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 are joined by a team from Sultan Qaboos University in Muscat, Oman.

First up, I'll introduce Dr.

Raghad Al-abdwani, who is a Senior Consultant and the Head of the Pediatric Intensive Care Unit.

Hi, it's Raghad.

Thank you very much for having us here today.

Next we have Dr.

Badriya Al Adawi, who is a medical microbiologist.

Hi, this is Badriya, thank you for having us today.

And rounding out our team, we have Dr.

Zaid Al Hinai.

Zaid serves currently as the Head of the Pediatric ID Unit at the Child Health Department.

This is Zaid.

Thank you for hosting us.

All right.

So as everyone's favorite cultured podcast, we always like to start by asking if folks would share a little piece of culture, really just something non-medical that brings you happiness.

So I have a particular knack or interest in hiking, trekking, abseiling.

And though I've done a number of international tracks, like, uh, Machu Picchu, Kilimanjaro, Everest Base Camp, but, Oman itself offers a lot of really beautiful mountains and caves and a number of very challenging canyons.

So sometimes people ask me like, don't you get enough adrenaline, uh, in the PICU?

But I always say to them that the adrenaline in these adventures are quite different.

And I see it as a way to help in like, um, you know, pressing the reset button.

Love it.

I don't know, I feel like the, um, the extreme hiking and PICU in my mind goes together perfectly.

It does.

It kind, it balances each other how I see it.

Um, so for me, I enjoy going back to my hometown Nizwa and, uh, a few months ago, I went with my kids and we went to the fort, the Fort of Nizwa.

And it was an amazing feeling.

I haven't been there for a very long time, so just walking around with my kids, it was just like, really, I cannot describe the feeling.

It felt like I went into a time machine with my kids and went, went to the past.

So it was really, really great.

That's lovely.

Mm.

Okay.

Uh, for me, actually, one thing that's really nice about living in the Middle East is the food.

There is like this really ancient recipes that have been perfected over like thousands of years.

And so, uh, I really enjoy learning some of these really old recipes.

Like ones my grandmother would, would have made.

I did learn, actually, one of the Middle Eastern recipes is a Palestinian recipe called, uh, musakhan.

Musakhan in Arabic just means something that's warmed up or cooked.

This one is really uniquely Palestinian and it's got this, uh, unique ingredients, onions and chicken.

Not, not very unique, but then they put sumac, which is a very, uh, unique Middle Eastern, like, kind of, uh, tangy, a sour spice.

And, uh, I, I learned how to make it, and they make it usually with bread.

And knowing me, like I always like to put a twist on things.

So what I did is I made it in a pie.

And that's from my years in America, put all this chicken into a pie and it came out really good.

I had good beginners luck on that.

You're going to have to share that with us Zaid!

that sounds really good.

Well, I think I've, I think I've told people on the podcast before, but, um, I love cooking and learning about cooking.

And I originally wanted to find some way to tie it in where people brought a recipe or a dish that they like to just talk about.

Um, but I couldn't find something clever to tie them together.

But I still have a special place in my heart for when people bring recipe or food related things as their culture.

Well, we have a very interesting case today.

I think Raghad is gonna, um, introduce us to the patient who's shown up in the hospital.

Yeah, so we started off with a PICU team visiting the emergency department.

Uh, we went to see a 4-year-old boy with sickle cell disease, Hemoglobin SS, on hydroxyurea and he had presented to the emergency department with a five day history of fever and fatigue, which was just getting worse over the days.

He even then started having significant abdominal pain.

He vomited a couple of times and he was looking quite pale to the parents.

And even had a yellowish discoloration as they described.

So they took him to the local health center just a day prior to presenting to us, and they did a CBC at that time, which showed that the hemoglobin was 5.4 grams per deciliter.

So basically much lower than his baseline, which is about eight or nine grams per deciliter.

So in the emergency department, um, the child appeared quite pale.

He was jaundiced and drowsy.

He was quite tachycardic with heart rates in the 160s, tachypneic and desaturating with sats of 85% in room air.

But with giving him supplemental oxygen, it was above 95%.

What was striking is that he was extremely cold to touch and he had poor peripheral pulses and delayed capillary refill of about five seconds, but his blood pressure was actually normal, normal high, even 120/70.

So when examined his chest, he had a hyperdynamic precordium and he had an ejection systolic murmur at the apex, but good air entry bilaterally with no added sounds.

His abdomen was very, very distended and it revealed also a very tender big liver, palpable at 15 centimeters below the costal margin.

But we couldn't palpate, uh, spleen, which is, you know, what we tend to see in those patients.

Um, he was drowsy and irritable, but he didn't have any meningeal signs and he had no apparent focal neurologic deficits.

We examined his ears, his nose, and his throat, and they were unremarkable.

Now in the emergency department, we have access to a blood gas machine.

So we did a venous blood gas, which showed that he had severe anemia with a hemoglobin of 2.3, and he had severe lactic metabolic acidosis.

So his pH was 7.05.

His bicarb was seven with a base deficit of 15, and his lactate was 22 milli moles per liter.

So taking all that into consideration our impressions that we've got a 4-year-old boy with sickle cell disease and he had shock and take into consideration that these kids are prone to encapsulated organisms, and the fever, you know, we thought along the lines of septic shock, and likely a sequestration because of the severe anemia plus minus a sickle cell, uh, crisis.

And of course, we were yet to look for evidence of multi-organ dysfunction.

So just a little about his past medical history.

As I mentioned, his sickle cell disease, and he had history of previous admissions because of vaso-occlusive crises and needs for blood transfusion.

But in the past, one year after starting hydroxyurea, the frequency of his admissions were much less.

So Zaid, now with all the above, are there any other additional information that you'd like to know about the patient?

Yeah.

So it sounds like the child is in the critical condition, septic shock.

There's some liver involvement.

You guys did a great job to look at a lot of the uh, systems that could be involved.

Uh, we also would like to know a little bit if there's any skin manifestations or joint manifestations in this child.

Uh, from the ID point of view, we always like to ask about exposure history, very important.

So, where does he live?

What kind of setting?

Was there anybody sick that he could have uh, been in contact with?

Did he travel anywhere?

Uh, does he, do they have any pets?

Do they, uh, go to any farms?

Is there any other animal exposure?

Do they consume un pasteurized dairy products or undercooked meat?

Is there anybody with tuberculosis potentially?

And did he have any insect bites or tick bites or mosquito bites?

And did he go swimming anywhere?

What is the water source?

Mm-hmm.

So, you know, it's interesting you mentioned that 'cause we did notice at that time that, you know, he had these multiple round hyper pigment, hyperpigmented macular rashes of about, I would say, two to three centimeters in diameter in his upper, but especially in his lower extremities, especially like in the pretibial, the bony prominences areas.

But, you know, uh, taking the nature of his dark skin, it was really hard to tell that time if these were bruises or there were insect, uh, like healing insect bites or maybe a rash of a different etiology.

It's not unusual that we see these dark pigmented, uh, spots in kids, generally speaking here with dark skin.

But his joint examination was otherwise unremarkable.

But in terms of exposures, um, he does live in a rural area of Oman in a house with a nearby farm.

But the parents, uh, upon asking them, had mentioned that they couldn't remember any history of contacts with any animals or cattle or birds, but they did say that he does get occasional ticks or mosquito bites.

Um, nothing about unpasteurized products that they had taken.

Um, and water source, they usually have like drink from bottles, bottled water.

Um, and there was no history of any recent travel.

His immunization was up to date.

The thing is, we, as you know, we have a really good immunization program in Oman, and locals tend to really adhere to it, uh, fortunately.

In terms of family history, I would say that, um, there wasn't anything that was really remarkable except from another, another family member who also has sickle cell disease.

And in terms of the immunizations, did he get any of those special immunizations additionally for sickle cell disease, like the pneumococcal vaccine?

Yes.

So, I mean, you know, again, it's integrated as part of what we have in the health centers.

Um, I'm really proud actually, of our immunization program here.

So yes, he, he, he did.

Um, so Zaid, I mean, take into consideration, you know, that impression of the septic shock and all this history into account, what infections do you think would be, uh, a likely cause over here?

I mean, this child is coming in very sick.

He's coming in from the community.

Uh, he's been progressively sick over five days.

You have to think about common things being common.

Um, as you mentioned, they can be susceptible to Streptococcus pneumonia, um, and salmonella in particular with, with sickle cell disease.

So those would be pretty high on the differential as far as septicemia.

Additionally, other organisms like Staph aureus, Haemophilus influenzae, Neisseria, should be in consideration.

Cholecystitis can happen in sickle cell disease and maybe that can, uh, perhaps, uh, predispose to septicemia and bacteremia.

I think although it's, it's looking more like a very acute maybe bacterial infection, they probably could be a respiratory virus involved, especially some viruses that have, uh, tropism to the liver.

Since the liver here is uniquely addedly involved.

So I would think about Enteroviruses, adenovirus, influenza, COVID, uh, EBV, uh, maybe some other herpes viruses, although we don't see specific, uh, vesicular skin manifestations, like for varicella or herpes simplex?

I think the hepatitis viruses definitely would think about, at that time that this child presented the Hepatitis A, uh, vaccine hadn't yet been in the schedule, it is now.

Um, so that was something that we would see from time to time.

Never discount something like HIV as being maybe potentially part of this, or, or dengue.

And dengue also is mosquito-borne illness.

There's a history here of insect bites.

And at that time, again, dengue was not an issue in, in, in Oman, but now has become endemic, so now we have to think about it.

So those would be, I think, the most common places to start.

You always have to keep an open mind though for other things, potentially fungal, although I can't think of much there, maybe histoplasmosis or uh, atypical bacteria.

Mycoplasma does tend to cause more significant disease and sickle cell disease and other rickettsia, Brucella, Q fever, tularemia leishmania.

Uh, mycobacterial, TB, parasitic, malaria.

Um, malaria would be, I think, an important differential, although we don't have much local transmission at all in Oman, usually always, uh, associated with travel.

But, it can also be always a consideration.

So, uh, besides that, maybe after infection, you, you should think about maybe some autoimmune diseases, uh uh, or, uh, maybe could this be an unusual presentation of MIS-C or Kawasaki?

But I think those are less likely possibilities.

Right?

Yes.

Thank you.

So, you know, at that point of time in the emergency department, we immediately started management.

So, you know, your usual ABCs, oxygen therapy, we gave him a small fluid bolus.

Not too much because we don't want him to go into heart failure when his hemoglobin is already 2.3.

Um, we started him with small aliquots of blood transfusions.

He got three small aliquots of packed red blood cells and again, small and slow to avoid heart failure.

Uh, we ended up intubating him, uh, with mechanical ventilation, taking to consideration, you know, his shocked state, uh, severe lactic acidosis.

His abdomen was quite distended, so, you know, compressing on his lungs.

Um, and also he was in a lot of pain and needed narcotics.

So, you know, that would make him even drowsier.

So he was intubated.

We sent off all the routine labs as well as, you know, those looking for multiorgan dysfunction, but also, those needed for looking for sepsis, inflammatory markers, cultures.

Blood, urine, tracheal secretions, you know, taking the fact that he was initially, um, tachypneic and desaturating.

We sent off the respiratory viral panel, mycoplasma PCR, in some serologies, as you'd mentioned.

EBV, CMV, HIV, and hepatitis especially because he was jaundiced and had a tender large liver.

Of course it was started on broad spectrum antimicrobials, so cefotaxime, vancomycin, and a, a dose of amikacin as well.

And that's when we started getting the lab results back.

Um, his, uh, CBC showed again, confirmed the hemoglobin of 2.3 with a reticulocytes percentage of 4%.

Um, he had some leukocytosis of 18.6.

Of which 34% were neutrophils, and he was thrombocytopenic, 73,000.

His CRP was quite elevated at almost 350, and his liver transaminases were quite high.

Um, his ALT was almost a thousand units per liter and AST was 4,200 right off the bat.

Um, he had hyperbilirubinemia.

Most of it was direct, some hypoalbuminemia 37, not too, too bad.

And he had some coagulopathy.

His INR was 1.6 with D Dimers of 12.9, but his electrolytes and renal parameters were normal.

His chest x-ray was unremarkable and his abdominal x-ray didn't show any evidence of perforation or intestinal obstruction.

You know, take into consideration that significant abdominal pain that he had.

So we did a quick bedside echo and it showed that ejection fraction was about 50%, so, you know, the lower side of normal.

So taking all the above, our findings confirmed that, you know, our initial thought that this is severe anemia, septic shock.

Um, and he had what, like it looked like hepatic sequestration with some multiorgan dysfunction.

And we took him for a quick CT, which which actually confirmed the evidence of hepatic sequestration.

So, um, we took him to the ICU after that.

We worked really hard on him for the first couple of days, and then the next like 24 to 36 hours, you know, by then we had raised his hemoglobin to his baseline.

He, after topping him up, we gave him an exchange transfusion as well to make sure his hemoglobin S levels were okay.

We made sure he was well volume repleted.

He was already on broad spectrum antimicrobials.

He was on a good amount of sedatives, analgesics.

He was supported with a ventilator and his blood gas is even normalized, but something was off because we noticed that at that time he was still really, really tachycardic even when he was afebrile.

And he was still quite vaso constricted and really cold to touch.

And we even started him on milrinone, which is, uh, as intensivist.

We call it an inodilator.

It helps with, uh, inotropy with a contraction, but it also helps in vasodilating and, you know, warming them up.

Um, we noted that he continued to have high fever, and also his inflammatory markers continued to rise.

It even reached to 500.

And so, although with the other biochemical profile, like his blood gases, the electrolytes were all fine, but his clinical picture wasn't still okay, and something just didn't feel right.

So at that point of time, I picked up the phone and I called my friend from the ID team Zaid, and I said, you know, Zaid, you know, are we missing out on something?

Should we be investigating for anything else?

Should I be adding another antimicrobial?

I can't put my finger on it.

But I feel something is not right.

So what did you say, Zaid?

Yes, I, I totally agreed at that point.

I remember driving into work that morning and this child was on my mind.

And I went first into the ICU before any morning meetings to see what is going on with this child, because, uh, he's quite critical.

Uh, he's maintaining his blood pressure, but extremities are very cold, um, turning dusky.

His laboratory parameters are not really improving and it's only been 24 hours.

But as you said, something really doesn't seem quite right with this child, and he's very, uh, critical or very worried about him.

Um, I was relatively new as an ID consultant and uh, I was really starting to panic a little bit.

Um, and, uh, and, um, so at, at this point, you know, we talked about, uh, atypical causes, like mycoplasma, rickettsia, things like anaplasmosis and ehrlichiosis, Rocky Mountain Spotted Fever.

These exist in the eastern coast of the United States and the northeast areas, maybe some other areas as well.

Uh, but, uh, we haven't, we don't see them so much in Oman, but in my training back in the day, going back to, um, our mentors, Dr.

Penelope Dennehy, uh, she taught us that, you know, you, you gotta think about these things in such situations, and you gotta also think about empiric doxycycline.

Um, in, in our mind, we, I tried to look around and, call for some help.

Um, and, uh, and there are some atypical bacteria and rickettsia-like, uh, organisms and, and more things that can involve the liver as well, and not respond to the usual empiric antibiotics like brucellosis, Q Fever possibilities for tularemia leishmaniasis.

Maybe syphilis, uh, is, uh, would be quite acute, but unusual presentation for that.

So, I decided to recommend to start empiric doxycycline and also call my good friend Dr.

Badriya from the microbiology lab to help me because we're really worried about this child and we're not making the progress we'd like to make.

So, Dr.

Badriya had some good ideas as well.

Yeah, so I actually bumped into Zaid while I was running to a meeting and, he expressed his concern about, uh, this child and lots of investigations were already done and some were already negative and some were still pending, but nothing positive so far.

So Zaid was particularly concerned about atypical causes, uh, like he just mentioned.

So we agreed that, uh, we need to do Brucella serology, uh, Q Fever serology, and because this is an acute presentation, so we thought of acute Q Fever.

So we specifically, uh, wanted a PCR from whole Blood.

So serology and PCR and the PCR we usually send to our reference lab in Oman, uh, along with, uh, Q fever PCR, they can do also Rickettsia PCR.

So that would be two, uh, in the differential list of Zaid to be tested for.

And again from the list of differentials.

Uh, Zaid was also still concerned about some viruses, uh, like herpes simplex, uh, VZV, human herpes virus six.

So PCRs for these were also requested.

Right.

So, um, we added the doxycycline.

It was, um, on day two now, going to day three, uh, for potential zoonosis.

And within 24 hours of initiation, we started seeing an improvement in terms of the fever pattern, the transaminases.

Um, thereafter the CRP levels started coming down as well, and we were able to start weaning the supportive measures.

So by day four, the fevers had resolved and, we were off inotropes and actually extubated, uh, the child, um, thereafter sending him to the ward.

And then during this, uh, period of time, we received a call from a very smart microbiologist Badriya, with some updates, uh, from the lab.

So, Badriya, would you like to describe them for us?

Yeah, so I actually myself got a phone call as well from the Central Public Health Lab, telling us that Coxiella burnetti DNA was detected in that whole blood specimen that we sent.

Uh, it was around, uh, hospital day two it was collected, and, uh, soon after that we also had the serology result.

So we only do ELISA.

We don't have IFA.

So Coxiella phase two antibodies were positive.

Uh, IGM was strongly positive and IgG was just above the cutoff.

Uh, whereas the phase one antibodies were both negative.

We repeated PCR after two weeks of the child's presentation, and it was negative, which was reassuring.

We also repeated serology, uh, after two weeks and then again after four weeks.

Phase two antibodies, both IGM and IgG remained positive.

Phase one IgG transiently appeared, uh, at the two week sample, but then disappeared from the following one, which was again, reassuring.

So, Zaid, uh, would you like to tell us what happened after that?

Yeah.

So the first thing we did is we went back.

So the patient's now doing much better, uh, after a few days of doxycycline.

And then we got this, uh, result about the Q fever.

So the first we go back to the family and say, are you sure there was no animal exposure and they're like, well, uh, he actually spent likes to spend a lot of time at grandma's house and she has a bunch of goats in her yard and he helps, he spent a lot of time with her helping her tend to her goats, and some of them had given birth recently and all of that.

And like, okay.

So, so that's, that's the, that's the exposure where, where this came from.

Thankfully everything was going very well at this point.

He had been transferred from the ICU to the ward.

The fever resolved for a few days, then started to come back.

But alone, and he was otherwise, everything else was getting better, and so we kept extending the doxycycline duration.

We did repeat blood cultures, we did the repeat Q fever, coxiella PCR, and nothing came back positive.

And so after being on doxycycline for three weeks, we decided that maybe this, uh, fever was, uh, at this point, maybe a drug fever.

We changed azithromycin and then the fever resolved.

And then, after one week of azithromycin, we stopped all of the antibiotics and he did really well after that.

Um, he recovered essentially fully.

The bilirubin, the albumin, the ALT, they took about three weeks to normalize.

The coagulation profile took about six weeks to, to normalize, and he kept following up in the hematology clinic and the sickle cell clinic for, uh, we have, uh, more than two years of follow up since then, and he's done very well.

Um, so he didn't have any kind of chronic complications or chronic infection as far as we can, we can tell, uh, after that.

So it was a happy ending to a very, uh, tense situation initially.

Yeah, I mean, what an incredible case.

I have not had a case of this, but the best part is hearing that he's doing well.

So maybe we can talk about, what is Q Fever?

I'm sure a lot of us need refreshers and we don't see it that often.

How's it present?

What should we look for?

Um, Zaid, maybe you can tell us about some more info about Q Fever.

Right.

So Q fever, it has this funny name.

It starts with the letter Q, and that apparently comes from query.

So the initial cases were not very clear as far as the etiology.

So they used to call them query fever, and then it became eventually Q Fever.

And then later on the bacteria was discovered, which is a Coxiella burnetii.

It's named after the people who, who discovered it.

Uh, it's an intracellular bacteria.

It's a zoonosis.

The main reservoir are, uh, there, different animals can be the reservoir, but for as far as human infection, uh, the most significant would be farm animals.

So, cattle, sheep, goats, they tend to get infected with this organism a lot.

Sometimes there can be also outbreaks that can cause kind of abortion outbreaks.

So like in a farm, there can be a lot of abortions all of a sudden among the animals.

And that could be related to the Coxiella.

So humans who are in close contact with farm animals mostly are the, uh, the highest risk usually to get infected.

The distribution is quite worldwide, so in the US there are dozens, sometimes over a hundred cases, uh, in a year.

Australia is another country where, uh, there's usually a lot of reports, uh, in the Middle East.

We also have a lot of Q fever, uh, and there's a lot of communities and farmers and people who spend a lot of time with the sheep and with other farm animals.

In Oman, our country specifically, the first case was diagnosed officially in the year 2000.

So our, our healthcare system was a little bit late to develop, more like in the 1970s and 1980s.

And so some of these diseases were not recognized by laboratory confirmation until maybe more recently.

At that time, they did a sero prevalence study, and they found about 10% of adults were seropositive at that time in our country.

So it's not that, uh, uncommon.

The fever itself, the symptomatic infection, is seen a lot more in adults than in children.

So children are only about 5% of all of the cases.

Uh, so it tends to be maybe more asymptomatic and self-limited when occurring in children.

The symptoms usually are a non-specific flu-like illness with fevers and maybe headaches and body aches.

It can be sometimes presenting as fever of unknown origin.

Uh, it has a tropism for the lungs and for the liver.

So you can see atypical pneumonia.

You can see hepatitis.

Sometimes less commonly, it can be associated with encephalitis or, or, uh, pericarditis.

Um, in children, the prognosis is usually good, but there are reports of severe cases, including deaths.

One of the severe manifestations is acute fulminant hepatitis, and, and that's been described in children and in adults.

There is also in about 1 - 5% patients, there's progression to chronic infection, and that usually manifests with osteomyelitis, which can be multifocal and also endocarditis.

And endocarditis usually here happens in the setting of patients who already have underlying, uh, heart disease like valvular heart disease.

Right.

So, uh, Badriya, As Zaid was just mentioning that, it's through reservoirs or farm animals, but what is the actual mode of transmission, uh, for Q Fever?

So, transmission to humans occurs mainly through the inhalation of contaminated aerosols from infected animals or infected environments.

Um, Coxiella is able to survive in the environment for a very long time.

So, even non-direct exposure to animals can still cause, uh, Q Fever and as Zaid mentioned, birth byproducts like placenta and amniotic fluid.

These particularly have very high numbers of bacteria.

And so exposure to these is a very high risk like this child had.

So he was basically, there at the wrong time.

So he was there in an environment where goats gave birth recently.

Uh, and so I think that's probably the way he got it unfortunately.

There are some other less common modes of transmission, but these are less common.

And some of them are actually rare and some are not even proven.

And these include, uh, percutaneous exposure like for example, through cuts in the skin while dealing with animal products.

It could also be through ingestion of, for example, unpasteurized milk.

Uh, and possibly it could be tick bone, possibly.

And there has been some rare instances of person to person transmission, like for example, vertical transmission, sexual, uh, through transfusion and through transplants.

Yeah, and you know, we talked a little bit about the testing that was sent for this patient, but maybe Badriya, if you could summarize again for us, how do we think about screening and confirming this diagnosis, particularly since it's so uncommon.

Right.

So, so to start with, uh, you know, a disclaimer, uh, I'm not an expert in Q Fever.

Maybe we should have invited somebody from Australia to go through this.

The CDC has actually published, uh, a very useful document in 2013, and I always go back, uh, to that document.

It's basically describes the diagnosis and the management of Q Fever.

And it also provides criteria for labeling a case as confirmed or as probable.

So in general, when it comes to testing for Q Fever, testing basically aims to either detect the organism itself, and that would be mostly by PCR.

But there are some other methods like, for example, culture.

Uh, which is generally not recommended as it is difficult and it has, you know, exposure risk, and, uh, there's also immunohistochemistry.

Uh, so this allows us to detect the organism.

The other way is to detect the antibodies against the organism, so that would be using serology.

And the best method would be by indirect immunofluorescence assay, because that actually provides titers and titers are very important in the diagnosis of Q Fever because, for example, a confirmed acute case of Q Fever requires either the detection of Coxiella in a clinical sample, or, the demonstration of a fourfold rise in phase two IgG titers between paired serum that are collected three to six weeks apart.

For, uh, chronic Q Fever, again, laboratory confirmation requires either the detection of the organism in a clinical sample or the demonstration of antibodies, but this time against phase one antigens that goes with chronic Q fever and the titers that are diagnostic are more than or equal to 800.

Uh, or if using doubling dilution, it'll be, uh, 1024.

So, in our lab, as I have mentioned earlier, we use ELISA, which does not provide titers.

However, fortunately because we managed to catch the organism on time and we managed to get a positive PCR result, this was a confirmed case by definition.

Yeah.

And you know, thinking about the other features about this case that are a bit unique is, um, this patient's history of sickle cell disease and I thought maybe I'd ask about this concept of acute sickle hepatopathy and and what that means.

Right.

So the, this case was very fascinating because of the presence of the sickle cell disease, the severe liver involvement, and then the Q fever.

So we really looked at the literature to see what is there about sickle cell disease and Q fever, and actually we couldn't find any case of Q fever reported in the setting of sickle cell disease itself.

So it's very fascinating in case this one, showing like the intersection of these two diseases.

Uh, so, but acute sickle hepatopathies, this is an entity that's quite known in patients with sickle cell disease, some studies estimate that up to 10% of patients with vaso-occlusive crisis can have, uh, hepatopathy or liver involvement.

It actually, they're quite dangerous.

So there can be, the mortality in some studies can be 11 to 14% in, in adults, uh, probably lower in children, thankfully.

There are different types of acute sickle hepatopathy.

So, the first one is, uh, thought to be the, uh, hepatic crisis, uh, which is basically vaso-occlusive crisis involving the liver.

There, there would be some tender hepatomegaly, elevated liver enzymes, fever, and mild jaundice.

But it's not very severe presentation.

Uh, but the next is what we started to see in our patient is hepatic sequestration.

And here there's sequestration within the sinusoids of the, of the liver and, and, and there you get very massive hepatomegaly.

It's very tender and you get severe anemia and you start to see direct hyperbilirubinemia, but the liver transminases are not yet severely elevated and maybe the most severe form, probably progressing from there is intra hepatic cholestasis, where then you have all of the previous findings plus the, uh, marked elevation of the transaminases and progressive liver failure, which is what we started to, which we we're seeing in in our patients.

And so, so what we think happened here is that the, the Coxiella having the hepatic tropism probably caused this liver inflammation, and that triggered maybe the more sickling of the red blood cells in the sinusoids leading to hepatic sequestration, which then leads to maybe sinusoidal dilatation, compression of the biliary tree, and intrahepatic cholestasis.

That's, you know, our hypothesis of the, of the process.

These acute sickle hepatopathies are well described with a lot of other infectious agents, especially those that affect the liver, like hepatitis viruses and Epstein-Barr virus and even autoimmune disease.

Uh, they can happen.

But with Q Fever, this seems to be for us as, as far as we could tell, this was the first report.

We also looked at maybe other Rickettsia.

Well, Q fever is not exactly a rickettsia disease.

It's a category of its own, but it's related, uh, they're kind of like cousins with rickettsia and legionella, if you could say, um.

So we, we did find there was some cases of uh, anaplasmosis, uh, there's one case of anaplasmosis and hemoglobin SC that was quite severe, presented multi-organ failure.

Uh, but besides that, I suppose there could be some similar presentations with ricketssial disease or maybe anaplasmosis or, or any hepatotropic basically, uh, bacteria or infectious agent could present with acute sickle hepatopathy.

So that was a very, uh, unique and fascinating aspect to, to this case.

And, uh, and we could be at, at least happy that the child had a very good recovery, although we were really worried about him at, at, at the time he presented.

Yeah.

Well, I always like to wrap up by opening it up just to ask if you have any additional comments or lessons that you've learned.

You've been really great at pointing out things that stood out to you as we went, but anything else you'd like to add?

Well, I mean, I would say is that, you know, whenever the clinical course doesn't go as expected, sometimes you get this gut feeling, even if you can't put your finger on it.

You know, think again, go back to the beginning, you know, what did we miss?

And don't hesitate to call up a friend and ask for help.

You know, different specialties, just putting their heads together and trying to come up with a solution.

From my side, I have to say that I really admired, um, Zaid's perseverance and he went back and actually asked again about the exposure history, even though he got a no, no, no, the first time.

Uh, but you know, he went again and he asked again.

So, uh, I really admired that and.

Another thing I would add is sometimes you really have to seize the moment, like they say, and catch the organisms at the right time.

So I'm really glad that we got that first sample for Coxiella PCR, because it soon disappears after that, and it did actually disappear after two weeks.

And since we don't have IFA, our ELISA wouldn't have been diagnostic.

Uh, but we caught it at the right time.

So I'm glad we did that.

From my, uh, point, uh, of view.

So one, one thing that was interesting about this case, why did we send the Q fever PCR?

And I was like, um, running around the hospital, worried about this patient, and, different people would offer their ideas as to what's going on.

And one of the residents, he stood in front of me and said, have you thought about Q Fever?

And I'm like, why?

Why are you thinking about Q Fever?

And apparently he had seen some cases in, in adults, like in adult in medicine rotations.

Uh, and, and that got me like reading about it.

I asked Badriya about it and she's like, yeah, we can send a PCR, I, because I, I never seen a case before.

It's not very common in children and we just read about it in textbooks.

Like it, uh, it's very rare to see the actual symptomatic case in a child, and so, uh, thankfully I had the humility to listen to the resident and go with that and, you know, so I think that's very important to, to listen to people even as we progress in our career, to always listen to everyone and take their ideas very seriously.

And I think that another important point here, empiric doxycycline sometimes when things are looking unusual atypical.

Um, I think it saved this child's life.

Uh, and in fact, if anything, I would say maybe we start a little bit late on the second day.

Maybe we could have even started earlier with the empiric doxycycline.

So, uh, that's I think another important lesson here.

Uh, so yeah and thank god for microbiologists, right?

Thanks so much to our guests today for joining Febrile.

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