Episode 39
39: Curious Congenital Conundrums - Seal of Approval
Drs. Ella Dzora and Jason Brophy discuss a case of congenital toxoplasmosis in the second case of the Febrile “Curious Congenital Conundrums” series.
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Transcript
Hello everyone.
Sara Dong:Welcome to Febrile- a cultured podcast about all things infectious disease.
Sara Dong:We use consult questions to dive into ID clinical reasoning, diagnostics, and antimicrobial management.
Sara Dong:I'm Sara Dong, your host and an adult and pediatric ID fellow.
Sara Dong:Here on Febrile, we use patient cases and consult questions to learn about high yield ID topics.
Sara Dong:We'll present pieces of the story of a patient's case, and then pause along the way to hear from our guest consultant.
Sara Dong:I am excited to welcome you back to our Febrile series entitled Curious Congenital Conundrums.
Sara Dong:This is our second case, and I'm fortunate to be here with Ella and Jason.
Sara Dong:Dr.
Sara Dong:Ella Dzora is a pediatric registrar in South Yorkshire, England.
Sara Dong:She is an interest in infectious diseases in global health, particularly migrant health.
Sara Dong:Our guest discussant today is Dr.
Sara Dong:Jason Brophy.
Sara Dong:He is a pediatric ID specialist and researcher at the Children's Hospital of Eastern Ontario, and an Associate Professor of Pediatrics at the University of Ottawa.
Sara Dong:His research and clinical interests are pediatric HIV and congenital infections, and he also works as a pediatric HIV clinical advisor with a Clinton Health Access Initiative, supporting the uptake and optimal pediatric HIV care in west central Africa and Southeast Asia.
Sara Dong:Thanks so much for being here, guys.
Ella Dzora:Thanks for having us.
Jason Brophy:Thanks very much.
Sara Dong:Uh, I'm so glad you're here.
Sara Dong:Um, before we jump into the case, I always like to do a quick pause and just see if you could share a piece of culture or something that you've enjoyed recently.
Jason Brophy:So I have one, it's not, I didn't enjoy it recently, but I've been thinking a lot about it over the course of the pandemic.
This book called "Polio:An American Story", which I think should be required reading for any infectious disease fellow or physician.
This book called "Polio:Uh, it's about the history of polio in the US, years of this yearly summer pandemic or epidemics, uh, and then the race to find a vaccine.
This book called "Polio:And then people being worried about taking the vaccine.
This book called "Polio:It's very reminiscent of what we're going sounds, and it's really well written.
This book called "Polio:It won a Pulitzer Prize.
This book called "Polio:So.
This book called "Polio:I've given it to our ID fellows as, as Christmas gifts for some time.
Sara Dong:That's a good idea.
Ella Dzora:I've actually just been reading a, a similar book, but, um, a bit broader called Plague's Progress, which charts, um, kind of humanities rise and fall on the background of the different plagues that have swept us through the centuries, which is very, very, very interesting as well.
Ella Dzora:That wasn't gonna be my cultural point, but it was
Sara Dong:You can share another one if you have.
Ella Dzora:Well, I, I I'm actually Scottish, although I, uh, live and work in south Yorkshire at the moment in England.
Ella Dzora:Um, but we had Burns night recently who-- Robbie Burns is our national poet.
Ella Dzora:Um, and it was really nice for the first time in three years, to be able to get together with some other Scots and just have some tunes and some haggis and just reminisce and celebrate actually, uh, you know, being Scottish and getting together and doing that.
Ella Dzora:So that was the first time we've done that in one, it was really lovely.
Ella Dzora:Yeah.
Sara Dong:Oh, that's wonderful.
Sara Dong:I actually had not heard of Burns night before, I will say.
Sara Dong:until one of my co-fellows, uh, suggested one for our fellow group.
Sara Dong:Um, so that's awesome.
Sara Dong:Great.
Sara Dong:Well, uh, I'm gonna throw it over you Ella, to walk us through the case.
Ella Dzora:So our case today, Jason, you receive a consult on the ward for a 23 day old baby who's been admitted with seizures.
Ella Dzora:The infant was flown down from the Northern Canadian territory of Nunavut two days earlier, due to clusters of generalized tonic, chronic movements.
Ella Dzora:A CT head has been done on arrival at your hospital, and that demonstrates intracranial calcifications and ventriculomegaly.
Ella Dzora:And, and the peds team is concerned about congenital infection as a cause of the infant seizures.
Ella Dzora:Can you describe your initial approach in gathering additional history in this case and what you'd be looking for in physical exam to work through your differential diagnosis?
Jason Brophy:Yeah.
Jason Brophy:So these are very interesting consults to get our, uh, trainees very, very excited, cuz they don't come along very often, thankfully, but I think there's a broad history that you would need to consider, but the, the first thing would just be what's gone on during this pregnancy?
Jason Brophy:What kinds of exposures has the mom had, uh, in terms of illnesses, febrile illnesses, mono like illnesses, in particular rash illnesses.
Jason Brophy:You'd also want to know was there any, uh, any findings on her prenatal investigations such as her antenatal ultrasounds?
Jason Brophy:And many of the congenital infections will have some typical findings on these, those antenatal fetal ultrasounds, uh, that can be telling.
Jason Brophy:And that may or may not actually lead to findings later at the time of birth, but maybe clues that we could, uh, have recognized a congenital infection earlier during the pregnancy.
Jason Brophy:We'd wanna know what were the findings at delivery with respect to the, the growth parameters, uh, and things like hepatosplenomegaly or rash or eye findings in particular, uh, head growth.
Jason Brophy:So microcephaly or macrocephaly, and then you would want to know what had gone on with the baby, since birth, uh, if they were growing well, if they were having any, uh, ongoing concerns that had been bringing them to medical attention or that the parents themselves had recognized as being a concern.
Jason Brophy:And then lastly would be a good exposure history.
Jason Brophy:So what's gone on in the mom's life, uh, with respect to her exposures in her environment, as well as her diet and, and in particular, uh, things like food intake that we know has/is associated with, uh, specific infections, like, uh, raw undercooked meat or unpasteurized dairy products, like goats milk.
Jason Brophy:For this, this case in particular, we know that there are some specific cultural practices or cultural habits in terms of eating, uh, with respect to raw meat that we know put, uh, patients at risk.
Jason Brophy:Lastly, I always like to ask about travel because, um, we always think of what's local or what's local to, uh, where the person's coming from, but they may have traveled during pregnancy.
Jason Brophy:We all remember what happened about five or six years ago with, uh, Zika, uh, and how that kind of took over the world, knowing what, well it took over the world in terms of panic.
Jason Brophy:I don't know that we saw that many cases, uh, but having that kind of full history is really important.
Ella Dzora:Uh, just shows how important it is to understand the cultural context that your patients are coming from for those exposures.
Ella Dzora:Yeah.
Ella Dzora:Um, so thankfully the baby hasn't seized since admission.
Ella Dzora:Um, they've been loaded with phenobarbital.
Ella Dzora:The peds neurology team is involved.
Ella Dzora:They've done a basic panel of blood work, including a CBC, electrolytes, renal function and liver enzymes, and that's all come back as normal.
Ella Dzora:The CRP measures 19, blood and urine cultures were taken prior to starting ampicillin, cefotaxime, acyclovir at the Northern referral center.
Ella Dzora:They've done a blood HSV PCR.
Ella Dzora:Um, but an LP was deferred because it was noticed that the child's head circumference was greater than the 99th centile (%ile).
Ella Dzora:When considering congenital infections in the differential diagnosis in a sick neonate, what would your approach be to requesting diagnostic tests and what are other specialties may be required to help you with further investigations?
Jason Brophy:So these patients, it it's very, there's a big tendency to throw the book at them, because there are so many things that it could be, uh, but a differential diagnosis in a case like this would, would take you to specific congenital infections, uh, particularly toxoplasmosis, uh, cytomegalovirus or CMV, other things like I talked about Zika virus, uh, West Nile virus is known to cause congenital infection rarely, but it's been described.
Jason Brophy:More common things like HSV and VZV can affect the brain as well.
Jason Brophy:So, so those are the things we would be thinking about in the infectious world.
Jason Brophy:There's like a, a broad non-infectious differential.
Jason Brophy:Um, but really that should be guided by your initial investigations.
Jason Brophy:And so, uh, for a child like this, you would want to start minimally with having some, uh, head imaging to know what's going on and in terms of the baby's seizing , and in particular , noting that the, that if the head circumference is, is elevated, uh, is there, is there hydrocephalus , happening, which in itself would require further management.
Jason Brophy:And so having, uh, having a good start with head imaging.
Jason Brophy:And head ultrasound is a very nice, uh, modality to start with in that there's no radiation involved and it's actually very good at picking up things like ventriculomegaly and calcifications, uh, as well as other potential things like bleeds, which could be playing a role in a patient like this.
Jason Brophy:We would also, uh, want to think about a lumbar puncture to have the information of what's going on there.
Jason Brophy:Um, especially if, if it's a, a child who presents with additional features like fever.
Jason Brophy:So not to forget the, the more common things like bacterial meningitis, uh, HSV encephalitis, particularly at this baby's age.
Jason Brophy:Uh, and then the, the less common causes of infection, things like Listeria meningitis, for example.
Jason Brophy:Having those initial investigations, depending on what you find in your initial TORCH investigation.
Jason Brophy:So say we do find on that initial workup with, uh, with head head ultrasound, that there is, uh, signs of calcification or hydrocephalus.
Jason Brophy:Obviously we would go on to other imaging like MRI or, or CT scan.
Jason Brophy:CT scan in the past would've been one of the most common investigations because it's very nice at picking up calcifications.
Jason Brophy:But we are more conscious of radiation exposure, uh, at this young age nowadays, and we're more inclined to get an MRI.
Jason Brophy:In a patient of this age, we, we can often bundle them and they would not require a general anesthetic.
Jason Brophy:So these are kind of the practicalities of working up these patients.
Jason Brophy:It's a balance between having the best investigation and having the one that you can get easily, or that has the least, uh, potential complications.
Jason Brophy:If we were to find, calcifications in the head or hydrocephalus, uh, ventriculomegaly, then we would go down the TORCH pathway, thinking about, serologic investigations, mostly, uh, for things like toxoplasmosis, cytomegalo virus.
Jason Brophy:And HSV, VZV, syphilis.
Jason Brophy:And then if there were additional potential exposures, like the travel part, then you think about Zika virus.
Jason Brophy:For CMV and Zika virus, PCR testing is often better investigation, at least if you know that there's been an exposure.
Jason Brophy:Like if the, if the CMV IgG is positive, then you know, that mom had CMV at some point.
Jason Brophy:And then you would want a urine or saliva PCR as the most sensitive test, uh, to have a sense of, if CMV was playing a role.
Jason Brophy:Likewise, for, for Zika virus, we can do, uh, blood or urine PCR for Zika to know if there was a congenital Zika infection.
Jason Brophy:Not a lot of Zika up in Nunavut, being close to the Arctic circle or in the Arctic circle.
Jason Brophy:Um, but, um, but yeah, People travel.
Jason Brophy:So, uh, if that was part of the history, then you would want to look at that.
Jason Brophy:And, and I didn't mention eye exam, but eye exam is very helpful in these patients because so many of these infections have eye manifestations.
Jason Brophy:And so, uh, things like chorioretinitis, uh, either active or healed or inactive, or scarred as well as cataracts.
Jason Brophy:And I've seen all three in, in patients with multiple of these infections
Ella Dzora:And Dr.
Ella Dzora:Brophy, would you mind maybe just touching on, you mentioned about maternal serology, um, but particularly thinking about toxoplasmosis, um, maybe just run us through serology in the neonate and maybe the use of IgA, which is a bit more unusual in toxoplasmosis, maybe than in other infections.
Jason Brophy:Yeah.
Jason Brophy:And so, so we usually start with a Toxoplasma IgG/IgM done locally, uh, which can be done on a number of different standard serology platforms.
Jason Brophy:And, uh, and that could be done on mom and baby.
Jason Brophy:Uh, and that would tell you if there's been toxoplasma infection in the past for mom.
Jason Brophy:Of course IgM doesn't pass from mom to baby.
Jason Brophy:So if a baby had an IgM, uh, that would be very suggestive.
Jason Brophy:And likewise, if mom had an IgM positive, then that would be very suggestive as well.
Jason Brophy:But the problem with, with IgM is (a) it's not very sensitive or not a hundred percent sensitive in infants, uh, they don't reliably make serology responses, especially in the, in premature babies.
Jason Brophy:Uh, that would not be the end of the story in terms of working them up.
Jason Brophy:And the other part is if a mom has an IgM, you, you need to think about the timing.
Jason Brophy:Because, uh, IgM can remain positive for a long period of time.
Jason Brophy:So in a patient like this, where a baby's already born, if the mom had an IgM positive, and we know that it can stay positive for up to a year, uh, then that would be very suggestive that something happened during the pregnancy.
Jason Brophy:But regardless, when you have this setup, you would want to go on to more definitive testing.
Jason Brophy:For most of us that requires sending it out to a reference lab.
Jason Brophy:The most common lab that's used is the, the laboratory in California, which provides really detailed serology, including IgA , which is a very sensitive test for toxoplasma.
Jason Brophy:It provides the reference IgM ISAGA uh, which is also very helpful.
Jason Brophy:And then you can compare mom and babies, uh, IgG, uh, titers with the dye test.
Jason Brophy:Uh, and as we say with most infections, uh, congenital infections, if baby has a fourfold higher titer of IgG than mom, then that's very suggestive.
Jason Brophy:Lastly, we can do PCR tests on amniotic fluid during pregnancy on placental tissue, uh, on baby CSF or blood.
Jason Brophy:Uh, I've seen it offered on urine as well.
Jason Brophy:And all of these are very helpful.
Jason Brophy:If we were getting involved during the pregnancy prior to the delivery of the baby, uh, and say it was either a setup where we knew mom had an exposure or mom had a, a suggestive illness, like a, uh, mononucleosis type illness, for example, or eye disease.
Jason Brophy:And we were thinking about toxoplasma and mom had positive, uh, serologic testing with IgG/IgM, then you can do the avidity testing on IgG, which, uh, gives us a sense for the timing of the infection.
Jason Brophy:Uh, and if predated the pregnancy, if there was high avidity versus, um, if it was likely in the last four months of pregnancy, uh, in the case of low validity.
Jason Brophy:And so that would be very helpful.
Jason Brophy:And then you need to figure out what is going on with the baby.
Jason Brophy:And so, uh, if the baby has no findings on ultrasound, then you don't know, has the infection happened yet or not?
Jason Brophy:So having an amniocentesis at, it's recommended at, at, or after 18 weeks, ideally to tell us if there is, uh, already congenital infection or not.
Jason Brophy:That is the recommendation when we know that a mom has had an infection of pregnancy.
Ella Dzora:Thank you.
Ella Dzora:That's really comprehensive.
Ella Dzora:That's great.
Ella Dzora:Um, so back to our case, uh, the general peds team, uh, has helped to arrange some diagnostic testing of the infant, including getting a neurosurgical consult and an urgent MRI is scheduled and that confirms severe hydrocephalus.
Ella Dzora:And, uh, so the neurosurgical team have placed an emergency shunt.
Ella Dzora:CSF from the shunt demonstrates an elevated protein of 1.9 g/dL, and further testing reveals a normal CBC, normal electrolytes, liver enzymes and bilirubin.
Ella Dzora:Toxoplasma serology is positive, so the dye titer is 1:256 and the IgM is positive.
Ella Dzora:Moms current toxoplasma serology is 1:64.
Ella Dzora:Blood toxoplasma PCR remains pending at present.
Ella Dzora:It's been sent to the reference lab.
Ella Dzora:Um, and unfortunately, no maternal lesion serum samples or placenta remains for testing.
Ella Dzora:The audiology exam is normal, uh, but ophthalmology exam, uh, reveals a large active retinal lesion, just adjacent to the fovea of the left eye.
Ella Dzora:So, Dr.
Ella Dzora:Brophy, can you discuss your approach, uh, to treatment of congenital toxoplasmosis?
Ella Dzora:How do you approach treatment discussions with your patient with parents?
Jason Brophy:The treatment of congenital toxo is a bit fraught in that, um, it's a, I usually introduce it to parents as being tough.
Jason Brophy:Uh, it's a very long treatment course, uh, in that they're, they should be treated for one year and it requires multiple medications with side effects that require at minimum, blood work monitoring.
Jason Brophy:And so, in a case of moderate to severe infection in a, in congenital infection, you would want to use a combination of pyrimethamine and sulfadiazine, and these are, uh, two medications that have been shown to work best for congenital infection.
Jason Brophy:In other scenarios, uh, like in adults with reactivation disease or, uh, with toxoplasma lymphadenitis, other other forms and there are, uh, other options for treatment, including trimethoprim sulfamethoxazole, uh, clindamycin and macrolides.
Jason Brophy:But in this setting of congenital infection, uh pyrimethamine and sulfadiazine are their recommended treatments.
Jason Brophy:Both of them can have side effects of, of, uh, marrow suppression, pyrimethamine in particular, causing anemia, macrocytic anemia, uh, and sulfadiazine in particular causing neutropenia.
Jason Brophy:We usually, uh, recommend in addition to these two medications, the addition of folinic acid or leucovorin three days a week, and that will help reduce the, the risk of pyrimethamine associated anemia and, and marrow suppression generally.
Jason Brophy:Uh, but these three medications need to be monitored closely with blood work, including complete blood count, as well as liver and renal screening for proteinuria, uh, as a side effect of pyrimethamine.
Jason Brophy:So it's recommended to do those more frequently in the first month of therapy and then, um, a monthly for the duration of the 12 months of treatment.
Jason Brophy:Uh, sulfadiazine is, uh, before you start it, you should check for a G6PD deficiency, uh, in that it's one of the G6PD triggers and, um, the medication dosing should be followed closely along with the child's weight over time.
Jason Brophy:One significant issue that has really plagued us, over the last number of years.
Jason Brophy:Not only in Canada, but in multiple countries around the world is, is a lack of these medications availability, uh, in particular sulfadiazine and so for example, we don't have, uh, any companies that make that product in Canada.
Jason Brophy:So we need to go through, through our federal regulatory agencies to bring in products from other countries.
Jason Brophy:And this is often a very difficult, uh, endeavor in that, uh, they're not made by very many companies.
Jason Brophy:It's not a very lucrative product I think, uh, and that is part of the, the issue.
Jason Brophy:And there's often a delay for us in terms of getting to start these medications because of these access issues.
Jason Brophy:And it, it really, I, in my mind, this is an advocacy issue for us in pediatric infectious disease.
Jason Brophy:In that these are, uh, medications that are the treatments of choice for this very severe infection at times.
Jason Brophy:And, uh, we need to have secure access for our programs.
Ella Dzora:And can I just clarify something you said earlier that if there was a suggestion that mom had, uh, exposure, you might do an amniocentesis at 18 weeks.
Ella Dzora:If that showed a potential infection, would you start treatment at that point?
Ella Dzora:If so, would it run for a year, from 18 weeks gestation or a year after delivery?
Jason Brophy:Right.
Jason Brophy:If a mom is diagnosed with acute toxo in pregnancy, uh, and that, like I said, those diagnoses can come in a variety of ways, either mom with an illness, uh, that triggered testing, um, mom with a finding on ultrasound that triggered testing, mom with a known exposure, uh, say to, cat feces, which I, I failed to mention earlier, which was the one that, the one thing that everybody knows, uh, about
Ella Dzora:It's probably in this side of the pond is definitely the bigger exposure compared to raw meat, I think.
Jason Brophy:Yeah.
Jason Brophy:Yeah.
Jason Brophy:And, and I have to say in, in the past, in patients who are local, like who haven't traveled, then the main risk factor is, uh, if they have a cat and they changed their litter before they knew they were pregnant, uh, or.
Jason Brophy:The, the main, the main, uh, risk factor I've always found in those patients is not so much that because everybody knows you're not supposed to change cat litter when you're pregnant.
Jason Brophy:Uh, but rather gardening.
Jason Brophy:And so I usually tell moms, uh, that, uh, uh, your garden looks like a giant litter box to a cat so, so there's, uh, that's like the main factor that are identified in local cases.
Jason Brophy:Uh, and those that have traveled, like to, um, to Africa in particular south America, uh, or our Northern patients, it's more often eating exposure that, that we suspect.
Jason Brophy:Um, but yeah, I, if we do make that diagnosis in pregnancy, uh, before the amniocentesis, if there's no suggestion of an infection, uh, on the imaging, then the fetal imaging, then you would put the, start the mom on spiramycin, which is a macrolide that we know will prevent infection from passing from mom to baby.
Jason Brophy:Cuz the risk of transmission early on, uh, is, is lower, but with more grave side effects, uh, or, uh, sequelae in the baby vs later in pregnancy, uh, we know that the transmission risk is much higher though with often less effect on the baby, if it happens on the third trimester.
Jason Brophy:So spiramycin until your amniocentesis is complete.
Jason Brophy:If the amniocentesis is negative, then the mom would be recommended to continue her spiramycin until delivery.
Jason Brophy:Uh, if on the other hand, the amniocentesis suggests the fetus is infected, then the recommendation would be to switch to sulfadiazine and pyrimethamine.
Jason Brophy:And I haven't had that scenario before where, uh, a baby did, uh, get that treatment prenatally.
Jason Brophy:Um, but my understanding is that the fetus should be treated for a year or the newborn to be treated for a year postnatally.
Ella Dzora:Thanks for clarifying that.
Jason Brophy:And then the last, the last thing I didn't mention with the, the treatment is anti-inflammatory or steroid therapy.
Jason Brophy:There are two criteria for the addition of a steroid like prednisone or prednisolone.
Jason Brophy:Uh, one would be if there's active eye disease and the other would be, if there is a very high protein level in the, the, uh, CSF.
Jason Brophy:Criteria would be, uh, one g/dL, um, or 10 g/L.
Ella Dzora:Good.
Ella Dzora:Thank you for that.
Ella Dzora:Um, so yeah, so our baby, um, is started on pyrimethamine +sulfadiazine uh, and some prednisolone for the significant eye disease, folic acid, as you said to cover up the marrow suppression and remains really stable.
Ella Dzora:So the general peds team is considering discharge.
Ella Dzora:What follow up would you, you recommend in that situation?
Jason Brophy:The followup should be quite close, uh, over time, be that with the infectious disease, uh, clinic or, uh, their primary care or pediatric, uh, care.
Jason Brophy:Sometimes we'll do a shared care model if they're, uh, far from the hospital, such as in the Arctic.
Jason Brophy:We would recommend the regular monitoring of, for those toxicities, uh, through blood work, uh, as well as close monitoring of their weight so that we can make dose adjustments.
Jason Brophy:I usually make a dose adjustment if, uh, there's been a 10% increase in the weight.
Jason Brophy:Uh, so that, uh, they're never outside of the 90% of their recommended, uh, dosing.
Jason Brophy:The steroids can be tapered, if they've been started, once the active eye disease resolves.
Jason Brophy:I've never had to do a repeat lumbar puncture to reassess protein.
Jason Brophy:But that would be, uh, I think it would be reasonable to, to wean the steroids after, uh, a certain period of time and, and notable improvement.
Jason Brophy:And obviously these patients need close follow up from, from the point of view of their eye disease.
Jason Brophy:If they have active eye disease, uh, some of them may develop cataracts.
Jason Brophy:It may require surgical intervention.
Jason Brophy:And then obviously neurologic and neurodevelopmental follow up, uh, so that we can identify any, uh, any problems that may arise and intervene as soon as we can with respect to therapies, speech therapy, uh, audiology, your hearing assessments would be very important as well, uh, to make sure that they can hear.
Jason Brophy:And if hearing is an issue, uh, then making sure that they have augmentation so that we really, I usually frame it to the families that we want to, we want to give them the best shot at being the best version of themselves.
Jason Brophy:And so, uh, many of these kids will have sequelae with respect to vision or hearing or, uh, neurologic function.
Jason Brophy:So when we can intervene early with, um, with therapies like occupational or physiotherapies or, um, supporting their mobility with respect to gross motor dysfunction, support their vision so that they can see and learn, um, likewise support their hearing so that they can hear and learn.
Jason Brophy:Um, then that is the best that we can do for them, and they can be the best versions of themselves.
Ella Dzora:And can I ask, uh, we don't have potentially the, um, as big a geographical area that we're covering as you over in England, how much-- cause it's quite a big burden of treatment for these kids.
Ella Dzora:How much would you expect of that to happen locally in the Northern territories and how much would they have to travel for?
Jason Brophy:Yeah.
Jason Brophy:So unfortunately I've had several of these patients over time.
Jason Brophy:We try to be as, um, efficient as possible.
Jason Brophy:And so, uh, I tend not to bring them back to see me alone.
Jason Brophy:I, I prefer to have combined follow up with other specialties.
Jason Brophy:So if the ophthalmologists or the neurosurgeons if they have, uh, shunts, uh, or the neurologists, uh, if they have neurologic complications like seizures, uh, I try to do a, a combined follow up with them.
Jason Brophy:And so typically we would wanna see within a couple of months of discharge, minimally, uh, and then again, usually at three to four month intervals for the course, the, of the follow up.
Jason Brophy:Um, here we're a bit lucky in that some of our specialists do traveling clinics and they go up to the Northern territories.
Jason Brophy:So patients don't have to travel quite as far.
Jason Brophy:So one 2-hour flight instead of two 2-hour flights uh, or three hour flights.
Jason Brophy:Um, We try to be as practical as we can.
Jason Brophy:And with the advent of virtual care, it's really made a big difference.
Jason Brophy:So doing, having that shared care model where we're supporting their, their local practitioners, or, uh, say their pediatrician who flies into their community, than it does help, um, make what's a very difficult situation, a bit more bearable for the families.
Ella Dzora:And just one more thing to clarify, cuz the eye disease can flare up, particularly adolescents and later in life.
Ella Dzora:If the eye disease was quiet in that first year of, of life, how often would you have to follow it up or would you wait till they had symptoms?
Jason Brophy:Yeah, so I usually defer those decisions to ophthalmologists.
Jason Brophy:I don't like telling people what to do.
Jason Brophy:Um, but, but generally they want to see them on a regular basis, like on, uh, I, I think if they're local, they'll see them more closely.
Jason Brophy:They'll follow 'em up more frequently.
Jason Brophy:Uh, but I think minimally on a yearly basis, especially when they're young and maybe can't verbalize their complaints.
Jason Brophy:But yeah, the expectation with congenital infection is that, there's definitely a risk for future reactivation of eye disease.
Jason Brophy:And that that risk is higher if, uh, they haven't been treated, like if the congenital infection wasn't diagnosed at the time, then it's very high risk of, of reactivation over their lifetime.
Jason Brophy:That varies according to the geography or serotype or subtype of, of, toxo.
Jason Brophy:Uh, the South American versions tending to be more aggressive, uh, than the, than the European versions.
Jason Brophy:Um, don't think we understand that as well for our Arctic versions.
Jason Brophy:Um, but, um, the, that follow up over time should.
Jason Brophy:Should be there.
Jason Brophy:And, and typically the, the bigger risk would be re reactivation usually in adolescents.
Ella Dzora:Thanks.
Ella Dzora:Um, so our neonate has done really well and the parents are shown how to crush and dissolve the medications for administration and infectious diseases follow up is arranged.
Ella Dzora:Mom's really keen to, to return to her home community as she has three older children at home.
Ella Dzora:And she's quite overwhelmed being so far away from home and alone and away from her family.
Ella Dzora:So infectious diseases, neurology, ophthalmology, audiology, and neurosurgery follow up is arranged and interim telehealth communication, as you suggested, is arranged to assess the progress.
Ella Dzora:Follow up drug toxicity blood work is arranged locally and at telehealth follow up three weeks later, mom asks whether or not this infection could have been prevented.
Jason Brophy:So that's a very good question.
Jason Brophy:We know that some jurisdictions of the world, uh, have prenatal testing that's routine for all.
Jason Brophy:So that it's most commonly known in France, owing to their culinary proclivities, um, but in my experience, we, in, in Ottawa, we have a lot of, a lot of migrants from, uh, Francophone Africa as well as, uh, places like Morocco and Lebanon.
Jason Brophy:Uh, and it's interesting where most of those places have toxoplasma screening practices, very similar to France because they were influenced by French through colonization over time.
Jason Brophy:In those, in those, uh, environments or jurisdictions, toxoplasma screening in pregnancy is routine.
Jason Brophy:Uh, and what tends to happen is you have a toxoplasma test during, uh, your initial intake into prenatal care.
Jason Brophy:If you're seropositive with an IgG positive and an IgM negative, then you'd be clear, in the clear.
Jason Brophy:If your IgG negative, then you'll be recommended to have, uh, repeat follow up over time and ideally a good counseling around what would be the things to do during pregnancy to reduce your risk, uh, primary infection during the pregnancy.
Jason Brophy:So, interestingly we, because we've had had, uh, several cases, uh, in Nunavut over the last few years, we're actively in the process of introducing a prenatal, uh, screening program up there.
Jason Brophy:The population is very small.
Jason Brophy:The number of births per year is something around 500 to 800, uh, depending on how much of the territory you're including.
Jason Brophy:But we have a high number of cases, uh, and it makes sense because there's increasing research showing that it it's not, it's not cat exposure up there.
Jason Brophy:There are no cats in the Arctic, uh, region, um, or well, I guess there are probably some domestic ones, uh, but there are no wild ones.
Jason Brophy:But we know that, uh, a number of animals that are consumed including marine mammals, like beluga and walrus and seal, well as, uh, ungulates like caribou, uh, and there's some findings from local researchers that show that, uh, some fish have, uh, evidence of, toxo uh, char and salmon and then Arctic goose as well apparently have toxo.
Jason Brophy:So, uh, it just tells you that, um, We need to do a, a better job of counseling in pregnancy, uh, because serology's only gonna tell you if there's a problem.
Jason Brophy:Primary prevention would be much better than secondary prevention.
Jason Brophy:And so, yeah, as you said, if we do identify, uh, some, a woman with a primary infection of pregnancy then would use the medication approach of spiramycin, uh, and then if, uh, fetal infection confirmed sulfadiazine/pyrimethamine.
Jason Brophy:And then, like I mentioned, the, the counseling part of, of when the mom's infection happens, uh, really dictates the risk of infection to the fetus with a lower risk of infection in first trimester.
Jason Brophy:But if that infection does happen, uh, then a very high risk of serious congenital anomalies, like brain and eye disease.
Jason Brophy:Uh, whereas if the primary infection happens later in the pregnancy, then the risk of transmission is quite high.
Jason Brophy:Um, but the risk of, uh, disease or obvious, uh, clinical sequelae in the child is lower.
Jason Brophy:That's presuming that you'll make the diagnosis and treat the child once they're, once they're born.
Ella Dzora:I think the CDC website gives prevalence in 14 to 44 year old women as 9%, but that's across the states.
Ella Dzora:Presumably there's hugely wide regional variation within that as you've highlighted.
Jason Brophy:Yeah.
Jason Brophy:I think we know, uh, at least in, in certain parts of the world, like, um, central Africa, uh, those rates can be like 50, 60, 70, even 80% reported.
Jason Brophy:I think it really varies around the world and according to cultural practices around food and what you do or don't do while you're pregnant.
Ella Dzora:That was really thorough.
Ella Dzora:Thank you very much.
Ella Dzora:To end, I just wanted to ask if there's any other kind of important points that you've not already highlighted that you'd like to just bring to our attention about congenital toxoplasmosis or other congenital infections in general.
Jason Brophy:Yeah, I it's interesting.
Jason Brophy:I find that there's such a, a wide range of parents, um, level of concern, right?
Jason Brophy:It ranges.
Jason Brophy:It's all natural.
Jason Brophy:I'm not gonna worry about anything to, uh, like a high level of anxiety, uh, and not knowing, uh, what, or if you can do anything during pregnancy.
Jason Brophy:It's, it's good to be, uh, rational.
Jason Brophy:Uh, and I think it's good to provide, uh, good prenatal counseling around high yield things.
Jason Brophy:And so with toxo, uh, it's around primary prevention strategies, like don't, don't take in, uh, raw or rare meats, avoid unpasteurized dairy products, like goats milk.
Jason Brophy:If you do garden, then please wear gloves and wash your hands while after you've done.
Jason Brophy:So, um, and if you have a cat, uh, consign your partner to, to that, in the pregnancy
Ella Dzora:and, and ongoing.
Sara Dong:Yeah.
Jason Brophy:Thank you very much.
Jason Brophy:Um, but then other other things like, uh, I didn't touch much on congenital CMV, but, uh, in my mind, that's one area that we don't talk about nearly enough in pregnancy and that, uh, literally almost every child with congenital CNV I've ever seen, uh, has a two year old sibling at home who's in daycare.
Jason Brophy:And so we know who to target our primary prevention strategies towards, and I don't think we're doing it.
Jason Brophy:And when we look at the other types of, um, infections that we screen for, or counsel around during pregnancy, uh, they're much lower prevalence than CMV.
Jason Brophy:And, uh, I think we need to do a better job on, on that particular congenital affection.
Jason Brophy:Here in Ontario, we've introduced a, an enhanced hearing screening program that includes CMV testing for every child born in the province.
Jason Brophy:And so we've identified, um, like a tenfold or even higher numbers of infants with congenital CMV over time.
Ella Dzora:That's huge.
Jason Brophy:And, and just like, just like with this case where the mom asked, um, why didn't I hear about this?
Jason Brophy:Or, or what could have been during the pregnancy?
Jason Brophy:That's what every mom asks me, like, except for except for moms who are healthcare workers or microbiologists.
Jason Brophy:No one else has ever heard of CMV uh, unless you've had, you've been touched by it in your own household already.
Jason Brophy:And so I think we need to do a better job of, of talking about these things, uh, and making it routine.
Sara Dong:Well, thank you guys, both so much for being here today.
Sara Dong:I learned a ton and had a lot of fun.
Ella Dzora:Thank you so much for having me.
Jason Brophy:Yes.
Jason Brophy:Thanks.
Jason Brophy:I appreciate it.
Sara Dong:Thanks to Ella and Jason for this great discussion on congenital toxo.
Sara Dong:Please stay tuned for the rest of our Curious Congenital Conundrum series.
Sara Dong:You can find the introduction and case one in our previous episodes and be on the lookout for our third and fourth cases coming up next.
Sara Dong: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.
Sara Dong:If you are new to febrile or haven't checked it out, I encourage you to take a peek at our website febrilepodcast.com to find Consult Notes, which are written complements to the show where there are links to references as well as our library of ID infographics that you can use to learn and teach others about ID.
