Brazil conducted a public vaccination campaign April – May 2016 that immunized 49 million people. However, Brazil’s Ministry of Health has reported 1,233 deaths through July 1, 2016 calling Brazil’s H1N1 p2009 season worse than at any time since the pandemic. With the “flu season” in Brazil usually from April through July, add severe H1N1 p2009 influenza as a hot topic about Brazil and Olympic travel, in addition to Zika virus and superbugs.
Listen in as Christopher J. Harrison, MD, discusses the possible implications for the U.S.?
Possible More Severe Influenza Season in USA 2016-17 – “The Brazil Effect”?
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Learn more about Christopher J. Harrison, MD
Christopher J. Harrison, MD
Christopher J. Harrison, MD, FAAP, FPIDS, is Director, Infectious Disease Research Laboratory; Director, Vaccine and Treatment Evaluation Unit; and Professor of Pediatrics, University of Missouri-Kansas City School of Medicine. He completed his medical degree and residency at the University of Kentucky, Lexington, KY and a fellowship in pediatric infectious diseases at Oklahoma Children’s Memorial Hospital, Oklahoma, City, OK. He is certified in pediatrics and pediatric infectious diseases and specializes in antimicrobials, drug resistance, immune responses to herpes viruses, otitis media, toll-like receptor signaling, and vaccines.Learn more about Christopher J. Harrison, MD
Transcription:
Possible More Severe Influenza Season in USA 2016-17 – “The Brazil Effect”?
Dr. Michael Smith (Host): Our topic today is “The Brazil Effect: Is a Severe Flu Season Coming Our Way?” My guest is Dr. Christopher J. Harrison. Dr. Harrison is the Director of Infectious Disease Research Laboratory and Director of the Vaccine and Treatment Evaluation Unit. He's also Professor of Pediatrics at the University of Missouri, Kansas City, School of Medicine. Dr. Harrison, welcome to the show.
Dr. Christopher J. Harrison (Guest): Thank you for having me.
Dr. Smith: So, in an article that I read that was published by you, I got this stat, “From April to May 2016, Brazil immunized has 49 million people, yet had reported 1233 deaths.” I know that's been updated to close to 1500 now. What does that mean to you? What exactly is the Brazil effect?
Dr. Harrison: Well, we don't know what the Brazil effect is, but this phenomenon arose in Brazil where, for an number of years, the H1N1--and listeners will remember that’s pandemic strain that we all got excited about in 2009--has been the major strain causing influenza in Brazil. But, the number of deaths has been in the 50 -120 range, for 4 to 5 years and then this year, for some reason, there's 1500 deaths. We don't think that it's something we can explain based on simply how many have been vaccinated versus not vaccinated. So, there must be something different going on in Brazil to lead to that. Luckily, the Brazil influenza season has died down just in time for the Olympics but it's still a concern that this death rate has increased despite what we know about the virus maybe not changing and increased efforts to vaccinate.
Dr. Smith: Yes. I actually, from your article, again, you quoted that, at least at the time you wrote the article, there were over 1200 deaths this year in Brazil so far and I think that was through July.
Dr. Harrison: Right.
Dr. Smith: This was that stat, versus only 163 from last year, which was a mild year for the southern hemisphere and the northern hemisphere, but it does seem that H1N1, which has been, I think, implicated in most of the severe infections, hospitalizations and deaths, is more severe. What you do think is going on there? Is it the vaccine? Is it the actual strain? What's your opinion?
Dr. Harrison: As you said, 80% of the severe hospitalizations and deaths attributed to influenza in Brazil have been H1N1 pandemic strain as the cause and you'd think after 6 years in the vaccine that we'd have most of the population immune, either from the vaccine or just from the virus going around year after year. So, there is something different and there are two concerns. One is, has the virus changed in some way that the vaccine-induced immunity is not as effective this year, at least in Brazil? Or, has there been some fatigue, so to speak, of the immune systems in the herd from repeated vaccination? There has been some evidence that if you give the same vaccine over and over and over, you get less effect from that vaccine at some point because the antigens in the vaccine actually get tied up by the antibody you already had and you don't get that nice little boost you're looking for to begin the season. So, it could be either of those things. We don't have sequence data to know whether the virus itself has mutated, if you want to use that word. It means that we need to be vigilant this coming season to see if we're going to have a rebound from last year's mild year, as you mentioned, to a more severe year, and the Brazil effect is “keep your eyes open”, because if it happened there, it could happen here.
Dr. Smith: A couple of things that I find interesting. The first one, let's talk about sequencing the H1N1 that is in Brazil right now. Is the CDC trying to make efforts to do that?
Dr. Harrison: They usually do that post hoc, meaning that it's not something you do during season, and I don't have specific personal information to know if they're doing it right now but my guess would be that any time you have this uptick in disease and they’re looking into the cause, that would be one of the first things to do. You have to find what you think is the most representative strain to start doing that kind of thing but I don't really have any information to give you on that. I'm sorry.
Dr. Smith: Let's talk, then, about the vaccine itself. You said something interesting, there, too. So, we've had the H1N1 in the current vaccine for 6 years now, correct? So, is that a concern or is it better to not include the same strain in every year? Should we be rotating the years with these strains that we know are out there? What's your opinion on that?
Dr. Harrison: I think you have to. There are people who are much smarter than me about this stuff, so I don't want to step on the CDC's toes too much here, but I think what you're saying is, if we get less effect from repeated use, would that be reason to not use it every year?
Dr. Smith: Right.
Dr. Harrison: There's not enough data to get us to that point yet but what we have seen is that in some years that, especially populations who are not the most responsive to vaccines, say, the youngest and the oldest, do not perhaps get as big a protective response if you use the same one year after year. That's one of those things that's under investigation, but we aren’t to the point where you want to make a public health decision about that. You really want to line up the vaccine to match with some truth. We've seen what happens in a mismatched year. Remember in the past two years ago when we had a mismatch and we had a really big uptick in disease related to that mismatch.
Dr. Smith: So, when we look at the number of deaths in Brazil right now--you gave me an updated number of 1500 or so--what's the average age in those deaths? I ask that because in 2009, H1N1, we saw a number of hospitalizations and even deaths in some younger adults, for instance. We attributed that to what we now call the “cytokine storm”, where there was such a massive immune response in these young kids or young adults to the virus, it was causing problems. Do we know if that's what's causing what's going on in Brazil right now with these 1500 deaths?
Dr. Harrison: It doesn't look like it's exactly the same phenomenon in that probably 3/4 of the deaths and the severe intensive care unit admissions have been in people you would consider high risk, so those with comorbidities or high-risk conditions or the elderly. So, it doesn't go after the young athlete, which is what it seemed to do in 2009. In part, that was due to the rise of the host immune response. It was also probably due to the fact that we had such a large population who had never seen anything like that before and there was some evidence that there was a new receptor that could get down deeper in the lungs as well.
Dr. Smith: Oh, okay. Got you. So, that would account for it. So, it wasn't just the inflammatory response; it was the virus itself as well.
Dr. Harrison: There was a two-fold factor. That double hit kind of thing.
Dr. Smith: So, what is your concern, though, about the athletes—and not just the athletes, right? A large number of people from the United States have gone to Brazil for the Olympics and are going to be coming back soon. I guess it's good news that the flu season seems to be waning a little bit but is there any concern for them bringing that which is potentially a new H1N1 strain and shedding that here in the United States?
Dr. Harrison: Well, I don't think that we have as big a concern as there was weeks ago when influenza season was still going strong and they were still adding frequent deaths to their list. Just about as the Olympics opened, the influenza season moved out of Brazil and moved further west in South America so that it really was waning there. What always raises concerns to public health people is when you pool together populations from all over the world into one small place, like Rio—sometimes it's not that small—but, you figure, there are people are coming from all different places where influenza has more or less activity, will we get some strains from other places that get passed on and brought back? But, if you think back to the Australian Olympics, which was the last time there was one in the southern hemisphere, as this time of year, we did not see that effect. So, I'm hoping that history repeats itself and we don't have some mix and match unusual strain come out of the Olympics.
Dr. Smith: Yes. Based on the fact that we travel so much, we're so connected now, is that less of a concern for different strains coming into a different area? It just seems that with how we commute and how we travel, that we're sharing more of these viruses. We're being more exposed to them over time. Is that true or is it still a concern when you have something like the Olympics when all these people are coming together?
Dr. Harrison: I think it would be more of a concern if you had a brand new pandemic kind of strain--something, at least, in the influenza family. It would need to be something that we, as a population worldwide, have not had any previous experience with a cousin or close relative so that we had some partial protection, and that was a big concern in 2009. It also would be a concern if it was outside of influenza--if there was something new. That's what raised the specter of Zika to a higher level for a while until people figured out how exactly it was transmitted. Now we have ways to think in terms of preventing it by doing some reasonable things, although as you, in keeping up with the news, I’m sure…
Dr. Smith: Right.
Dr. Harrison: …along with the rest of us know that it is creeping into the US.
Dr. Smith: Yes. So, back to influenza, back to the community physicians, the frontline doctors, if you will, what's your advice for them? Obviously, they're already quite aware of looking for the signs of influenza going into any flu season. Should they be more cautious this year? What advice do you have?
Dr. Harrison: I think the one thing to put into perspective iss that the Brazilian government did immunize 50 million people in their country but they have 240 million people in their country. So, if we look at it from that perspective, herd immunity has no chance when only about 40% of your population is immunized.
Dr. Smith: Right.
Dr. Harrison: So, it may not that the vaccine is the culprit; it may be that the virus is and this is a worse year than usual because everybody in Brazil is going somewhere to help support the Olympics and we have a lot more cross-country kinds of travel within Brazil, which is a big country itself. So, what that leads me to believe is, if we can get our own population immunized closer to that 60% level--we've never done that before, even in a pandemic year--but if we could get there, that would provide a better chance for herd immunity so that these vulnerable populations that look to be the ones suffering the most in Brazil could be better protected because they're just not exposed as much. The people who do get responses from the vaccines aren't getting infected as much, so that protects the less immune, robust people amongst us. So, my thought is, this is a year, given the fact that we know it was worse in Brazil--they immunized 20-30% of the population; maybe a little better than that with that big push they had in Sao Paolo--but I think that we need to be more vigilant than ever. The fact that we don't have the live, attenuated is going to make it tougher to sell to kids in some ways. So, we've got to be at our best getting people to be immunized with the injectable.
Dr. Smith: Well, Dr. Harrison, it’s a lot to think about. I want to thank you for the work that you're doing and I know you're going to stay on top of it as we go into the flu season. Maybe we can have you come back on when we're in the middle of it and just get your opinion on how things are going. Of course, thanks for coming on the show today. You're listening to Transformational Pediatrics with Children's Mercy Kansas City. For more information, you can go to childrensmercy.org. That's childrensmercy.org. I'm Dr. Mike Smith. Thanks for listening.
Possible More Severe Influenza Season in USA 2016-17 – “The Brazil Effect”?
Dr. Michael Smith (Host): Our topic today is “The Brazil Effect: Is a Severe Flu Season Coming Our Way?” My guest is Dr. Christopher J. Harrison. Dr. Harrison is the Director of Infectious Disease Research Laboratory and Director of the Vaccine and Treatment Evaluation Unit. He's also Professor of Pediatrics at the University of Missouri, Kansas City, School of Medicine. Dr. Harrison, welcome to the show.
Dr. Christopher J. Harrison (Guest): Thank you for having me.
Dr. Smith: So, in an article that I read that was published by you, I got this stat, “From April to May 2016, Brazil immunized has 49 million people, yet had reported 1233 deaths.” I know that's been updated to close to 1500 now. What does that mean to you? What exactly is the Brazil effect?
Dr. Harrison: Well, we don't know what the Brazil effect is, but this phenomenon arose in Brazil where, for an number of years, the H1N1--and listeners will remember that’s pandemic strain that we all got excited about in 2009--has been the major strain causing influenza in Brazil. But, the number of deaths has been in the 50 -120 range, for 4 to 5 years and then this year, for some reason, there's 1500 deaths. We don't think that it's something we can explain based on simply how many have been vaccinated versus not vaccinated. So, there must be something different going on in Brazil to lead to that. Luckily, the Brazil influenza season has died down just in time for the Olympics but it's still a concern that this death rate has increased despite what we know about the virus maybe not changing and increased efforts to vaccinate.
Dr. Smith: Yes. I actually, from your article, again, you quoted that, at least at the time you wrote the article, there were over 1200 deaths this year in Brazil so far and I think that was through July.
Dr. Harrison: Right.
Dr. Smith: This was that stat, versus only 163 from last year, which was a mild year for the southern hemisphere and the northern hemisphere, but it does seem that H1N1, which has been, I think, implicated in most of the severe infections, hospitalizations and deaths, is more severe. What you do think is going on there? Is it the vaccine? Is it the actual strain? What's your opinion?
Dr. Harrison: As you said, 80% of the severe hospitalizations and deaths attributed to influenza in Brazil have been H1N1 pandemic strain as the cause and you'd think after 6 years in the vaccine that we'd have most of the population immune, either from the vaccine or just from the virus going around year after year. So, there is something different and there are two concerns. One is, has the virus changed in some way that the vaccine-induced immunity is not as effective this year, at least in Brazil? Or, has there been some fatigue, so to speak, of the immune systems in the herd from repeated vaccination? There has been some evidence that if you give the same vaccine over and over and over, you get less effect from that vaccine at some point because the antigens in the vaccine actually get tied up by the antibody you already had and you don't get that nice little boost you're looking for to begin the season. So, it could be either of those things. We don't have sequence data to know whether the virus itself has mutated, if you want to use that word. It means that we need to be vigilant this coming season to see if we're going to have a rebound from last year's mild year, as you mentioned, to a more severe year, and the Brazil effect is “keep your eyes open”, because if it happened there, it could happen here.
Dr. Smith: A couple of things that I find interesting. The first one, let's talk about sequencing the H1N1 that is in Brazil right now. Is the CDC trying to make efforts to do that?
Dr. Harrison: They usually do that post hoc, meaning that it's not something you do during season, and I don't have specific personal information to know if they're doing it right now but my guess would be that any time you have this uptick in disease and they’re looking into the cause, that would be one of the first things to do. You have to find what you think is the most representative strain to start doing that kind of thing but I don't really have any information to give you on that. I'm sorry.
Dr. Smith: Let's talk, then, about the vaccine itself. You said something interesting, there, too. So, we've had the H1N1 in the current vaccine for 6 years now, correct? So, is that a concern or is it better to not include the same strain in every year? Should we be rotating the years with these strains that we know are out there? What's your opinion on that?
Dr. Harrison: I think you have to. There are people who are much smarter than me about this stuff, so I don't want to step on the CDC's toes too much here, but I think what you're saying is, if we get less effect from repeated use, would that be reason to not use it every year?
Dr. Smith: Right.
Dr. Harrison: There's not enough data to get us to that point yet but what we have seen is that in some years that, especially populations who are not the most responsive to vaccines, say, the youngest and the oldest, do not perhaps get as big a protective response if you use the same one year after year. That's one of those things that's under investigation, but we aren’t to the point where you want to make a public health decision about that. You really want to line up the vaccine to match with some truth. We've seen what happens in a mismatched year. Remember in the past two years ago when we had a mismatch and we had a really big uptick in disease related to that mismatch.
Dr. Smith: So, when we look at the number of deaths in Brazil right now--you gave me an updated number of 1500 or so--what's the average age in those deaths? I ask that because in 2009, H1N1, we saw a number of hospitalizations and even deaths in some younger adults, for instance. We attributed that to what we now call the “cytokine storm”, where there was such a massive immune response in these young kids or young adults to the virus, it was causing problems. Do we know if that's what's causing what's going on in Brazil right now with these 1500 deaths?
Dr. Harrison: It doesn't look like it's exactly the same phenomenon in that probably 3/4 of the deaths and the severe intensive care unit admissions have been in people you would consider high risk, so those with comorbidities or high-risk conditions or the elderly. So, it doesn't go after the young athlete, which is what it seemed to do in 2009. In part, that was due to the rise of the host immune response. It was also probably due to the fact that we had such a large population who had never seen anything like that before and there was some evidence that there was a new receptor that could get down deeper in the lungs as well.
Dr. Smith: Oh, okay. Got you. So, that would account for it. So, it wasn't just the inflammatory response; it was the virus itself as well.
Dr. Harrison: There was a two-fold factor. That double hit kind of thing.
Dr. Smith: So, what is your concern, though, about the athletes—and not just the athletes, right? A large number of people from the United States have gone to Brazil for the Olympics and are going to be coming back soon. I guess it's good news that the flu season seems to be waning a little bit but is there any concern for them bringing that which is potentially a new H1N1 strain and shedding that here in the United States?
Dr. Harrison: Well, I don't think that we have as big a concern as there was weeks ago when influenza season was still going strong and they were still adding frequent deaths to their list. Just about as the Olympics opened, the influenza season moved out of Brazil and moved further west in South America so that it really was waning there. What always raises concerns to public health people is when you pool together populations from all over the world into one small place, like Rio—sometimes it's not that small—but, you figure, there are people are coming from all different places where influenza has more or less activity, will we get some strains from other places that get passed on and brought back? But, if you think back to the Australian Olympics, which was the last time there was one in the southern hemisphere, as this time of year, we did not see that effect. So, I'm hoping that history repeats itself and we don't have some mix and match unusual strain come out of the Olympics.
Dr. Smith: Yes. Based on the fact that we travel so much, we're so connected now, is that less of a concern for different strains coming into a different area? It just seems that with how we commute and how we travel, that we're sharing more of these viruses. We're being more exposed to them over time. Is that true or is it still a concern when you have something like the Olympics when all these people are coming together?
Dr. Harrison: I think it would be more of a concern if you had a brand new pandemic kind of strain--something, at least, in the influenza family. It would need to be something that we, as a population worldwide, have not had any previous experience with a cousin or close relative so that we had some partial protection, and that was a big concern in 2009. It also would be a concern if it was outside of influenza--if there was something new. That's what raised the specter of Zika to a higher level for a while until people figured out how exactly it was transmitted. Now we have ways to think in terms of preventing it by doing some reasonable things, although as you, in keeping up with the news, I’m sure…
Dr. Smith: Right.
Dr. Harrison: …along with the rest of us know that it is creeping into the US.
Dr. Smith: Yes. So, back to influenza, back to the community physicians, the frontline doctors, if you will, what's your advice for them? Obviously, they're already quite aware of looking for the signs of influenza going into any flu season. Should they be more cautious this year? What advice do you have?
Dr. Harrison: I think the one thing to put into perspective iss that the Brazilian government did immunize 50 million people in their country but they have 240 million people in their country. So, if we look at it from that perspective, herd immunity has no chance when only about 40% of your population is immunized.
Dr. Smith: Right.
Dr. Harrison: So, it may not that the vaccine is the culprit; it may be that the virus is and this is a worse year than usual because everybody in Brazil is going somewhere to help support the Olympics and we have a lot more cross-country kinds of travel within Brazil, which is a big country itself. So, what that leads me to believe is, if we can get our own population immunized closer to that 60% level--we've never done that before, even in a pandemic year--but if we could get there, that would provide a better chance for herd immunity so that these vulnerable populations that look to be the ones suffering the most in Brazil could be better protected because they're just not exposed as much. The people who do get responses from the vaccines aren't getting infected as much, so that protects the less immune, robust people amongst us. So, my thought is, this is a year, given the fact that we know it was worse in Brazil--they immunized 20-30% of the population; maybe a little better than that with that big push they had in Sao Paolo--but I think that we need to be more vigilant than ever. The fact that we don't have the live, attenuated is going to make it tougher to sell to kids in some ways. So, we've got to be at our best getting people to be immunized with the injectable.
Dr. Smith: Well, Dr. Harrison, it’s a lot to think about. I want to thank you for the work that you're doing and I know you're going to stay on top of it as we go into the flu season. Maybe we can have you come back on when we're in the middle of it and just get your opinion on how things are going. Of course, thanks for coming on the show today. You're listening to Transformational Pediatrics with Children's Mercy Kansas City. For more information, you can go to childrensmercy.org. That's childrensmercy.org. I'm Dr. Mike Smith. Thanks for listening.