Episode 173: What Is Safe and Effective?

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 Dahl, reporter for CIDRAP news, and I'm your host for these conversations. Welcome back, everyone, to another episode of the Osterholm Update podcast. We are nearing the end of 2024, and it's been a long and active year in the world of infectious diseases. We started the year in the midst of what was one of the biggest surges in COVID-19 cases since the Omicron wave. Then in late March, we had the first reports of an H5N1 avian flu outbreak in dairy cows that remains very active. In April, there was news out of the Democratic Republic of Congo of a new, deadlier strain of mpox. Along the way, we've also had an outbreak of Marburg disease in Rwanda, measles outbreaks here in the United States. New estimates on the deadly toll of antibiotic resistant bacterial infections and foodborne disease outbreaks. And to top it all off, we've recently had reports of an outbreak caused by a mystery disease in a remote region of the Democratic Republic of Congo. And of course, there's still COVID-19, which is where we'll start on this December 19th episode of the podcast. Our last episode of 2024. We'll also provide an update on developments in the H5N1 avian flu outbreak. Tell you what we know and don't know about the mystery outbreak in the DRC. Answer an ID query about the meaning of the phrase safe and effective when it comes to vaccines and discuss some of the comments made by Robert F. Kennedy Jr. and President elect Trump about childhood vaccines. And we'll bring you the latest installment of This Week in Public health history. But before we get started, we'll begin with Doctor Osterholm opening comments and dedication.

Michael Osterholm: Thanks, Chris, and welcome back to all the podcast family members. It's been a long year, but a special year to be with you. I also want to welcome anyone who might be listening to this for the first time, or those who have only been infrequent listeners, and you happen to be joining us for this end of the year podcast session. Let me start out by saying, Chris, I want to thank you and all the podcast production team members for helping to support this ongoing effort. It's hard to believe we're approaching five years in the podcast business. We thought when we started this, maybe it would be a few months. So, it's been quite an experience. And I also want to acknowledge to each of you who have been long term podcast listeners, thank you again and again and again for your feedback, your suppor, your comments. Sometimes there are comments that we need to take seriously, which we didn't wish to have to hear, but they're very helpful. And so please know that this has been a very special time for us to be with you. Now, let me begin by saying that as some of you know, the winter solstice is nearly upon us. It's not like I need to tell you that on December 21st, which will be the shortest day of the year in terms of sunlight here in Minneapolis, we're expecting to have just eight hours and 49 minutes of sunlight, with the sun rising at 7:46 a.m. and setting at 4:36 p.m. Despite the exciting promise of more sun ahead, the darkness we're living in right now can at times feel overwhelming.

Michael Osterholm: As we approach the solstice, I'm reminded of the powerful relationship between light and well-being. For many, this season marks a shift not just in the weather, but in the mood. The longer nights and the reduced sunlight can take a real toll, contributing to what we call Seasonal Affective Disorder, or SAD, a condition that affects millions of people worldwide. I'm one of them. I welcome every morning my 30 minutes before my bright light. While the darkness often is associated with the feelings of sadness or low energy. It serves as a reminder of how deeply our environment can influence our health. The solstice comes at the end of a year that has seen its fair share of both light and darkness. This year brought natural disasters, violent conflicts and widening political divides. It also saw breakthroughs in research and medicine, exciting new music and films, improvements in the quality of life, inspiration from the Olympics and moving acts of humanitarianism from the global moments of light to darkness to the personal moments in our own lives, we likely all experienced a range of moments that reflects both the light that uplifts us and the darkness that can sometimes pull us under. For those of you who are regular listeners, you know that I always include a segment in this podcast where I talk about the light and update you on how much sunlight we're getting here in Minneapolis, Minnesota, and how much our friends in Auckland, New Zealand are seen sharing these sunlight updates with you all.

Michael Osterholm: Brings me warmth and comfort, because I need the reminder that even when the world is dark, my friends across the world are enjoying their sunshine, and I know that the sun will always come back, even in the darkest times. Light will return. And in that regard, let me just share with you exactly what's happening here today on December 19th in Minneapolis and Saint Paul, sunrise this morning 7:47 a.m., sunset at 4:33 p.m. We now have 8 hours, 46 minutes and 17 seconds of sunlight. I do have to note that on December 14th, this past week was actually the last day in which the sun set at 4:31 p.m., which was the earliest of sets we're now seeing. Those afternoons get a bit brighter, but unfortunately the mornings get even darker until January 5th. And as you know, on December 21st, the two will match up to give us the shortest day of the year. We are about to turn the tide now in terms of our dear, dear friends and colleagues in Auckland, New Zealand, at the Occidental Belgian Beer House on Vulcan Lane today, your sun rises at 5:57 a.m., sunset at 8:39 p.m. you had a whopping 14 hours, 14 minutes and 27 seconds of sunlight. You're gaining about 10s a day. And two of those visitors to Auckland who are podcast listeners and share your pictures with us of you being at the Occidental Belgian Beer House. Keep them coming. We welcome it very much. Aren't they great people there? They really are. So welcome on board. Buckle up. Here we go.

Chris Dall: Mike. As I noted in the intro, COVID started with a bang in 2024 but is going out with something more like a whimper compared to where we have been. And I say that acknowledging that COVID, as we know, still causes severe disease and it causes deaths, and we can't forget that. But what are you seeing in the latest COVID data?

Michael Osterholm: Well, Chris, in keeping with the mood of that last comment you made, I want to say that I have tremendous respect for the virus SARS-CoV-2 and what it can do to us as humans. And so, no matter what it's doing at any given moment, I know that other moments could be much worse. And so, I always have this healthy respect for us versus this virus. And it's in that regard that I can say we're beginning to see early signs of increasing COVID activity. Wastewater levels are still considered low nationally, but are increasing in every region, with the exception of the northeast, which has remained steady over the past few weeks. Looking at the state level, six states are considered minimal, 15 low and ten in the District of Columbia are moderate, 12 are high and six, including Minnesota, are considered very high. Remember, wastewater data is a leading indicator, meaning it's a warning about what is likely to be coming. I also want to add that we're still trying to understand just what the actual levels mean in terms of case numbers. Could there in fact be situations where certain variants result in more shedding of virus into the waste system in such a way that it would mean apparently more cases, but in fact, it's a lower number, just more shedding of the virus. So, we don't really know that, but it surely gives us some sense that there is something beginning to happen. Now in terms of looking at the severe outcome issue. Let's start again with hospitalization. It's one of the most reliable indicators of COVID severity we have, especially when reporting is high.

Michael Osterholm: For the first week of December, 83.5% of all hospitals in the United States reported inpatient hospitalization data, and nearly 1% of the beds were occupied by COVID-19 patients, or around 6220 patients. To try to put this increase in number, which is now at 6220 patients hospitalized. Let me remind you where we've been. In January of 2022, we had 160,000 patients hospitalized, as opposed to 6200 in January 2021. We had 138,000. And finally in September of 2021, we had 103,000. So yes, we're in a much, much better place right now than we have been before in terms of weekly deaths, which is, you know, a lagging indicator in terms of COVID severity. We decreased again this week, November 16th, which is the most recent week for complete data. During that week, we lost 488 Americans to COVID-19. These 488 individuals were our loved ones. They're our family, our friends, our colleagues. So, it's nothing to celebrate. But I do want to note that this week marks the first time. Let me repeat that the first time in 22 weeks. The weekly deaths have been below 500. This is really, truly an indication that we are seeing less severe illness, with just 20% of US adults and 9.5% of kids being vaccinated. With the current vaccines, we have a very unprotected population, even among those who are previously ill. This past summer, as we now are beginning to see your waning immunity show up, and so I'm sure we're going to be seeing some increases in activity in the coming weeks.

Michael Osterholm: We'll have to wait and see how that shakes out over the holidays. The combination of mixing of a lot of people, along with waning immunity from an infection at least 4 or 5 months ago, as well as no vaccination. It'll be interesting to see what happens. And now, in terms of looking at how variants might play into that, we are seeing a shifting of the variant distribution XEC, the variant we've been talking about for several weeks has taken over as the predominant variant, making up about 44% of US cases. The variant KP3.1.1 now represents 39% of cases. Last episode we mentioned MC.1, a descendant of KP3.1.1, which has been growing in prevalence. And I realize for many of you, this kind of alphabet number soup may not mean a lot. But let me just remind you of what's happening here are these variants which may have increased ability to be transmitted or also cause more severe illness is something we track. I think the good news is that if we even look at these variants, including another one LP.8, which has drawn some attention globally over the past few weeks, we haven't seen any evidence that the variants that we're dealing with now are somehow have a growth advantage over the other variants, and therefore, it doesn't appear to me that at least that is going to be a cause of a significant wave of cases this winter. We'll have to wait and see. And we'll keep you updated.

Chris Dall: Mike, it also looks like flu activity is on the rise. What is the latest flu data telling us?

Michael Osterholm: That's right Chris, as we expect for this time of year, influenza activity is increasing and it's above the national baseline levels. The test positivity rate at clinical labs last week was about 5.1%, up from 3.5% the previous week. Outpatient visits for influenza like illness increased slightly from 3.2% to 3.4% last week. This means that last week, 3.4% of patients visits to a healthcare provider were due to respiratory illness, including a fever and a cough or sore throat. During previous flu seasons, this number peaks anywhere from 4.9% to 7.4% and takes place right around the new year. As far as hospitalizations are concerned, data shows about 2750 inpatient beds occupied by influenza patients, up from 2000, 2 weeks ago. But again, about half of what we're seeing for patients with COVID hospitalized at this time. Now, let me remind you that not every patient who comes into a clinic who has a fever, a cough and a sore throat has influenza. We are also seeing a number of other respiratory viruses, and in one case, even a bacteria that may be causing some of these illnesses. But it's a good indication of increasing flu activity, and it still gives us a good sense of what's happening with influenza. Nationally, influenza wastewater concentrations are considered low, but with three states California, Idaho and Oregon being rated as high, and New Mexico and Washington, D.C. being very high. I hesitate to draw any conclusions from this influenza wastewater data, though, because we don't know exactly what these concentrations are actually telling us.

Michael Osterholm: But they do give us a sense that there is increasing influenza activity. We just don't understand how much and what this means in terms of human illness. These are some of the research efforts were undertaken to better understand what wastewater is telling us. These concentrations do tell us how much Influenza A is in wastewater, but not its source. That being said, wastewater surveillance still is a powerful tool, but it's unclear how we interpret and act on these results. Stay tuned as we learn more about that. Adult flu vaccine coverage is right on track with typical years. With just under 40% of U.S. adults having received a vaccine by the end of November. Unfortunately, that is not the case for kids. 36.6% of kids have received a flu shot by November 30th, which is significantly lower than the 41 to 48% by the end of November the past five years. Let me remind you that the flu vaccine will not necessarily prevent you from getting influenza. However, the data are clear and compelling. If you do get influenza and you've been vaccinated, you will most likely experience a much less severe illness, reduce the risk of hospitalization and even deaths. So again, this is a vaccine worth getting. If we look at RSV activity, one of those other viruses for which we are very concerned with in terms of seasonal transmission, it's clear that the activity is increasing despite national wastewater levels being considered low. 14 states have either high or very high concentrations, and emergency department visits and hospitalizations are increasing, especially in children.

Michael Osterholm: Data shows that about 3450 inpatient beds are occupied by RSV patients, up from 2000, 2 weeks ago. So, you can see now we've got COVID and the number one spot for hospitalizations, RSV number two with influenza drawing up in the third spot. I do want to note, though, that by force, a preventive monoclonal antibody given to infants and kids was very effective in the 2023-2024 season to significantly reduce RSV. Severity in young children, and I expect it will continue to have an impact this year. Though the data is not yet available, during the 2023-24 RSV season, there was an overall 82% reduction in infant hospitalizations compared to infants who received no RSV intervention. Those are impressive numbers as far as vaccination coverage is concerned, about 32% of high-risk individuals 60 to 74 and 43% of people 75 and older have received their RSV vaccines. It's not too late to get these. I urge you, if you're in these age categories, please avail yourself to the vaccine and potentially avoid a hospitalization or even a worse outcome. The numbers I just shared with you are all in tracked with what we expect for these seasonal viruses, and I'm sure we'll continue to see increasing activity in the coming weeks. The best thing you can do right now is get vaccinated. If you haven't already done so, and encourage those around you to do the same.

Chris Dall: That brings us to avian flu. And Mike, we continue to see more H5N1 detections in dairy cattle in California, which leads the country with 645 detections. We've also had reports of a young boy in California who tested positive for Influenza A and is reported to have experienced fever and vomiting after drinking raw milk, along with suspected avian flu, in two cats in Los Angeles. Mike, what is going on in California and how do we make sense of what's happening with this virus?

Michael Osterholm: Well, Chris, I'm inclined to call a spade a spade here and say that the ongoing situation in California is literally a disaster. Yesterday afternoon, Governor Gavin Newsom of California actually agreed with that when he declared a state of emergency around the situation with what's happening with H5N1, particularly in the dairy herds of California. You know, as you've heard me say often on this podcast, that this is not rocket science. Some of the things we do are more complicated. Well, I think this is exactly that. These are the numbers as of yesterday, and I have to say yesterday, Wednesday, December 18th, because they're changing so quickly. If you listen to this podcast on the 19th to the 20th, it may be different. But if we look at what's happening with H5N1 and dairy herds, there are now 865 herds with infection documented around the country. However, 649 of those are in California for 75% of the total. Now, I do have to acknowledge that 56 herds in California have emerged from their quarantine, meaning that supposedly the virus has been eliminated from that herd. We have had one farm recently that had emerged from quarantine but then went back in, and it's unclear to me what's happening there. When I look at these numbers of herds, my first reaction was epidemiologist. Wow, that's a lot of data. We should really be able to lock in what's happening and why this transmission continues to occur. However, in conversations with USDA officials, I think it's a rather muddy picture, one that we're not clear on.

Michael Osterholm: And I feel at this point, I'm not sure we have a strategy in this country to really deal with eliminating this virus from these dairy herds. What do I mean? Well, they have identified the transfer of animals from one farm to another, which continues to occur in some locations in California. The lack of good biosecurity, meaning that people are moving from farm to farm. Same clothing, same vehicles, etc., in which, in fact, the virus could very well move with these individuals and in general, just a lack of really an understanding of how and why this virus continues to move. So, when we look at this in California, I've got to believe this is happening more often in other states also. And in that regard, the USDA finally, I think, has taken a strategy that's going to help us with what's called the National Milk Testing Strategy, which was launched December 6th. And it now requires all raw or unpasteurized milk samples nationwide to be collected and shared with USDA for testing. There were six states included in the initial order. And then just recently, a second order went out and now includes the states of Indiana, Maryland, Montana, New York, Ohio, Vermont, and Washington. With these 13 total states now being tested in more states to be added, we will get a sense. Is this virus much more widespread than we have right now in terms of surveillance data? I think the answer will be absolutely. It's going to be like that. So, the question is what is finally going to make a difference? Bovine vaccines for H5N1 are still a long ways off.

Michael Osterholm: I think we're going to find that with more testing of milk, we're going to be pressured to understand why we're seeing more dairies with infection in different states. This is a real challenge, and it's one that is a really a significant issue relative to the season. What do I mean with H5N1 doing well in the udder of these dairy cattle? We now know, of course, that that udder has receptor sites for both avian viruses and human viruses, so that should there be a seasonal flu virus circulating and workers are near the cattle, and they then transmit the virus to the cattle, which is yet unclear how that might happen. We could actually see a co-infection in the udder of a cow, which could result in a recombination or reassortment, where we bring together two different viruses that morph into one with different genes. At that point, that could very well be the next pandemic strain. Will it be? We have no idea. We don't really know. And I think that's the challenge we're faced with today. Now, let me shift a little bit and cover more about the virus itself. And then I'll talk about what's happening with human illness. What we've seen happen is the emergence of two different genotypes. Genotypes are like the fingerprint of the virus. You've heard us talk about clades. Clades are like the big family name. There's a single clade today that is infecting both cattle and domestic and migratory birds.

Michael Osterholm: This clade 2.3.4.4b you've heard me talk about often can be further characterized into what we call genotypes, like the real fingerprint. And what we've seen in the cattle so far has been largely B3.13. And this virus appears to be quite stable. We're not seeing it change. We're continuing to see it circulate through the cattle in such a way as to say, well, this one at least is not moving towards more of a human like virus. And I'll talk more about the human cases in a moment. Exposed to the cattle operations, we have a different genotype we're seeing in birds, both those in poultry operations as well as wild birds. And that genotype is D.1.1 and D.1.2. Now that one is a bit of a different situation where we are more concerned about how that virus may operate or what it might do. As we have discussed many times, the situation that is of most concern is when these viruses start changing both their hemagglutinin and neuraminidase. The hemagglutinin, the ability to attach to and enter a cell of an animal or a human, and the neuraminidase, which is in a sense the hand grenade of the virus, which blows up the cell once the virus has begun replicating in it so that it can escape and then be available to infect other cells, or for that matter, to be breathed out and potentially inhaled in and infect someone else. When we look at the D.1.1 and D.1.2, in general, these viruses have actually picked up a different neuraminidase than the one that was originally seen circulating with the virus.

Michael Osterholm: Now that puts a certain amount of pressure on the hemagglutinin to potentially change. Doesn't mean that it'll happen, but it surely could encourage that type of change. The previous situation where with B3.13 and the old neuraminidase, this virus appeared to be more stable. Now that may be changing and we don't know. Why is this important? Because this too could mark a movement of the virus towards one that is easier, more transmissible to and by humans or cause more severe illness. And the human illness is what I want to talk about now as we look at what is happening with these viruses. You may recall from our last podcast that there was an individual in British Columbia that was infected with H5N1 that turned out to be a D.1.1 genotype. That individual became severely ill and still is in the hospital, but fortunately recovering. That was a concern to see the very serious illness show up in this individual when all the previous cases had been much milder. Well, now we have a second case here in Louisiana. This individual is hospitalized at the current time. It was a person who was picked up through routine surveillance. However, this individual also had a backyard flock of birds for which they too were sick and dying at the time that this person had onset. This person's virus is also a D.1.1 genotype.

Michael Osterholm: So, the second human infection. Again, we don't know that these two make for what will happen with a third or a fourth or a fifth, but it's enough to keep us concerned. And so, at this point, all I can say is, is that things are changing. We're following them closely. If we take a look at human illnesses across the board, to date, there have been 61 confirmed total reported human cases in the United States of H5N1. Now, many of these were very mild and don't represent what we've typically seen in the past a virus that kills up to half of the people infected. When we look at it by state, 34 of the cases have occurred in California. 33 of those, 34 were associated with dairy herd, cattle or contact. One of the cases had a source unknown. The second highest number of cases in a state were in Colorado, where there was one case associated with a dairy herd, but nine associated with a poultry farm and culling operations. Literally an outbreak that occurred among workers culling specific barns. And then, of course, there's the case in Louisiana and the state of Washington also had an outbreak associated with human contact in bird and bird culling, where they have 11 cases. So, in short, if we look at overall cases, 37 of the 61 had dairy herd exposure, 21 had poultry farm exposure, one had another animal exposure, which was the Louisiana case. Two had no known exposures for the 61 cases.

Michael Osterholm: What will this look like in the future? Will it continue to be largely mild or to almost asymptomatic infections? We don't know. But the point is the virus is changing. Stay tuned. I think the world is paying a bit more attention to H5N1 since Governor Newsom declared the emergency state in California yesterday. I think this was really done to help provide additional resources to respond to the dairy herd situation. It's not because there has suddenly been a big increase in human cases, particularly those who may actually be seriously ill and potentially associated with the D.1.1 genotype. Let me just make two additional observations. One is we continue to see the situation come up with raw milk. There was a potential case in California recently with a child who developed influenza, for which it could not be confirmed it was H5N1. It was thought to be. And this child had consumed raw milk. We're going to see a number of cases in California of influenza associated with raw milk consumption, but not because of it necessarily at the rate of raw milk consumption in California, which is as high as it is. It's just likely by chance alone, someone could pick up a seasonal flu virus that has nothing to do with drinking raw milk, but the person did drink it. So, we're going to have to be cautious about interpreting additional new data coming out about infections. With raw milk consumption, it is possible that H5N1 might be transmitted via raw milk consumption, and for me is the reason why I think all raw milk should be avoided at all costs.

Michael Osterholm: I know this is counter to the popular beliefs that this is a healthier or safer product, when in fact it is not. I have worked up many outbreaks of raw milk associated illness in consumers and would just say, as I've said in previous podcasts, avoid this at all costs. One other piece of news, though, that I think is worth noting. The CDC has a paper being published this week that looks at an H5 vaccine in ferrets, which then were challenged with the current H5N1 virus, and the results were actually very favorable in that the ferrets still became infected. But there was a substantial decrease in the seriousness of the illness in the ferrets, meaning that in fact, a vaccine like this could very well be important should we see an H5N1 spillover into humans? Meaning that I might still get infected with H5, but if in fact I'm vaccinated, it would surely help protect me against serious illness. So, the bottom-line message is, Chris, this is a mess. It's just continuing on and on. In the dairy cattle. We continue to see migratory birds moving the H5N1 D.1.1 genotype virus around, and anyone who tells you they know what's happening here right now, be careful, because they probably also have a bridge to sell you. I can just tell you that surely demands are very watchful eye and I hope more can be done to eliminate this virus in both dairy herds and poultry operations.

Chris Dall: Now I want to turn to the mystery outbreak in the Democratic Republic of Congo. On December 5th, DRC officials announced they were investigating the cause of an outbreak of an unknown disease in a remote region of the country. And Mike, obviously in the wake of COVID, these types of reports alarm a lot of people. And DRC officials did not know what was causing this outbreak until just earlier this week, when they finally found an answer. What can you tell our listeners about this?

Michael Osterholm: Well, Chris, I can understand why many listeners are feeling nervous about seeing the reports of an unknown disease causing illness and death in the DRC. For many, it probably sparked some of the feelings of Deja vu from the earliest days of the COVID pandemic, when we all saw reports of a pneumonia cluster with an unknown cause in Wuhan, China. I have to say that people were surprised to hear me comment over the past several weeks that I wasn't that concerned about this. Now, why was that? You know, most people would say I probably border on the edge of alarmist. First of all, the initial reports out of the Panzi area of the DRC, which is in fact where this occurred, it's in the southwestern part of the country, a very remote area, two and a half day's drive from Kinshasa, the largest metropolitan area there, and over some of the most difficult roads you ever imagined, dirt roads that were almost impassable in many occasions. But what was notable to me was when we saw the first real data coming out in early December, reaching back to late October. There were these, yes, unexplained deaths. There were these unexplained illnesses, but they were not increasing over time. When I looked at the what we call the epidemiologic curve, the case numbers per week, they were pretty flat. If this was a new explosive virus that was emerging. We could have expected to see it go from 2 to 8 to 16 to 30 to 64 cases per week after week after week, and we didn't see that. So, to me, this was not an immediate virus of great concern. Well, what have we found out since that time? The African CDC, along with the DRC Ministry of Health, have now been in the Panzi area for several weeks and have really done a much more exhaustive review of potential case reports.

Michael Osterholm: And what they found was, in fact, that this was an area that had increased occurrence of malaria showing up on top of a severely malnourished population. Earlier this year, it was noted that, in fact, this area of DRC was experiencing severe food shortages, with malnutrition as a common part of the health concerns. Well, you add in malaria to that and suddenly it becomes clear that what could happen. There have been 592 cases now recognized, 143 of these died. Most of the ones who did die were children, which again, is not unexpected. So, it's a tragic situation. It's horrible, but it's also one that is not going to cause an international crisis. And I think that for me, I was disappointed to see the response of the news media and some public health agencies early on declaring this a thing called disease X. This is a term we used for an unknown, unrecognized disease that suddenly shows up. Now that means that it's one that every other laboratory test that we would normally apply has been used and found to be negative. So, what this is telling us is that this is a brand-new disease. It's not just an old disease for which we've missed. And in this case, this never had any element to me of disease X. And so, for all of you in the media, for all of you who are listening to this, please don't use disease X until you have reason to think this is a brand-new virus and this is what this could do.

Chris Dall: It's time now for our ID query. And our question this week is from Linden, who wrote. I noticed that you and other medical professionals say that vaccines approved by the FDA or CDC are, quote, safe and effective, unquote, but do not discuss what safe and effective mean. As a strong believer in user of vaccines, I find that most laypeople I talk to have no idea of what is meant by safe and effective, and it causes confusion when they still get an infection or have a side effect or reaction. Mike, this is a great question that gets to the heart of a discussion and debate about vaccines that we could hear during the confirmation hearings for Robert F. Kennedy to be secretary of the Department of Health and Human Services, and over the next few years, if he is indeed confirmed. What can you tell Linden?

Michael Osterholm: Thank you, Linden, for your very important question. I really think you hit the nail on the head. Many people, including those who support vaccines, don't necessarily always have a great understanding of what it means for a vaccine to be safe and effective, which can make it difficult to navigate conversations about these issues. I promise you; we will always be as transparent as possible here so that we can share with you what we know and what we don't know. And how do we address the issue of vaccine safety going forward in a way that is most easily understood by the general public? This is not a gray area for me. It's not something that scientists have yet to reach consensus about. I suspect that very few people who believe otherwise would choose to listen to our podcast. But many of you may have people in your lives who feel differently about this topic than you do. So, I want to address this question to help you better understand this issue so that you too can advocate for vaccines while talking with friends and family. First of all, today I'm going to focus my initial answer on the issue of safety, and we will come back and revisit both safety and effectiveness in future podcasts so that you can explore these issues with us. Let me start by saying I want to be clear that a vaccine being safe and effective does not mean that it is entirely without some risk to the person receiving the vaccines.

Michael Osterholm: Vaccines are widely accepted as safe can still cause very rare complications. It is essential that we properly communicate this to the public in order to reestablish trust in public health, we need to be transparent about these risks while also assuring that the general public understands that the risks that occur due to infection are much greater. Let me give you an example. If we look at the MMR vaccine, it's one that's often cited as potentially a risk to individuals. One possible complication associated with the measles vaccine is a condition called immune thrombocytopenic purpura, ITP. This is a disorder that decreases the body's ability to stop bleeding. Studies have found that in the six weeks following vaccination, the incidence of ITP is about 1 in 40,000 children. In fact, the risk of ITP is 13.2 times higher after measles infection. So yes, it can occur among a vaccine. However, the risk of your child having ITP is so, so much higher with the disease itself. The same thing is true with MMR vaccine and encephalitis, an inflammation of the brain, which it develops in about 1 to 2 children per million that receive the vaccine. Encephalitis is a serious medical condition that can be fatal, but also much more common following infection than vaccination.

Michael Osterholm: As I just pointed out, 1 to 2 children per million. Let me repeat that 1 to 2 children per million can experience this as a result of vaccination, whereas 1 to 3 children infected with measles per thousand will develop primary measles encephalitis, and an additional 1 in 1000 will develop an acute post-infectious encephalitis within 30 days of the infection. This means that the risk of encephalitis from measles infection is 2000 times greater than the risk of contracting it from the vaccine. Now, I've often heard people say, well, but any risk is too great. Let me use an analogy I hope hits home a little bit. Imagine you're driving along one day in your car. Your seat belts on, and all of a sudden, you're in an accident. Horrible situation. But even worse is your seat belt has jammed, you can't get it off, and your car starts on fire and tragically, you burn to death. People would say we should get rid of seat belts. They're dangerous. That's why John Doe is dead. Well, however, if we look at how many people's lives were saved because of seat belts, then it's a risk relationship issue that says, no, you should wear your seat belt. The risk is much, much higher. Not wearing your seat belt than it is there safe relative to what they are supposed to accomplish.

Michael Osterholm: But in fact, they're not perfect. And this is true with what we see with vaccines. And so, I want to just point out to you that when we talk about safe, we're not trying to hide the potential impact that a vaccine can have. But it is very, very rare. Now, why do we want a vaccine that's perfectly safe, meaning never experiencing any adverse outcomes because one, we're giving it to a healthy individual. Two, we're giving it to kids. That by itself should be a reason to get the vaccine reactions even lower and lower and lower at the same time. Look at the other side of the scale today when you are being treated for a cancer. You use very toxic drugs, drugs that basically can make you very sick. They can cause other organ involvement, unintended. And yet we take those because the risk of dying from your cancer is so great. You are sick. You're older typically. And so, you're willing to accept that risk of saying, I know, you know, this could be really bad for me, but it's a better way to go than the cancer. And so, we work between those two extremes, one where there should never be an adverse event to one where we expect adverse events. But in the big picture, they're worth it. So, what we will do over the days ahead in future podcasts is explore more and more.

Michael Osterholm: What do we mean when we're talking about safety and effectiveness? I just want to add that when we talk about the benefits of vaccines clearly outweighing the risk, that does not mean that we stop prioritizing vaccine safety as an area where we can improve our current vaccines are clearly safe, as I've defined that. Not perfect, but can we always strive to do better? One approach that I think is worth considering was described in a 2004 paper by Solomon, Moulton and Housley, which we will link to our episode notes. The authors proposed creating an independent vaccine safety board similar to the National Transportation Safety Board, which would function separately from government organizations and private vaccine manufacturers to provide oversight on vaccine safety in the US. This type of group could help restore vaccine confidence among those who have grown skeptical of government organizations, and it could also help detect potential safety concerns with new and existing vaccines, so we can do more. I think this discussion right now is really healthy about vaccine safety, but please do not be confused by what you're hearing out of the likes of RFK Jr. and his colleagues there. They're talking about extremely, extremely exaggerated risk with Vaccines without any consideration of the benefits. And that discussion is not helpful. It's scary, and it's going to be responsible for kids not getting vaccinated and eventually kids getting infected with vaccine preventable diseases and dying.

Michael Osterholm: What we're talking about here, how can we take a good system and make it even better? And let me just point out that for me, my entire career has been marked, you might say, by vaccine safety issues. In 1976, I was an intern at the Minnesota Department of Health, working with other interns there, in which we as a group were the ones that first uncovered the risk of Guillain-Barre syndrome with the 1976 swine flu vaccine campaign. And it was because of our work that ultimately resulted in the program being shut down and abandoned, of which then subsequently, we were able to show that there was an increased risk of Guillain-Barre syndrome with the swine flu vaccine administration. Now, swine flu never showed up, so there was no benefit from the vaccine relative to what it did for public health. And it really helped shape me to understand, keep an open mind, make sure that you just don't dismiss a potential challenge to vaccine safety, because that's what we do. We don't. And I feel very confident that as a nation, we are already doing a great job with vaccine safety. But I know we can even do better. And we'll be talking about that more over the days ahead with this podcast.

Chris Dall: Well, Mike, it's fitting that you use the MMR vaccine as an example because the theory that childhood vaccines, the MMR vaccine in particular, are behind the increase in autism cases we've seen over the past 30 years, is one that has been pushed by RFK Jr. and his allies and has really fueled the anti-vaccine movement in this country and actually around the world. And even though this conspiracy has been thoroughly debunked, the president elect brought it up in a recent interview as something that needs to be studied. Mike, can you just remind our listeners how this all got started and how much this issue has been studied?

Michael Osterholm: Well, Chris, I'm going to use an analogy here for those who know me well, know that's my life story, using analogies. I don't understand things if they're too complicated. Let's just say I've lost my car keys. I'm trying to find them. So, I look in my junk drawer. I don't see them there. I decide to look again. Take everything out. Still not in there. I open the drawer and look again. Still not there. Maybe I'll look one more time, but still not in the drawer. That's how I feel every time this autism and vaccine conversation comes up. It may have been reasonable to look in the drawer the first time, but it's absolutely ridiculous to keep looking at the same place when we know it's not there. At this point, it's wasting time and money and representing something that could be spent actually improving the lives of autistic individuals and their families. There's been a lot of ink spilled on this topic, but the bottom line is, time and time again. Researchers have found no link between autism and vaccines, and these studies are extensive. The myth was accelerated by a study that was published in The Lancet in 1998 by Andrew Wakefield and colleagues. The study was conducted in a group of just 12 children that received the MMR vaccine and reported developmental delays. In addition to the small sample size, the study was full of methodological and ethical problems. The study has been thoroughly debunked and the paper has since been retracted from the journal. Additionally, well qualified researchers and organizations like the CDC, the Cochrane Library, and the American Academy of Pediatrics have all concluded that there is absolutely no causal relationship between autism and immunization.

Michael Osterholm: And if you really want to get a good understanding of this, I urge you to read Doctor Peter Hotez book about his daughter, Rachel, and the fact that why she has autism had nothing to do with her vaccines. Besides the Wakefield study, proponents of the myth that autism is caused by childhood vaccines point to a correlation between the increasing rates of autism and the complex modern schedule of vaccines and early childhood. The media, even mainstream sources like the National Geographic, have played into this narrative with misleading and inflammatory articles that gain a great deal of public attention as clickbait. The changing epidemiology of autism is far more complicated than a simple correlation with the immunization schedule. Experienced researchers have far more credible data to explain these rising rates. First is a rise in the number of diagnoses as a result of improved awareness, screening programs and special education services. This has been especially apparent for groups where autism was traditionally under-recognized, such as in girls and women, and in racial and ethnic minorities. Next is the change in the diagnostic criteria for autism. Changes to the Diagnostic and Statistical Manual of Mental Disorders, or DSM, which clinicians use to diagnose autism spectrum disorder and improved provider training shifted the way we characterize autism amidst the broader landscape of intellectual and developmental disabilities. Many researchers hypothesize that increased diagnoses do not account for the entirety of this phenomenon, and that there may be a modest increase in the actual incidence of autism in the population.

Michael Osterholm: Some credible hypotheses include a rising rate of births in older parents, particularly older fathers, which has been linked to autism. Additionally, there has been a link between prematurity and autism with modern NICU’s and treatment methods. More children are surviving prematurity more than any years in the past. As you can tell, this is a complex issue, but one that often mixes credible evidence with that which is misguided at best and dips into the conspiratorial. The autism and vaccine issues has been referred to as the most damaging medical hoax of the 21st century. It is incredibly frustrating to hear this misinformation touted not just by fringe individuals or social media, but by key leaders in this nation's government. I hope that our listeners now have some of the talking points to address these falsehoods when they hear them from their friends, families, and workplaces. At the end of the day, this prolific lie hurts people with disabilities and their families the most. They never asked to be the target of an anti-science campaign. I hope that with more people fighting for the truth on this issue, we can someday put this myth to rest. And in the meantime, please be assured there have been ample studies, well done, studies that support the fact that there is no relationship between vaccination and autism. So, if you know someone who's on the fence about getting their child vaccinated, please help them understand. The real risk of serious outcomes is all about not getting the vaccine, not about getting the vaccine.

Chris Dall: Mike, we discussed some of president elect Trump's other nominees for health-related agencies in our last episode. Is there anything else you want to say on that topic at this time?

Michael Osterholm: Well, I think one thing is playing out, as I had indicated in previous podcasts, we're following carefully is that while we will focus and appropriately so on those nominations that have been made to head these organizations, it really is often at two and three levels below the senior leadership that often drive decisions day in and day out about what will or won't be done, or what priority certain programs will take, or what strategies might be used. And this is playing out exactly as I indicated might happen in the Department of Health and Human Services. We've learned this past week that Mr. Siri, a lawyer who is the person responsible for filing the petition to end polio vaccine distribution, is also vetting all the senior candidates for potential positions at HHS. Now, imagine if you were to apply for a job at HHS right now and you're interviewed by Mr. Siri. Do you think that he would be sympathetic to your pro-vaccine views? He is someone that has right now had more influence than RFK Jr. has had relative to the day to day vetting process. So, this is what I talked about before. We will continue to follow very closely not just who is the head of the organization, who gets confirmed, who doesn't get confirmed, but also who's number two, three, four, five. What influence do they have in the overall program activities? And that's what we'll keep you updated on. And finally, let me also just say, as I pointed out before, you know, everything is transactional right now in Washington, D.C. I don't know what will happen with the confirmation hearings for Mr. Kennedy. Right now, we're hearing of more and more people who are very concerned about his various positions.

Michael Osterholm: You know, I've been commenting in the media that I wish I knew what his positions were. And earlier this week, I was on CNN and asked about, you know, what would be the one question I'd want to ask Mr. Kennedy if I could? And I said, well, just remember, when someone tries to tell you who they are, listen to them, believe them. Okay, Mr. Kennedy, I can't do that because I don't know what he believes. He's like nailing Jell-O to the wall. He has said so many different things that are so contradictory, and he's one of the few people that feels confident in saying, I didn't say something when it's actually on tape. You know, when you have it and yet he denies that he said it. So, at this point, we're still really in a wait and see mode to see what happens with confirmation. We're in a wait and see mode to see who is actually brought into these different agencies, whether it be CDC, NIH, FDA, etc. So, hold on. You know, we're not giving up. We're not we're not slowing down, but we're basically responding and reacting reasonably, I think, to what is the current new news. And we will keep you posted on every podcast. And I expect probably shortly after the inauguration, we're going to have a lot more information to be able to share with you what's happening with these new additional appointments and what that means for us at the local level, at the state level, you know, how can you be more involved in responding to what might be coming out of the current public health leadership, if you call it that, with regard to this administration?

Chris Dall: And now it's time for this week in public health history. Mike, who are we celebrating this week?

Michael Osterholm: Well, Chris, this week we're actually featuring a what instead of who for Public Health History. During the Nigerian Civil War of the late 1960s, the people of Biafra, a newly independent nation in the southeast of the country, were facing brutal conditions. There was a blockade surrounding the territory, limiting access to food and resources and causing mass starvation in addition to the wounds of war. A group of volunteer doctors with the French Red Cross gained access to the region to provide health care and establish feeding centers. These volunteers and some accompanying journalists, witnessed horrible atrocities against civilians and spoke out against both the Nigerian government and the Red Cross for their disregard for human rights. This prompted the volunteers to form a new organization that would prioritize the welfare of individuals and speak out against the political religious powers to be. On December 22nd, 1971, the organization Médecins Sans Frontieres, or known as MSF or Doctors Without Borders, was formed. Since its founding, MSF has responded to emergencies caused by natural disasters and political conflict, cared for refugees and migrants, provided primary care and resource limited settings, and launched widespread vaccination campaigns.

Michael Osterholm: The organization is a prominent advocate on the global stage for protecting humanitarian law and promoting health care as a human right, especially for ostracized groups. Their work has expanded to now more than 70 countries, and was recognized with the Nobel Peace Prize in 1999. While their activities have not been without controversy, it is evident that their mission and impact have saved countless lives across the globe, but their service has not been without sacrifice. MSF staff are willing to enter some of the most dangerous situations to provide care and attention to those in need. MSF staff, along with other aid workers, are subjected to targeted violence despite their legal protection under humanitarian law. Almost 100 aid workers with MSF have lost their lives since its inception. So, on this 53rd anniversary of this organization's founding, I hope we can recognize that many aid workers and civilians have lost their lives due to natural and man-made emergencies. Let their legacy serve as an example of the importance of kindness and service in our own lives. We must never forget what these brave people do to make this a better world.

Chris Dall: And now, before we wrap up this final episode of 2024, I want to take a moment for just a little bit of business as we near the end of the year. I want to thank our listeners who help make this podcast possible here at CIDRAP. It is important to us that we can bring you the Osterholm Update without advertisements or a paywall, and we rely on donations from listeners like you to be able to do that and keep this podcast going. A lot of behind-the-scenes staff time goes into this podcast to ensure that you get the most timely, accurate and insightful information possible. And with public health funding so uncertain in the years ahead, we need your support now more than ever before to ensure that we can keep doing what we love sharing information about infectious diseases and public health with you. If you'd like to make a donation or sign up to become a monthly supporter of CIDRAP, please visit CIDRAP.edu/support. You can find a link in our show notes. Mike, is there anything you'd like to add?

Michael Osterholm: Well, as the staff at CIDRAP know, I hate to ask for money. I don't find that at all a comfortable position, but I do want to say at CIDRAP we are committed to making all of what we offer to the world free of charge. Absolutely no paywalls. I am committed to that. Everyone should have access to this kind of information. And today I can tell you with regard to my own needs for information, I have so many paywalls I have to pay into in order to get the information. So, your support helps us keep that paywall promise, which we will never violate. We will always make everything we do for all of you free of charge. And so, your support is really appreciated. Thank you very, very much. I can say that with heartfelt feelings. We appreciate you so, so much and I hope that we will always be there for you when you need us and how you need us.

Chris Dall: And just one other bit of housekeeping here, a reminder that we're taking an extra week off over the holidays. So, the next episode you'll hear from us will be three weeks from today on January 9th. We will then resume our every other week schedule. Mike, what are your take home messages for today?

Michael Osterholm: Well, Chris, first of all, we're still in a wait and see mode regarding the Trump administration public health agenda. Not much has been disclosed, but what we have seen, obviously, with those who have been nominated to head up government agencies, there's still lots of concern. Will RFK Jr. get confirmed. Don't know who will serve as their senior staff in the different agencies. What does that mean? How do we respond? We are watching this very closely and we will stay on top of it and share that information with you. The second point is that vaccine safety and effectiveness are front and center right now as a public health priority. We in this podcast will continue to cover more on this topic in future podcasts. We will be as transparent and as open as we can be. Vaccines from a benefit standpoint far, far outweigh anything that we can talk about with cost. Now, having said that, if you are one of those very rare cases where someone has had an adverse vaccine event, we recognize how important it is that you be fully compensated for that event, and we will also advocate for that. Finally, the respiratory season is starting while we still see more activity from at least a disease severity standpoint with COVID and then RSV and then influenza. All three of them could be increasing in the near future, or even 1 or 2 of them. So now is the time to get your doses of vaccine. Really, I can't emphasize that enough, particularly for those who are older or have underlying immune conditions that might put you at higher risk for serious illness. Now is the time. You don't want to have to think about getting your flu shot. The day that you're hospitalized for influenza won't work much.

Chris Dall: And, Mike, since it's that time of year, I think I know what our closing is.

Michael Osterholm: Well, Chris, you probably do, but, Chris, this is an oldie but goodie. Many of you may recall that one of the more human moments in this entire pandemic for me, took place on December 25th of 2020. That first Christmas, when it was such a challenging situation, our families were distant from each other, and I had the opportunity to share with my grandkids and my kids via zoom a reading of the Polar Express. I had read this book every Christmas for my kids, dating back to its publication in the 1980s, and I still have not missed reading of The Polar Express each year, and in the process have gotten to know Chris Van Allsburg, the incredible author and illustrator of that book, and his wonderful wife, Lisa. This book has come to mean so much to me. So, for today, we're going to share with you a repeat episode. This was the original December 25th, 2020 episode that we did when we were all distant apart, reminding us of where we've been, where we're at and where we're going, and that hopefully all of you can always hear the bells. That is my wish for all of you. I want to also just take this last moment here to say thank you again for your support this past year. It's been remarkable. One heck of a ride and it's been challenging, but also one incredibly supportive ride. And so, thank you very, very much. On behalf of all the entire podcast team here, I want to thank you to the podcast family, to those who are the occasional listeners. It's been a very special situation. Please know you are a Christmas gift to us every day of the year and we never take that for granted. So be kind. Know the days are going to start getting brighter again. And also, never forget that we are here for each other and that is one of the greatest gifts of all. Merry Christmas and Happy New Year. Happy holidays. We appreciate you so much.

Grandchild: Grandpa, can you read us the Polar Express?

Michael Osterholm: Written and illustrated by Chris Van Allsburg. On Christmas Eve, many years ago, I lay quietly in my bed. I did not rustle the sheets. I breathed slowly and silently. I was listening for a sound; a sound a friend had told me I'd never hear. The ringing bells of Santa's sleigh. There is no Santa, my friend had insisted, but I knew he was wrong. Late that night I did hear sounds, though not of ringing bells. From outside came the sound of hissing steam and squeaking metal. I looked through my window and saw a train standing perfectly still in front of my house. It was wrapped in an apron of steam. Snowflakes fell lightly around it. A conductor stood at the open door of one of the cars. He took a large pocket watch from his vest, then looked up at my window. I put on my slippers and robe. I tiptoed downstairs and out the door. All aboard! The conductor cried out. I ran up to him. Well, he said, are you coming? Where? I asked. Why? To the North Pole, of course, was his answer. This is the Polar Express. I took his outstretched hand and he pulled me aboard. The train was filled with other children, all in their pajamas and nightgowns. We sang Christmas carols and ate candies with nougat centers as white as snow. We drank hot cocoa as thick and rich as melted chocolate bars. Outside, the lights of towns and villages flickered in the distance as the Polar Express raced northward. Soon there was no more lights to be seen.

Michael Osterholm: We traveled through cold, dark forest where lean wolves roamed and white-tailed rabbits hid from our train as it thundered through the quiet wilderness. We climbed mountains so high it seemed as if we would scrape the moon. But the polar express never slowed down. Faster and faster, we ran along, rolling over peaks and through valleys like a car on a roller coaster. The mountains turned into hills. The hills to snow covered plains. We crossed a barren desert of ice. The great polar ice cap. Lights appeared in the distance. They looked like the lights of a strange ocean liner sailing on a frozen sea. There, said the conductor, is the North Pole. The North Pole. It was a huge city, standing alone at the top of the world, filled with factories where every Christmas toy was made. At first, we saw no elves. They are gathering at the center of the city. The conductor told us. That is where Santa will give the first gift of Christmas. Who receives the first gift? We all asked. The conductor answered. He will choose one of you. Look! Shouted one of the children. The elves. Outside we saw hundreds of elves. As our train drew closer to the center of the North Pole, we slowed to a crawl. So crowded were the streets with Santa's helpers. When the Polar Express could go no further, we stopped and the conductor led us outside, repressed through the crowd to the edge of a large open circle. In front of us stood Santa's sleigh.

Michael Osterholm: The reindeer were excited. They pranced and paced, wringing the silver sleigh bells that hung from their harness. It was a magical sound, like nothing had ever heard. Across the circle, the elves moved apart and Santa Claus appeared. The elves cheered wildly. He marched over to us and pointed to me and said, let's have this fellow here. He jumped into his sleigh. The conductor handed me up. I sat on Santa's knee and he asked, now, what would you like for Christmas? I knew that I could have any gift I could imagine, but the thing that I wanted most for Christmas was not inside Santa's giant bag. What I wanted more than anything was one silver bell from Santa's sleigh. When I asked, Santa smiled. Then he gave me a hug and told an elf to cut a bell from a reindeer’s harness. The elf tossed it up to Santa. He stood holding the bell high above him and called out, oh, the first gift of Christmas! A clock struck midnight as the elves roared their approval. Santa handed the bell to me and I put it in my bathrobe pocket. The conductor helped me down from the sleigh. Santa shouted out the reindeer's names and cracked his whip. His team charged forward and climbed into the air. Santa circled once above us, then disappeared into the cold, dark polar sky. As soon as we were back inside the Polar Express, the other children asked to see the bell. I reached into my pocket, but the only thing I felt was a hole. I had lost the silver bell from Santa Claus's sleigh.

Michael Osterholm: Let's hurry outside and look for it, one of the children said. But the train gave a sudden lurch and started moving. We were on our way home. It broke my heart to lose the bell. When the train reached my house, I sadly left the other children. I stood at my doorway and waved goodbye. The conductor said something from the moving train, but I couldn't hear him. What? I yelled out. He cupped his hands around his mouth. Merry Christmas, he shouted. The Polar Express let out a loud blast from its whistle and sped away. On Christmas morning, my little sister Sarah and I opened our presents. When it looked as if everything had been unwrapped, Sarah found one last small box behind the tree. It had my name on it. Inside was the silver bell. There was a note. Found this on the seat of my sleigh. Fix that hole in your pocket. Signed, Mr. C. I shook the bell. It made the most beautiful sound my sister and I had ever heard. But my mother said. Oh, that's too bad. Yes, said my father, it's broken. When I'd shaken the bell, my parents had not heard a sound. At one time most of my friends could hear the bell, but as years passed, it fell silent for all of them. Even Sarah found one Christmas that she could no longer hear its sweet sound. Though I've grown old, the bell still rings for me, as it does for all who truly believe. The end.

Grandchild: Merry Christmas grandpa!

Chris Dall: Thanks for listening to the latest episode of the Osterholm Update. If you enjoy 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.edu. This podcast is supported in part by you, our listeners. If you would like to donate, please go to CIDRAP.edu/support. The Osterholm Update is produced by Sydney Redepenning and Elise Holmes. Our researchers are Cory Anderson, Angela Ulrich, Meredith Arpey, Clare Stoddart, and Leah Moat.