Without further ado, I'd like to introduce our next speaker, Dr. Wendy Tanasi, also came to Occupational Medicine through Emergency Medicine as a Dr. Berman. She's the Chief of the Occupational Health Service at the Palo Alto VA Healthcare System, Associate Professor of Primary Care and Population Health at Stanford Hospital and Clinics, and a beloved member of our section. Please welcome Dr. Wendy Tanasi. Here's what we're going to do. So tuberculosis, right, second, like world's largest killer worldwide ever since the pre-mummification days that Dr. Rusci mentioned. We got some epidemiology, we got policy, we got practice, all to handle in a really short period of time. I have no conflicts of interest. What's happened in the last hundred years, this actually, this slide is out of date, but bear with me. I mean, it's out of order. Not going through the history, but around 1890, Dr. Koch both identified the mycobacterium tuberculosis bacillus, so you could now see what was happening. This was right after germ theory. And then a couple of years later, helped identify the tuberculin that became the tuberculin that we use in the TST or the tuberculin skin test or skin test. By 1921, the BCG vaccine was here. So this BCG vaccine is still used worldwide. It's used in England, it's used in Germany. People who are born in Europe are still getting the BCG vaccine, named after three people. The interesting thing about the BCG vaccine is that it's not the same worldwide. It's not one vaccine. So if you're in Japan, they have a BCG vaccine facility that's making a different variant of BCG than they're making in India, than they're making in England, which I think is very interesting. It's also being used very differently. So you've got populations in your healthcare system coming in from all over the world. Japan's given BCG every five years, right? Philippines is just giving it at birth, but they have the ninth highest rate of tuberculosis in the world. So you will see a great variety of both the BCG vaccine and its use. And I'm going to encourage you essentially to ignore that it ever happened. Okay, 1943, big innovation in TB. TB antibiotics start to finally treat, especially active tuberculosis. And then I'd say that around 2001, when the interferon gamma release assays, which is the blood test for TB, came out, this was another huge intervention in TB diagnosis and potentially in treatment. I'm looking at this from a first world point of view. But look where we are. We're like over 110 years of a couple of major milestones. Well, now I think things are really different and they're ramping up. And that's a really slow timeline. Going forward, we're going to be able to make a lot of improvements based on new antibiotic regimens and new blood tests. So I want to go back to the very basics. Some of our staff is MDs. Some of them are not MDs. Some have not thought about tuberculosis in 30 or 40 years. Just so you know, sort of this iceberg picture that I just pulled off the CDC website this morning, I will confess, the very tippy top is the people with active tuberculosis. And this big iceberg, the sort of three quarters below, are people with latent tuberculosis. Some of that terminology is a little bit outdated, but the concept is, and it's really important for people new to tuberculosis to understand this, and this will screw you up all the time in the hospital, because the rest of the people in the hospital don't understand that tuberculosis is like a continuum. It's like a, I don't know, it's art deco things that just go up. So there's a whole stage of tuberculosis where people have breathed it in, and it's living quietly generally in their lungs. And it's waiting to reactivate and become that top part there where it's active disease. So we call it infection in primarily its latent stage. So latent tuberculosis infection is all of that infection that exists, but is sort of below the surface where you don't really see it. Maybe you see it in a chest x-ray, maybe you pick it up ideally in a blood test. But then when that latent TB wakes up and becomes reactivated by the diseases I'll show you later, it can become active and infectious and potentially fatal tuberculosis. So when you talk to your staff and they freak out, somebody calls you and says, I have a patient on 3C, he has TB. Or did they just see a blood test that was positive and they have latent TB and there's nothing infectious about it? Or did they actually get an AFB and that person is expelling infectious tuberculosis that will infect people? You kind of dealt with this with COVID, right? People saying like, my office mate was exposed to her son's soccer coach. Do I have COVID? Right? You're going to get the same thing with tuberculosis. Think of it similarly, okay? So we have latent tuberculosis down there. They can't spread it when they have latent tuberculosis. There are millions in the U.S. who have it, who have latent tuberculosis. Only about 10% of people who get TB in their lifetime will get the active stage. Of those 10% who get it, 10% will die. So once you get a reactivation TB in your healthcare system among one of your healthcare workers or among your patients, that's a 10% mortality, very serious disease. Who will reactivate? People who will reactivate are most commonly, I think I have a slide on it, we'll all get there. Okay. So just for those of you who don't know TB that well, historically, it's the one you hear of, it's consumption. We could go through a million slides like Dr. Rusci has of the past, back to the mummy in that first slide where these, where tuberculosis is detected in Egyptian mummies. To an Edward Munch, that's a painting of his sister, Sophia, who eventually succumbs to tuberculosis. To tuberculosis in that third picture, India, Bangladesh, you can see the consumption. You can see the metabolic increase that it takes for the body to try to fight this mycobacterium so that all of their calories are consumed and they eventually die. And there's a picture there of the bacillus. So one third of people on this planet are currently thought to have tuberculosis. We don't know for sure because we can't test everybody in India, South Africa, but it looks like it's about 30% of the planet has latent tuberculosis. About 10 million of those will become the top of the iceberg. They will get active TB in its contagious form and about 1.5 million of those will die this year from tuberculosis. There's the active TB that we hear about commonly and then in lesser developed countries and not commonly here, there is MDR, which is multi-drug resistant TB, XDR, which is extensively drug resistant TB, and TDR, which is totally drug resistant TB. None of those are good. All of those have higher mortality rates than the regular active TB. It is the number one infectious disease killer in the world until COVID, which surpassed it just for one year. So it was TB, TB, TB, and then COVID. How many people died of COVID? I don't know exactly. Five million? Six and a quarter million. How many years of active TB deaths does that make? About three or four. Right? So put it into perspective. We have one and a half million people dying every year on this planet from tuberculosis. And all of a sudden, there's a big thing when two million people die of COVID. All right? Like, I get it. It was important. But also, coming from a TB perspective, why aren't we paying attention to this worldwide? Why aren't we really innovating and moving forward? Well, we have a problem because at the bottom of the iceberg, there's a whole harbor of disease. It's all sitting there in its latent pocket, right, waiting to reactivate. Well, that's where you all and we can come into play, and that's what I'd like to have us get to at the end of this conference is understanding that you have the power to cut down on these numbers worldwide. All right. Let's move forward. Real quick. Symptoms. You all can look it up. Night sweats, fever, hemoptysis, weight loss, cough. You have a 50-something-year-old female who comes in and says they have these things. You think menopause, right? Sorry. Perimenopause. They're kind of similar, but that's exactly who gets missed. Who gets missed? It's always the women, right? It's always the perimenopausal women because the symptoms overlap so many other disease states. Keep in mind that it might not be that and it might be their latent tuberculosis activating. That's what happened in RVA. So there's a difference between who will get TB and who will move from that latent state to the active state. This is a slide of the people who will move from the latent state to the active state. They are not more likely to get TB, but they're more likely to move from the bottom of the iceberg to the top. If they already have TB, they need to be treated for their latent TB infection so that they don't become active. All right. Let's look at it in the world. So on the vertical axis, the red lines is the incidence per 100,000 cases of active TB. On the X axis, down on the bottom, are the names of countries. In between all of those lines are more countries. The higher the vertical line, the more TB you have. Where is the United States? If I had chocolate, I'd throw it at you. About where? Because I'm going to run over time, so you've got to answer quick. Where is the United States? Anybody? On the right. Very good. How far on the right? Way? Who said way? Dr. Brucie, for a gold star. The United States, it has as little tuberculosis as Iceland, the British Virgin Islands, and Monaco. We do not have TB compared to the world. We have a little reservoir, but when you look at the incidence in the world, we are so far below it as to be unmeasurable. I can't even pop it up on this map. We're at, like, below 2.3 right now. So I want you to keep that in mind when there's all sorts of fear and loathing about TB in your hospital, okay? I'm going to get you, if I can go fast enough, to understand why we changed the policy on TB testing. So, the United States compared to the world, not much TB. In the United States, where is that TB, that little bit? It's in a few states, okay? It's in states with high immigration. New York, Florida, and Texas, California, because we're on the Mexico border, all right? These are the places where TB is. Where in these states is it? Is it up on a giant 4,000-acre farm in northern Texas? No. It's in a city, and it's down by the border. So even within a state, use your logic. It's not just because you're in New York that you have to worry about TB, but if you're in New York City, Manhattan, you're going to have more of a concern than upstate New York. Okay, so all those other states out there, almost unmeasurable, all right? So where else is TB? Interestingly, and I should have quizzed you on this, why do I have arrows pointing to Alaska and Hawaii? That's exactly right. Indigenous people for Alaska and for Hawaii? Sorry? Tourism. Almost. Tourism. Who's their native population and where are their tourists coming from? Asia. Huh? Asia. Someone over there said Asia. So it's because Japan, Philippines, China are coming over to Hawaii. So they have the highest per capita rates as opposed to the highest overall amount of TB. Okay? Alaska, it's very hard to treat the native population. They're way out. It's very difficult to get community services. It's very difficult to get treatment and follow up. And in Hawaii, it's more because of the incoming from the Philippines and these other nations. So now you've got a little bit of TB in New York, California, Texas. Well, within that cohort, who actually has TB? Eighty-four percent, and this is a California slide, but it almost mimics the national slide, which is that tuberculosis is in the population that's born outside of the United States. Okay? Eighty-four percent in California, about 80% nationwide. So we have in California the population from Mexico and the Philippines, and this is the same population in our hospitals, right? That we have a very high Filipina population in our hospitals in California and a very high population from Mexico. It's that subset of a subset of a subset of a subset who probably do have latent TB. Okay? Probably not your healthcare worker who moved in from Missouri. Poughkeepsie. Poughkeepsie. Oh, it's upstate New York, true. But Missouri. So when you're thinking about your incoming healthcare worker and you're thinking, do they have latent TB? Do I believe it? What is my pretest probability that this test, when I do it, is going to show me latent TB? You know who it's going to be. It's going to be the foreign-born or it's going to be people who transferred into you potentially from Brooklyn Hospital, and it's not going to be usually Americans. Within that group of born in the United States, it's very disproportionately African-Americans. Okay. Okay. And that's probably because of demographic issues and what cities they actually came in from. Obviously not based on some sort of genetics. Okay, so we've got a population that we're worried about that are our healthcare workers that we need to take care of. And then we worry about ourselves, right? So you think a lot about, am I going to get TB as a healthcare worker? Are you? Give me a yes or no. Huh? Not because you're a healthcare worker. That's a good answer. And basically, no, because we have PPE. And who are healthcare workers? We're educated, more so by the end of today, I hope, Dr. Swift. We're well-fed, speaking for myself. And we're in the middle ages, right? We're not the babies and we're not the elderly. So who gets and dies of TB? Those edges of society. 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HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HIV, HI can tell, much to my shame, gets tested when he goes and works at the Stanford camp. There's no risk at all. So the trickle down of the policies that we make, and we implement, and we support is dramatic. And what does that mean for our planet? Well, let's just look at these quantiferon tubes. They're actually made in Austria, right? So you've got all the plastics and all the supplies that make them in Austria. And we'll just start at their production. Then they get on a plane. And in my case, they fly to Los Angeles, where they get offloaded at a port and put on a truck and driven to Palo Alto, where they then get driven by truck to our pre-employment facility, which is in Mountain View, where we draw the labs and we put them on a truck back to Palo Alto, where they will then get run in a lab. Well, they will then get accessioned and labeled and put on a truck to Valencia, where we'll get the result. What's the carbon footprint of doing that 20 million times in the United States every year just for health care workers? Add on all these others 30 million times. Well, what if you then look at when T-Spot then flies it to Memphis? Now think about the tens of millions of tubes, needles, bags, ELISA plates that then go in the garbage from this. When the results are all, say it. Negative. So let's also be stewards of our financial resources, and let's start to be stewards of our earth, because medical waste is appalling. And we should not be participating in that. So I want to give you all the language to talk to your leadership about. This is wasteful. This is expensive. These tests will be negative anyway. And they'll be negative because of all the things I showed you in those previous slides. So how did that data finally inform the policy? The old policy that everybody went by was in 2005. It was the CDC MMWR guidelines. Then in 2010, the new guidelines came out, and they said you can use the interferon gamma release assays instead of the skin test, which I'll get to in a little bit. But you've got to keep doing this thing. You all remember this? This is this. They may not. Oh, you might be new. So your infection control is going to do this giant, onerous, unpleasant every year. What is this thing called? The risk assessment. The facility risk assessment. This does need to continue. So the facility risk assessment, which was in 2005, was modified in the JOEM article that we have in there. But it's actually an appendix, so you've got to find it. We modified it to take out the part about annual testing. That's all approved by the CDC. But the facility needs to keep doing their risk assessment every year. Recognize here, I'm not saying an individual risk assessment, a facility one. The facility risk assessment says, how many air negative rooms do you have? How many TB positive patients did you have that year? What's your ventilation control? That keeps being done every year. But we wanted to cut the testing. So the NTCA, the National TB Controllers Association, great organization, worked together with the CDC to write the new guidelines in 2019. And then the National TB Controllers Association worked together with ACOM, this group, to put out a guidance document in JOEM that's in your books there. The MMWR is only like 2,000 words, of which like half of them are like, how did we come to these conclusions? Like, what's the lit search? So for those of us who work in the field, you have all these nuances of, what if I do if they were previously treated? And what do I do with a false positive? And so we tried to go through all those scenarios for you in the operational document that's in there, which is the JOEM guidelines put together by a lot of people here who did chapters. Dr. Russe did a chapter. Dr. Berman did a chapter. Dr. Swift did a chapter. So really recommend that you lean heavily on that. This is the 2019 guidance. This is what it looks like in the, sorry, this is the MMWR guidance. And then this is what we called the companion document. In those appendices are what we tried to make as bite-sized graphics that you could print out and post for your nursing staff or post for yourself, use for yourself as quick resources. Like I said, when it ultimately got printed, though, they weren't printed as appendices or printed as these little links. So you've got to go online and find the link. Or maybe we can email it to you later. OK. There are five components on it. I'm going to run through this now, because we're going to start to operationalize what happens. OK, on the pre-placement, what we are being asked to do now with the 2019 guidance is an individual risk assessment. All right, I talked to you about pre-test probability. If you don't know who your employee is, you don't have your pre-test probability. So you look at somebody and ask them, where were you born? Oh, I was, you know, I look like this, but I was born in this place, right? And that's a real risk factor. So you've got to know where they were born. You've got to ask them their symptoms in case they've already developed an active TB. And then you've got to do a test. OK, this is on hire, quite straightforward. Here's an example of an individual risk assessment. I do not like this number one part where it says temporary or permanent residence for greater than one month, because there is no supporting data for that. So don't be rigid on a month. The idea is, did you live or work in a high risk situation? If you went and worked in Tokyo in a high rise, that's really different than being out on a farm with your village family for a long time. So the one month is less important than the fact that you spent a concerted amount of time, particularly if you were born in a different country. If you have current or planned immunosuppression, that's really important. And if you've had close contact with someone, not who is exposed to their neighbor's kid's soccer coach who has TB, but somebody who actually had active TB. And that's a lot of people. So my husband's mom died of tuberculosis, hemoptysis in the bathtub. She was born to Polish immigrants, and it was very common back then. So my husband's whole family is latent TB positive. So you've got to ask about that close contact with the aunts, the uncles, the coughing Turkish grandmother who just moved in with them. So do a good pre-placement assessment. All right, I'm going to go back to basics here, because I don't know how much you know. We have three options for tests. One is the skin test, and two are different types of blood tests that behave quite similarly. The skin test, God bless its soul, was developed in 1880 and should have been buried in 1980. All right, never mind. Oh no, we can talk if that was a cough. Could you disagree? Let's talk about it. When is it? Oh, it wasn't? There are a lot of people who are still TST defenders. It is inaccurate in the case of having a BCG vaccine. I'll get to that. But if somebody was born in another country and they have the vaccine, the vaccine has a whole smorgasbord of stuff in it that will then react when one does a skin test. That means your very highest risk population is being tested with an inaccurate test. That makes no sense. It is ridiculous. Your highest risk population is being tested with an inaccurate test. You can't do that. You could get a positive, give them a high five, and be like, you're positive. Yeah, I've been positive my whole life. High five, I'm going back to work. Doesn't make any sense, because you can't tell them at that point if it's a true positive or not, because there's interaction with their childhood vaccine. Ignore the fact that someone had a vaccine and keep going and doing the right tests. We all know it's very time intensive, right? One test, you come back 10 days later, or seven days later, you get another one. 10 days later, you get the read, blah, blah, blah. They have to come in four times. Your nurses have to do it. They have to record it by hand. People have to leave work two, three, four times in order to do the pre-employment testing versus one blood draw that you're doing anyway, because Dr. Berman told you to get all these titers. All right, what's the read? The read is subjective, right? Oh, it looks pretty big to me. You know, maybe you get out a little paper tape, and do you lay it flat, or do you curve it? Does anybody in the entire world place a control anymore? Do you know that you're supposed to? Yeah, there's a control that goes on the other arm. I never saw it my whole life except on the CDC videos. All right, there's a terrible patient compliance. It's less than 60%. That means you place the first test. They don't come back at the right time to have the second one placed. Then you're a couple weeks out. You gotta do it again. You start the series. The whole thing is ridiculous. Or they come in at four days, and you're like, ooh, do I read it? Do I count it? Do I start all over? Terrible compliance. And then I mentioned the training compliance. You're also supposed to get trained every single year on how to place and how to read the skin test, which is just under the skin. You gotta get the whole amount in, not have it leak out and drip down their arm like you see all the time. So. It's an eight-hour training. Is it an eight-hour training? It's an eight-hour training module. Yeah, nobody does it. Anybody met anybody who does it? You did it? What do you think about ECG ratings after about five days positive? Yeah. So somebody who's 28 years old and they got it 20 years ago? Yeah, it's a terrific question. The question is, what do I think about the BCG waning? It definitely wanes. The problem is not in everybody. So you don't really know what the reaction will be. That's why the short story, as I say, just ignore that they had BCG. Look at your pretest probability based on your science. Where were they born? What were their contacts? Where have they lived? But don't even factor BCG into the way you interpret your tests. Let's look at the skin test again. We don't have controls placed. You have to do manual data entry. You can't even audit your own data, right? It's a text file. Oh, and I mentioned it's outdated. So in January 2009, when I started at the Palo Alto VA, I started on the condition that we would eliminate the tuberculin skin test. We don't order it. We don't do it. We don't know how to do it. We don't know where to buy it, I hope. And if I find it, I get rid of it. So we eliminated TFC. We've been using the interferon gamma release assays since then. Let me give you a little proof. A lot of you have seen this slide many times. Some of you may never have seen it. It looks confusing. It's not. The upper left-hand corner will show you the tuberculosis strains that are in the first three columns there, ESAT-6, CFP-10, and TB 7.7 are the antigens that are in the blood test, okay? So those first three orange columns in the upper left-hand corner are in the blood test. And then the furthest one is what is in the skin test. So if somebody is infected with mycobacterium tuberculosis, they will be positive on the blood test and they will be positive on the skin test. And there's some cross-reactivity with M. bovis, bovis being cow, not a problem for us, and M. africanum, which is another mycobacterium, but very exceedingly rare in humans. But look at what happens if you had a BCG. So if somebody had a BCG already, their skin test will also be positive because all of those things were in the BCG. So they got inoculated with all of those things and now their skin test is positive based on that old BCG. What about all these mycobacterium that are naturally occurring in nature but are not mycobacterium tuberculosis? They're a different mycobacterium. So if they're out there in the environment, their skin test will still react to all that huge chain of mycobacterium, but their blood tests will not. So the blood test is highly specific for TB only. And back to the gentleman who asked about BCG, that's why we do this on our high-risk population and not the skin test, because you can tell them you have tuberculosis. You don't have something else. It's not a question. It's not a high five. It's not go about your business. You say you have been exposed to tuberculosis. Your body may be harboring it inside. Let's talk about next steps. That you can do with a blood test and that you cannot do with a skin test. Does that make sense? Does everyone understand? Okay, then go forward. You either understand or you just wanna go to lunch. All right, so next. All right, this is one of the tests and I don't wanna give it short shrift. I just don't use it very much and I don't personally like it because it has to be mailed out to Memphis to run it and I like I'm controlling. I like to be able to walk into the lab and see the bubbles in the tube and talk to laboratorians and understand what their challenges are. So since it's always a send out, I don't choose it. This is the TBT spot, but it's easy. It's a green top in a box. You draw a green top, you literally drop it in their box and it gets FedExed off to Memphis to the laboratory that is now owned by LabQuest, not owned by the company itself. So that's a big change. The company used to have it all done internally, their own staff, their own reporting. I didn't trust it, nobody trusted it. But now it is run by LabQuest. So it's run by a separate entity. It's CLIA authorized and you can trust their results. The problem is it's difficult to run. It's a FICOL separation assay. So it uses these like basically these impregnated papers and then different fluids are run through that and when the TB antigen is detected, it creates a spot on the paper. That spot used to be manually counted. It's now counted automatically, which is also good. So it's been automated. So that in the United States, because Europe has different data. So if any of you are looking at papers about T spot in Europe, they have different cutoffs. We have over eight spots or more is positive in the United States. So you'll get a report back from them that somebody had 10 spots or 50 spots or too numerous to count. There's a little borderline zone, five to seven spots and then a fewer than four spots so they'll report it out as negative. All right. Buckle your seatbelts. All right, here we go. This is the quantaferron assay. It got worse when they went from the third generation to the fourth generation, unfortunately, but bear with me. I think it's still way better than the skin test. So we just gotta do what we gotta do. All right, both of these assays have a negative control and a positive control. So both of these assays are really good. Negative control, y'all remember this, right? Everything in a lab has a control. Oh, the skin tests. Yeah, okay. So every qualified laboratory test has a control, right? You make sure that the test is working right. The gray tube, so you can draw the quantaferron into a single red top, but then the lab is gonna aliquot it into four tubes. Or you can draw it into the four tubes yourself. Only one mil per tube. So it's less than a total green top, which is seven to 10 mLs. Again, I want y'all to have the discussion. So people say, oh, I don't wanna get four tubes. You know, it's one mil each. It's less than one tube of blood, okay? So people will actually be concerned about that. Like, they're gonna run out. Anyway, so the negative control has nothing in it. It's a nil tube, and it's gonna measure the background interferon gamma that's in their blood. It's gonna look at their immune system and say, like, okay, you're doing well. Well, you're healthy today. The bottom tube here is the mitogen, the purple top. And you can see on the T-spot that they also have a positive control. Who can tell me real quick, wake up, what's the positive control for? What does that mean? Not you. No, who knows what the positive control tube is for? What does that mean? Who said that? The test is functioning properly. That's the nil tube, the negative control. Keep going. Immunocompetence. More chocolate for you. Okay, so immunocompetence. Who gets TB in the world? Remember our graphs? Remember the red bars? Remember the skinny guy? Who gets TB? The immune-compromised, HIV, malnutrition, under-resourced, right? No access to healthcare. They are immune-incompetent and they can get TB and activation TB at a much higher rate, of course, than the rest of the world. So what if you do a test and somebody's so immune-compromised that they can't mount a positive response? And then you get a negative test back. They could die, right? Because you're like, oh no, you don't have TB. Does that make sense? So if they do not have a good functioning immune system and you do a test and it comes back negative because their immune system is so bad, you could miss their diagnosis of TB. So these companies knew what they were doing. They knew their audience was not healthy American healthcare workers, that this test is made for the people who can potentially die of this disease and will die of this disease, to the millions this year. And it's gonna get much worse after COVID because we pulled all the resources away. So that mitogen tube is phytohemagglutin and as Dr. Swift said, I just call it a garbage can because for simplicity's sake, the tube is coated with all sorts of really immunogenic stuff that actually come from a kidney bean slurry. So that when blood is drawn into that tube and then the tube is inverted, the blood comes in contact with the walls of the tube which are coated in this PHA. Now, this is really cool. Get this. This is the only test in the world where the assay actually occurs inside the tube, not in the laboratory. When the blood comes in contact with the walls of the tube, which is why you'll see that people with quantiferon have to rock it. They have to get the whole blood in contact with all of the edges of the tube. Then the reaction occurs and the interferon gamma is released. Since it's an interferon gamma release assay, the cells go, oh, badness, ah. My army, I'll release my army. And then you measure how much interferon gamma there was. The reason we have a positive control tube is you test it against basically a garbage can that anybody should respond to. So draw the blood, look at the mitogen tube. That tube better be positive. That's the positive control that says my immune system is good. You will get these questions. You're gonna need to know the results of all four tubes because you're gonna need to look at the negative control and you're gonna need to look at the positive control before you even look at the results of the other two tubes. Okay, moving forward. Did I, oh, what did I do? End of slideshow. Okay, so let me, oh, we're, thank you very much. No, I'm kidding, I'm sorry. Ah, false, false alarm. Sorry. Ah, you thought you were getting lunch right now. You can still walk out and get lunch. We'll just throw it up to the whole screen. Okay, so then there's the two tubes in the middle. So the two tubes in the middle are the TB1 and the TB2 tube. They have the ESAT6 and the CFP10. They have CD4, CD8 predilections. They're short chains and long chains. Nuances can be read about online. The gist is, those are the two tubes where the wall is coated with TB antigens. Remember the ugly slide with all the different columns? Those TB antigens are specific to mycobacterium tuberculosis. When those are positive, they have TB, except if they don't. But except if their value is very, very low. Because the cutoff on this for what makes a positive test is the CDC said you have to be 99.7% be able to say with 99.7% certainty that a negative test is truly a negative test, not that a positive test is truly a positive test. So they just drew a line at 0.35. So if someone tests 0.36, that's not a direct indication of TB. You don't look under a microscope and get a direct result. It's an indirect indicator of disease. There was a lot of immune response to interferon gamma. But maybe they hit 0.36 or 0.39 or 0.40 instead of 0.35. Does that really mean they have TB, or does it mean that they're 99.4% likely to be negative and not 99.7%? So I want you all to get really used to looking at the numbers on these results. The 2010 MMWR, or maybe it was the 12, said that laboratories should be reporting the quantitative results. Look at the quantitative results. Make sure you see the whole picture of your patient. All right, pop quiz. This tube is negative, meaning it's less than 8. Good or bad? This test tube is positive. Good or bad? See how your pros are ready. These two tubes are negative. They're less than 0.35. What does that mean? Negative. All right, pop quiz number two. This tube is negative. Good or bad? This one. Good. What about this? What does that imply? It does. I didn't even show you the next tube yet, right? OK, there's a problem with this test right now, with this generation. The lab is going to read it out as positive, which is good, every time one of the two tubes is positive. So you're going to look at the numbers, and you're going to look at the second tube. And if the first tube is 0.37 and the second tube is 0.20, what would you do? Repeat the test. A plus. If you're in the ER, Dr. Berman, and somebody comes back, they're sitting there on their phone, and they have a potassium of 6.6, do you believe it? Probably not. Probably not. So how often do we, as clinicians, rerun our tests? We run them all the time. Because you look at the pretest probability, you go, like, they're sitting there on their phone. They're probably not having an MI, probably not having an arrhythmia. You run the test again. Don't be afraid to run this test again. When you see a result that you don't believe, it doesn't fit your pretest probability, or there's a discordance between tube 1 and tube 2, send it again. If you're in nursing, if you're a physician, sometimes people will just go ahead and go with it being negative based on their pretest probability. OK, so yeah, those are probably TB. Now, if their number is 2, 5, 7, and they were born in especially India, Philippines, Mexico, Bangladesh, just don't repeat the test. Say it's positive. We know you come from a place with high incidence. You have latent TB. But not to worry, because we'll tell you what to do next. All right, OK, we're going to run out of time. I'm going to do this real quickly. This was a study we did years ago, 28,800 quantaferrons. I ran with a friend of mine, Dave Marder, at University of Illinois Chicago. So I came into Palo Alto, where they had all done skin tests. We had about a 30% positivity rate in our employees. Not surprising, right? Not surprising. Their nursing staff and our maintenance staff. So Dave Marder had exactly the same thing in Chicago. He had about 30% positivity rate. So we took all those, and we ran our whole staff again. And we ran them on quantaferron. And then we ran them again on quantaferron. So this is with three tests. What we found is when you run, see the big red pie there, all the people who are skin test positive? You know what's inside that red pie? People. Inside those numbers and inside that red pie are humans who have been told that they have tuberculosis. They are living in fear, even if they pretend they're not. They know inside that they could reactivate. They could infect a baby. They could infect a grandma. And they're scared. Maybe they're scared of being deported, right? So those are people in that red box who think they're living with a chronic and potentially fatal disease. When you can do a test that's accurate on that same population, and you can cut that big red pie down to that little tiny red sliver, all of those people are relieved and happy and grateful. And you're the one who gave it to them. So do the IGRA. Tell them the truth. Because what will happen is 75% or more of those people who are skin test positive will test IGRA negative. They will be negative on the T spot or negative on the quantaferron. And with a, what, 99.7% likelihood, that is true. They are negative. Give them that relief. They will thank you. They may even cry. I've seen it many times. So please do the right test. Go back and look at your skin test positive population and test them with an IGRA. All right, but then there's that little red slice where they're still positive. And they're probably high, 2, 3, 8 on their IGRA. Same thing. Now you tell them with confidence, you know what? You weren't really sure when you had that skin test whether it had reacted with your vaccine or not. But now we know you actually did get TB. And this is what we're gonna do about it. What about that tiny little slide that's red and green? That's this group that we used to call the wobblers, the ups and downs, you know, the discordance. To make a many hour lecture easy, test them again. Look at your pre-test probability, decide what you think, but run the test again. And actually the CDC in our guidance in 2019 says run all positives again because the pre-test probability based on people's history is so spurious. Maybe they were born in India, moved a week later. Like you just run the positives again unless your pre-test probability is really high. You know, they're like, yeah, I've been IGRA positive in the past or my mom had TB. If you know that this is TB, you don't have to run it again. But if they're in this low range, you know, they're 0.7, they're 0.2, it's potentially false. 10 minutes, okay, I think we're okay. I think, I don't know what slide number I'm on. Okay, so look, that's the study. This is really great. Basically what we did is we ran a multivariate analysis looking at why are some people positive, but then they test negative the next time. And when we did that, we ran 10 different variables. And there was no predictor that they would be positive or negative the next time if the initial value was under 1.1. This is when there were only three tubes. So I'll say that again. This is a product of the test and of that FDA cutoff. It is not related to the patient when there is a low positive test. Low positive tests will be positive because we are using the test wrong because our pretest probability that these people are positive is low. We are using it on healthy, middle-aged, overfed, overeducated American healthcare workers. And our pretest probability that we're gonna have a false positive is gonna start to exceed the likelihood that it's a true positive. And so what we found was that we wanted to retest everybody when there was only three tubes at under 1.1. That gave you a 76% likelihood of being negative the next time. And if you were over 1.1, between 1.1 and 10, there was like a 26% chance anyway. But the gist is the low positives repeated to negative. Oh, that's the second bar. The low positives repeated to negative 76% of the time when we tested them under 1.1. All right, real quickly, annual testing. What did we learn from the epidemiology of the United States and TB? Should we be doing annual testing? No. Who lives in a state where annual testing is still required? 11 states, only you? All right, well, forget it. Preach into the choir. Have you stopped doing, oh, here's a better question. For those of you who live in a state where you're not required to do it annually, have you stopped doing it? Yes. Who is still doing annual testing because you're being pushed to do it? One, two, and a half. Okay, so hopefully you've now got the arguments you can use to stop doing it. Post-exposure, the MMWR guidance says we keep doing the same thing we've always been doing post-exposure. So you wanna test them initially, and then you wanna test them at eight to 12 weeks, depending on the timing of that exposure. You wanna get that baseline because you wanna know whether they were positive before or not, okay? So you get the baseline more as like a worker's comp, OSHA pre-test probability thing. And then if they're positive on that initial, it gets complicated. But I have a really good graphic in the appendices that I mentioned. So you can look up a workflow on what to do with post-exposure. What happens when you have a reactivation TB in your facility? Let's say you got a bunch of pre-hire people, they're positive, but nothing has happened. They haven't been treated. Next year, next year, next year, five years later, finally their primary care person says that they're positive. You get an outbreak that lands you in the newspaper. And that's on occupational health because you knew they were positive already. And why is it in the newspaper? It's in the newspaper because it's dangerous. It's in the newspaper because maybe a thousand of your patients have been exposed by now. Maybe three of your colleagues are positive by now. It's not in the newspaper because it's just bad press. It's in the newspaper because it's dangerous, and we missed the boat, okay? We had the opportunity to intervene. This is, I didn't put the one, oh yeah, I did. I don't do that when I'm at the VA because they get really upset. But, so this was at our VA in 2016. We had a reactivation of a nurse from the Philippines in her 50s, positive in 2012. I was testing people every year so I could understand the testing dynamics. And we did 2012, 13, 14, 15, she was positive. 16, she had these perimenopausal complaints. Four months later, Kaiser finally diagnosed, I'm not blaming Kaiser, but four months into her workup, it was finally figured out that it was actually tuberculosis. She had been working in our post-op unit, our PACU, spending about 40 minutes with our post-surgical patients doing their notes and everything. The very first patient who developed active tuberculosis from this nurse was a heart transplant. They're on a million immunosuppressives, they're on warfarin, and now you gotta put them on four antibiotics, it was a cluster. This guy's 62 years old, he's from Arizona, Palo Alto just said, bill us whatever you want. We put out an incident report to Washington, DC and just said our fault. Second person who became positive from her, 24-year-old nurse who had been put on Embryol. She was put on Embryol a year before, so we knew she was negative. She worked right alongside this nurse in the PACU. Next year she was positive, but not only was she positive, she was coughing, she was febrile, she was weak. She had active tuberculosis, 24 years old. The third one who I think became active from this was a 92-year-old gentleman, World War II vet, he's Japanese, he had a previous positive skin test, died of a pulmonary abscess in our nursing home about six months after we figured out she was positive. Now it had been almost over a year since we had done everything and got to the end. His family didn't want an autopsy. We know that it was a tuberculous abscess. So that may have also been a fatality from this one. And then there were the conversions. So that costs the hospital millions and millions of dollars. It costs our tiny Ock Health team, pre-COVID, thousands and thousands and thousands of hours of time involving infection control in the laboratory. So what are we gonna do? We're not gonna make my mistakes, right? Here's the graphic I showed you for different things to consider when you're doing post-exposure testing. This is an appendix. What we're gonna do is we're gonna treat it and or we're gonna prevent it. So the New England Journal of Medicine in 2011, and this is what, again, this is a quote directly from the MMWR 2019. That's what each of these wedges is. Direct quote, prevention of reactivation TB disease is the mainstay of TB elimination. Remember the iceberg? In the United States and should be strongly encouraged for everyone diagnosed with latent TB infection. We're the ones who know they have LTBI. We're the TB experts in the country. Because ID sees one or two, whatever, every now and then. You see hundreds. Maybe you see thousands. We're the experts. You guys are the keepers of the knowledge and you're the keeper of the ability to eliminate latent TB in this country, certainly in your hospital. So 2011, a long time ago, New England Journal of Medicine says, you know that six months or nine months of daily INH? You know that was good, it worked, but it also caused hepatocellular toxicity and death, which is part of why people weren't being treated. So what do we have now? We have 3-HP, three months, INH plus rifapentine. It's a bad name because it's actually 12 weeks once a week, which means I market it as 12 doses of antibiotics. 12 days, I say 12 days. It's not 12 doses because it's kind of like you gotta take kind of a cup full, but anyway. You only have to do that once a week. So 12 weeks, once a week of INH plus rifapentine with 12 days of treatment, that whole bottom part of the iceberg, the latent TB is done, treated. They are not gonna reactivate. They are not gonna infect their grandchild. They're not gonna infect their grandma or the 92-year-old or their co-nurse or a heart transplant. And you're gonna save your hospital millions and millions and millions of dollars because in your careers in occupational health, you will get reactivation TB. Are any of you, have any of you had it yet? Are you experienced doc health? You have, you have, several. Yeah, I know you two did. Because I know, and I did. So anyone who's been around this game for long enough, you're gonna have reactivation TB and it's gonna be a giant cluster. And it's gonna, you're gonna lose a lot of sleep over it. So 3-HP, what happens? You get high compliance. You get no hepatocellular toxicity, liver failure, or death. So this is the, and you get equal efficacy. That's a New England Journal article. This is what you take to your ID and your pharmacy when you set up your TB Tuesdays clinic. That's what we're all gonna do. Nevermind the taco Tuesdays. Let's do TB Tuesdays. Bring them in once a week, INH plus rifapentine. The cost is under $200. You will not have everybody, as Dr. Berman had in her slideshow, you will not have everybody accept treatment from you. But you can show them the New England Journal article and you can show them this other thing I'm gonna show you. And it's a handout in your, will you hold that up, Amy? Thank you. This handout that I gave you, this two-sided handout, it's in your booklets. I recommend, it's the paper. I recommend that you copy this in your clinic and you make stacks of it. And when you have your new hires, your new onboards, or you go back and check your TST people and they're really positive, you have these available for them to hand out and either bring to their primary care physician and say, this is the one I want, not the nine months of INH. This is the treatment, 12 days of antibiotics, because they're not gonna be familiar with it. Primary care doesn't know about this yet, even though it's 10 years old. So I want you to make a lot of those copies and be able to talk with your staff about it. Okay, so these are other short course regimens. They're all recommended over INH. This is again a handout in that appendix that you have to look up. Or we'll send them out by email, maybe, Melanie, to everybody on the team. Maybe we should send a PDF of all the appendices to everybody who attended. Okay, and so I'm gonna go back to that. What the MMWR does say is that now every year, instead of doing testing, I think they say you're still supposed to do a symptom questionnaire, but there's no data to support that. So, la, la, la. But what you do wanna do is education around TB. You wanna educate people. This is what active TB looks like. This is who reactivates. Oh, you've been positive, you haven't been treated, but now you have diabetes. Well, because you have diabetes, you have a two to three times higher likelihood of becoming one of those active people at the top of the iceberg. And so when you can do that touchpoint with people, you'll see what their medical situation is. They'll tell you they're coughing, Turkish grandpa, because this happened to me in our group, moved in with them, and you can start to talk to them about different options. All right, here's the handout. This is how you do the education. Final slide. Recap. There's very, very, very, very little tuberculosis in the United States. This is why we're not doing annual testing anymore. Within the US, it's mostly in California, Hawaii, Alaska, New York, and actually Texas. Healthcare workers have lower TB rates than the general public. Healthcare workers are not getting occupational TB. Remember the slide I showed you? We're not getting it, especially post-COVID now, right? We're really good now at our environmental controls. About 80% of TB in the United States is in the foreign born. Pre-test probability. Who to test, who to believe the positive. Occupational health is uniquely poised to eliminate this reservoir of latent tuberculosis by preventing reactivation. In our VA, occupational health is not allowed to treat disease, but we are allowed to prevent disease. We can give MMR-VZV. We can give COVID vaccines. We can give flu vaccines. This is a vaccine against active TB. So you can solve this, and this is what I'm doing in the VA. This is not a treatment. This is a prevention, all right? And we all, I think, need to start shifting our language because I think everybody's gonna have a similar situation. We want to prevent active TB in your hospital, all right? That's what we're doing. We're not treating latent TB, and that's pretty much the true case. 3-HP is your friend, and let's make the world safer. So that should be it. Thank you very much. It's time for lunch. Thank you.

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