47: Bad Air

Sara Dong: 00:00:12

Hi everyone.

Sara Dong: 00:00:13

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

Sara Dong: 00:00:17

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

Sara Dong: 00:00:22

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

Sara Dong: 00:00:26

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

Sara Dong: 00:00:30

Joining me as co-host today is Dr.

Sara Dong: 00:00:32

Shilpa Vasishta.

Sara Dong: 00:00:34

. 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.

Shilpa Vasishta: 00:00:40

Hi, excited to be here.

Sara Dong: 00:00:43

And our guests consultant today is Dr.

Sara Dong: 00:00:44

Christina Coyle.

Sara Dong: 00:00:46

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

Sara Dong: 00:00:53

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

Christina Coyle: 00:01:01

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

Sara Dong: 00:01:03

Awesome.

Sara Dong: 00:01:04

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,

Christina Coyle: 00:01:17

I'll start.

Christina Coyle: 00:01:18

Um, so what brings me joy?

Christina Coyle: 00:01:20

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

Christina Coyle: 00:01:24

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.

Christina Coyle: 00:01:30

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

Christina Coyle: 00:01:35

So it's a real passion of mine.

Shilpa Vasishta: 00:01:39

Dr.

Shilpa Vasishta: 00:01:39

Coyle, that is so awesome.

Shilpa Vasishta: 00:01:40

I too love ballet.

Shilpa Vasishta: 00:01:42

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.

Shilpa Vasishta: 00:01:49

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.

Shilpa Vasishta: 00:02:02

Um, and my son loves to imitate it.

Shilpa Vasishta: 00:02:03

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

Sara Dong: 00:02:08

Excellent!

Christina Coyle: 00:02:08

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

Sara Dong: 00:02:13

Yes.

Sara Dong: 00:02:15

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

Sara Dong: 00:02:21

The consult question is about worsening fevers.

Sara Dong: 00:02:24

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

Shilpa Vasishta: 00:02:27

Thank you.

Shilpa Vasishta: 00:02:28

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

Shilpa Vasishta: 00:02:33

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

Shilpa Vasishta: 00:02:39

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

Shilpa Vasishta: 00:02:43

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

Shilpa Vasishta: 00:02:50

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

Shilpa Vasishta: 00:02:56

And for medications, she takes an oral contraceptive.

Shilpa Vasishta: 00:02:59

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.

Shilpa Vasishta: 00:03:09

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

Shilpa Vasishta: 00:03:13

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

Shilpa Vasishta: 00:03:21

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

Shilpa Vasishta: 00:03:26

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

Shilpa Vasishta: 00:03:34

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

Shilpa Vasishta: 00:03:37

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

Shilpa Vasishta: 00:03:42

She is tachycardic.

Shilpa Vasishta: 00:03:43

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

Shilpa Vasishta: 00:03:47

Her abdomen is nontender.

Shilpa Vasishta: 00:03:49

Liver and spleen are nonpalpable and she has no rashes.

Shilpa Vasishta: 00:03:53

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

Shilpa Vasishta: 00:03:58

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

Shilpa Vasishta: 00:04:03

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

Shilpa Vasishta: 00:04:14

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

Shilpa Vasishta: 00:04:20

What are your initial thoughts in hearing this case?

Shilpa Vasishta: 00:04:22

And what additional information would you like?

Christina Coyle: 00:04:24

Okay.

Christina Coyle: 00:04:25

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.

Christina Coyle: 00:04:36

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.

Christina Coyle: 00:04:48

We don't hear a urine.

Christina Coyle: 00:04:49

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.

Christina Coyle: 00:05:02

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

Christina Coyle: 00:05:06

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

Christina Coyle: 00:05:08

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

Christina Coyle: 00:05:10

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.

Christina Coyle: 00:05:23

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

Christina Coyle: 00:05:30

What is treatable, right?

Christina Coyle: 00:05:32

And what's transmissible.

Christina Coyle: 00:05:33

Do I need to isolate this person?

Christina Coyle: 00:05:35

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

Christina Coyle: 00:05:39

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

Christina Coyle: 00:05:44

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.

Christina Coyle: 00:05:55

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.

Christina Coyle: 00:06:03

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

Christina Coyle: 00:06:10

COVID has a short incubation.

Christina Coyle: 00:06:12

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

Christina Coyle: 00:06:19

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

Christina Coyle: 00:06:25

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

Christina Coyle: 00:06:30

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

Christina Coyle: 00:06:34

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

Christina Coyle: 00:06:37

Once you're within a month, right?

Christina Coyle: 00:06:39

You're always thinking about falciparum malaria.

Christina Coyle: 00:06:42

So malaria one, two, and three.

Christina Coyle: 00:06:44

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).

Christina Coyle: 00:06:55

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

Christina Coyle: 00:06:59

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.

Christina Coyle: 00:07:11

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.

Christina Coyle: 00:07:20

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

Christina Coyle: 00:07:27

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

Christina Coyle: 00:07:31

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

Christina Coyle: 00:07:37

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

Christina Coyle: 00:07:42

So I normally ask patients, why did you go?

Christina Coyle: 00:07:45

Did you go for fun?

Christina Coyle: 00:07:46

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

Christina Coyle: 00:07:51

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

Christina Coyle: 00:07:58

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.

Christina Coyle: 00:08:10

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

Christina Coyle: 00:08:16

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

Christina Coyle: 00:08:22

So this is really important.

Christina Coyle: 00:08:23

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

Christina Coyle: 00:08:29

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.

Christina Coyle: 00:08:37

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

Christina Coyle: 00:08:40

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

Christina Coyle: 00:08:42

And obviously I ask for an itinerary.

Christina Coyle: 00:08:45

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.

Christina Coyle: 00:08:54

Travel history really takes quite a while.

Christina Coyle: 00:08:57

I ask everything you can think about, obviously.

Christina Coyle: 00:09:01

Sexual activity during the trip.

Christina Coyle: 00:09:04

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

Christina Coyle: 00:09:07

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

Christina Coyle: 00:09:17

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

Christina Coyle: 00:09:22

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

Christina Coyle: 00:09:25

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

Christina Coyle: 00:09:29

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

Christina Coyle: 00:09:35

We always ask about food and water.

Christina Coyle: 00:09:36

Right?

Christina Coyle: 00:09:37

We ask about bottled water.

Christina Coyle: 00:09:38

Everyone says they use bottled water.

Christina Coyle: 00:09:40

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

Christina Coyle: 00:09:46

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

Christina Coyle: 00:09:50

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.

Christina Coyle: 00:10:02

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

Christina Coyle: 00:10:06

I do a geographicgeographic, right?.

Christina Coyle: 00:10:08

So that helps me hone down.

Christina Coyle: 00:10:10

Exposures.

Christina Coyle: 00:10:11

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

Christina Coyle: 00:10:16

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

Christina Coyle: 00:10:22

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

Christina Coyle: 00:10:27

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.

Christina Coyle: 00:10:34

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.

Sara Dong: 00:10:44

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?

Christina Coyle: 00:10:54

I ask a lot about pre-travel.

Christina Coyle: 00:10:56

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

Christina Coyle: 00:10:58

You can go to CDC.

Christina Coyle: 00:10:59

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

Christina Coyle: 00:11:03

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

Christina Coyle: 00:11:11

It's called GTEN.

Christina Coyle: 00:11:13

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

Christina Coyle: 00:11:16

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.

Christina Coyle: 00:11:32

So it's going to come up with vaccines.

Christina Coyle: 00:11:34

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.

Christina Coyle: 00:11:43

So she probably had yellow fever.

Christina Coyle: 00:11:45

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.

Christina Coyle: 00:11:51

Meningo[coccus] comes up during the dry season.

Christina Coyle: 00:11:53

So that's important.

Christina Coyle: 00:11:54

She has a headache.

Christina Coyle: 00:11:55

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

Christina Coyle: 00:11:57

Hepatitis A.

Christina Coyle: 00:11:58

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

Christina Coyle: 00:12:02

Hepatitis B.

Christina Coyle: 00:12:03

. Flu vaccine.

Christina Coyle: 00:12:03

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

Christina Coyle: 00:12:09

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

Christina Coyle: 00:12:12

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.

Christina Coyle: 00:12:19

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

Christina Coyle: 00:12:23

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

Christina Coyle: 00:12:30

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

Christina Coyle: 00:12:33

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

Christina Coyle: 00:12:40

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

Christina Coyle: 00:12:47

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.

Christina Coyle: 00:12:55

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

Christina Coyle: 00:13:01

And of course the most important thing is malaria prophylaxis.

Christina Coyle: 00:13:04

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

Christina Coyle: 00:13:10

That's number one.

Christina Coyle: 00:13:11

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

Christina Coyle: 00:13:14

Right.

Christina Coyle: 00:13:14

So any breaks in malaria prophylaxis?

Christina Coyle: 00:13:16

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

Christina Coyle: 00:13:22

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

Christina Coyle: 00:13:29

And a lot of people aren't always compliant.

Christina Coyle: 00:13:31

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

Christina Coyle: 00:13:37

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.

Christina Coyle: 00:13:46

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

Christina Coyle: 00:13:51

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

Christina Coyle: 00:13:58

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.

Christina Coyle: 00:14:09

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

Christina Coyle: 00:14:13

So you're going in with that mindset.

Christina Coyle: 00:14:15

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

Christina Coyle: 00:14:21

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.

Christina Coyle: 00:14:28

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.

Christina Coyle: 00:14:41

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

Christina Coyle: 00:14:46

And the fever may not be what they complain about.

Christina Coyle: 00:14:49

And so you can get derailed and misdiagnosed.

Christina Coyle: 00:14:53

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.

Christina Coyle: 00:15:03

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

Christina Coyle: 00:15:11

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

Sara Dong: 00:15:15

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

Christina Coyle: 00:15:18

This patient kind of checks the boxes.

Christina Coyle: 00:15:21

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.

Christina Coyle: 00:15:33

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

Christina Coyle: 00:15:37

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

Christina Coyle: 00:15:40

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

Christina Coyle: 00:15:44

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

Christina Coyle: 00:15:47

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

Christina Coyle: 00:15:52

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

Christina Coyle: 00:15:56

So we rarely don't see it.

Christina Coyle: 00:15:58

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

Christina Coyle: 00:16:04

It doesn't mean it's not, I'm still gonna rule it out, but thrombocytopenia is normally the rule.

Christina Coyle: 00:16:09

It is not prognostic of how sick the patient is.

Christina Coyle: 00:16:13

The prognosis is really going to be on end organ and also parasitemia.

Christina Coyle: 00:16:18

Right.

Christina Coyle: 00:16:19

We can see any white count in malaria.

Christina Coyle: 00:16:21

We could see a low white count.

Christina Coyle: 00:16:22

We normally don't see high white count similarly.

Christina Coyle: 00:16:25

So if you start seeing a white count of 25, that's gonna make malaria either less likely or dual infection.

Christina Coyle: 00:16:32

The person might have a bacterial infection plus malaria.

Christina Coyle: 00:16:35

Also, we're a bit worried about that bicarb of 16, and that should be something that's a red flag for us.

Christina Coyle: 00:16:42

And the creatinine is slightly elevated.

Christina Coyle: 00:16:44

So these things are red flags when we get called on the phone phone, we also hear that she's from Brazil.

Christina Coyle: 00:16:51

So we're not sure if she's ever had malaria before.

Christina Coyle: 00:16:53

There is some malaria in Brazil.

Christina Coyle: 00:16:55

So, but it was years ago, right?

Christina Coyle: 00:16:58

She's a long-term long time out of Brazil.

Christina Coyle: 00:17:01

So we're assuming she's non-immune so that's also making us worried.

Christina Coyle: 00:17:05

So this is all my malaria brain going on, but I don't want to get too focused on malaria and missed other things.

Christina Coyle: 00:17:11

Right.

Christina Coyle: 00:17:12

So the other things you're going to ask for are going to be urine, right?

Christina Coyle: 00:17:16

I'm going to ask for obviously, um, a blood smear, I'm going to ask for an LDH.

Christina Coyle: 00:17:22

I'm going to ask for a lactate.

Christina Coyle: 00:17:24

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.

Christina Coyle: 00:17:31

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.

Shilpa Vasishta: 00:17:39

Yeah, sure.

Shilpa Vasishta: 00:17:40

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.

Shilpa Vasishta: 00:17:48

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.

Shilpa Vasishta: 00:17:57

Uh, she drank exclusively bottled water.

Shilpa Vasishta: 00:18:00

She did make one weekend trip during which she hiked in a wooded area and swam in a freshwater lake.

Shilpa Vasishta: 00:18:06

She does not recall any contact with animals though, does endorse mosquito bites despite use of mosquito netting.

Shilpa Vasishta: 00:18:12

And she was not sexually active during her travel.

Shilpa Vasishta: 00:18:15

She had a pre-travel consultation where she completed yellow fever vaccination, and was offered typhoid vaccination, but declined.

Shilpa Vasishta: 00:18:23

She was otherwise noted to be up to date on routine immunizations.

Shilpa Vasishta: 00:18:27

She was prescribed doxycycline, which she reports not taking consistently during her two weeks of travel.

Christina Coyle: 00:18:32

Okay, great.

Christina Coyle: 00:18:33

So let's go over the history that you just told me.

Christina Coyle: 00:18:36

So I'm on the phone now.

Christina Coyle: 00:18:37

I'm still the ID fellow on the phone.

Christina Coyle: 00:18:39

And so she's, uh, she's a short-term traveler.

Christina Coyle: 00:18:42

She's been there for two weeks.

Christina Coyle: 00:18:44

she was in a hotel, but she did have some high risk behavior in terms of her eating.

Christina Coyle: 00:18:48

Right?

Christina Coyle: 00:18:48

So, um, she went to an outdoor, uh, food vendors.

Christina Coyle: 00:18:52

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.

Christina Coyle: 00:19:03

She made a weekend trip where she hiked in a wooded area.

Christina Coyle: 00:19:07

So that would pique my interest.

Christina Coyle: 00:19:08

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]

Christina Coyle: 00:19:28

so they're at risk for being exposed to schisto and that's your rule.

Christina Coyle: 00:19:31

All right.

Christina Coyle: 00:19:32

You don't have to look that one up.

Christina Coyle: 00:19:34

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.

Christina Coyle: 00:19:41

We'll forget about it.

Christina Coyle: 00:19:42

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.

Christina Coyle: 00:19:50

So malaria was big, big, big.

Christina Coyle: 00:19:53

Big big, big, um, she had a pre-con, uh, travel consultation.

Christina Coyle: 00:19:57

She got her yellow fever vaccination.

Christina Coyle: 00:20:00

Um, and, she wasn't compliant with her doxy or was she, I can't remember.

Christina Coyle: 00:20:05

Did she, did she take her anymore?

Shilpa Vasishta: 00:20:07

Uh, she was prescribed them, um, and reports not taking them.

Christina Coyle: 00:20:11

Okay.

Christina Coyle: 00:20:12

So that's important.

Christina Coyle: 00:20:14

For this, we talked about risk factors, so we just went over some of her risk factors.

Christina Coyle: 00:20:20

And so this is where we now did geographic.

Christina Coyle: 00:20:24

And we took her risk factors and we talked about the things within west Africa that might cause fever.

Christina Coyle: 00:20:30

And now we then might think about syndromic.

Christina Coyle: 00:20:34

And so for this patient, although she's got a headache, I would really put her into an undifferentiated fever.

Christina Coyle: 00:20:42

And then I break it into malarial versus non malarial.

Christina Coyle: 00:20:47

Um, and that's how I would approach her.

Christina Coyle: 00:20:49

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.

Christina Coyle: 00:21:00

Uh, when we think about an undifferentiated fever, we have to be really careful about not, not only thinking about tropical diseases.

Christina Coyle: 00:21:10

So we need to think about UTI.

Christina Coyle: 00:21:12

We need to think about respiratory infection.

Christina Coyle: 00:21:14

She's got a negative chest x-ray so that's really unlikely.

Christina Coyle: 00:21:17

We talked about influenza.

Christina Coyle: 00:21:18

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.

Christina Coyle: 00:21:28

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.

Christina Coyle: 00:21:42

Um, and then, a rash always changes things.

Christina Coyle: 00:21:45

A rash puts us into dengue, chik[ungunya] again, acute HIV, measles, and then acute schisto[somiasis].

Christina Coyle: 00:21:52

Um, and then within the rash, I always look for a eschar.

Christina Coyle: 00:21:56

The patient has to take their clothes off.

Christina Coyle: 00:21:59

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.

Christina Coyle: 00:22:09

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.

Christina Coyle: 00:22:17

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.

Christina Coyle: 00:22:26

And if you're not looking, you'll miss an eschar.

Christina Coyle: 00:22:29

. So then, you know, there's other syndromes in this patient right now, doesn't meet them.

Christina Coyle: 00:22:33

So fever with jaundice.

Christina Coyle: 00:22:35

So if I see that, I start thinking severe malaria, hemorrhagic, fevers, et cetera.

Christina Coyle: 00:22:40

Fever with GI complaints.

Christina Coyle: 00:22:42

And so we can supply you with a nice list of syndromic approach to fever and the traveler.

Christina Coyle: 00:22:49

I just wanted to spend a few minutes on each thing to think about.

Christina Coyle: 00:22:53

So dengue.

Christina Coyle: 00:22:54

After malaria, the most common when we look at Geo Sentinel, which is a worldwide surveillance site, um, and, uh, supported by CDC.

Christina Coyle: 00:23:04

The most common cause of fever on the traveler after malaria is dengue.

Christina Coyle: 00:23:09

Dengue is transmitted by, um, Aedes aegypti or albopictus and, um, it's worldwide.

Christina Coyle: 00:23:16

And it's found in Africa.

Christina Coyle: 00:23:19

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.

Christina Coyle: 00:23:30

They really do tell you that.

Christina Coyle: 00:23:32

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.

Christina Coyle: 00:23:42

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.

Christina Coyle: 00:23:54

So on a person with white skin or light skin, it's called islands of white in a sea of red.

Christina Coyle: 00:24:01

This is harder to see in darker skinned individuals.

Christina Coyle: 00:24:04

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.

Christina Coyle: 00:24:12

It's really important for us to recognize different rashes on different, uh, different skin colors.

Christina Coyle: 00:24:18

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.

Christina Coyle: 00:24:25

And it's got a very short incubation.

Christina Coyle: 00:24:28

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.

Christina Coyle: 00:24:38

Um, and risk factors are obviously everything that this patient has and leukopenia and thrombocytopenia like this patient are characteristic.

Christina Coyle: 00:24:47

When you, you look at dengue, it's most common to be reported from Asia.

Christina Coyle: 00:24:51

It is reported from Africa, but not commonly.

Christina Coyle: 00:24:54

I'll tell you in my experience, I've definitely, um, diagnosed people with dengue from, um, Africa.

Christina Coyle: 00:24:59

It is on my differential.

Christina Coyle: 00:25:01

For this patient, I would probably rule out malaria first, before I even sent a dengue serology, me personally.

Christina Coyle: 00:25:07

, but when you're talking about getting bit by mosquitoes and there's Aedes aegypti and albopictus in Africa.

Christina Coyle: 00:25:13

So you have to think about chikungunya and Zika.

Christina Coyle: 00:25:16

Chikungunya has a short incubation and here arthralgias are the prominent symptoms

Christina Coyle: 00:25:22

. 70% of patients are going to complain of arthralgia.

Christina Coyle: 00:25:25

And if you've ever seen somebody with chikungunya, which means bent over, they really are bent over.

Christina Coyle: 00:25:30

This patient has no rheumatologic symptoms.

Christina Coyle: 00:25:33

I don't think I would even send a chikungunya serology.

Christina Coyle: 00:25:36

, Skin manifestations are also reported in chikungunyah, but we don't share that in this patient.

Christina Coyle: 00:25:43

I'm going to spend two seconds on Zika.

Christina Coyle: 00:25:45

You can look it up and see where Zika outbreaks are occurring.

Christina Coyle: 00:25:48

Again, it's transmitted by the same mosquitoes as dengue and chikungunya.

Christina Coyle: 00:25:54

The illness tends to be mild and even asymptomatic in many individuals.

Christina Coyle: 00:25:58

And here there's a pruritic rash and patients can have arthritis,

Christina Coyle: 00:26:02

and conjunctivitis.

Christina Coyle: 00:26:04

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.

Christina Coyle: 00:26:14

So I would think that would be unlikely.

Christina Coyle: 00:26:16

Let's spend some time on typhoid fever cause this individual ate off of roadside stands.

Christina Coyle: 00:26:22

And so for me, we're going to do blood cultures and that's how we'll establish a diagnosis.

Christina Coyle: 00:26:27

But for me, this wouldn't be high on my differential.

Christina Coyle: 00:26:29

Definitely doing the blood cultures, but normally in, patients present, they've normally traveled to Southeast Asia.

Christina Coyle: 00:26:36

They've normally had prolonged fever for greater than seven days.

Christina Coyle: 00:26:40

They normally have chills, but they're not having rigors.

Christina Coyle: 00:26:43

So they tend to come in a little bit later . And, um, it's, caused by Salmonella enterica serotype typhi or para typhi.

Christina Coyle: 00:26:54

Um, incubation can be up to three weeks, early as five days.

Christina Coyle: 00:26:57

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.

Christina Coyle: 00:27:11

There is a rash, it's very hard to see, it's a salmon colored macules, rose spots.

Christina Coyle: 00:27:18

Um, and I really check my patients carefully.

Christina Coyle: 00:27:21

For the majority of patients in our institution are normally from, um, Bangladesh.

Christina Coyle: 00:27:27

So I really really check and we see it mostly in children that haven't gotten vaccinated before they've left.

Christina Coyle: 00:27:32

So there's, there's some clues.

Christina Coyle: 00:27:34

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.

Christina Coyle: 00:27:45

So it's still on the list still in the running.

Christina Coyle: 00:27:48

Let's spend two seconds on rickettsia because it comes up on the list.

Christina Coyle: 00:27:52

So I think for Africa, you need to know about, um, African tick typhus, which is caused by Rickettsia africae.

Christina Coyle: 00:28:00

It is most common in South Africa.

Christina Coyle: 00:28:02

It's really not well described in west Africa, but I do think you need to know about it.

Christina Coyle: 00:28:08

the vector is an, a tick, an Amblyomma species and it's a tick of large ruminants and wildlife.

Christina Coyle: 00:28:15

And it's a very aggressive feeder on humans.

Christina Coyle: 00:28:17

And that's important.

Christina Coyle: 00:28:18

At the site of inoculation, you can get an escahar and you can have regional lymphadnopothy.

Christina Coyle: 00:28:24

Although the patient can actually present with just really headache and fever.

Christina Coyle: 00:28:29

And if you don't look, you'll miss the eschar.

Christina Coyle: 00:28:32

And as I said, you know, many times patients have a number of eschars if you look closely.

Christina Coyle: 00:28:38

Um, and it's normally in people who have been camping, hiking, such as this patient traveling.

Christina Coyle: 00:28:43

It's very common or in safari or in grassy areas, walking in grassy areas.

Christina Coyle: 00:28:49

Again, because they're from west Africa, it makes it less likely.

Christina Coyle: 00:28:54

Lab wise,

Christina Coyle: 00:28:55

they have leukopenia and thrombocytopenia, a low bicarb would.

Christina Coyle: 00:28:59

Go against it.

Christina Coyle: 00:29:00

Right?

Christina Coyle: 00:29:00

You don't look systemically ill, you respond promptly to doxycycline.

Christina Coyle: 00:29:04

You make the diagnosis, you establish it by clinical picture and serology.

Christina Coyle: 00:29:08

So normally we just treat presumptively and they really respond quite rapidly.

Christina Coyle: 00:29:14

Rickettsia conorii or Mediterranean tick typhus, although it's circulating, it's not a common cause of rickettsial diseases in Africa.

Christina Coyle: 00:29:22

So the one that I would know as a, as a fellow would be, um, African tick typhus or Rickettsia africae.

Christina Coyle: 00:29:29

Okay.

Christina Coyle: 00:29:30

So it's really important.

Christina Coyle: 00:29:31

The epi here doesn't support it.

Christina Coyle: 00:29:33

We heard that the patient is not sexually active, but do not forget to ask about a sexual history or blood exposures.

Christina Coyle: 00:29:40

So things like, um, uh, basically body piercing, people get tattoos, people have accidents and they sometimes don't tell you about it.

Christina Coyle: 00:29:49

Minor accidents where somebody actually stitches them, uh, in rural areas with needles.

Christina Coyle: 00:29:55

And you don't know if the needle has been cleaned, so you really need to dig down a bloodborne exposures.

Christina Coyle: 00:30:01

And obviously I don't need to tell this audience about acute HIV and how it can present.

Christina Coyle: 00:30:06

Um, and so then we heard about freshwater, so let's talk about leptospirosis.

Christina Coyle: 00:30:11

And so there's lots of emerging data on people that do go rafting or kayaking.

Christina Coyle: 00:30:16

And coming back with leptospirosis.

Christina Coyle: 00:30:18

So we as ID people need to keep it on our radar.

Christina Coyle: 00:30:22

The incubation is two to 26 days, but it's an average of 10 days.

Christina Coyle: 00:30:26

So this patient, um, is within that.

Christina Coyle: 00:30:29

Although I don't know when they were in fresh water.

Christina Coyle: 00:30:31

The clinical course is variable, but early on, patients can come in with fever, rigors, myalgias, and headaches.

Christina Coyle: 00:30:38

A lot like this patient and conjunctival suffusion is characteristic, but often overlooked.

Christina Coyle: 00:30:46

I need to talk about acute schisto because we don't talk about it enough.

Christina Coyle: 00:30:50

It occurs four to eight weeks after exposure.

Christina Coyle: 00:30:53

So this would be on the very early side, if it was just schistosomiasis.

Christina Coyle: 00:30:57

And I think it's too early for acute schisto because if you do the math, she's back 10 days.

Christina Coyle: 00:31:02

So she'd be right on the cusp.

Christina Coyle: 00:31:04

It's important.

Christina Coyle: 00:31:05

It's a cause of a fever and normally individuals complain of a rash.

Christina Coyle: 00:31:11

Now, not everybody is symptomatic, but those individuals with fever, commonly have urticaria.

Christina Coyle: 00:31:18

And they normally have profound eosinophilia.

Christina Coyle: 00:31:21

So they can have non-specific symptoms.

Christina Coyle: 00:31:24

Two thirds of individual will actually have a cough and they'll have an abnormal chest x-ray, which will be reticulonodular.

Christina Coyle: 00:31:32

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.

Christina Coyle: 00:31:49

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.

Christina Coyle: 00:31:58

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.

Christina Coyle: 00:32:14

So even though you're not going to get hepatosplenic disease or hematuria , it's really more about, um, those complications.

Christina Coyle: 00:32:22

So that's just an FYI.

Christina Coyle: 00:32:24

Um, and then of course, fever associated with hemorrhage.

Christina Coyle: 00:32:27

You're going to look up and see whether or not there are any of the hemorrhagic fever.

Christina Coyle: 00:32:32

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.

Christina Coyle: 00:32:48

And so that's an important thing to always keep on our list.

Christina Coyle: 00:32:51

So what would I do next blood cultures, a UA, a flu swab or respiratory panel?

Christina Coyle: 00:32:57

COVID I might repeat it.

Christina Coyle: 00:32:59

HIV tests, we talked about, , pregnancy tests.

Christina Coyle: 00:33:03

, why would I do that?

Christina Coyle: 00:33:04

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.

Christina Coyle: 00:33:11

And then of course I would do a peripheral blood smear and I would do, um, a rapid diagnostic test for malaria.

Christina Coyle: 00:33:19

And remember your rapid diagnostic is great for falciparum, but not as great for the other malaria.

Christina Coyle: 00:33:26

And the most other important thing is it may miss low parasitemias and, and you don't get a percentage parasitemia.

Christina Coyle: 00:33:34

So there are only good to say, yeah, this patient's got malaria.

Christina Coyle: 00:33:38

And so that's important because the patient has a low bicarb is not immune.

Christina Coyle: 00:33:42

You might jump on this patient a little bit differently.

Christina Coyle: 00:33:44

Um, I'd ask for an LDH, a lactate.

Christina Coyle: 00:33:47

I'd make sure I got a bilirubin.

Christina Coyle: 00:33:49

Would I get the serologies, dengue??

Christina Coyle: 00:33:53

I probably wouldn't, me personally, I would probably rule out my malaria, get the blood cultures that night.

Christina Coyle: 00:33:58

So I can get a malaria smear pretty quickly.

Christina Coyle: 00:34:01

And I, am actually very good at reading smears myself.

Christina Coyle: 00:34:04

So of course, when we see a patient we're seeing a smear within the next 15 minutes, not everybody has access to that.

Christina Coyle: 00:34:11

So a lot of times patients with headaches, you have to worry about, CNS infections.

Christina Coyle: 00:34:15

And sometimes people get CT scans and LPs.

Christina Coyle: 00:34:18

And I think that depends on how the patient looks.

Shilpa Vasishta: 00:34:20

Great.

Shilpa Vasishta: 00:34:22

Um, so we do obtain some further workup, um, and admission urinalysis and urine pregnancy tests are negative as are COVID and flu swabs.

Shilpa Vasishta: 00:34:32

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.

Shilpa Vasishta: 00:34:46

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.

Shilpa Vasishta: 00:34:54

Dr.

Shilpa Vasishta: 00:34:54

Coyle, how would you interpret these findings and how would you characterize or classify this patient's illness?

Christina Coyle: 00:35:00

Great.

Christina Coyle: 00:35:01

This is the most important thing that we do as ID clinicians is we interpret the blood smear.

Christina Coyle: 00:35:06

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.

Christina Coyle: 00:35:12

And so we heard that these were normal RBC.

Christina Coyle: 00:35:15

So when we're talking about normal size RBCs, it's moving us towards falciparum and malariae.

Christina Coyle: 00:35:22

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.

Christina Coyle: 00:35:30

When we talk about enlarged, red cells that are, those are the forms of malaria that, in fact, younger red cells.

Christina Coyle: 00:35:40

And so that's your vivax and your ovale.

Christina Coyle: 00:35:43

All right.

Christina Coyle: 00:35:43

And so that's the way you think about.

Christina Coyle: 00:35:45

You're hearing only rings.

Christina Coyle: 00:35:47

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.

Christina Coyle: 00:35:59

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.

Christina Coyle: 00:36:09

And so, uh, when we only see that, and they're not enlarged, it's really pushing us to falcip[arum]..

Christina Coyle: 00:36:16

If it turns out it's malariae.

Christina Coyle: 00:36:18

So be it.

Christina Coyle: 00:36:18

But they tend to have very low parasitemia, malariae.

Christina Coyle: 00:36:22

They actually infect senescent red cells.

Christina Coyle: 00:36:25

And we're hearing a lot of red cells infected here.

Christina Coyle: 00:36:27

So this is really pushing us towards falciparum.

Christina Coyle: 00:36:30

The other thing is that we only see rings in this patient.

Christina Coyle: 00:36:35

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.

Christina Coyle: 00:36:44

And it has two ways that it can go.

Christina Coyle: 00:36:46

It can develop into what we call a blood schizont, which is what I always say, a blue bag full of merozoites.

Christina Coyle: 00:36:52

Um, and when that ruptures, you're going to get fever or schizogony, and each of those merozoites will then infect another red cell.

Christina Coyle: 00:37:01

So for malaria, it's about 10 merozoites.

Christina Coyle: 00:37:03

So for every infected schizont, you're going to get 10 to 13 red cells infected after that schizogony.

Christina Coyle: 00:37:09

, and then of course there's gametocytes and the gametocytes do go in the periphery.

Christina Coyle: 00:37:13

And we know in falciparum they look like banana shaped.

Christina Coyle: 00:37:18

So that's going to get picked up by a mosquito.

Christina Coyle: 00:37:21

That causes no symptoms.

Christina Coyle: 00:37:22

It just tells you that the person's been infected for at least two weeks.

Christina Coyle: 00:37:26

So those later stages that you normally, will occur in the life cycle in falciparum are sequestered.

Christina Coyle: 00:37:34

So when you see a parasitemia of like say 3%, they could have a fever and schizogony.

Christina Coyle: 00:37:41

And the next eight hours that parasitemia, especially in a non-immune host, can increased quite a lot.

Christina Coyle: 00:37:48

Um, I've seen 2% in the morning in non-immune hosts and 20% in the evenings.

Christina Coyle: 00:37:54

So what you're seeing on a blood smear, isn't representing exactly what's going on in the patient.

Christina Coyle: 00:37:59

And there could be a sequestered biomass that you're not accounting for.

Christina Coyle: 00:38:03

And that's why getting a blood smear and parasitemia on falciparum, you should definitely, you're taking everything into consideration, right?

Christina Coyle: 00:38:11

You're taking the immunity into consideration and you're knowing that in eight hours, this might be different.

Christina Coyle: 00:38:17

That's why you're looking at your end organ, your brain, right.

Christina Coyle: 00:38:20

You're looking at your kidneys.

Christina Coyle: 00:38:22

You're looking at the blood pressure.

Christina Coyle: 00:38:23

You're looking at pulmonary, you're looking at all of these things and of course you're looking at acidosis.

Christina Coyle: 00:38:29

Right.

Christina Coyle: 00:38:30

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,

Christina Coyle: 00:38:38

so somebody that isn't being exposed all the time, right.

Christina Coyle: 00:38:43

It's going to be severe malaria.

Christina Coyle: 00:38:45

You're also going to be worried about somebody with 3.5%, 2%.

Christina Coyle: 00:38:49

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.

Christina Coyle: 00:38:55

So these are the things that we're thinking about when we're looking at this blood smear.

Christina Coyle: 00:39:00

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.

Christina Coyle: 00:39:20

Um, and so that's the way that you're going to look at this smear.

Christina Coyle: 00:39:24

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.

Christina Coyle: 00:39:35

Right.

Christina Coyle: 00:39:36

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.

Christina Coyle: 00:39:51

So all you do is you basically look at the number of parasitized, the total RBCs you're doing per field.

Christina Coyle: 00:39:58

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.

Christina Coyle: 00:40:07

So I do number of parasitized RBCs in the number of total RBCs per field.

Christina Coyle: 00:40:13

And I do an average.

Christina Coyle: 00:40:14

So if there's a lot, sometimes I only need to look at five fields.

Christina Coyle: 00:40:18

Um, if, if there's not, then I look at five to 10 fields and then I average them out.

Christina Coyle: 00:40:22

Of course, I multiply it by a hundred and I get around about percentage because I need to know how sick this patient is.

Christina Coyle: 00:40:29

And I need to have an idea if we're talking a high parasitemia.

Christina Coyle: 00:40:32

So we're talking that this person has a parasitemia, of greater than 4%.

Christina Coyle: 00:40:37

So we're worried.

Christina Coyle: 00:40:39

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.

Christina Coyle: 00:40:50

So those individuals that I see that have been out of the endemic region for years and years and years, right?

Christina Coyle: 00:40:58

Um, the, basically the low parasitemia, , doesn't reflect a high sequestered biomass and shouldn't reassure you.

Christina Coyle: 00:41:06

So you have to be on top of this patient and make sure that you're getting a smear eight hours later.

Christina Coyle: 00:41:12

So if they look sick and they have a low parasitemia and not low, low, like less than one, but not 4%.

Christina Coyle: 00:41:19

I'm still very worried about them.

Christina Coyle: 00:41:22

Patients can look well and if they're not treated properly, umand promptly, um, they can deteriorate very, very, uh, rapidly.

Christina Coyle: 00:41:29

So treatment of malaria is an emergency.

Christina Coyle: 00:41:32

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.

Shilpa Vasishta: 00:41:47

I can just, uh, provide, uh, uh, some of that, the data that you referenced there for our patient.

Shilpa Vasishta: 00:41:52

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.

Shilpa Vasishta: 00:42:12

A repeat peripheral blood smear is obtained eight hours later and reveals an increase in parasite burden to 15%.

Shilpa Vasishta: 00:42:19

She remains well appearing.

Shilpa Vasishta: 00:42:21

What are your management recommendations for this patient?

Christina Coyle: 00:42:23

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.

Christina Coyle: 00:42:33

That initial bicarb of 16, the elevated creatinine a bit trickier.

Christina Coyle: 00:42:38

I think, um, you have to remember that patients come in severely dehydrated with malaria.

Christina Coyle: 00:42:44

So a lot of times we can't say anything until we hydrate them.

Christina Coyle: 00:42:47

So I tend not to say anything until they're hydrated.

Christina Coyle: 00:42:50

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.

Christina Coyle: 00:43:00

So for us, she needs criteria for severe disease.

Christina Coyle: 00:43:05

If she had had mild disease, we could have used oral, but she didn't.

Christina Coyle: 00:43:09

And, and I just want to remind you that anywhere in Sub-Saharan Africa is considered chloroquine resistant.

Christina Coyle: 00:43:15

So you only have three choices in non-severe disease and that's artemether / lumefantrine, which would be your number one choice.

Christina Coyle: 00:43:23

Atovaquone proguanil, which you could use (Malarone) in non-severe disease or quinine plus doxycycline or in pregnant women, quinine plus clindamycin.

Christina Coyle: 00:43:33

If you don't have the other two available.

Christina Coyle: 00:43:37

So this patient meets criteria for severe disease.

Christina Coyle: 00:43:41

So I would, especially as a fellow, I would call a lifeline.

Christina Coyle: 00:43:46

And so your lifeline will be CDC.

Christina Coyle: 00:43:49

And so in the middle of the night, it's always worth calling CDC.

Christina Coyle: 00:43:52

And, um, you can either get artesunate from them or it's commercially available right now.

Christina Coyle: 00:43:59

I just wanted to spend two seconds on severe disease in adults.

Christina Coyle: 00:44:04

So when you look at most of your disease that you get taught in medical school, you get taught about children.

Christina Coyle: 00:44:10

And so in Africa, the burden of disease of malaria is really seen in children under the age of five years.

Christina Coyle: 00:44:17

And so for those individuals, we see cerebral malaria and there's a literature on this.

Christina Coyle: 00:44:22

Um, and then acidosis.

Christina Coyle: 00:44:24

And of course we see severe, uh, malaria anemia.

Christina Coyle: 00:44:28

As we start moving to adulthood, and we start looking at the data coming out of Asia, where, um, malaria is not holo endemic.

Christina Coyle: 00:44:37

So you get a lot of adults with severe disease.

Christina Coyle: 00:44:40

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.

Christina Coyle: 00:45:02

So I always get a pregnancy test on my patients.

Christina Coyle: 00:45:05

And so this patient, , we would definitely give artesunate.

Christina Coyle: 00:45:09

There would be no doubt that we would give artesunate.

Christina Coyle: 00:45:13

One minute on artesunate.

Christina Coyle: 00:45:14

In the United States, uh, IV quinidine used to be available.

Christina Coyle: 00:45:19

But as of two years ago, um, it's no longer available.

Christina Coyle: 00:45:22

Worldwide, artesunate is felt to be the drug of choice for, , severe disease.

Christina Coyle: 00:45:28

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.

Christina Coyle: 00:45:42

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.

Christina Coyle: 00:45:52

So there's more rapid killing and so more rapid activity.

Christina Coyle: 00:45:57

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.

Christina Coyle: 00:46:03

I just want to say one other thing.

Christina Coyle: 00:46:05

I want to talk about dehydration.

Christina Coyle: 00:46:08

These patients are very dehydrated, so as ID person, we don't normally do, um, management of fluids.

Christina Coyle: 00:46:14

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,

Christina Coyle: 00:46:26

some people feel you can get these leaky capillaries and that you're more likely to get a non cardiogenic pulmonary edema.

Christina Coyle: 00:46:34

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.

Christina Coyle: 00:46:42

And at that point match their I's and O's, and I think most people feel that.

Christina Coyle: 00:46:47

And obviously I tell them about this non-cardiogenic pulmonary edema.

Christina Coyle: 00:46:51

And the other thing is you can get hypoglycemia, especially in somebody with poor oral intake.

Christina Coyle: 00:46:57

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.

Christina Coyle: 00:47:03

So those are some things that I do when I'm managing patients.

Christina Coyle: 00:47:06

And then the last thing is, is that patients vomit a lot.

Christina Coyle: 00:47:09

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.

Christina Coyle: 00:47:21

So even though they don't meet criteria for severe disease.

Shilpa Vasishta: 00:47:24

Great.

Shilpa Vasishta: 00:47:26

Um, so this patient does receive IV therapy with artesunate, uh, 2.4 milligrams per kilogram, dosed Q 12 hours.

Shilpa Vasishta: 00:47:34

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%.

Shilpa Vasishta: 00:47:48

She's then transitioned to oral artemether and lumefantrine to be continued for an additional three days after discharge.

Shilpa Vasishta: 00:47:55

Uh, what further followup will she need upon discharge?

Shilpa Vasishta: 00:47:58

And how would you counsel this patient on preventive measures for future travel?

Christina Coyle: 00:48:02

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.

Christina Coyle: 00:48:15

That's the way to think about it.

Christina Coyle: 00:48:16

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.

Christina Coyle: 00:48:28

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.

Christina Coyle: 00:48:36

And the reason why is it's due to that, that clearance of the young ring stages that we talked about.

Christina Coyle: 00:48:43

And so it rapidly kills them, but the dead parasite becomes what's called pyknotic.

Christina Coyle: 00:48:49

And so it circulates for a while, and then it gets taken out of circulation late.

Christina Coyle: 00:48:54

And so we started seeing delayed hemolysis due to that.

Christina Coyle: 00:48:57

And so we'll see it in non-immune travelers with high parasitemia.

Christina Coyle: 00:49:01

This patient is at huge risk.

Christina Coyle: 00:49:02

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.

Christina Coyle: 00:49:12

I educate them on symptoms of anemia.

Christina Coyle: 00:49:15

Um, because sometimes they'll just become short of breath.

Christina Coyle: 00:49:17

So I want to let them know to call me immediately and the way to treat it normally is to actually transfuse them.

Christina Coyle: 00:49:24

And, uh, and then we check them at two weeks.

Christina Coyle: 00:49:27

So the most important thing is also to educate them about that.

Christina Coyle: 00:49:30

And this is a patient that you also want to reinforce malaria prophylaxis the next time she goes.

Christina Coyle: 00:49:38

Um, and so for her, there are three choices of, , malaria prophylaxis and she has doxycycline, which is daily.

Christina Coyle: 00:49:47

And then there is Malarone and that is, also daily.

Christina Coyle: 00:49:52

The difference between doxy and Malarone is that, um, doxy just has more breakthroughs if you miss doses and also for women.

Christina Coyle: 00:50:02

Um, there's the risk of getting, uh, vaginal candidiasis.

Christina Coyle: 00:50:06

So I always send people with Fluconazole and of course it makes you more sun sensitive.

Christina Coyle: 00:50:12

So you really need to emphasize sunscreen no matter what in all individuals.

Christina Coyle: 00:50:18

And, um, and then you can get a pill esophagitis.

Christina Coyle: 00:50:20

Some people who take it just love it and their adherent.

Christina Coyle: 00:50:23

So it's a great drug for them.

Christina Coyle: 00:50:25

Malarone is really well tolerated, but for longer trips can be quite expensive.

Christina Coyle: 00:50:30

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.

Christina Coyle: 00:50:40

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.

Christina Coyle: 00:50:49

So you're going to really emphasize to her that when she goes, she needs to listen to our pre-travel advice.

Christina Coyle: 00:50:55

Um, great that she sought it out, but she's got to listen to it.

Christina Coyle: 00:50:58

And, um, I think that's what I would say.

Sara Dong: 00:51:02

Thank you to Shilpa and Christina for joining us today and talking through this awesome case.

Sara Dong: 00:51:09

We are planning to have several more episodes related to fever in the summer or fever in a returning traveler.

Sara Dong: 00:51:16

So stay tuned for those.

Sara Dong: 00:51:18

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.

Sara Dong: 00:51:30

Please reach out if you have any suggestions for future shows or just want to be more involved with Febrile.

Sara Dong: 00:51:35

Thanks for listening, stay safe.