TWiV 1370: Clinical Update with Dr. Daniel Griffin

0:00This Week in Virology, the podcast about viruses, the kind that make you sick.

0:10From Microbe TV, this is TWIV, This Week in Virology, episode 1370, recorded on October 29th, 2026. I'm Vincent Racaniello, and you're listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin. Hello, everyone. Yes, back in New York, both of us. And the last TWIV clinical update for October. And the last clinical update that will drop before the midterms. I hope when we record next week, we have good news. Good news for science. We're not partisan, right? No, good news for science and public health because, you know, things are looking bad in terms of public health.

1:01It really is. And we're going to be talking a lot about that. And it is. It's been difficult times. And as we approach, well, this is going to drop on Halloween. Is that right? Is Saturday Halloween? Saturday is Halloween. It is. All right. Well, with that in mind, I thought to quote Edgar Allan Poe. Perfect for Halloween. Yes. And, you know, he actually has some really great one-liners, some great quotations. I was actually a little bit – I mean, I love his stories, right? You know, they're perfect to read this time of the year, right? Yep, for sure. But this seemed very appropriate considering the comment you just made.

1:41And so Edgar Allan Poe, the believer is happy. The doubter is wise.

1:50it's an uncharacteristically laconic for edgar allen poe right laconic what does that big fancy word mean uh he doesn't use a lot of words that's the opposite of loquacious opposite of like loquacious means you you you talk a lot yeah yeah the gift of gab um i was uh i got together with a friend of mine who's a sales salesman. We were talking about another mutual friend who has the gift of gab, a born extrovert, which really, if you're going to be in sales, is the thing to be born with. Of course. Yeah, I would not do well in sales. Yeah, maybe I would. But okay. So CDC, this is news, CDC deputy director resigns after four months in the job, on the job.

2:41And so Dr. Jennifer Shuford, a former state health commissioner whom President Trump appointed to a top post at the CDC to help steady the agency, is leaving after just four months in the job. Last day is going to be November 12th, the CDC said in a statement. Her departure was reported by the Washington Post. Dr. Erica Schwartz, the CDC director, announced the news to staff at an email Tuesday morning. News of Dr. Shuford's exit comes as the CDC faces criticism over its response to unrelenting measles outbreaks in the country. We'll leave in a link to it. I mean, this is a doctor with a great reputation, which she gained in part from being a data-driven epidemiologist who really understood the importance of childhood vaccines.

3:35She joined the CDC in June. She's out now. So this is another loss to the CDC. And this is someone who's pro-vaccine, clearly clashing with the administration and can't get anything done. So she leaves. But I think it's unfortunate because we need people like this. I mean, you know, public health should not be a partisan issue. I mean, we do not want children sick and dying. We don't want adults sick and dying. So there should be no opposition to vaccines. Yeah. At the highest levels of the government, vaccines work. They're safe. They save lives. The idea that you cannot be in CDC unless you're anti-vaccine is just absurd and has no place in the real world.

4:19Yeah. Yeah. Vote, people. Vote. Yeah. And we're going to talk a little bit about – well, we'll get a little deeper into why that is such an important comment that you just made there, Vincent. So, okay, bird flu. What's up with the mink? Bird flu in mink. It's funny you picked this paper. I also found it this week, and we're going to do a deep dive tomorrow. So that's excellent. So I'm glad that—so it's a preliminary report on H5N1, highly pathogenic avian influenza in Utah, mink, August 2026. And here they're describing an outbreak of bird flu, highly pathogenic avian influenza viruses belonging to H5N1, clade 2.3.4.4b in August 2026 that caused high mortality on a mink farm in Salt Lake County, Utah, using data generated from the USDA.

5:14Genetic sequencing of the mink viruses identified the genotype as B3.13, which currently circulates in U.S. dairy cow. Do remember our mnemonic for this? B for bovine. B for bovine. And what was D? The other one was D, is that right? Yep. Deadly? Was that deadly? Yes. B for deadly, B for bovine. Okay, listen, it worked. Well, it worked for you. We'll find out if it worked for anyone else. So this was reported on those dairies in Utah, Texas, and Idaho in 2026. So based on 10 genome sequences in Utah mink collected August 7, 2026. The mink outbreak is positioned within the 2026 cattle clade. The most closely related viruses were sampled in May 2026 in Texas cattle.

6:06Several months of unsampled transmission chains between the Texas cattle and Utah mink outbreaks leave many open questions about how the virus actually entered the mink farm. Now, additional PB2 mammalian adaptations were not selected for in mink since the cattle adapted B3.13 virus already had a PB2-M61L amino acid substitution. I just, I can't believe they can't, because they get it straight in the next sentence. And that amino acid substitution is associated with increased replication in mammals. All 10 Utah mink viruses that they sequenced had a PB1 K388R, so a K to R substitution at 388. This was previously observed in an H5N1 mink outbreak in Spain.

7:00Not much you see in avian hosts wasn't seen in the cattle. So why do we care? Well, there's going to be a deep So we're going to learn in depth why we care. But alongside pigs, infection of mink with avian influenza viruses is a particular concern. Relative to other susceptible mammals, both swine and mink express a high proportion of the alpha-2 ,6-linked sialic acids, similar to those found in the human upper respiratory tract. You know, ferrets are in the same genus. They're mustelids. And ferrets are used as models for influenza virus infection. So this is concerning that it's now in the mink.

7:46And, you know, it's good that Spain, which had an outbreak, culled all the mink. That's a good idea. I think we should do the same. But I don't think that's happening in this administration. Yeah, I mean, it's very, not only is there this potential adaptation opportunity, but But also, you know, this can be a mixing vesicle, right? Because they can get human, they can get avian, and it all can mix up. Mink is not an essential commodity, right? Yeah, what are we doing with mink? Well, mink people wear coats, mink coats, right? No, nobody does that. Do they? What else are you going to do with the mink?

8:25You can't eat it. It's tiny. Anyway, it does, you know, it employs people. So I don't want to say things that cost people jobs. But, you know, in what was it, the Netherlands, when COVID got into mink, they banned mink farming in the whole country, which was the wise thing to do. Yeah. I mean, this is just this is really risky, right? You know, and so, yeah. Also, it's inhumane, you know, to kill these poor mink. Yeah. Yeah. Yeah, I think most people at this point are not comfortable with the idea of raising mink and everything that's involved in the generation of and wearing of these fur coats.

9:11All right, I'll leave that there. But more, this is in emerging infectious diseases. We have a little bit of a theme here. The article, Evidence of Exposure to Highly Pathogenic Avian Influenza H5 Viruses in East Greenland Polar Bears. Greenland, hey, that's the country we want to take over. I think we now own it.

9:34That's a joke. So, sorry. So, here's the problem. Seasonal bird migrations to Arctic nesting grounds creates a hotspot for highly pathogenic avian influenza outbreaks, amplifying interspecies interactions and the risk for viral reassortment and dissemination across migratory flyways, right? So, you got the birds, they're all flying over and they end up in these Arctic nesting grounds. Now, there have been recent detection of highly pathogenic avian influenza in wild Arctic mammals. I'm worried about the mammals. I was reading earlier today about, what was it, seal rabies, rabid seals attacking kayakers.

10:13But okay, so the poor Arctic mammals. So one, we care about these animals. They also have an impact on indigenous peoples, nutritional, cultural relevance. Now, the polar bears are Arctic apex predators that face increased challenges associated with their ecological position at the interface between marine and terrestrial ecosystems. Now, climate warming, I'm going to go ahead and say anthropogenic, our fault, climate warming. And the subsequent loss of sea ice leads to increased time spent on land and exposure to terrestrial pathogens through the exploitation of new food sources, right? I mean, the polar bears are starving and they're trying to figure out what can they eat.

10:54So they spend more time on land, more exposures. Now, cases of deceased, so dead polar bears infected with bird flu have been reported in Alaska. That was H5N1 in 2023. In Norway, that was H5N5 in 2026. So here they go. They've got this ongoing collaboration with the indigenous hunters. And through this collaboration, heart blood was collected during subsistence harvest from polar bears that appeared healthy near the Scoresby Sound in East Greenland during the hunting season. They screened 109 plasma samples collected during 2016 through 2025 for antibodies against all the influenza A viruses.

11:43So prior to 2024, no influenza A virus antibodies. But 2024, three bears, all male harvested in 2024, had signal-to-noise values within the positive range. So here we're going to see three of 14. So 21 % of the male bears that they checked were positive. By 2025, it had increased to 43 % of the bears they checked. They conducted further screening on the positive samples, basically using an avian influenza virus representative H5 and H7 subtypes in the assay. Plasma from four animals harvested in 2025 were positive, with greater than 1 to 40 for for antibodies to H5N1 falling within clade 2.3.4.4b.

12:40Does that sound familiar? I'm suggesting that the animals had been exposed to a highly pathogenic avian influenza virus in this clade. And so I like the figures they have. They've got these nice like cartoons sort of showing you how the polar bears might interact, how they might congregate. You can see them sort of touching their noses. But then you also see, you know, eating birds and eggs, including dead birds. Polar bears will scavenge. Eating infected mammals, they'll actually hunt those. Potential transmission from mothered offspring through lactation. Potential environmental contamination.

13:19And then what I really like is this figure, you got to go to the appendix and look at the flyways and you can see how these birds can spread stuff all around. hmm so yeah it's uh that's surprising that they're getting them the birds go up there yep yeah so hopefully people watching on youtube can see this so you've got these north the north american atlantic fly flyway where basically the birds come up through the northeast into canada some kind of head west into parts of canada some continue end up in greenland but you've also got this flyway path where they're going back and forth from Iceland, parts of Europe.

14:00So, yeah. Boy, Greenland is a big country. Well, maybe it's the curvature of the Earth. Yeah, part of it's the projection. They do this like a Mercator projection where the farther north you get, the bigger you look and the closer to the equator, the smaller you look. So we like to use this in the US to make our country and Europe seem huge and then Africa seem tiny. Yeah. OK. So, yeah. When we do our Parasites Without Borders projection, we do it from like polar down, kind of like the UN or the WHO or something. OK. Florida dengue cases. This is crazy, Vincent. About a month after three Florida counties declared states of emergency over what officials described as a, I like this, wildly unusual dengue outbreak, infections of dengue have continued to climb.

14:53Since September, the total reported cases in Florida have doubled from 392 to 721. Now, Ira Longini, a biostatistician and infectious disease modeler at the University of Florida, that means they create these models. They're not up there on the runway. They say they're not surprised by dengue's continued spread. It was just a matter of time, Longini said. Longini explained that climate change, anthropomorphic climate change, our fault, is increasing mosquito populations, lengthening their active seasons, contributing to dengue's spread globally. Yeah, I remember years ago when we just had a few cases and it just increased more and more and more mosquitoes, Aedes aegypti, and this is what's going to happen.

15:39It's going to move further and further north. People, politicians don't seem to care. This is a huge problem. I mean, now Florida has basically endemic, autochthonous dengue cases. So we have a vaccine licensed in the U.S.? I don't think so, right? So right now there's no accessible licensed dengue vaccine in the U.S. So this might need to be revisited. Yeah, right? People go to Florida all the time. We're going to start having like tourists going to Disney. They're going to end up getting dengue. Little kids, right? I mean, there's always this idea with dengue that the worst dengue is the second case of dengue.

16:16But the worst case of dengue is dengue and little kids. And lots of comments. Sort of enjoyed looking through the comments. People are very annoyed with... the way Florida public health is being managed at the moment. Yeah, it really was. The comments basically were pretty much frustration and sarcasm regarding the handling of public health issues in Florida. A lot of criticisms of the current governor and Dr. LeDepo. Well, the governor is out now. He's finished, right? I think, right? Isn't this the end? Like someone new gets elected next Tuesday? But the problem with Florida is they don't realize what is happening in this country, and they are not following the right trend of voting.

17:04Even think about themselves, right? You want to start, like, being worried. Your grandkids come down to visit you, and now they end up in the hospital with, like, hemorrhagic, severe dengue. I mean, that's— There's a lot of elderly people in Florida. Yep. And you know, Daniel, who is the most susceptible to severe infectious diseases, right? The elderly. Yeah, yeah. The youngest, the oldest.

17:29Screwworm's out of control. Look at this, Vincent. Wow. So we are up to a total number of 66 cases. Also found it in a sheep, I think, or a goat, other than a cow. Yeah. What were the – if you go, you can actually go to this page and they list all the different detections and which animals have been. So it's mostly – they're mostly domestic cases. So far only one wildlife case. But another 14. I mean it was sort of moving down like 14 cases, four cases, three cases. And then we've already got 14 and October is not even over. The wild elk was positive. Yeah. So that's wildlife. That was wildlife.

18:16First wildlife, yeah. So. All right. So Ebola, let's talk a bit about Ebola. And we're going to start actually with the article, Cross-Reactive T-Cell Responses Against BDBV. That's easier for me to say. But the Bougio virus in humans. There you go. You got it. You got it. After the VSV Delta G Zeboff GP vaccination. This was published actually as a correspondence in the Lancet Infectious Diseases. So the recombinant stomatitis virus, Zaire, Ebola virus glycoprotein vaccine, Rovebo, is a highly efficacious vaccine against the phylogenetically related Ebola virus consisting of a recombinant VSV viral vector that encodes the glycoprotein of the Kikwit 1995 EBOV isolate.

19:19But here, the point is, this is a vaccine for Zaire Ebola, not Bundabugio Ebola virus. So although vaccine-induced antibodies are considered a putative correlate of protection against diseases caused by EBOV, so that's the Zaire Ebola, it remains unknown if these cross-reactive responses are actually sufficient to protect humans against disease caused by Bundabugio. So enter the T cells. This is what caught my eye. Virus-specific T cell responses are associated with virus control and protection against severe disease. And potentially, we've talked about this, you guys have talked about quite a bit on the deep dives, can potentially provide broader cross-reactivity and greater resilience to viral escape by targeting multiple, often conserved linear peptide epitopes.

20:14However, whether this vaccination induces these Bundabugio reactive T cells in humans was not known. So to address this, this group analyzed and mapped T cell reactivity and investigated whether conserved regions within the glycoprotein are targeted. Now, they're actually pretty different, these glycoproteins. They're only about 66.3 % amino acid identity. It's really quite different, right? Yeah, it sure is. Yeah. So by multiple sequence alignment, they identified several amino acid sequences that are highly conserved, generated some peptide pools covering these regions. They then assessed the cross-reactive T cells at day 28, right after vaccination in 20 folks.

21:02And they're doing, you know, think of this as like those interferon gamma assays that we do for like tuberculosis, for instance. They're basically doing that. They're looking for memory T-cells using this interferon gamma LE spot. And they have a nice graphic where you can sort of see how they lay this out. But most vaccinees with a positive response to the EBOV had Bundabugio virus reactive T-cells. That's good. Yeah. Yeah. Well, I hope it works because this is what's being rolled out now. Yeah. So we're hoping that it's encouraging, encouraging data. What's not encouraging is the epidemic is continuing.

21:45Kenya reported the second death as Nigeria races to understand transmission of index patient. And we'll leave a link into this. It's really a CIDRAP piece where they talk about it. So as we learn more, it turns out Nigeria's index Ebola case patient was airlifted to Switzerland, stable condition. The index patient was clinically improving, stable, conscious, able to communicate. Their lab data was moving towards baseline. This doesn't mean they're no longer infectious or anything. So all the protocols are still in place. And the patient was actually evacuated along with her spouse, so woman who we're talking about here.

22:29The patient is a 42-year-old Ugandan woman who's married to a Swiss national who works in Nigeria. She and her husband had recently traveled to Uganda but African CDC said the index patient in both Kenya and Nigeria traveled through Uganda's Entebbe International Airport on October 3rd, which may have been the scene of transmission. So that'll sort of get more news as we – we'll share more news as we get it. But if you look at the epi curve, it is still on its way up, not starting to plateau. we are now at over 10 ,000 cases, almost 5 ,000. Actually, the update when we're recording this is already up to about 5 ,000 confirmed deaths from Ebola already.

23:18Yes, it's very concerning. Yeah. And this is very quickly on its way to becoming the worst Ebola outbreak in history. And we're not doing a lot to help, just by the way. And they're making it hard or those of us who might want to help to go over there and help with this weird third country 21-day quarantine thing that they've got going. So, yeah. All right, measles. So a deep dive, Vincent, for the last TWIV. It's where they discuss, where you guys discuss the article, Projected Effects of Removing School Entry Vaccination Requirements on Measles Transmission in Florida, published in PNAS. And so we're going to leave in a link.

24:05Go ahead, listen to TWIV 1369. But why do we care? Why is it anyone else's business whether or not you and your child get the measles vaccine? the safe, effective measles vaccine that lots of folks are spreading misinformation about. Well, the upshot is that using a mathematical model, these researchers show that repealing the mandate could trigger the largest measles epidemic in the United States in nearly half a century with projected pediatric children and babies deaths numbering in the hundreds within five years. So just for all our people listening, I mean, that's what you're voting on. You're voting on whether or not you're okay with hundreds of little children dying in the next five years because that's where we're headed.

25:03It's just unbelievable that they're thinking about doing this. And this is just Florida. This is just Florida. Hundreds of little children dying in Florida because of decisions that we make. that a certain party makes, not us. Yeah. All right. So Vincent, I actually, I got through the text observations made during the epidemic of measles on the Faroe Islands in the year 1846. That's great. Did you get the books in the library, Daniel, or did you buy it? So I bought it, but I'm going to say don't buy the book. So I bought the book, but it's like reproduced and it's not a very good printing. So there's actually a society that allows you to access a really higher quality scanned PDF.

25:47So that's how I read it. But it was really interesting. It's long-winded. It's great. Like sit down. It's, you know, it's like it's not one of these like nature papers where like every single word, you know, has to be, you know, weighed and measured because you're only allowed like so many per abstract, et cetera. I mean, this is like 74 pages of like describing the salt that cakes on the boat, the, you know, the weather, the different types of food that people eat, how they cook it. But really the meat of it is this one observation and just sort of the quote. And this is – because people keep asking, like, if you get measles, can you get it a second time?

26:33And people used to say, I don't know, maybe. Well, the old people who had had the disease, measles, in 1781 were exempt without exception. There were, however, several houses and small villages that had not been invaded in 1781. And in these, the older folk were attacked just as the others. Willen, Rosenstein, and Thucink in their long experience with many great epidemics have also observed the same protective power without exception. So, you know, you get measles once and that's it. Yeah, it's a great study. Yeah. Really, it's fun to read, actually, I have to say. It made me, you know, miss like the outer like Heberdeeds in Scotland, you know, where it's just – he describes with the wind, these gusts come along and you basically have to drop to the ground because otherwise like you'll go humbling away.

27:27Okay. All right. So Nature Medicine, we have the article, Global and Regional Burden of Measles and Vaccine Coverage Among Children Under Five Years, 1990 to 2023, a Global Burden of Disease Study. Not good news. Using the Global Burden of Diseases, Injury, and Risk Factors Study 2023, this group systematically assessed measles incidence, mortality, disability-adjusted life years, those are those delays and vaccine coverage, either getting one shot or vaccine-containing vaccine getting two shots among children under five years of age across 204 countries and territories from 1990 to 2023. Between 1990 and 2019, global measles incidence and mortality declined by approximately 80 % and 90 % respectively, but then it rebounds in 2020 with 15.6 million cases, 118 ,000 deaths in 2023.

28:35So that's a 40 % increase in the cases, 12 % increases in the number of deaths between just 2019 and 2023. Sub-Saharan Africa, South Asia really is where we're seeing most of this. Now, the coverage from getting a single shot in 1990 was at 67.2. We get up to 83.6 in 2019, but then it actually stalls and drops to 81 % in 2023. That second shot was only 14.4 % in 1990, gets up to 68.4 % in 2019, got up to 71.4 by 2023. but we are basically not at that 90 % in so much of the world. So expect millions of more measles cases, expect tens of thousands, 100 ,000 deaths per year if we don't turn this around.

29:31And this increase in 2000 is probably COVID related. You know, part of the 2020 was all kinds of disruptions with COVID. But sort of going on from there, we're seeing a lot of evidence for a really, unfortunately, successful misinformation campaign. The kids will pay. That's it. Totally unfair. Yeah. All right. Right, and I'll leave a link into a CIDRAP article where as measles soars in Pennsylvania, some parents are vaccinating their babies early, right? So let's talk about the science here. And so got an article, Immunogenicity, Effectiveness and Safety of Measles Vaccination in Infants Younger Than Nine Months, a systematic review meta-analysis published.

30:23This is back in 2019. So I wanted to go back and give some context to this decision. This was published in the Lancet Infectious Diseases, and they did a systematic review, meta-analysis. They searched Medline, Embase, Scopus, ProQuest, Global Health, the WHO Library Database, the WHO Institutionary Repository for Information Sharing Database. They consulted experts. They included randomized and quasi-randomized control trials, outbreak investigations, cohort and case control studies. I mean, this is really robust. They did the literature search on June 2nd, 2015. They updated it on January 14th, 2019.

31:05And they assessed a number of things. The proportion of infants that seroconverted, the geometric mean antibody titer, right? So that's the way we do a mean when we've got an exponential thing like a titer. They looked at avidity, cellular immunity, duration of immunity, vaccine efficacy, vaccine effectiveness and safety. They ultimately identified 1 ,156 studies, of which 1 ,071 were screened for eligibility. 351 were eligible for full-text screening and data from 56 studies that met all inclusion criteria we used for the analysis. So here is what they found. We've got a nice figure here. So the pooled estimate of the proportion of infants who seroconverted increased from 50 % at age four months to 67 % if given at five months, 76 % at six months, 72 % at seven months, 85 % at eight months.

32:07Now, that's great and all, but you can just look at the really wide confidence intervals. There's really a lot of variability here. But we have the pooled geometric mean titer ratio for infants vaccinated with the first dose at age 4 to 8 months compared with infants vaccinated at age 9 months or older, 0.46. And so we have this nice figure three where applying the ratio to the pool geometric mean titer estimate of 248 for infants younger than nine at vaccination gave an estimated geometric mean titer for infants age nine or older at 539. But really a lot of variability in the studies. Folks that are watching on YouTube can kind of see the forest plots that we've got going here and basically looking at these different antibody titers, right?

33:04And then we've got eight studies that actually assessed vaccine effectiveness of the first dose given to infants younger than nine months against clinically diagnosed measles. And the pooled vaccine effectiveness was, I'm going to say, only 58%, but a lot of variability. Well, you know, this getting the vaccine between, you know, six and eight months, it's going to be variable depending on how much antibody you get from your mother, your response. And so that's why we see big error bars on these. I mean, but you do, you can see the graph, the bar graph is quite clear. If you get it younger, fewer infants seroconverted.

33:46That's interference with maternal antibody. Yeah. Yeah. Yeah. And so it is a, yeah, it's a challenge when you've got measles all around these children. That's the problem. Yeah, if there's measles, it should not be. There should not be measles circulating. Yeah. And this is the problem with the current situation. Yeah. But, you know, if you are living in an area with a lot of measles, like Pennsylvania, it's probably not a bad idea to get that. Look, it looks like six to eight months is about as good as it gets until 12 months, probably. Yeah, so you don't want to do it before six. Current recommendation is 12, but WHO says you might go down to the six to nine-month window.

34:24So like in basically a current outbreak situation, which is where – That's where we are. Yeah. Yeah, and that is where we are. So if you look at the Hopkins tracker, we're up to 4 ,730. And you can see the hotspots. I mean there's a lot going on in Pennsylvania. Another 85 new cases just the last seven days, 1 ,398 total cases so far in Pennsylvania alone. I looked at a graph in the New York Times of why MAGA voters are turning against Trump. And the biggest issue was the price of goods. The lowest issue, 4 % only of voters made it an issue, was public health. I don't understand why people are not responding to this and other outbreaks with their vote.

35:18What is your problem? Yeah. It doesn't say a lot. I care more about the price of gas than babies dying, right? I mean, also down at 6 % or 8 % was democracy. People don't care that the democracy is being destroyed. I don't understand people. Get cheap gas and you can have my freedom. Oh, my gosh. I don't get it. I really thought we were better than this. Well, let's prove that we're better than this. We'll find out in a week if we are or not. But we've got them here in New York as well. We've got a New York dashboard. word. We're up to 170 measles cases in the state of New York. And this was interesting.

35:57Okay, so here's this article. You know, like you think like, oh, we know everything. Well, it's amazing how much we don't know. So here's the article published in CMI, first evidence of measles virus detected from exhaled breath in humans. Do you believe that, Vincent? Yeah, it's hard to believe that this hasn't been done before. Yeah, I'm a little, so maybe people scour the literature, like maybe we're missing something. But here they studied a 23-year-old unvaccinated woman with lab-confirmed measles. From day 10 post-symptom onset, longitudinal sampling was performed for six consecutive days, duplicate specimens.

36:33They collect them from the throat, the face, cutaneous lesions, exhaled breath, using these special, it's kind of funky mask with these strips in there, these polyvinyl alcohol sampling strips. But the measles virus RNA was consistently detected in exhaled breath. And they've got some kinetics. And they basically conclude, this study provides the first empirical evidence that measles virus RNA can be captured directly from the exhaled breath of an individual with measles. So I don't know, I'm just sort of thrown that you think this would have been done before. Yeah, they could have used infectious virus assays before, right?

37:10Yeah, yeah. So it says first evidence. Yeah. All right. So New York State Department of Health launched its own respiratory disease tracking dashboard. So I'm going to leave in a link. You know, it's barely started. You can't really see much of the trends yet, but I'll keep an eye on this. But I guess this is sort of this movement, right? Now that the CDC is falling down and we're not sure if we can trust them or not. And I have to say, right now, we're kind of in this sort of surge of flu. We've got a bunch of folks in the hospital with flu right now. I'm not thinking it's a good year. If you look at the flu maps, you don't see a lot of activity on the CDC flu maps, which is a little weird considering we're like, you know, mask mandates in the hospital.

37:56We got all kinds of folks coming in, you know, with flu requiring oxygen support. So yeah, it might not be quite as rosy as the charts and graphs are suggesting. Yeah, the map shows low activity. Yeah, it looks like everything's all good here, nothing to see, but that's not really true. But if you look at the epidemic trend from CDC, the flu line is rising. Yeah. Yeah, it's definitely on the way up. So we are, the flu, the flu is here. So if you haven't gotten your flu shot, you know, don't walk, run, get that, get that shot. And, you know, and you're not doing it just because, oh, I've had the flu, I was just fine.

38:37You know, remember, we've talked quite a bit about those flu vaccines might not only keep you out of the hospital, they might keep you from having a heart attack or a stroke. So another article to hammer that home, effectiveness of high dose versus standard dose flu vaccines against severe respiratory and secondary cardiovascular outcomes in adults aged 80 or older, was published in CMI. Retrospective population cohort study conducted in Spain, included 279 ,649 vaccinated adults based on sociodemographic characteristics, influenza vaccines, chronic diseases, clinical outcomes were looked at. They're comparing the standard dose to the high dose.

39:18Now, the high dose was associated with a lower risk of hospitalization, 34 % lower. The high dose also showed improved effectiveness against lab-confirmed flu. So that was a 42%. Now, hospitalization for acute MI. Remember, we keep talking about get those flu shots. And here they're saying the high dose is even better than standard dose with a relative vaccine effectiveness of 26.4%. So these are in addition to the protection you get from the standard dose, I presume, right? Yeah, this is extra. So 26.4 % RVE for having a heart attack, 32.9%, about a one-third reduction in your risk of having a stroke.

40:01Pulmonary embolism, 27%. Just overall cardiovascular outcomes is effective. Yeah. Get that high dose, folks. Yeah. And get something, but if you can, get the high dose. But what about the new mRNA flu shot? I'm all excited about mRNA flu shots. You got this right. I wanted to get it, but I ended up getting the flu cell vax. Oh, okay. I might go get this too. No, that was actually an interesting issue. We're going to talk about that in a moment, but maybe we'll get to it in our emailers. But yeah, so here's the article, Humeral Immunogenicity of mRNA-1010, an mRNA-based seasonal influenza vaccine in adults 50 and over.

40:44That would be me. Published in open forum infectious disease. So basically one-to-one, either the mRNA or standard flu shot. They're going to look at those antibody titers. Pretty good, actually, right? We've got some nice data here. And you can actually see a little bit better with the mRNA than the standard when you look at the different potential flus that one might get. Yeah. So the HAI titers are better. We'll see if that translates into clinical betterness. Yeah, I think that's the issue, right? At this time, we just have serology data, surrogate data. We'll see at the end of this season, right?

41:29Yeah, yeah. And hopefully we'll have that data at the end of the season. RSV, still rather quiet. Just a little bit of activity starting in Florida. That's about on track. So we should, as we get into November, start to see RSV. That's kind of the typical. COVID kind of bouncing around. We're still seeing a little bit of COVID, but kind of bouncing around. But it's very regional where the COVID activity is, right? Florida, I don't know what's going on in Florida, man. Florida's very high. So is Montana, right? Montana and Washington. Yeah, pretty high activity in California, Nevada. Yeah, Tennessee's got some stuff going on.

42:10But it's very regional where we're seeing the activity. But remember, it's kind of the same model. If, you know, this is probably so, you know, let's say you've got the flu. Let's say you've got COVID. Then if you've got the flu, we have early antiviral treatment. If you've got COVID, we've got early antiviral treatment. But what about all the people that you've exposed, right? Let's say you live or you go and you hang out with your parents or your grandparents. In both, there's a parallel here. For flu, there's post-exposure prophylaxis for those people that have been exposed. They can come in and get treatment.

42:46And for COVID, there's post-exposure prophylaxis with Zocova, the X-Pak, which is better than the Z-Pak, which everyone seems to get whether they need it or usually not. Okay, this is really interesting, Vincent. This makes no sense to me. So you tell me what's going on. So this is this study, Familial Factors in SARS-CoV-2 Susceptibility and COVID-19 Severity, a nationwide Danish study of adult twins and their spouses published in International Journal of Epidemiology. Right? So you're kind of thinking, right? Like your COVID, the severity, it probably all comes down to kind of genetics. It probably doesn't matter who you're married to.

43:31It's not like, oh, I'm married to this person, so my COVID is going to be more similar to theirs. No, the spouse is the control, right? Because they're not genetically related, but the twins are. Yeah. Okay. So Danish registry-linked study that included 83 ,902 twins and 37 ,719 spouses matched to 839 ,020 population controls and 379 ,190 spouse controls. They followed them from February 1st, 2020 to 31 October 2022, testing positive for SARS-CoV-2 infection and COVID-19 hospitalizations served as proxies for SARS-CoV-2 susceptibility and disease severity, right? You end up in the hospital, we're thinking that's a little bit worse.

44:16They compared concordance rates and calculated heritability from biometric modeling of these traits. What does concordance rates mean, Daniel? Like two things kind of matching. Okay. Yeah. So they found no evidence of a genetic influence on infection susceptibility in the first two waves of the pandemic and a modest influence in the third wave. Now, spouses showed the highest concordance rates by a large margin in all waves. The study found no evidence of genetic predisposition to disease severity. Co-twins of hospitalized twins had no increased risk of hospitalization. By contrast, this is weird, the risk of being hospitalized with COVID-19 was higher.

45:10This is a relative risk of 3.56 with really good confidence intervals among the spouses of the hospitalized twins than among the controls. So you shouldn't marry a twin. It's stressful. Is that what it means? I'm very surprised that there's no genetic influence on disease severity. I think in this study, I mean, I'm not ready to write it out. One of the issues here, and this is, you know, because you think about what's going on here, is, you know, maybe the Danish population is sort of similar enough that what you really want to compare is the Danes to, I don't know, the Spaniards. Well, they certainly are small, right?

45:52It's 9 million or something like that? And it may be more homogeneous than, say, the U.S., for sure, right? Yeah. No, the population is small, not the Danes. I was like, I'm not sure the Danes are small. Population, yeah. So I don't think this applies universally because we know there are genetic facts. For example, there are people who don't make interferons properly, and that's a genetic factor. Yeah. I mean, and there were whole families where, like, the whole family would, you know, all the kids would get sick. Yeah. Yeah. So I just thought it was – So it's just we should not emulate Denmark.

46:28That's all I'm saying. I get – you know, it's just the reality is Denmark is, you know, quite a bit different than the world. So it's quite a bit different. They own Greenland, right? They – well, it's interesting. They have a wonderful relationship with Greenland. Greenland actually has, you know, sort of its own kind of separate control and – yeah. But they have a very nice relationship, yeah. I'm not sure it's ownership, but anyway. Greenland. Not like the way we own it, Vincent. Daniel, Greenland population is 55 ,000 people. Yeah, I think somebody was going to like pay them. Like, I'll give you 20 grand each if you just, you know, become the 51st.

47:07It's less than the block that I'm on here in New York City. It's amazing, right? Oh, my gosh. Yeah. So, all right. So, closing words, no one is safe until everyone is safe. You know, we're wrapping this up. This is the last episode that's going to be part of our American Society of Tropical Medicine and Hygiene fundraiser. We may do a little bit of an overlap because I know folks at Notre Dame might be trying to do a fundraiser for Dixon. So, you know, just let us know if there's a little bit of an overlap there because we're going to be doing that one health lecture series in memory of Dixon.

47:44But this is it. And then we're going to do Vincent's favorite fundraiser, which will be Microbe TV. So go to parasiteswithoutborders.com, click on that Donate button. It's time for your questions for Daniel. You can send yours to Daniel at microbe.tv. Ken writes, I would never drink raw milk, but what I'm wondering is if it is okay to eat cheese made from raw milk. When I wanted to rebuild my microbiome after antibiotics, I was advised to eat a very wide variety of fermented foods. I was told all cheeses aged at least six months were safe. Now, my wife recently had antibiotics and we're wondering about raw milk cheeses.

48:27Yeah. So, Ken, it's kind of interesting what you're asking. So, you want there to be bacteria in the cheese. Then you're asking if it's safe. So, in the US, we have this FDA rule where if the cheeses are aged more than 60 days, then they're considered safe. But I put my little, you know, quotes up there. And so the idea is there's a certain amount of salt, there's a pH effect, but it's not the same with all cheeses. Like your hard cheeses are gonna be safer than some of your softer cheeses. But yeah, if you're trying to restore your microbiome, which is kind of a separate issue, you might wanna actually do stuff where there are live cultures, your probiotics, things that have like bifidobacterium, things like that.

49:13Yogurts, right? Yeah. Live culture yogurts. Deirdre writes, I love your clinical updates. As an NP and family practice, we often see many different types of infections, and I really appreciate your updates. I will share that I recently had a patient who was exposed to a bat and needed rabies vaccination. They were not bitten, and they were able to see RAG vaccination, rabies immune globulin vaccination, between her third and fourth doses of the vaccine, they developed a rash treated with prednisone. The question then arose, did they need a fifth dose because she received prednisone? I tried the county rabies contact who told me they didn't know.

49:53Our practice tried consulting ID as well as other specialists. However, we weren't able to get an answer. When we sent them to the county location to get the fifth dose, they wouldn't give it to them as they were afraid the rash was an allergic reaction. I don't think it was an allergic reaction. So I tried to call the CDC in Atlanta. I left a voicemail. It took over a week for a response, and the response was to contact the State Department of Health representative for rabies. Oh, my God. We were finally able to get our fifth dose via the emergency room. Any clinical pearls would be appreciated, given the nature of rabies.

50:29The wait-and-see option didn't seem wise. An additional detail, we ordered rabies titers. Those take up to a month, so no benefit there. Thank you and your team for all your knowledge and updates. Yeah. Oh, my gosh. Right? What a disaster, Vincent. You know, this is not the way. I mean, the CDC drops the ball. They can't give advice. Remember that you had a quote from a guy at CDC last week who said, oh, we're staffed. We can handle rabies inquiries. Yeah. Apparently not, right? Apparently you go to voicemail and no one calls you back. And then when they do, they're like, I don't know. So this falls into sort of an interesting category.

51:04So, you know, I'm sort of, you know, why did someone give someone in the middle of their rabies vaccination course prednisone? Because the problem there is now you're interfering with their immune system. You're not sure how well the rabies series is gonna work. You then fall into the category of, hey, I'm trying to do vaccination in someone who is immunocompromised, immunosuppressed. And we do have recommendations for that. And so, and your email's good because it gives me sort of a little bit of information. So in general, if you're not sure about a person's immune system or they're immunocompromised, and there actually is a CDC link where you can find, but just sort of have to think it through.

51:43You say, okay, they got prednisone. I'm going to consider this an immunocompromised person. The fifth dose is recommended. But also, as you point out, you know, checking the rabies titers also. So give that fifth dose because you're not sure if the abbreviated, it was really a few years back that we switched to the four dose instead of five in the US. Give that fifth dose, but then three weeks later, and think about timing, right? You want to do it right away. Three weeks after that fifth dose, check the titers. See if it's there because you may actually even end up doing more because you want to get the titers above a defined threshold.

52:20Tim writes, I'm a 54-year-old anesthesiologist in Oregon. I developed allergic asthma with eosinophilia in 2022, shortly after receiving a Pfizer mRNA COVID booster. My asthma is now well-controlled on inhaled corticosteroids and the biologic benrolizumab. I understand that association does not mean causation, but I'm also aware that in rare instances, patients can develop an eosinophilia following mRNA vaccines. The mechanism appears to involve a Th2 immune skewing effect in susceptible individuals with preexisting asthma or atopy. I have received annual Pfizer mRNA COVID vaccine subsequent to developing asthma.

53:02My question is, should I consider switching to the Novavax COVID vaccine in the setting of my eosinophilia on the off chance that continued mRNA vaccines are contributing causative or exacerbating eosinophilic asthma? I'd like to continue to protect myself with immunization. Thanks for your input, and thanks for your outstanding and informative podcast. Yeah. So Tim, this is a great question. And just to sort of lay it out for our listeners as well, when you're developing a vaccine, one of the things the FDA is going to require is that you show that you're getting a nice balance between a Th1 and a Th2 response, right?

53:42This is sort of an old way of breaking down the immune system, but it's still actually relatively valid. And the idea idea is, you know, the Th1 is going to be much more of a cellular response, which seems to make a lot of sense in the world of viruses. Th2 is going to be more of an antibody, also an eosinophilic response, right? So that's going to be something we think about with like parasites and bacteria. So you want to have this balance. So I understand the concept of this. Now, putting it into practice, Is it likely that it's related to the mRNA vaccine? Probably not. I mean, this isn't something that we saw with a high enough signal that it sort of warranted further testing.

54:30Is there some advantage to switching to Novavax over the mRNA? I don't know if we know enough here. It's a reasonable thing to consider. You know, if you're kind of going along at a plateau and your asthma is requiring inhaled corticosteroids, biologics. You might say, hey, this next round, I'll try Novavax and see if this plateau that I'm on, maybe I can use less inhaled corticosteroids, et cetera. So worth considering, but it's nothing really compelling here that there's a causal link. Susan writes, I'm a loyal TWIV listener. Can't thank you enough for years of providing your knowledge, common sense, humor at times, and great quotations.

55:13I have a few questions. My healthy 13-month-old granddaughter started daycare one month ago and completed the initial two-dose spike vaccine series in July. Having read the AAP recommendations, it's not clear to me if she also needs to get the updated vaccine against XFG this season. If so, should she wait until mid-November, which is four months from her last shot, or wait a full six months to maximize the benefit? Okay, take that one first, please. Yeah, so it's interesting. So the way they did the studies and the way they package insert actually is for the new COVID shots this year, the new XFG, is that you're not supposed to have gotten a COVID vaccine within the past two years.

55:59I mean two months. Sorry about that. So the last two months. So I was looking at this. So it was July. So August, mid-September. So we're in end of October. So you would look at this and say, here's a person that previously completed their series. They're now eligible, no contraindication to sort of entering the adult world of a once-a-year COVID vaccine. The XFG, this is actually not even – not a booster, right? It's an annual because that prior spike vax was not XFG. So, yeah. So, yeah. That's the first part. Okay. Also, she completed the two-dose flu series in March. Should she get the flu shot now or wait until October, November for timing for the holidays?

56:49Yeah. So as we mentioned before, flu is here. It is on the way up. Yeah. Get it now before you end up with the flu. And finally, for our healthy adult children in their mid-30s and healthy adults like my husband and myself, 70, last vaccinated in late October, can we all wait until the end of October or early November to get flu and COVID vaccinations? Okay. So the problem, I guess, we have with the flu shot, as I'm pointing out, is the flu's here now. So there's no point getting your flu shot after you got the flu, right? You want to get it before you got the flu. So, you know, we've got a dozen folks in the hospital where I was at earlier today, oxygen, bad flu.

57:31So unfortunately, the flu's here early, COVID's active right now, might as well go ahead and get them. Okay. And Helen writes, Oh, actually, I want to comment about the next part here. Okay. I'll read it then. I was so much surprised that you have already received both. I assume that even though protection wanes, you believe you'll be protected through the winter season. I read there might be an early flu surge on the West Coast. I know there are no guarantees with all of this. Yeah. So Susan, yeah, I was looking through the emails earlier. So, and I saw this. And it's an interesting issue because I remember, Vincent, it was a number of years ago when you were talking about the timing of the flu vaccine.

58:14And so there's two aspects to this. So one is that you get your flu shot, right? Two to three weeks later, you get your peak of the antibodies. And then those antibodies are going to drop about 10 % a month, right? But what's interesting too, and this came up at the ID week, someone asked a question about this, like, yeah, but that's antibody levels. Does that really correlate with susceptibility to the flu? And there was actually a nice Canadian study where it really showed that there was a kind of a tracking for every 10 % drop in the antibodies per month. You're also seeing a 10%, you know, decrease in your protection from the flu.

58:51So yeah, it's not just antibodies that drop 10%. The protection drops 10%. So there is kind of a, like they say, you know, try to time the market. But yeah, you do kind of want to time the flu season. But protection against what? People ending up with, it was clinically like relevant, identified, going for medical attention flu. Okay. Yeah. But I know I'm glad you asked that because I think the protection against severe disease is probably more sustained. Okay. And Helen writes, thank you for all you do to promote science education. I am a formerly vaccine-hesitant person who chose to educate herself during early COVID, and now I'm a huge supporter of vaccines with a new hobby studying virology and public health.

59:35MicrobTV was a major player in my enlightenment. Great to hear that. Much to my dismay, however, I tend to have strong reactions to vaccines, especially, it seems, to mRNA COVID jabs. I have gotten all the recommended doses since 2020. I have consistently ended up in bed for two to four days with body aches, migraine, vomiting, and sometimes other symptoms, followed by a week or two of digestive trouble. You can imagine my joy in hearing that there might be a vaccine with less reactogenicity. I wasn't able to acquire Novavax in a timely fashion last year, but I was able to get new Vaxovit at my local CVS last Friday.

1:00:13I waited till the weekend in case I ended up in bed. I'm happy to report that I felt crummy on Saturday and spent a portion of the day under the covers. There was neither migraine nor vomiting, and I felt fine by Sunday. I wouldn't have known about this alternative if it hadn't been consistently mentioned during your clinical update. I had to go out of my way to request it, but I'm so glad I did. I have friends who stopped getting COVID vaccine because they don't think the reactogenicity is worth it. I'm delighted to have an alternative to suggest to them with profound gratitude. Helen from Pittsburgh.

1:00:47Great, Helen. No, thank you. That's excellent to hear. That's TWIV Weekly Clinical Update with Dr. Daniel Griffin. Thank you, Daniel. Thank you, and everyone be safe.