Drs. Nuria Sanchez-Clemente and Hermione Lyall discuss a case of congenital CMV in the first case of the Febrile “Curious Congenital Conundrums” series

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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 your host, Sara Dong.

I'm an adult and pediatric ID fellow.

Here on Febrile, we use patient cases and consult questions to learn about high yield ID topics.

We'll present pieces of the story of a patient's case, and then pause along the way to hear from our guest consultant.

This is our first case in the newest Febrile series entitled "Curious Congenital Conundrums.".

You can check out our introduction episode in last week's Febrile Digest with Justin Penner, but today I am joined by Nuria and Hermione.

Now I'll give him a quick introduction.

Our co-host today is Dr.

Nuria Sanchez-Clemente.

She is a pediatric registrar and National Institute for Health Research (NIHR) Academic Clinical Lecturer in pediatric infection and immunity at St.

George's University in London.

She completed a MSc in Tropical Medicine at the London School of Hygiene and Tropical Medicine and undertook the first systematic review of Peruvian bartonellosis.

She also has previously lived in Brazil where she did her PhD on congenital Zika syndrome, studying the perinatal outcomes of Zika pregnancy cohort in a state of Sao Paulo.

And since then she has continued to work with teams in Brazil, the London School of Hygiene and Tropical Medicine, and WHO to study the long term consequences for children born with congenital Zika.

In addition to all of this, she has more recently been focused on migrant health and health inequalities.

She's been studying patterns of pediatric primary and secondary healthcare usage between migrants and non migrants in the UK, and has also been working on the "Respond" refugee family project at University College London Hospitals, leading ID clinics for unaccompanied asylum seeking children.

Our guest discussant today is Dr.

Hermione Lyall.

She is a consultant in pediatric ID at the Imperial College Healthcare NHS Trust and a Professor of Practice at Imperial College.

She runs both HIV and congenital infection clinics at St Mary's hospital in London, and is ward attending consultant for pediatric infectious diseases four months per year.

She is a member of Penta ID or Pediatric European Network for Treatment of Aids, and participates in HIV treatment trials for children.

She has been actively involved in development of international courses for education of pediatric infections for many years, working with Penta and the European Society for Pediatric ID or ESPID.

From 2018 to 2021, she was a member of the board of ESPID and is now a trustee on the board for the ESPID foundation.

In 2020, with colleagues from around Europe, she set up CCMVNet, an international network built around registry of children with congenital CMV, and she's currently the chair of the network.

Welcome to the show!

Thank you.

Before we jump into the case, we always ask one non-medical question.

Um, if you would be willing to share a little piece of culture that you enjoyed recently, such as a book or a song or anything that you like.

What do you think, Hermione?

Well, I recently read the latest book by Anthony Doerr called Cloud Cuckoo Land and if you want to read an amazing book that has everything about humanity in it, uh, in the past, the present and the future, go there.

Excellent.

Thank you so much for sharing.

Uh, alright, well, I'll hand it over to Neuria to get us started.

Okay.

So Hermione, it's a Friday afternoon and you are called by your pediatric colleague from a local district general hospital with a patient conundrum that they would like your advice about.

So the patient was referred to the local pediatric infectious diseases multidisciplinary meeting by the obstetrics team at 14 weeks gestation.

The patient is a 29 year old G2P1 previously healthy woman, whom was initially referred to the obstetrics team two weeks earlier with a rash and low grade fever.

The rash was described as macular, blanching and non-pruritic.

She had a mild cough, pharyngitis, rhinorrhea, and a temperature of 38.2 Celsius.

The patient felt otherwise well, had unremarkable antenatal course so far with routine antenatal care with her GP.

She had a previously uneventful pregnancy carried to term three years previously.

She has no significant past medical history.

After completing 18 months of maternity leave that time, she went back to work as an early childhood educator almost a year ago where she continues to work now.

She doesn't take any medication and has no allergies.

As part of the obstetric evaluation, basic bloods were taken including an FBC, CRP, liver enzymes, electrolytes, blood culture, and serology for EBV, CMV, Toxoplasma, parvovirus, rubella and syphilis.

She recovered well from her illness within seven days, and her bloods have now returned with the following results.

Her EBV is IgM negative, but IgG positive.

Her CMV is IgM positive and IgG negative.

Toxoplasma IgM negative and IgG negative.

Parvovirus IgM and IgG negative, and Rubella IgM negative, but IgG positive.

Syphilis wise, TPPA was negative and RPR as well.

Her Hb is 122, platelets 298, white cell count of 12.7, monocytes of 1.5, eosinophils 0.4.

Her CRP is 29 and her electrolytes are normal.

Her ALT is 47 and her blood culture is negative.

So Dr.

Lyall, are there any additional questions that you have in the history that you would like to clarify with your colleagues and are there any important clues in the history already provided?

Okay, so I think there are some interesting things going on here and this lady is currently 14 weeks, became unwell when she was 12 weeks, has got an IgM positive in her serology to CMV and all the other serologies and blood tests are not really telling anything that we would be worried about.

But I think we would be concerned that she's IgM positive to CMV and IgG negative.

So, I guess, what would be interesting to know is has she had any scan yet?

So do we know for sure, uh, about her, the timing of her pregnancy, is she definitely at 14 weeks?

So is that being confirmed?

And I think the other thing we kind of want to know is that, has she had any booking bloods done, so has had any antenatal basic serology, um, and was that done a month ago or six weeks ago?

I'm going to say in this country, in the UK, we don't do antenatal screening for CMV.

In the UK, we only do antenatal screening for HIV, hepatitis B and syphilis.

In some countries, they do do screening at baseline for CMV, but if there is a blood that has already been taken on this lady a few weeks earlier, it would be very useful to know whether she had any CMV antibodies on that earlier sample.

Especially if it was a few weeks, uh, if it was before she became unwell.

Many people when they get, uh, prior CMV actually have no symptoms at all, and the symptoms that she's got could be anything.

It could be any virus.

And sometimes you can get cross reactive IgMs in pregnancy that don't mean anything very much.

So I think we have to try and see if we can get some morphology.

Uh, we might also want to get some virology, see if she's actually got CMV viremia or got CMV in the urine.

And that might help us to clarify a bit more closely, whether we think she is having a primary CMV infection.

The other thing, which is in the history here.

Well, there are two things, which are a concern, is that we know that women who are having their second baby, if they are seronegative, they're probably the ones who are most at risk of seroconverting.

Uh, there's some very nice French studies that have demonstrated that.

Uh, and we also know that women who work in childcare, so with young children and are exposed to lot, lots of snotty, grubby toddlers, are also more at risk of getting CMV from snot and saliva and urine and toys and all the rest of it.

So this lady CMV have some risks that we would be worried, uh, about for getting primary CMV if she hasn't had it before.

Okay, brilliant.

So I think that covers a lot of additional tests, a lot of what we, the tests that have already been done as well.

So I think we will fast forward to 12, another 12 days, and you get another call, uh, from your colleagues with some of the results of the, the tests that you have mentioned.

HIV serology is negative.

Hep B surface antigen is negative, core antibody negative, and, surface antibodies positive.

Hep C serology is negative.

The repeat CMV serology, um, is IgM positive, and IgG is now positive as well with a low validity of 10%.

Initial booking bloods from the current pregnancy have been requested.

At this time at booking, mom was IgM, CMV IgM negative, and IgG negative.

Current CMV urine is PCR positive and blood PCR is positive as well.

Also of note, so the ultrasound showed normal single fetus, appropriate size for dates, no abnormalities noted.

Um, and also amniocentesis was offered, but the family declined.

So what management advice would you give to your colleagues at this stage?

Okay.

So I think it's pretty clear then that this mom has had a primary seroconversion for CMV infection in the first trimester of pregnancy, because we see here that she's still IgM positive.

She's now beginning to produce IgG and that IgG is of low avidity, which tells us that it is new IgG, and that goes along with recent seroconversion.

And that is kind of confirmed by the fact, uh, that her very first booking blood was completely negative.

We don't know how many weeks that was actually done.

Uh, but she has got, she is, she is viremic and she's got, uh, CMV in the urine.

So I think, um, this is obviously a worrying situation because if we look at seroconversion, uh, to CMV in pregnancy.

If you have primary seroconversion, overall, there is about a 30 to 40% risk of transmission to the fetus.

The risk actually increases as pregnancy progresses.

So it's higher in the third trimester and lower in the first trimester.

So it's about 20 to 30% if you're just talking about the first trimester.

But the danger is that we know that first trimester infection, primary infection, is associated with the highest risk of damage to the fetus.

And there is a, uh, a very good study that has been undertaken by our French colleagues, uh, Marianne Leruez-Ville and Madam Faure-Bardon which was done in the kind of 2010, 11 to 17, I think, where they followed up more than two high hundred and 50 women who had primary infection, uh, in pregnancy.

And they followed their babies up to 24 months of age.

And overall about 16% of those babies had significant sequelae including neurological and sensory neural healing loss.

And those babies were more or less all born in, were all infected in the first trimester.

So it is highest risk and the highest risk of damage.

So is there anything that we can do about it?

And I think there's a key that is beginning to unlock something here because, uh, in the Lancet in 2020, our colleagues from Israel published, uh, a randomized control trial of treating women who sero convert in the first trimester with high dose valcyclovir.

This is a placebo control randomized trial where they looked for evidence of seroconversion, uh, before 16 weeks.

And, uh, if women were had evidence of seroconversion, then they started them on high dose valacyclovir.

And overall the risk of transmission to the fetus was reduced by about 63% in the treated women.

And if they separated out between periconceptual infection and actually first trimester infection, it was more like 77% for the women where it was first trimester infection.

And the crucial thing really was the time it took to get started on the valacyclovir in relation to the timing of seroconversion and the shorter that was, the better the risk, the better the chance of the fetus not being infected.

So our mother was definitely seronegative at the beginning.

So I think she's probably not a periconceptual.

So I think we could definitely offer this woman the possibility of going on high dose valacyclovir to reduce the risk of transmission.

And if she was living in Israel or in Northern Italy or in Paris, then she would definitely be offered this kind of treatment.

If she was living in Germany, uh, she might be offered the possibility of, um, CMV hyperimmune globulin.

Uh, there are some randomized controlled trials of using this treatment, which have not been particularly effective, but that is probably because the dosing was not adequate and it isn't given frequently enough.

And there is some data from Germany where if you give, uh, high dose treatment frequently early on, you can probably reduce the transmission.

But this is obviously a very expensive and very interventional treatment that isn't going to be applicable in most parts of the world.

Whereas high dose valacyclovir is, uh, although it's quite an undertaking because it's eight grams.

So it's two pills, four times a day.

Uh, and as long as women know, they have to remain well hydrated, it's actually relatively well tolerated.

And in terms of teratogenicity we know that it is safe.

So I, I would definitely be saying to this mom, it would be a good idea to be on treatment.

Now in the valacyclovir study, the women only took the treatment up until 21 weeks gestation, uh, and then they stopped then.

And in that study they had an amniocentesis and, uh, although the primary endpoint was actually transmission at birth.

So I think it's important to say that that, uh, period of trying to prevent transmission is just during the actual, uh, initial viremia in that early phase.

So the mother doesn't necessarily have to be on treatment all the way through the pregnancy.

Okay.

Excellent.

You get a call, however, several months later from the same colleagues, uh, for advice regarding the same patient.

And they say that preventative treatment was offered, but unfortunately declined.

So the patient delivered at 37 weeks of gestation with Apgars of eight and nine at one and five minutes.

And no resuscitation was required at the time.

And the weight of the female infant, uh, was on the sixth centile (%ile).

And the head circumference on the fourth centile (%ile).

The remainder of the neonatal exam is normal.

They spent 24 hours in hospital initially, and mom is breastfeeding and the child has now been referred back to the infectious diseases team at 12 days of life, as she failed her newborn hearing screen.

Repeated, auditory, brain stem responses demonstrated severe sensory neural hearing loss in the left ear.

So now at this point, what additional tests would you recommend?

Okay, so I think, um, we are obviously concerned that this baby could actually, uh, be infected with CMV and it's a bit disappointing that the baby didn't actually have urine or saliva tested on the first day of life.

If somebody had actually paid attention to the mother's antenatal history, they would know that we should have been testing this baby right at the very beginning to see if it had congenital CMV.

So, uh, it's a real shame that they didn't do on day one.

Um, so the fact that the baby has got confirmed sensorineural hearing loss in the left ear, uh, makes us worried that this baby is infected.

Um, I mean, the baby is a little bit small, but it's not particularly out of proportion, but that doesn't mean to say that this baby hasn't got CNS effects of CMV.

So I think we have to go through all the systems where we can get end organ disease and look for trouble that CMV might have caused.

So my normal thing would be to send saliva, urine, and blood to look for the virus.

Um, and I'm going to do everything, rather than just sending the saliva and waiting, because we're already on day 12.

And if we're going to treat this baby, we want to have done all the investigations in time to get the treatments started a soon as possible, really, but ideally before a month of age, as was the case in the original, uh, Kimberlin study.

So we want to send saliva, urine and blood for CMV.

We want to look and see is the bone marrow affected.

So what is the full blood count?

Is this baby thrombocytopenic or neutropenic?

We want to know about the liver.

Does the baby have hepatitis, uh, or conjugated hyperbilirubinemia as we sometimes see.

Uh, we want to get our ophthalmology colleagues to have a look in the back of the eyes, has the baby got any retinitis or any scarring.

And then we want to look in the most important place, which is actually the brain.

And, uh, what I would normally do, uh, is both a brain MRI and an ultrasound scan.

The ultrasound scan is useful, particularly because it's good for showing calcification, but the MRI, uh, can show us much more.

So the MRI can show us the classic signs that we're looking for, whether there are periventricular cysts, whether there's any increased intensity in the white matter, uh, and perhaps most worrying of all, whether there is polymicrogyria, which is the migration disorder, which is associated with early infection, uh, and the most serious consequences.

And often with polymicrogyria, you may see what looked like slightly dilated ventricles, but this is more really about actually loss of brain tissue, uh, so that you have, and, and that is when you may have a smaller head as well.

So I think we want to bring the baby in, uh, and do all of these things.

Um, people would say, well, you know, what about getting out the Guthrie card and doing the dry blood spot testing?

Um, I mean, I dunno what it's like, where you are, but where I work that is a complete palava uh, and it takes quite a lot, a long time, and we'll be lucky if we get the result back in two weeks, uh, which is gonna put a lot of delay.

And it's important for everybody to know that the dry blood spot, uh, at best only has between 80 and 85% sensitivity.

So a positive, dry blood spot is useful, but a negative dry blood spot does not exclude congenital CMV.

So if I'm within the 21 days of doing the tests, then I'm going to send the urine, saliva and blood.

So they call you back with an update on the results.

Um, so they, they did manage to get a newborn blood spot which was negative and saliva are PCR positive with more than 80,000 counts per mL.

The blood PCR is indeterminant.

There was an error in processing, um, and the MRI unfortunately shows polymicrogyria with, but with normal internal auditory meatus views.

Uh, the ophthalmology exam is thankfully normal.

The ALT is normal and the full blood count has also got normal platelets, HB and cell counts.

So based on this, would you recommend treatment?

And if so, how would you monitor for drug toxicity?

I definitely would recommend treatment for this baby because I know that it has been infected in the first trimester.

And I know that it has polymicrogyria, which is, uh, a significant finding on the MRI scan.

But actually, if you went back to the David Kimberlin randomization, uh, and you looked at this baby, uh, and in those early studies there weren't MRI scans done.

Uh, so they didn't have the kind of vision into the brain that we have now.

You might actually say that this, oh, no, you wouldn't.

Well it's deaf in one year.

So it's only got hearing loss in one year and in some countries that would still be considered to be asymptomatic.

In other countries that would be considered to be symptomatic.

Uh, but certainly I think, uh, we have in, in, in the UK, we have taken a relatively aggressive approach and for a baby who is deaf in one ear and has polymicrogyria, I would definitely, uh, advise treatment.

And the other important thing to say is that we know, uh, from some of the earlier USA studies that babies who are deaf in one year have up to a 50% chance of progressive hearing loss in the other, their ear.

So that is, to me, a really important reason for treatment.

And although the David Kimberlin trial showed a relatively modest, uh, reduction in progression of hearing loss and improvement in neurodevelopmental outcomes at 24 months, it doesn't cure things.

Um, and we still have to monitor these children carefully in terms of hearing, uh, and, and, and development.

Um, so whilst, uh, the child's on treatment and we're talking about six months of oral valganciclovir 16 mg/kg/dose BID.

Uh, valganciclovir is a drug with toxicity.

Um, so it can have short term toxicities, including bone marrow suppression and abnormal liver function, and it can have potential long term toxicity too.

Personally, I see these babies on a monthly basis when they're on treatment.

Uh, and I check their blood count and their liver tests, and that enables me to make sure that they're tolerating the medication okay.

But that also enables me to increase the dose on a monthly basis as they are growing bigger.

I always inform the parents that, uh, valganciclovir is a drug, which has the potential to cause damage to DNA, and that has been shown in some animal studies, uh, and that might at some time increase the a risk of malignancy.

However that hasn't been shown to date in any children who've been treated with congenital CMV.

So it's a potential, but you know, when you put this in the balance, what we're trying to do here is give this baby the best outcome that we can, bearing in mind what has already happened to it, and it, if it was my baby, I would still, uh, go ahead and treat it.

So, uh, yeah, I think that, you know, that's an important discussion to have with the parents.

And it's also important to remember that, uh, valganciclovir is actually, uh, not licensed for treatment of newborns either.

So it is, if you like, important that parents recognize that.

So far, the child has received three months of valganciclovir, um, and thankfully has tolerated the treatment very well without any side effects.

Um, and so what, what other kind of followup would you recommend for this, for this child in terms of sort of the multidisciplinary team?

This baby is going to be at risk of having neurodevelopmental issues.

And you're going to be monitoring quite closely how the head circumference is progressing.

Certainly, uh, this baby, we've got to keep a very close eye on the hearing.

So at least six monthly hearing assessments.

Um, and actually, you know, some parts of the world will do more frequent hearing assessments.

Uh, so we've gotta keep a close eye on that.

And then we're going to be monitoring, how is this baby doing in term sort of its uh, neurodevelopmental milestones.

And, uh, even if doing all right at three months, um, you know, these babies, it may not necessarily be motor issues that they have.

But they are more at risk also of developing seizures.

And we've just recently been looking in our cohort at the babies who have gone on to develop seizures.

And they were almost entirely babies who had polymicrogyria and, um, they usually developed towards the end of the first year of life.

So they weren't usually there earlier, uh, in the first six months.

Um, so we need to watch out for that.

And then I think it's all the important input from physio and speech and language and occupational, uh, therapy.

Um, and commonly children with congenital CMV have problems with communication and learning, and it's not uncommon for them to be on that autistic spectrum as well and have difficulties with communicating.

So the patient completes six months of valganciclovir, uh, now without any complications and the medication is discontinued.

Her left-sided hearing loss is stable, but remains severe.

And so she's referred to ENT for consideration of hearing, hearing augmentation surgery and the right ear, um, hearing has remained unchanged and normal to date.

The mom asked if there are any additional precautions she should take in future pregnancies, and if there are any family groups she could go to for peer support?

I mean, it's interesting because cochlear implantation, uh, the kind of access to cochlear implantation is very different, uh, again, in different parts of the world.

In the UK, for example, to get access to cochlear implantation, if you only have hearing loss in one ear would be extremely difficult.

But I know that in Canada, that is, uh, that is available and it is something to think about in a baby who is at still at risk of losing the hearing in the good ear that if you've already augmented the bad ear, then you might be sort of protecting the options of this child.

So that I think is a debate in the CMV world.

Um, I think it's a very important question about what do I do for subsequent pregnancies?

The first thing to say is that there's quite a bit of randomized controlled trial data, uh, that demonstrates that if women know about CMV and unfortunately so many people have never even heard of this virus, but if people know about it, then they can take action to reduce the risk of transmission.

And there are some relatively simple things to do, uh, which is, uh, not coming into contact with saliva, so not kissing your child on the mouth, not eating the food that your child is half finished on the plate, uh, washing your hands after changing nappies, washing your hands after tidying up all the mess.

Now that is easy enough to say but it's kind of hard to do when you're running around a wild toddler and it's probably even harder when you are actually working in a, in a nursery looking after several children.

But I think, you know, COVID has taught us a lot about how to reduce exposure to viruses.

And I think actually health, well, women who are working in nursery education, you know, should be thinking about how often do they wash their hands and are they wearing gloves when they're changing nappies and all that so sort of thing.

It is interesting that women who work in healthcare, so nurses and doctors who work in pediatrics, uh, who you might think might also be more at risk of getting CMV probably aren't.

They probably don't have any increased risk over other healthcare workers, and that's because they don't treat their babies, the babies and children that they're looking after, in the same way, as somebody in a nursery.

You're already putting gloves on everything and, you know, you've, you're taking a much more aseptic kind of approach.

So I think we need to give this mom the advice about how to avoid contact with CMV in future, but we can also reassure her that if you are already seropositive at the beginning of the pregnancy, so if you've had CMV before, then your risk of transmission to the fetus is much, much less than in primary seroconversion.

And in resource rich settings is probably less than 3%.

So being seropositive already protects your baby quite considerably, the next one coming along.

That doesn't mean to say you can't actually be reinfected by another strain and in the world as a whole, that is probably the way that most babies in resource poor settings get infected.

And from the baby's perspective, uh, it doesn't matter whether it's primary infection or reinfection, the baby can still be as severely infected if they get infected, but the overall risk is much, much smaller.

And in the UK, we have a really fantastic organization called CMV Action, uh, which is a charity, which is run by families of children with congenital CMV, which has beautiful, uh, information for families, for healthcare workers, for the population in general.

Um, and you know, where, uh, a mom can actually go to get peer support as well.

So I direct all my families to CMV Action, and I think there are similar groups, uh, in other countries as well.

Thank you.

Just to finish off really is whether there's any other additional concepts, um, regarding CMV or anything else that you think is worth mentioning at this point.

Um, I think that a couple of things that, uh, that come to mind.

The first thing is, now that we have this randomized controlled trial evidence that we could prevent transmission in the most, at the most dangerous time, when there's more, most risk of damage.

I think we, I think countries, healthcare systems should be reviewing, uh, how they manage CMV in pregnancy and thinking about whether all women should be getting access to screening, antenatal screening, but that really means very early antenatal screening.

I mean, ideally it means doing your first blood test at like four to six weeks and your second blood test at like, you know, eight to 10 weeks or something like that.

If you want to get in there and give the treatment in a timely fashion.

I think that is something that in our center, we are going to start looking at how could we try to offer that to, to women?

And I think if women knew about CMV and if they knew this was available, they would want to have that option.

Uh, so I think we've got to focus on preventing those really damaging first trimester infections.

And then the other thing, which, I mean, I, there is so much about congenital CMV that we really don't understand, but we don't understand why it is that some babies are so much more severely affected than others.

Why it is that some babies, for example, have hearing loss and others do not.

And indeed why it is that you can have hearing loss at birth, but then you can develop hearing loss at kind of two or three or four.

And what is going on there?

Is that virological or immunological or a mixture of both?

Is that genetically determined in your immune response to the virus or something?

So there's an awful lot that we still need to understand better.

We focused here on the more severely affected baby in the first trimester, but actually there are far more infants who are probably infected later on and who may not be so severe, don't necessarily have polymicrogyria, but can certainly have, uh, other CNS effects and hearing loss.

And we still don't know enough about whether treatment for those babies can really improve the outcomes for them.

Particularly in terms of learning and communication and so on.

And there are some clinical trials going on at the moment, looking at these less symptomatic babies and whether early treatment, uh, is, is good for them.

We need, I mean, if you look at all the CMV studies.

Many of them have relatively small numbers, a hundred children or 200 children or something like that.

We need to collect much larger numbers so that we have a really big cohort of children and we can far better understand and look into these issues of, uh, you know, where we might get some clues about genetic susceptibility or whatever.

And, uh, we have set up in Europe, uh, what we call CCMVNet, uh, which is based, uh, on, around, uh, originally the Spanish cohort.

Uh, and Danny Blazquez-Gamero has a brilliant, uh, uh, database, and we're now trying to enroll children and babies from all over Europe, as much as we can, uh, and to try and better understand all the different early biomarkers, uh, and learn more about the outcomes.

How important are the findings on the MRI scan?

What does it mean if you've got cysts or white matter abnormalities, will that lead to more or less issues later on?

We just, we have so much more to learn is the bottom line.

Um, but if we can prevent it well, that is obviously a really good thing.

I'm so grateful for Nuria and Hermione for joining Febrile today and teaching us about CMV.

Please stay tuned for the rest of our Curious Congenital Conundrum series.

This is just the first of four cases on the way.

Our usual disclaimer, all presented patients on this podcast are inspired by patient experiences, but cases are constructed or significantly altered and de-identified for learning purposes.

If you are new to Febrile or haven't checked it out before, please look at our website febrilepodcast.com where you can find Consult Notes, which are written complements of the show with links to references, as well as a library of ID infographics, which you can use to learn and teach others about ID.