Episode 158: An Unfolding Saga

Chris Dall: Hello and welcome to the Osterholm Update, a podcast on COVID-19 and other infectious diseases with Doctor Michael Osterholm. Doctor Osterholm is an internationally recognized medical detective and director of the center for Infectious Disease Research and Policy, or CIDRAP, at the University of Minnesota. In this podcast, Doctor Osterholm draws on nearly 50 years of experience investigating infectious disease outbreaks to provide straight talk on the latest infectious disease and public health threats. I'm Chris Dall, reporter for CIDRAP news, and I'm your host for these conversations. Welcome back, everyone, to another episode of the Osterholm Update podcast. Last week, the Michigan Department of Health and Human Services announced an H5N1 avian influenza case in a Michigan farm worker who had regular exposure to infected livestock. It marked the second human case in the US related to the H5N1 outbreaks in dairy cattle, and it was just one of several updates in the evolving H5N1 story. Meanwhile, in Singapore, health officials announced that they were closely monitoring a rise in COVID-19 cases that appear to be driven by variants with FLiRT mutations. And it's not the only country that's seeing COVID upticks. Those are the two items we're going to lead with on this May 30th episode of the podcast. We'll follow that up with a look at the latest news on long COVID, an update on the surge in measles cases across Europe, and a conversation about the ongoing negotiations on a plan for how the world will fight the next pandemic. We'll also answer an ID query about what the H and the N stand for in influenza designations, and bring you the latest installment of This Week in Public Health history. But before we get started, we'll begin with Doctor Osterholm's opening comments and dedication.

Dr. Osterholm: Thanks, Chris, and welcome back to the podcast family for another episode. Uh, and to anyone who might be joining us for the first time, I hope we're able to provide you with the kind of information you're looking for. Uh, we tend to be a bit of an unusual podcast in that we cover everything from the hard science to those things that, uh, uh, some people would say are of the soul. As you know, this podcast is coming out after a long weekend here in the United States in observance of Memorial Day. I know we've got quite a few listeners who tune in from other countries, but for those of you with us here in the States, I hope you've enjoyed a safe and relaxing holiday weekend. For many, this actually marks the first week of summer. Even though the summer solstice is still a few weeks off, the meaning of Memorial Day can sometimes get lost when we treat it as only a long holiday that kicks off summer. This holiday is really a chance for us to take a moment to take stock of all that we can accomplish, express and enjoy because of the dedication and the contributions of those in our military. So before we get to our discussion on the latest public health news and infectious disease issues, I'd like to take this dedication segment to remember the countless heroes who have dedicated their lives to serving our country. I want to express my gratitude for the bravery, sacrifice, and valor of the men and women who have served in our military, and especially around Memorial Day. I'm also grateful for those who have made the ultimate sacrifice while defending our freedoms.

Dr. Osterholm: And in noting that issue of sacrifice, it's also a very sad chapter in our history to talk about not just those 7000 US service members who have died in action since 911, but the fact that four times as many service members have died by suicide than in combat over that same time period. We have a major challenge today in this country supporting those who have given so much in military service. And for that reason, this dedication is not just to those families who have suffered with fallen warriors, but also to those families who have suffered with loved ones who were real warriors, but who coming back out of military service have suffered from the stresses of what they've gone through. Most of you are aware that the red poppy is a significant symbol to honor those who died serving our country during war. Maybe you saw people wearing a poppy pin over the weekend. The connection between poppies and honoring fallen soldiers goes back to 1915 from the poem In Flanders Fields by Lieutenant Colonel John McCrae, where the flower was used to symbolize both the blood shed during war as well as resiliency, since poppies can lay dormant for many years, then reappear in great numbers, it is an inspiring message for all of us that out of rocky and barren times of grief and loss, there's always hope for another bloom. It's in this regard I want to add a very personal note, a note that is still very difficult for me to talk about. When I was a young boy growing up in rural Iowa, I looked forward so much to the weekend in which the local Veterans of Foreign Wars chapter would hold the poppy sales for our community.

Dr. Osterholm: And another good friend of mine and I would always jostle [00:05:00] for the lead in who sold the most poppies on a given weekend. And this happened year after year after year. Well, this same friend of mine, James Francis Riley, was unfortunately one of those great warriors who gave his life in the honor of the country. He died in November of 1970 at age 20, in Vietnam. I still never forget all of those days competing with Jim on poppy sales. I also will never forget the moment I heard about his death in battle in Vietnam. It will forever be a reminder to me of what that ultimate sacrifice looks like. And now let me move to a bit of a brighter subject today. And that, of course, is our light. Uh, it is an incredible time of the year for me today. Sunrise in Minneapolis-St. Paul is at 5:30 a.m., sunset at 8:51. That's 15 hours, 20 minutes and 49 seconds of sunlight. Today we gained one minute and 33 seconds compared to yesterday. And of course, our dear, dear friends in Oakland at the Occidental Belgian Beer House on Vulcan Lane. Today, your sun rises at 7:23. Your sun sets at 5:13. You're now down to nine hours and 49 minutes of sunlight. You're losing about one minute and four seconds a day. Again, we share our light with you, but more importantly, we share our thoughts with you.

Chris Dall: So, Mike, it's been hard to keep up with all the H5N1 news in recent weeks because there's been so much of it. But I want to start with two items. The first is the human case on the Michigan farm, and the second is a study that showed that mice fed droplets of raw milk infected with H5N1, quickly became ill with high virus levels in their respiratory tissue. Which of these items is more significant?

Dr. Osterholm: Chris, this is a saga. It's an unfolding story. We mentioned that in previous podcasts that this would likely be what would happen. But first of all, let me just start out and say that this podcast, which is obviously recorded before its Thursday morning release, uh, may actually be behind the times because I have some information today that suggests there may be a third human case that's going to be reported in the next 24 to 36 hours. We'll see if that in fact materializes. But the most recent case, the second of the H5N1 cases in humans, occurred in Michigan. Both cases, the one in Texas a few weeks ago and this more recent one in Michigan, were in farm workers who were in regular contact with infected animals, and both experienced mild symptoms, specifically conjunctivitis, and recovered. The details of the Michigan farm workers symptoms were not made public, but CDC released a statement saying the nasal swab was negative for H5 influenza, but the eye swab was positive. Again, not a surprise. Remember, we talked about that in previous podcasts that the alpha two three sialic acid receptors are in our eyes, and these are the receptor sites that the bird viruses actually use to gain entry to the cells of their host. So this most recent case is surely consistent with the case in Texas.

Dr. Osterholm: The CDC completed a genetic analysis of the virus from the Michigan patient and found that it did not have the PB2E627K mutation linked to enhanced replication in mammals, which the Texas patient did. But the Michigan patient did have PB2IM631L mutation, which has been seen in cattle and has been linked to increased replication in mice. Despite these minor differences, the risk to the general public has not changed. I still believe it's a very, very low risk. But let's go back to the cattle. What's happening? Well, we have 69 farms across the United States that have documented infection in their dairy cattle. These are in nine different states. But of note, 22 of the 69 are in the state of Michigan. We'll come back to that later. Why? I think that, in fact, is such an important finding. But in terms of what this means for humans, we still do not see changes in this virus, even though it's circulating in cattle. That in fact puts humans at a much greater risk for developing a true influenza like illness, which is necessary to actually have transmission of the virus. So in other words, if I get infected in the eye, the likelihood of me transmitting that virus is very low and it's a virus that is not yet adapted to the alpha two six sialic acid receptors as opposed to two three.

Dr. Osterholm: The two six is the one that is related to human viruses. So at this point, like the Who and CDC, I continue to see this as a low risk situation for humans. It's horrible for some mammal species. Uh, and this is an area that we still really are unclear as to why we're seeing the clinical presentations. We are a number of mammals who have become infected, have had fulminating illness, multi-organ involvement, and have died, whereas yet we still see with dairy cows a situation where it's [00:10:00] not necessarily just mild illness, as it was illustrated in a report from a Michigan farm. But these animals are not dying from the influenza virus itself, and it's unclear what this means. Why do some animals, uh, actually get infected and have fulminating illness and a species like bovine? Not we don't know. And so far again, that is largely been the case we've seen with humans with this H5N1 virus. Now, what will happen in the future? I don't know. I do have concerns that if this virus continues to infect cattle, over time, we'll get closer and closer to the human influenza season of next fall or early winter, in which then we could see human viruses in those workers, in those dairy operations with close contact to the udder and therefore potential for transmitting the virus, even if through mechanical touching of the udder, in which now we could have both bird and human viruses in that same udder.

Dr. Osterholm: And that's the big question. What does that mean? Does that mean there would be a higher risk for potential reassortment having a co-infection with both a human and a bird virus? We just don't know at this point. Now, I would be willing to bet, though, if we see this virus continue to circulate as it is, we're going to end up with a number of immune animals where it will likely slow down in terms of transmission and dairy cattle. Remember, this is kind of a first hit, uh, front that we're seeing. And so we have many, many animals that are surely, uh, susceptible to this virus. But with infection, they may not be in the future. So it could be by next fall or early winter, the activity in the bovine population will have been greatly diminished. Now, Chris, you asked about the study. It was published by a team from the University of Wisconsin in Madison and Texas A&M Veterinary Medical Diagnostic Laboratory. They took five mice and fed them 20 drops of contaminated raw milk from a herd in New Mexico. Let me again emphasize that this was raw milk that did not go through the pasteurization process.

Dr. Osterholm: So it is not the milk you find in your grocery store shelves. On day one, all of the mice showed symptoms of lethargy and ruffled fur. They survived to day four before being euthanized to determine the virus levels in various organs. The virus found was at high levels in the nasal passages, trachea and lungs, and low to moderate levels in other organs, despite not lactating. There was also H5N1 detected in the mammary glands of two of the five mice, which is similar to the high viral loads in the mammary glands found in the lactating cows. This is a fascinating finding and really does again raise this issue. Why this multi-organ a very serious kind of infection picture take place in some animal species, not in others. We will have to continue to follow this to try to understand that and what the implications might be one day for human infection. This study also investigated the impact of heat treatment on the contaminated raw milk at different temperatures and time intervals. They found that heating the milk to 145 degrees for any intervals ranging from 5 to 30 minutes killed all the virus. They found that heating it to 161 degrees for shorter time periods, including just 15 and 20 seconds, significantly reduced the virus titers but did not inactivate it.

Dr. Osterholm: Finally, this study monitored virus levels of refrigerated raw milk over five weeks. The milk, which was stored at 39°F, showed only small decline in virus levels, suggesting that contaminated raw milk could be infectious for at least five weeks if refrigerated. These findings are significant, and, I believe, of real concern. I don't believe that the current pasteurization temperatures we're using are at risk right now of also resulting in surviving virus coming through in the milk system. But this is something we need to continue to study and study closely to make sure that we're not seeing, with different time temperature combinations, the potential for virus to make it through into the final milk product. So again, I want to emphasize feel free to go drink your pasteurized milk. Please, please don't drink raw milk. I have personally worked up far too many outbreaks in which I've watched young children become seriously ill with Campylobacter infection with E. Coli infection from contaminated milk. Um, you know, as I've described in this podcast before, I led the investigation on a new disease called Brainerd diarrhea, a chronic diarrheal disease lasting often more than a year to two years. Uh, again associated with raw milk. So the bottom line message here is, is that what you're buying on the store shelves is safe, but the raw milk is simply not.

Chris Dall: Mike, I also want to note here that a lot of the information we're getting on this outbreak is coming from Michigan. Why is that?

Dr. Osterholm: Well, Chris, it really takes me back to a statement [00:15:00] I've used many times on this podcast. And that is the absence of evidence is not evidence of absence. And what I mean by that is, is that the fact that Michigan is finding so many farms with infection and a number of animals infected is substantial when the rest of the country is finding little. And I think it really goes back to the leadership that has been put forward by the Michigan state government officials, including their Commissioner of Agriculture and their head of their health department. They've had a very swift response together and as a result, issued a determination of extraordinary emergency HpaI Risk Reduction and Response Order on May 1st. The order requires dairy farms to enhance biosecurity and reduce potential virus risk to the farms. Additionally, the state has taken actions to monitor and test farm workers for even mild symptoms, which resulted in the identification of the second human case associated with this outbreak that I just discussed. As the state said in their statement about human cases, it's not unexpected that comprehensive testing results in identifying a case. So my hat is off to the Michigan officials. The fact that 22 of the 69 farms in this country that have infected dairy cattle are in Michigan should not be seen as a major problem for Michigan compared to other states. The real problem is all the other states that are likely scene of virus activity but are missing it. Which does beg the question of just how prepared are we again to see an emerging influenza problem in the future in many locations where, again, this same kind of surveillance may mean we miss it. Interestingly, when you look at the wastewater surveillance that we've all talked about, there were only minimal, low and moderate levels of influenza A across the Michigan sites.

Dr. Osterholm: So we're not seeing influenza viruses getting into the Michigan sewer systems. The only states with above average and high activity levels in their wastewater include California, Florida, Illinois, Kansas, New York, Oregon, and Texas. Let me add, there has not been any confirmation of any affected herds identified in California, Florida, Illinois, New York, or Oregon, but also that the wastewater data cannot distinguish between influenza A subtypes or between human and animal waste. It's my bet, however, that this activity that is being picked up is in fact H5 activity. And it's very possible that what we're seeing also is the impact on the waste stream of byproducts of the dairy industry, i.e. when in fact they are processing milk. There is a lot of biosolids that get created that end up in the sewer system, as well as the potential for slaughtering plants that actually are also on municipal waste systems, and therefore they could be also adding their load of potential virus activity. So this could mean that it's not about human infections at this point, but we don't know. I again want to highlight, I think the absolute importance of wastewater testing is going to provide in the future in terms of monitoring what's going on in our communities. I look forward to in the very near term, actually having specific H5 probes, not just influenza A probes that will be able to tell us specifically is this, in fact H5 infection as opposed to just influenza A? So my hat's off to Michigan. Uh, you may look like you have the worst record, but I know for a fact it's because you're doing the best job and we congratulate you on that.

Chris Dall: Now to COVID-19. As I said in the intro, Singapore and other countries have been reporting upticks in COVID cases and in the case of Singapore at least, the uptick appears to be driven by the Jan one offshoots, Cp1 and Cp2. Meanwhile, the CDC reported last Friday that Cp2 and CP3 now make up more than 40% of sequenced viruses here in the United States. Mike, are we still in a wait and see mode on whether these variants are going to drive a global increase in cases?

Dr. Osterholm: Well, Chris, this always seems to be the age old question we're left asking ourselves in times like these. According to the most recent wastewater data that was published by CDC, there surely are some signs of a slight rise. That being said, on a regional basis, it's actually the western US where most of the wastewater increases have been reported, and overall, fortunately the levels were seen are still really quite low. However, it's always difficult to predict what will happen in the weeks ahead, especially with all the existing unknowns. Is this rise an early sign of upticks brought about by the FLiRT variants that includes CP1 one, CP2 and CP3 that you mentioned? Possibly. It's hard to know, especially when you consider the role of other factors like waning immunity. The same thing is true when trying to guess just how steep a sustained upward trajectory might climb, and where would it peak. So all I can say is that there are still a lot of unknowns, [00:20:00] but at the very least, we can feel good that the current levels which any increases would build off of are very low. Now, we've heard a lot over the last several weeks about activity, particularly in Asia. Chris, you mentioned there are reports from a number of places like Australia, New Zealand, Singapore and the United Kingdom showing the rise in activity. And in Singapore, notably, the rise has occurred at the same time that the FLiRT variants climbed in prevalence, accounting for more than 2 in 3 cases. But let me put this into perspective Singapore has a population of about 5.6 million people, very similar to that of Minnesota. In the second week of May, they saw 250 people hospitalized in Singapore. That's up from 181 the first week of May.

Dr. Osterholm: Here in Minnesota. Throughout the month of April, we averaged about 70 hospitalized cases per week. So compared to the number that we're currently seeing in Singapore of 250, we're still significantly below that. But for both areas, these numbers are dramatically below the thousands of hospitalizations that were occurring 1 to 2 years ago. And so I think it's important to keep in mind that even in a place like Minnesota, if we were to see an upward drift, uh, from our 70 hospitalizations per week now, in the 5.7 million people who live in our state, that would still represent a very small increase relative to what we've seen in the past. So I can say that for the summer months coming ahead, I believe that even with the first, uh, variant potentially impacting case numbers, we really are still at a very, very good point in this pandemic. And I don't want to minimize those 70 hospitalizations a week in Minnesota or the 250 hospitalized people in Singapore, or the deaths that also occur. But I think it's really important to understand that any new increase in cases are coming off of very, very low point. And that was so different than during much of the pandemic, where every time a new variant would take off, it often was taking off from what was already a large number of cases occurring. So stay tuned. We'll we'll learn much more about the variants over the next several weeks here in this country. Uh, and at that point have a better sense of what has happened in Asia. And what does that portend for what might happen here in the United States? In the meantime, I just want to say, enjoy your summer. Enjoy your summer.

Chris Dall: So we've had some listeners asking us about when they'll be able to get their next COVID shot, but that's going to rely in part on what variants will be targeted in the updated shot. Mike, do you have a timeline on when that decision is going to be made?

Dr. Osterholm: Uh, just as you mentioned, Chris, this is something that many of our listeners are thinking about, especially with most of us now, 3 to 8 months out from the most recent dose of vaccine. I wish we had more information for you on when you'll be able to get your next dose, and which variants that dose will target, but unfortunately, we're still a few weeks away from having those answers. We'll know more after the FDA's Vaccines and Related Biological Products Advisory Committee, or known as VRBPAC, meets on June 5th. But as a reminder, the most recent booster dose recommendations, which were made on February 28th, 2024, allowed those over age 65 and those with immune compromising conditions to get an additional dose of vaccines four months after their previous dose. I hope that we see the next booster dose recommendation apply to everyone who wishes to receive an additional dose, and not only those at increased risk for severe disease. We know that most individuals, regardless of their risk for severe disease, will likely choose not to get an additional dose. So we certainly won't be experiencing a shortage of these vaccines.

Dr. Osterholm: Because of this, I see no reason to withhold a dose from anyone who wants one, especially because these vaccines have such strong safety profiles, and the data have become abundantly clear that the most protection from these vaccines is not related to how many doses you've had. But how long ago was it you had your last dose of vaccine? So I know that this answer may be frustrating to those who are hoping that we would have more complete information at this time, but I'm optimistic we'll have details to share with you during our next episode in mid-June. Just to remind you that currently the recommendations are you have to wait four months between vaccine doses to get your additional new approved dose, and it's been recommended three months after infection. I'm not quite sure why those differences are there, uh, in terms of which months. But if you want to go get your dose now, uh, if you have not yet had that extra dose, do so knowing that this fall you'll want to get an additional dose to.

Chris Dall: So as our listeners know, we're trying to provide an update on the latest long COVID news and research in every podcast. Mike and I [00:25:00] understand our friend Eric Topol has a recent blog post that you thought was quite interesting and worthy of discussion. So what? What did Eric say in that blog post?

Dr. Osterholm: Well, yes, I am a very avid follower of Eric Topol's work and his various postings, and many of you know that he is someone that I work with very closely. We have a weekly call in which information is shared with him and with a few other colleagues. Eric has just posted in his Substack site an interview that he did with Akiko Iwasaki in. It's entitled The Immunology of COVID and the future. We've linked this on the podcast website and I urge you to listen to this. It's about 40 minutes long, but the first 20 minutes is really. What is the latest news on long COVID? Now, for those that aren't aware of it, Akiko is really, I think, probably one of the 1 or 2 world's best experts on the immunology of COVID and in particular, looking at long COVID issues. And together with Eric in these discussions, they really fleshed out, uh, the issues I think, that are front and center right now on long COVID. In particular, they emphasized in the interview that long COVID is not really one disease. It's a collection of multiple diseases, and they unfortunately end up kind of getting lumped together. There are now over 200 symptoms identified with long COVID, and not everyone has the same set of symptoms. And that is something that's important to understand because you can have different presentations for long COVID issues. They identified three different hypotheses that can explain long COVID, and all of these could be operative in the community. First is, is there still persistent virus or remnants of virus that are driving the disease itself, meaning that we don't find the virus completely cleared after X number of days, but it may persist for months.

Dr. Osterholm: Could the remnants of the virus, meaning all that PCR positive testing that we see in individuals days and sometimes months after being infected may not be full viruses, but it's enough to stimulate the immune response. So that's the first area that needs to be addressed in. Akiko is actually very involved in some studies looking at can Paxlovid taken over time actually help make a difference that way? The second hypothesis that she is working on is that of an autoimmune disease. This is where once the COVID infection occurred, it stimulated the immune system in such a way that it continues to keep functioning and doesn't shut down, meaning that even though the virus is gone, it's still causing inflammation and response that could explain the symptoms. And finally, the third hypothesis is actually the reactivation of herpes viruses. So many of us as adults have multiple latent herpes virus in our body. For example, we see reactivation of viruses like Epstein-Barr virus or varicella zoster, both herpes virus members. And that too could cause many of the symptoms we're seeing. So I would refer you to this piece. It's outstanding. It's very understandable. Uh, and, you know, to have Eric and Akiko together, uh, was a real gift. So, uh, if you have no other piece on long covet that you have read or planned to read in the days ahead, this should be the one.

Chris Dall: It's time now for our ID query. We had a listener this week ask us two questions regarding influenza. They asked, what do the H and N stand for regarding influenza and what differentiates an H one subtype, for example from h two or H5.

Dr. Osterholm: Well, Chris, this is actually a question that many people have, but often don't ask. They just keep hearing about the alphabet soup of H and N and these different numbers. But it really is very important to understand the difference because it says everything about what is the concerns that we should have about a given flu virus, for example, there are really four primary kinds of influenza viruses A, B, C, and D influenza A viruses, which we'll talk more about in a moment. Here are those which regularly infect humans and are also the ones that can quickly change in such a way that they can cause pandemics where the population does not have immunity to that virus. Influenza B also occurs in our communities, and it's of note that these are not pandemic related. They don't we don't see these changes. And one of the strains, Yamagata literally just disappeared from the scene over the course of the past year and a half. And we don't understand exactly why that happened. But we still have one other strain of influenza B that circulates. It still can cause marked and severe disease. But again, it doesn't have that pandemic potential that A does. Influenza [00:30:00] C viruses largely affect animals. Rarely. Rarely it can infect humans. And the same is true with influenza D, this one where it again is largely all animals with no human infections. So that gives us the kind of families of A, B, C, and D. So let's take a look at influenza viruses. First of all, it's important to understand that these viruses are circulating in the guts of wild aquatic birds long before humans were on the face of the earth.

Dr. Osterholm: So this has been a natural viral, uh, partner of these birds. And in terms of what it caused for illness or didn't, it's unclear, but it seemed to survive quite well with these bird species. When we worry about humans, it's when the bird viruses change in such a way to actually become able to infect humans. And it's when that happens, there's enough change in the virus, and it can either occur through mutations that collectively occur or more likely, reassortment, where you have a certain animal species that can be infected by both bird viruses and human viruses. And with co-infection, the viruses in those same respiratory tree cells ends up swapping out genetic material, resulting in a new virus. This is exactly what happened in 2009 with H1n1 in central Mexico and the swine operations there. Pigs are one of those or, uh, animal species that can be infected by both bird and by human viruses. So now where does that get us with the H and the Ns? Well, the H stands for a hemagglutinin. There are 18 of these. Notably, the last two, which were more recently discovered were both came from bats viruses. And these hemagglutinins are a key lock and key kind of parts of the flu virus that actually are able to attach to certain receptor sites in the lungs or respiratory tract of humans and of birds. H1, H2, and H3 have been regularly found in humans and have caused the pandemics that we can identify. Since the ability to culture viruses over the last 100 years.

Dr. Osterholm: Although there are the other 15 H types, only a couple of those have had any potential implications for humans, notably age five, age seven, and age nine. So when we talk about the H type, we're talking about the virus and its ability to actually latch on to a receptor site in a host in terms of what the N is, that's a neuraminidase. I like to think of the neuraminidase as part of the flu virus. That's basically the hand grenade for the flu virus. That is the part of the virus that basically causes the human cell, once infected with virus, to explode, and to allow all the new viruses that have grown in that cell to be released and to infect other cells nearby. As you may also remember, neuraminidase is one of the things that has been a key factor in what we treat flu with. If the neuraminidase inhibitor drugs are the ones that try to shut this down so it doesn't keep you from getting infected the first time, but it keeps the virus from basically blowing up the cell and spreading its virus. Now, all of these H and N types that come together still have to basically attach to an animal or a human cell. There are two different kinds of receptors. There's the alpha two three sialic acid receptor, which is the one you see in birds and largely animal species. The alpha two six sialic receptor is the one that we as humans have. And that in fact, then is the where those new viruses that have a.

Dr. Osterholm: Adapted to that can infect humans. It's notable to add that in the case of pigs, which have for a long time been seen as the mixing vessel for flu viruses, where both bird and human viruses can infect the the lungs of the pig is because they have receptor sites for both. And this is where you'll likely see reassortment. We've just learned that the mammary glands of cows also have both sets of receptor sites, and poses new challenges about what that means. So when you hear H and N, just know that H1, H2, and H3 are by far still the seasonal virus causes that we are concerned about, and they're the ones that still could be involved with future pandemics. H5 h7 h9 will continue to circulate, with H5 being by far uh, the virus of concern for animal species, and is what we're seeing right now. Remember the humans that have been infected with the virus so far in this H5, uh, situation with the cattle have all been infected in the eyes. And the humans do have two, three receptor sites in our eyes. So I hope this gives some glimpse of what hemagglutinin and neuraminidase [00:35:00] are all about, why they make a difference in terms of what the flu virus might do or not do, and why. We look carefully at why H5, as much as it's causing a problem right now, is an avian virus in so many mammal species has yet not posed a significant risk for humans in terms of widespread population spread of the virus.

Chris Dall: Now to some other infectious disease. News. The W.H.O. reported earlier this week that measles cases are surging in Europe, with the number of cases recorded this year soon to exceed the number of cases that were reported in all of 2023. Mike, we've discussed the rise in measles outbreaks here in the United States, but the issue appears to be worse in Europe. What's going on there?

Dr. Osterholm: Well, unfortunately, Chris, this measles situation does continue to worsen. As of May 28th, there have been 142 identified cases of measles in the United States. It's not yet June, and we have more than double the number of measles cases for the entire year of 2023. While very alarming, Europe is experiencing even a much more significant outbreak, and I believe it's a harbinger of things to come for this country. Now, think about these numbers. As concerned as we are with what's happening in the United States. With 142 cases this year. Measles cases begin to rise in Europe in 2023, particularly in the Who eastern region. Last year, the region reported over 61,000 cases and 60 fold rise compared to 2022. Close to half of those cases required hospitalization. W.h.o. and Unicef are calling for urgent action on this issue in a press release from Tuesday, May 28th. From just the first three months of 2024, 45 out of the 53 countries in the region have reported cases, totals exceed 56,000 cases for just the first few months of the year. But this isn't just a US or a European issue, it's worldwide. Who estimates that in 2022, only 83% of the world's children received at least one dose of the measles vaccine. That is the lowest coverage we've seen in many, many years across the globe. In 2022, there were over 9 million cases of measles and 130,000 deaths, mostly in young children. This is something we have an incredibly effective vaccine for and are almost entirely preventable. This is a public health disaster for cases in Europe identified last year. In children under age five, 99% had not received two doses of the measles vaccine.

Dr. Osterholm: The COVID pandemic has put immense strain on public health systems to maintain all the necessary functions, and children's immunization programs are certainly some of the most critical interventions public health has to offer. Urgent action is needed, including significant funding to provide targeted vaccination campaigns and improve health care capacity to manage these case numbers and reduce mortality. This will only continue to worsen without swift, dedicated effort at a global scale. And please, for those of you in the United States thinking, well, 142 cases and that many just know that we very well one day could look much more like Europe than we do in the United States now. And let me also emphasize that of all the vaccines that we deal with, measles has by far the most durable, broad protection of any vaccine in our public health portfolio. This is not a good vaccine. This is a great vaccine, and it's one that can save so many lives. So I hope that we take seriously what we're seeing happen in the rest of the world. We help the rest of the world vaccinate their children in particular, because, again, an infection acquired in any part of the world that enters the United States is just one more opportunity for this virus to actually spread in the United States. So I hope that this is a wake up call to everyone. And again, think about those numbers. 61,000 cases in Europe, uh, a 60 fold rise just compared to 2022. And what that could look like here in this country.

Chris Dall: Finally, negotiations on a global treaty to fight pandemics like COVID-19 broke down last week as countries were unable to come up with a draft agreement that would set guidelines for how the WTO's 194 member countries might stop future pandemics and better share resources. Mike, what are the main sticking points here?

Dr. Osterholm: Well, Chris, I have to say I'm very disappointed about this, but it's not a surprise to see countries not able to reach an agreement. Even though this is a very important effort. We know that there will be future pandemics, so it's critical that we do everything we can to learn from this one to improve our global responses in the years to come. As you mentioned, the purpose of this global pandemic treaty was for the W.H.O. to be able to create guidelines to help the world [00:40:00] avoid the same mistakes made during the COVID-19 pandemic. This includes efforts to prevent inequitable distribution of vaccines and other pandemic technologies, which has many listeners likely recall, was a major issue when COVID-19 vaccines, tests and treatments first became available. Unfortunately, and not surprisingly, countries were unable to agree on a draft, mostly due to disagreements surrounding sharing of information and physical resources like vaccines and tests. In the most recent draft, it was proposed as W.H.O. get 20% of the production of any pandemic related technology, whether they be vaccines or treatments. Many low and middle income countries felt this was not enough, considering they might be providing a virus sample used to develop these products. Of note, US elected Republicans felt that the proposal actually shredded the intellectual property rights, and Britain's health department stated they would only agree to a treaty that protected British sovereignty and national interest. In addition to the disagreement over information and resource allocation, there was also disagreement on whether a pandemic related product should be free for all or available for purchase at a not for profit cost.

Dr. Osterholm: Finally, some oppose the treaty, as there is currently no way to hold countries accountable if they do not comply with the agreement. Now that the W.H.O. discussions have ended, it is currently up to governments to determine whether to continue that process of negotiations to reach an agreement. I hope this is something that we prioritize because, again, there will be future pandemics, and we will need to create a path forward that will prioritize the health of people in all countries, not just wealthy ones. Now, let me be clear. I'm not naive. I understand why for even high income countries, there will be a reluctance to share vaccines until everyone is covered in that country. And we have to acknowledge that's a reality. But what it really speaks to is can we build more capacity now for vaccine manufacturing that could make them more readily available in low and middle income countries? And if we do that, how will you pay for it? Will you continue to use the vaccine manufacturing capacity for other types of vaccines when the pandemic is not occurring? Big questions, but they need to be addressed. And right now, if another pandemic were to emerge, we would not be in any better shape in terms of dealing with the inequity in vaccine distribution than we were at the beginning of the COVID pandemic.

Chris Dall: Now for this week in public health history. Mike, how are we celebrating this week?

Dr. Osterholm: Chris, we're wrapping up the end of May, which also happens to be Asian American, Native Hawaiian and Pacific Islander Heritage Month. Similar to our segment in February celebrating some notable public health heroes for Black History Month, I'd like to touch on just a few of the many heroes we can celebrate this May. It was in 1859 when Queen Emma of Hawaii established a public hospital for Native Hawaiians facing deadly outbreaks of foreign induced diseases, including smallpox. Her hospital offered care free of charge, and she was a frequent visitor of patients in recovery. Another woman with considerable impact on patient care was Margaret Chung, the first American born Chinese female physician. Doctor Chung established her clinic in San Francisco in the 1920s after being denied many opportunities based on her race and ethnicity. After providing exceptional care to American military service members, even hosting over 175 members at her home for Thanksgiving, she was given the nickname mom by her many adopted sons. There are also notable bookends in the role of the Surgeon General of the United States. The first Asian American to serve as US Surgeon General in 2002 was Doctor Kenneth Moritsugu, a third generation Japanese American. Today, Surgeons General Doctor Vivek Murthy, a first generation Indian American, continues a legacy of exceptional service to national and global health. We will close with one figure still alive today, who has made a historic impact on public health and may be especially interesting to our leaders.

Dr. Osterholm: I believe this individual's work has saved more lives than we can ever count. Peter Tsai, a Taiwanese American inventor, grew up on a farm in Taiwan and went on to study chemical engineering. He then moved to the United States for his post-graduate studies, where he completed over 500 hours of coursework while at the University of Tennessee. He led a team of researchers to develop a material that was electrostatically charged and could attract and prevent microparticles like dust to pass through. Sai patented a technology in 1995. Not long after, in 1996, researchers at the CDC discovered these electrostatic fibers were also effective at blocking harmful microorganisms even as small as viruses. Combined with 3M's mask design size technology results in the invention of the N95 respirator. He continued to refine this technology, even doubling the filtration efficiency of these respirators [00:45:00] by 2018. In 2020, Sai came out of retirement in the wake of the deadly COVID pandemic and a critical shortage of N95s. He worked 18 to 20 hours a day to research how to most effectively sanitize the respirators so they could be used multiple times given their supply. There are so many other Asian American, Native Hawaiian and Pacific Islanders that we could and should celebrate. I just hope that these few examples can demonstrate some of their incredible legacies and the contributions they've made to the world's public health.

Chris Dall: Mike, what are your take home messages for today?

Dr. Osterholm: Well, Chris, uh, three, three take homes today, one age five. We're learning a lot. We now have had to understand a whole different picture of what goes on inside of that mammary gland of that bovine, and we don't yet know. But we also have realized that this H5 virus is going to constantly be at the human doorstep, given the number of animal species that are now infected and how we interact with them. I still believe that the low risk of human to human transmission as a result of being infected with H5 is in fact still very low, but that could change overnight with a reassortant picture, uh, in which we see a bird and a human virus either in a pig lung or in that of a mammary gland of a bovine. Right now, this is a deadly virus for so many animals, and yet for others, it infects but doesn't kill. Why? What is that all about? We don't know. Finally, pasteurized milk is safe as what we see on our store shelves today feel confident in that milk do not have one ounce of confidence for raw milk. It clearly continues to serve as a very significant vehicle of infectious agents. Number two, you know, COVID appears to be returning some. But again, we're in a much, much, much better place than we've been throughout the entire pandemic. Even if we see the increases that are being experienced right now in places like Singapore potentially associated with the variants, we still are going to only see a limited increase in transmission and cases here in this country.

Dr. Osterholm: So we'll stay on top of it, though, as best we can. As you know, we have many of our previously conducted surveillance systems are no longer in operation, and we're going to be counting on things like hospitalization data from only selected areas, wastewater data, etc. but we'll do our best to keep everyone informed. And finally, I so worry that measles is about to take off for the world. And when I say take off, it's bad. Now imagine what it could be. And I hope everyone today got a glimpse of what's happening in Europe right now with measles. So by the way, if you go there on vacation, and particularly if you bring your children, I hope that you're fully vaccinated for measles. But whatever happens with measles in this country, it doesn't look good. And we have a lot of work to do. And I know that there are many grandparents who listen to this podcast. I hope that you're interacting with your kids and where they have decided not to vaccinate your grandchildren, their children. Uh, you can help educate them from a period of time when measles was so deadly that why the measles vaccine remains so important.

Chris Dall: And I understand that you have a closing speech for us today.

Dr. Osterholm: You know, the opening dedication for me, um, is very emotional. I tried not to portray that too much on this podcast, but, you know, I've never stopped thinking about Jim Riley and all the days we spent together and why his draft number took him to Vietnam. And my draft number didn't take me into the military. I think about all the people I know that have suffered immeasurably because of combat service. And then I think about where our country is right now. And I must say that there was one speech in my lifetime I had to memorize this as a freshman in high school, and I still remember it. The Gettysburg Address to me, will remain one of the most important messages this country has ever had delivered. And of note, as many of you know, this came from President Lincoln. It also had a very significant public health tie to it. It turned out that Lincoln was actually incubating smallpox the day he gave the Gettysburg Address. And a few days later, he actually developed a rash all over his body, followed by the classic blisters. Although the diagnosis suggested a milder case of smallpox, Lincoln was ordered to quarantine and didn't resume official duties for almost a month after that Gettysburg Address. Some researchers actually speculate his case wasn't that mild, but that his doctors had intentionally softened the diagnosis to avoid stirring panic in a war torn country. Lincoln survived, [00:50:00] of course, only to end up at Ford's Theater.

Dr. Osterholm: His valet, however, died of smallpox shortly after the president's recovery. And it's very likely that, in fact, he caught the virus from the president. And so today, I share with you this address. Think of it as it was delivered back in November 19th of 1863. And think of the implications of what it means for today, the Gettysburg Address. Abraham Lincoln fourscore and seven years ago, our fathers brought forth on this continent a new nation, conceived in liberty and dedicated to the proposition that all men are created equal. Now we are engaged in a great civil war, testing whether that nation or any nation so conceived and so dedicated can long endure. We are met on a great battlefield of that war. We have come to dedicate a portion of that field as a final resting place for those who here gave their lives that this nation might live. It is altogether fitting and proper that we should do this. But in a larger sense, we cannot dedicate, we cannot consecrate, we cannot hallow this ground. The brave men, living and dead, who struggled here have consecrated it far above our poor power to add or detract. The world will little note, nor long remember what we say here. But it can never forget what they did here. It is for us the living rather to be dedicated here to the unfinished work which they who fought here have thus far so nobly advanced. It is rather for us to be here, dedicated to the great task remaining before us, that from these honored dead we take increased devotion to the cause for which they gave their last full measure of devotion, that we here highly resolve that these dead shall not have died in vain, that this nation under God shall have a new birth of freedom, and the government of the people, by the people.

Dr. Osterholm: For the people shall not perish from the earth. Abraham Lincoln. Thank you again for being with us for another podcast update. I hope the information we shared was helpful. I hope that the dedication reminds all of us that we still live in a world where people make incredible sacrifices, and we have to thank them every day for that. We also live in a world that, with an infectious disease standpoint, continues to throw challenge after challenge at us. And I also want to remember all the grandfathers, grandmothers, mothers and fathers, the brothers and sisters who are in hospitals right now with COVID and the fact that we can't ever forget about that disease, at least it come back and bite us in ways that we had not anticipated. So thank you very much. Enjoy summer again. For those from outside the United States, thank you for indulging us with our Memorial Day dedication. And if I can say anything that means anything, just be kind. Try to be kind. It's a crazy tough world right now. Be kind. Thank you.

Chris Dall: Thanks for listening to the latest episode of the Osterholm update. If you enjoyed the podcast, please subscribe, rate and review wherever you get your podcasts, and be sure to keep up with the latest infectious disease news by visiting our website cidrap.umn.edu. This podcast is supported in part by you, our listeners. If you would like to donate, please go to cidrap.umn.edu/support. The Osterholm Update is produced by Sydney Redepenning, Elise Holmes, Cory Anderson, Angela Ulrich, Meredith Arpey, Clare Stoddart, and Leah Moat.