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Sara Dong: Hi everyone.

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

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We use consult questions to dive into ID clinical reasoning, diagnostics, and anti-microbial management.

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I'm Sara, your host and a Med-Peds ID fellow.

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

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Joining me as co-host today is Dr.

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Shilpa Vasishta.

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. She is a first-year ID fellow at the Icahn School of Medicine in Mount Sinai in New York with an interest in medical education.

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Shilpa Vasishta: Hi, excited to be here.

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Sara Dong: And our guests consultant today is Dr.

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Christina Coyle.

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Christina is a Infectious Disease physician and Professor of Medicine and Pathology at the Albert Einstein College of Medicine.

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She has practiced tropical medicine for over 25 years and oversees the largest tropical medicine clinic in the Bronx at Jacobi Medical Center.

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Christina Coyle: Hi, it's Christina Coyle, excited to be here.

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Sara Dong: Awesome.

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And, uh, before we start the case, we always ask this one nonmedical question and we call ourselves a cultured podcast and would love it if you'd be willing to share a piece of culture that brought you happiness or joy recently,

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Christina Coyle: I'll start.

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Um, so what brings me joy?

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I think, uh, for me, I'm passionate about ballet.

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Most people know I'm obsessed with it and I've been dancing since I'm seven and I'm 60, so you can do the math.

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I certainly wouldn't call it dancing now, but I'm obsessed also with, uh, ballet performances.

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So it's a real passion of mine.

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Shilpa Vasishta: Dr.

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Coyle, that is so awesome.

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I too love ballet.

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And what I was actually going to plug today is not specifically ballet, but a related art form that my son has taken interest in, which is tap dancing.

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Um, I say this kind of loosely because he's only 15 months old, but he loves the movie Happy Feet, which actually features spectacular tap dancing, um, from one of arguably the world's best tap dancers Savion Glover.

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Um, and my son loves to imitate it.

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And so I would highly recommend it for any family that loves dance and maybe has a one-year-old boy

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Sara Dong: Excellent!

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Christina Coyle: The main thing here, Sara, is that dance equal joy!

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Sara Dong: Yes.

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Um, well I love these little pieces of culture, but, um, so we'll jump into today's case.

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The consult question is about worsening fevers.

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Uh, so Shilpa, I'll hand it over to you.

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Shilpa Vasishta: Thank you.

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So we have today, a 38 year old female who's presenting to medical attention with fevers.

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Her symptoms began three days ago and are accompanied by headache and nausea.

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They have progressively worsened prompting her to present to the emergency department today.

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She denies any associated sore throat, rhinorrhea, cough, abdominal pain, vomiting, diarrhea, or dysuria.

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Her past medical history includes prediabetes within hemoglobin A1C of 6.0.

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And for medications, she takes an oral contraceptive.

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The patient is originally from Brazil, moved to the U S at age 25, and she recalls being hospitalized once in her early twenties for a kidney infection.

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She currently lives in the Northeast with her husband and two pet cats.

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She works in technology and travels approximately twice yearly for work, last to Nigeria 10 days ago.

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On presentation, the patient is febrile to a maximum temperature of 103.5 degrees Fahrenheit.

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She's tachycardic to a heart rate of 130, she's normotensive and saturating 99% on room air.

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On exam, she is well-appearing with moist mucus membranes.

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She has no jaundice or scleral actress and her neck is supple.

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She is tachycardic.

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However respirations are non labored and lungs are clear to auscultation.

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Her abdomen is nontender.

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Liver and spleen are nonpalpable and she has no rashes.

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Neurologically she's alert and oriented times four with no deficits on initial lab work.

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She has a white blood cell count of three, a hemoglobin of 10 and platelets of 90.

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On chemistries she's hyponatremic to 128, has a metabolic acidosis with a bicarb of 16, and an elevated creatinine to 1.2.

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Her transaminases are elevated to the sixties and chest x-ray demonstrates clear lungs.

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What are your initial thoughts in hearing this case?

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And what additional information would you like?

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Christina Coyle: Okay.

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So, um, we have a 38 year old, born in Brazil, but residing now in the states (USA) who now travels to Nigeria less than 10 days ago, who's complaining of a fever.

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She's also complaining of a headache and, her labs are significant, as you said, for a low white count, thrombocytopenia, a bicarb on the low-ish side, a chest x-ray that's negative.

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We don't hear a urine.

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So we'll talk about what else we'll want, but the minute you're called as a fellow for somebody with a fever, the first thing you want to know is obviously where they traveled to and how long they've been back from the region.

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Knowing the geographic area is critical to your assessment as an ID fellow.

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So that's the first thing you're going to do.

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I'm going to just tell you some tips and tricks.

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So if you don't know anything about the region, you can go to cdc.gov and travel and look up the region there, and it will give you everything that is in that region that's infectious.

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And  you're thinking as the ID fellow when you get this phone call, is, what is life-threatening in this particular patient?

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What is treatable, right?

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And what's transmissible.

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Do I need to isolate this person?

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Those are the three questions that you asked yourself when you get this phone call.

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And then of course, we talked about the time that they came back from their trips.

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So we're looking at incubation, we're going to be focusing on the exposure history, uh, the time course, and of course the associated signs, signs, and symptoms.

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And so in terms of onset of fever from the trip,  I kind of break it up into less than a month and greater than a month.

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And even with that, I kind of think less than two weeks because we know things like the flu have a short incubation.

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COVID has a short incubation.

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And then we know things like dengue, chikungunya, um, all have incubations of less than two weeks.

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So if the person's already greater than two weeks out, that's making those less likely.

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This person is within the two weeks, so the differential diagnosis gets very, very large, right?

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Once you go past two weeks, that becomes much less likely.

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And that's very helpful for you to think about.

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Once you're within a month, right?

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You're always thinking about falciparum malaria.

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So malaria one, two, and three.

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And then once you move outside of a month, you  start thinking about things like hepatitis, schistosomiasis (because we're talking about Africa right now).

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So these are causes of fevers that are, are greater than a month.

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Um, and then I do want to add in there,  we don't see P.vivax  normally from West Africa because it needs the Duffy antigen to enter and it's tends to be lacking in west Africans.

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We can see from East Africa, um, and of course, most P.vivax in the United States in travelers is, is reported from Southeast Asia.

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But P.vivax, because of the hypnozoites or the liver stage can be a cause of late fever and malaria.

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The other thing you want to know is where the patient was born and you already told me that.

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Because that's going to tell you whether or not the patient has a likelihood of being exposed to certain diseases.

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And so we, um, also talked about the type of traveler people are.

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So I normally ask patients, why did you go?

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Did you go for fun?

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Did you go for business or,  are you visiting friends and family?

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There is a whole literature on visiting friends and family, and  they are referred to as VFR.

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And so VFRs, are individuals that are returning home to their own country or a spouse's country or a parent's country, where there's a higher infectious disease risks than the country that they're currently residing in.

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And so when we look at these individuals, they are less likely to have had a pre-travel assessment.

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And they're more likely to come back home with a vaccine preventable illness.

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So this is really important.

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This individual's not a VFR, but as an ID specialist, that's something you want to really think about.

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And you also want to think about it when you're caring for individuals that are migrants, because they do tend to go back home and visit their friends and family.

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We talked a little bit about length of time in the country.

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So you want to know how long the person's been in the country.

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And obviously I ask for an itinerary.

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So if the person's a short-term traveler in one city, it's not a big deal, but once somebody's somewhere for awhile, I actually make them write out their itinerary for me.

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Travel history  really takes quite a while.

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I ask everything you can think about, obviously.

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Sexual activity during the trip.

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Um, the stuff you normally think about mosquitoes, right?

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Exposure to animals,  fresh water exposure, always in Africa, but really anywhere, but, uh, especially in Africa because of the risk of uh schisto.

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Then I also ask about whether or not they used repellent and whether or not they were good at it.

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It's not going to change whether or not I'm going to be worried about malaria.

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It also gives me an idea of what type of a traveler they are.

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I also ask if they use bed nets or if they use screens, uh, or if they stayed in a room with screens.

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We always ask about food and water.

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Right?

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We ask about bottled water.

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Everyone says they use bottled water.

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Um, and so before someone goes, we always say, boil it, cook it, peel it or forget it.

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The reality is that's really hard to do, uh, for an entire trip.

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And so, , the more you stray from that, the more you're at risk for foodborne illnesses, such as hepatitis, , and typhoid, especially in areas with poor sanitation, so if you're in more rural areas.

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Your differential diagnosis, I put it in like almost three buckets.

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I do a geographicgeographic, right?.

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So that helps me hone down.

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Exposures.

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And then the syndromic, and then I kind of put them together and I see where they intersect.

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This is what makes the returning traveler with fevers  so much fun because it really is like being a detective.

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So you're putting all the puzzle pieces together and then I see where they intersect.

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And then of course I'm rating the thing that if I don't recognize it and treat it that evening, it could cause harm.

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And so I'm doing a risk assessment also on what's the most likely, or what's the thing that that's going to, um, really harm this patient if I don't make the diagnosis.

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Sara Dong: And I'm guessing that some of your risk assessment tackles pre-travel considerations, are there any tools or suggestions you have for approaching that?

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Christina Coyle: I ask a lot about pre-travel.

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So I'll spend a few minutes here  on a website.

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You can go to CDC.

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Um, many of you might have actually pre-travel programs.

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For those fellows that don't, there was a lovely website, and that is supported by CDCs Global TravEpiNet.

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It's called GTEN.

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And it's called, called "Heading Home Healthy.".

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It's actually a pre-travel, but if you're seeing the patient post travel, you can put the patient in there and you put in the age of this patient and you put that they went to Nigeria and, um, any allergies or whatever else they might have asked for pregnancy and some other things.

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So it's going to come up with vaccines.

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And so yellow fever is going to come up, but you're going to find out that you are going to need proof of vaccination to even get in to Nigeria.

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So she probably had yellow fever.

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You, of course, you're going to ask are typhoid comes up, but I'm going to tell you it's pretty uncommon in Africa.

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Meningo[coccus] comes up during the dry season.

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So that's important.

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She has a headache.

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You're not sure if she took the meningo vaccine.

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Hepatitis A.

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You want to know whether or not she's immune or whether or not she was vaccinated.

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Hepatitis B.

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. Flu vaccine.

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And obviously COVID vaccine right now is easy because you need to show it to, to fly.

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Um, but I added it on the list for completeness.

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Um, you should make sure they're up to date on their routine immunizations, just because measles outbreaks are very common, uh, throughout the world.

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And it's something we have to think about, and we don't see a lot of it anymore.

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And especially younger people who trained in the States normally have never even seen a case of measles.

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So it's really important for us to ask about vaccination.

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And then you can either, when you go on CDC or Heading Home Healthy, they will tell you about our outbreaks.

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And that's super important because you'll know, oh, wow, there's an outbreak of X going on in this particular region.

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And so they'll warn you and you'll know going in there, there's an Ebola outbreak wherever this patient has traveled or whatever it might be.

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For the most part, we're pretty good about knowing outbreaks as ID people, but it's always good to refresh ourselves.

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And of course the most important thing is malaria prophylaxis.

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Did this person have a pre-travel assessment and were they offered malaria prophylaxis?

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That's number one.

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And then number two, did they take their malaria prophylaxis?

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Right.

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So any breaks in malaria prophylaxis?

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First of all, it's not completely, you're not going to be a hundred percent effective with malaria prophylaxis.

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That's why we always tell people to use, uh, insect repellent et cetera, in addition to the, the prophylaxis.

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And a lot of people aren't always compliant.

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And if you think about something like doxycycline, for example, you miss one dose and you can break through.

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We will do a differential, but, you know, before we even walk in the room, despite what she tells us, we're going to be thinking malaria one, two, and three.

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No matter what she looks like, whether she's febrile, no matter we are going to be thinking malaria.

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Malaria is the most important cause of fever amongst those individuals traveling back from Africa.

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90% of cases in the US um, are acquired in Sub-Saharan Africa, and the number of cases of malaria in the US have been increasing since 1970s.

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And so when you look at it, the majority of those cases are from West Africa.

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So you're going in with that mindset.

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I will tell you the most common reason for travel in those individuals is normally those individuals visiting friends and family.

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Your main thing that you're thinking about is I need to get malaria in, or out of the picture as ID fellow when you're on the phone.

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And the other thing I wanted to say to you, which I think is really important, not as that appropriate to this patient, is that many times, in up to 40% of cases, patients can present with other symptoms.

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So their GI symptoms, so they can have diarrhea predominating the picture.

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And the fever may not be what they complain about.

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And so you can get derailed and misdiagnosed.

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And so if you look, there's a couple of studies from the states, also one from my institution, uh, one in Canada that shows that there's a fair amount of misdiagnosis in these individuals.

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So again, lack of fever and having other symptoms besides headache and myalgias,  you must rule out malaria.

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You just must, it has to be on your list.

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Sara Dong: So how do we approach these labs when we're getting this call as the ID fellow.

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Christina Coyle: This patient kind of checks the boxes.

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So we see a lot of malaria uh, the I'm in the Bronx and we have the largest numbers of malaria in the United States, up here in the, new York does, and then within New York, the Bronx and upper Manhattan.

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So I get called a fair amount for the returning traveler from West Africa.

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So once I I'm obviously thinking malaria, malaria.

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So what are the questions that I'm going to ask, I'm going to start?

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Or what are the things that are going to get me worried about this patient?

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So we normally see thrombocytopenia, it's rare to not see thrombocytopenia.

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There's sequestration in the spleen, spleen of platelets..

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So we rarely don't see it.

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So if I see here someone's got a platelet count of 350, that actually makes it less likely that it's malaria.

201
00:16:04,869 --> 00:16:09,819
It doesn't mean it's not, I'm still gonna rule it out, but thrombocytopenia is normally the rule.

202
00:16:09,819 --> 00:16:13,229
It is not prognostic of how sick the patient is.

203
00:16:13,559 --> 00:16:18,329
The prognosis is really going to be on end organ and also parasitemia.

204
00:16:18,599 --> 00:16:19,019
Right.

205
00:16:19,229 --> 00:16:21,239
We can see any white count in malaria.

206
00:16:21,239 --> 00:16:22,679
We could see a low white count.

207
00:16:22,709 --> 00:16:25,369
We normally don't see high white count similarly.

208
00:16:25,389 --> 00:16:32,939
So if you start seeing a white count of 25, that's gonna make malaria either less likely or dual infection.

209
00:16:32,939 --> 00:16:35,819
The person might have a bacterial infection plus malaria.

210
00:16:35,979 --> 00:16:42,279
Also, we're a bit worried about that bicarb of 16, and that should be something that's a red flag for us.

211
00:16:42,279 --> 00:16:43,989
And the creatinine is slightly elevated.

212
00:16:44,049 --> 00:16:50,719
So these things are red flags when we get called on the phone phone, we also hear that she's from Brazil.

213
00:16:51,259 --> 00:16:53,989
So we're not sure if she's ever had malaria before.

214
00:16:53,989 --> 00:16:55,729
There is some malaria in Brazil.

215
00:16:55,999 --> 00:16:58,249
So, but it was years ago, right?

216
00:16:58,249 --> 00:17:01,549
She's a long-term long time out of Brazil.

217
00:17:01,789 --> 00:17:05,630
So we're assuming she's non-immune so that's also making us worried.

218
00:17:05,630 --> 00:17:11,900
So this is all my malaria brain going on, but I don't want to get too focused on malaria and missed other things.

219
00:17:11,900 --> 00:17:12,319
Right.

220
00:17:12,369 --> 00:17:16,659
So the other things you're going to ask for are going to be urine, right?

221
00:17:16,689 --> 00:17:22,329
I'm going to ask for obviously, um, a blood smear, I'm going to ask for an LDH.

222
00:17:22,359 --> 00:17:24,159
I'm going to ask for a lactate.

223
00:17:24,339 --> 00:17:31,300
You already have a chest x-ray and I'm going to ask for blood cultures, but what ID person isn't going to ask for blood cultures.

224
00:17:31,659 --> 00:17:39,489
Um, so I think we'll stop there and hear what happened and then, based on this patient then start saying what's likely and what's not.

225
00:17:39,499 --> 00:17:40,100
Shilpa Vasishta: Yeah, sure.

226
00:17:40,159 --> 00:17:48,050
Um, so a little bit of additional history, patient reports staying in an urban area of Nigeria for two weeks during her most recent period of travel.

227
00:17:48,409 --> 00:17:57,510
She resided in a hotel where she ate most of her meals, uh, though did also eat food,  including both cooked foods and fresh produce obtained from outdoor vendors.

228
00:17:57,780 --> 00:17:59,909
Uh, she drank exclusively bottled water.

229
00:18:00,449 --> 00:18:05,580
She did make one weekend trip during which she hiked in a wooded area and swam in a freshwater lake.

230
00:18:06,000 --> 00:18:12,149
She does not recall any contact with animals though, does endorse mosquito bites despite use of mosquito netting.

231
00:18:12,490 --> 00:18:14,670
And she was not sexually active during her travel.

232
00:18:15,670 --> 00:18:23,420
She had a pre-travel consultation where she completed yellow fever vaccination, and was offered typhoid vaccination, but declined.

233
00:18:23,900 --> 00:18:26,960
She was otherwise noted to be up to date on routine immunizations.

234
00:18:27,380 --> 00:18:32,150
She was prescribed doxycycline, which she reports not taking consistently during her two weeks of travel.

235
00:18:32,330 --> 00:18:33,110
Christina Coyle: Okay, great.

236
00:18:33,410 --> 00:18:36,380
So let's go over the history that you just told me.

237
00:18:36,380 --> 00:18:37,520
So I'm on the phone now.

238
00:18:37,520 --> 00:18:39,350
I'm still the ID fellow on the phone.

239
00:18:39,380 --> 00:18:41,930
And so she's, uh, she's a short-term traveler.

240
00:18:42,260 --> 00:18:43,910
She's been there for two weeks.

241
00:18:44,260 --> 00:18:48,199
she was in a hotel, but she did have some high risk behavior in terms of her eating.

242
00:18:48,219 --> 00:18:48,550
Right?

243
00:18:48,550 --> 00:18:52,629
So, um, she went to an outdoor, uh, food vendors.

244
00:18:52,629 --> 00:19:02,889
So we know that she's at risk for typhoid, hepatitis A, um, and, and other GI pathogens, although we don't hear a lot of GI complaints.

245
00:19:03,250 --> 00:19:06,894
She made a weekend trip where she hiked in a wooded area.

246
00:19:07,374 --> 00:19:08,814
So that would pique my interest.

247
00:19:08,814 --> 00:19:28,534
I'm going to talk to you about that, about tick-borne illnesses, but not as much in west Africa, more in South Africa, . Um, and then she swam in fresh water and I always ask my patient if they swim in fresh water, um, and any single body of fresh water in Sub-Saharan Africa should be considered to be, uh, infected with Schisto[somiasis]

248
00:19:28,664 --> 00:19:31,934
so they're at risk for being exposed to schisto and that's your rule.

249
00:19:31,995 --> 00:19:32,294
All right.

250
00:19:32,294 --> 00:19:33,644
You don't have to look that one up.

251
00:19:34,124 --> 00:19:41,454
Um, and of course we always worry about leptospirosis, and that's something that we can, we always have to think about as ID people, because we don't keep it on our list.

252
00:19:41,604 --> 00:19:42,474
We'll forget about it.

253
00:19:42,984 --> 00:19:50,004
Um, she doesn't really talk about contact with animals, so I don't have to go in that direction, but she endorsed a lot of mosquito bites.

254
00:19:50,004 --> 00:19:52,254
So malaria was big, big, big.

255
00:19:53,114 --> 00:19:57,854
Big big, big, um, she had a pre-con, uh, travel consultation.

256
00:19:57,884 --> 00:20:00,134
She got her yellow fever vaccination.

257
00:20:00,495 --> 00:20:05,425
Um, and, she wasn't compliant with her doxy or was she, I can't remember.

258
00:20:05,425 --> 00:20:07,074
Did she, did she take her anymore?

259
00:20:07,344 --> 00:20:11,004
Shilpa Vasishta: Uh, she was prescribed them, um, and reports not taking them.

260
00:20:11,465 --> 00:20:11,905
Christina Coyle: Okay.

261
00:20:12,235 --> 00:20:14,394
So that's important.

262
00:20:14,445 --> 00:20:19,665
For this, we talked about risk factors, so we just went over some of her risk factors.

263
00:20:20,115 --> 00:20:23,685
And so this is where we now did geographic.

264
00:20:24,564 --> 00:20:30,624
And we took her risk factors and we talked about the things within west Africa that might cause fever.

265
00:20:30,924 --> 00:20:34,524
And now we then might think about syndromic.

266
00:20:34,884 --> 00:20:42,504
And so for this patient, although she's got a headache, I would really put her into an undifferentiated fever.

267
00:20:42,794 --> 00:20:46,864
And then I break it into malarial versus non malarial.

268
00:20:47,144 --> 00:20:49,455
Um, and that's how I would approach her.

269
00:20:49,764 --> 00:20:58,495
So the first thing we're going to do is rule out malaria, uh, but other things to consider as we're walking down to see her and get all her bloods.

270
00:21:00,430 --> 00:21:09,899
Uh, when we think about an undifferentiated fever, we have to be really careful about not, not only thinking about tropical diseases.

271
00:21:10,199 --> 00:21:12,419
So we need to think about UTI.

272
00:21:12,749 --> 00:21:14,699
We need to think about respiratory infection.

273
00:21:14,709 --> 00:21:17,129
She's got a negative chest x-ray so that's really unlikely.

274
00:21:17,179 --> 00:21:18,649
We talked about influenza.

275
00:21:18,679 --> 00:21:28,429
We talk about COVID she's not sexually active, but we always need to think about STDs, including acute HIV with an, an undifferentiated fever.

276
00:21:28,789 --> 00:21:42,019
Um, and then it puts us into our tropical dengue, rickettsial infections, leptospirosis, and she's got a lot of risk factors that you went over that put her at risk for these illnesses.

277
00:21:42,319 --> 00:21:45,709
Um, and then, a rash always changes things.

278
00:21:45,949 --> 00:21:52,214
A rash puts us into dengue, chik[ungunya] again, acute HIV, measles,  and then acute schisto[somiasis].

279
00:21:52,264 --> 00:21:56,424
Um, and then within the rash, I always look for a eschar.

280
00:21:56,734 --> 00:21:59,494
The patient has to take their clothes off.

281
00:21:59,914 --> 00:22:09,004
Um, because a lot of times it's normally at the bite of the, in terms of Africa, the bite of the tick, in terms of uh Asia, it's a chigger.

282
00:22:09,484 --> 00:22:17,644
Um, and so, you know, sometimes it's behind the knee, it's, uh, in places that if you're not really looking at the patient wholly, you might miss.

283
00:22:17,644 --> 00:22:26,104
So I'm always looking for eschars, regional adenopathy, um, because a lot of times with rickettsial illnesses, the patient will only complain a fever and headache.

284
00:22:26,404 --> 00:22:28,664
And if you're not looking, you'll miss an eschar.

285
00:22:29,334 --> 00:22:33,714
.  So then, you know, there's other syndromes in this patient right now, doesn't meet them.

286
00:22:33,954 --> 00:22:35,874
So fever with jaundice.

287
00:22:35,904 --> 00:22:40,344
So if I see that, I start thinking severe malaria, hemorrhagic, fevers, et cetera.

288
00:22:40,674 --> 00:22:42,294
Fever with GI complaints.

289
00:22:42,474 --> 00:22:49,104
And so we can supply you with a nice list of syndromic approach to fever and the traveler.

290
00:22:49,564 --> 00:22:53,764
I just wanted to spend a few minutes on each thing to think about.

291
00:22:53,764 --> 00:22:54,364
So dengue.

292
00:22:54,434 --> 00:23:03,989
After malaria, the most common when we look at Geo Sentinel, which is a  worldwide surveillance site, um, and, uh, supported by CDC.

293
00:23:04,169 --> 00:23:09,539
The most common cause of fever on the traveler after malaria is dengue.

294
00:23:09,849 --> 00:23:16,779
Dengue is transmitted by, um, Aedes aegypti or albopictus and, um, it's worldwide.

295
00:23:16,839 --> 00:23:18,879
And it's found in Africa.

296
00:23:19,329 --> 00:23:30,219
And the classic that you think about and that we see at my institution, is fever obviously, by a severe headache and patients classically tell you that it's retro orbital.

297
00:23:30,219 --> 00:23:31,989
They really do tell you that.

298
00:23:32,199 --> 00:23:40,719
So I actually asked them that, or a lot of times they'll supply that history and they'll have severe myalgias and arthralgias giving it the name breakbone fever.

299
00:23:42,064 --> 00:23:54,224
The fever lasts about five to seven days and the rash is pretty, um,  if you've ever seen it, it's a macular  eruption and basically it's erythematous with small areas of normal skin.

300
00:23:54,494 --> 00:24:01,034
So on a person with white skin or light skin, it's called  islands of white in a sea of red.

301
00:24:01,184 --> 00:24:04,004
This is harder to see in darker skinned individuals.

302
00:24:04,274 --> 00:24:12,734
And that's why it's very important as an ID person to make sure that when you're looking at skin rashes, you look at rashes on people of all skin colors.

303
00:24:12,734 --> 00:24:17,964
It's really important for us to recognize different rashes on different, uh, different skin colors.

304
00:24:18,324 --> 00:24:24,474
Um, but that's the classic way that it's described, and the more important thing is that there's areas of sparing to the erythema.

305
00:24:25,879 --> 00:24:28,129
And it's got a very short incubation.

306
00:24:28,529 --> 00:24:37,819
I use 14 days as your cutoff when I first started this talk, but it can be five to 10 days so people can get ill during travel and might not even be reported.

307
00:24:38,149 --> 00:24:47,149
Um, and risk factors are obviously everything that this patient has and leukopenia and thrombocytopenia like this patient are characteristic.

308
00:24:47,399 --> 00:24:51,179
When you, you look at dengue, it's most common to be reported from Asia.

309
00:24:51,540 --> 00:24:54,370
It is reported from Africa, but not commonly.

310
00:24:54,649 --> 00:24:59,570
I'll tell you in my experience, I've definitely, um, diagnosed people with dengue from, um, Africa.

311
00:24:59,600 --> 00:25:01,070
It is on my differential.

312
00:25:01,399 --> 00:25:07,040
For this patient, I would probably rule out malaria first, before I even sent a dengue serology, me personally.

313
00:25:07,379 --> 00:25:13,649
, but when you're talking about getting bit by mosquitoes and there's Aedes aegypti and albopictus in Africa.

314
00:25:13,649 --> 00:25:16,529
So you have to think about chikungunya and Zika.

315
00:25:16,659 --> 00:25:22,580
Chikungunya has a short incubation and here arthralgias are the prominent symptoms

316
00:25:22,580 --> 00:25:25,360
.
70% of patients are going to complain of arthralgia.

317
00:25:25,400 --> 00:25:30,710
And if you've ever seen somebody with chikungunya, which means bent over, they really are bent over.

318
00:25:30,960 --> 00:25:33,460
This patient has no rheumatologic symptoms.

319
00:25:33,480 --> 00:25:36,600
I don't think I would even send a chikungunya serology.

320
00:25:36,850 --> 00:25:42,430
, Skin manifestations are also reported in chikungunyah, but we don't share that in this patient.

321
00:25:43,000 --> 00:25:45,020
I'm going to spend two seconds on Zika.

322
00:25:45,040 --> 00:25:48,610
You can look it up and see where Zika outbreaks are occurring.

323
00:25:48,940 --> 00:25:53,790
Again, it's transmitted by the same mosquitoes as dengue and chikungunya.

324
00:25:54,120 --> 00:25:58,080
The illness tends to be mild and even asymptomatic in many individuals.

325
00:25:58,350 --> 00:26:02,220
And here there's a pruritic rash and patients can have arthritis,

326
00:26:02,895 --> 00:26:04,365
and conjunctivitis.

327
00:26:04,695 --> 00:26:14,024
Um, and so headaches and orbital pain are also reported, but there's no outbreak currently going on in Nigeria and we hear nothing really to support Zika.

328
00:26:14,024 --> 00:26:16,004
So I would think that would be unlikely.

329
00:26:16,544 --> 00:26:21,995
Let's spend some time on typhoid fever cause this individual ate off of roadside stands.

330
00:26:22,324 --> 00:26:27,234
And so for me, we're going to do blood cultures and that's how we'll establish a diagnosis.

331
00:26:27,474 --> 00:26:29,814
But for me, this wouldn't be high on my differential.

332
00:26:29,904 --> 00:26:36,614
Definitely doing the blood cultures, but normally in, patients present, they've normally traveled to Southeast Asia.

333
00:26:36,884 --> 00:26:40,304
They've normally had prolonged fever for greater than seven days.

334
00:26:40,544 --> 00:26:43,294
They normally have chills, but they're not having rigors.

335
00:26:43,424 --> 00:26:54,139
So they tend to come in a little bit later . And, um, it's, caused by Salmonella enterica serotype typhi or para typhi.

336
00:26:54,439 --> 00:26:57,649
Um, incubation can be up to three weeks, early as five days.

337
00:26:57,879 --> 00:27:11,649
So about 80% of cases in the United States, , diagnosed with, , typhoid, uh, individuals diagnosed with typhoid have traveled to Southeast Asia and the majority of individuals present with abdominal pain, fevers, and chills.

338
00:27:11,949 --> 00:27:17,919
There is a rash, it's very hard to see, it's a salmon colored macules, rose spots.

339
00:27:18,309 --> 00:27:21,639
Um, and I really check my patients carefully.

340
00:27:21,639 --> 00:27:27,009
For the majority of patients in our institution are normally from, um, Bangladesh.

341
00:27:27,159 --> 00:27:32,499
So I really really check and we see it mostly in children that haven't gotten vaccinated before they've left.

342
00:27:32,779 --> 00:27:33,949
So there's, there's some clues.

343
00:27:34,069 --> 00:27:45,529
So this makes, um, typhoid fever a little bit less likely, it's an acute fever, um, that's number one, if the patients from Africa, so that makes it a little bit less likely, although she does have risk factors.

344
00:27:45,529 --> 00:27:48,109
So it's still on the list still in the running.

345
00:27:48,349 --> 00:27:51,979
Let's spend two seconds on rickettsia because it comes up on the list.

346
00:27:52,249 --> 00:27:59,759
So I think for Africa, you need to know about, um, African tick typhus, which is caused by Rickettsia africae.

347
00:28:00,079 --> 00:28:02,709
It is  most common in South Africa.

348
00:28:02,739 --> 00:28:08,904
It's really not well described in west Africa, but I do think you need to know about it.

349
00:28:08,954 --> 00:28:15,014
the vector is an, a tick, an Amblyomma species and it's a tick of large ruminants and wildlife.

350
00:28:15,044 --> 00:28:17,354
And it's a very aggressive feeder on humans.

351
00:28:17,354 --> 00:28:18,494
And that's important.

352
00:28:18,794 --> 00:28:23,864
At the site of inoculation, you can get an escahar and you can have regional lymphadnopothy.

353
00:28:24,104 --> 00:28:29,134
Although the patient can actually present with just really headache and fever.

354
00:28:29,404 --> 00:28:31,864
And if you don't look, you'll miss the eschar.

355
00:28:32,134 --> 00:28:37,894
And as I said, you know, many times patients have a number of eschars if you look closely.

356
00:28:38,284 --> 00:28:43,774
Um, and it's normally in people who have been camping, hiking, such as this patient traveling.

357
00:28:43,774 --> 00:28:49,264
It's very common or in safari or in grassy areas, walking in grassy areas.

358
00:28:49,564 --> 00:28:54,274
Again, because they're from west Africa, it makes it less likely.

359
00:28:54,514 --> 00:28:55,324
Lab wise,

360
00:28:55,354 --> 00:28:59,254
they have leukopenia and thrombocytopenia, a low bicarb would.

361
00:28:59,254 --> 00:29:00,184
Go against it.

362
00:29:00,214 --> 00:29:00,484
Right?

363
00:29:00,484 --> 00:29:04,545
You don't look systemically ill, you respond promptly to doxycycline.

364
00:29:04,615 --> 00:29:08,755
You make the diagnosis, you establish it by clinical picture and serology.

365
00:29:08,875 --> 00:29:13,675
So normally we just treat presumptively and they really respond quite rapidly.

366
00:29:14,165 --> 00:29:22,715
Rickettsia conorii or Mediterranean tick typhus, although it's circulating, it's not a common cause of rickettsial diseases in Africa.

367
00:29:22,715 --> 00:29:29,555
So the one that I would know as a, as a fellow would be, um, African tick typhus or Rickettsia africae.

368
00:29:29,675 --> 00:29:30,095
Okay.

369
00:29:30,155 --> 00:29:31,415
So it's really important.

370
00:29:31,445 --> 00:29:33,185
The epi here doesn't support it.

371
00:29:33,395 --> 00:29:40,385
We heard that the patient is not sexually active, but do not forget to ask about a sexual history or blood exposures.

372
00:29:40,625 --> 00:29:49,915
So things like, um, uh, basically body piercing, people get tattoos, people have accidents and they sometimes don't tell you about it.

373
00:29:49,915 --> 00:29:55,405
Minor accidents where somebody actually stitches them, uh, in rural areas with needles.

374
00:29:55,405 --> 00:30:00,595
And you don't know if the needle has been cleaned, so you really need to dig down a bloodborne exposures.

375
00:30:01,240 --> 00:30:06,490
And obviously I don't need to tell this audience about acute HIV and how it can present.

376
00:30:06,880 --> 00:30:11,200
Um, and so then we heard about freshwater, so let's talk about leptospirosis.

377
00:30:11,410 --> 00:30:16,240
And so there's lots of emerging data on people that do go rafting or kayaking.

378
00:30:16,510 --> 00:30:18,280
And  coming back with leptospirosis.

379
00:30:18,280 --> 00:30:22,270
So we as ID people need to keep it on our radar.

380
00:30:22,480 --> 00:30:26,830
The incubation is two to 26 days, but it's an average of 10 days.

381
00:30:26,830 --> 00:30:29,200
So this patient, um, is within that.

382
00:30:29,200 --> 00:30:31,180
Although I don't know when they were in fresh water.

383
00:30:31,450 --> 00:30:38,680
The clinical course is variable, but early on, patients can come in with fever, rigors, myalgias, and headaches.

384
00:30:38,920 --> 00:30:45,990
A lot like this patient and conjunctival suffusion is characteristic, but often overlooked.

385
00:30:46,200 --> 00:30:50,220
I need to talk about acute schisto because we don't talk about it enough.

386
00:30:50,460 --> 00:30:53,220
It occurs four to eight weeks after exposure.

387
00:30:53,340 --> 00:30:57,110
So this would be on the very early side, if it was just schistosomiasis.

388
00:30:57,360 --> 00:31:02,970
And I think it's too early for acute schisto because if you do the math, she's back 10 days.

389
00:31:02,970 --> 00:31:04,650
So she'd be right on the cusp.

390
00:31:04,980 --> 00:31:05,910
It's important.

391
00:31:05,910 --> 00:31:11,160
It's a cause of a fever and normally individuals complain of a rash.

392
00:31:11,370 --> 00:31:18,300
Now, not everybody is symptomatic, but those individuals with fever, commonly have urticaria.

393
00:31:18,660 --> 00:31:21,150
And they normally have profound eosinophilia.

394
00:31:21,390 --> 00:31:23,970
So they can have non-specific symptoms.

395
00:31:24,120 --> 00:31:30,900
Two thirds of individual will actually have a cough and they'll have an abnormal chest x-ray, which will be reticulonodular.

396
00:31:32,240 --> 00:31:49,080
And so it's really important for you to think about this in your patients that return with eosinophilia and a fever . So, um, that's acute schisto and the one thing I want to say to you about schisto is eggs normally are only present in 25% of individuals in the urine or stool depending on the species.

397
00:31:49,380 --> 00:31:57,990
And so the way we make that diagnosis is basically clinical and we treat presumptively while we're waiting for the serology to come back.

398
00:31:58,350 --> 00:32:14,730
Um, by the way CDC recommends anybody that's been in freshwater in Sub-Saharan Africa should be screened for schisto because not everybody is symptomatic and you can have a wayward pair of worms that find their way into Batson's plexus and shoot eggs off into your spine and your brain.

399
00:32:14,970 --> 00:32:22,350
So even though you're not going to get hepatosplenic disease or hematuria , it's really more about, um, those complications.

400
00:32:22,350 --> 00:32:24,030
So that's just an FYI.

401
00:32:24,420 --> 00:32:27,720
Um, and then of course, fever associated with hemorrhage.

402
00:32:27,720 --> 00:32:32,220
You're going to look up and see whether or not there are any of the hemorrhagic fever.

403
00:32:32,730 --> 00:32:48,170
If there's outbreaks, in Nigeria and you're always going to keep, you're going to keep them on your list, because again, we talked about the fact that that's a public health issue, and so these patients may need to be isolated and anybody that cares for them, um, may need to be protected.

404
00:32:48,170 --> 00:32:51,260
And so that's an important thing to always keep on our list.

405
00:32:51,690 --> 00:32:56,910
So what would I do next blood cultures, a UA, a flu swab or respiratory panel?

406
00:32:57,330 --> 00:32:59,460
COVID I might repeat it.

407
00:32:59,560 --> 00:33:02,700
HIV tests, we talked about, , pregnancy tests.

408
00:33:03,010 --> 00:33:04,030
, why would I do that?

409
00:33:04,030 --> 00:33:11,200
Because I'd be worried about malaria and those individuals that are pregnant are more likely to have severe malaria and it changes the way I approach them.

410
00:33:11,590 --> 00:33:18,340
And then of course I would do a peripheral blood smear and I would do, um, a rapid diagnostic test for malaria.

411
00:33:19,395 --> 00:33:25,825
And remember your rapid diagnostic is great for falciparum, but not as great for the other malaria.

412
00:33:26,035 --> 00:33:34,055
And the most other important thing is it may miss low parasitemias and, and you don't get a percentage parasitemia.

413
00:33:34,375 --> 00:33:37,795
So there are only good to say, yeah, this patient's got malaria.

414
00:33:38,065 --> 00:33:42,115
And so that's important because the patient has a low bicarb is not immune.

415
00:33:42,115 --> 00:33:44,455
You might jump on this patient a little bit differently.

416
00:33:44,815 --> 00:33:47,655
Um, I'd ask for an LDH, a lactate.

417
00:33:47,675 --> 00:33:49,375
I'd make sure I got a bilirubin.

418
00:33:49,675 --> 00:33:52,385
Would I get the serologies, dengue??

419
00:33:53,035 --> 00:33:58,645
I probably wouldn't, me personally, I would probably rule out my malaria, get the blood cultures that night.

420
00:33:58,835 --> 00:34:01,145
So I can get a malaria smear pretty quickly.

421
00:34:01,385 --> 00:34:04,375
And I, am actually very good at reading smears myself.

422
00:34:04,375 --> 00:34:10,825
So of course, when we see a patient we're seeing a smear within the next 15 minutes, not everybody has access to that.

423
00:34:11,065 --> 00:34:15,995
So a lot of times patients with headaches, you have to worry about,  CNS infections.

424
00:34:15,995 --> 00:34:18,575
And sometimes people get CT scans and LPs.

425
00:34:18,575 --> 00:34:20,855
And I think that depends on how the patient looks.

426
00:34:20,905 --> 00:34:21,415
Shilpa Vasishta: Great.

427
00:34:22,165 --> 00:34:32,515
Um, so we do obtain some further workup, um, and admission urinalysis and urine pregnancy tests are negative as are COVID and flu swabs.

428
00:34:32,765 --> 00:34:45,695
Blood culture, as well as serologies for HIV and viral hepatitis are in process and a peripheral blood smear obtained overnight at your advising reveals normal sized red blood cells, some containing ring forms.

429
00:34:46,325 --> 00:34:53,105
So the patient's blood smear is followed by thin smear on which an average of 10 to 12 ring forms are noted per high power field.

430
00:34:54,675 --> 00:34:54,965
Dr.

431
00:34:54,965 --> 00:34:59,765
Coyle, how would you interpret these findings and how would you characterize or classify this patient's illness?

432
00:35:00,515 --> 00:35:00,905
Christina Coyle: Great.

433
00:35:01,025 --> 00:35:05,765
This is the most important thing that we do as ID clinicians is we interpret the blood smear.

434
00:35:06,185 --> 00:35:12,105
And so when we're looking at a blood smear, the first thing we do is we look at the size of the red cells.

435
00:35:12,405 --> 00:35:15,910
And so we heard that these were normal RBC.

436
00:35:15,920 --> 00:35:22,200
So when we're talking about normal size RBCs, it's moving us towards falciparum and malariae.

437
00:35:22,570 --> 00:35:30,370
I'm going to leave knowlesi out of this, just because it, it occurs in Malaysia and it's not even part of the epi here.

438
00:35:30,650 --> 00:35:40,340
When we talk about enlarged, red cells that are, those are the forms of malaria that, in fact, younger red cells.

439
00:35:40,610 --> 00:35:42,720
And so that's your vivax and your ovale.

440
00:35:43,310 --> 00:35:43,730
All right.

441
00:35:43,730 --> 00:35:45,290
And so that's the way you think about.

442
00:35:45,690 --> 00:35:47,510
You're hearing only rings.

443
00:35:47,720 --> 00:35:59,690
And so these rings are normally when someone, especially from the lab says rings, what they mean is that it looks like the signet ring, like a diamond ring or sometimes like headphones.

444
00:35:59,960 --> 00:36:09,070
And so that's the chromatin and the ring itself is the very thin cytoplasm and the diamond on the signet ring is the chromatin dot.

445
00:36:09,370 --> 00:36:15,720
And so, uh, when we only see that, and they're not enlarged, it's really pushing us to falcip[arum]..

446
00:36:16,120 --> 00:36:17,880
If it turns out it's malariae.

447
00:36:18,180 --> 00:36:18,900
So be it.

448
00:36:18,900 --> 00:36:22,150
But they tend to have very low parasitemia, malariae.

449
00:36:22,470 --> 00:36:25,200
They actually infect senescent red cells.

450
00:36:25,420 --> 00:36:27,850
And we're hearing a lot of red cells infected here.

451
00:36:27,850 --> 00:36:30,540
So this is really pushing us towards falciparum.

452
00:36:30,940 --> 00:36:35,230
The other thing is that we only see rings in this patient.

453
00:36:35,530 --> 00:36:44,440
And so what that's telling us that cytoplasm from that signet ring, right, that, that blue part of the ring is going to actually enlarge over time.

454
00:36:44,470 --> 00:36:46,240
And it has two ways that it can go.

455
00:36:46,510 --> 00:36:52,535
It can develop into what we call a blood schizont, which is what I always say, a blue bag full of merozoites.

456
00:36:52,865 --> 00:37:00,725
Um, and when that ruptures, you're going to get fever or schizogony, and each of those merozoites will then infect another red cell.

457
00:37:01,025 --> 00:37:03,515
So for malaria, it's about 10 merozoites.

458
00:37:03,605 --> 00:37:09,515
So for every infected schizont, you're going to get  10 to 13 red cells infected after that schizogony.

459
00:37:09,685 --> 00:37:13,455
, and then of course there's gametocytes and the gametocytes do go in the periphery.

460
00:37:13,485 --> 00:37:17,085
And we know in falciparum they look like banana shaped.

461
00:37:18,350 --> 00:37:20,830
So that's going to get picked up by a mosquito.

462
00:37:21,100 --> 00:37:22,690
That causes no symptoms.

463
00:37:22,690 --> 00:37:25,960
It just tells you that the person's been infected for at least two weeks.

464
00:37:26,330 --> 00:37:34,050
So those later stages that you normally,  will occur in the life cycle in falciparum are sequestered.

465
00:37:34,430 --> 00:37:41,240
So when you see a parasitemia of like say 3%, they could have a fever and  schizogony.

466
00:37:41,780 --> 00:37:48,470
And the next eight hours that parasitemia, especially in a non-immune host, can increased quite a lot.

467
00:37:48,860 --> 00:37:53,900
Um, I've seen 2% in the morning in non-immune hosts and 20% in the evenings.

468
00:37:54,170 --> 00:37:59,780
So what you're seeing on a blood smear, isn't representing exactly what's going on in the patient.

469
00:37:59,780 --> 00:38:03,200
And there could be a sequestered biomass that you're not accounting for.

470
00:38:03,500 --> 00:38:11,630
And that's why getting a blood smear and parasitemia on falciparum, you should definitely, you're taking everything into consideration, right?

471
00:38:11,630 --> 00:38:17,150
You're taking the immunity into consideration and you're knowing that in eight hours, this might be different.

472
00:38:17,150 --> 00:38:20,480
That's why you're looking at your end organ, your brain, right.

473
00:38:20,480 --> 00:38:22,070
You're looking at your kidneys.

474
00:38:22,340 --> 00:38:23,960
You're looking at the blood pressure.

475
00:38:23,990 --> 00:38:29,200
You're looking at pulmonary, you're looking at all of these things and of course you're looking at acidosis.

476
00:38:29,465 --> 00:38:29,885
Right.

477
00:38:30,125 --> 00:38:38,945
And so these are all the things that you're looking at because you know that parasitemia although, once it's greater than 4% in some, in a non-endemic region,

478
00:38:38,975 --> 00:38:42,935
so somebody that isn't being exposed all the time, right.

479
00:38:43,265 --> 00:38:44,855
It's going to be severe malaria.

480
00:38:45,005 --> 00:38:49,055
You're also going to be worried about somebody with 3.5%, 2%.

481
00:38:49,265 --> 00:38:55,265
They're going to make you worried if they're non-immune and they've got end organ  damage, and they don't look well, they just don't look well.

482
00:38:55,565 --> 00:39:00,125
So these are the things that we're thinking about when we're looking at this blood smear.

483
00:39:00,155 --> 00:39:20,360
And this is the reason why you only see early forms in  P.falciparum, as opposed to be P.vivax and P.ovale, where you're going to see the later stages, you're going to see the schizonts in there and they're going to be enlarge and  there's something called Schuffner dots that, you know, you're not going to see in the middle of the night, your parasitologist is going to pick up.

484
00:39:20,630 --> 00:39:23,990
Um, and so that's the way that you're going to look at this smear.

485
00:39:24,260 --> 00:39:35,585
And so then you're going to calculate out the parasitemia and to be frank, I personally always say to my residents, because we're normally there in the middle of the night, this never happens during the day.

486
00:39:35,615 --> 00:39:36,005
Right.

487
00:39:36,245 --> 00:39:51,215
So I normally say let's go up to hematology lab and sit there and look at the smear with the hematologist because they basically have done a smear and we're not going to wait until the morning and I kind of ballpark it.

488
00:39:51,485 --> 00:39:58,285
So all you do is you basically look at the number of parasitized, the total RBCs you're doing per field.

489
00:39:58,505 --> 00:40:07,395
I kind of, I, you know, it's a gross, but I normally somewhere within a couple of percentages and then the number of parasitized RBC.

490
00:40:07,415 --> 00:40:13,035
So I do number of parasitized RBCs in the number of total RBCs per field.

491
00:40:13,245 --> 00:40:13,935
And I do an average.

492
00:40:14,515 --> 00:40:17,695
So if there's a lot, sometimes I only need to look at five fields.

493
00:40:18,025 --> 00:40:22,405
Um, if, if there's not, then I look at five to 10 fields and then I average them out.

494
00:40:22,465 --> 00:40:29,275
Of course, I multiply it by a hundred and I get around about percentage because I need to know how sick this patient is.

495
00:40:29,275 --> 00:40:32,645
And I need to have an idea if we're talking a high parasitemia.

496
00:40:32,835 --> 00:40:37,705
So we're talking that this person has a parasitemia, of greater than 4%.

497
00:40:37,705 --> 00:40:39,595
So we're worried.

498
00:40:39,775 --> 00:40:50,755
So high parastiemia in the absence of signs of severity is associated with an increased mortality in a non-immune individual, and I'm going to add or waning immunity.

499
00:40:50,755 --> 00:40:58,365
So those individuals that I see that have been out of the endemic region for years and years and years, right?

500
00:40:58,665 --> 00:41:06,655
Um, the, basically the low parasitemia, ,  doesn't reflect a high sequestered biomass and shouldn't reassure you.

501
00:41:06,865 --> 00:41:11,935
So you have to be on top of this patient and make sure that you're getting a smear eight hours later.

502
00:41:12,015 --> 00:41:19,735
So if they look sick and they have a low parasitemia and not low, low, like less than one, but not 4%.

503
00:41:19,735 --> 00:41:21,505
I'm still very worried about them.

504
00:41:22,045 --> 00:41:29,525
Patients can look well and if they're not treated properly,  umand promptly, um, they can deteriorate very, very, uh, rapidly.

505
00:41:29,525 --> 00:41:32,255
So treatment of malaria is an emergency.

506
00:41:32,345 --> 00:41:46,805
It's an absolute emergency and deciding whether or not we, we want to do IV or oral is really critical for us as ID people, because we only have a window the same way we do in gram negative sepsis.

507
00:41:47,025 --> 00:41:52,275
Shilpa Vasishta: I can just, uh, provide, uh, uh, some of that, the data that you referenced there for our patient.

508
00:41:52,695 --> 00:42:11,615
Uh, so the patient is, uh, as you described, diagnosed with severe Plasmodium falciparum malaria,  based on confirmed parasitemia on smear with initial 2% burden and severe features, including acute anemia, metabolic acidosis, and acute kidney injury.

509
00:42:12,365 --> 00:42:18,755
A repeat peripheral blood smear is obtained eight hours later and reveals an increase in parasite burden to 15%.

510
00:42:19,085 --> 00:42:20,465
She remains well appearing.

511
00:42:21,065 --> 00:42:23,225
What are your management recommendations for this patient?

512
00:42:23,310 --> 00:42:33,540
Christina Coyle: First of all, so  I think that's such a great example of how somebody like this really had a sequestered bio-mass when she first had a smear.

513
00:42:33,790 --> 00:42:38,390
That initial bicarb of 16, the elevated creatinine a bit trickier.

514
00:42:38,410 --> 00:42:43,930
I think, um, you have to remember that patients come in severely dehydrated with malaria.

515
00:42:44,080 --> 00:42:46,990
So a lot of times we can't say anything until we hydrate them.

516
00:42:47,230 --> 00:42:50,440
So I tend not to say anything until they're hydrated.

517
00:42:50,490 --> 00:43:00,720
So for us, the most important thing, um, is now we've got a high parasitemia, and we've got a low bicarb and we've got a non-immune host.

518
00:43:00,900 --> 00:43:05,070
So for us, she needs criteria for severe disease.

519
00:43:05,380 --> 00:43:09,330
If she had had mild disease, we could have used oral, but she didn't.

520
00:43:09,390 --> 00:43:15,600
And, and I just want to remind you that anywhere in Sub-Saharan Africa is considered chloroquine resistant.

521
00:43:15,910 --> 00:43:23,380
So you only have three choices in non-severe disease and that's artemether / lumefantrine, which would be your number one choice.

522
00:43:23,710 --> 00:43:33,880
Atovaquone proguanil, which you could use (Malarone) in non-severe disease or quinine plus doxycycline or in pregnant women, quinine plus clindamycin.

523
00:43:33,880 --> 00:43:35,980
If you don't have the other two available.

524
00:43:37,390 --> 00:43:41,680
So this patient meets criteria for severe disease.

525
00:43:41,890 --> 00:43:46,630
So I would, especially as a fellow, I would call a lifeline.

526
00:43:46,630 --> 00:43:48,940
And so your lifeline will be CDC.

527
00:43:49,210 --> 00:43:52,580
And so in the middle of the night, it's always worth calling CDC.

528
00:43:52,880 --> 00:43:58,880
And, um, you can either get artesunate from them or it's commercially available right now.

529
00:43:59,220 --> 00:44:03,810
I just wanted to spend two seconds on severe disease in adults.

530
00:44:04,170 --> 00:44:09,960
So when you look at most of your disease that you get taught in medical school, you get taught about children.

531
00:44:10,230 --> 00:44:17,140
And so in Africa, the burden of disease of malaria is really  seen in children under the age of five years.

532
00:44:17,470 --> 00:44:22,480
And so for those individuals, we see cerebral malaria and there's a literature on this.

533
00:44:22,840 --> 00:44:24,610
Um, and then acidosis.

534
00:44:24,670 --> 00:44:28,510
And of course we see severe, uh, malaria anemia.

535
00:44:28,960 --> 00:44:37,360
As we start moving to adulthood, and we start looking at the data coming out of Asia, where, um, malaria is not holo endemic.

536
00:44:37,390 --> 00:44:39,790
So you get a lot of adults with severe disease.

537
00:44:40,150 --> 00:45:02,210
We actually see yes, cerebral malaria in those individuals, um, and it acts a bit different than kids,  but we see non-cardiogenic pulmonary edema more, kidney failure more, um, and so we have to be on the lookout for this as when we see an adult with malaria, I already mentioned that in pregnancy, especially the third trimester -mester uh, malaria can be more severe.

538
00:45:02,210 --> 00:45:05,540
So I always get a pregnancy test on my patients.

539
00:45:05,830 --> 00:45:09,410
And so this patient, , we would definitely give artesunate.

540
00:45:09,430 --> 00:45:12,320
There would be no doubt that we would give artesunate.

541
00:45:13,470 --> 00:45:14,830
One minute on artesunate.

542
00:45:14,850 --> 00:45:19,020
In the United States, uh, IV quinidine used to be available.

543
00:45:19,270 --> 00:45:22,590
But as of two years ago, um, it's no longer available.

544
00:45:22,800 --> 00:45:28,230
Worldwide, artesunate is felt to be the drug of choice for, , severe disease.

545
00:45:28,500 --> 00:45:42,655
Um, it's well tolerated, but the more important piece to artesunate, there were two landmark trials looking at artesunate vs IV quinidine in severe malaria and IV artesunate was superior.

546
00:45:42,895 --> 00:45:52,705
And that is because it works on killing those young circulating ring stage parasites that you saw on the blood smear, which quinidine doesn't.

547
00:45:52,825 --> 00:45:57,385
So there's more rapid killing and so more rapid activity.

548
00:45:57,475 --> 00:46:03,865
Um, and that's important because we're going to talk about a side effect of artesunate that you have to worry about in this particular patient.

549
00:46:03,925 --> 00:46:05,485
I just want to say one other thing.

550
00:46:05,935 --> 00:46:08,005
I want to talk about dehydration.

551
00:46:08,215 --> 00:46:14,545
These patients are very dehydrated, so  as ID person, we don't normally do, um, management of fluids.

552
00:46:14,755 --> 00:46:25,835
This is the one situation where I really get involved because they're hypovolemic and  if you over hydrate them or really give them too much fluid, too quickly,

553
00:46:26,105 --> 00:46:33,725
some people feel you can get these leaky capillaries and  that you're more likely to get a non cardiogenic pulmonary edema.

554
00:46:34,025 --> 00:46:42,645
So what I normally tell my, uh, house staff and my emergency room and my ICU is to basically hydrate them and bring them to euvolemia.

555
00:46:42,785 --> 00:46:47,435
And at that point match their I's and O's, and I think most people feel that.

556
00:46:47,435 --> 00:46:51,305
And obviously I tell them about this non-cardiogenic pulmonary edema.

557
00:46:51,695 --> 00:46:57,285
And the other thing is you can get hypoglycemia, especially in somebody with poor oral intake.

558
00:46:57,435 --> 00:47:03,825
So I'm always just, I just always remember that if there's a change in mental status and I make sure that we give them some glucose.

559
00:47:03,825 --> 00:47:06,495
So those are some things that I do when I'm managing patients.

560
00:47:06,855 --> 00:47:09,585
And then the last thing is, is that patients vomit a lot.

561
00:47:09,855 --> 00:47:21,405
And so it's very important if you've chosen to go oral, which we're not doing with this patient that you watch, because some patients actually have to get IV artesunate, especially pregnant patients, because they're not tolerating orals.

562
00:47:21,555 --> 00:47:24,945
So even though they don't meet criteria for severe disease.

563
00:47:24,995 --> 00:47:25,505
Shilpa Vasishta: Great.

564
00:47:26,045 --> 00:47:34,145
Um, so this patient does receive IV therapy with artesunate, uh, 2.4 milligrams per kilogram, dosed Q 12 hours.

565
00:47:34,535 --> 00:47:47,915
A repeat peripheral smear after the third dose demonstrates persistent 4% parasitemia, therefore therapy has continued for an additional 48 hours with daily smears until her parasite burden drops to less than 1%.

566
00:47:48,425 --> 00:47:55,355
She's then transitioned to oral artemether and lumefantrine to be continued for an additional three days after discharge.

567
00:47:55,985 --> 00:47:58,865
Uh, what further followup will she need upon discharge?

568
00:47:58,865 --> 00:48:02,375
And how would you counsel this patient on preventive measures for future travel?

569
00:48:02,522 --> 00:48:15,022
Christina Coyle: For this case, what CDC recommends is that once you started artesunate, the way to think about it is that once they're at 1% or less, you're kind of treating them as uncomplicated malaria.

570
00:48:15,022 --> 00:48:16,192
That's the way to think about it.

571
00:48:16,192 --> 00:48:28,593
So the most important thing in a patient like this is that, um, in non-immune travelers, there's something called delayed onset hemolysis or post artesunate delayed onset hemolysis.

572
00:48:28,973 --> 00:48:36,713
And you can almost assume, and I don't know if this patient had it, you can almost assume that patients with high parasitemia are going to get it.

573
00:48:36,713 --> 00:48:42,813
And the reason why is it's due to that, that clearance of the young ring stages that we talked about.

574
00:48:43,143 --> 00:48:49,073
And so it rapidly kills them, but the dead parasite becomes what's called pyknotic.

575
00:48:49,473 --> 00:48:54,513
And so it circulates for a while, and then it gets taken out of circulation late.

576
00:48:54,513 --> 00:48:57,693
And so we started seeing delayed hemolysis due to that.

577
00:48:57,963 --> 00:49:01,173
And so we'll see it in non-immune travelers with high parasitemia.

578
00:49:01,173 --> 00:49:02,523
This patient is at huge risk.

579
00:49:02,583 --> 00:49:12,483
So the two things that I do is yes, I see them at two weeks and I check, I normally see patients a week after, myself personally, and make sure that their labs, everything looks normal.

580
00:49:12,483 --> 00:49:14,893
I educate them on symptoms of anemia.

581
00:49:15,668 --> 00:49:17,888
Um, because sometimes they'll just become short of breath.

582
00:49:17,888 --> 00:49:24,308
So I want to let them know to call me immediately and the way to treat it normally is to actually transfuse them.

583
00:49:24,923 --> 00:49:27,113
And, uh, and then we check them at two weeks.

584
00:49:27,113 --> 00:49:30,023
So the most important thing is also to educate them about that.

585
00:49:30,293 --> 00:49:38,193
And this is a patient that you also want to reinforce  malaria prophylaxis the next time she goes.

586
00:49:38,463 --> 00:49:47,373
Um, and so for her, there are three choices of, , malaria prophylaxis and she has doxycycline, which is daily.

587
00:49:47,653 --> 00:49:52,493
And then there is Malarone and that is,  also daily.

588
00:49:52,773 --> 00:50:02,693
The difference between doxy and Malarone is that, um, doxy just has more breakthroughs if you miss doses and also for women.

589
00:50:02,858 --> 00:50:06,728
Um, there's the risk of getting, uh, vaginal candidiasis.

590
00:50:06,728 --> 00:50:12,428
So I always send people with Fluconazole and of course it makes you more sun sensitive.

591
00:50:12,428 --> 00:50:18,068
So you really need to emphasize sunscreen no matter what  in all individuals.

592
00:50:18,128 --> 00:50:20,898
And, um, and then you can get a pill esophagitis.

593
00:50:20,918 --> 00:50:23,718
Some people who take it just love it and their adherent.

594
00:50:23,738 --> 00:50:25,088
So it's a great drug for them.

595
00:50:25,358 --> 00:50:29,798
Malarone is really well tolerated, but for longer trips can be quite expensive.

596
00:50:30,068 --> 00:50:40,068
And that leaves us then with mefloquine which is weekly and  great for longer trips, but important because it has a black box warning for it's CNS side effects.

597
00:50:40,648 --> 00:50:49,318
It's super important before you give mefloquine and the dosing we use for treatment, we tend not to use Mefloquine because of its side effect profile for treatment.

598
00:50:49,558 --> 00:50:55,258
So you're going to really emphasize to her that when she goes, she needs to listen to our pre-travel advice.

599
00:50:55,528 --> 00:50:58,168
Um, great that she sought it out, but she's got to listen to it.

600
00:50:58,468 --> 00:51:00,778
And, um, I think that's what I would say.

601
00:51:02,918 --> 00:51:09,308
Sara Dong: Thank you to Shilpa and Christina for joining us today and talking through this awesome case.

602
00:51:09,878 --> 00:51:15,788
We are planning to have several more episodes related to fever in the summer or fever in a returning traveler.

603
00:51:16,058 --> 00:51:17,978
So stay tuned for those.

604
00:51:18,488 --> 00:51:29,948
Uh, don't forget to check out the website febrilepodcast.com, where you can find the Consult Notes, which are written summaries from the show with links to references, our library of ID infographics and a link to our merch store.

605
00:51:30,458 --> 00:51:34,688
Please reach out if you have any suggestions for future shows or just want to be more involved with Febrile.

606
00:51:35,198 --> 00:51:36,608
Thanks for listening, stay safe.

607
00:51:36,638 --> 00:51:38,148
And I'll see you next time,