Michael Dunne: Confronting the Antibiotic Resistance Crisis

Harlan Krumholz: Welcome to Health & Veritas. I’m Harlan Krumholz.‌

Howard Forman: And I’m Howie Forman. We’re physicians and professors at Yale University. We’re trying to get closer to the truth about health and healthcare. Our guest today is Dr. Michael Dunne, but first, we always check in on current or hot topics in health and healthcare. And today, Harlan, you’re in the news right now because of exactly what we talked about last week. And just to start off and remind our listeners about, that you published a very important pre-print and a manuscript with Akiko Iwasaki, and it’s controversial. Do you want to just mention a little about why it’s controversial? Well,‌

Harlan Krumholz: Thanks, Howie. This grows out of the experience I’ve had over the last week or so because I’ve been getting a lot of questions lately on whether we should have pre-printed our recent study. Remember, this is a study, like you said, on this chronic debilitating syndrome that some people are reporting after having been vaccinated with the COVID vaccine. And what am I doing in this area? It’s just that, like I said last week, I got involved in COVID research and published a ton of stuff during COVID, and I met Akiko, and we encountered people who were suffering what seemed to be a syndrome after infection, what became to be known as “long COVID.” And we started working together on that and then we met a bunch of people who were also reporting a syndrome that followed vaccination, and we thought if we’re willing to study long COVID, we should be willing to study that.‌

And we have researched it, and Akiko’s got a world-class lab, and we’d like to think of ourselves as a world-class clinical research operation. And we were able to pull together people, characterize their symptoms, and then to do deep immune phenotyping to understand whether or not there were signatures, what we call immune signatures, patterns, profiles of the way in which their immune systems were working that distinguished people who were reporting this condition. And we finished the study and have submitted it to a journal.‌

But we’ve actually done another study before this looking at what people were reporting, just simply describing the experience of individuals who were reporting this and it was impossible to publish. We had submitted it to Vaccine, which is a pretty good journal on—guess what it’s on, Howie?‌

Howard Forman: I’m going to guess it’s “vaccines,” but you never know.‌

Harlan Krumholz: It’s the vaccines. A-plus, it’s on vaccines. But it’s a good journal. They went through two rounds of review. When you go through two rounds of review with a journal, you’re pretty certain of getting in. We were able to address everything that they asked, and then suddenly—and I’ll put it like this—they lost their nerve. They just basically wrote us back and said, “Not interested,” without an explanation or clarity. Then they said, “You can try our open-access journal, Vaccine X.” Vaccine X barely has an impact factor. It’s a place that I wouldn’t normally be submitting to, but we had this thing and it seemed like we wanted to get it out and we would submit it to peer review. Like they would be lucky to get an Iwasaki article. They didn’t even review it. They basically said, “Nope, not interested.” You could tell this was a hot potato. And so that was our prior experience.‌

This one is really under review, but we didn’t know how long it would take and information was already leaking about this study. We had, by the way, had a town hall with the participants in the study and explained to them what we were finding because we respect people in our study, and we want to share with them what the study finds. And we’re very participant-centric in our approach. And yet, that information leaked out from that meeting. And there were prominent people like Alex Berenson and others who were writing about this on Substack. So it was already getting out into the ether. And then so the question for us is, should we pre-print it? Now we know it’s early stage science, it’s got limitations. We don’t want anyone to act on it, but we think it can be an opportunity for us to show it out for people, faster dissemination of research, and to combat misinformation, gossip, rumor about this research.‌

But we did realize that in this politically charged area, that people might want to take this in a direction that served their purposes. And I believed in the role of pre-prints and science for a long time. I’m in disclosure, I’m a co-founder of medRxiv. I’ve said that before. But we knew that if we came out, there would likely be some pushback. I don’t think we anticipated it to be quite like this. What’s happened in the last week is that anything from people who are totally anti-vax taking this and totally misconstruing it, distorting it.‌

For example, people writing and saying, “Yale scientists just proved COVID vaccines cause AIDS.” There were a whole range of anti-vaxxers who attacked us. And then on the other side, academics started coming after us and saying, “That was irresponsible. It should have gone through peer review. And we’re trying to say that I think this mixed outcry would have occurred even if it had gone through peer review. And for us, it was an opportunity to archive on the web what we found, to be able to say, this is what I call the director’s cut. It’s for us to be able to say, here’s how we interpreted it, here’s what we think. And anyone can look at it. Anyone who hears something like Yale scientists have proven something crazy, can actually go back to this pre-print because it’s open-access, anyone in the world can read it, no fee, no firewall, and see what exactly did we say.‌

And in it, we’re very circumspect. We say this is providing early clues, this is providing a direction for future research. This doesn’t prove anything yet. We shouldn’t be afraid to follow the science even if the science is inconvenient. We shouldn’t be afraid to say the truth as we see it. We shouldn’t be afraid to follow this line of work when we know people are suffering and we don’t know why and they’re being dismissed broadly otherwise.‌

Howard Forman: And importantly, because you’ve said it, so I’m just going to state it again, you and Akiko Iwasaki are pro-COVID vaccine at this point, at least for yourselves. So it’s not like you have done this research and now are trying to warn people off of getting vaccinated.‌

Harlan Krumholz: We’re not on a crusade against vaccines. We’re on a crusade for science and knowledge.‌

Howard Forman: For our listeners, you have weathered this extremely well. There are people who would fold under this pressure. It is not—this is not tame.‌

Harlan Krumholz: Well, how do you know I didn’t fold?‌

Howard Forman: Yep. Not yet.‌

Harlan Krumholz: No, no. Look, all I know is that we ought to be doing the right thing the best we can. And you’re damned if you do and you’re damned if you don’t.‌

Howard Forman: Right.‌

Harlan Krumholz: I think if you try to protect the public from knowledge because you’re worried that people will overreact to it or not react well to it, where does that lead you? Where does that end? And who’s going to make the decisions on what the public should be protected from?‌

Howard Forman: Thank you.‌

Harlan Krumholz: Thanks. Hey, let’s get onto our guest, who’s also an expert in infectious disease. We get plenty of questions for him.‌

Howard Forman: Dr. Michael Dunne is a biopharmaceutical executive, trained as an infectious disease physician and has vast experience and expertise in anti-infective drug development. Until recently, he served as Chief Medical Officer and Head of Development at the Bill and Melinda Gates Medical Research Institute, where he oversees clinical trials. Prior to that, Dr. Dunne founded two biotech companies, Iterum Therapeutics, and he remains on the board of that, and Durata Therapeutics, where he led the development and approval of the antibiotics sulopenem and dalbavancin. He has also held leadership positions at Actavis and Pfizer, where he was responsible for the development of infectious disease compounds there.‌

Dr. Dunne currently serves on the Board of Directors at Iterum Therapeutics and on the editorial review board of Clinical Infectious Diseases journal, and he’s a Fellow of the Infectious Diseases Society of America. He received his bachelor’s degree in economics from Northwestern and his medical degree from SUNY Downstate, or SUNY New York Health Science Center at Brooklyn, before completing internal medicine residency and fellowships in pulmonary medicine and infectious diseases at Yale University, at Yale New Haven Hospital here.‌

So first of all, I want to welcome you to the podcast. Thank you very much for joining us on this. I go back a little over a year ago, I think, and we first started talking about controversies about how do we innovate for new antimicrobials, and I’d love to hear you lay out the challenges that you see in society between the fact that society does consume antibiotics in large numbers, and it’s very common that patients are demanding antibiotics, physicians are prescribing antibiotics, and the fact that, that behavioral pattern leads to more antimicrobial resistance and the ultimate shortage of drugs that can overcome that. So if you could just help us understand that a little bit more.‌

Michael Dunne: Yeah. First, thank you for having me. Pleasure to be here. This is a great topic, important to me overall. I’m happy to chat about it. Yeah, we have a challenge in development of antibiotics. I’m going to say specifically antibacterial agents for a second. The challenge is that unlike other therapeutic areas, the more we use the antibiotics, the more we select for the problems that make it/them not useful over time. That is very unusual. I think as I look back over 30 years of doing this, I’m getting concerned that we’re not in a good place on how to manage this cycle of basically resistance that’s developed because of appropriate use, not inappropriate but of appropriate use over time. And how do we figure that out? And I don’t think we have a good balance right now between the use of established antibiotics, which is incredibly important. Stewardship, we got to do that. But also leaving enough space to incentivize new antibiotics to replace the older antibiotics that we know, at some point, are not going to be useful.‌

I think the incentives for developing new antibiotics are lacking, and the process by which we are managing the antibiotics that we have, many of which come from the 1950s and 1970, older antibiotics, the process by which we’re managing those things wisely is also causing challenges in incentivizing others to come in and develop new antibiotics.‌

Howard Forman: Do you have a preferred incentive structure set up? Because what prompted me on this topic was, again, over a year ago, there was a bill that was proposed to create a subscription plan for these novel antibiotics, and our colleagues at Emory were absolutely in direct opposition to our colleagues at Yale about whether that was a correct approach. Do you have an opinion about what might be a good incentive structure?‌

Michael Dunne: Yeah. Okay. Thanks for bringing that up, yes. So let me just step back a little bit. So this problem of incentives to bring antibiotics for it is important, and it’s important from the commercial and market and support for investment side. We have to get that right. And as you know, big pharma is not doing this anymore because the incentives are not there relative to other therapeutic areas, and that’s not wrong. We need cancer therapies, ALS, we need those therapies, but the incentives in anti-infectives and antibacterials are just not there anymore. And it’s partly because it’s a genericized market. So everybody’s spending $50 on amoxicillin and that’s fine, but no one’s going to spend a thousand dollars on a new antibiotic because you could spend $50. So there’s a tension in the marketplace about that even though that’s not the best for patients. Right.‌

There is a group of companies that work under something called the Antimicrobial Working Group, they’re pre-revenue biotechnology companies that are trying to work on anti-infectives. And we had all gotten together over the last 7, 8, 9 years to try to figure out how can we get incentives to help new companies come forward and be successful. I’m giving you an example now of what we can do to fix some of the problems. So we came up with a bill called the DISARM Act, and I’m getting to your point just a second. There’s another one there I think you’re referring to. But this DISARM Act was very simple. All it wanted to do is take intravenous antibiotics that are used in the hospital and pull the billing for that out of the diagnosis-related groupings that generally pay for a hospitalization. So if someone gets hospitalized for pneumonia, the hospital gets $12,000, you can spend $50 an antibiotic or $2,000, it doesn’t matter, you get $12,000.‌

So we wanted to pull that out like it’s been done in other areas. We had a bill put forward to that. We talked to senators and Congress. Got support in the office; didn’t go anywhere. The Infectious Disease Society of America had another bill put forward called the PASTEUR Act that has some of the features I think you were talking about, and that gave some incentives to developing this work, especially for the launch, which is very expensive. It was 102 million dollars to launch an antibiotic in the outpatient sector, and there was some way to make that work. Push that, didn’t go anywhere either. So we don’t have the societal support for the things that would incentivize anti-infectives to be developed either as out-patients or an in-patient antibiotics. And that’s disappointing. To me, that means that either we’re not doing a good job of relaying what the true problem is or there’s just too many things going on for us to worry about it.‌

But the resistance rates out in the community now—and I’ll just be a little alarmist for a minute because it gets us thinking—are really bad. I mean, it’s really bad. So in urinary tract infection, we just published a paper with 2 million isolates that we collected over in various different places over 10 years, and resistance to all the major classes of oral antibiotics is higher than 20%. The IDSA says you can’t use those drugs for empiric therapy when you get above 20%. And we just finished a set of studies in about 2,000 women with UTI, the same thing. Within a few percentage points we mimic what we saw in that survey. That’s really bad. We can’t treat empirically for something that has a 20% resistance rate.‌

So I think we need incentives on the back end to bring new companies into the game, but we have a challenge because we have this tension between being able to afford care, which is going to require that the antibiotics don’t cost very much, versus paying for new antibiotics, which will cost $250 million to develop, another $100 million to launch, and where’s that resource coming from? That’s the problem. And I just think we need to work together a little bit more to figure out how do we balance that need for new antibiotics? And yes, maybe we have to pay some more for the new ones to incentivize other people to come in and do work while we’re using our stewardship guidelines optimally to use generics. There’s no problem with that.‌

I think some of the solution to that is technical. We need better diagnostic tests so we can diagnose people’s organisms to the sequence, not genus and species. That’s like a Leeuwenhoek era thing. We need DNA sequencing so we understand what resistance mutations are in the organisms that we’re trying to treat so we can put the appropriate antibiotic for. That’s something I think the academic community could really do a lot with because there are technologies there and we could show that these newer technologies could get us diagnosis quickly so we use the right antibiotic at the right time.‌

Harlan Krumholz: What’s our path here to create a burning platform to get people to want to invest in this? And is this really a public good that the government should be saying that, because antibiotic resistance develops. The whole point here is that companies are reluctant to go into this because there’s this low return on investment. The resistance develops quickly, limiting the long-term profitability of these antibiotics and that the regulatory process is complex and costly so that it’s the perfect storm. It’s not easy. Regulatory is complex and what you’ve got has got a short shelf life because, not because of regulatory protection—for many other things you can say, well, you’ve got regulatory protection where you’re going to be able to have exclusive sales of your product for a while—but here, the shelf life might be shorter because of resistance that naturally accrues.‌

So it just raises the question about, does there need to be a multi-pronged approach to creating incentives for people to want to do this? And then what do we need to be doing in the meantime about judicious use of the antibiotics that are prescribed?‌

Michael Dunne: Yes, we have to use the antibiotics judiciously, and stewardship is important. It’s built into every hospital system, out-patient systems. We have to do that because as you’re saying, Harlan, the new antibiotics won’t last if we don’t have appropriate stewardship, so that’s got to happen. But it’s a weird story because that forces more use of the older antibiotics, which makes them resistant more quickly. They go out of use even more quickly. So that’s not the whole story. We need the new ones to come in, and we need to understand when to use the new ones and what time. That’s saying the diagnostics are probably going to be really important. I think we have great technologies now that could let us do that. So we get this balance between not overusing the newer antibiotics to keep them, at least for the patent cycle so that the companies can get their return on investment, to keep them still useful to people, but also good for patients at the end of the day.‌

Yeah, I mean, this is all good. This is the right conversation. I don’t want to sound like I have an answer. I don’t have a perfect answer to that, but I do think it’s a different market than other markets because you literally, the more you use it, the less useful it becomes over time, but you have to use it or you have bad outcomes. So where’s the middle ground? I think it’s in diagnostics. That’s what I have to say, and I think that’s a scientific problem we can put in front of us. You’re right about people that go to the office and they have a cold or something and they want to get antibiotic. We can’t do that. That, I think, will gut us. We can’t do that. That’s important. I think the community knows that, but in the out-patient sector, there’s not the same supervision of antibiotic use as you see in a hospital sector.‌

That’s known, well-known, and I don’t have a great answer for how to communicate that to the docs in the field who are just trying to manage their busy practice and take care of patients, and they don’t always have the tools they need. That is a problem. But we do need, there is a place for new antibiotics and investment that’s required to make that happen. What can the government do? There’s always a role. Yes, and I think the two bills that are sitting out there, let’s go. That’s a role. Step up, sign these things off. That would help. That only can happen from government funding, only that. But it can’t be the only thing. We can’t have the government funding everything.‌

There is an opportunity in the private sector to make this work. There are historical antibiotics that have done really well, so it’s not like the market has completely failed. The problem right now is the pricing that you can get for new antibiotics is under incredible constraint, and that makes it difficult for someone that’s in, say, someone like myself that was out trying to start companies. You go out to venture [capital] and you say, “Well, we have a new antibiotic, could look really good, but everything’s restricted.” Half of those companies in that antimicrobial work group I was talking about, they’re now out of business. It’s really hard to generate the argument.‌

Harlan Krumholz: Well, I want to ask you just one other quick question just about this that always occurs to me, which is people talk about pharmaceutical waste from antibiotic production plants being dumped into rivers and soil leading to this “environmental reservoirs of resistance.” And then the fact that we’re giving so many antibiotics to animals, cows, and such, it gets excreted in animal waste into the water systems. How much is this contributing to this antibiotic resistance problem?‌

Michael Dunne: It does contribute, especially for selecting for specific resistant pathogens; that’s been documented, that specific pathogens that resistant antibiotics come because of animal use. The animal use thing, though, is under a lot more surveillance than it ever has been, Harlan. When I started a long time ago, no one’s paying attention to that. Now, there really is a lot of focus on not using antibiotics that we use in humans, in animals. So it’s better than it was, but I’m not disagreeing with you. I’m just saying that’s a bit. Mostly what’s happening is that—okay, in UTI, let’s talk about that for one second specifically.‌

Howard Forman: So urinary tract infection, just for the people listening.‌

Michael Dunne: Yeah, sorry about that. Urinary tract infections. Women get urinary tract infections all the time, that’s what happens. As you get older, you’ve taken many, many, many courses of antibiotics and now you have selected for organisms in your flora, which are now resistant, also, to antibiotics. We just documented that nicely in these last two studies showing that increased resistance rate to antibiotics as you got older. All classes. We have 3% of all the people we studied were resistant to all antibiotics, all oral antibiotics. That’s over a million women a year have a UTI, with... and they cannot be treated with an oral antibiotic. That’s unbelievable. Really. That’s unbelievable. And it’s always happening in older women. It happens more often in older women who cannot tolerate an untreated UTI. They get complicated UTIs and fever and problems. So I think we need better diagnostic. I keep saying that, that’s really what we need to get at.‌

Howard Forman: Thinking of what Harlan said about this being a public good and how do we appropriately fund and incentivize it. You’ve worked for the Bill and Melinda Gates Foundation. Right now, we’re at this time in history where the federal government’s desire, and ability maybe, to pay for things is reduced, and we look to these foundations to help fill in some of these gaps. Can you speak to how they think about what their role is compared to private pharmaceutical companies?‌

Michael Dunne: Yeah, the foundation is fabulous. They’re spending hundreds of millions of dollars on a TB vaccine study that we have running in like 20 countries. That is unbelievable. No one would do that. That’s a GSK product, which you can’t ask GSK to spend hundreds of millions of dollars for a TB vaccine that’ll take a long time to come back. But they stepped right up and did, that is unbelievably important.‌

At the same time, it’s hard to ask the foundation to pay for everything. At some point we have to all step up. I know what you’re saying, can they fill in the gaps? I think that there’s a possibility for that in certain specific situations where there may not be any market forces behind the product at the end of the day. Early research gets funded through the foundation, which is fabulous. And the MRI [medical research institute] can definitely help do that phase. They can do the development afterwards, right through registration, but not for everything. It’s just hard to imagine it. But they can be a convening power, which can help.‌

Harlan Krumholz: Right. One question I have is, as I’ve thought about this, is should we be treating infectious disease like we treat cancer? What I mean by that is for cancer, we have a pairing of a diagnostic and a therapeutic, and we think about this in a precision medicine approach. We don’t sit there and say, you’ve got lung cancer, and then we’ve got our basic lung cancer chemotherapy that we’ve had for many years and we just see whether you respond or not. And then some people are resistant to our usual treatment pattern. What we do is we characterize your cancer. On a molecular level we understand what is it you have and what do we have in our armamentarium that we can direct towards your type of cancer that’s likely to be most effective.‌

I don’t understand why we’re not doing that in infectious disease where we make infectious disease a precision medicine art where it’s like I know exactly the infection you have. I know it down to the level of the genome of the bug that’s in your blood, and I know what exactly I need to do to address that bug. But we don’t have these pairings like we do in cancer, where it’s like, I need the diagnostic and the therapeutic as a joint package in order to know how I can treat you. We do test for antibiotic resistance, but it’s just not the same as actually getting down to the level of actually understanding what is that bug. We do it for surveillance, but we don’t do it on an individual patient level. We shower them with antibiotics first, and then when we try to see what’s going on. What’s your thought about that?‌

Michael Dunne: Oh, that is such a good point. So I’ll just tell you a little story about it. So during the trial that we did, we were doing culture and sensitivity in the usual stuff, and I realized quickly that, that was not going to work because the susceptibility patterns are “yes, it’s susceptible/no, it’s not.” But the organisms are totally different. We totally were not comparing up. So we actually went back and did whole genome sequencing on all of the organisms, all of them. That was a little too much for the regulatory agencies to absorb because that’s not an approved technology. But it’s very important for us to understand that bug is not the same as the bug you started with.‌

So I agree with you completely. We should be having more diagnostics. And I think with AI, with nanopore sequencing, with other things that are in place, we can do exactly what you’re saying, but there’s got to become some pressure to do that. Where’s that coming from?‌

Harlan Krumholz: Well, we need a cost-effective way to do this pairing, and then we need to be able to say, “Here’s exactly what you’ve got.” In the long term, this is going to be a much better strategy to help people, right?‌

Michael Dunne: Totally agree. We’re using Leeuwenhoek-era, 100-year-old strategies to try this. We don’t need to do that. And I think that would help us target the new antibiotics to exactly the patients that need them, that would justify the cost, which we could easily justify because you’re not going to get hospitalized. You don’t tell the nursing home patient, get them in an ambulance, go to the ER, five days, you don’t have to do any of that anymore. You just know what the person has right there at the bedside and treat. So you’re onto something there, Harlan. We should do that. But where does that come from? Who’s investing in doing that? You’re not going to get pharma to do it, because they can’t.‌

Harlan Krumholz: We need a mindset change about how exactly we’re approaching this. No question.‌

Michael Dunne: That’s right. To me, that is the answer, infectious disease, we need to know what you’re treating. We do it for HIV. “We know what you have, we know exactly what you have, we know what we’re doing with any of this—just for three days.” No, that’s not right. We need to do a better job bedside sequencing. It’s really sequencing is what we need to be able to do, and we can do that with AI and with data…more sequencing. We could do that now.‌

Howard Forman: Great. We are grateful for what you’ve done and for what you continue to do and for joining us today. So thank you very much.‌

Michael Dunne: Very welcome.‌

Harlan Krumholz: What a pleasure to meet you and to hear about this. Hey, that was terrific interview. I really enjoyed that. But Howie, now I get to hear your part of the show, which is always one of my favorites.‌

Howard Forman: Thanks, Harlan. Since our last podcast, the number of [measles] cases in West Texas has more than doubled, to 124 cases. There’s no reason to suspect that we’re not going to see many, many more. And then just this morning, we’re taping this on Wednesday, the Department of Public Health in Texas revealed that a child from Lubbock, Texas, who is not immunized and had been hospitalized, has now died from measles. This is the first death from this outbreak. I’ve avoided talking about a topic on consecutive weeks, but for me, this is really important, and if we keep talking about it, hopefully our listeners will learn a bit more. And it’s important.‌

Harlan Krumholz: So Howie, I just want to ask you one quick question. How does someone die of measles? Because you’re basically talking about a healthy kid who gets measles. What happens?‌

Howard Forman: There’s three big categories, I think. The biggest one is measles pneumonia, where it’s basically they’re predisposed to getting a bacterial pneumonia after measles. The second one is a measles encephalitis, which is pretty rare. And the other really rare one is a measles colitis. And last week we talked about the child in the Beck case that we talked about died of measles. She died of a measles colitis that developed a bacterial colitis. So I think that the common thread is that measles reduces your immune response to many things and makes you somewhat immunocompromised and puts you at risk of other diseases that you then die of proximate to the measles infection.‌

Harlan Krumholz: And I think the reason I just was saying that, and sorry to interrupt, but I just wanted to make the point that I think sometimes people are hearing this and they’re thinking like, “Yeah, so it gets inconvenient and I’d like my child to get natural immunity. So they’re sick for a couple days and it’s not a big deal.” But the thing is, it can be a big deal, and for many people—‌

Howard Forman: One in 300 to one in 500, maybe one in 1,000, depending on the person, dies of measles one way or the other. And this is not dying with measles. This is dying of measles.‌

Harlan Krumholz: This is not just being sick for a couple of days. This is actually a big deal.‌

Howard Forman: Right. No, it’s a very big deal. And I want people to understand also that we’re not just watching this burn out in Texas. We’re doing a lot down there. The public health professionals in Texas are testing, they’re screening, they’re isolating and quarantining. They’re vaccinating because even if you’ve been exposed, vaccination can occasionally help if it’s early enough, they’re communicating to the public and public health professionals, and they’re trying to reduce this outbreak. But nonetheless, we’re going to see many more cases and, perhaps, more deaths.‌

And I want to just point out, it goes back to what you talked about in the beginning. Measles, mumps, and rubella vaccine safety is well established. There are reports of very severe reactions occurring, but these are so rare. They’re occurring in a frequency of maybe one in a million or less range. There are many other side effects and adverse events that are more common, but for the most part, these are self-limiting. Kids may have a febrile seizure associated with the vaccine, but they recover fully. And because you and I talked about it this morning, you asked me, “What about us? Did we get the right measles vaccine?” From 1963 to 1967, if you got your vaccine during that window, you may have received the inactivated vaccine that turned out to be less effective. So many of us, including me, got a booster shot in order to have full immunity later on in life than we vaccinate people right now.‌

Harlan Krumholz: This was a big question, by the way. Lots of people asking me, Howie, “So I don’t know if I got a booster. What do I do?”‌

Howard Forman: So there’s a couple things you can do. Number one, it’s extremely unlikely that you’re—in an area that has no outbreak, it’s extremely unlikely that you can get measles, really extremely unlikely. But you can go get measles titers. And in fact, I think, at least at one of the hospitals that I became credentialed at over the last 35 years, I had to have titers from all of my childhood immunity. They weren’t willing to rely on self-report of immunity. They wanted to actually see that I still had antibodies that represented immunity. So that’s another thing you could do. Or you can just get a booster. There’s no opposition to getting a booster, and the risk to you is relatively small, again. But it is worth just remembering, of all the vaccines that are out there, measles, mumps, rubella is probably the safest. DPT, otherwise known as diphtheria, pertussis, tetanus, and has a higher risk profile. Polio has a higher risk profile. This is extremely safe stuff.‌

Harlan Krumholz: And if you get it [the shot], again, there’s nothing—there’s nothing bad about it, right?‌

Howard Forman: No. Like I said, we’re dealing with a vaccine that has a very good safety profile.‌

Harlan Krumholz: This is the irony. The person who died—no one should die of measles, right?‌

Howard Forman: No. And this was absolutely an unvaccinated individual. In today’s day and age, nobody should die. And yet, hundreds of thousands of people worldwide still die of measles right now because they’re not vaccinated. As recently as a few years ago, it was over a million. So we’re making progress globally. In the United States, I think this is the first death in over 10 years or maybe 10 years.‌

Harlan Krumholz: I remember at the beginning of the pandemic, we were talking about how many people would be infected from each person who was infected. I remember it was something like four or five was a big number, sometimes it was three. It was something like that. But weren’t people saying that measles was like 60? It’s one of the largest numbers.‌

Howard Forman: Yeah, I think it’s in the teens. But yeah, it’s a very high number. And the good news is that if you have a vaccinated population, the number is dramatically reduced. So right now, the rate of growth in cases in Texas is about doubling every week. But as they do all the mitigation factors, hopefully that rate of growth will slow down and we won’t end up with a thousand or more cases. But I do think this is going to be an epic year for measles.‌

Harlan Krumholz: Yeah, that’s a good point though, too. The number of people it’ll spread to depends on how many people around you have been vaccinated.‌

Howard Forman: Exactly. The child who died in Lubbock, Lubbock is much better vaccinated than in Gaines County. The cases in Lubbock are actually very small compared to Gaines County right now. Gaines is the area that has the Mennonite population that is more averse and looking for vaccine exemptions.‌

Harlan Krumholz: But to be clear, the Mennonite communities there, it’s true that they are averse to vaccination, but there’s a wide range of people throughout the entire population who are now choosing not to vaccinate.‌

Howard Forman: No question. But in fairness, at this moment, our biggest outbreaks, the most recent one, which was centered in New York six or seven years ago, that was an Orthodox Jewish Community.‌

Harlan Krumholz: Yeah, yeah.‌

Howard Forman: It tends to be religious communities, the Amish.‌

Harlan Krumholz: Maybe because you get a critical mass of people around.‌

Howard Forman: Exactly.‌

Harlan Krumholz: That’s great. Thank you. Great report. You’ve been listening to Health & Veritas with Harlan Krumholz and Howie Forman.‌

Howard Forman: So how did we do? To give us your feedback or to keep the conversation going ,email us at health.veritas@yale.edu or follow us on any of social media, including LinkedIn and Bluesky.‌

Harlan Krumholz: And we want to hear your feedback questions, your own experiences with these topics. And if you like the podcast, rate us, review us, helps people find us.‌

Howard Forman: Absolutely. And if you have questions about the MBA for Executives program at the Yale School of Management, reach out via email for more information or check out our website at som.yale.edu/emba.‌

Harlan Krumholz: Health & Veritas is produced with the Yale School of Management and the Yale School of Public Health. Thanks to our amazing super researchers, Inès Gilles, Sophia Stumpf, Tobias Liu, and to our remarkable producer, Miranda Shafer. Very lucky. Talk to you soon, Howie.‌

Howard Forman: Thanks very much, Harlan. Talk to you soon.‌