1 00:00:07,685 --> 00:00:08,465 Hi everyone. 2 00:00:08,495 --> 00:00:12,815 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:12,882 --> 00:00:16,872 We use consult questions to dive into ID clinical reasoning, diagnostics 4 00:00:16,872 --> 00:00:18,282 and antimicrobial management. 5 00:00:18,382 --> 00:00:21,382 I'm Sara Dong, your host and a Med Peds ID doc. 6 00:00:21,793 --> 00:00:25,243 Today we have a ID podcast crossover. 7 00:00:25,693 --> 00:00:29,683 I am joined by two of the three hosts of the German speaking 8 00:00:29,683 --> 00:00:32,213 ID podcast called Infektiopod. 9 00:00:32,455 --> 00:00:34,336 I'll first introduce Dr. Till Koch. 10 00:00:34,781 --> 00:00:37,781 He is an attending in infectious diseases and antibiotic 11 00:00:37,781 --> 00:00:39,641 stewardship in Itzehoe, Germany. 12 00:00:39,971 --> 00:00:43,841 He divides his time between the inpatient ID ward, consultation 13 00:00:43,841 --> 00:00:47,051 service, and antibiotic stewardship efforts in his rural hospital. 14 00:00:47,199 --> 00:00:50,169 Yeah, hi, and my name is Till, and I'm super excited to be here. 15 00:00:50,469 --> 00:00:51,849 Looking forward to the episode. 16 00:00:51,966 --> 00:00:55,296 Also on the podcast today is Dr. Annette Hennigs. 17 00:00:55,656 --> 00:00:59,076 She's a senior fellow in infectious diseases at the University Medical 18 00:00:59,076 --> 00:01:01,536 Center Hamburg Eppendorf in Germany. 19 00:01:01,620 --> 00:01:05,090 Her daily business is leading the consultation service and her main focus 20 00:01:05,090 --> 00:01:07,370 of interest is cardiovascular infections. 21 00:01:08,133 --> 00:01:09,213 Hello, I'm Annette. 22 00:01:09,213 --> 00:01:14,078 I'm so happy to be here to do this cross Atlantic Crossover, uh, podcast episode. 23 00:01:14,328 --> 00:01:15,198 Happy to be here. 24 00:01:17,351 --> 00:01:20,691 Their third host, I'll just give a shout out to is Dr. Elena Terhalle. 25 00:01:21,376 --> 00:01:27,256 So as Febrile is a cultured podcast, we ask our guests to share a little piece 26 00:01:27,256 --> 00:01:30,852 of culture, basically just something fun and non-medical that you like. 27 00:01:30,876 --> 00:01:33,666 What have you guys been interested in recently? 28 00:01:34,446 --> 00:01:38,536 Yeah, so, I'm actually been more, uh, outgoing these days. 29 00:01:38,586 --> 00:01:40,656 My kids are getting a little older right now. 30 00:01:40,656 --> 00:01:46,956 They're 10 and 12, and we all try to, you know, keep ourselves when they're toddlers 31 00:01:46,956 --> 00:01:48,906 and little, but it's not really happening. 32 00:01:48,906 --> 00:01:53,256 But now, um, we've been going out with them to concerts and everything. 33 00:01:53,256 --> 00:01:56,496 So I went with my daughter to Taylor Swift last summer and 34 00:01:56,826 --> 00:01:58,336 we're gonna go see Ed Sheeran. 35 00:01:58,356 --> 00:02:02,366 And it's really nice that obviously, my husband and me have made a little bit 36 00:02:02,366 --> 00:02:07,016 of an impression with their music taste, and so it's really fun to see them grow 37 00:02:07,016 --> 00:02:11,486 up and, and, uh, be a little more, more outgoing with them or going out with them. 38 00:02:12,136 --> 00:02:12,646 I love it. 39 00:02:13,336 --> 00:02:14,116 Very nice. 40 00:02:15,016 --> 00:02:15,196 Yeah. 41 00:02:15,196 --> 00:02:19,486 And for me, something that really, uh, brings me joy, um, is carpentry. 42 00:02:19,546 --> 00:02:23,806 So, uh, building furniture actually, and I, in the last two years, I 43 00:02:23,806 --> 00:02:27,436 managed to set up like a tiny little workshop for myself and when I was 44 00:02:27,436 --> 00:02:30,526 studying medicine, I used to do it a lot actually and find more time for it. 45 00:02:30,526 --> 00:02:33,436 But, uh, since I've been working, I've, yeah, I can't, just 46 00:02:33,436 --> 00:02:34,456 can't do it so much anymore. 47 00:02:34,456 --> 00:02:37,846 But yeah, creating something with your hands, really that brings me joy. 48 00:02:37,985 --> 00:02:42,335 That's a skill that I fantasize that one day I will be good with 49 00:02:42,335 --> 00:02:44,045 no training and no experience. 50 00:02:45,605 --> 00:02:49,295 Um, well I am so excited that you guys are here. 51 00:02:49,375 --> 00:02:55,720 You have been working on Infektiopod since 2019, right and you are expert 52 00:02:55,720 --> 00:02:59,320 ID docs we're doing this crossover podcast, but I was hoping that you 53 00:02:59,320 --> 00:03:03,970 could introduce everyone to your podcast, um, and tell them a little 54 00:03:03,970 --> 00:03:05,170 bit more about how they can find it. 55 00:03:05,473 --> 00:03:11,413 Yeah, so we, uh, started in Infektiopod in January of 2019 as a podcast on infectious 56 00:03:11,413 --> 00:03:13,213 diseases in, uh, German, obviously. 57 00:03:13,287 --> 00:03:17,007 First I started by myself because I like podcasts and I was passionate 58 00:03:17,007 --> 00:03:21,477 about ID and at the time I was also working in the Institute for Tropical 59 00:03:21,477 --> 00:03:25,137 Medicine in Hamburg, and I was listening to, uh, famous other podcasts. 60 00:03:25,227 --> 00:03:29,322 Uh, one that I started with I think was This Week in Parasitism featuring, uh, 61 00:03:29,322 --> 00:03:33,242 Vincent Racaniello and Daniel Griffin, and then also the original Puscast by 62 00:03:33,242 --> 00:03:34,962 Mike Crislip, which I really enjoyed. 63 00:03:34,962 --> 00:03:38,132 And then, yeah, of course the podcast universe has been growing since then. 64 00:03:38,612 --> 00:03:44,077 Um, so the first episodes of Infektiopod were really just on specific pathogens. 65 00:03:44,077 --> 00:03:48,597 And then in 2020 we shifted a bit towards COVID and the, uh, team 66 00:03:48,597 --> 00:03:50,637 grew as Annette and Elena joined in. 67 00:03:50,637 --> 00:03:55,137 And uh, ever since then, we've been doing it as the three of us, this podcast. 68 00:03:55,617 --> 00:04:00,237 And yeah, so we produced a little over 90 episodes so far. 69 00:04:00,237 --> 00:04:02,757 Most of them, or all of them, actually almost in German. 70 00:04:03,147 --> 00:04:06,027 And we covered a wide range of ID topics, I would say. 71 00:04:06,297 --> 00:04:08,997 And most recently we've also covered a few conferences. 72 00:04:09,242 --> 00:04:11,792 Um, ESCMID and ID week, for example. 73 00:04:11,822 --> 00:04:12,032 Yeah. 74 00:04:12,602 --> 00:04:17,162 And, uh, we've also written down what we want to do with a podcast as a poster 75 00:04:17,162 --> 00:04:18,992 for this year's ESCMID, for example. 76 00:04:19,262 --> 00:04:23,042 I don't know if it's, uh, readily available online, but, uh, we can find it. 77 00:04:23,342 --> 00:04:25,982 And we wrote down what we want to do with the podcast. 78 00:04:25,982 --> 00:04:28,622 So basically we said we have three goals. 79 00:04:28,622 --> 00:04:31,922 We want to, uh, give a direct knowledge transfer. 80 00:04:32,312 --> 00:04:33,812 I think that's pretty straightforward. 81 00:04:34,212 --> 00:04:36,222 Then we want to build trust in science. 82 00:04:36,242 --> 00:04:39,602 That was a big topic here, um, in the, in the whole COVID 83 00:04:39,602 --> 00:04:43,652 pandemic, but also, uh, take part a little bit in societal debates. 84 00:04:43,652 --> 00:04:47,132 So especially around COVID, we also said what we thought about vaccines 85 00:04:47,132 --> 00:04:48,842 and, uh, that that's also important. 86 00:04:49,062 --> 00:04:50,082 Yeah, I love it. 87 00:04:50,112 --> 00:04:56,022 And I should say we, we got to meet at ID week, which is how this all blossomed. 88 00:04:56,022 --> 00:04:59,602 And yeah, I, we should definitely share your poster from ESCMID. 89 00:04:59,622 --> 00:05:01,842 We can, um, put it on the webpage too. 90 00:05:02,052 --> 00:05:05,682 But, uh, I'm excited that you're here 'cause you're gonna help us walk 91 00:05:05,682 --> 00:05:07,962 through a pretty challenging case. 92 00:05:07,962 --> 00:05:12,742 So I, I'll start us off and then we're gonna cover a lot of info 93 00:05:12,742 --> 00:05:14,752 today about some, a viral infection. 94 00:05:14,902 --> 00:05:20,692 So we have a 56-year-old woman who has a history of ischemic cardiomyopathy. 95 00:05:21,112 --> 00:05:23,452 She's now status post heart transplant. 96 00:05:23,752 --> 00:05:26,777 She was CMV donor negative recipient negative. 97 00:05:27,392 --> 00:05:31,022 Her post-transplant course has been complicated by some postoperative 98 00:05:31,022 --> 00:05:34,952 renal failure, so she is requiring dialysis, but at this point she's 99 00:05:34,952 --> 00:05:38,342 improving and she's been transferred to the normal post-transplant ward. 100 00:05:39,002 --> 00:05:43,262 So at around six weeks after transplantation, um, we'll say 101 00:05:43,262 --> 00:05:44,192 she was still hospitalized. 102 00:05:44,192 --> 00:05:47,372 We're not given sort of full details here, but um. 103 00:05:47,547 --> 00:05:51,717 We at this point notice that the patient has these newly formed vesicles 104 00:05:51,717 --> 00:05:53,787 and erythema on the chest and back. 105 00:05:54,327 --> 00:05:57,207 Dermatology was consulted and took a biopsy. 106 00:05:57,627 --> 00:06:00,537 Um, and then there was some suspicion for TEN. 107 00:06:00,567 --> 00:06:04,767 So the patient also was placed on pulse therapy with steroids. 108 00:06:05,367 --> 00:06:09,117 Um, swabs of the vesicles were obtained and they came back with a very 109 00:06:09,117 --> 00:06:11,307 high viral load of varicella virus. 110 00:06:11,637 --> 00:06:16,377 And this was, oh, I should have done it in my head before 1.4. 111 00:06:16,727 --> 00:06:17,477 Is that billion 112 00:06:17,552 --> 00:06:17,842 Yeah. 113 00:06:18,977 --> 00:06:25,007 Billion 1.4 billion copies per ml. And she had a subsequent PCR from 114 00:06:25,007 --> 00:06:30,767 blood that, uh, showed a VZV viral load that was 700,000 copies per ml. 115 00:06:31,307 --> 00:06:34,217 Um, so here we have a heart transplant recipient who has 116 00:06:34,217 --> 00:06:35,897 this diffuse vesicular rash. 117 00:06:36,227 --> 00:06:39,978 We now have confirmation of VZV from an unroofed vesicle. 118 00:06:40,277 --> 00:06:42,557 So, you know, do we have our diagnosis here? 119 00:06:42,557 --> 00:06:47,297 Is there anything else that you want to make sure we consider for next steps? 120 00:06:48,127 --> 00:06:49,647 So I think, yeah, we see here. 121 00:06:49,687 --> 00:06:52,477 Now that we established the diagnosis with the PCR. 122 00:06:52,477 --> 00:06:57,577 So that's actually confirmed with a disseminated varicella infection. 123 00:06:57,877 --> 00:07:00,937 We have to figure out what kind of infection it is. 124 00:07:00,937 --> 00:07:03,007 So we have to check the pre-transplant serologies. 125 00:07:04,197 --> 00:07:08,457 Um, which in this, yeah, if it's, if the patient was, um, seropositive 126 00:07:08,457 --> 00:07:12,207 before transplantation, so we would be dealing with kind of a reactivation or 127 00:07:12,207 --> 00:07:16,907 if it would be at age 56, a rare case of a seronegative patient that was, 128 00:07:16,907 --> 00:07:21,617 uh, transplanted and now has a primary varicella infection, which is not so 129 00:07:21,617 --> 00:07:25,122 much different in treatment, but it's something that would be interesting. 130 00:07:25,512 --> 00:07:29,652 And, um, so the sero prevalence is, is really high in adults. 131 00:07:29,742 --> 00:07:34,782 Around 90% in this age range is mostly due to previous infection. 132 00:07:34,782 --> 00:07:37,542 The, the younger people are now getting vaccinated, but we're 133 00:07:37,782 --> 00:07:39,272 think we'll cover that later on. 134 00:07:39,552 --> 00:07:45,082 After infection, the virus has latency in different parts of the body, in the 135 00:07:45,082 --> 00:07:50,222 cranial nerve and dorsal root ganglia and can reactivate at any time in life. 136 00:07:50,222 --> 00:07:54,092 So, around 20% is the lifetime risk of reactivation as 137 00:07:54,152 --> 00:07:55,472 herpes zoster as we call it. 138 00:07:55,472 --> 00:08:00,362 Now, the classical symptom would be a dermatome, like a localized, uh, skin 139 00:08:00,362 --> 00:08:05,582 infection or skin reactivation and in transplant patients or in solid organ 140 00:08:05,582 --> 00:08:10,012 transplant recipients, it's around up to 10, 11% in the first four 141 00:08:10,012 --> 00:08:14,182 years after transplantations with heart and lung transplant recipients 142 00:08:14,182 --> 00:08:18,082 having the highest risk 'cause of the more aggressive immunosuppression, 143 00:08:18,332 --> 00:08:20,412 in comparison to other organs. 144 00:08:20,662 --> 00:08:25,537 With this diagnosis we have to see if there's any other, um, 145 00:08:25,627 --> 00:08:27,697 affection of any other organs. 146 00:08:27,697 --> 00:08:30,247 So if there's like pulmonary, um, affection of the other, 147 00:08:30,247 --> 00:08:32,977 like hepatic, um, um, affection. 148 00:08:32,977 --> 00:08:36,697 So we should definitely do clinical monitoring lab parameters in 149 00:08:36,697 --> 00:08:40,297 case of, you know, she's having problems breathing or dyspnea, we 150 00:08:40,297 --> 00:08:41,917 should do imaging of the chest. 151 00:08:41,917 --> 00:08:45,697 We should check for neurologic symptoms to, to rule out 152 00:08:45,797 --> 00:08:47,657 cerebral reactivation as well. 153 00:08:47,837 --> 00:08:53,077 So that has to be like a really good clinical workup of the patient and then 154 00:08:53,077 --> 00:08:59,437 guided by that additional lab maybe, or, or imaging, um, that should be performed. 155 00:08:59,681 --> 00:09:05,051 Perhaps we can take a step back again also and re reiterate the primary 156 00:09:05,051 --> 00:09:08,141 manifestations of varicella zoster virus. 157 00:09:08,501 --> 00:09:12,701 And, we divide the clinical symptoms in either the, uh, reactivation that 158 00:09:12,701 --> 00:09:16,431 Annette has already spoken about, or before that, the primary varicella. 159 00:09:16,451 --> 00:09:21,261 So that would be the chicken pox in English or the windpocken in, uh, German. 160 00:09:21,261 --> 00:09:21,411 So. 161 00:09:21,541 --> 00:09:22,771 The wind pox basically. 162 00:09:22,831 --> 00:09:27,751 And this is, I think, the super highly contagious disease of childhood that 163 00:09:27,751 --> 00:09:30,271 we, or usually childhood, that we know. 164 00:09:30,491 --> 00:09:32,391 Quick side to the epidemiology again. 165 00:09:32,391 --> 00:09:36,561 Um, the, the seroprevalence is actually much lower in tropical regions, so it's 166 00:09:36,561 --> 00:09:40,781 not so uncommon to see here someone who grew up in a tropical region, for 167 00:09:40,781 --> 00:09:45,231 example, who migrated to Germany, have a primary VZV infection in their adulthood. 168 00:09:45,276 --> 00:09:47,686 But yeah, I think this clinical presentation. 169 00:09:47,686 --> 00:09:52,576 We, we know mostly it has different, uh, different stages at the same time. 170 00:09:52,876 --> 00:09:55,126 So this, uh, how's it called in English? 171 00:09:55,126 --> 00:09:58,396 This star, this, 172 00:09:58,451 --> 00:10:01,571 Oh, the, um, dew on a petal. 173 00:10:02,471 --> 00:10:02,831 Yeah, 174 00:10:02,841 --> 00:10:03,081 I can. 175 00:10:03,271 --> 00:10:03,561 Okay. 176 00:10:03,751 --> 00:10:08,221 Um, so yeah, so it had has different stages at the same time of skin 177 00:10:08,221 --> 00:10:12,181 manifestation, so it can have vesicular and macular papular at the same time. 178 00:10:12,571 --> 00:10:16,981 And a bit different from that is the clinical presentation of the reactivated 179 00:10:17,001 --> 00:10:19,561 VZV infection, what we call herpes zoster. 180 00:10:19,981 --> 00:10:24,351 Um, because normally in immunocompetent persons, the rash is typically 181 00:10:24,381 --> 00:10:26,781 restricted to one dermatome, right? 182 00:10:26,851 --> 00:10:31,481 Apart from the rash, which has been described as this, um, dew on a rose 183 00:10:31,481 --> 00:10:35,038 petal, so like a dew drop on a rose petal, apart from this rash, the 184 00:10:35,038 --> 00:10:40,098 other, uh, clinical sign is the pain or the neuritis that is described. 185 00:10:40,098 --> 00:10:44,408 So if you see rash and it's painful, then you should think about zoster and 186 00:10:44,438 --> 00:10:46,838 the, uh, pain can also vary clinically. 187 00:10:46,838 --> 00:10:49,448 So some people don't even feel a lot of pain. 188 00:10:49,448 --> 00:10:52,118 Some people feel pain even before the rash develops. 189 00:10:52,118 --> 00:10:56,028 And some people, um, develop the pain only only after the rash comes. 190 00:10:56,418 --> 00:10:59,428 And one clinical pearl that I learned that you could do if you 191 00:10:59,428 --> 00:11:03,568 want to test for this neuritis is, uh, that you test the hyperesthesia. 192 00:11:03,568 --> 00:11:08,108 So you take a little wood, wood spatula, and you kind of move it, 193 00:11:08,168 --> 00:11:09,638 uh, around, around on the rash. 194 00:11:09,638 --> 00:11:13,598 And then it should hurt more than on unaffected, uh, sites. 195 00:11:13,718 --> 00:11:17,198 And maybe another question to ask the patients is if it's itching, because 196 00:11:17,198 --> 00:11:21,098 this would really not be very typical of zoster and really, uh, push you in 197 00:11:21,098 --> 00:11:22,808 other clinical directions, I would say. 198 00:11:24,138 --> 00:11:27,228 So this is the typical presentation of herpes zoster. 199 00:11:27,244 --> 00:11:30,874 But then, uh, we already mentioned also that there are some complications 200 00:11:30,874 --> 00:11:34,774 and I think the most common one, and that most people know, uh, probably 201 00:11:34,774 --> 00:11:36,574 is this post hepatic neuralgia. 202 00:11:37,054 --> 00:11:41,914 It affects around 15%, uh, of the patients as especially the older patients. 203 00:11:42,004 --> 00:11:46,209 And this can really be a very severe complication because some people 204 00:11:46,209 --> 00:11:50,599 have to take long lasting pain medications to deal with the pain. 205 00:11:50,899 --> 00:11:52,669 So that's the most common complication. 206 00:11:52,669 --> 00:11:56,809 But then there are also, uh, a lot of other complications from herpes zoster 207 00:11:57,349 --> 00:12:03,534 reactivation, um, mostly, uh, affecting either the eyes, which can be blindness 208 00:12:03,534 --> 00:12:08,844 inducing or, sight threatening, um, or infecting the ear, which can, then 209 00:12:08,874 --> 00:12:12,584 lead to something, for example, called this Ramsey Hunt Syndrome, where you 210 00:12:12,584 --> 00:12:14,914 have like a facial nerve paralysis. 211 00:12:14,929 --> 00:12:18,162 And these zoster vesicles in your ear and also pain. 212 00:12:18,412 --> 00:12:21,892 And then, I think Anna to mentioned it briefly also, that you can have a 213 00:12:21,922 --> 00:12:23,272 central nervous system involvement. 214 00:12:23,272 --> 00:12:26,792 So you can have, have either meningitis or encephalitis. 215 00:12:27,092 --> 00:12:30,692 And of course the worst complication is what we have here, which 216 00:12:30,692 --> 00:12:32,162 is a disseminated infection. 217 00:12:32,162 --> 00:12:36,722 And, uh, that occurs, um, exclusively in severely immunocompromised host. 218 00:12:37,131 --> 00:12:37,671 Yeah. 219 00:12:38,091 --> 00:12:42,451 And so in this case we have quite typical vesicular lesions, which were 220 00:12:42,451 --> 00:12:44,551 not maybe typical in the beginning. 221 00:12:44,551 --> 00:12:48,001 So that's why dermatology was consulted and there was histopathology 222 00:12:48,001 --> 00:12:51,456 that showed something, you know, for severe, like drug reaction. 223 00:12:51,661 --> 00:12:54,721 So I think that's, that's what happened here, but then you can really. 224 00:12:55,726 --> 00:12:58,876 Depending on where your hospital is localized and how quick your access to 225 00:12:58,876 --> 00:13:02,956 microbiology is, you can establish the diagnosis pretty sensitively with PCR 226 00:13:02,956 --> 00:13:08,216 and PCR can be done good from, from the swabs from the vesicles, ideally 227 00:13:08,456 --> 00:13:10,286 with like a freshly open vesicular. 228 00:13:10,286 --> 00:13:12,836 But you know, if you have open, um, vesicles, you can do it there. 229 00:13:13,046 --> 00:13:16,586 Or then if you have an immunocompromised host, as in this case also in blood, 230 00:13:16,586 --> 00:13:20,386 and then you can see if you have a systemic reactivation in that case. 231 00:13:20,716 --> 00:13:25,421 And the quickness of the diagnosis is, especially in immunocompromised 232 00:13:25,421 --> 00:13:29,231 hosts is obviously very important so that you can, you know, start 233 00:13:29,231 --> 00:13:34,561 treatment, um, really quickly to prevent further complications in that case. 234 00:13:35,281 --> 00:13:39,871 Yeah, so what we would do now when we establish the diagnosis is we would start 235 00:13:39,901 --> 00:13:44,291 treating and the first line treatment would be Acyclovir in high dose. 236 00:13:44,351 --> 00:13:48,761 Um, and this patient was on hemodialysis, but this is like the 237 00:13:48,786 --> 00:13:50,926 first line and preferred treatment. 238 00:13:50,926 --> 00:13:53,866 So we would do it in irrespective of the renal failure. 239 00:13:54,376 --> 00:13:58,546 And, um, one thing I actually learned, uh, with one case that we treated 240 00:13:58,546 --> 00:14:02,716 with Acyclovir, there was another patient, uh, unrelated to this, and 241 00:14:02,806 --> 00:14:07,066 he had like a very quick and very sharp rise in the creatinine after 242 00:14:07,066 --> 00:14:08,926 one day of treatment with Acyclovir. 243 00:14:09,286 --> 00:14:12,376 We stopped acyclovir because we thought something weird is going on here. 244 00:14:12,376 --> 00:14:15,196 And then the, the creatinine went down really quickly and we 245 00:14:15,196 --> 00:14:17,987 talked to pharmacology this to our pharmacist and they said it. 246 00:14:18,421 --> 00:14:24,031 It's, it's, it's a known complication that, um, if you give it intravenously and 247 00:14:24,031 --> 00:14:28,481 you infuse it too quickly then you have obviously high plasma levels right away. 248 00:14:28,781 --> 00:14:32,681 And it's, it's primarily excreted through the kidney unchanged, um, and, 249 00:14:32,681 --> 00:14:34,991 but has a poor solubility in the urine. 250 00:14:34,991 --> 00:14:38,531 So if it is in these high concentrations, goes directly into 251 00:14:38,531 --> 00:14:42,401 the urine, it precipitates and can cause acute tubular ne necrosis. 252 00:14:42,701 --> 00:14:47,251 And this is shown by this very steep rise, and then, then quick fall 253 00:14:47,251 --> 00:14:48,961 again, after, after stopping it. 254 00:14:49,351 --> 00:14:54,836 It can, these patients can get acyclovir again with slow infusion speed or 255 00:14:54,836 --> 00:14:58,026 as an oral, antiviral because then the, the spike is, so the really, 256 00:14:58,026 --> 00:14:59,286 the quick spike is the problem here. 257 00:14:59,526 --> 00:15:01,836 I, I just learned that pretty recently. 258 00:15:01,836 --> 00:15:03,276 I don't know if maybe it's common knowledge, but it 259 00:15:03,276 --> 00:15:04,356 was very interesting to me. 260 00:15:04,686 --> 00:15:09,436 It's different to be like chronic toxicity with long-term or longer term acyclovir. 261 00:15:10,151 --> 00:15:12,101 So this is what, what should be done right away. 262 00:15:12,101 --> 00:15:16,291 You know, start the patient on Acyclovir, and then monitor the clinical response. 263 00:15:16,631 --> 00:15:21,701 So the, the role of steroids is a bit, um, controversial, especially in zoster. 264 00:15:21,971 --> 00:15:26,401 Some people say it's might prevent occurrence of post zoster neuralgia, 265 00:15:26,611 --> 00:15:30,981 but obviously you wanna try to lower the immunosuppression as much as possible. 266 00:15:31,071 --> 00:15:35,541 And if it's not easy for like recently transplanted host, but as 267 00:15:35,541 --> 00:15:39,891 the diagnosis of the severe cutaneous allergic reaction is not confirmed, 268 00:15:39,891 --> 00:15:41,781 we would, um, try to tackle that. 269 00:15:41,781 --> 00:15:44,841 Or, I mean, go back to the baseline where, where she was before. 270 00:15:44,841 --> 00:15:44,901 Yeah. 271 00:15:45,724 --> 00:15:48,394 And one thing we should also do in this, um, patient is screen 272 00:15:48,394 --> 00:15:50,554 for other viral reactivation. 273 00:15:50,554 --> 00:15:54,424 So what is usually done anyways is regular screening for 274 00:15:54,424 --> 00:15:57,624 CMV viremia, and also HSV. 275 00:15:57,654 --> 00:16:00,684 This should be, should be done in this situation as well, where 276 00:16:00,684 --> 00:16:04,594 you have this unclear rash like in when it was unclear at first. 277 00:16:04,654 --> 00:16:04,804 Yeah. 278 00:16:04,804 --> 00:16:06,304 So this, this should be done as well. 279 00:16:06,454 --> 00:16:09,724 I do feel like that is one of the challenges is sometimes these patients 280 00:16:10,024 --> 00:16:13,354 have a vesicular rash and maybe you don't have a super compelling 281 00:16:13,354 --> 00:16:17,944 story for VZV versus HSV and, um, that PCR really helps you out. 282 00:16:18,255 --> 00:16:18,435 Yeah. 283 00:16:18,435 --> 00:16:22,415 And I just want to underscore this point of making the diagnosis of generalized 284 00:16:22,415 --> 00:16:26,125 herpes zoster infection, but also frankly about a normal herpes zoster 285 00:16:26,125 --> 00:16:28,255 reactivation in immunocompromised host. 286 00:16:28,255 --> 00:16:31,585 This can be a bit challenging because we all know the pictures of, uh, these 287 00:16:31,585 --> 00:16:33,205 patients where it's a clear cut case. 288 00:16:33,205 --> 00:16:37,465 You have one dermatome that has a typical rash, then it's a clinical diagnosis. 289 00:16:37,495 --> 00:16:42,150 But really keep in mind that you can do, uh, if you have the suspicion, a PCR from 290 00:16:42,150 --> 00:16:46,020 the vesicles, and this will definitely give you the diagnosis or rule it out. 291 00:16:46,256 --> 00:16:46,556 Okay. 292 00:16:46,556 --> 00:16:49,916 So in this case, acyclovir was quickly started. 293 00:16:50,446 --> 00:16:54,526 At this point the patient has received about two weeks of acyclovir. 294 00:16:54,796 --> 00:16:58,276 Some of the skin lesions, particularly on the extremities, do seem to be 295 00:16:58,276 --> 00:17:02,476 improving, but the viremia present in the blood has still remained 296 00:17:02,476 --> 00:17:04,276 quite high and persistently high. 297 00:17:04,786 --> 00:17:09,706 Um, so what might you be wondering about now given this persistent viremia? 298 00:17:09,706 --> 00:17:13,021 And I think it's probably just a good place for us to take a step 299 00:17:13,021 --> 00:17:16,681 back and think about our antiviral options that are available to us. 300 00:17:16,681 --> 00:17:20,401 We obviously focus and everyone's very comfortable with knowing 301 00:17:20,401 --> 00:17:23,491 aciclovir as our drug of choice, especially in someone who's 302 00:17:23,671 --> 00:17:25,471 critically ill and immunocompromised. 303 00:17:25,471 --> 00:17:27,301 But what other options are out there? 304 00:17:28,276 --> 00:17:28,696 Yeah. 305 00:17:28,696 --> 00:17:31,756 So when I think about antiviral treatment, I first go back a step 306 00:17:31,756 --> 00:17:33,736 and think about what I want to treat. 307 00:17:33,736 --> 00:17:38,596 And in our case, it's VZV and for me it always helps to conceptualize these 308 00:17:38,596 --> 00:17:41,396 viruses within the herpes virus family. 309 00:17:41,816 --> 00:17:43,466 I know it's not so common. 310 00:17:43,526 --> 00:17:48,626 Um, but the, uh, usual herpes viruses like HS V one and two can also be 311 00:17:48,626 --> 00:17:50,666 classified as a human herpes virus. 312 00:17:50,666 --> 00:17:56,426 So HH V one, and then we have HH V one to eight, and uh, the 313 00:17:56,426 --> 00:17:57,926 VZV is actually number three. 314 00:17:57,926 --> 00:18:03,236 So we have HHV-1, which is HS V one, and then HHV two, which is HSV 315 00:18:03,236 --> 00:18:06,566 two, and then we HHV3, which is VZV. 316 00:18:07,406 --> 00:18:11,096 I'm saying this because, not all antivirals are active again. 317 00:18:11,486 --> 00:18:15,266 All herpes viruses and the ones that we want to look at, uh, today are 318 00:18:15,266 --> 00:18:20,186 mostly active against the HHV one to three, so against the two herpes 319 00:18:20,236 --> 00:18:22,836 simplex viruses and against the VZV. 320 00:18:23,726 --> 00:18:24,026 Yeah. 321 00:18:24,026 --> 00:18:28,916 And uh, one other commentary about the antivirals is that all these substances 322 00:18:28,916 --> 00:18:31,136 have a relatively narrow dose range. 323 00:18:31,136 --> 00:18:35,076 So it's really not as the penicillins, for example, that have like a huge 324 00:18:35,076 --> 00:18:39,336 dose range and you can give big dosage without much side effects. 325 00:18:39,976 --> 00:18:44,006 And then, many of them are pro drugs, so they need to get activated. 326 00:18:44,396 --> 00:18:48,216 And the ones that we will cover now are all, nucleoside analogue, 327 00:18:48,236 --> 00:18:51,206 and they have all all have a pretty cool mechanism of action. 328 00:18:51,266 --> 00:18:55,826 Because as a nucleoside, they need to be phosphorylated, three times to be active. 329 00:18:56,306 --> 00:19:01,486 And the first phosphorylation can only occur through a thymidine kinase that's 330 00:19:01,486 --> 00:19:03,766 coded for by the herpes virus itself. 331 00:19:04,366 --> 00:19:09,636 So this means that our drug can mostly or almost exclusively get activated in 332 00:19:09,636 --> 00:19:14,366 virus infected cells, whereas uninfected cells lack this thymidine kinase 333 00:19:14,366 --> 00:19:18,616 because it's encoded by the virus, and, thus they can't activate it or 334 00:19:18,616 --> 00:19:20,476 activations at least much more unlikely. 335 00:19:20,476 --> 00:19:22,756 And so the toxicity's really reduced. 336 00:19:24,131 --> 00:19:29,641 So basically, I would say we have four different nucleoside analogue substances. 337 00:19:29,731 --> 00:19:33,651 And we already heard, acyclovir, which is also a pro-drug. 338 00:19:33,771 --> 00:19:37,851 And this is really the substance that has a very low oral bioavailability, 339 00:19:37,851 --> 00:19:42,526 so mostly we would actually use it, given as an IV formulation. 340 00:19:43,006 --> 00:19:47,516 And we already heard about the biggest side effect which is, nephrotoxicity, but 341 00:19:47,516 --> 00:19:50,246 it also has in rare cases a neurotoxicity. 342 00:19:50,246 --> 00:19:53,606 So you could have patients that develop delirium or 343 00:19:53,606 --> 00:19:55,196 tremors or hallucinations even. 344 00:19:55,196 --> 00:19:57,566 But this is not so common with acyclovir generally. 345 00:19:57,566 --> 00:19:59,096 It's pretty well tolerated, I would say. 346 00:19:59,626 --> 00:20:03,186 And then we have, the oral version of acyclovir. 347 00:20:03,186 --> 00:20:05,646 As I often say, it's valacyclovir. 348 00:20:05,666 --> 00:20:09,386 And that is, a pro drug of acyclovir, which is in turn a prodrug. 349 00:20:09,406 --> 00:20:10,716 So it's a prodrug of the prodrug. 350 00:20:11,086 --> 00:20:14,716 And this has a, a much higher oral bioavailability. 351 00:20:14,716 --> 00:20:17,336 So it's a, more than 50% are absorbed actually. 352 00:20:17,766 --> 00:20:19,356 And the side effects are around the same. 353 00:20:20,286 --> 00:20:24,636 Then we have, famiciclovir, which is also a product that is transformed into 354 00:20:25,146 --> 00:20:27,496 acyclovir, but it's very similar also. 355 00:20:27,676 --> 00:20:31,696 And then we have another substance, the fourth, uh, that's, I think it's not used 356 00:20:31,696 --> 00:20:33,576 in the US it's called, uh, brivudine. 357 00:20:33,796 --> 00:20:35,991 And it's also on nucleoside analogue. 358 00:20:36,016 --> 00:20:41,416 Um, and yeah, it's also pretty similar, but it has fallen kind of out of, uh, 359 00:20:41,416 --> 00:20:45,289 fashion, I would say, because there has been a label warning in, uh, Germany or 360 00:20:45,289 --> 00:20:49,959 in the EU at least because it had, uh, some like very rare, deadly interactions 361 00:20:49,959 --> 00:20:51,839 with certain anti-cancer medications. 362 00:20:52,229 --> 00:20:56,039 The, uh, 5FU specifically, that's pretty widely used. 363 00:20:56,039 --> 00:21:01,499 Um, and there were some cases where this, because the brivudine actually inhibits 364 00:21:01,499 --> 00:21:05,939 the degradation of the cancer medication, this, it has developed some toxic levels. 365 00:21:06,929 --> 00:21:09,239 So these are the four core antivirals. 366 00:21:09,299 --> 00:21:12,569 But we should also mention one more, which is the foscarnet. 367 00:21:12,599 --> 00:21:16,719 That's usually a substance that we would use against CMV infection, but 368 00:21:16,959 --> 00:21:21,109 there's also substance that can be occasionally used to treat VZV. 369 00:21:22,079 --> 00:21:24,669 And this interesting enough, it's not a nucleoside analogue, 370 00:21:24,689 --> 00:21:26,799 but it's a anion pyrophosphate. 371 00:21:26,799 --> 00:21:30,359 So it's basically the, the little phosphate that the others gets 372 00:21:30,479 --> 00:21:32,799 phosphated with the, the ones that we talked about before. 373 00:21:34,421 --> 00:21:39,186 So, um, these were the substances and now that we have the substances, we need to 374 00:21:39,186 --> 00:21:42,726 ask ourself what do we hope to achieve or what are the goals of treatment? 375 00:21:43,611 --> 00:21:47,154 And in a normal herpes zoster reactivation, it's to hasten the 376 00:21:47,154 --> 00:21:51,854 healing of the cutaneous lesions, both because we hope that less pain develops 377 00:21:52,224 --> 00:21:54,384 that the rash subsides more quickly. 378 00:21:54,384 --> 00:21:59,564 But also we hope that people are less likely to spread it to others because like 379 00:21:59,564 --> 00:22:04,219 we said before, the varicella zoster, even as a zoster reactivation is pretty 380 00:22:04,219 --> 00:22:07,049 contagious to people who are immuno naive. 381 00:22:07,809 --> 00:22:12,029 And what's a bit unclear is if this major complication of a post herpetic neuralgia 382 00:22:12,029 --> 00:22:16,439 can actually be prevented by giving antivirals, the data's a bit mixed there. 383 00:22:17,409 --> 00:22:21,209 And then the last question that we need to ask ourselves is, who do we treat? 384 00:22:21,209 --> 00:22:22,199 Do we treat everyone? 385 00:22:22,589 --> 00:22:25,769 And, um, this depends if we have an immunocompromised 386 00:22:25,769 --> 00:22:27,329 or immunocompetent patient. 387 00:22:27,569 --> 00:22:32,129 For our normal immunocompetent patients, we say that we want to treat, um, at 388 00:22:32,129 --> 00:22:34,949 least within 72 hours of symptom onset. 389 00:22:34,949 --> 00:22:37,499 This is ideal because we have an antiviral substance. 390 00:22:37,499 --> 00:22:40,419 Of course, we want to treat with it early in infection. 391 00:22:40,549 --> 00:22:43,726 And after that, the data's a bit mixed also, if we should do 392 00:22:43,726 --> 00:22:46,906 it or not, but I guess it's a, yeah, it's a canned decision. 393 00:22:47,476 --> 00:22:51,486 For our immunocompromised patients we always want to treat. 394 00:22:51,936 --> 00:22:56,936 And also for pregnant people, usually because they have a higher risk also. 395 00:22:57,489 --> 00:22:57,669 Yeah. 396 00:22:57,669 --> 00:23:01,979 And so in this patient with a persistent viremia, I think there, there's one 397 00:23:01,979 --> 00:23:06,539 concern definitely of acyclovir resistance that can develop during treatment. 398 00:23:06,789 --> 00:23:12,004 It's not very common, but it can be, so you could try to send off the virus for 399 00:23:12,004 --> 00:23:13,744 resistance testing, this is possible. 400 00:23:14,044 --> 00:23:17,254 There are some mutations that are known that lead to resistance. 401 00:23:17,254 --> 00:23:21,364 So one is definitely the thymidine kinase that can have a mutation in 402 00:23:21,364 --> 00:23:23,764 one gene that can reduce the activity. 403 00:23:24,359 --> 00:23:29,009 So it's the UL 36 gene, or it can reduce the substrate specificity. 404 00:23:29,129 --> 00:23:32,369 And then there are other even less common, uh, mutations. 405 00:23:32,519 --> 00:23:37,069 For example, UL 33 in the polymerase gene that impairs acyclovirs 406 00:23:37,089 --> 00:23:38,529 binding to the polymerase. 407 00:23:38,829 --> 00:23:43,679 And risk factors are all present here, which is like prolonged treatment with 408 00:23:44,069 --> 00:23:46,139 acyclovir and severe immunosuppression. 409 00:23:46,319 --> 00:23:48,569 So this is definitely one possibility. 410 00:23:48,899 --> 00:23:53,409 The other thing that could be when you still have like very large cutaneous 411 00:23:53,409 --> 00:23:58,599 lesions with very high concentrations of, of very high, um, yeah, concentration 412 00:23:58,719 --> 00:24:02,279 of varicella virus, that that could be like a spillover viremia in the 413 00:24:02,279 --> 00:24:06,989 blood as an explanation may be, and not like a true ongoing reactivation. 414 00:24:07,379 --> 00:24:11,429 This might be depending on how the levels in the blood are going. 415 00:24:11,429 --> 00:24:14,759 So, and for treatment options, I think this is definitely a 416 00:24:14,759 --> 00:24:18,439 patient we would continue to treat with intravenous acyclovir. 417 00:24:18,594 --> 00:24:23,379 The, the oral option is, I think a good option for non-severe infections, non 418 00:24:23,379 --> 00:24:28,389 immunocompromised host, adult patients with zoster that can be shifted to, or 419 00:24:28,419 --> 00:24:30,929 primarily treated with with valacyclovir. 420 00:24:31,209 --> 00:24:37,094 But this patient definitely has to stay on the acyclovir or maybe switch to 421 00:24:37,094 --> 00:24:40,084 something in case resistance is detected. 422 00:24:40,354 --> 00:24:45,154 Another thing that's often discussed or suggested by primary teams is 423 00:24:45,154 --> 00:24:49,614 the addition of immunoglobulins to help , immune clearance of the virus. 424 00:24:49,614 --> 00:24:52,789 The guidelines don't give any recommendations to use it. 425 00:24:52,789 --> 00:24:55,159 So it's not recommended to use that routinely. 426 00:24:55,579 --> 00:24:59,329 In severe immunocompromised patients, it can be an individual decision, 427 00:24:59,749 --> 00:25:03,349 but it's not a recommendation to do that on a, on a regular basis. 428 00:25:03,654 --> 00:25:08,324 Yeah, for me also, I know this varicella zoster immunoglobulin mostly in the 429 00:25:08,384 --> 00:25:12,464 context of a post-exposure prophylaxis, where it's, uh, occasionally recommended. 430 00:25:12,744 --> 00:25:12,984 Yeah. 431 00:25:13,879 --> 00:25:17,499 Um, in this case, because there was a question of resistance, 432 00:25:17,499 --> 00:25:19,629 foscarnet was added to the regimen. 433 00:25:19,869 --> 00:25:22,809 The specimens were sent off for resistance, like you were mentioning. 434 00:25:23,319 --> 00:25:26,499 Um, and then sort of just thinking about complications, this patient 435 00:25:26,739 --> 00:25:30,399 also has been stuck in the hospital and has been bedridden, so some of 436 00:25:30,429 --> 00:25:35,169 the lesions on the back did have some what seems to be secondary infection. 437 00:25:35,409 --> 00:25:40,449 The patient had some recurrent bacteremia episodes that required antibiotics, so, 438 00:25:40,869 --> 00:25:45,754 um, anything else that, uh, you want to add as far as thinking about complications 439 00:25:45,754 --> 00:25:48,214 of these types of infections? 440 00:25:49,174 --> 00:25:53,134 Yeah, so I think that's, that's definitely a very common complication. 441 00:25:53,134 --> 00:25:57,954 So the viremia and the reactivation eventually can be controlled with 442 00:25:57,954 --> 00:26:02,064 medication, but then you still have these open wounds and especially in patients 443 00:26:02,064 --> 00:26:07,004 that are maybe not able to stand up or being mobilized out of the bed are and, 444 00:26:07,004 --> 00:26:11,554 and are developing super infections of these really severe open wounds. 445 00:26:11,824 --> 00:26:14,824 This is definitely a complication that is common in that case. 446 00:26:14,824 --> 00:26:19,684 And so it's really important to try to get the patients out of bed and try to get 447 00:26:19,684 --> 00:26:23,884 them mobilized in the bed to get pressure off the wounds, have good wound care 448 00:26:23,884 --> 00:26:29,344 management involved very early on to maybe also prevent some kind of complications. 449 00:26:29,344 --> 00:26:32,204 But, we all know these patients that have been stuck in the hospital 450 00:26:32,204 --> 00:26:35,984 for long and, you know, um, and not, not being able to move. 451 00:26:36,224 --> 00:26:38,834 This is definitely something we see not only in varicella, but with 452 00:26:38,834 --> 00:26:42,584 everyone having like, uh, pressure ulcers, from being in there too long. 453 00:26:42,824 --> 00:26:45,554 This is something that's really hard to, um, avoid. 454 00:26:45,554 --> 00:26:49,514 But this is definitely something to, to look out for, um, in that patient. 455 00:26:52,764 --> 00:26:57,464 Yeah, and she ultimately received many weeks of IV acyclovir has been 456 00:26:57,464 --> 00:27:01,994 in the hospital, as you can kind of guess from the story, and, um, was not 457 00:27:01,994 --> 00:27:04,964 able to transition to oral treatment just like you were talking about. 458 00:27:04,964 --> 00:27:08,844 And, before we sort of close this case, I, I wanna see if you have 459 00:27:08,844 --> 00:27:13,104 any additional thoughts on treatment of VZV in our immunocompromised or 460 00:27:13,104 --> 00:27:14,694 solid organ transplant patients. 461 00:27:15,084 --> 00:27:18,504 You know, this is obviously a more rare complication, but we talk about and 462 00:27:18,504 --> 00:27:20,304 think about prevention all the time. 463 00:27:20,304 --> 00:27:22,674 So maybe we can also touch on that too. 464 00:27:22,674 --> 00:27:26,584 How do we think about prevention of VZV infection? 465 00:27:26,869 --> 00:27:30,919 Yeah, so there's really no like systemic data on how to 466 00:27:30,919 --> 00:27:32,749 prevent VZV in these patients. 467 00:27:32,749 --> 00:27:36,919 So I think one important cornerstone in prevention is vaccination. 468 00:27:36,919 --> 00:27:41,779 So, um, check the serologies before transplantation and try 469 00:27:41,779 --> 00:27:43,819 to update vaccines of patients. 470 00:27:43,819 --> 00:27:47,549 So as long as you can still, um, give a live attenuated vaccine. 471 00:27:47,569 --> 00:27:49,759 So you should do that before transplantation. 472 00:27:49,969 --> 00:27:52,579 If it's not like an emergency transplantation, you have the time. 473 00:27:52,879 --> 00:27:55,419 And then also check on post transplantation if you 474 00:27:55,419 --> 00:27:57,129 can do zoster vaccination. 475 00:27:57,129 --> 00:27:58,989 But we think we'll get to that later. 476 00:27:59,109 --> 00:28:04,349 And then the question is, is there any role of medication in preventing 477 00:28:04,349 --> 00:28:06,329 reactivation after transplantation? 478 00:28:06,329 --> 00:28:11,914 And so if you have a patient that receives CMV prophylaxis after transplantation. 479 00:28:11,914 --> 00:28:16,444 So if you're an inter intermediate or high risk category with a VZV donor and 480 00:28:16,444 --> 00:28:20,824 recipient status and you're receiving, um, valganciclovir, for example, this has 481 00:28:20,824 --> 00:28:22,624 some activity against varicella zoster. 482 00:28:22,624 --> 00:28:26,224 So this is considered to be an effective prophylaxis against 483 00:28:26,274 --> 00:28:30,244 reactivation, not letermovir, which is very widely used in Germany for 484 00:28:30,244 --> 00:28:31,954 the stem cell transplant patients. 485 00:28:32,134 --> 00:28:35,769 So this has no activity against varicella. 486 00:28:35,769 --> 00:28:40,449 So then you might think about maybe adding acyclovir, but it's really not sure. 487 00:28:40,689 --> 00:28:44,499 Um, who will profit of this, depending on the level of 488 00:28:44,499 --> 00:28:45,939 immunosuppression you're getting. 489 00:28:45,989 --> 00:28:49,289 And probably stem cell transplantations are in a higher risk credit. 490 00:28:49,319 --> 00:28:54,539 Solid organ transplant patients, um, usually don't get acyclovir prophylaxis 491 00:28:54,749 --> 00:28:57,529 for varicella zoster routinely. 492 00:28:57,889 --> 00:28:58,399 Um. 493 00:28:59,029 --> 00:29:00,719 Yeah, so it's really unclear. 494 00:29:00,779 --> 00:29:05,824 You can maybe, depending on how your HSV, so yourherpes simplex, um, 495 00:29:06,149 --> 00:29:09,479 um, serology is you might consider a short term prophylaxis with 496 00:29:09,479 --> 00:29:11,009 aciclovir, which is recommended. 497 00:29:11,009 --> 00:29:14,759 This also helps against varicella zoster, but there's no recommendations 498 00:29:14,759 --> 00:29:20,379 for varicella in general in, in, for, for, um, uh, reactivation prophylaxis. 499 00:29:20,786 --> 00:29:23,936 so we're gonna transition and say we're in clinic. 500 00:29:24,386 --> 00:29:27,386 We can say a few weeks, maybe we'll be generous and say a couple months 501 00:29:27,386 --> 00:29:29,871 later, uh, the patient has recovered. 502 00:29:30,916 --> 00:29:34,066 Was finally discharged and they've come back in and so they're asking 503 00:29:34,066 --> 00:29:38,956 about vaccination and I thought since we are from two different places, that 504 00:29:38,956 --> 00:29:42,526 we can talk a little bit comparing and contrasting vaccination schedules and 505 00:29:42,526 --> 00:29:44,536 just talking about vaccines in general. 506 00:29:44,896 --> 00:29:49,426 Um, that, you know, I think sometimes for these vaccine preventable infections 507 00:29:49,426 --> 00:29:53,896 we take for granted that we don't often see them or think about them as much. 508 00:29:53,896 --> 00:29:57,946 So maybe I'll hand over to Till first to just kind of introduce 509 00:29:57,946 --> 00:29:59,986 what vaccines are available. 510 00:30:00,256 --> 00:30:00,526 Yeah. 511 00:30:00,526 --> 00:30:05,896 So as VZV vaccines go, we have three different vaccines available, at 512 00:30:05,896 --> 00:30:09,286 least worldwide, and I, we could like group them in two different buckets. 513 00:30:09,286 --> 00:30:13,516 So the first bucket would be, uh, the bucket of the live attenuated vaccines. 514 00:30:13,956 --> 00:30:18,046 So these are what we would refer, uh, to as a chickenpox vaccine. 515 00:30:18,046 --> 00:30:20,146 So this is a vaccine, uh, for kids. 516 00:30:20,146 --> 00:30:24,616 The first one that we would use in order to prevent the primary VZV infection. 517 00:30:24,856 --> 00:30:27,406 And it's different marketed under different names. 518 00:30:27,406 --> 00:30:32,446 It's either, uh, varivax think it's the name in the US or uh, uh, viral rigs. 519 00:30:32,596 --> 00:30:34,246 Is in, it's called in the EU. 520 00:30:34,726 --> 00:30:37,036 And so this is the, yeah, the vaccine for kids. 521 00:30:37,606 --> 00:30:40,786 The second one is, that's also in the bucket of live attenuated 522 00:30:40,786 --> 00:30:44,026 vaccines is, uh, very similar, but this is a shingles vaccine. 523 00:30:44,026 --> 00:30:48,886 So this is a vaccine that we want to give to adults to prevent the reactivation. 524 00:30:49,036 --> 00:30:53,336 And this is a vaccine that was called, or is called Zostavax. 525 00:30:53,406 --> 00:30:56,166 And I think in the US it's not, uh, in use anymore. 526 00:30:56,166 --> 00:30:59,556 And also the German, um, vaccine recommendations 527 00:30:59,556 --> 00:31:01,176 recommend against using it. 528 00:31:01,266 --> 00:31:04,146 And it's actually very similar to the children one, except 529 00:31:04,146 --> 00:31:05,316 that it's much higher dose. 530 00:31:05,316 --> 00:31:07,296 So it has a bottle one, one. 531 00:31:07,326 --> 00:31:08,346 Um, so like. 532 00:31:08,681 --> 00:31:15,281 10 times more particle forming units of this, uh, attenuated strain of the VZV. 533 00:31:15,851 --> 00:31:18,971 Um, so basically it's the same as the kids, but just higher dose. 534 00:31:19,481 --> 00:31:23,201 And then the third vaccine is the recombinant glycoprotein vaccine. 535 00:31:23,201 --> 00:31:24,761 So that's not a live vaccine. 536 00:31:24,761 --> 00:31:28,541 And this is, offers a major advantage because we can now, uh, offer this 537 00:31:28,541 --> 00:31:30,161 vaccine basically to everyone. 538 00:31:30,471 --> 00:31:34,061 Especially our immunocompromised host, especially our pregnant people. 539 00:31:34,071 --> 00:31:37,911 Also, and it's marketed under the name of Shingrix and it hasn't been 540 00:31:37,911 --> 00:31:39,771 around that long actually, in Germany. 541 00:31:39,771 --> 00:31:44,061 It came to market in 2018 in other countries, I think one year before. 542 00:31:44,601 --> 00:31:48,861 And yeah, it has a excellent, um, vaccine effectiveness. 543 00:31:48,891 --> 00:31:51,531 The thing that we want to do with this vaccine, again, because it's 544 00:31:51,531 --> 00:31:55,131 a a shingles vaccine, we want to, uh, prevent the reactivation. 545 00:31:55,461 --> 00:32:00,756 So we want to prevent herpes zoster and in the landmark paper after which it 546 00:32:00,756 --> 00:32:05,596 was introduced to market, described a vaccine effectiveness of more than 95%. 547 00:32:06,046 --> 00:32:10,816 But we now also have some, uh, long-term data that showed that , still around 548 00:32:10,816 --> 00:32:15,436 80% vaccine effectiveness after 10 years of the vaccination course. 549 00:32:15,721 --> 00:32:19,801 So those are really encouraging, uh, data both for the effectiveness 550 00:32:19,801 --> 00:32:22,681 but then also for the safety of the vaccine because this is something that 551 00:32:22,681 --> 00:32:27,121 you also have to stress that these vaccines are, uh, extremely safe, these 552 00:32:27,121 --> 00:32:29,161 recombinant glycoprotein vaccines. 553 00:32:29,554 --> 00:32:29,854 Yeah. 554 00:32:30,064 --> 00:32:31,144 And so, um, just. 555 00:32:31,144 --> 00:32:36,034 Like you're saying in the US for the Varivax, that initial chicken 556 00:32:36,034 --> 00:32:40,354 pox vaccine, we recommend two childhood doses of varicella vaccine. 557 00:32:40,354 --> 00:32:43,594 So the first is when they're 12 to 15 months of age. 558 00:32:43,834 --> 00:32:46,354 So they're 1-year-old shots and then they get a second one 559 00:32:46,654 --> 00:32:48,784 at four to six years of age. 560 00:32:49,174 --> 00:32:53,794 Um, but I, you know, I know from hearing cases and, and talking to others that 561 00:32:53,794 --> 00:32:57,809 varicella vaccination childhood actually isn't you know, it's not something 562 00:32:57,809 --> 00:33:01,739 that's part of every country's schedule, and I actually don't know if it's part 563 00:33:01,739 --> 00:33:03,599 of the routine schedule in Germany. 564 00:33:03,599 --> 00:33:05,219 So, um, how do you guys use 565 00:33:05,284 --> 00:33:09,844 Yeah, it's a little bit different as so in Germany, uh, first dose is recommended 566 00:33:09,844 --> 00:33:15,154 alongside the first MMR vaccine around 11 months or maybe 11 to 14 months of age. 567 00:33:15,394 --> 00:33:19,414 And however, there's a, a slight peculiarity in the German recommendations 568 00:33:19,414 --> 00:33:23,254 because it's written, not recommended to give it, uh, combined in one 569 00:33:23,254 --> 00:33:24,874 syringe with the MMR vaccine. 570 00:33:24,874 --> 00:33:27,844 So, because we could also use the MMRV. 571 00:33:28,454 --> 00:33:32,214 Instead it's recommended to do it simultaneously, but to use 572 00:33:32,214 --> 00:33:33,324 different parts of the body. 573 00:33:33,324 --> 00:33:37,254 So basically you could use a different leg also, and this is apparently 574 00:33:37,254 --> 00:33:41,744 because, some data on increased febrile seizures when applied 575 00:33:42,044 --> 00:33:43,754 in this within the same syringe. 576 00:33:43,994 --> 00:33:48,339 I, yeah, I think there's limited data on this, but this is what the 577 00:33:48,339 --> 00:33:51,019 German vaccine recommendations state. 578 00:33:51,349 --> 00:33:55,999 Alternatively, you could wait four weeks between the MMR and the varicella vaccine, 579 00:33:56,779 --> 00:33:58,879 but this only goes for the first dose. 580 00:33:58,879 --> 00:34:04,129 And then for the second dose, which we usually, um, uh, give around six months, 581 00:34:04,159 --> 00:34:08,389 um, after the first one, you can use the MMRV, so the combination of the four. 582 00:34:09,139 --> 00:34:09,439 Yeah. 583 00:34:09,799 --> 00:34:13,029 And then there's also one more recommendation, which is a 584 00:34:13,029 --> 00:34:14,439 work related recommendation. 585 00:34:14,439 --> 00:34:19,229 So, basically all healthcare workers, but also everyone who works with lots 586 00:34:19,229 --> 00:34:23,879 of people, uh, is recommended to have their, uh, routines vaccine schedule 587 00:34:23,879 --> 00:34:27,929 up to date or have it updated in case they report no vaccines as a child. 588 00:34:28,334 --> 00:34:33,774 And then for the zoster vaccination, just like you said, the Zostavax 589 00:34:33,794 --> 00:34:36,794 is not available in the US anymore. 590 00:34:36,794 --> 00:34:41,234 We currently recommend two doses of the recombinant zoster vaccine 591 00:34:41,234 --> 00:34:43,994 for adults that are 50 and over. 592 00:34:43,994 --> 00:34:47,204 So whether or not they've had a history of herpes zoster, whether or not 593 00:34:47,204 --> 00:34:52,004 they've had Zostavax, those patients don't necessarily get screened, 594 00:34:52,064 --> 00:34:54,284 you know, by history or serology. 595 00:34:54,674 --> 00:34:57,764 Um, with a titer for evidence of prior varicella infection. 596 00:34:57,764 --> 00:34:59,204 They can just get the vaccine. 597 00:34:59,574 --> 00:35:02,604 There is also a recommendation for essentially all adult patients. 598 00:35:03,169 --> 00:35:08,549 Um, who are or will be immunosuppressed to get the Shingrix is the brand 599 00:35:08,549 --> 00:35:12,419 name and then we, it's two doses separated by two to six months. 600 00:35:13,179 --> 00:35:17,229 If it has been more than six months after the first dose, we just give them dose 601 00:35:17,229 --> 00:35:19,299 number two, we don't restart the series. 602 00:35:19,389 --> 00:35:22,599 Um, and then if the patient's immunocompromised, we can sort of 603 00:35:22,689 --> 00:35:26,319 squeeze that window if we need to and give the second dose after one month. 604 00:35:26,939 --> 00:35:30,689 The other question that occasionally comes up, we're not routinely doing, but 605 00:35:30,784 --> 00:35:34,839 I, I think people have asked about will one day we be able to think about the 606 00:35:34,839 --> 00:35:40,169 recombinant zoster vaccine as primary immunization in an immunocompromised host. 607 00:35:40,169 --> 00:35:45,299 I think that's a, um, interesting question that we don't have a great 608 00:35:45,299 --> 00:35:47,069 answer for yet, but maybe in the future 609 00:35:47,319 --> 00:35:47,539 Mm. 610 00:35:48,299 --> 00:35:49,439 What about you guys for Germany? 611 00:35:49,439 --> 00:35:52,154 Yeah, the recommendations are, I have to say unfortunately, a 612 00:35:52,154 --> 00:35:53,584 little bit different in Germany. 613 00:35:53,584 --> 00:35:57,344 So, the vaccine recommendations state that it's recommended for 614 00:35:57,344 --> 00:35:59,264 all adults 60 years and older. 615 00:35:59,264 --> 00:35:59,594 Okay. 616 00:35:59,594 --> 00:36:01,504 So that's maybe 10 years difference. 617 00:36:01,504 --> 00:36:04,414 But then it also states that, that it's recommended for adults 618 00:36:04,414 --> 00:36:07,444 who are immunocompromised only when they're 50 years or older. 619 00:36:07,504 --> 00:36:10,654 And this is something where I have to say I disagree a bit because 620 00:36:10,654 --> 00:36:13,834 of course, it really depends on the level of immunosuppression. 621 00:36:14,164 --> 00:36:17,534 So people like we've discussed before those that are severely 622 00:36:17,534 --> 00:36:21,784 immunosuppressed, should definitely receive a vaccine regardless of their age. 623 00:36:22,281 --> 00:36:25,551 Is it easy for them to get vaccination if someone, for example, 624 00:36:25,551 --> 00:36:26,926 suggest it but they're under 50. 625 00:36:26,931 --> 00:36:27,351 Yes. 626 00:36:27,351 --> 00:36:27,561 Yeah. 627 00:36:27,561 --> 00:36:31,521 in this case that the patients are, um, severely immunosuppressed. 628 00:36:31,551 --> 00:36:34,731 Uh, I think the, I'm pretty sure that it should be covered. 629 00:36:35,661 --> 00:36:37,461 But apart from that, actually it's not so easy. 630 00:36:37,461 --> 00:36:40,551 So if you're not severely immunosuppressed, it's um, a bit 631 00:36:40,551 --> 00:36:41,646 unlikely that you will get it. 632 00:36:41,646 --> 00:36:41,926 Yeah. 633 00:36:42,182 --> 00:36:42,542 Yeah. 634 00:36:42,812 --> 00:36:42,992 Yeah. 635 00:36:42,992 --> 00:36:47,492 Sometimes it's hard for folks to get vaccines outside of a 636 00:36:47,492 --> 00:36:51,362 recommendation, or, or they can, but it costs more money than it should. 637 00:36:52,052 --> 00:36:55,792 Um, and, uh, I, I think the other question that's come up for me with 638 00:36:55,792 --> 00:36:59,852 a patient who had a similar scenario is, you know, say that this patient 639 00:36:59,852 --> 00:37:03,722 had not received a zoster vaccination, they're interested, but they've had 640 00:37:03,722 --> 00:37:06,342 this pretty significant infection. 641 00:37:06,552 --> 00:37:12,222 When is the right timing to give them the recombinant zoster vaccination? 642 00:37:12,852 --> 00:37:13,782 What do you guys think? 643 00:37:14,287 --> 00:37:18,277 Yeah, I think also there's no, no real good guidance where you have like a 644 00:37:18,277 --> 00:37:20,227 cutoff of three or six or 12 months. 645 00:37:20,227 --> 00:37:23,947 So it's really depending on patient and, and your recommendation. 646 00:37:24,217 --> 00:37:27,097 So, um, what we would do is definitely only recommend obviously 647 00:37:27,097 --> 00:37:28,657 the, the Shingrix vaccine. 648 00:37:28,667 --> 00:37:33,077 So the CDC, um, says there's no specific length of time that you need to wait. 649 00:37:33,317 --> 00:37:37,277 The rash has to be gone, which kind of makes sense generally, and 650 00:37:37,277 --> 00:37:40,872 the Australian guidance says maybe three months, wait three months. 651 00:37:40,872 --> 00:37:44,502 So I think if the patient is there, she's feeling well, she or he's 652 00:37:44,502 --> 00:37:46,272 feeling well, the rash is gone. 653 00:37:46,272 --> 00:37:50,442 And if the patient is stable, I would use the opportunity to vaccinate. 654 00:37:50,532 --> 00:37:53,022 Um, so in, in consent with the patient. 655 00:37:53,082 --> 00:37:55,962 So maybe not, you know, fresh out of the hospital, just 656 00:37:55,962 --> 00:37:57,312 getting settled at home again. 657 00:37:57,612 --> 00:38:00,832 But I think every opportunity you have where the patient sits 658 00:38:00,832 --> 00:38:02,002 and wants to get vaccinated. 659 00:38:02,152 --> 00:38:05,077 We should use if it makes sense and there's, there's no 660 00:38:05,357 --> 00:38:09,057 specific recommendation or I would, I would do that then. 661 00:38:09,327 --> 00:38:09,617 Yeah. 662 00:38:10,682 --> 00:38:14,342 And I think it's also just important to remember to even give the patient the 663 00:38:14,342 --> 00:38:17,852 Shingrix vaccine against zoster, even though they just had an episode of zoster. 664 00:38:17,852 --> 00:38:20,822 So that's, that might be something that some patients, uh, would ask, 665 00:38:20,822 --> 00:38:22,172 like, why should I take the vaccine? 666 00:38:22,172 --> 00:38:25,442 But this is something that we are also pretty confident in, that it reduces 667 00:38:25,442 --> 00:38:28,352 the probability because actually people who've had zoster also have 668 00:38:28,352 --> 00:38:31,862 a high chance on of having another zoster episode in the, in the future. 669 00:38:32,267 --> 00:38:32,567 Yeah. 670 00:38:32,856 --> 00:38:37,146 Um, and we've covered a ton of ground today, but, I open up at the end just 671 00:38:37,146 --> 00:38:40,606 to see if there's anything else that you guys wanna make sure we mention 672 00:38:40,606 --> 00:38:44,836 or sort of take home points from this case or anything we've discussed today. 673 00:38:46,336 --> 00:38:51,906 So for me, recently transplanted patients are always very critical and have to be 674 00:38:51,906 --> 00:38:53,706 treated like a little bit like a raw egg. 675 00:38:53,706 --> 00:38:57,786 So I think definitely be very alert in anything that occurs. 676 00:38:57,786 --> 00:39:00,186 If it's something on the skin, if it's something in the lung, just 677 00:39:00,276 --> 00:39:05,106 be really aggressive and quick with diagnosing whatever is is coming up. 678 00:39:05,376 --> 00:39:08,816 Do the screenings regularly of viral reactivations in the blood 679 00:39:08,816 --> 00:39:10,256 as according to the guidelines. 680 00:39:10,566 --> 00:39:12,006 And then yeah, be quick to react. 681 00:39:12,006 --> 00:39:15,586 'cause they're really they can they can deteriorate pretty quickly. 682 00:39:15,646 --> 00:39:17,746 Um, that, that was that for me. 683 00:39:17,746 --> 00:39:21,136 So be really aggressive and diagnostic and don't, don't wait. 684 00:39:21,196 --> 00:39:21,316 Yeah. 685 00:39:22,546 --> 00:39:22,836 Yeah. 686 00:39:22,841 --> 00:39:25,996 And use the PCR, uh, from the swab from the vesicles. 687 00:39:27,676 --> 00:39:28,036 Yeah. 688 00:39:29,146 --> 00:39:29,386 Yeah. 689 00:39:29,386 --> 00:39:30,826 Confirm the diagnosis. 690 00:39:33,986 --> 00:39:35,606 And a quick note on immunology. 691 00:39:35,606 --> 00:39:40,026 The serology is a varied marker if you want to see if the patient 692 00:39:40,026 --> 00:39:42,936 has, uh, had contact before with a varicella zoster virus. 693 00:39:42,936 --> 00:39:47,856 But the main immunity to contain VZV is actually driven through T cells. 694 00:39:48,156 --> 00:39:51,756 So the cellular immunoresponse response actually plays a critical 695 00:39:51,756 --> 00:39:57,416 role in controlling the VZV latency and to prevent it from reactivation. 696 00:39:58,232 --> 00:40:01,172 Thanks again to Til and Annette for joining us today. 697 00:40:01,812 --> 00:40:05,952 You can check out the website febrile podcast.com, where we keep our Consult 698 00:40:05,952 --> 00:40:09,882 Notes, which are written complements of the episodes with links to references, 699 00:40:10,152 --> 00:40:13,572 our library of ID infographics, and a link to our merch store. 700 00:40:14,382 --> 00:40:18,432 Febrile is produced with support from the Infectious Diseases Society of America. 701 00:40:19,242 --> 00:40:22,242 Please reach out if you have any suggestions for future shows or 702 00:40:22,242 --> 00:40:23,862 wanna be more involved with Febrile. 703 00:40:24,252 --> 00:40:25,152 Thanks for listening. 704 00:40:25,602 --> 00:40:27,107 Stay safe and I'll see you next time.