Thanks everyone for joining and sharing your afternoon with me and I will hopefully get uh lots of time for discussion. I always want as many questions as answered and make this more interactive as possible because I, I tend to want to focus on real life, clinical challenges and things that you have. So we can help navigate through that system. My um objectives or outlines are as here, I'll try to focus on some things a little bit more than the other. So they're not equally rated um objectives, but hopefully it'll all um elucidate a little bit more of your clinical practice and real life circumstances. I do wanna uh give a shout out to David Jagannath who is my colleague and he does a lot of TV research both globally and here um at U CS F as well. And he, he um had put together the slides um initially, so which I piggybacked on, I'll start with a couple of cases. These are the patients that I have been involved with. So if you guys have more questions about them, please put them in the chat or Q and A Q and A is a little bit more helpful. Um, but we'll start with a 10 year old who was seen by a community pediatrician. Um, and as a first time visit back in August of 2022. And, um, as you can imagine what was going on in, at that time, we were on the heels of coming out of 2020 2021 where there was a lot of delay in care. Kids were not being seen in person. So she came to the pediatrician's office for the first time with abdominal pain distension and there was concern for constipation because it was her first time. She noted a little bit more fullness in her abdomen. She looked a little bale. So the pediatrician ended up getting a white blood cell count like a CBC which showed a white blood cell count of 9.6. The diff was unremarkable. Hemoglobin was remarkable at 6.7. Uh crit was 23 in platelets were 3 93. The pediatrician was a student and she noticed that the girl had a positive back in 2020 she had a negative chest x-ray and um from a previous PC P and she wasn't treated at the time. There's always this a little bit of a back and forth, you know, the, the story that she got from the family is that um, oh, we were told that this doesn't need treatment. You're ok because your chest x-ray is negative. So she also ended up getting a repeat, Ron at this time and, and her question to me was really with the positive quan, what do I do? She was gonna follow up with hematology for this low hemoglobin. Um And, and to me, I was very concerned for her now having active disease in the setting of, of this positive quan, she had profound weight loss, she had uh profound anemia. Um And this was her chest x-ray, which was not normal. You can see that there's a lot of like there's not a cave lesion, but um hopefully, you guys can all appreciate that there's jagged borders right here and her heart is not well defined. There's something here, there's something here and, and the best way I could tell you is that when I looked at this x-ray, something seemed abnor, I couldn't say what it was abnormal and I talked to the radiologist and she's, he's like, yeah, it's so um we also got, because her belly was very descended. We also got ac T um abdomen and, and I have outlined the, the exact findings that there were, but she basically had lots and lots of lymph nodes throughout her chest abdomen. And um they, they were spread everywhere. So we'll pause on that case and II, I will sort of revisit it and, and if there are questions there, we can explore a little bit more. I'll skip to this the second case that we recently saw, this is a seven year old with a positive quan back in September of 2022. After a household exposure to a maternal uncle who had active pulmonary TB, he was seen in ID Clinic um or at that time, he was given a strip for a um and was told that you should um take it for four months and um parents walked away with the impression that um it was optional. So I, I specifically mentioned that this was not a pediatrician's office that he saw, he, he saw an ID physician and, um, and the parents still walked away with the impression that this is something that they can choose to do. They don't have to do it. And, um, his x-ray at that time was negative. Now, he presents, you know, almost, um, six to a year later, uh, with right sided pneumonia, multi loculated plural fusions. And by Hema in the context of really high fevers, mild cough. And in, in the meantime, from the last time that he was seen to this time, the family had also traveled to Mongolia, uh, for an extended period of time. This is his x-ray from nine, last year. You can see it's pretty unremarkable. Um, it, it was read as normal and this, this is his x-ray when he came back, um, admitted in August of 2023. So just this, this month and you can see that there's a large loculated plural fusion here. So um I'm happy to go into the details of both of those cases, but I, I wanted to give you a context and a pretext of like why we are here, why we are talking about it? This isn't something that you're going to see, you know, if you travel elsewhere, this is going to be your practice, your patient population. And, and this is a generic slide that we almost feel obligated to put together. But it is what is TB TB is an infectious disease that's caused by mycobacterium tuberculosis complex. Um It includes M TB, but it also includes other TB complex organisms which are m uh Afrikan ambo. Um I'm not gonna pronounce the other two, but the, the really the one to focus on is a bovis. So um a lot of times patient populations are they endorsed, you know, eating fresh cheese, queso fresco, you can have similar symptoms from um M TB complex but secondary to M bovis and the treatment implications are slightly different. So, keep that in mind, it is respiratory transmission in droplets that are inhaled once it's exposed, there is a spectrum of responses from what we call latent infection. And, and the terminology is changing slightly and we'll try to use the term TB infection versus TB disease. Um And um if infected, you can always have this chance of reactivation, especially if you become, you know, co compromised. There's a large burden of um TB. Globally, there's 10 million cases of TB disease annually, about quarter of them uh of the world is, is infected with TB and there is millions of deaths annually uh contributing from this, this illness. Um and COVID-19 only um accentuated these, these illnesses and especially with the stress of public health and everything else like we see it now and, and quite honestly, this year, we, we saw have seen the highest number of TB cases that we, we have at least in the last five or six years since I have been part of children's Oakland. And I think it's a direct conduit of, of public health system being super stressed and, and lack of contact investigations and other things that, that ultimately led people to have um continuation of active disease. So in a, in a context of putting it together in us, you can see California is bright purple or dark purple and dark blue in both of these contexts. So the blue figure is non US Born United States in 2021 and then the purple is US born persons. Uh And that's TV incidents for both of those maps and, and California is, is number, I wanna say like number four New York and, and II, I think Florida uh for, for the incidence of, of uh uh TB in terms of um who is at risk TB is 40 times higher in non us born Asian and black communities than us born white communities. TB rates um vary by birth race and ethnicity. And this is from CDC data that uh that talked about from 2020. You can see that there is uh the disparity there as well. And then TB in California and particularly TB cases in California, you can see the Hispanic population is disproportionately affected uh versus a non Hispanic black population is also disproportionately affected and this is looking just at pediatric TB cases and particularly in California. Um This is also something to keep in mind, Mexico, Philippines, Vietnam, China and India contribute to 76% of California's non US based cases in 2019 and at least half of them occurred well, after people had um immigrated to United States. So over 20 years later, um you can still have um transmission. So it doesn't really matter like if it's a recent immigrant versus a person who has been here for, for quite some time severe TV. In Children, you can see that graph unfortunately went up and up. I don't necessarily need to orient you to this. That other than the staggering numbers that we have seen in terms of percentage of cases for extensive disease um from um 2000 going up to 2020. So kids are presenting sicker and with more severe presentations. Um and, and I'll elucidate one of the cases that we re more recently saw in the hospital towards the end of the presentation if we have time. Um So, you know, I won't be labor this fact, but more, more than 80% of TB diseases in California result from a progression of previously acquired L TB I infection, which plays into the factor of how can we prevent TB? Is, is we'll spend a lot of time talking about TB um infection versus TB disease. I think TB disease is an entity that is in treated, in collaboration with public health, with ID, experts with pediatricians. But I, I do think that there's a large burden in our community that sort of go goes unfocused because public health doesn't really um track uh TB infection numbers or L TB I numbers. And it, and the burden bears on the community, pediatricians and um infectious disease specialists and PS ID people to, to really help families go towards um treatment for L TB I. And a very small percentage of, of these TB infections are generated with the result of relapse or previously treated active disease or reinfection that that does not happen very often. So what are the risk factors for uh TB disease? Um The younger you are non us, born, travel or resident to an endemic setting TB contact or contacts with high risk populations, especially recent immigrants, incarcerated individuals. I would say that incarcerated individuals. I'm not really sure how true that is in today's day and age because people are generally screened when they are about to be incarcerated. So I'm not sure if that truly truly holds true. I know historically, it's been carried out that they are at high risk. Malnutrition plays a huge component and certainly even a compromise state plays a factor and clinical presentation of TB disease. We're not talking about TB infection. Remember, we're talking about somebody who has active TB disease. It can be very not specific weight loss, failure to thrive prolonged cough, lethargy fever. I think that's part of the reason why some of the kids fell through the cracks is because they really don't look sick. They don't feel sick until they're kind of like this, like slow decline where it's hard for parents to kind of feel like. Is this you being like changing? Like are you becoming a teenager? And that's why you're being moody or temperamental or taking daytime naps, it's very kind of hard to predict. And it's, it's just not one of those things and, and, and these families invariably are also not the families that are well connected. They're not being seen by um a consistent or same provider multiple times. So there, there's harder to track them in general as you all know, pulmonary is the most common type of um A TB disease that we see. But extra pulmonary is more frequently seen in adults. So from the time on onset, in terms of your exposure to when you would develop, like for example TB lympho, it can vary. So generally, it's between 4 to 12 months. There's abdominal TB, there's TB meningitis, there's disseminated TB as well. And that generally happens 2 to 6 months after infection. And, and it's not uncommon for patients to get, um, trial of antibiotics when they have like a non-specific lung infection or they, you know, they have fevers and other things. The one thing that I think we do better in pediatrics than the adults do it is that we, we don't typically treat with a flu quin lungs. They're not our first line. So not, not everybody or who barely anybody gets love a Quin. But a lot of people, what they don't realize is Leviquin is actually active against TB. So they may see partial improvement, but you're not treating the whole um disease state and ultimately, they're going to relapse. So I I see this many times to, to um residents. There is definitely a difference in between presentation of a child versus an adult or an adolescent and how they present with TB disease. You are not going to see a cavitary lesion in a child. Cavitary lesion by definition is reactivation of disease. They haven't been alive long enough to reactivate their infection. So they're going to see what you're going to see is higher annoy. What you're going to see is like this nonspecific infiltrate that's gonna be there. What you're gonna see is what you saw in the initial case presentation of the 10 year old where there isn't a cavitary lesion, it just doesn't look like there's disease everywhere. Excuse me. So, in terms of adults, like I said, it's reactivation that the traditional teaching, it's the right upper lobe. Um, cavitation is common annoy is rare. Symptoms are very consistent. They have, they have consistent cough, they have weight loss, um they have very high bacterial burdens. So when any time a child gets admitted for rule out V or suspicion for TV, I'm actually not worried about the four year old being contagious. The reason why I really want them in airborne is because who's with them and who gave the TV to the kid if the kid in fact does have TV. So a lot of times it's that who is in the room with the child is gonna be the contagious person or entity, not the kid himself because they have low contagion level. They have low FFB burden. They don't really have like a lot of symptoms. So the typical teaching of that, do you have weight loss night? So that's, you know, those kind of things they don't happen in kids, kid toddlers don't have those symptoms. Typically they, they, they will have very few symptoms and we'll go into like why that is important because to me TB is, is one of those infections that I would say that has the highest level of what we do as ID physicians is a history. The money lies in the history that you're not gonna get a perfect test, you're not gonna get a x-ray. It is going to be where they were, who they were, talked to, who lives with them. It's all about that sort of your level or index of suspicion of. So how worried or not worried we are. So, as I talk about like, how you're going to go into diagnostics or how do you go into diagnosing? We, we'll, we'll spend probably a good amount of time in diagnostic testing for TV. Because oftentimes, I feel like the questions that come to me or when I discuss that there are challenges in the interpretation of these tests and their who to do it on when to do it. When is it appropriate to do it when you think? So, I, I try to put together the life and hopefully they'll have some flow to them, but I really try to put them together in a way of like, well, what do they, what, what questions do they come up with? Like it's easy to order a TSD or a quant front, but when do you order it? So hopefully that will kind of make sense as we go through the next couple of minutes, active TB cannot be determined based on a single test. So a thorough history and a physical exam in addition to your diagnostic testing is imperative in diagnosis. And there are TB tests that exist but the TSD or an I cannot differentiate between active and latent infection and, and going into that, it, there are two types of tests that are available for detection of TB infection. It's either a skin test or a TST or there is something called the Interferon gramma release assay or, and there are two companies or sort of two tests that are available. One is called the teapot and one is called Quan Gold. Most labs. Most quest most people will order a Quran, although there are some that, that have t spot testing available to them. And I'll spend the majority of the time discussing the quantum front gold essay. And, and um I will show what the teapot kind of looks like. They're both indirect tests for mycobacterium tuberculosis that measure a cellular response um to your immune response to the mycobacteria antigens. And if positive, like I said before, you must rule out active disease by careful history examination and, and I might sound redundant, but it really do want people when they, you know, as you guys are going in and out and, and uh targeting multiple things, if there is one consistent message that I want to send through is, is that so this is sort of like a pictorial depiction of what we talked about in the previous slide. When you have a presentation of mycobacterial antigens to your memory T cells, I the top is when you do a TSD, the, the um in Interferon gamma released is released and that causes the in duration and sometimes er but what you're really capturing is the in duration, which is caused by the inner front gamma release versus a blood test like a teapot or quo front. Gold is releasing that intra front gamma by stimulation of that memory T cell to the antigens that are on mycobacterium. And what you're measuring is the amount of in interf front gamma. So talking about TST first, it's a purified protein derivative or PPD and you inject about five units of this tubercle under your skin or forearm. And the idea is that there is a T cell delayed hypersensitivity response after 48 to 72 hours. And you measure it in terms of your induration, it's cheap, it's easy to administer. The downsides are many. Um and we'll go into them and, and we're really trying to kind of specify a very specific population in which you would want to consider TSD testing. There are of course false negatives. Um There's a phenomenon called energy where your immune system is basically so wrapped up that it's not even like recognizing the, the T cells are, are, are not um they're, they're basically, they're not recognizing the antigens. And then that's when you get a false uh test measles vaccine can suppress reactivity for 4 to 6 weeks. So think about you can't, if a patient is coming in, let's say they need um you know, you can give the MMR vaccine the same day as you do A PP. That's ok. But if they have recently received an MMR vaccine within the past month or six weeks, then you have to wait um for a certain amount of time. And I, and I forget what that amount is. I wanna say it's eight weeks but it's in the red book and, and how long you have to wait before you can administer the PPT. Um and, and the caveat to that is if it's positive, it's positive. If it's negative, you can't rely on the negative. So if you're really worried about a kid who might have active TB, you can do a quant front on that kid or a TST on that kid even if they received Mmr recently because if it's positive, your immune system doesn't care that it received. Mmr it's not distracted, it's still responding to your TSD or the quant front. And, and the question oftentimes comes up like how does the BC G vaccine affect the utility of a TST? Having received ABC G vaccine as an infant may not explain a positive skin test much later in life. So if you are, you know, 18 years old and you got BC G vaccine when you're two months of age, having that context is not really neces really gonna affect your TST. What does happen is that you have to keep in mind that the person who did get the BC G vaccine, they likely were at minimum exposed to an endemic region. W which is why they got the BC G vaccine. So a positive test should make you pause and not dismiss it because they had ABC G vaccine. Um in terms of like induration, I'm not gonna believe it um the um for, for uh in duration and other things. Um but it's, it's fairly accessible on up to date and um red book and other things like what do you call a positive test. So inner gamma release assay or the quan. So this is the quant front gold or quantum front TB test. And there are four components to this test. One is the mitogen which is the positive control. Um A low response may indicate an ability in general for you to generate in front gamma without even being exposed to your mycobacterium tuberculosis antigens. Negative control is basically your baseline in front gamma, right? It controls for that TB one, it primarily detects CD four T cell response and TB two is optimized for detection of CD eight T cell response. So where we don't generally look at it in the context of the true test. But in theory CD four cell is supposed to say like you have a longer term exposure versus if your CD eight is positive, then you more have a recent exposure. So um I'll go through it several different ways because I think it is important for us to know what the test involves because when we come up with the context of like, what am I, why am I testing this child? Am I testing this child? Because I worry that he has an active infection. I worry because he has um L TB I or am I doing this test because parents are coming in and the kid needs to volunteer in the hospital. They've never stepped outside in a very high endemic region or no risk factors. And we are doing it as a sort of a screening thing. So um nil is basically your basic baseline uh gamma, inner front, it should be low. Your immune system should not be activated. The mitogen should response like this is where it's like your body. We're trying to test like is your body otherwise normal. And if I give you a mitogen, are you gonna produce the in front gamma regardless of if you have seen TB or not in your life? And these two TB one and TB two antigen, they should only respond if you have seen TB in your life, if that makes sense. So the, the one on the left is in front gold is basically you have these four tubes you in, you have an incubation time. This is where it's important and that's why the TV one gold cannot come back in 12 hours because there is an, there is an incubation time that's mandatory essentially for the test to happen. Um And then you remove the plasma and then you add the antigen presenting cells and then you basically measure how much an in front gamma your body produced. Whereas the tea spot is basically these counting um uh the same thing but in the wells and then basically over eight spots positive is a positive test. So the positives of Ron is like one and done, you um don't have to come back. It's not in uh subject to provider, sort of like, hm I think this is 11 millimeter. I think this is the in duration is this and the kit is struck. So you don't necessarily have to feel like I'm kind of making this up or I'm kind of being subjective and it is universally at this point, I would say is recommended for anybody to win over. And there is a good amount of studies that support that, that fact, like I said, there are three possible combinations that you can get either you have a positive, either you have a negative and then either you have indeterminate when you have an indeterminant unless you're really looking at what happened and we'll go into that. You have to kind of say that the test failed and most of the times that's what I recommend to the pediatricians that you cannot make any meaningful interpretation out of the indeterminant. You cannot say that it's weakly positive or may, it basically means that the test failed, did the test fail because their control failed, did the test failed because it was an inadequate sample. We don't know. So remember when I went back uh in the way, in the beginning, when I talked about this, the seven year old who came into our clinic and um he had an exposure from his uncle, he had a positive quanti front at the time and his x-ray at the time was negative and this was his quant front and I hope you are able to see this. So the nil meaning like we want that number to be um uh at some, some kind of a baseline and that was there, the mitogen minus nil was less than zero. The TB one and TB two were greater than 10 and it was reported as positive this time around when he came back, if you look nil is greater than 10, mitogen is greater than 10 TB one and TB two are, his immune system is so hyperactive. That is basically responding to everything, right? Like it's like my mitogen is positive. My TB one is positive, my TB two is positive. The the fact that this is indeterminant in the setting of a kid who has potentially active disease. I cannot dismiss this. I cannot say that he probably doesn't have TV right now because of the fact that he had a positive test because of the fact that he had an uncle who was living in the same household with a high uh burden of disease. And, and because he never got treatment for L TB, I, the fact now that he's presenting with plural effusion makes me pause. It doesn't matter what his quant of front is. And when I do look under the hood for the quant Front, I can see his immune system is basically wrapped up. Um And that's why the test is, is putting out indeterminate or, or we can theorize, right? So TST versus I is based on age um BC G immunization is not a contraindication to a TST. Generally. What happens is that if a patient is closer to the time, like let's say it's a baby, a four month old baby, right? Um And they just came and they got BC G vaccine in their endemic in their country of origin and they came here and you do a TST that TST might be positive because the BC G antigens and the PD antigens do have um some similarities but it, it's, it, it's ultimately, it's not a contraindication to it because if it's positive, you have to put into context to why is it positive? But if it's negative, it may be that the baby is too young. So the baby is less than 12 months or older, a little bit tricky to screen for those things. TST is generally recommended at least three months and over because that at that time you feel like their immune system is a little bit better primed. Um And I is universally two years and older. So this is another table from red book describing like, um the same thing that we talked about when is it preferred versus A TSD? And, and there are clear recommendations and, and guidelines and, and also in the fact, like, when do you want to do sort of both. So what do you do when A TSD is positive? And a quarter, one is negative because I'm sure that has happened to you guys. Um and I wanna show you a couple of studies that, that looked at this very thing. So it, there's a study from Canada that looked at the rate of progression to TB disease among untreated Children who had a positive TSD and a negative. And this was done as part of a contact investigation. So they had a legitimate person who was exposed like in their circle who had po like TB and they were um a product of the contact investigation that the public health did. And, and there were 55 people with positive TSTS and negative quant of fronts. Majority of them because they were a contact of direct contact investigation, they received INH therapy out of that subset. There were also 201 Children that had a positive TST and a negative point of 145 of them did not receive treatment and none of them developed TB disease. In a year, there was another study out of UK, which was a prospective multi center trial. 431 Children who were exposed to TB in their household to an infectious case, 18 had positive TSD and a negative and they were not treated and none of them developed TB disease. A United States money Center trial over 3000 cohort TSD and I was done um, and, and evaluated for risk of TB infection and or progression to TB disease. And, and that was done because they had a birth country with higher burden of disease and fif 533 Children with a positive TSD and a negative I, they were not treated for TB infection including 54 Children who are younger than two years of age. Um and none of them progressed to disease over two years of age. So I I give you this data but it is not all and all and, and, and there is a little bit more layering to this. And then within California itself, they looked at this registry where there were 4000 Children with a positive TSD and before entry to California. And then only 23% of them had a positive after entry into the United States. And these are immigrants coming into California. So how do I approach these discordant TST versus IRA despite the greater specificity of IRA decision to treat or not to treat in a patient with a positive TST and a negative should be based on clinical judgment, taking into consideration their risk of progression to disease, their degree of exposure. For example, if you call me and you say I have a six year old whose mom was recently diagnosed um with active pulmonary TV, with four plus A and the child ended up has, you know, definitely fear of needles and they ended up getting a TSD and the TSD is 10 millimeters, but then they change their mind and their ire is negative. What do I do? That kid in my mind has high enough indexes exposure that I'm not sure why the IRA didn't respond. But if they have a negative chest x-ray, they should, I would recommend L TB I therapy. But so the bottom line is when you want a high specificity and low risk population, let's say a child who got BC G vaccinated and they have a positive TSD and you're trying to sort of differentiate like they don't have an active case in their household. They, you know, but they ended up they were, they got BC G vaccine when they were a baby. That kid you can probably do an and the is negative, then you can give the family the option of saying like we, we can choose not to treat. However, if you have a high sensitivity, like I wanna capture any, I wanna capture TSD positive or quantum positive doesn't matter because this is a kid living in a household with active TB. Then I don't care, then you take one of the positives and you go with the therapy and that's it. And that applies to kids who are also um needing immunosuppressive therapy. So sometimes we do both, we do TSD and quantum front and you take the positive of the two and you run with that if it's negative. Great. So how do I minimize the risk of false positive test? Only the Children with legitimate risk factors for TB infection? And and what are those risk factors? Um This is per the A ap the Children who need immediate testing are people who are confirmed cases of a suspected contact. So basically public health calling you and telling you that we need you to test this child um radiographic or clinical findings suggested about TB disease, which is a very different entity, but you still want to do your diagnostics, Children. Um immigrating from countries with endemic infection, Asia, Middle East Africa, Latin America countries from former Soviet Union, including international adoptees. Children who have significant travel. How do you define significant travel greater than a month with endemic infection who have substantial contact with the resident population? Meaning most of those Children are not going to resorts, they are living with family members, they're spending time with their uncles and aunties and grandmas. Um And you want to do it at least 8 to 10 weeks after return. So they tell you the last week they came from India, you don't want to do it right then. And there you want to wait at least two months before their, their last travel. I apologize. I, I forgot our gardener comes on Tuesday. So there you might hear a little bit of background noise. Um annual testing. Um Children living with uh HIV infection um uh need annual testing and before initiating immunosuppressive therapy, like with corticosteroids, organ transplantation, TNF alpha antagonists. A lot of these IBD kids um should get a screen uh um DS T or A whenever a applicable, this is direct screening tool from CD PH, I wanted to put a snapshot out there. So if you're ever wondering or curious about these, you can always reflect back to CD PH TB. This is what I used to encourage families to take L TB I treatment. The younger you are the higher the risk for progression to TB disease if you're untreated. So if you are less than 12 months of age, you have 50% chance of doing developing TV disease. If you're a school age kid, the risk goes down about 5 to 10% and then it goes a little bit higher in, in adolescence. And then as an adult, you have about 5% chance. So when I, when the families come to me and I was like as an adult, you have a 5% chance your kid has a and I do feel like I inflate the numbers just a tiny bit but I, I think that, that risk, I assume and take by inflating the numbers just a teeny bit, but it's not negligible like a two year old child, kid has 25% chance of developing uh TB disease. So it, it is, it is something to, to kind of like, it kind of informs families. It's like, why do I think it's so important because I get it, it's not negligible to treat a kid with four months of a single drug when they feel like they're healthy. What are you talking about? They're, they're, they're fine. Um And then a lot of it is that where they're coming from in their region in, in growing up, it's not a thing like people don't treat L TB I, people treat TB disease. So there's a little bit of a stigma element attached to that as well, especially if they're coming in from a place where they grew up. Not knowing that L TB I is a treatable entity or TB prevention is a lot to do with L TB I treatment. So what do you do when you have a positive I or A TST, you had to, I have to identify the appropriate patient testing. Basically, you did it and then you did a TST and I, now it's positive. Now you do the evaluation part. Now it's not just about chest. Like I put that number three chest x-ray two views. It's about signs and symptoms of TB disease. Remember, it can be nonspecific. Remember, it can have anemia rece, remember it can just not have high fevers. They don't have to have a cough, they don't have to have night sweats. You do a full physical exam, you make sure you do a good lymph node exam. And I'm not talking about these like little two mobile shoddy lymph nodes. I'm talking about fixed immobile large lymph nodes. And, and if you do feel like there's a little bit of an abnormality, you know where you're not sure they just had a cold and now they have a little bit of a lymph node. It's OK to wait, it's OK to bring them back. Um And that sort of depends on your patient population is the family reliable. Do they? Will they come back versus like it's imperative for you to get the evaluation and that where you're gonna triage a little bit one way or the other, how you're gonna do it. So it, let's say all evaluation is negative. You don't need an ID doctor to kind of like um help you navigate in terms of TB uh disease. But now you're at a point where your evaluation is negative, your chest exit is negative. You're gonna treat for L TB I or TB infection. Um Th this is sort of like it goes into like if you treat TB or L TB, I, your risk for TB elimination is, is really, really good or high. Um And that's what the side is trying to, to hallucinate. But talking about treatment now, the preferred treatment is INH proin, which is uh a 12 weekly, 12 week regimen. Once a week. I do like it for my teenagers and I usually do it on a Friday because on a Friday they kind of like it's a high pill burden. They don't really feel too great. They feel a little bit of a nausea, but then they have Saturday and Sunday to recover before they go back to school. And it's really, really nice. The one thing though is that there, it does need to have what we do in our clinic. We essentially set up weekly video visits and we watch them take um the medicine because then, or um now public health has uh video assisted uh therapy. So they, they do that. If it's a reliable family, then that's the preferred. And there's a high um rate of adherence. It's not recommended for Children under two years of age. And the downside of this is that it does have come with a significant pill burden revamp is usually my go to as well. It's a four month regimen. You have to finish um take 1 20 doses, I believe within a six month period of time. There are other ones, there's INH plus or for three months and then there's INH good old for 6 to 9 months. Um, but I would say the INH has really fallen out of favor. There's some nice, uh, websites and I can, if I, if time allows, I can go and show you there's a nice medication tracker that the CDC has. Um, for this INH rent one caveat I would say is that, um, you can always refer them to ID. That's ok. But you can always take ownership uh take, you know, if you feel comfortable, um You can also initiate it yourself, it doesn't necessarily need ID involvement. Um But we're happy to see them in clinic if, if that be the case. Um I had a tough time sometime um having pharmacy getting uh rent. And uh I, before I, I initiate that I just call to the local pharmacies and make sure that they have the entire course with them rather than like enough for two courses. And then you're kind of stuck because if you miss more than uh a week or two weeks, then you have to restart the treatment course over. So that's INH rain and then this sort of elucidates like the completion rates versus adverse events associated with nine months INH versus four month revamping. You can see that there is higher completion rate with revamp and revamp is in the green. There's um lesser sort of adverse events associated with RAFA and the completion rate is higher um even in pediatric population with Rafa, this is comparing the INH plus for pente versus INH alone, a higher risk of rate of completion, both for adults and pediatric population. Um It's a less common, but I do feel like it's a great alternative for some of the teenage populations that don't want to take a daily pill for four months. Um And you can see here as well. Entine is, is very comparable to revamp. So I really give them an option. It was like, look, if, if it's not a problem for you to take reven once daily for four months and you really don't want to take 12 pills in one day, then that's fine. Take the Reva for four months and that's OK. Um So all, all Children with L TB, I should be treated. Hopefully, we, we went through that and then um sometimes the question comes up. Um How early or when should you, if you have a kid with L TB, I who also needs a TNF alpha inhibitor question, the SFDPH has guidance that ideally it should be about a month before starting and that's usually what I try to do as well. Like if they have a Crohn's or U Ce and they need, they, they um have quantified and positivity. I want them to be on treatment for one month at least before they start it, talking to families and Children about a positive test. Um I generally say that TB germ is in your child's body. But fortunately it's sleeping. You don't have any active disease or progression. I usually draw it out for them. Like right now you have that infection somewhere in your body. You, you don't necessarily have the progression to the disease, but invariably it will happen, the younger you are, the higher the chances that will happen, the older you are lesser the chance. But if it were me, I would not take any chance and basically um do this regimen and and make sure that the germ is essentially killed and the germ is easily killed. Um A lot of times families will ask questions about like, do I do repeat testing? Can we do Quran? And then I have to remind them like, remember it's not checking for the germ, it's checking your immune system. Have you ever seen the germ and the immune system will always have the memory? Yes, I have seen the germ. So it repeating the Quran or repeating the, the PPD is not a helpful thing. Um Even if you have completed the therapy, we give them like a documentation where it says like the date of completion, date of completion of therapy and we give them a letter of completion and I always tell them that you have um that'll stay part of our record. So if when the kid grows up and they will have to go to college or other things that you can always have that documentation of completion of therapy. And I also try to emphasize to them that this is important and people are gonna ask you these questions again and again. So if you don't want to remember it, that's OK. But remember where you kept the paper that you can show other people. Um We're not gonna talk about the anti TV regimen. We all know that there's usually a four drug regimen That's standard. We do a two month of intensive phase, um followed by a four month of INH drift. Kids generally tolerate it pretty well and they generally tend to do pretty well with it. When do you worry about drug resistant TB? I didn't, I didn't talk about it a lot. It really depends on where we think that the source case is from. And there are certain regions where there's high prevalence of drug resistant TB. I usually make that decision based on consultation with public health II. I don't usually make that decision in, in, in silo by myself. Like if I'm worried about drug resistant TB and some special considerations in a newborn nursery, if you will have, are you hear that mom has TB I or mom has TB disease? The first things first is to make sure that, you know, his mom has symptomatic. Has there been a chest x-ray that was negative if mom is asymptomatic, no separation is required from the mom to the baby. Um Mom would be a candidate for TB infection treatment and mom can breastfeed. There are also indications when mom has a positive TST, she has some abnormal findings. Now, granted, you know, sometimes a lot of times what happens is that as you get older, you'll get scarring from one reason to the other. So it's not always that you have an abnormal chest x-ray as an adult that it, it sort of like rings alarm bells to obese or other people. Um However, this is where that differentiation happens is, is, is the ob consulting an adult ID per se in which I would recommend that they do and they really tease that apart. How worried or how not worried are you about active TB? If you're not worried and this is an abnormal chest x-ray that was over run or there's like old granuloma or calcification, then you don't need to separate the mom and the baby. But if they're worried, then you do want to separate the mom and the baby. And at least in the time that mom is starting on therapy and other things, I don't take that lightly and I feel like I, I would, I think that's a very, very judicious thing for us to do and, and it's not wrong for us to push the obese to involve ID at that time because it's, it's, it's something that's um you know, like we're, we're making a very active decision to separate a newborn baby from my mom. Um, pediatric contact. Usually the incubation period can be as short as two weeks versus uh to 10 weeks. Um, the, in, in, in terms of like CD ph basically views negative testing at, at, at less than eight weeks as unreliable if you had your grandma who is active TB and you got um, quant testing at six weeks or TSD at six weeks, that's not enough time. You'll need to repeat it two weeks later, which is a minimum eight weeks since the time that they were active TB. And then window prophylaxis um is needed. It's, it's kind of like a misnomer. It should really be window treatment for any kid under five years of age who has been exposed to active TB or unless they are immunocompromised and babies less than six months should continue on window treatment at least under the last six months and you can retest them with the TSD because any time less than six months is considered to be unreliable. Um There are tips for giving TV medicines. Um, you can give all at once but don't mix too much with food. If you have vomiting less than 30 minutes. After retaking, you can re re redose it, iron h and liquid form will give you um osmotic diarrhea. So we tend not to, it's a very small pill, you can crush it. So and make a jelly sandwich and, and give it to the kids. Um outcomes are generally good. Um And adverse events are rare and I'm gonna skip through the MD R slide and, and um take maybe 30 seconds to talk about one other case. So key points essentially is that TB is very, very important locally and globally, clinical suspicion should remain really, really high um to make sure that you're not missing something in terms of your diagnosing and screening and treatment is generally well tolerated in Children. And the main mitigation factor that we have in our arm mentum to prevent TB disease is treating the L TB I infection. So I'll end with another case that we saw this year. This is a 15 month old with no past medical history, meaning otherwise healthy lives with mom, dad, two older siblings who are six and eight, they're from Stockton and he was admitted back earlier in February for bilateral mastoiditis. His cultures were negative. He got ear tubes placed. He completed a four week course of Augmentin was seen in outpatient um ID clinic was near his neurologic baseline was ok. And then mom notes that around July 31st and she remembered the date because it was her birthday. He started to not behave quite himself. He started to have lethargy and not feeling well. English was not, is not their primary language. So the the best that they could describe that this toddler was behaving was not quite himself. He was seen in urgent care multiple times he didn't have high grade fevers, he didn't look all that terrible. And, and with the symptoms that the parents were describing the natural tangential point was that he had a age or a viral illness. The fourth time he was seen in the Ed, he, the parents said he's making these like really weird eye movements. Um And, and, and I mean, I remember talking to dad and dad was like, I wasn't ready to leave the ed at that time. I told them that you're gonna watch my child die. Um And um I'm not leaving so that I'm not sure this if that truly happened. Um But that was what dad said and, and he had ac T done which showed marked hydrocephalus and he was transferred to the R IC U. He had EVD placement because of his hydrocephalus, his brain MRI and, and I only included like very high level things, but it showed leptomeningeal enhancement and a Basler stroke. When I saw him, he had these writhing movements on his one side clearly indicated that his basal ganglia was affected CD chest and lymph nodes had like some supercar lymph nodes with some central necrosis. His quan was positive and, and this is important to note because we talked about it, right? Like in the setting of, of this, if you look, his numbers are like he was barely positive, he's 0.39. But oftentimes for Extra Pulmonary disease, when you have especially CNS disease. You're not gonna get a rip roaring positive quan response or infer gamma response. And his diagnosis ultimately came to be TB meningitis. He spent a long time in the rehab. He has um a VP shun he has a G tube. He is able to localize to sound, he's not verbal and he's gonna need intensive therapy. And the contact investigation from this for me, mom was negative. Father was negative livings were negative. He did travel to Mexico back in December for about a month. Parents were very hesitant to talk more about it and and this is still an ongoing case. So we we may know later um who may his in index case would be or we may never know. Um but he's, he's now on um two drug regimen INH and that's all I have. I do see some questions. I'm a um OK. The Yeah, so Sophia I heard says mitogen is supposed to be greater than five. The the absolute numbers probably vary a little bit. And II I showed you guys that information more so to have a background context. But in the day to day when you are screening, just make sure that a you do it on the right patient and you do a do have a index ex of their pretest probability. And when you look at the results, you look at the results as positive negative indeterminant when you have an indeterminant, just make sure that you don't have a patient who is your screening for active disease? If you're not screening for active disease, you're screening because they have risk factors, you repeat the test, you do a different test or you get a TSD and that's really it, the test failed. And, and that's what you go off on. Rifapentine is covered uh by medical and, and, and it's ok. Um, window therapy is essentially for patients who have been exposed to active TB um from their household contact and they're under five years of age because the risk is so high for them to develop active disease. We basically say we're not gonna wait for you to show us a positive QFT or A TST. We're gonna treat you and then we're gonna recheck your TST or your Quran two months since your active time of exposure to that family member. And if that's positive, we give you L TB I treatment. If it's negative, we stop there. But that's essentially the point is that window therapy is needed for patients who have high risk grade less than five. And, and also we're welcome to take, we, we and ID, welcome those patients as well and usually they have um public health already involved as part of the contact investigation and other things. And some of the counties, especially Alameda County is really good about like prompting those things, some of the other counties, you know, it, there, there's a, at least from my point of time, it, it, it can be variable. You, you screen for recurrent TB is by symptom screening. You don't get a repeat quant front um on them, you do a symptom screen and you say basically at that point, if they have completed a course of TB I treatment, then you do symptom screening with any active disease and if they have symptoms or they have concerns, then you do get a chest x-ray. But uh that's essentially what the, the, what you do. It, it's in elegant. I also don't really like it, but that's kind of the recommendations for it. Um, a five month old baby who traveled to endemic area should have a TST. Um, can you wait till 12 months? A five month old baby who has traveled to endemic area for greater than a month who's visited their family and they're at least two months out from their travel time. You can get a TST. You don't have to wait till 12 months. Do you recommend BC G for patients who will travel? You won't be able to get BC G. I don't think we are able to get PC G here. And I, to me the, the reason why endemic areas recommend BFCG is that in really young infants, it prevents against severe disease like TB meningitis. So it, it, it becomes your proportionality of like your risk benefit. And, and um, you know, I can't say that it's wrong to be able to do BC G like if you're traveling with your newborn baby and you're gonna go, I'll, I'll pick up India. Um because uh you know, I have family there but like I um and you, you take your baby there and you're gonna be there for six months. Maybe that would be something that you can think about. I have had family where you have kind of gone through that practice. It was like, OK, so after the six months, are you gonna come back to us? If your BC G is positive, then your child will have limitations in terms of the testing for screening that they'll be able to get, it'll be a false positive. How much of that risk mitigation do you want to take? Versus for example, if they're telling me that their, you know, grandparent has active pulmonary TV, and they really want to take their baby to see the grandpa and they're gonna stay there for three months. Uh that baby, I'm there. It doesn't matter. You, you, you get your BC G and, and we'll deal with the consequences of a false positive TC after the fact. So um doctor Hu asked um um the, so in your case example, with the kid who had initially tested positive and then tested in determinant in the test was positive. Can you explain the Mitel results? I will try, I also looked at that and I was like, wait, that doesn't make sense to me too much because I did that like two minutes prior to the talk, I'll go back to it and I'll see if I can explain it. Maybe I'll, and I, or I'll follow it up with the email because to me it feels like the mitogen should also be higher than what he responded to, but we can go back to it. Um, and that doctor Jackson said I live on the border. Um I see patients who travel to Tijuana several times a month for a weekend. How often should they be tested? Um I would say I repeat testing, especially for TSD. There is a booster phenomena so I wouldn't keep testing them and, and it depends on um you know, like a weekend travel where they're staying in their local setting, it doesn't make sense to keep testing them. I would say if the risk is high enough yearly quantum front testing is appropriate for them. Um But a lot of times that's not a high enough exposure time unless they're really um you know, assimilated within that society. Um A TST positive. Next step. Quan, when is chess ordered? It depends. I hope I was able to elucidate when your TST is positive. I would only get a, if you really think that it's a low risk situation. If a TST was done on a kid who has lived his entire life in Berkeley and he's never traveled outside the country. He's not born in a different, you know, like non U he was born in us and the parents are like, why is the TST positive? We're perplexed about this. I would get a quant front. If the quant front is negative, you're done. If the quantum front is positive, then he has a chest x-ray. I am so appreciative and thankful for all the questions because that's when I feel like I have engaged the audience enough to kind of stimulate a little bit of questions. Let me see if I can go back to the and, and you know, one of the things that um it could be that I might have copy, pasted the initial test results um from a different patient because I was looking up several different patients. So that, that, that could very well be like I said, I did it right before the the presentation so I can go back and look, but it could be from a different patient. And I apologize about that. I was gonna say you did a great job getting through all those questions. Thank you. I, I really do interacting like interacting with through questions like that. That to me feels like the most. I, I agree. So if you look here when he had a positive, the nil this, this seems flip to me and, and it could be the way they reported it because the the the way the lab enters these things, it it's manual. So to me, it looks like the m the nil should be zero and the mitogen is seven, which would then make sense. Um And I think these two numbers are flipped. So that would be my easiest expla like the most plausible and the logical explanation and the fact that his TB one and TB two nil are, are greater than 10. Thank you so much for speaking to us today. We're at time. So I wanna make sure we um are people's times, please make sure you fill out your evaluation after this lecture so you can get your CME credit. You'll also get it in an email. If you can turn that in tomorrow by tomorrow, you'll be able to get your credit that way and again, thank you again for speaking and thank you all for attending and we hope you have a great rest, rest of your week. We'll see you later. Thanks again and if your your feedback is appreciated. So thank you. Thanks for filling out the emails. Yeah, great. Thank you. Bye.