who died were in this age range what would you expect would happen to our actuarial statistics well this is what happened in one year we lost 15 years of life expectancy because the most productive members of society died and this is really what happened in Africa with HIV the difference is that we recovered obviously because this wasn't a continuing epidemic but now it looks like this in Africa now as I said there were a lot of theories and in fact the leading theory was that influenza in 1918 was caused by a bacterial bug called Pfeiffer's bacillus then now which we call Hamas influenza and in truth a substantial number of the people who died of influenza actually died of the bacterial super infections that occurred primarily pneumonia following the onset of influenza but in 1930 Robert Shope isolated the influenza virus from swine for the first time and showed that indeed was a and these were swine that had been in contact with humans and and he showed for the first time that influenza was a viral infection and and presumably the 1918 epidemic obviously was due to an influenza virus of some sort and in 1934 the influenza virus was initially isolated from human beings but we had no viral preparations from anyone who died in 1918 people were long dead no material was saved in a way that you could recover virus that would be active I'd like to say live virus but you know what I mean by live right oh and so this epidemic was essentially forgotten in for all intents and purposes although it had severe impact over a short period of time on the global economy and on the US economy and had social consequences it it really didn't it just disappeared from view yeah any questions okay how am i doing alright so the question is if a woman is infected during her pregnancy or even before the pregnancy well yes she will have some of the mothers antibodies but they won't last very long they might last about three months but then they'll disappear from the circulation because the baby himself longer six months okay you like six months he's a pediatrician he knows more than I do but but yes there is a passage of maternal antibody to the fetus which then as the baby matures it you know dissipates essentially so well so 1918 was forgotten and now we get to 1976 I hope you'll figure out why I'm jumping to 1976 but this is the pandemic that never was and there's a lesson here that really resonates back to 1918 what happened is in February of 76 there were five cases of influenza that occurred at Fort Dix which is a recruitment center for initial training of army recruits and one of these five cases died and as it turns out after more investigation was done about a total of 11 men who were at this army base where they basically aren't allowed to go anywhere during this training period became ill and it turned out that all 11 of these had a severe case of flu one person out of eleven died which is a maybe it's not statistically significant but it it was alarming and as it turned out after they did the studies of the antibodies that were in the bloodstream of 500 more of these army recruits who didn't have any symptoms they found out that you know this strain which is a brand new strain and it came from a swine it was a swine virus an h1n1 virus they had antibodies which suggested this thing actually had spread somewhat throughout Fort Dix now this wasn't known immediately but pretty quickly there was a very rapid investigation by the people at Fort Dix and by several other government agencies including the CDC and as it turns out which no one else knew at the time that virus was never isolated again after March of 1976 on the other hand right after these first few cases were observed David Sencer who was then the director of the CDC met with his advisory group the ACIP which I was a member of were you Phil no okay and and many other experts in flu to talk about could this be the next pandemic that would have occurred after 1918 or ya know after 1968 sorry could this be the next pandemic and sensor made a decision based on talking with a lot of different people and on basically his own gut feeling about this he recommended the president United States who was Gerald Ford that there was a possibility that this strain of swine flu might become the next pandemic bear in mind we didn't know we thought actually 1918 was a swine virus and it was called the swine flu in some places but we didn't really know what it was because it was dead and other people thought you know maybe this could be as catastrophic as the virus was in 1918 it was a possibly a swine virus in 1918 10 times as many people died and therefore his recommendation to Ford was we need to have a national vaccine campaign to try to protect the American public and so President Ford elected to try to vaccinate 95% of the population that was the goal initial target well it's a long story but and it was very difficult to get vaccine manufacturers to want to make vaccine when they weren't sure it would be worthwhile it wouldn't pay well there could be enormous liability if there were adverse events etc Congress eventually authorized essentially a tort reform bill that would indemnify the vaccine manufacturers but they didn't really get any vaccine made until November and then the vaccine campaign started and as it turns out some states did very well in vaccinating a large proportion of the population other states barely made a dent does this begin sound familiar and but in order to to kind of get people to take the vaccine you know Ford had himself vaccinated on television I thought this was dr. Salk but it turns out it wasn't it was someone else who gave him his shot on television and and actually the reason he did this is because a couple of days before three people who had gone to one clinic to get their shot dropped dead shortly thereafter and the news reports picked this up and made a big hullabaloo about well maybe it was really the vaccine and even one reporter noted that the vaccine wasn't safe so in order to convince people that the vaccine was safe Ford had himself accented to show people he wasn't afraid of it would be perfectly safe so a total of 40 million Americans were vaccinated against this virus and as it turns out about one in a hundred thousand plus people develop this syndrome which had not been seen very much prior to that called the Gambhir a syndrome which is a kind of a sending paralysis and of those about one out of a million people died so basically because the fits and starts and because now they're nearly not been an isolate of this same strain in many months nine months and because of the fear about the vaccine and the gamba ray which turned out to be associated with the vaccine the whole campaign stopped in 76 the end result is it contributed probably to President Ford's losing the election which occurred in November David Sencer was fired by the new Secretary of HW Josif Califano and two years later doctors professor Neustadt and dr. Feinberg actually were asked to write a report for Califano about the the swine flu affair and in reading their report which was written in 78 they're just so many warnings for what would happen the next time we tried to vaccinate the whole US population we have learned quite a bit since then but some of the same problems still come up and I don't I think their conclusion was that Ford really didn't have any choice and he wanted to err on what he felt was the save side but the issue about gamba Rey and the influenza vaccine has dogged people for all these years since 76 and has contributed significantly to some of the people who are very afraid of the vaccine it doesn't account for the people who think the vaccines cause autism they have other reasons having their beliefs but it has contributed to some of the unease about taking a new a new vaccine and I would like to end up with some comments about that so let's go back to 1918 so why should we worry about what happened in 1918 anyway well first of all there's something very funny about that virus and if we knew more about why that was such a virulent virus we it would tell us a great deal of what to look for in the future and perhaps ways to prevent something like that from occurring again so we didn't understand any of the virulence determinants and indeed another strain like the 1918 strain could certainly evolve it happened once it could certainly happen again and as I said you know if we knew more about the 1918 strain in particular we might even have some novel therapeutic targets and some other ways to prevent infection in the first place in terms of our immunization programs so how we gonna resurrect a dead virus well jeffery taubenberger as a young pathologist who was at the Armed Forces Institute of Pathology and now-defunct organization thanks to our wise Congress which is was a repository of a massive amount of pathological D material from the Armed Forces and and going back decades including boxes and boxes and boxes of formalin-fixed tissue material taken from soldiers who died in the 1918 influenza pandemic now we bring we carry forward to the the modern era of sequencing and DNA technology and PCR amplification and Gavin burger this started in the mid 90s to see if he couldn't extract some pieces of the influenza virus RNA from fixed tissue materials and use PCR amplification to then get the sequence of the virus and essentially figure out what virus it was put all those pieces together and look at the huge database of information that's now known about influenza viruses and figure out what virus it really was well so he started this and he wrote an initial paper that appeared in a very prestigious Journal identifying the beginnings of the gene that encodes for the hemagglutinin of the 1918 virus I was actually able to get little bits and pieces of nucleic acid material out of some of these paraffin blocks that have taken him and his colleague and rich years to get this far and now we come to dr. Holton this is how I got interested in flu Johan Holton who's shown in both pictures in 1951 was a visiting medical student from Norway and he went to the University of Iowa I think is sort of a postdoc of sorts and during his time there and he was working in the laboratory I think on some viruses but during his time here there was a visiting speaker who talked about the 1918 pandemic and what a mystery it was and Holden being in our region knew all about the permafrost and that he realized that people who were buried in the permafrost could be still frozen and he looked at the at the regions of the permafrost in the world and then he cross-referenced that with the regions of the world where people had died of influenza and I have to tell you that virtually every component of the world was affected by the 1918 pandemic except for two tiny little remote islands and he found this place called Brevig mission which is a intimate village and northwestern Alaska that's in the region of the permafrost and he decided he would try to go there have access to some of the bodies that were buried in this village where virtually everyone had died of flu and tried to see if he couldn't resurrect the virus the live virus get it to grow in culture so he went there basically on his own I think the University of Iowa got him $1,000 to travel money and he met the village elders and finally succeeded in getting their confidence and permission to exhume the grave which is what he's standing in here on the picture on the left and found some of the bodies indeed were still frozen and he took some samples but he didn't really have much of a way to transport these back to Iowa he sort of made a dry ice concoction as I remember his story and took the stuff back to the lab at the University of Iowa and tried to get the virus to grow essentially in tissue culture cells completely unsuccessfully so it was a bust but he remained really intrigued by influenza especially 1918 and he read talbin burgers article in nature magazine and he thought and and I I guess he realized from that article and then he subsequently called jeffery taubenberger thing that town burgers having a awful hard time of getting intact sequences and he was just getting a little bits of a few nucleotides and so forth and that he really needed more material and if he could get more fresh material not formalin-fixed paraffin-embedded material he'd have a better chance of getting more of the viral sequences out and so Halton said I'd like I can go back to the same village and I can this time with the right materials and was better support I can get you some more material from frozen bodies and so dr. Holton went back in 1997 to the same village again got permission to exhume the grave and took found one body that was still really relatively intact not thawed and took samples of her lung and brought them back to town when Berger subsequently Calvin Berger and Reid and their colleagues have now determined the entire sequence of the 1918 virus all the different all eight genes and this is what they've done they've taken the pathological specimens that they had and that Hultin brought back they've done PCR amplification sequenced the genes reconstructed them in the test tube essentially built them again put them into the influenza virus through processor called reverse genetics looked at the contribution of each one of these eight genes to the ability of the virus to cause disease in different models including into tissue culture and also into a mouse model of influenza the bottom line is I'm not going to show you the data but the bottom line is is that the entire 1918 virus is indeed about ten times more lethal to mice than the background virus and that several of the genes seem to be important it's still not clear if there's a single gene that probably isn't a single one of these genes but we're getting a lot closer to understanding the 1918 virus and we now know that it was not a swine virus it has the typical signatures of a bird-like virus but not any bird virus that was ever been isolated subsequently that we've ever sequenced so it wasn't a swine flu and in fact the pigs that were having the flu at the time of the 1918 pandemic among humans probably got it from the humans not the other way around and it was an h1n1 we know that because of not only his sequences but you can actually tell when you look at specific antibodies from people you can type the antibodies and you can see if they react with an h1 hemagglutinin or an h2 or an h3 so in fact many years before we knew that it was an h1n1 virus but we didn't know what it looked like and then you see the next pandemic was an h2 n2 and it was much milder and it had a much more typical affect on it mostly the mortality was in babies and in elderly people and then at 68 we had another virus that emerged h3n2 and that's what's been circulating for the last 40 years predominantly and again a mild a milder flu but about the same death rate is we normally see again in babies and elderly people and then we get to 2009 where we have a swine h1n1 which is actually all of these viruses to one extent or another are actually derived from the 1918 virus they have genes in common or pieces of genes in common with a 1918 strain but this is different enough that the and of course we don't have anybody really any significant number of people left over from 1918 to test how they would react to the new California virus but I mean I think it's substantially different and I just put a few figures here I'm gonna theory n talk about you know what our actual experience is in California as well as in the United States with this latest pandemic flu virus in 2005 when we thought the next pandemic might be the bird flu h5n1 the CDC and the w8 show and started making estimates of the impact of something like the 1918 virus or something more like the 1958 firs on the number of illnesses and the number of deaths how much hospitalization would be required and so forth and just look at what happened if it had been h5n1 which I think there are the reasons to believe it probably never will be but we would have had 45 million visits to doctors offices this many millions of people would have been hospitalized this many people would have been a nice to use this many ventilators it would have been required which is I don't know how many fold more than what we actually have and we would have expected and then this is United States only at two million deaths now a modest or a moderate flu like the 1958 if you just scale up the numbers for our current population size we can anticipate 209,000 somewhere between 90 and 200 9,000 deaths and actually and I think that our current swine flu h1n1 is going to be like this and that we're going to see a lot more people in the hospital needing a lot more intensive care than we've ever experienced before and last thing I read today was a report from state of California it was just published today showing that indeed we're ramping up and our hospitals are experiencing and our primary care physicians are experiencing a massive onslaught of patients so that brings me to the current time and as you know in the spring of this year following our typical seasonal flu season which was just winding down there were these reports of this outbreak of influenza in Mexico and actually common only in California and in fact the first isolate was actually derived from California and so it the new name of the virus is actually California a California h1n1 and it is a swine virus but these are the early data that came from Mexico about who's affected by this new pandemic virus and just the key point on this slide is that the median age of people is 20 pretty young and and then if you look at the age groups where people were now these are hospitalized patients but it has a spooky similarity to 1918 in that people you wouldn't expect necessarily to be most at risk for acquiring infection or in these younger age young adult age groups now I want you to look at the right hand part of the slide this is what we know about that virus of course now we have we I think this virus was sequenced in a matter of days maybe a day so we knew what the new strain looked like and on the right you can see that there are four different colors of jeans so there's one gene in this new pandemic virus that is a human this was from the old seasonal h3n2 virus there are two yellow genes these came from a bird in North America there are three blue jeans which are from swine from North America and then there are now two red genes these are from the array jhin's wine so it's it's got genes from four different mammalian species now look on the left this is a virus that was endemic in pigs in several locations in the United States was causing swine influenza in several locations in the United States and eleven people who were in closed contact almost all of whom were in very close contact with these pigs came down with a moderately severe case of flu nobody died this duck hurt in 2005 nobody died that was the end of the human cases this for like 1976 nothing else happened in the human population but now when you look at the comparison between this virus which was in swine and a triple reasserting in other words it's got three different mammalian species genes and now you look at the new human one this is a classic example of a reassortant virus that this virus got together with h3n2 and mixed up all their genes and this is what came out now we don't know where the swine are that might have had this combination and it might have arisen in a human actually who also was infected with the swine it's it's just not clear at all there's no epidemiologic connection with pigs in either California or Mexico to show exactly how this occurred but it obviously did and so it does again exemplify this whole idea of why influenza can create pandemic strains by mixing and matching its genes once they get in the same cell now this is the percent of visits to doctors with influenza like illness that's this axis and this is the year and then the the week of the year that's how CDC represents the data so in 2007 we had our peak of influenza which started in 2006 in about February and then then influenza cases went down or influenza like illness and then if you look at 2008 the peak of the season occurred a little bit later like first of March and then it went down and then you get to the 2000 the end of 2008 we started to see seasonal influenza and it peaked here then all of a sudden get this blip in April and then it kind of went down and that's is where we are today this is probably a little spurious and that this is influenza like illness is and if you remember or maybe don't realize it but when the whole news got out about what was going on in Mexico and stuff our emergency room for instance at Stanford which is flooded with people who are afraid they might have flu and so a lot of the stuff that came through the door as influenza like illness wasn't actually flu at all other viruses so I'm not sure that this is real but one thing to note that is real is that even though it looks like over the summer things went down this is still a whole lot higher number of visits than usual and indeed that's exactly what we observed here and I think it all around Northern California is that flu continued to occur throughout the summer and now we're really into full swing and the in region 9 which includes California in the state of California we haven't hit our peak of flu cases yet and I don't know how high this is going to go and this is just data from our own biology laboratory at Stanford Hospital and if just look at the bottom for a minute it tells you what kind of viruses we've been isolating from specimens and the blue bars are the new strain of influenza A and virtually all of the influenza that we get right now is all the new strain there is a little bit of another virus called pair influenza that's now in the community and there's another virus called RSV that's now in the community but for flu-like illness it's all the new strain and this is what's happening to our biology lab the number of tests that are being ordered it's also going up dramatically and then finally these are the data of hot off the press from the CDC and this is our region 9 and the red line is 2009 and I think that's right it's influenza visits or influenza like illness visits and we're going this way if you looked if I if I showed you the the data from the east coast of the United States like Boston in Philadelphia in New York they've had their peak already and they're on their way down and in terms of the number of cases but we're just on the way up and that's classic for influenza it goes from the east coast to the coasts and from the eastern part of the world to the western part of the world in seasonal pattern and there are you know a lot of speculation about why is influenza seasonal and in temperate climates where the winters are cold it's a time when people stay indoors they're in more crowded places the transmission is easier and that's one explanation there's more humidity in temperate climates and that that promotes the survival of the virus but probably even bigger factor I'm just guessing now even in hot climates where there really isn't much of a seasonal temperature change the winter months still there that's when influenza Peaks and what happens all around the world is that kids are in school in the winter months and I think it's the fact that kids are in school and kids are usually the vectors of contagion to the rest of us I mean the kids are the ones who are affected first they have the least amount of immunity they get everything that comes by and they bring it home and I think that's a big contributor to why it's a seasonal disease the vaccine as you know is made in hens eggs and we have two kinds of vaccines that have been made for the last several years the major one is an inactivated virus that means although live virus is inoculated into the eggs then when the material is pulled out of the eggs the virus isn't inactivated with chemicals to essentially make it incapable of dividing and multiplying inside yourselves so all you're getting really the proteins the human the neuraminidase proteins of the virus are what's used for the vaccine and therefore you can't get the flu from the inactivated vaccine you just make antibodies to it there is a live virus preparation and this is an attenuated virus so they've taken the h1n1 strain and the seasonal flu trains pass them through eggs to the point that they really have lost their ability to multiply very well they do multiply inside the cells of the nasal mucosa for a few days and they elicit an antibody response but then they essentially stop because they're weak and the whole idea of explanation is actually to make antibodies to these two major proteins that are on the surface of the verse yep you have a question sure I want to know before airplanes how did influenza virus move around the globe probably not through the wild birds it probably is it is coming through humans humans do travel they've been traveling for hundreds of years yeah but before airplanes in 1918 we had ship troops and we had people going on ocean liners and and it's true that wild birds carry the h5n1 to the several regions of the world and that was a concern about these migrating birds bringing the h5n1 virus directly to us there was not any evidence that it ever reached the United States it's a good question but I think since it's a human adapted virus that it really is people it doesn't have an environmental reservoir yes right two great questions let me let me finish up with those questions and I'm almost finished with my formal presentation and so we've got plenty of times to answer really good questions like that first of all right now you know we have a shortage and it's and the reasons for this are entirely predictable our vaccine manufacturers had already started on making the seasonal flu vaccine at the time when this new virus emerged so in order to even try to get people immunized this year they committed to diverting their manufacturing plants to make the new vaccine but they had to start late obviously couldn't start until later and they actually didn't start until August and this is usually a six month process so what's happened is that some of the manufacturers actually had to stop making the seasonal flu vaccine and so we've actually run out of seasonal flu vaccine temporarily that we had started inoculating people against and and tried to you know move over to the new to the new strain but it's going to take time it is an old technology and the distribution it has always been a problem actually our country first of all vaccine manufacturing generally is a market-based economic situation only two of the current manufacturers of flu vaccine are actually in the United States there are four vaccines that are licensed by the United States but two of the companies are actually their manufacturing plants are outside the United States and we don't have any control over those secondly there's a huge risk involved in any company making a new vaccine and especially with the specter of 1976 Andy amber a a lot of negotiation had to go forth by the NIH and the federal government with the vaccine manufacturers to induce them to make the new vaccine and they all did they are being subsidized by a federal government which is I think entirely appropriate but the next step in the most critical step which is the distribution of the vaccine from the manufacturers out to the public and out to public health departments has never been a streamlined thing so they end up in the pit typically the vaccine manufacturers have middle people or middlemen who are the distributors of vaccine and sell their product to institutions to doctors offices etc they don't go through the state health department's and and if you might remember when we were starting making plans for bioterrorism stuff it came to the attention I hope of the public that our state health departments are woefully understaffed under supported and it's even worse now than it ever was because of the recession so in Santa Clara County for instance we have had to layoff many of our public health nurses we only have three MDS in this whole of Santa Clara County who are involved in our public health program and so and in our particular case it looks like communication between our County's health department's and our state health department was not great and so there were misunderstandings about how would be distributed and how many doses people get anyway we're on the short end of the stick here in California in terms of getting vaccine so who should get the I I'll get all those questions who should get the vaccine that's available right this minute I think you all know this already but these are the priority people who should be first in the line pregnant women they are substantial risk for death if they acquire influenza especially in the second and third trimesters health care workers with patient care duties if you don't have anybody to take care of the sick people then that's a problem children and adults between the ages of 6 and 24 years adults in this a marriage older adults with chronic medical conditions like asthma diabetes obesity young children and then people who have infants under the age of 6 months because we can't immunize those babies now let's look let me answer some of the questions that you have right now before I finish up yes is it possible anybody had h1n1 as Christmas not as far as we know yes well actually you said all the manufacturers are flu vaccine are outside the United States it's not true Sanofi is in Pennsylvania and one other XE manufacturer is in the states Novartis is is in Europe and they and the fourth company is in Europe I think what protects us right now first of all these are allies if you will and and I think the negotiations that were carried out this year are exemplary in terms of understanding what the vaccine manufacturers needed to have in order to go forward in converting their facilities and that is that is our best line of defense there's no question about it the vaccine is our best line of defense there are a lot of reasons why many companies don't want to manufacture vaccines it's not it's not a big item you know it doesn't make much money if any and the liability is huge and then you wanted to know if there's new technology that we're moving toward besides these this old technology that's been around since the 40s and the answer is yes several of the companies have the ability now to grow the viruses in animal cells which is a whole lot easier faster and safer in terms of not getting it contaminated and we're just not to the point of Licensing by the FDA and in order to use a vaccine in the United States the FDA has to approve it so we it will become those new vaccines will be coming down the pike my friend who runs the vaccine program for Novartis thinks that within two years we'll have animal tissue culture cells the next scene you have a question yeah yeah it means probably that we'll start to see some declines I would guess by December but that doesn't mean it'll be okay it'll be gone it just means that that the largest number of infections will have occurred by then but we'll still see h1n1 for some period of time I think it's not really predictable about how long you know there's actually flew around every week of every month of the year it's just it's it's a matter of numbers I mean people can get flu in this summer as long as there are people who have influenza they can transmit it to other individuals it's just that the largest number of people with flu occurs in the winter months and we also expect that the old back of the old viruses will also return and we've had just a very few in Santa Clara County so far of the old seasonal virus isn't shown up it's just completely overwhelmed by the h1n1 right now but we don't know what the mix will be say in April of next next year in 2010 we are encouraging everybody to get vaccinated both the old three strange that are in the seasonal flu vaccine as well as in the new strain as soon as you can as soon as it's possible yes two really good questions one is there's some kind of genetic selection for and could it be passed on to the sentence of 1918 and as far as we know know that there don't seem to be any specific genotypes of humans who seem to be more or less resistant now how bad the flu is has a tremendous amount of variability and that does depend on individual host factors if you will but as far as I know there's no genetic basis for susceptibility to the flu because in a pandemic at least 30% of the global population gets sick that's that's essentially everybody is equally likely and I'm sorry what was your first question Oh how long the immunity lasts well the immunity to the hemagglutinin and neuraminidase probably lasts for several months two years but because the virus keeps making these minor modifications over the course of time it's it's really important if you really want to have the most effective vaccine to make a new vaccine to make sure you've tuned up the vaccine to match the most recent strains and it's probably not those two proteins are not as the antibodies aren't as the long-lived as one would like the the other thing that manufacturers really need for is a universal vaccine in other words a component of influenza virus not the hemagglutinin the neurone amenities but something that's stable so that we could immunize people once and that might last years and years and years so far Magic Bullet hasn't been found though yes like variations so what if you start getting vaccinated when the time is saved starting age two and now you get vaccinated every year for the next six years would that have any negative or positive impact on you and the answer I think is no our bodies are programmed to be able to recognize no is it a million some at least a million different proteins or antigens and so looking at 60 over the course of your lifetime is a drop in the bucket it certainly doesn't use up any any of your immune system to do that and that's one of the reasons why I think the the concern that some parents have for instance about their babies or their kids having to get you know as many 37 shots for childhood diseases and worrying about whether that puts a big burden on their immune system to see that many different vaccines for their body to see that many vaccines this is really not a not a problem at all for the immune system it's it's tuned to be able to to deal with millions essentially of different antigens and in fact in the course of just eating things and being exposed to what's around us we're being constantly challenged by a myriad of different antigens all the time yes yeah it depends on if you're very sure that they got the new h1n1 which is highly likely if they had documented influence and now there are other things that look like influenza certainly it wouldn't hurt to get vaccinated I would say if there's a shortage of vaccine and there are other kids at college who haven't been able to get vaccinated then I kind of step aside on the line and come in a little bit later but it certainly wouldn't hurt to get vaccinated and you can't be absolutely certain unless specific tests were done which in fact mostly weren't done by September because we just assumed virtually every influenza like illness where every flu illness was was the new strain yes you wanted me to ask someone oh one more on this side good question um it is an exposure to 1957 because as you're right it was an h2n2 verse it is true that people over the age of 60 probably 65 for sure seem to have a level of antibody that reacts with the new strain and if we look at the curves of who's getting infected very much many fewer elderly individuals are getting infected than we would anticipate so they are more protected and it's not clear at all what they would have seen 60 years ago it's it's just a hypothesis that they that they have been exposed and I don't think it was the 1976 vaccine campaign that was a swine h1n1 at least I haven't seen any recent reports and I just checked today to see if there's anything more about the 76 vaccine but I think it's still too early I mean it had to have occurred 60 years ago before for these people to be protected and we don't know what virus it was and we it's possible is something one of the seasonal flu viruses or whatever that was used but I think it's it's it's not known one thing at one point I do want to make though is even though older people are relatively protected compared to younger people if they get flu they're much more likely to die so there's a much higher mortality rate when adjusted for the number of people in that group of people who've gotten flu we're going to die and primarily this because older people are much more likely to have other comorbid conditions like diabetes heart disease lung disease asthma etc then young children so the kids are having the highest hospitalization rate but they actually have a very low death rate pregnant women on the other hand are not any more susceptible to getting infection but they are much greater risk for death and much complications so I think we've used up our time and I'll stick around if anybody wants to talk with me later thanks a lot so in thanking again dr. Thompkins this was a talk just looking around the room that I think really riveted everyone's attention for obvious reasons and I think it's hopefully one that both informed you and I think to some degree reassured you as well I want to just let you know in case you wanted to continue with us as time goes on we are going to be posting the winter session of this course on November 5th and registration needs to be completed by November 30th so start starts of it starts November 30th so if you want to come back and I can tell you the program in January and Beyond that's fantastic you're welcome to do it and but till then we'll see you next week next week we're going to be talking about the environment and risk for certain infections as well so see you then for more please visit us at stanford.edu

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Views: 178,249

Rating: 4.5536771 out of 5

Keywords: Science, biology, medicine, infectious disease, vaccine, vaccination, H1N1, swine flu, capsid, RNA, respiratory system, pathogens, hemagglutinin, neuraminidase, amino acid, antigenic drift, antigenic shift, Cholera, immunity, mutation, pharmaceuticals, sa

Id: fLGNrC9k418

Length: 109min 38sec (6578 seconds)

Published: Thu Feb 25 2010