Episode 121
121: Windpocken with Infektiopod
Drs. Till Koch and Annette Hennigs join to discuss their ID podcast Infektiopod and dive into varicella!
Check out Infektiopod here!
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Transcript
Hi everyone.
Speaker:Welcome to Febrile, a cultured podcast about all things infectious disease.
Speaker:We use consult questions to dive into ID clinical reasoning, diagnostics
Speaker:and antimicrobial management.
Speaker:I'm Sara Dong, your host and a Med Peds ID doc.
Speaker:Today we have a ID podcast crossover.
Speaker:I am joined by two of the three hosts of the German speaking
Speaker:ID podcast called Infektiopod.
Speaker:I'll first introduce Dr. Till Koch.
Speaker:He is an attending in infectious diseases and antibiotic
Speaker:stewardship in Itzehoe, Germany.
Speaker:He divides his time between the inpatient ID ward, consultation
Speaker:service, and antibiotic stewardship efforts in his rural hospital.
Speaker:Yeah, hi, and my name is Till, and I'm super excited to be here.
Speaker:Looking forward to the episode.
Speaker:Also on the podcast today is Dr. Annette Hennigs.
Speaker:She's a senior fellow in infectious diseases at the University Medical
Speaker:Center Hamburg Eppendorf in Germany.
Speaker:Her daily business is leading the consultation service and her main focus
Speaker:of interest is cardiovascular infections.
Speaker:Hello, I'm Annette.
Speaker:I'm so happy to be here to do this cross Atlantic Crossover, uh, podcast episode.
Speaker:Happy to be here.
Speaker:Their third host, I'll just give a shout out to is Dr. Elena Terhalle.
Speaker:So as Febrile is a cultured podcast, we ask our guests to share a little piece
Speaker:of culture, basically just something fun and non-medical that you like.
Speaker:What have you guys been interested in recently?
Speaker:Yeah, so, I'm actually been more, uh, outgoing these days.
Speaker:My kids are getting a little older right now.
Speaker:They're 10 and 12, and we all try to, you know, keep ourselves when they're toddlers
Speaker:and little, but it's not really happening.
Speaker:But now, um, we've been going out with them to concerts and everything.
Speaker:So I went with my daughter to Taylor Swift last summer and
Speaker:we're gonna go see Ed Sheeran.
Speaker:And it's really nice that obviously, my husband and me have made a little bit
Speaker:of an impression with their music taste, and so it's really fun to see them grow
Speaker:up and, and, uh, be a little more, more outgoing with them or going out with them.
Speaker:I love it.
Speaker:Very nice.
Speaker:Yeah.
Speaker:And for me, something that really, uh, brings me joy, um, is carpentry.
Speaker:So, uh, building furniture actually, and I, in the last two years, I
Speaker:managed to set up like a tiny little workshop for myself and when I was
Speaker:studying medicine, I used to do it a lot actually and find more time for it.
Speaker:But, uh, since I've been working, I've, yeah, I can't, just
Speaker:can't do it so much anymore.
Speaker:But yeah, creating something with your hands, really that brings me joy.
Speaker:That's a skill that I fantasize that one day I will be good with
Speaker:no training and no experience.
Speaker:Um, well I am so excited that you guys are here.
Speaker:You have been working on Infektiopod since 2019, right and you are expert
Speaker:ID docs we're doing this crossover podcast, but I was hoping that you
Speaker:could introduce everyone to your podcast, um, and tell them a little
Speaker:bit more about how they can find it.
Speaker:Yeah, so we, uh, started in Infektiopod in January of 2019 as a podcast on infectious
Speaker:diseases in, uh, German, obviously.
Speaker:First I started by myself because I like podcasts and I was passionate
Speaker:about ID and at the time I was also working in the Institute for Tropical
Speaker:Medicine in Hamburg, and I was listening to, uh, famous other podcasts.
Speaker:Uh, one that I started with I think was This Week in Parasitism featuring, uh,
Speaker:Vincent Racaniello and Daniel Griffin, and then also the original Puscast by
Speaker:Mike Crislip, which I really enjoyed.
Speaker:And then, yeah, of course the podcast universe has been growing since then.
Speaker:Um, so the first episodes of Infektiopod were really just on specific pathogens.
Speaker:And then in 2020 we shifted a bit towards COVID and the, uh, team
Speaker:grew as Annette and Elena joined in.
Speaker:And uh, ever since then, we've been doing it as the three of us, this podcast.
Speaker:And yeah, so we produced a little over 90 episodes so far.
Speaker:Most of them, or all of them, actually almost in German.
Speaker:And we covered a wide range of ID topics, I would say.
Speaker:And most recently we've also covered a few conferences.
Speaker:Um, ESCMID and ID week, for example.
Speaker:Yeah.
Speaker:And, uh, we've also written down what we want to do with a podcast as a poster
Speaker:for this year's ESCMID, for example.
Speaker:I don't know if it's, uh, readily available online, but, uh, we can find it.
Speaker:And we wrote down what we want to do with the podcast.
Speaker:So basically we said we have three goals.
Speaker:We want to, uh, give a direct knowledge transfer.
Speaker:I think that's pretty straightforward.
Speaker:Then we want to build trust in science.
Speaker:That was a big topic here, um, in the, in the whole COVID
Speaker:pandemic, but also, uh, take part a little bit in societal debates.
Speaker:So especially around COVID, we also said what we thought about vaccines
Speaker:and, uh, that that's also important.
Speaker:Yeah, I love it.
Speaker:And I should say we, we got to meet at ID week, which is how this all blossomed.
Speaker:And yeah, I, we should definitely share your poster from ESCMID.
Speaker:We can, um, put it on the webpage too.
Speaker:But, uh, I'm excited that you're here 'cause you're gonna help us walk
Speaker:through a pretty challenging case.
Speaker:So I, I'll start us off and then we're gonna cover a lot of info
Speaker:today about some, a viral infection.
Speaker:So we have a 56-year-old woman who has a history of ischemic cardiomyopathy.
Speaker:She's now status post heart transplant.
Speaker:She was CMV donor negative recipient negative.
Speaker:Her post-transplant course has been complicated by some postoperative
Speaker:renal failure, so she is requiring dialysis, but at this point she's
Speaker:improving and she's been transferred to the normal post-transplant ward.
Speaker:So at around six weeks after transplantation, um, we'll say
Speaker:she was still hospitalized.
Speaker:We're not given sort of full details here, but um.
Speaker:We at this point notice that the patient has these newly formed vesicles
Speaker:and erythema on the chest and back.
Speaker:Dermatology was consulted and took a biopsy.
Speaker:Um, and then there was some suspicion for TEN.
Speaker:So the patient also was placed on pulse therapy with steroids.
Speaker:Um, swabs of the vesicles were obtained and they came back with a very
Speaker:high viral load of varicella virus.
Speaker:And this was, oh, I should have done it in my head before 1.4.
Speaker:Is that billion
Speaker:Yeah.
Speaker:Billion 1.4 billion copies per ml. And she had a subsequent PCR from
Speaker:blood that, uh, showed a VZV viral load that was 700,000 copies per ml.
Speaker:Um, so here we have a heart transplant recipient who has
Speaker:this diffuse vesicular rash.
Speaker:We now have confirmation of VZV from an unroofed vesicle.
Speaker:So, you know, do we have our diagnosis here?
Speaker:Is there anything else that you want to make sure we consider for next steps?
Speaker:So I think, yeah, we see here.
Speaker:Now that we established the diagnosis with the PCR.
Speaker:So that's actually confirmed with a disseminated varicella infection.
Speaker:We have to figure out what kind of infection it is.
Speaker:So we have to check the pre-transplant serologies.
Speaker:Um, which in this, yeah, if it's, if the patient was, um, seropositive
Speaker:before transplantation, so we would be dealing with kind of a reactivation or
Speaker:if it would be at age 56, a rare case of a seronegative patient that was,
Speaker:uh, transplanted and now has a primary varicella infection, which is not so
Speaker:much different in treatment, but it's something that would be interesting.
Speaker:And, um, so the sero prevalence is, is really high in adults.
Speaker:Around 90% in this age range is mostly due to previous infection.
Speaker:The, the younger people are now getting vaccinated, but we're
Speaker:think we'll cover that later on.
Speaker:After infection, the virus has latency in different parts of the body, in the
Speaker:cranial nerve and dorsal root ganglia and can reactivate at any time in life.
Speaker:So, around 20% is the lifetime risk of reactivation as
Speaker:herpes zoster as we call it.
Speaker:Now, the classical symptom would be a dermatome, like a localized, uh, skin
Speaker:infection or skin reactivation and in transplant patients or in solid organ
Speaker:transplant recipients, it's around up to 10, 11% in the first four
Speaker:years after transplantations with heart and lung transplant recipients
Speaker:having the highest risk 'cause of the more aggressive immunosuppression,
Speaker:in comparison to other organs.
Speaker:With this diagnosis we have to see if there's any other, um,
Speaker:affection of any other organs.
Speaker:So if there's like pulmonary, um, affection of the other,
Speaker:like hepatic, um, um, affection.
Speaker:So we should definitely do clinical monitoring lab parameters in
Speaker:case of, you know, she's having problems breathing or dyspnea, we
Speaker:should do imaging of the chest.
Speaker:We should check for neurologic symptoms to, to rule out
Speaker:cerebral reactivation as well.
Speaker:So that has to be like a really good clinical workup of the patient and then
Speaker:guided by that additional lab maybe, or, or imaging, um, that should be performed.
Speaker:Perhaps we can take a step back again also and re reiterate the primary
Speaker:manifestations of varicella zoster virus.
Speaker:And, we divide the clinical symptoms in either the, uh, reactivation that
Speaker:Annette has already spoken about, or before that, the primary varicella.
Speaker:So that would be the chicken pox in English or the windpocken in, uh, German.
Speaker:So.
Speaker:The wind pox basically.
Speaker:And this is, I think, the super highly contagious disease of childhood that
Speaker:we, or usually childhood, that we know.
Speaker:Quick side to the epidemiology again.
Speaker:Um, the, the seroprevalence is actually much lower in tropical regions, so it's
Speaker:not so uncommon to see here someone who grew up in a tropical region, for
Speaker:example, who migrated to Germany, have a primary VZV infection in their adulthood.
Speaker:But yeah, I think this clinical presentation.
Speaker:We, we know mostly it has different, uh, different stages at the same time.
Speaker:So this, uh, how's it called in English?
Speaker:This star, this,
Speaker:Oh, the, um, dew on a petal.
Speaker:Yeah,
Speaker:I can.
Speaker:Okay.
Speaker:Um, so yeah, so it had has different stages at the same time of skin
Speaker:manifestation, so it can have vesicular and macular papular at the same time.
Speaker:And a bit different from that is the clinical presentation of the reactivated
Speaker:VZV infection, what we call herpes zoster.
Speaker:Um, because normally in immunocompetent persons, the rash is typically
Speaker:restricted to one dermatome, right?
Speaker:Apart from the rash, which has been described as this, um, dew on a rose
Speaker:petal, so like a dew drop on a rose petal, apart from this rash, the
Speaker:other, uh, clinical sign is the pain or the neuritis that is described.
Speaker:So if you see rash and it's painful, then you should think about zoster and
Speaker:the, uh, pain can also vary clinically.
Speaker:So some people don't even feel a lot of pain.
Speaker:Some people feel pain even before the rash develops.
Speaker:And some people, um, develop the pain only only after the rash comes.
Speaker:And one clinical pearl that I learned that you could do if you
Speaker:want to test for this neuritis is, uh, that you test the hyperesthesia.
Speaker:So you take a little wood, wood spatula, and you kind of move it,
Speaker:uh, around, around on the rash.
Speaker:And then it should hurt more than on unaffected, uh, sites.
Speaker:And maybe another question to ask the patients is if it's itching, because
Speaker:this would really not be very typical of zoster and really, uh, push you in
Speaker:other clinical directions, I would say.
Speaker:So this is the typical presentation of herpes zoster.
Speaker:But then, uh, we already mentioned also that there are some complications
Speaker:and I think the most common one, and that most people know, uh, probably
Speaker:is this post hepatic neuralgia.
Speaker:It affects around 15%, uh, of the patients as especially the older patients.
Speaker:And this can really be a very severe complication because some people
Speaker:have to take long lasting pain medications to deal with the pain.
Speaker:So that's the most common complication.
Speaker:But then there are also, uh, a lot of other complications from herpes zoster
Speaker:reactivation, um, mostly, uh, affecting either the eyes, which can be blindness
Speaker:inducing or, sight threatening, um, or infecting the ear, which can, then
Speaker:lead to something, for example, called this Ramsey Hunt Syndrome, where you
Speaker:have like a facial nerve paralysis.
Speaker:And these zoster vesicles in your ear and also pain.
Speaker:And then, I think Anna to mentioned it briefly also, that you can have a
Speaker:central nervous system involvement.
Speaker:So you can have, have either meningitis or encephalitis.
Speaker:And of course the worst complication is what we have here, which
Speaker:is a disseminated infection.
Speaker:And, uh, that occurs, um, exclusively in severely immunocompromised host.
Speaker:Yeah.
Speaker:And so in this case we have quite typical vesicular lesions, which were
Speaker:not maybe typical in the beginning.
Speaker:So that's why dermatology was consulted and there was histopathology
Speaker:that showed something, you know, for severe, like drug reaction.
Speaker:So I think that's, that's what happened here, but then you can really.
Speaker:Depending on where your hospital is localized and how quick your access to
Speaker:microbiology is, you can establish the diagnosis pretty sensitively with PCR
Speaker:and PCR can be done good from, from the swabs from the vesicles, ideally
Speaker:with like a freshly open vesicular.
Speaker:But you know, if you have open, um, vesicles, you can do it there.
Speaker:Or then if you have an immunocompromised host, as in this case also in blood,
Speaker:and then you can see if you have a systemic reactivation in that case.
Speaker:And the quickness of the diagnosis is, especially in immunocompromised
Speaker:hosts is obviously very important so that you can, you know, start
Speaker:treatment, um, really quickly to prevent further complications in that case.
Speaker:Yeah, so what we would do now when we establish the diagnosis is we would start
Speaker:treating and the first line treatment would be Acyclovir in high dose.
Speaker:Um, and this patient was on hemodialysis, but this is like the
Speaker:first line and preferred treatment.
Speaker:So we would do it in irrespective of the renal failure.
Speaker:And, um, one thing I actually learned, uh, with one case that we treated
Speaker:with Acyclovir, there was another patient, uh, unrelated to this, and
Speaker:he had like a very quick and very sharp rise in the creatinine after
Speaker:one day of treatment with Acyclovir.
Speaker:We stopped acyclovir because we thought something weird is going on here.
Speaker:And then the, the creatinine went down really quickly and we
Speaker:talked to pharmacology this to our pharmacist and they said it.
Speaker:It's, it's, it's a known complication that, um, if you give it intravenously and
Speaker:you infuse it too quickly then you have obviously high plasma levels right away.
Speaker:And it's, it's primarily excreted through the kidney unchanged, um, and,
Speaker:but has a poor solubility in the urine.
Speaker:So if it is in these high concentrations, goes directly into
Speaker:the urine, it precipitates and can cause acute tubular ne necrosis.
Speaker:And this is shown by this very steep rise, and then, then quick fall
Speaker:again, after, after stopping it.
Speaker:It can, these patients can get acyclovir again with slow infusion speed or
Speaker:as an oral, antiviral because then the, the spike is, so the really,
Speaker:the quick spike is the problem here.
Speaker:I, I just learned that pretty recently.
Speaker:I don't know if maybe it's common knowledge, but it
Speaker:was very interesting to me.
Speaker:It's different to be like chronic toxicity with long-term or longer term acyclovir.
Speaker:So this is what, what should be done right away.
Speaker:You know, start the patient on Acyclovir, and then monitor the clinical response.
Speaker:So the, the role of steroids is a bit, um, controversial, especially in zoster.
Speaker:Some people say it's might prevent occurrence of post zoster neuralgia,
Speaker:but obviously you wanna try to lower the immunosuppression as much as possible.
Speaker:And if it's not easy for like recently transplanted host, but as
Speaker:the diagnosis of the severe cutaneous allergic reaction is not confirmed,
Speaker:we would, um, try to tackle that.
Speaker:Or, I mean, go back to the baseline where, where she was before.
Speaker:Yeah.
Speaker:And one thing we should also do in this, um, patient is screen
Speaker:for other viral reactivation.
Speaker:So what is usually done anyways is regular screening for
Speaker:CMV viremia, and also HSV.
Speaker:This should be, should be done in this situation as well, where
Speaker:you have this unclear rash like in when it was unclear at first.
Speaker:Yeah.
Speaker:So this, this should be done as well.
Speaker:I do feel like that is one of the challenges is sometimes these patients
Speaker:have a vesicular rash and maybe you don't have a super compelling
Speaker:story for VZV versus HSV and, um, that PCR really helps you out.
Speaker:Yeah.
Speaker:And I just want to underscore this point of making the diagnosis of generalized
Speaker:herpes zoster infection, but also frankly about a normal herpes zoster
Speaker:reactivation in immunocompromised host.
Speaker:This can be a bit challenging because we all know the pictures of, uh, these
Speaker:patients where it's a clear cut case.
Speaker:You have one dermatome that has a typical rash, then it's a clinical diagnosis.
Speaker:But really keep in mind that you can do, uh, if you have the suspicion, a PCR from
Speaker:the vesicles, and this will definitely give you the diagnosis or rule it out.
Speaker:Okay.
Speaker:So in this case, acyclovir was quickly started.
Speaker:At this point the patient has received about two weeks of acyclovir.
Speaker:Some of the skin lesions, particularly on the extremities, do seem to be
Speaker:improving, but the viremia present in the blood has still remained
Speaker:quite high and persistently high.
Speaker:Um, so what might you be wondering about now given this persistent viremia?
Speaker:And I think it's probably just a good place for us to take a step
Speaker:back and think about our antiviral options that are available to us.
Speaker:We obviously focus and everyone's very comfortable with knowing
Speaker:aciclovir as our drug of choice, especially in someone who's
Speaker:critically ill and immunocompromised.
Speaker:But what other options are out there?
Speaker:Yeah.
Speaker:So when I think about antiviral treatment, I first go back a step
Speaker:and think about what I want to treat.
Speaker:And in our case, it's VZV and for me it always helps to conceptualize these
Speaker:viruses within the herpes virus family.
Speaker:I know it's not so common.
Speaker:Um, but the, uh, usual herpes viruses like HS V one and two can also be
Speaker:classified as a human herpes virus.
Speaker:So HH V one, and then we have HH V one to eight, and uh, the
Speaker:VZV is actually number three.
Speaker:So we have HHV-1, which is HS V one, and then HHV two, which is HSV
Speaker:two, and then we HHV3, which is VZV.
Speaker:I'm saying this because, not all antivirals are active again.
Speaker:All herpes viruses and the ones that we want to look at, uh, today are
Speaker:mostly active against the HHV one to three, so against the two herpes
Speaker:simplex viruses and against the VZV.
Speaker:Yeah.
Speaker:And uh, one other commentary about the antivirals is that all these substances
Speaker:have a relatively narrow dose range.
Speaker:So it's really not as the penicillins, for example, that have like a huge
Speaker:dose range and you can give big dosage without much side effects.
Speaker:And then, many of them are pro drugs, so they need to get activated.
Speaker:And the ones that we will cover now are all, nucleoside analogue,
Speaker:and they have all all have a pretty cool mechanism of action.
Speaker:Because as a nucleoside, they need to be phosphorylated, three times to be active.
Speaker:And the first phosphorylation can only occur through a thymidine kinase that's
Speaker:coded for by the herpes virus itself.
Speaker:So this means that our drug can mostly or almost exclusively get activated in
Speaker:virus infected cells, whereas uninfected cells lack this thymidine kinase
Speaker:because it's encoded by the virus, and, thus they can't activate it or
Speaker:activations at least much more unlikely.
Speaker:And so the toxicity's really reduced.
Speaker:So basically, I would say we have four different nucleoside analogue substances.
Speaker:And we already heard, acyclovir, which is also a pro-drug.
Speaker:And this is really the substance that has a very low oral bioavailability,
Speaker:so mostly we would actually use it, given as an IV formulation.
Speaker:And we already heard about the biggest side effect which is, nephrotoxicity, but
Speaker:it also has in rare cases a neurotoxicity.
Speaker:So you could have patients that develop delirium or
Speaker:tremors or hallucinations even.
Speaker:But this is not so common with acyclovir generally.
Speaker:It's pretty well tolerated, I would say.
Speaker:And then we have, the oral version of acyclovir.
Speaker:As I often say, it's valacyclovir.
Speaker:And that is, a pro drug of acyclovir, which is in turn a prodrug.
Speaker:So it's a prodrug of the prodrug.
Speaker:And this has a, a much higher oral bioavailability.
Speaker:So it's a, more than 50% are absorbed actually.
Speaker:And the side effects are around the same.
Speaker:Then we have, famiciclovir, which is also a product that is transformed into
Speaker:acyclovir, but it's very similar also.
Speaker:And then we have another substance, the fourth, uh, that's, I think it's not used
Speaker:in the US it's called, uh, brivudine.
Speaker:And it's also on nucleoside analogue.
Speaker:Um, and yeah, it's also pretty similar, but it has fallen kind of out of, uh,
Speaker:fashion, I would say, because there has been a label warning in, uh, Germany or
Speaker:in the EU at least because it had, uh, some like very rare, deadly interactions
Speaker:with certain anti-cancer medications.
Speaker:The, uh, 5FU specifically, that's pretty widely used.
Speaker:Um, and there were some cases where this, because the brivudine actually inhibits
Speaker:the degradation of the cancer medication, this, it has developed some toxic levels.
Speaker:So these are the four core antivirals.
Speaker:But we should also mention one more, which is the foscarnet.
Speaker:That's usually a substance that we would use against CMV infection, but
Speaker:there's also substance that can be occasionally used to treat VZV.
Speaker:And this interesting enough, it's not a nucleoside analogue,
Speaker:but it's a anion pyrophosphate.
Speaker:So it's basically the, the little phosphate that the others gets
Speaker:phosphated with the, the ones that we talked about before.
Speaker:So, um, these were the substances and now that we have the substances, we need to
Speaker:ask ourself what do we hope to achieve or what are the goals of treatment?
Speaker:And in a normal herpes zoster reactivation, it's to hasten the
Speaker:healing of the cutaneous lesions, both because we hope that less pain develops
Speaker:that the rash subsides more quickly.
Speaker:But also we hope that people are less likely to spread it to others because like
Speaker:we said before, the varicella zoster, even as a zoster reactivation is pretty
Speaker:contagious to people who are immuno naive.
Speaker:And what's a bit unclear is if this major complication of a post herpetic neuralgia
Speaker:can actually be prevented by giving antivirals, the data's a bit mixed there.
Speaker:And then the last question that we need to ask ourselves is, who do we treat?
Speaker:Do we treat everyone?
Speaker:And, um, this depends if we have an immunocompromised
Speaker:or immunocompetent patient.
Speaker:For our normal immunocompetent patients, we say that we want to treat, um, at
Speaker:least within 72 hours of symptom onset.
Speaker:This is ideal because we have an antiviral substance.
Speaker:Of course, we want to treat with it early in infection.
Speaker:And after that, the data's a bit mixed also, if we should do
Speaker:it or not, but I guess it's a, yeah, it's a canned decision.
Speaker:For our immunocompromised patients we always want to treat.
Speaker:And also for pregnant people, usually because they have a higher risk also.
Speaker:Yeah.
Speaker:And so in this patient with a persistent viremia, I think there, there's one
Speaker:concern definitely of acyclovir resistance that can develop during treatment.
Speaker:It's not very common, but it can be, so you could try to send off the virus for
Speaker:resistance testing, this is possible.
Speaker:There are some mutations that are known that lead to resistance.
Speaker:So one is definitely the thymidine kinase that can have a mutation in
Speaker:one gene that can reduce the activity.
Speaker:So it's the UL 36 gene, or it can reduce the substrate specificity.
Speaker:And then there are other even less common, uh, mutations.
Speaker:For example, UL 33 in the polymerase gene that impairs acyclovirs
Speaker:binding to the polymerase.
Speaker:And risk factors are all present here, which is like prolonged treatment with
Speaker:acyclovir and severe immunosuppression.
Speaker:So this is definitely one possibility.
Speaker:The other thing that could be when you still have like very large cutaneous
Speaker:lesions with very high concentrations of, of very high, um, yeah, concentration
Speaker:of varicella virus, that that could be like a spillover viremia in the
Speaker:blood as an explanation may be, and not like a true ongoing reactivation.
Speaker:This might be depending on how the levels in the blood are going.
Speaker:So, and for treatment options, I think this is definitely a
Speaker:patient we would continue to treat with intravenous acyclovir.
Speaker:The, the oral option is, I think a good option for non-severe infections, non
Speaker:immunocompromised host, adult patients with zoster that can be shifted to, or
Speaker:primarily treated with with valacyclovir.
Speaker:But this patient definitely has to stay on the acyclovir or maybe switch to
Speaker:something in case resistance is detected.
Speaker:Another thing that's often discussed or suggested by primary teams is
Speaker:the addition of immunoglobulins to help , immune clearance of the virus.
Speaker:The guidelines don't give any recommendations to use it.
Speaker:So it's not recommended to use that routinely.
Speaker:In severe immunocompromised patients, it can be an individual decision,
Speaker:but it's not a recommendation to do that on a, on a regular basis.
Speaker:Yeah, for me also, I know this varicella zoster immunoglobulin mostly in the
Speaker:context of a post-exposure prophylaxis, where it's, uh, occasionally recommended.
Speaker:Yeah.
Speaker:Um, in this case, because there was a question of resistance,
Speaker:foscarnet was added to the regimen.
Speaker:The specimens were sent off for resistance, like you were mentioning.
Speaker:Um, and then sort of just thinking about complications, this patient
Speaker:also has been stuck in the hospital and has been bedridden, so some of
Speaker:the lesions on the back did have some what seems to be secondary infection.
Speaker:The patient had some recurrent bacteremia episodes that required antibiotics, so,
Speaker:um, anything else that, uh, you want to add as far as thinking about complications
Speaker:of these types of infections?
Speaker:Yeah, so I think that's, that's definitely a very common complication.
Speaker:So the viremia and the reactivation eventually can be controlled with
Speaker:medication, but then you still have these open wounds and especially in patients
Speaker:that are maybe not able to stand up or being mobilized out of the bed are and,
Speaker:and are developing super infections of these really severe open wounds.
Speaker:This is definitely a complication that is common in that case.
Speaker:And so it's really important to try to get the patients out of bed and try to get
Speaker:them mobilized in the bed to get pressure off the wounds, have good wound care
Speaker:management involved very early on to maybe also prevent some kind of complications.
Speaker:But, we all know these patients that have been stuck in the hospital
Speaker:for long and, you know, um, and not, not being able to move.
Speaker:This is definitely something we see not only in varicella, but with
Speaker:everyone having like, uh, pressure ulcers, from being in there too long.
Speaker:This is something that's really hard to, um, avoid.
Speaker:But this is definitely something to, to look out for, um, in that patient.
Speaker:Yeah, and she ultimately received many weeks of IV acyclovir has been
Speaker:in the hospital, as you can kind of guess from the story, and, um, was not
Speaker:able to transition to oral treatment just like you were talking about.
Speaker:And, before we sort of close this case, I, I wanna see if you have
Speaker:any additional thoughts on treatment of VZV in our immunocompromised or
Speaker:solid organ transplant patients.
Speaker:You know, this is obviously a more rare complication, but we talk about and
Speaker:think about prevention all the time.
Speaker:So maybe we can also touch on that too.
Speaker:How do we think about prevention of VZV infection?
Speaker:Yeah, so there's really no like systemic data on how to
Speaker:prevent VZV in these patients.
Speaker:So I think one important cornerstone in prevention is vaccination.
Speaker:So, um, check the serologies before transplantation and try
Speaker:to update vaccines of patients.
Speaker:So as long as you can still, um, give a live attenuated vaccine.
Speaker:So you should do that before transplantation.
Speaker:If it's not like an emergency transplantation, you have the time.
Speaker:And then also check on post transplantation if you
Speaker:can do zoster vaccination.
Speaker:But we think we'll get to that later.
Speaker:And then the question is, is there any role of medication in preventing
Speaker:reactivation after transplantation?
Speaker:And so if you have a patient that receives CMV prophylaxis after transplantation.
Speaker:So if you're an inter intermediate or high risk category with a VZV donor and
Speaker:recipient status and you're receiving, um, valganciclovir, for example, this has
Speaker:some activity against varicella zoster.
Speaker:So this is considered to be an effective prophylaxis against
Speaker:reactivation, not letermovir, which is very widely used in Germany for
Speaker:the stem cell transplant patients.
Speaker:So this has no activity against varicella.
Speaker:So then you might think about maybe adding acyclovir, but it's really not sure.
Speaker:Um, who will profit of this, depending on the level of
Speaker:immunosuppression you're getting.
Speaker:And probably stem cell transplantations are in a higher risk credit.
Speaker:Solid organ transplant patients, um, usually don't get acyclovir prophylaxis
Speaker:for varicella zoster routinely.
Speaker:Um.
Speaker:Yeah, so it's really unclear.
Speaker:You can maybe, depending on how your HSV, so yourherpes simplex, um,
Speaker:um, serology is you might consider a short term prophylaxis with
Speaker:aciclovir, which is recommended.
Speaker:This also helps against varicella zoster, but there's no recommendations
Speaker:for varicella in general in, in, for, for, um, uh, reactivation prophylaxis.
Speaker:so we're gonna transition and say we're in clinic.
Speaker:We can say a few weeks, maybe we'll be generous and say a couple months
Speaker:later, uh, the patient has recovered.
Speaker:Was finally discharged and they've come back in and so they're asking
Speaker:about vaccination and I thought since we are from two different places, that
Speaker:we can talk a little bit comparing and contrasting vaccination schedules and
Speaker:just talking about vaccines in general.
Speaker:Um, that, you know, I think sometimes for these vaccine preventable infections
Speaker:we take for granted that we don't often see them or think about them as much.
Speaker:So maybe I'll hand over to Till first to just kind of introduce
Speaker:what vaccines are available.
Speaker:Yeah.
Speaker:So as VZV vaccines go, we have three different vaccines available, at
Speaker:least worldwide, and I, we could like group them in two different buckets.
Speaker:So the first bucket would be, uh, the bucket of the live attenuated vaccines.
Speaker:So these are what we would refer, uh, to as a chickenpox vaccine.
Speaker:So this is a vaccine, uh, for kids.
Speaker:The first one that we would use in order to prevent the primary VZV infection.
Speaker:And it's different marketed under different names.
Speaker:It's either, uh, varivax think it's the name in the US or uh, uh, viral rigs.
Speaker:Is in, it's called in the EU.
Speaker:And so this is the, yeah, the vaccine for kids.
Speaker:The second one is, that's also in the bucket of live attenuated
Speaker:vaccines is, uh, very similar, but this is a shingles vaccine.
Speaker:So this is a vaccine that we want to give to adults to prevent the reactivation.
Speaker:And this is a vaccine that was called, or is called Zostavax.
Speaker:And I think in the US it's not, uh, in use anymore.
Speaker:And also the German, um, vaccine recommendations
Speaker:recommend against using it.
Speaker:And it's actually very similar to the children one, except
Speaker:that it's much higher dose.
Speaker:So it has a bottle one, one.
Speaker:Um, so like.
Speaker:10 times more particle forming units of this, uh, attenuated strain of the VZV.
Speaker:Um, so basically it's the same as the kids, but just higher dose.
Speaker:And then the third vaccine is the recombinant glycoprotein vaccine.
Speaker:So that's not a live vaccine.
Speaker:And this is, offers a major advantage because we can now, uh, offer this
Speaker:vaccine basically to everyone.
Speaker:Especially our immunocompromised host, especially our pregnant people.
Speaker:Also, and it's marketed under the name of Shingrix and it hasn't been
Speaker:around that long actually, in Germany.
Speaker:It came to market in 2018 in other countries, I think one year before.
Speaker:And yeah, it has a excellent, um, vaccine effectiveness.
Speaker:The thing that we want to do with this vaccine, again, because it's
Speaker:a a shingles vaccine, we want to, uh, prevent the reactivation.
Speaker:So we want to prevent herpes zoster and in the landmark paper after which it
Speaker:was introduced to market, described a vaccine effectiveness of more than 95%.
Speaker:But we now also have some, uh, long-term data that showed that , still around
Speaker:80% vaccine effectiveness after 10 years of the vaccination course.
Speaker:So those are really encouraging, uh, data both for the effectiveness
Speaker:but then also for the safety of the vaccine because this is something that
Speaker:you also have to stress that these vaccines are, uh, extremely safe, these
Speaker:recombinant glycoprotein vaccines.
Speaker:Yeah.
Speaker:And so, um, just.
Speaker:Like you're saying in the US for the Varivax, that initial chicken
Speaker:pox vaccine, we recommend two childhood doses of varicella vaccine.
Speaker:So the first is when they're 12 to 15 months of age.
Speaker:So they're 1-year-old shots and then they get a second one
Speaker:at four to six years of age.
Speaker:Um, but I, you know, I know from hearing cases and, and talking to others that
Speaker:varicella vaccination childhood actually isn't you know, it's not something
Speaker:that's part of every country's schedule, and I actually don't know if it's part
Speaker:of the routine schedule in Germany.
Speaker:So, um, how do you guys use
Speaker:Yeah, it's a little bit different as so in Germany, uh, first dose is recommended
Speaker:alongside the first MMR vaccine around 11 months or maybe 11 to 14 months of age.
Speaker:And however, there's a, a slight peculiarity in the German recommendations
Speaker:because it's written, not recommended to give it, uh, combined in one
Speaker:syringe with the MMR vaccine.
Speaker:So, because we could also use the MMRV.
Speaker:Instead it's recommended to do it simultaneously, but to use
Speaker:different parts of the body.
Speaker:So basically you could use a different leg also, and this is apparently
Speaker:because, some data on increased febrile seizures when applied
Speaker:in this within the same syringe.
Speaker:I, yeah, I think there's limited data on this, but this is what the
Speaker:German vaccine recommendations state.
Speaker:Alternatively, you could wait four weeks between the MMR and the varicella vaccine,
Speaker:but this only goes for the first dose.
Speaker:And then for the second dose, which we usually, um, uh, give around six months,
Speaker:um, after the first one, you can use the MMRV, so the combination of the four.
Speaker:Yeah.
Speaker:And then there's also one more recommendation, which is a
Speaker:work related recommendation.
Speaker:So, basically all healthcare workers, but also everyone who works with lots
Speaker:of people, uh, is recommended to have their, uh, routines vaccine schedule
Speaker:up to date or have it updated in case they report no vaccines as a child.
Speaker:And then for the zoster vaccination, just like you said, the Zostavax
Speaker:is not available in the US anymore.
Speaker:We currently recommend two doses of the recombinant zoster vaccine
Speaker:for adults that are 50 and over.
Speaker:So whether or not they've had a history of herpes zoster, whether or not
Speaker:they've had Zostavax, those patients don't necessarily get screened,
Speaker:you know, by history or serology.
Speaker:Um, with a titer for evidence of prior varicella infection.
Speaker:They can just get the vaccine.
Speaker:There is also a recommendation for essentially all adult patients.
Speaker:Um, who are or will be immunosuppressed to get the Shingrix is the brand
Speaker:name and then we, it's two doses separated by two to six months.
Speaker:If it has been more than six months after the first dose, we just give them dose
Speaker:number two, we don't restart the series.
Speaker:Um, and then if the patient's immunocompromised, we can sort of
Speaker:squeeze that window if we need to and give the second dose after one month.
Speaker:The other question that occasionally comes up, we're not routinely doing, but
Speaker:I, I think people have asked about will one day we be able to think about the
Speaker:recombinant zoster vaccine as primary immunization in an immunocompromised host.
Speaker:I think that's a, um, interesting question that we don't have a great
Speaker:answer for yet, but maybe in the future
Speaker:Mm.
Speaker:What about you guys for Germany?
Speaker:Yeah, the recommendations are, I have to say unfortunately, a
Speaker:little bit different in Germany.
Speaker:So, the vaccine recommendations state that it's recommended for
Speaker:all adults 60 years and older.
Speaker:Okay.
Speaker:So that's maybe 10 years difference.
Speaker:But then it also states that, that it's recommended for adults
Speaker:who are immunocompromised only when they're 50 years or older.
Speaker:And this is something where I have to say I disagree a bit because
Speaker:of course, it really depends on the level of immunosuppression.
Speaker:So people like we've discussed before those that are severely
Speaker:immunosuppressed, should definitely receive a vaccine regardless of their age.
Speaker:Is it easy for them to get vaccination if someone, for example,
Speaker:suggest it but they're under 50.
Speaker:Yes.
Speaker:Yeah.
Speaker:in this case that the patients are, um, severely immunosuppressed.
Speaker:Uh, I think the, I'm pretty sure that it should be covered.
Speaker:But apart from that, actually it's not so easy.
Speaker:So if you're not severely immunosuppressed, it's um, a bit
Speaker:unlikely that you will get it.
Speaker:Yeah.
Speaker:Yeah.
Speaker:Yeah.
Speaker:Sometimes it's hard for folks to get vaccines outside of a
Speaker:recommendation, or, or they can, but it costs more money than it should.
Speaker:Um, and, uh, I, I think the other question that's come up for me with
Speaker:a patient who had a similar scenario is, you know, say that this patient
Speaker:had not received a zoster vaccination, they're interested, but they've had
Speaker:this pretty significant infection.
Speaker:When is the right timing to give them the recombinant zoster vaccination?
Speaker:What do you guys think?
Speaker:Yeah, I think also there's no, no real good guidance where you have like a
Speaker:cutoff of three or six or 12 months.
Speaker:So it's really depending on patient and, and your recommendation.
Speaker:So, um, what we would do is definitely only recommend obviously
Speaker:the, the Shingrix vaccine.
Speaker:So the CDC, um, says there's no specific length of time that you need to wait.
Speaker:The rash has to be gone, which kind of makes sense generally, and
Speaker:the Australian guidance says maybe three months, wait three months.
Speaker:So I think if the patient is there, she's feeling well, she or he's
Speaker:feeling well, the rash is gone.
Speaker:And if the patient is stable, I would use the opportunity to vaccinate.
Speaker:Um, so in, in consent with the patient.
Speaker:So maybe not, you know, fresh out of the hospital, just
Speaker:getting settled at home again.
Speaker:But I think every opportunity you have where the patient sits
Speaker:and wants to get vaccinated.
Speaker:We should use if it makes sense and there's, there's no
Speaker:specific recommendation or I would, I would do that then.
Speaker:Yeah.
Speaker:And I think it's also just important to remember to even give the patient the
Speaker:Shingrix vaccine against zoster, even though they just had an episode of zoster.
Speaker:So that's, that might be something that some patients, uh, would ask,
Speaker:like, why should I take the vaccine?
Speaker:But this is something that we are also pretty confident in, that it reduces
Speaker:the probability because actually people who've had zoster also have
Speaker:a high chance on of having another zoster episode in the, in the future.
Speaker:Yeah.
Speaker:Um, and we've covered a ton of ground today, but, I open up at the end just
Speaker:to see if there's anything else that you guys wanna make sure we mention
Speaker:or sort of take home points from this case or anything we've discussed today.
Speaker:So for me, recently transplanted patients are always very critical and have to be
Speaker:treated like a little bit like a raw egg.
Speaker:So I think definitely be very alert in anything that occurs.
Speaker:If it's something on the skin, if it's something in the lung, just
Speaker:be really aggressive and quick with diagnosing whatever is is coming up.
Speaker:Do the screenings regularly of viral reactivations in the blood
Speaker:as according to the guidelines.
Speaker:And then yeah, be quick to react.
Speaker:'cause they're really they can they can deteriorate pretty quickly.
Speaker:Um, that, that was that for me.
Speaker:So be really aggressive and diagnostic and don't, don't wait.
Speaker:Yeah.
Speaker:Yeah.
Speaker:And use the PCR, uh, from the swab from the vesicles.
Speaker:Yeah.
Speaker:Yeah.
Speaker:Confirm the diagnosis.
Speaker:And a quick note on immunology.
Speaker:The serology is a varied marker if you want to see if the patient
Speaker:has, uh, had contact before with a varicella zoster virus.
Speaker:But the main immunity to contain VZV is actually driven through T cells.
Speaker:So the cellular immunoresponse response actually plays a critical
Speaker:role in controlling the VZV latency and to prevent it from reactivation.
Speaker:Thanks again to Til and Annette for joining us today.
Speaker:You can check out the website febrile podcast.com, where we keep our Consult
Speaker:Notes, which are written complements of the episodes with links to references,
Speaker:our library of ID infographics, and a link to our merch store.
Speaker:Febrile is produced with support from the Infectious Diseases Society of America.
Speaker:Please reach out if you have any suggestions for future shows or
Speaker:wanna be more involved with Febrile.
Speaker:Thanks for listening.
Speaker:Stay safe and I'll see you next time.
