Hi everyone.

Welcome to Febrile, a cultured podcast about all things infectious disease.

We use consult questions to dive into ID clinical reasoning, diagnostics and antimicrobial management.

I'm Sara Dong, your host and a Med Peds ID doc.

Today we have a ID podcast crossover.

I am joined by two of the three hosts of the German speaking ID podcast called Infektiopod.

I'll first introduce Dr.

Till Koch.

He is an attending in infectious diseases and antibiotic stewardship in Itzehoe, Germany.

He divides his time between the inpatient ID ward, consultation service, and antibiotic stewardship efforts in his rural hospital.

Yeah, hi, and my name is Till, and I'm super excited to be here.

Looking forward to the episode.

Also on the podcast today is Dr.

Annette Hennigs.

She's a senior fellow in infectious diseases at the University Medical Center Hamburg Eppendorf in Germany.

Her daily business is leading the consultation service and her main focus of interest is cardiovascular infections.

Hello, I'm Annette.

I'm so happy to be here to do this cross Atlantic Crossover, uh, podcast episode.

Happy to be here.

Their third host, I'll just give a shout out to is Dr.

Elena Terhalle.

So as Febrile is a cultured podcast, we ask our guests to share a little piece of culture, basically just something fun and non-medical that you like.

What have you guys been interested in recently?

Yeah, so, I'm actually been more, uh, outgoing these days.

My kids are getting a little older right now.

They're 10 and 12, and we all try to, you know, keep ourselves when they're toddlers and little, but it's not really happening.

But now, um, we've been going out with them to concerts and everything.

So I went with my daughter to Taylor Swift last summer and we're gonna go see Ed Sheeran.

And it's really nice that obviously, my husband and me have made a little bit of an impression with their music taste, and so it's really fun to see them grow up and, and, uh, be a little more, more outgoing with them or going out with them.

I love it.

Very nice.

Yeah.

And for me, something that really, uh, brings me joy, um, is carpentry.

So, uh, building furniture actually, and I, in the last two years, I managed to set up like a tiny little workshop for myself and when I was studying medicine, I used to do it a lot actually and find more time for it.

But, uh, since I've been working, I've, yeah, I can't, just can't do it so much anymore.

But yeah, creating something with your hands, really that brings me joy.

That's a skill that I fantasize that one day I will be good with no training and no experience.

Um, well I am so excited that you guys are here.

You have been working on Infektiopod since 2019, right and you are expert ID docs we're doing this crossover podcast, but I was hoping that you could introduce everyone to your podcast, um, and tell them a little bit more about how they can find it.

Yeah, so we, uh, started in Infektiopod in January of 2019 as a podcast on infectious diseases in, uh, German, obviously.

First I started by myself because I like podcasts and I was passionate about ID and at the time I was also working in the Institute for Tropical Medicine in Hamburg, and I was listening to, uh, famous other podcasts.

Uh, one that I started with I think was This Week in Parasitism featuring, uh, Vincent Racaniello and Daniel Griffin, and then also the original Puscast by Mike Crislip, which I really enjoyed.

And then, yeah, of course the podcast universe has been growing since then.

Um, so the first episodes of Infektiopod were really just on specific pathogens.

And then in 2020 we shifted a bit towards COVID and the, uh, team grew as Annette and Elena joined in.

And uh, ever since then, we've been doing it as the three of us, this podcast.

And yeah, so we produced a little over 90 episodes so far.

Most of them, or all of them, actually almost in German.

And we covered a wide range of ID topics, I would say.

And most recently we've also covered a few conferences.

Um, ESCMID and ID week, for example.

Yeah.

And, uh, we've also written down what we want to do with a podcast as a poster for this year's ESCMID, for example.

I don't know if it's, uh, readily available online, but, uh, we can find it.

And we wrote down what we want to do with the podcast.

So basically we said we have three goals.

We want to, uh, give a direct knowledge transfer.

I think that's pretty straightforward.

Then we want to build trust in science.

That was a big topic here, um, in the, in the whole COVID pandemic, but also, uh, take part a little bit in societal debates.

So especially around COVID, we also said what we thought about vaccines and, uh, that that's also important.

Yeah, I love it.

And I should say we, we got to meet at ID week, which is how this all blossomed.

And yeah, I, we should definitely share your poster from ESCMID.

We can, um, put it on the webpage too.

But, uh, I'm excited that you're here 'cause you're gonna help us walk through a pretty challenging case.

So I, I'll start us off and then we're gonna cover a lot of info today about some, a viral infection.

So we have a 56-year-old woman who has a history of ischemic cardiomyopathy.

She's now status post heart transplant.

She was CMV donor negative recipient negative.

Her post-transplant course has been complicated by some postoperative renal failure, so she is requiring dialysis, but at this point she's improving and she's been transferred to the normal post-transplant ward.

So at around six weeks after transplantation, um, we'll say she was still hospitalized.

We're not given sort of full details here, but um.

We at this point notice that the patient has these newly formed vesicles and erythema on the chest and back.

Dermatology was consulted and took a biopsy.

Um, and then there was some suspicion for TEN.

So the patient also was placed on pulse therapy with steroids.

Um, swabs of the vesicles were obtained and they came back with a very high viral load of varicella virus.

And this was, oh, I should have done it in my head before 1.4.

Is that billion Yeah.

Billion 1.4 billion copies per ml.

And she had a subsequent PCR from blood that, uh, showed a VZV viral load that was 700,000 copies per ml.

Um, so here we have a heart transplant recipient who has this diffuse vesicular rash.

We now have confirmation of VZV from an unroofed vesicle.

So, you know, do we have our diagnosis here?

Is there anything else that you want to make sure we consider for next steps?

So I think, yeah, we see here.

Now that we established the diagnosis with the PCR.

So that's actually confirmed with a disseminated varicella infection.

We have to figure out what kind of infection it is.

So we have to check the pre-transplant serologies.

Um, which in this, yeah, if it's, if the patient was, um, seropositive before transplantation, so we would be dealing with kind of a reactivation or if it would be at age 56, a rare case of a seronegative patient that was, uh, transplanted and now has a primary varicella infection, which is not so much different in treatment, but it's something that would be interesting.

And, um, so the sero prevalence is, is really high in adults.

Around 90% in this age range is mostly due to previous infection.

The, the younger people are now getting vaccinated, but we're think we'll cover that later on.

After infection, the virus has latency in different parts of the body, in the cranial nerve and dorsal root ganglia and can reactivate at any time in life.

So, around 20% is the lifetime risk of reactivation as herpes zoster as we call it.

Now, the classical symptom would be a dermatome, like a localized, uh, skin infection or skin reactivation and in transplant patients or in solid organ transplant recipients, it's around up to 10, 11% in the first four years after transplantations with heart and lung transplant recipients having the highest risk 'cause of the more aggressive immunosuppression, in comparison to other organs.

With this diagnosis we have to see if there's any other, um, affection of any other organs.

So if there's like pulmonary, um, affection of the other, like hepatic, um, um, affection.

So we should definitely do clinical monitoring lab parameters in case of, you know, she's having problems breathing or dyspnea, we should do imaging of the chest.

We should check for neurologic symptoms to, to rule out cerebral reactivation as well.

So that has to be like a really good clinical workup of the patient and then guided by that additional lab maybe, or, or imaging, um, that should be performed.

Perhaps we can take a step back again also and re reiterate the primary manifestations of varicella zoster virus.

And, we divide the clinical symptoms in either the, uh, reactivation that Annette has already spoken about, or before that, the primary varicella.

So that would be the chicken pox in English or the windpocken in, uh, German.

So.

The wind pox basically.

And this is, I think, the super highly contagious disease of childhood that we, or usually childhood, that we know.

Quick side to the epidemiology again.

Um, the, the seroprevalence is actually much lower in tropical regions, so it's not so uncommon to see here someone who grew up in a tropical region, for example, who migrated to Germany, have a primary VZV infection in their adulthood.

But yeah, I think this clinical presentation.

We, we know mostly it has different, uh, different stages at the same time.

So this, uh, how's it called in English?

This star, this, Oh, the, um, dew on a petal.

Yeah, I can.

Okay.

Um, so yeah, so it had has different stages at the same time of skin manifestation, so it can have vesicular and macular papular at the same time.

And a bit different from that is the clinical presentation of the reactivated VZV infection, what we call herpes zoster.

Um, because normally in immunocompetent persons, the rash is typically restricted to one dermatome, right?

Apart from the rash, which has been described as this, um, dew on a rose petal, so like a dew drop on a rose petal, apart from this rash, the other, uh, clinical sign is the pain or the neuritis that is described.

So if you see rash and it's painful, then you should think about zoster and the, uh, pain can also vary clinically.

So some people don't even feel a lot of pain.

Some people feel pain even before the rash develops.

And some people, um, develop the pain only only after the rash comes.

And one clinical pearl that I learned that you could do if you want to test for this neuritis is, uh, that you test the hyperesthesia.

So you take a little wood, wood spatula, and you kind of move it, uh, around, around on the rash.

And then it should hurt more than on unaffected, uh, sites.

And maybe another question to ask the patients is if it's itching, because this would really not be very typical of zoster and really, uh, push you in other clinical directions, I would say.

So this is the typical presentation of herpes zoster.

But then, uh, we already mentioned also that there are some complications and I think the most common one, and that most people know, uh, probably is this post hepatic neuralgia.

It affects around 15%, uh, of the patients as especially the older patients.

And this can really be a very severe complication because some people have to take long lasting pain medications to deal with the pain.

So that's the most common complication.

But then there are also, uh, a lot of other complications from herpes zoster reactivation, um, mostly, uh, affecting either the eyes, which can be blindness inducing or, sight threatening, um, or infecting the ear, which can, then lead to something, for example, called this Ramsey Hunt Syndrome, where you have like a facial nerve paralysis.

And these zoster vesicles in your ear and also pain.

And then, I think Anna to mentioned it briefly also, that you can have a central nervous system involvement.

So you can have, have either meningitis or encephalitis.

And of course the worst complication is what we have here, which is a disseminated infection.

And, uh, that occurs, um, exclusively in severely immunocompromised host.

Yeah.

And so in this case we have quite typical vesicular lesions, which were not maybe typical in the beginning.

So that's why dermatology was consulted and there was histopathology that showed something, you know, for severe, like drug reaction.

So I think that's, that's what happened here, but then you can really.

Depending on where your hospital is localized and how quick your access to microbiology is, you can establish the diagnosis pretty sensitively with PCR and PCR can be done good from, from the swabs from the vesicles, ideally with like a freshly open vesicular.

But you know, if you have open, um, vesicles, you can do it there.

Or then if you have an immunocompromised host, as in this case also in blood, and then you can see if you have a systemic reactivation in that case.

And the quickness of the diagnosis is, especially in immunocompromised hosts is obviously very important so that you can, you know, start treatment, um, really quickly to prevent further complications in that case.

Yeah, so what we would do now when we establish the diagnosis is we would start treating and the first line treatment would be Acyclovir in high dose.

Um, and this patient was on hemodialysis, but this is like the first line and preferred treatment.

So we would do it in irrespective of the renal failure.

And, um, one thing I actually learned, uh, with one case that we treated with Acyclovir, there was another patient, uh, unrelated to this, and he had like a very quick and very sharp rise in the creatinine after one day of treatment with Acyclovir.

We stopped acyclovir because we thought something weird is going on here.

And then the, the creatinine went down really quickly and we talked to pharmacology this to our pharmacist and they said it.

It's, it's, it's a known complication that, um, if you give it intravenously and you infuse it too quickly then you have obviously high plasma levels right away.

And it's, it's primarily excreted through the kidney unchanged, um, and, but has a poor solubility in the urine.

So if it is in these high concentrations, goes directly into the urine, it precipitates and can cause acute tubular ne necrosis.

And this is shown by this very steep rise, and then, then quick fall again, after, after stopping it.

It can, these patients can get acyclovir again with slow infusion speed or as an oral, antiviral because then the, the spike is, so the really, the quick spike is the problem here.

I, I just learned that pretty recently.

I don't know if maybe it's common knowledge, but it was very interesting to me.

It's different to be like chronic toxicity with long-term or longer term acyclovir.

So this is what, what should be done right away.

You know, start the patient on Acyclovir, and then monitor the clinical response.

So the, the role of steroids is a bit, um, controversial, especially in zoster.

Some people say it's might prevent occurrence of post zoster neuralgia, but obviously you wanna try to lower the immunosuppression as much as possible.

And if it's not easy for like recently transplanted host, but as the diagnosis of the severe cutaneous allergic reaction is not confirmed, we would, um, try to tackle that.

Or, I mean, go back to the baseline where, where she was before.

Yeah.

And one thing we should also do in this, um, patient is screen for other viral reactivation.

So what is usually done anyways is regular screening for CMV viremia, and also HSV.

This should be, should be done in this situation as well, where you have this unclear rash like in when it was unclear at first.

Yeah.

So this, this should be done as well.

I do feel like that is one of the challenges is sometimes these patients have a vesicular rash and maybe you don't have a super compelling story for VZV versus HSV and, um, that PCR really helps you out.

Yeah.

And I just want to underscore this point of making the diagnosis of generalized herpes zoster infection, but also frankly about a normal herpes zoster reactivation in immunocompromised host.

This can be a bit challenging because we all know the pictures of, uh, these patients where it's a clear cut case.

You have one dermatome that has a typical rash, then it's a clinical diagnosis.

But really keep in mind that you can do, uh, if you have the suspicion, a PCR from the vesicles, and this will definitely give you the diagnosis or rule it out.

Okay.

So in this case, acyclovir was quickly started.

At this point the patient has received about two weeks of acyclovir.

Some of the skin lesions, particularly on the extremities, do seem to be improving, but the viremia present in the blood has still remained quite high and persistently high.

Um, so what might you be wondering about now given this persistent viremia?

And I think it's probably just a good place for us to take a step back and think about our antiviral options that are available to us.

We obviously focus and everyone's very comfortable with knowing aciclovir as our drug of choice, especially in someone who's critically ill and immunocompromised.

But what other options are out there?

Yeah.

So when I think about antiviral treatment, I first go back a step and think about what I want to treat.

And in our case, it's VZV and for me it always helps to conceptualize these viruses within the herpes virus family.

I know it's not so common.

Um, but the, uh, usual herpes viruses like HS V one and two can also be classified as a human herpes virus.

So HH V one, and then we have HH V one to eight, and uh, the VZV is actually number three.

So we have HHV-1, which is HS V one, and then HHV two, which is HSV two, and then we HHV3, which is VZV.

I'm saying this because, not all antivirals are active again.

All herpes viruses and the ones that we want to look at, uh, today are mostly active against the HHV one to three, so against the two herpes simplex viruses and against the VZV.

Yeah.

And uh, one other commentary about the antivirals is that all these substances have a relatively narrow dose range.

So it's really not as the penicillins, for example, that have like a huge dose range and you can give big dosage without much side effects.

And then, many of them are pro drugs, so they need to get activated.

And the ones that we will cover now are all, nucleoside analogue, and they have all all have a pretty cool mechanism of action.

Because as a nucleoside, they need to be phosphorylated, three times to be active.

And the first phosphorylation can only occur through a thymidine kinase that's coded for by the herpes virus itself.

So this means that our drug can mostly or almost exclusively get activated in virus infected cells, whereas uninfected cells lack this thymidine kinase because it's encoded by the virus, and, thus they can't activate it or activations at least much more unlikely.

And so the toxicity's really reduced.

So basically, I would say we have four different nucleoside analogue substances.

And we already heard, acyclovir, which is also a pro-drug.

And this is really the substance that has a very low oral bioavailability, so mostly we would actually use it, given as an IV formulation.

And we already heard about the biggest side effect which is, nephrotoxicity, but it also has in rare cases a neurotoxicity.

So you could have patients that develop delirium or tremors or hallucinations even.

But this is not so common with acyclovir generally.

It's pretty well tolerated, I would say.

And then we have, the oral version of acyclovir.

As I often say, it's valacyclovir.

And that is, a pro drug of acyclovir, which is in turn a prodrug.

So it's a prodrug of the prodrug.

And this has a, a much higher oral bioavailability.

So it's a, more than 50% are absorbed actually.

And the side effects are around the same.

Then we have, famiciclovir, which is also a product that is transformed into acyclovir, but it's very similar also.

And then we have another substance, the fourth, uh, that's, I think it's not used in the US it's called, uh, brivudine.

And it's also on nucleoside analogue.

Um, and yeah, it's also pretty similar, but it has fallen kind of out of, uh, fashion, I would say, because there has been a label warning in, uh, Germany or in the EU at least because it had, uh, some like very rare, deadly interactions with certain anti-cancer medications.

The, uh, 5FU specifically, that's pretty widely used.

Um, and there were some cases where this, because the brivudine actually inhibits the degradation of the cancer medication, this, it has developed some toxic levels.

So these are the four core antivirals.

But we should also mention one more, which is the foscarnet.

That's usually a substance that we would use against CMV infection, but there's also substance that can be occasionally used to treat VZV.

And this interesting enough, it's not a nucleoside analogue, but it's a anion pyrophosphate.

So it's basically the, the little phosphate that the others gets phosphated with the, the ones that we talked about before.

So, um, these were the substances and now that we have the substances, we need to ask ourself what do we hope to achieve or what are the goals of treatment?

And in a normal herpes zoster reactivation, it's to hasten the healing of the cutaneous lesions, both because we hope that less pain develops that the rash subsides more quickly.

But also we hope that people are less likely to spread it to others because like we said before, the varicella zoster, even as a zoster reactivation is pretty contagious to people who are immuno naive.

And what's a bit unclear is if this major complication of a post herpetic neuralgia can actually be prevented by giving antivirals, the data's a bit mixed there.

And then the last question that we need to ask ourselves is, who do we treat?

Do we treat everyone?

And, um, this depends if we have an immunocompromised or immunocompetent patient.

For our normal immunocompetent patients, we say that we want to treat, um, at least within 72 hours of symptom onset.

This is ideal because we have an antiviral substance.

Of course, we want to treat with it early in infection.

And after that, the data's a bit mixed also, if we should do it or not, but I guess it's a, yeah, it's a canned decision.

For our immunocompromised patients we always want to treat.

And also for pregnant people, usually because they have a higher risk also.

Yeah.

And so in this patient with a persistent viremia, I think there, there's one concern definitely of acyclovir resistance that can develop during treatment.

It's not very common, but it can be, so you could try to send off the virus for resistance testing, this is possible.

There are some mutations that are known that lead to resistance.

So one is definitely the thymidine kinase that can have a mutation in one gene that can reduce the activity.

So it's the UL 36 gene, or it can reduce the substrate specificity.

And then there are other even less common, uh, mutations.

For example, UL 33 in the polymerase gene that impairs acyclovirs binding to the polymerase.

And risk factors are all present here, which is like prolonged treatment with acyclovir and severe immunosuppression.

So this is definitely one possibility.

The other thing that could be when you still have like very large cutaneous lesions with very high concentrations of, of very high, um, yeah, concentration of varicella virus, that that could be like a spillover viremia in the blood as an explanation may be, and not like a true ongoing reactivation.

This might be depending on how the levels in the blood are going.

So, and for treatment options, I think this is definitely a patient we would continue to treat with intravenous acyclovir.

The, the oral option is, I think a good option for non-severe infections, non immunocompromised host, adult patients with zoster that can be shifted to, or primarily treated with with valacyclovir.

But this patient definitely has to stay on the acyclovir or maybe switch to something in case resistance is detected.

Another thing that's often discussed or suggested by primary teams is the addition of immunoglobulins to help , immune clearance of the virus.

The guidelines don't give any recommendations to use it.

So it's not recommended to use that routinely.

In severe immunocompromised patients, it can be an individual decision, but it's not a recommendation to do that on a, on a regular basis.

Yeah, for me also, I know this varicella zoster immunoglobulin mostly in the context of a post-exposure prophylaxis, where it's, uh, occasionally recommended.

Yeah.

Um, in this case, because there was a question of resistance, foscarnet was added to the regimen.

The specimens were sent off for resistance, like you were mentioning.

Um, and then sort of just thinking about complications, this patient also has been stuck in the hospital and has been bedridden, so some of the lesions on the back did have some what seems to be secondary infection.

The patient had some recurrent bacteremia episodes that required antibiotics, so, um, anything else that, uh, you want to add as far as thinking about complications of these types of infections?

Yeah, so I think that's, that's definitely a very common complication.

So the viremia and the reactivation eventually can be controlled with medication, but then you still have these open wounds and especially in patients that are maybe not able to stand up or being mobilized out of the bed are and, and are developing super infections of these really severe open wounds.

This is definitely a complication that is common in that case.

And so it's really important to try to get the patients out of bed and try to get them mobilized in the bed to get pressure off the wounds, have good wound care management involved very early on to maybe also prevent some kind of complications.

But, we all know these patients that have been stuck in the hospital for long and, you know, um, and not, not being able to move.

This is definitely something we see not only in varicella, but with everyone having like, uh, pressure ulcers, from being in there too long.

This is something that's really hard to, um, avoid.

But this is definitely something to, to look out for, um, in that patient.

Yeah, and she ultimately received many weeks of IV acyclovir has been in the hospital, as you can kind of guess from the story, and, um, was not able to transition to oral treatment just like you were talking about.

And, before we sort of close this case, I, I wanna see if you have any additional thoughts on treatment of VZV in our immunocompromised or solid organ transplant patients.

You know, this is obviously a more rare complication, but we talk about and think about prevention all the time.

So maybe we can also touch on that too.

How do we think about prevention of VZV infection?

Yeah, so there's really no like systemic data on how to prevent VZV in these patients.

So I think one important cornerstone in prevention is vaccination.

So, um, check the serologies before transplantation and try to update vaccines of patients.

So as long as you can still, um, give a live attenuated vaccine.

So you should do that before transplantation.

If it's not like an emergency transplantation, you have the time.

And then also check on post transplantation if you can do zoster vaccination.

But we think we'll get to that later.

And then the question is, is there any role of medication in preventing reactivation after transplantation?

And so if you have a patient that receives CMV prophylaxis after transplantation.

So if you're an inter intermediate or high risk category with a VZV donor and recipient status and you're receiving, um, valganciclovir, for example, this has some activity against varicella zoster.

So this is considered to be an effective prophylaxis against reactivation, not letermovir, which is very widely used in Germany for the stem cell transplant patients.

So this has no activity against varicella.

So then you might think about maybe adding acyclovir, but it's really not sure.

Um, who will profit of this, depending on the level of immunosuppression you're getting.

And probably stem cell transplantations are in a higher risk credit.

Solid organ transplant patients, um, usually don't get acyclovir prophylaxis for varicella zoster routinely.

Um.

Yeah, so it's really unclear.

You can maybe, depending on how your HSV, so yourherpes simplex, um, um, serology is you might consider a short term prophylaxis with aciclovir, which is recommended.

This also helps against varicella zoster, but there's no recommendations for varicella in general in, in, for, for, um, uh, reactivation prophylaxis.

so we're gonna transition and say we're in clinic.

We can say a few weeks, maybe we'll be generous and say a couple months later, uh, the patient has recovered.

Was finally discharged and they've come back in and so they're asking about vaccination and I thought since we are from two different places, that we can talk a little bit comparing and contrasting vaccination schedules and just talking about vaccines in general.

Um, that, you know, I think sometimes for these vaccine preventable infections we take for granted that we don't often see them or think about them as much.

So maybe I'll hand over to Till first to just kind of introduce what vaccines are available.

Yeah.

So as VZV vaccines go, we have three different vaccines available, at least worldwide, and I, we could like group them in two different buckets.

So the first bucket would be, uh, the bucket of the live attenuated vaccines.

So these are what we would refer, uh, to as a chickenpox vaccine.

So this is a vaccine, uh, for kids.

The first one that we would use in order to prevent the primary VZV infection.

And it's different marketed under different names.

It's either, uh, varivax think it's the name in the US or uh, uh, viral rigs.

Is in, it's called in the EU.

And so this is the, yeah, the vaccine for kids.

The second one is, that's also in the bucket of live attenuated vaccines is, uh, very similar, but this is a shingles vaccine.

So this is a vaccine that we want to give to adults to prevent the reactivation.

And this is a vaccine that was called, or is called Zostavax.

And I think in the US it's not, uh, in use anymore.

And also the German, um, vaccine recommendations recommend against using it.

And it's actually very similar to the children one, except that it's much higher dose.

So it has a bottle one, one.

Um, so like.

10 times more particle forming units of this, uh, attenuated strain of the VZV.

Um, so basically it's the same as the kids, but just higher dose.

And then the third vaccine is the recombinant glycoprotein vaccine.

So that's not a live vaccine.

And this is, offers a major advantage because we can now, uh, offer this vaccine basically to everyone.

Especially our immunocompromised host, especially our pregnant people.

Also, and it's marketed under the name of Shingrix and it hasn't been around that long actually, in Germany.

It came to market in 2018 in other countries, I think one year before.

And yeah, it has a excellent, um, vaccine effectiveness.

The thing that we want to do with this vaccine, again, because it's a a shingles vaccine, we want to, uh, prevent the reactivation.

So we want to prevent herpes zoster and in the landmark paper after which it was introduced to market, described a vaccine effectiveness of more than 95%.

But we now also have some, uh, long-term data that showed that , still around 80% vaccine effectiveness after 10 years of the vaccination course.

So those are really encouraging, uh, data both for the effectiveness but then also for the safety of the vaccine because this is something that you also have to stress that these vaccines are, uh, extremely safe, these recombinant glycoprotein vaccines.

Yeah.

And so, um, just.

Like you're saying in the US for the Varivax, that initial chicken pox vaccine, we recommend two childhood doses of varicella vaccine.

So the first is when they're 12 to 15 months of age.

So they're 1-year-old shots and then they get a second one at four to six years of age.

Um, but I, you know, I know from hearing cases and, and talking to others that varicella vaccination childhood actually isn't you know, it's not something that's part of every country's schedule, and I actually don't know if it's part of the routine schedule in Germany.

So, um, how do you guys use Yeah, it's a little bit different as so in Germany, uh, first dose is recommended alongside the first MMR vaccine around 11 months or maybe 11 to 14 months of age.

And however, there's a, a slight peculiarity in the German recommendations because it's written, not recommended to give it, uh, combined in one syringe with the MMR vaccine.

So, because we could also use the MMRV.

Instead it's recommended to do it simultaneously, but to use different parts of the body.

So basically you could use a different leg also, and this is apparently because, some data on increased febrile seizures when applied in this within the same syringe.

I, yeah, I think there's limited data on this, but this is what the German vaccine recommendations state.

Alternatively, you could wait four weeks between the MMR and the varicella vaccine, but this only goes for the first dose.

And then for the second dose, which we usually, um, uh, give around six months, um, after the first one, you can use the MMRV, so the combination of the four.

Yeah.

And then there's also one more recommendation, which is a work related recommendation.

So, basically all healthcare workers, but also everyone who works with lots of people, uh, is recommended to have their, uh, routines vaccine schedule up to date or have it updated in case they report no vaccines as a child.

And then for the zoster vaccination, just like you said, the Zostavax is not available in the US anymore.

We currently recommend two doses of the recombinant zoster vaccine for adults that are 50 and over.

So whether or not they've had a history of herpes zoster, whether or not they've had Zostavax, those patients don't necessarily get screened, you know, by history or serology.

Um, with a titer for evidence of prior varicella infection.

They can just get the vaccine.

There is also a recommendation for essentially all adult patients.

Um, who are or will be immunosuppressed to get the Shingrix is the brand name and then we, it's two doses separated by two to six months.

If it has been more than six months after the first dose, we just give them dose number two, we don't restart the series.

Um, and then if the patient's immunocompromised, we can sort of squeeze that window if we need to and give the second dose after one month.

The other question that occasionally comes up, we're not routinely doing, but I, I think people have asked about will one day we be able to think about the recombinant zoster vaccine as primary immunization in an immunocompromised host.

I think that's a, um, interesting question that we don't have a great answer for yet, but maybe in the future Mm.

What about you guys for Germany?

Yeah, the recommendations are, I have to say unfortunately, a little bit different in Germany.

So, the vaccine recommendations state that it's recommended for all adults 60 years and older.

Okay.

So that's maybe 10 years difference.

But then it also states that, that it's recommended for adults who are immunocompromised only when they're 50 years or older.

And this is something where I have to say I disagree a bit because of course, it really depends on the level of immunosuppression.

So people like we've discussed before those that are severely immunosuppressed, should definitely receive a vaccine regardless of their age.

Is it easy for them to get vaccination if someone, for example, suggest it but they're under 50.

Yes.

Yeah.

in this case that the patients are, um, severely immunosuppressed.

Uh, I think the, I'm pretty sure that it should be covered.

But apart from that, actually it's not so easy.

So if you're not severely immunosuppressed, it's um, a bit unlikely that you will get it.

Yeah.

Yeah.

Yeah.

Sometimes it's hard for folks to get vaccines outside of a recommendation, or, or they can, but it costs more money than it should.

Um, and, uh, I, I think the other question that's come up for me with a patient who had a similar scenario is, you know, say that this patient had not received a zoster vaccination, they're interested, but they've had this pretty significant infection.

When is the right timing to give them the recombinant zoster vaccination?

What do you guys think?

Yeah, I think also there's no, no real good guidance where you have like a cutoff of three or six or 12 months.

So it's really depending on patient and, and your recommendation.

So, um, what we would do is definitely only recommend obviously the, the Shingrix vaccine.

So the CDC, um, says there's no specific length of time that you need to wait.

The rash has to be gone, which kind of makes sense generally, and the Australian guidance says maybe three months, wait three months.

So I think if the patient is there, she's feeling well, she or he's feeling well, the rash is gone.

And if the patient is stable, I would use the opportunity to vaccinate.

Um, so in, in consent with the patient.

So maybe not, you know, fresh out of the hospital, just getting settled at home again.

But I think every opportunity you have where the patient sits and wants to get vaccinated.

We should use if it makes sense and there's, there's no specific recommendation or I would, I would do that then.

Yeah.

And I think it's also just important to remember to even give the patient the Shingrix vaccine against zoster, even though they just had an episode of zoster.

So that's, that might be something that some patients, uh, would ask, like, why should I take the vaccine?

But this is something that we are also pretty confident in, that it reduces the probability because actually people who've had zoster also have a high chance on of having another zoster episode in the, in the future.

Yeah.

Um, and we've covered a ton of ground today, but, I open up at the end just to see if there's anything else that you guys wanna make sure we mention or sort of take home points from this case or anything we've discussed today.

So for me, recently transplanted patients are always very critical and have to be treated like a little bit like a raw egg.

So I think definitely be very alert in anything that occurs.

If it's something on the skin, if it's something in the lung, just be really aggressive and quick with diagnosing whatever is is coming up.

Do the screenings regularly of viral reactivations in the blood as according to the guidelines.

And then yeah, be quick to react.

'cause they're really they can they can deteriorate pretty quickly.

Um, that, that was that for me.

So be really aggressive and diagnostic and don't, don't wait.

Yeah.

Yeah.

And use the PCR, uh, from the swab from the vesicles.

Yeah.

Yeah.

Confirm the diagnosis.

And a quick note on immunology.

The serology is a varied marker if you want to see if the patient has, uh, had contact before with a varicella zoster virus.

But the main immunity to contain VZV is actually driven through T cells.

So the cellular immunoresponse response actually plays a critical role in controlling the VZV latency and to prevent it from reactivation.

Thanks again to Til and Annette for joining us today.

You can check out the website febrile podcast.com, where we keep our Consult Notes, which are written complements of the episodes with links to references, our library of ID infographics, and a link to our merch store.

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