Okay, hey, everybody. It's lovely to see you. My name is Dr. Tenassi Wendy, and I'm the chief of workforce health and wellness at Stanford Medicine, rebranded occupational health to workforce health and wellness, rebranded Stanford Healthcare to Stanford Medicine. It's apparently a thing they like to do. It's a pleasure to be here today. Thank you very much. This is going to be a session on basics, TB basics. Look, tuberculosis has been around thousands of years, so the odds that Amy and I, even as good as we are, can cover it in 35 minutes, pretty slim. So we're going to give you the points that we think people have asked us about the most over the last few decades. So I'm going to focus on the testing, because when I get done with my talks, everybody comes back and says, oh, those are the slides I needed. And Amy's going to help you with the practical, life-saving parts of the talk. So again, I'm from Palo Alto, California, and I'll be speaking today with my dear friend and colleague and your local hero, Amy Berman, from right here in very own Philadelphia, Pennsylvania. Is the volume okay? Because I don't want to be too loud. It's okay or it's too loud? It's okay? Okay. Okay, terrific. Now, here's another thing. Being as, seeing as I'm from California, with a home in Ghirardelli, I tend to throw candy at people. However, some of you are kind of far away. So you are welcome to come here, or I might actually hit you with the candy, or I can like toss, save it for you or toss it somewhere and you come up and get it, okay? Let me get this going. I don't know where my candy points are. All right. Thank you all for very much for being here today. It's going to be weird to look that way. Okay, let's just talk about TB really quickly. It's all over the place, right? Everybody knows that about a third of the people on this planet have tuberculosis. Pretty much everybody know that? Yeah? Why? Like, does that make any sense at all? We just saw a COVID-19 outbreak. Part of the planet got infected. The whole world mobilized all of its resources to rally to the defense of this disease that didn't infect nearly as many people as tuberculosis does today, and as it kills every year. Why is TB so prevalent? There's some hints on the slide, right? So it's very hard to prevent getting TB. It's airborne respiratory disease, like COVID is, right? It's very hard to detect it. It's got a waxy coat on it. That's the mycolic acids on the mycobacterium. That's the mycolic acid. That's the myco in the name of mycobacterium. It's very hard to treat once it becomes active, and that's the trick. It's not very hard to treat in its latent stage. It's very hard to treat once it becomes active. The treatment is a four-drug antibiotic therapy that lasts for months. About 1.5 million people die every single year of TB. Compare that to COVID, and you're covering just a couple of years in the COVID pandemic. We have every single year. So if you got up to about 3 to 5 million people died of COVID this past year, that's a couple years' worth of dying of TB, which happens every single year, and has for hundreds if not thousands of years. You remember that TB was called consumption? Who remembers that? Yeah, very good. It used to be called consumption because it's so metabolically demanding. Now where is tuberculosis? So what I want to talk to you about is tuberculosis in the United States, but we have to frame this with tuberculosis in the world, and that's what I've mentioned before. I'm still going to poke these up a little bit. Where is TB? This is a graph of incidents, okay? So the vertical lines are the incidents per 100,000, and the horizontal line is a list of countries. In between each of those vertical lines, so on the far left, you've got a country like South Africa, which is approaching 900 cases per 100,000 of active TB a year. In between all of those lines are other countries. So this is a world map, and most of them are up there at the top. For chocolate number one, where is the United States? Come on, you're going to have to be quick because we're going to run out of time. Where is TB? What? Right there. Where's the United States? Come on. Dark chocolate. What, Glenn? One-third up from the right. One-third up from the right. Who else? What was that? Down by Sweden. That's somebody who's been to my talk before because Sweden's not on the list. Okay. I'll give Sweden the winner. Okay. Here's the United States. We are off the map. We're down in the flatlands. We keep company in our big... I know. It is a round of applause. Good for you. Everybody in public health. This is unbelievable, isn't it? 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Who has TB, right? Active AIDS, malnutrition, the desperately elderly, the severely immune compromised in this world have active tuberculosis, okay? So what the companies needed to do, and both companies have the controls, the T-Spot has it also, so they also have a negative control and a positive control, and in fact they use the same proteins, ESAT6 and CFP10, which are both TB-specific antigens, so they can not, they can not interact with a BCG. Everybody hear that? They can not cross-react with a BCG. Somebody who has a BCG cannot be the reason that they have a positive IGRA, because the BCG does not have ESAT6 and CFP10. These are specific to mycobacterium tuberculosis infection. Okay, the negative tube is a nil, it's a control on the test. The positive tube is a control on the person's immune system. That means the result in that tube, when you put the blood in the tube and you expose it to all the garbage that's in that tube, called PHA, phytohemagglutin, what should the result be? Very good, positive, whoever in that corner said it, it should be positive, okay? That's a control that their immune system is working. If you're supposed to be checking people who are out there in Namibia and they have a terrible immune system and you do a TB test on them to diagnose a life-threatening illness and it's negative, but they have no immune system, you're going to hurt people. And the test companies understood this, so they controlled and they said, let's make sure that they have an immune system that's adequate to respond to this garbage. And then they would also be able to respond to TB-specific antigens, which are in the other two tubes. Now it's TB1 and TB2. They have the same antigens, they have just long-chain versus short-chain. Okay, this is where I'd be throwing a lot of chocolate at you. This was like nine chocolates, okay. The nil tube is negative, are we happy? The mitogen tube is positive, are we happy? Okay, those two are negative. What's the result? Negative, fabulous. All right, let's look at this. Nil tube is negative, that's awesome. Mitogen tube is positive, what's that, good or bad? That's good, that's what we want. So I want you to get the lab values from your lab, and I want you to be able to read your own values and look at them. That's why I'm telling you this, so that you can go back and dissect what's going on. Okay, let's look at the TB1 and 2. They're both positive, which is greater than 0.35. That is a very low bar to get that little. I heard over here some background nil. People will have a little background to interfere on gamma in their system if they've been exposed to a virus lately. That will be subtracted from the amount of response that they have with the TB1 and 2. What's the result of the bottom test? Positive. All right, does that look easy? Uh-huh. Okay, let's look at it again. Nil tube, this is the next level. Nil tube is negative, mitogen tube is positive. We're good to go? TB1, positive, what's the result? Don't know yet, and positive. Who said positive? Oh, good. Okay, chocolates. This confuses people, as you can understand, but what the company's going to do is it's going to defer to the positive. So when there's one tube that's negative and one tube that's positive, if you do not get the values, the only thing you will see is positive. Do you believe that the 16-year-old boy from Kansas, who's never been out of the country and was born in the United States, is positive with this result? No. Do you know that if the only thing you get from your lab is positive? No. That's the value of what we're talking about here. You need to know what's truly positive and what isn't. What are you going to do with this one, gentleman in the blue jacket? Retest. Very good, very good. It reads as positive. Your nurses will have to report it as positive, but if you educate them to look at the values and look at these splits, they can defer to you and they can retest them, or you can make it a standing order. All right, next test set. Negative nil, positive mitogen. Good to go. Negative TB1, positive TB2, result? Huh? I haven't learned anything. Louder. Retest. Retest, but the result that will come from the lab is? Positive. Positive, very good. Okay, they're positive, but they might not be. This is where we have job security as physicians and PAs and NPs. This is your job security. This is where you're going to use your medical diagnostic powers. You're going to say, where were you born? Who do you live with? Where did you travel? Where did you stay when you traveled? Have you had a positive test before? Have you had a positive PPD? Have you had a BCG? Have you had a positive QFT in the past? Show me the results. Go through the series with them. Decide if you think that this is really positive or negative, and if you think it's negative, retest it. Over 97% of them will retest negative. No, over 87% of them will retest negative. I think it's closer to 97% on the splits. I don't want to go into the values because we don't have time. I need Amy to get to her important part. Here's where it gets really ugly. What's a QFT indeterminate? It means that that mitogen tube, that it's really, this is easy and they don't tell you it, indeterminate is almost always because of the mitogen tube. The mitogen tube is very sensitive to temperature at over 74 degrees Celsius or 25 degrees, 25 degrees Celsius, 74 degrees Fahrenheit. The PHA that is coating the tube can go bad. That will cause a lack of immune response. That means that the mitogen will test low, and the result that the company will give you is an indeterminate. What do you do? Retest it. This is where the 97% of the repeats will be negative. Don't worry about it, just like, don't, it's no big deal, send a retest. How soon? Fabulous question. We did a big logistic regression analysis of that. It doesn't matter because it's a test fault. The only thing that matters is if you can identify that you have a bad set of tubes, like we had over 1,000 that got too hot on a box truck when it was being driven up from Valencia in the summer, so that was a thing. We actually tracked it back to the shipping container through the Panama Canal legitimately, and now they put them all in cooled containers because of that experience. So if the mitogen tube gets too hot, the mitogen will be low, the result will be indeterminate. Retest it any time as long as you're convinced your tubes are good. Next one is T-spot can report as borderline. Again, that's easy. That's in the five to seven spot range. Just repeat it. Remember, there's no borderline in Europe. If a test is invalid, that means something went wrong with the test, and that is more to do with the nil tube, okay? It could be that the cap came off. It could be that there are bubbles in it because whole blood will bubble. So an invalid test, and both of the companies have invalids, retest it again. It was a flaw with the way the processing happened. Now, what I didn't tell you, and I got it. Amy, how are we doing? This is my last slide. We're good. Okay, we're good. Let me give you one more thing to think about. The reason this quantiferon assay is so cool is it's one of its kind in the world. The assay happens in the tube, not in the lab, okay? The diagnostics happen in the tube, not in the lab. The tubes themselves are coated. I don't actually know how the company got this past the FDA because that's part of why we've had some of the troubles. The reason you see your staff having to shake the tubes is not because they have to agitate the blood. It's that they have to expose the whole blood to the walls of the tube because the tubes are coated with the ESAT-6 and CFP-10. So you take the whole blood, and you have to rock it like 10 times. That's what they extract them. So that the blood all comes into contact with the ESAT-6 and the CFP-10 so that the immune response can happen. So the interferon gamma can be released into the blood, and then you go to the lab and analyze the blood. But the reaction happened in the tube, and there is no other test on the market in the world where the reaction happens in the tube. Okay, everybody follow that? This is a really advanced question. It's at least a two-chocolate. What is the result of the test if the tube is not properly shaken? Huh? Louder. Negative. You really know your stuff. I know you, though, too. If you've been here before, whoever's been here before, I apologize. I'm sorry that you're going through it again. The test will be negative if they don't shake it because the blood was not exposed to the TB1 and the TB2. But the control on the test is that the mitogen should also be too low because it also wasn't exposed to the mitogen tube. So once again, when we think about the nuances of this test, the test will defer to the positive. The test will always defer to a positive. Even if your mitogen tube is inadequate, as I mentioned here with the indeterminate, they actually won't always report it as indeterminate. If they get an immune response in TB1 or TB2, that will override. As I said, trump, bad word. But that will trump the indeterminate, or good word, but it's a presidential name. The positive will trump the indeterminate. So even if the test is bad, even if the immune system is really bad and it doesn't amount to an immune response, occasionally you will get a positive TB. Trust that positive TB. They must be really positive if they can mount it. Does that make sense? Are you all feeling okay about interpreting the QFT to understand the value of why you need to get those results? How to look at the more nuanced? All right. Well, then, we're getting there. Why are we talking about this? We're talking about this because when you make this diagnosis, which will be latent tuberculosis, you can treat it, which means you can save lives. There's a lot that we do all day, every day with our lives in occupational health, and there is not a lot we do that saves lives. If we can move this audience and you experts to treating latent tuberculosis, you will save lives. This is a big movement for us in TB, and to that, I would like to introduce Amy Berman, my dear colleague, to talk to you about how you can really make a difference in the world. And that should not be happening. So if you'll kill my deck, please, in the back and put Dr. Berman's on, those are my extras. All right. Thank you all very much. Hi, everybody. I hope you get hungry. You're not going to let me through? I'm going to have to go. Hi, everybody. I hope you get hungry. You're not going to let me through? I'm going to have to go. I'm Amy Berman from the University of Pennsylvania, and I don't, there we go, okay. So I'm going to, I have no disclosures, but in a lot of ways, this is going to be a marketing talk. I also don't know in this wonderful, large room with all of you wonderful people in it, how many people are kind of ahead of my curve and how many aren't. So I hope you would feel free to interrupt me at any point if I'm either not making sense or it's so obvious that you want me to move on. So basically, I'm going to run through in this super short outline here, the reason we treat, which you already know, how you can integrate latent TB detection and treatment into a workplace paradigm, how you can really embrace treating latent TB in the workplace. And as long as I'm at this, can I just have a show of hands for people who routinely treat latent TB in their clinics? Okay, so great. A mix, a good mix. Give us lots to talk about. I'm mainly going to be talking about healthcare, but I will also touch on occupational TB exposure and reasons to treat latent TB in other occupational settings, and then I'll try to convince you that this will work for your own occupational health service. The real, this is probably the same, okay, I don't know why my patient has actually swallowed a little device there, but basically, the purpose of this talk, the purpose of treating latent TB is to prevent the x-ray on the left from becoming the x-ray on the right. Hopefully we won't let more than 10% of those people die, hopefully it'll be less, but it is much better to treat when you can keep your patient's lungs looking like they look on the left and never get to the point of illness, transmission, or any complications. So that's where I come from. I'm going to present myself as a case study that I hope will be useful to you, and this is a warts and all thing, just kind of, you know, how I learned on the job. I've actually spent my entire adult life at Penn, and most of it in the Occupational Health Service, which I started at in 1994. Now 1994, I'm trying to look at ages and gray hair here, 1994 was at the end of a kind of scary period for tuberculosis, just ignore the left and look at the right hand screen for a minute. After many, many years of TB declining in terms of case rates and deaths, there was a bump in the late 80s and early 90s. This was driven by a number of factors, a number of social factors, including the fact that the public health services had, you know, maybe become a little bit complacent about TB with the advent of good TB medication, that our incarceration rate was ticking up massively, and that's a great source of tuberculosis in general, but certainly in this period. And the HIV epidemic was going bananas, and it became clear, eventually, that that was a huge driver of tuberculosis reactivation and eventually multi-drug resistant TB. There was active transmission going on in this period, it was infecting and affecting health care personnel, some of whom acquired multi-drug resistant TB and died. So it was kind of a scary time, a time, there we go, that called, I think, for action. So when I was offered the job at Penn, this was in that context. In point of fact, the tide was going to turn very soon, but you know, you don't know that when you're in the moment. I knew that our hospital admissions were up, our hospital exposures were up, the city rates were up. This is a large, poor city with a lot of immigrants in a huge incarcerated population at that point, and a burgeoning HIV population. When I took the job, we were running 12 to 15 percent of people TST positive, and remember, this is long before the advent of the interfering gamma release assay, so just trust me on this. But the enormous majority of those people were detected on hire, not from conversion in the workplace. Now, that's partly because we actually weren't doing a fabulous job of annual testing at that point, or even post-exposure testing, but we certainly knew we had plenty of people who clearly made the definition of latent TB. And when I was negotiating for the job, I told them, you know, the biggest task in that first year was going to be to get our TB control program up and running, and that was very definitely true. It took me about two years to get the first year done. And I also seemed pretty obvious that we should follow the American Thoracic Society guidelines and the fine print of the 1994 TB guidance for healthcare personnel, and treat those people with latent TB. In my naivete, I couldn't see any reason that you wouldn't treat somebody who came in as a new hire, as opposed to somebody who converted after an exposure in the emergency department in the MICU. It's the same disease, the same risk of reactivation, and I was horrified to be told that I could only treat work-related illnesses and injuries. And I was so horrified that I actually walked away. I went home for the month of August and just waited, honestly. And they must have been really hard up because they came back to me in September and said, look, okay, just please start. So I did, and we have been treating latent TB in the workplace ever since that time. I negotiated that we would be able to treat people without billing them, without charging them, without charging for the medication, without charging for the lab tests, without charging for the visits, and without charging for pulmonary consultation, which I expected would be frequently needed. And we've been doing it, really, ever since then. Our goal, which we hopefully get close to, is to offer latent TB treatment to everybody with latent TB, everybody who, once you go through all the nuances that Dr. Tenassi so beautifully laid forth, once their Bayesian priors are addressed and you actually believe that this person is at risk for reactivation, I think maybe a better way of saying latent TB, that you will offer them treatment, if medically appropriate. It's not required. It's not mandated. All we require is you have to listen to me or one of my colleagues go on and on about this and see if you want to be treated. Of course, we have the option, as we all do, of engaging the person's primary care provider or specialist, their rheumatologist, perhaps, and our local public health colleagues to treat. And we have the, many of us are in the fortunate position, I know I am, to have ID and pulmonary consultants if we need them. It turns out you don't really need them very often. This is actually very straightforward. And that part of the cost kind of fell away. It's nice to have when you need it, but it's really rarely needed. Happily, the tide turned, I think, partly as a result, well, as a result of many, many factors, including control of the HIV immune compromise epidemic, to some extent, control of transmission in incarcerated populations and homeless shelters to some extent, and to some extent, just treatment recognizing, again, the importance of treating latent TB. Ten years later, this is 2005, the next version of the TB guidance came out from the CDC, and it said in the somewhat fine print, you really think about treating people with latent TB if it's medically appropriate and you can handle it. It doesn't say treat people with latent TB if it's work-related, and don't treat people with latent TB if they acquired it in childhood. It just says treat them if you can. So this has been there in the guidelines at this point for a long time, I mean 30 years it's been in the guidelines. The most recent iteration of the TB guidance, and you'll probably notice there's a lot of years in between these, came out in 2019. On the left, you will see the original MMWR from May 2019, which was extensively discussed at ACOM and at our AOHC conferences since that time. You'll notice in the author group a lot of people that you know, including Dr. Tenassi. And this was a kind of very concise but radical change in the way TB screening was recommended in the guidance. It eliminated annual screening because the TB case rates, as you just heard, had fallen to so low a level that it no longer made sense. It did not eliminate TB screening for new hires, and of course, did not eliminate it post-exposure. We expanded that guidance into the ACOM TB guidance document, which is posted on the other side of the slide. And in that, we tried to spell out a number of things, including how to embrace latent TB treatment, as well as detection in an occupational health service. This is kind of a busy slide. Sorry about that. I'm trying to point out the pertinent differences and non-differences between 2005 and 2019. But I really want you to focus on the one that is conveniently in bold red letters with underlining in the lower right-hand corner that says that they now unambiguously, with no caveats whatsoever, recommend treating latent TB in healthcare personnel, who aren't that different from other people with latent TB, unless there, of course, is a medical contraindication to doing that. So the question is, is this something that we, that I, that you can consider doing in your own service, and if not, in your own clinic or your own practice or your own employer? And if not, can you optimize your referrals to make sure people are strongly recommended to be treated and actually have access? So again, of course, we're going to be tracking workplace exposures. If anything, with the elimination of annual screening, this has become more important rather than less important. It is absolutely true, as you heard in the first half of this talk, that there's a lot less TB around, and that's great. But there still is TB around. I mean, we certainly have seen TB admissions, and we certainly have seen TB exposures throughout COVID over the last three years. And I suspect that's true in most locations where you have TB to begin with. But despite that, or as you would expect, the overwhelming majority of latent TB cases that you find will still be among new hires. They will be identified at the post-offer pre-placement exam, and we can do something about it then. That is your best opportunity to find people. That is your best opportunity to refer people. And if it works for you, that is your best opportunity, in my opinion, to treat people. And also, it helps if you can get them before they get sucked into their house officership or their NICU-charged nurse life, when they really will have less space in their heads to listen to you about this. We know, I won't belabor, actually, maybe I will slightly belabor the point. Latent TB treatment works, and we have known that for a very long time. The diagnostics are difficult, but the treatment is straightforward, and it is absolutely effective. Nothing I'm saying hasn't been recommended by the ATS and other countries' public health services for many, many decades, long preceding 1994. We know that for the isoniazid regimen. We know that for the rifampin-based regimens, including the hyper-short course 3HP that Dr. Tenassi introduced. And we know that there is toxicity, and we know how to manage that toxicity. I certainly see the argument for letting people's primary care providers or their specialists or their local public health department handle this treatment. I mean, they presumably have the knowledge. They presumably have the resources. They presumably have the access to the medications and people's records. Faster? Oh. But my experience has been that they're very wary of treating. And I'd like to say this has changed radically over the last 20 years, but it hasn't changed radically to me over the last 20 years. The public health departments have been fabulous, but have you noticed they've been a little busy lately? So I think in terms of access, being able to make this available in the workplace is really a huge advantage, not only to your health care personnel, but to people in other industries, and not only to the workers, but also to their communities and their families. Granted, we're treating them to keep them well 20 years from now instead of perhaps next year, but if you think long term, as I think we should, this is an easily achievable way to keep our communities and our workplaces in good shape. So this is just summarizing what I was just saying. If you can offer in-house treatment, please believe me, based on 30 years' experience, it's not that hard to do. It's so much simpler than most of what you're managing in terms of work injury treatment. And if you can't treat them, at least counsel them and refer them, regardless of whether they were infected during their training in sub-Saharan Africa, or when they are actually in your hospital in Minnesota, or wherever it might be. If you can minimize the barriers in terms of access, in terms of cost, in terms of billing, then all the better. If you need to bill, then you bill. I will not belabor these, just looking at my time a little bit. The risks for progression were summarized in the prior slide set, and are here as well. I would just give a quick shout out to the immune-modulating rheumatologic medications, which are in ever greater use, and are letting people be active in our workplaces who would not previously have been able to do that. That's fantastic, but they are immune-compromised, and they are at risk of progressing from latent to active TB. Also true for our increasing number of people doing really well in the workplace with organ transplants and chronic malignancies. So at the same time that we have more tools, we also have more people, I think, at increased risk of progression. Don't forget to rule out active transmissible TB disease, meaning pulmonary or laryngeal. Just for the record, you just heard from Dr. Tenassi that 80% of TB is pulmonary and 20% isn't. So if you have somebody with TB of the bone or the pericardium I've seen people present, do they need to be treated for active TB? Are they contagious? They're not. If it's not laryngeal and it's not pulmonary, it's not contagious. So those people can actually be managed even in an active setting in the workplace. This is not trivial. You do need to take a look at people. You do need to assess their prior probability of whether their EGRA or their TB skin test is a true positive. You do need to take a history not only for their risk of progression, but also for their risk of complications and drug-drug interactions with these medications, which are not trivial. Then you have a number of regimens to choose from. Out of these, the rifampin-based short courses look to be more effective, less toxic, better tolerated, and more likely to be completed. So we are putting an increasing emphasis on the four months of daily rifampin, 4R, or three months of weekly isoniazid and rifapentine, 3HP, for those reasons. I'm clearly an enthusiast. I'm fairly passionate about this, but you do have to look out for those drug-drug interactions. This is just a copy and paste from the CDC, including those two well-established, well-documented, very effective regimens, along with one that's just a little bit newer. I haven't personally started using it, which is three months of daily isoniazid and rifampin. And the one we least like to deal with, which is the long-course daily isoniazid, ideally for nine months, still may be the right regimen for people who can't tolerate the rifamicins either by themselves or for drug-drug interactions. Just whatever you do, just if you're any drug, including isoniazid, but especially including the rifamicins, do make sure you check every single drug-drug interaction. The most notable ones that we see, especially in the healthcare workplace, where people tend to be, frankly, of childbearing age, are the decreased effectiveness of steroid-based oral contraceptives, and also the decreased effectiveness of a lot of the HIV and PrEP medications, which are in increasing usage. And then maybe in our older population, the warfarin, and across all ages, some of the antidepressants. Please take your time and check, as I'm sure we all do, for all new prescriptions. Monthly monitoring is recommended. I don't know if you've got that. That's part of the slide that Dr. Tenassi put up as her last slide. I'm pretty much an enthusiast for doing serial liver function tests, because it's just such a sensitive way of picking up issues and potentially reevaluating your regimen before people become symptomatic. So that's not in the guidelines, but it's a personal recommendation. People miss doses. They should not double up. The goal, the definition of completion for 3-HP is to get 12 doses done in 16 weeks. If it takes 14 weeks instead of 12 weeks, that's fine. We don't split the small stuff. We just want to get most of the doses in without putting them too close together, putting them too close together, and creating some unnecessary toxicity. And kind of the way I tell people to remember this is, never double up, and do complete all the doses. Just, if it takes a little longer, it takes a little longer. Very briefly, I will just mention that this is not just a health care worker occupational concern for patient safety. It is also a huge concern for your non-human primate workers, both for their own sakes, but also because most non-human primates are more susceptible to lethal TB, and you can wipe out a valuable colony in a matter of weeks if you have an infected animal care technician involved in their care, and that's just a bunch of references proving that point. And a really pretty picture from an island, which is a primate study colony off the coast of Puerto Rico, Cayo Santiago. So we want to pay just as much attention to screening these folks, but shouldn't we be treating them as well if we find that they're positive? It's not just macaques. This is a not-dead elephant, by the way. It's an anesthetized elephant being checked for TB, but mammals in general are susceptible to TB, so this may become a concern in other areas of animal husbandry, and certainly in your folks who may be doing academic fieldwork into primate areas, or even non-primate areas. Okay. I have used a little more time than I probably should have. I have a few cases here to run through, but I'm equally happy to just stop talking, take questions, and Wendy and I will be happy to do our best. Yes, hi. Wonderful talk. Thank you very much. Checkful of good information. I work with a lot of animal health technicians and veterinarians in the field that may be exposed to M. bovis. What are the sensitivity or the predictive value, actually, of the IGRA test with regards to that? Well, that's a great question. I defer to Dr. Genassi. I don't know the exact details. It's all part of the MTP complex, and it should have a sub-sensitivity for a lot of animals. Sorry. And I guess the follow-up question, in comparison to a TST. Yeah. I mean, TST is what's still being used in a lot of cases. You can see that in the macaques and in elephants, I know that they are running IGRA. Specific sensitivities and specificities, I don't know. It's an increasing area of interest to me because of migrant workers and farm workers. And there's a new FDA rule that's coming out that's going to require that farm workers be tested annually for TB, because cattle have such a problem with TB. You might have been following England or watched that show, Clarkson's Farm. But yeah, it's actually a terrible problem in the cattle population. So I don't know the sensitivities and specificities. They're both part of the MTB complex. They both have ESET-6 and CFP-10, the MTBC. So it should be relatively the same, and I don't know the details. These are the veterinarians that are detecting it in the cows. Right, for M. bovis, because M. bovis is in the MTB complex. It should be the same. I don't know the details, but I'm learning more about it. We're looking at a new test using PKAS-5 soon, specifically for the animal handlers and veterinarians. And thank you. That's a great question. Great question. Yes. Oh, hi. Hi. That's Gwen. Great talk. Thank you very much. Both of you, Wendy and Amy. Could you talk a little bit about where we are with vaccines that would prevent the progression from latent to active TB? Yeah. I mean, vaccines is great, Gwen. I'm going to talk about that a little bit tomorrow. I'm going to talk about that a little bit tomorrow. We're not in a really good place. There's things in the pipeline. There's definitely a lot in the pipeline. There's no mRNA. You know, tuberculosis is terrifically difficult to vaccinate against, and I think I should probably look at more tonight and give you better details. Do you have a specific one you're thinking about? I think it was the GSK one. The GSK. In the original studies, there's been like a 50% reduction in progression from latent to active TB. How it compares with actually treating, I don't know the comparison. Yeah. I haven't looked at the GSK in a year, so I'm going to look at it tonight. And I think it's going to Stage 3. Part of the Stage 3. Yeah. It will be in a year. It will be in a year. It will be in a year. It will be in a year. It will be in a year. It will be in a year. It will be in a year. It will be in a year. It will be in a year. I apologize. Thank you. Good question. I mean, vaccines would be great. Look at how the world is suffering with this disease. Yes, ma'am. I treat, or I don't treat, actually. I do a lot of consults with new hires within our health system, as well as like the county employees. They come back with a positive Q-gold. I'm wondering if you have any, like, questions about that. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. 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tuberculosis

TB

prevention

detection

treatment

global prevalence

latent TB infection

interferon-gamma release assay

workplace healthcare services

guidelines