Step into the role of a hospital epidemiologist managing a measles outbreak response with Drs. Palak Patel, Emily Landon, and David Zhang from the University of Chicago!

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Febrile is produced with support from the Infectious Diseases Society of America (IDSA)

Sara Dong 0:06

Hi everyone, welcome to Febrile: a cultured podcast about all things infectious disease. We use consult questions to dive into ID clinical reasoning, diagnostics, and antimicrobial management. I'm Sara Dong, your host and a Med-Peds ID doc. We have a team joining us from the University of Chicago today. Dr. Palak Patel is a first year ID fellow at the University of Chicago and she is pursuing a career in hospital epidemiology.

Palak Patel 0:34

Hi. I'm Palak. I'm very excited to be here.

Sara Dong 0:36

Dr. Emily Landon is an Associate Professor of Medicine at the University of Chicago in the Section of Infectious Diseases & Global Health where she also serves as the Hospital Epidemiologist and Executive Medical Director of the Infection Prevention & Control Program.

Emily Landon 0:51

Hi, I'm Emily, and I'm so excited to finally be on the Febrile podcast

Sara Dong 0:56

Dr. David Zhang is an Assistant Professor of Pediatrics in the Section of Infectious Diseases at the University of Chicago Medicine Comer Children’s Hospital. He currently serves as the Associate Medical Director of Infection Prevention & Control.

David Zhang 1:07

Hi. This is David Zhang. I am happy to be here.

Sara Dong 1:10

So before we talk about the case or example that we have for today, we like to ask as everyone's favorite cultured podcast, if you'd be willing to share a little piece of culture, you know something that has brought you happiness recently, maybe Palak I'll start with you.

Palak Patel 1:26

Sure. I actually love Hindi films And I recently saw a movie on Netflix called Laapataa Ladies, and it just came out, but I already saw it twice already. It's so good. It's it's about a mix up that happens from with two brides from a village in India on their train to their husband's house. They get mixed up and it's really empowering and it's really well done I really like it because I think a lot of people, when they think about Bollywood, they usually think like music, singing, dancing, colorful outfits, which a lot of it is, and that is honestly my favorite part. But this one, um it's not really like that. It's lot it's like deeper and really empowering know, I just feel like a lot of these movies, they don't get the recognition they deserve. And so even if you're not a huge Bollywood fan, I recommend that you watch it.

Sara Dong 2:11

Love it, I'll have to add it to my list. How about you, David?

David Zhang 2:14

Yeah. Apart from taking care of two young boys, I do like to play the drums, especially after a stressful day. I just like taking it out on the drum set. Contrary to what one may think, you don't actually need a drum set to first start learning rhythms. All the times I've spent daydreaming in school when I should have been paying attention, I was conjuring rhythms in my head and just tapping my fingers on the desk and tapping my feet on the floor. So, if I ever get a chance to be in a band with likeminded, infectious disease centric individuals, you know, the band name would be. Get ready for it. The Fluoroquinotones. I'll be here all day.

Sara Dong 2:55

Someone sent me a message recently about how we need more puns, and I very much appreciate it.

David Zhang 3:01

Happy to do it again next time.

Emily Landon 3:05

My significant other says that my hobby is getting new hobbies and so I always have a million things that I've got going on. And so I'll, I'll talk about a couple of things that are happening right now. It's spring and the weather in Chicago is a little bit better. And so I love to grow new seedlings in my house because I honestly think it's it's largely because the the light from the lights that you have to use to grow the seedlings is probably helping with my some sort of seasonal depression because it's like 16 hours a day in my bedroom. But now it's it's time to take the plants outside. And last weekend I was able to plant everything out on the balcony. I can sit down on the balcony and do all of my other cool hobby things, whatever I feel like I'm going to do that day, but I'm really looking forward to next. Another one of my hobbies is I like to sew things and I make a lot of my own clothes and I have this. This is so niche, right? There's this thing coming up in Chicago called Frocktails, which is where you make your own dresses and go to this big cocktail party with other people that made their own clothes. And I need to make a dress. I'm going with one of our one of the people that helps with our research stuff at the university anyway. So I'm really excited. So next up, now that my plants are outside I need to draw out what I'm going to make for my Frocktails dress

Sara Dong 4:30

I love it. Well, I think today we are going to be hospital epidemiologists, so I'll hand over to Palak to get us started.

Palak Patel 4:39

Okay, So you are the hospital epidemiologist on call today and you get a page from the ED stating that they're concerned they have a patient with measles. So before we jump right into the infection control aspect, what are some features you would be listening for that would be consistent with measles?

Emily Landon 4:54

So I mean, I want gonna jump right in here because I have been this person for so many calls like this one. And I think that the first thing that - you got it right here Palak is you're asking the right question first, because the first thing you need to do, no matter what somebody calls you about, concerned about as as the hospital epidemiologist, is to make sure that's what's actually happening. I cannot tell you how many times I've been called because there's a measles outbreak on a floor and it turns out they all just have positive IgG for measles. Or at one time there was a resident outbreak of a food poisoning related to the cafeteria. It turns out they were all just they were giving away free candy with sorbitol in it and everybody just got gas and bloating from the sorbitol. So, so, you know, you have to sort of figure out that you've got a problem. And then the second piece of that is understanding if what you're hearing about is unusual for your area and for that time of year, somebody calling you because they got a patient with influenza in February is not a surprise, whereas measles is something that we don't see very much. And so if there's real genuine concern for measles, then you really do need to think about that. The first thing that I think about and this may seem sort of obvious, right, it sort of seems like you're sort of putting words on the obvious, but it's really important to be incredibly deliberate about the way that you investigate the beginnings of an outbreak investigation. And so the first thing to do is to confirm the diagnosis as I said. And then you really need to think about this thing called the case definition, which sounds simple, right? Well, it's people with measles, but in reality, case definitions actually you have sort of different parts to them. There is not a case that means definitely don't have measles. In this case, that would be definitely don't have measles no matter what. There's definitely measles, which is already have their tests done. And as clinicians, we know that there's this time in the middle where they might have measles, they might not have measles, and we need to sort of maybe behave like they do have measles. And that's the part where you say maybe probable measles or possible measles and you can find that out. You say people with an exposure in this case, maybe people with an exposure who haven't been vaccinated and have symptoms of measles, that's going to be a probable case, whereas people who have been vaccinated but inadequately and have some symptoms. But not all of the symptoms might be a possible case of measles and understanding what buckets you can put patients into can really help you as you move your way through this investigation and can really help you sort out the first steps to take if you're a little overwhelmed the first time you hear about something. But in order to do that, you need to know a little bit more about measles. And we haven't. Most people, I mean, till now, have not seen a lot of measles. So I think, Palak You might tell us a little bit more about what measles is, what it isn't, and how it works.

Palak Patel 7:34

Yeah. So as a refresher, measles is an acute febrile rash caused by a single stranded enveloped RNA virus. And you can see high fevers up to 105 degrees. The fever usually peaks when the rash starts. And if we recall from our med school days, the three C's: cough, coryza, and conjunctivitis are also a part of usually seen in measles, and the rash is usually maculopapular that starts in the hairline or the face and spreads to the trunk and extremities. the rash may coalesce. It's usually not itchy and it does not include the palms and soles, which may help you distinguish it from other differentials. You can also see Koplik spots on the buccal mucosa. So for the case definition, the Council of the State and Territorial Epidemiologists define a case as having a rash, having a fever and having one of the three CS. That's kind of a framework for what defines a case.

David Zhang 8:26

And so, you know, the next the next part that I just want to get into is really just the diagnostics of measles. Diagnostics is obviously very important for anything that we do in the wonderful world of medicine, but especially so and when we're formulating our case definitions. But really the first thing you do before thinking about sending off any diagnostic testing is what's your pretest probability? And that's kind of what Emily had alluded to, because really your pretest probability is what informs the interpretation of your tests that we'll be talking about. And really that pretest probability is informed by the clinical and the epi factors as well. There's definitely other things on the differential that we kind of mentioned already, a little bit like a lot of other viral febrile rashes, you know, hand, foot and mouth, roseola, varicella, etc.. And, you know, you obviously have to take into account someone's immune status and any relevant exposures. And that all informs your pretest probability. So say your concern is on the higher side in terms of the testing that we do send out for measles. The recommendation still is to send off serum testing and that is an IgM and IgG and to do real time PCR testing. There are definite inherent issues with serologies. As with any serologic testing, there's actually a good amount of false negatives with the IgM, especially if you obtain it too early on in the illness In those who are vaccinated, IgM may appear temporarily or may not even appear at all. And so which is all this really just say that a negative IgM does not rule out measles. On the other hand, there's also false positives with measles serology, especially in areas where there's not a high incidence or in settings where there's not an outbreak happening let's say. It can also cross react with other causes of febrile illnesses, which, you know, I mentioned. So really, that's all to say that the real time PCR is really just a better test all around. It's more sensitive, it's more specific than your serologic testing. This could be sent on oropharyngeal, nasopharyngeal or even urine samples. And you really just want to collect this as soon as your suspicion is there for measles, but preferably as soon as after the rash develops because the yield of the PCR does decline to a degree over time. There is another advantage of sending off PCR testing. It's really that those samples can be used for for genotyping, which can then be used to determine transmission patterns and tracking those. There's some other higher level testing as well. I won't really get into the details of that. But you can you can have a febrile rash after getting the measles vaccine, especially if they're in the setting of an exposure. And so there's something called the measles vaccine assay that can really only be done in in certain reference labs that can distinguish whether it's wildtype measles or vaccine derived measles.

Great so now that we know what a case definition is and how to diagnose, we call the ED back they say that they have a four year old girl who's presenting with a maculopapular rash that started on her face and spread to her trunk. They give you a little bit more history and tell you she actually presented to the ED initially a week ago. At that time, she just had a sore throat and runny nose that started after she was returning home from visiting her family in Florida. When she initially presented, they sent her home with supportive care. But now she's re-presenting with this rash that was described earlier. She meets the case definition and is now confirmed to have measles. So how do we proceed?

Well, first, you probably scream into a pillow if you're in the hospital epidemiologist, because measles is the most contagious disease known to man. So you definitely do not want to deal with this problem. But should you find yourself dealing with this problem, which I will assure you we all have, is, you have to move fast now because the exposures - we're going to have to talk about the scope of the problem. How big of a deal measles is? How contagious is it really? Who's at risk? How great is that vaccine? And then you're starting to wonder for yourself, that vaccine I got when I was one year old and four years old, now that I'm an adult, is that really working or am I at risk, too? Like, there's all sorts of questions that go through your mind, and this is when it's really important to take a minute to sort of figure out what you have, look up the R0 you remember this from when you were doing when we talked about COVID, right? R0, by the way, is the number of individuals that a sick individual usually infects in a regular setting and that R0 is flexible. It changes based on immunity. It changes based on the immunity of the population that's exposed. It changes based on the time of the exposure to the individual that was sick. And so you have to keep that into consideration, but you want to know the R0. It gives you some idea how it compares to other diseases. For measles, it's usually 15 to 18. For COVID, we were looking at numbers like maybe three or four at the worst point in in this sort of Omicron peak and things like primary chicken pox amongst unimmunized individuals is high at maybe 8 to 10. This is really significantly higher. That's that is a lot more. But the individuals have to be unprotected by their vaccine and so the question of how well the vaccine continues to work into adulthood, who's really at risk and then how many and then how you're going to deal with them. Can you give post-exposure prophylaxis? Do you have to isolate people that can't get or didn't get their post-exposure prophylaxis within a defined time period? Those are all the questions and ducks that you need to get in a row in order to even begin addressing this situation. But I will tell you, the more contagious the disease is and the more unimmune or the less immunity you have in your population, the more people you're going to have to call and talk to and explain how they got exposed. And in the case of measles, I think we should talk about how people get exposed and then how good the vaccine really is.

Yeah. And because of how high the R0 is, you can you can already imagine how it's getting transmitted and it's usually by, airborne route and sometimes droplet route when you're at smaller distances between you and the index patient. So, I would say it's so quote unquote airborne that you know, it does persist in the air for a couple of hours even after the infected patient leaves the room. It's also worth knowing what the incubation period is and that can inform, you know, how you do your contact tracing that we'll likely get into later. But the incubation periods generally 10 to 14 days from exposure to the onset of the prodromal symptoms. And these prodromal symptoms, you know, the three Cs, as Palak mentioned, really can last anywhere from 2 to 4 days prior to the onset of rash. And so all of us in infection control really care about the day that the rash started. We deem that as day zero because your infectious period is four days before and four days after the onset of the rash. And so that gives us as infection preventionists and you know, public health officials a framework in which to perform contact tracing and determining exposures and so on and so forth. And, you know, if you're immunocompromised, that infectious window can even be longer as that measles virus stays in your secretions a little bit longer. The big challenge is, as you can imagine, is that you are infectious prior to the onset of rash. And so since the prodromal symptoms, the cough, conjunctivitis, coryza, since that can mimic any other viral illness, suspicion for measles may not be high during that time, which, you know, can potentially lead to a lot of exposures.

And this sort of like ties in to how we make recommendations about what to do when there is measles circulating in a community. And we get back to that case definition of like who is probable, who's high risk, who's low risk for an exposure. And those things come down to if you're vaccinated, if you're not vaccinated, if your exposure was during the known infectious period, how close that exposure was, how much time you spent around a patient. When it comes to measles, like there's a study from way back, it's like one of those things you have to get on microfiche, which I know I'm old enough to know what that is, and most of you are not. But the point is, it looked at cases of measles that happened 2 hours after somebody was in an elevator. The person with measles was on the elevator for however long it is to be on an elevator and then they left the elevator and the air exchanges were so low in that elevator because there's really not a lot of ventilation in elevators that people 2 hours later, it just went in that elevator to go from floor to floor, still got measles. And so you can imagine that this is going to be a pretty significant outbreak. So this kid who was here and based on the dates that you really want to know when the dates that the rash started and all, spoilers, we know that the rash started within four days of when she was had originally presented to our emergency department. And so she wasn't isolated at that time. So a lot of individuals were probably exposed from that first visit. But now that we know measles is circulating in the community, we can take steps to prevent that kind of outbreak from happening or that kind of exposure situation is happening by saying, listen, now that there's measles in the community, anybody who is not immune. So babies under the age of 12 months because they haven't been able to get a vaccination yet, individuals who are unvaccinated for whatever reason, if they've come in with any symptoms of measles, the first thing you need to ask them is could you have been exposed to this measles. The health department keeps really great records online about where people went when they were exposed. You can look things up. You can say, you know, were you in the South Loop Target on this day at this time? And if you were and you're not in the immune category, then you can get isolated even before your rash starts. And even if it's not measles, just to be out of an abundance of caution because the last thing you need is more exposures like the one that happens here.

Yeah. And the vaccine part is really the for me just the most important thing in a way. It's kind of unfortunate that we're talking about measles circulating in the community because that means that our vaccination efforts are likely not as robust as it could be. You know, that being said, the MMR vaccine really has been and will continue to be the way out from any further measles outbreaks and preventing measles and overall its transmission through our communities. And just, you know, I'll just take a minute just to talk about the vaccine. The vaccine is extremely effective. You know, one dose is 93% effective, two doses is 97%. The typical schedule is that you get the first MMR at 12 to 15 months and the second MMR at the beginning of school entry at 4 to 6 years of age. The reason why we give the second dose is that a minority will have primary vaccine failure. So it's not technically considered a booster. It's really just to bring those who do not necessarily respond to the first vaccine to have their immune system respond to the second vaccine. You know, there are indications to give the MMR dose outside of the routine vaccination schedule. So if you are traveling internationally and you are in that 6 to 12 month old range, you should get an MMR. As we know, measles outbreaks are probably happening everywhere around the world, both in developed and underdeveloped nations. However, this vaccine doesn't count as part of the routine series and the thinking that there's passive interference from possibly still circulating maternal antibodies that can interfere with the response. So for those who do get the MMR before 12 months, they should still continue to get their two dose series at the appropriate age intervals

Sometimes it is referred to as a zero dose. And so if you see a kid's chart that says that they have a zero dose, that means that they got a dose when they might have had maternal circulating antibodies. So they still need their full

Yeah. There's also consideration for kids to get an accelerated second dose, which is getting it at least 28 days after the first dose. And this dose will count as the second dose and would really preclude the need for getting an MMR at the 4 to 6 year range. And so that's something that should also be considered. you know, there are definitely side effects to this vaccine, as with any vaccine, but generally it's well tolerated, you know, fever, rash and in a minority of individuals lymphadenopathy are those common side effects. The rash is very self-limiting and it really should be, you know, shorter in duration than the rash that you would see with natural infection.

And it protects you well into adulthood, into, into old age. Now those vaccines you get as a child are still good, even when you are a 50 year old nurse or doctor taking care of patients in the ED. So that's really, really important because you can really second guess yourself. You're like, is it true that that measles vaccine that those people got in like first grade is really enough? Yeah, it totally is. And so you can be confident that the health care workers that received both doses of vaccine, whether or not they have immunity demonstrated by titers, so some people don't - their titers wane over time or they don't make titers to the particular antibody that we check but they are still immune. So documented two doses of the vaccine or previously diagnosed IgG positivity is good enough to protect you from measles, so there's no need to go back and revaccinate all of your health care workers or re test everybody that already got checked for this when they were employed at whatever hospital you're working at.

So going back to our case, our patient had a delayed diagnosis, which David mentioned before is a huge concern, given that the patients are infectious before the rash even begins and have a confirmed case, we know that many people were likely exposed in the ED during her initial visit. So what are the next steps we need to address these exposures?

Yeah. So it's going to be a big task, right? You're going to have to identify every single person that was in that peds ER during the time that that kid was there. So the first thing to do is to figure out exactly what the time frame was from when that child checked in on the first visit until they were out and exactly where they went. Now, electronic medical records are making this easier than ever. It used to be really hard before we had electronic medical records and you're just trying to remember stuff. But now you can usually see what room they put the kid in or the adult or whatever situation you have and who took care of them and how long they were in the waiting area. Then you have to figure out who else was in the waiting area, who else was in a room. If they got put into a room that didn't wasn't a negative pressure or airborne isolation room (an AIIR), then you would need to make sure of everybody else that was in that area in the same ventilation compartment as that patient. And that usually includes the other rooms and the work spaces associated. They are all going to be considered exposed from the time the child arrived through the time 2 hours after the child was discharged. And that's going to be a lot of people. Now, the good news is, in most hospitals, your health care workers are all checked for measles immunity on entry to employment. Right. So in Illinois, where we work, it's required that everybody demonstrate - you have to have a plan for figuring out whether or not or how people are immune. And so all of our employees, for the most part, except for a couple of outliers, were immune. And those that were outliers we knew about because we had records about them in the occupational medicine area. So the health care workers were largely protected, but all of the other kids and their families, any siblings, visitors, anybody else that came into that space we needed to know about. And that meant making a bazillion phone calls and finding out what was going on with them. And because post-exposure prophylaxis can be given. So you can either use the vaccine as post-exposure prophylaxis in a very short time period after exposure. Or you can use IM Ig or IVIG, not measles specific, just plain old IVIG or IM IgG to help prevent infection in people. You could if we had if we'd known about this earlier, we could have prevented the non immunized individuals. Unfortunately we didn't. So instead the only thing to do is to say during X time period, which for measles is going to be about four or five days after exposure through about 14 to 21 days after exposure, you have to stay away from other people if you're not immune and you need to, you can't go to daycare, you can't go to preschool, you can't go to the classroom, you need to be at home and away from other people. And if you get sick at all, you need to call us first. Come in and then we'll isolate you properly. The good news is that we worked with our local health department. I mean, you're going to have to always work closely with your local health department and we have to do that contact tracing, call all those people, track them down, make sure they all know. And the good news is the vast majority of the people over the age of 12 months were vaccinated. Right. And so they didn't require a lot. But there were some babies that were exposed that were under the age of 12 months or children that were immunocompromised that couldn't be vaccinated for whatever reason. And so there were definitely some people who got some sort of watchful waiting and observation.

So now two weeks have passed and there's been a rise in measles cases in the local migrant shelters. One of the shelters near the hospital sends over a child who has a fever and a rash consistent with measles. What are the next steps that we should be taking?

Yeah. So at this point, you know, Emily said that she was going to scream into a pillow? like this is something higher than that. Like my drums would be broken at this point because, you know, you know, just in terms of the giving, giving you guys the context, you know, these are migrants coming from countries where they lack public health infrastructure. So in other words, their vaccine efforts are not great. In other words, they're not vaccinated for these vaccine preventable illnesses, or most of them, I should say, and so that long 10,000 foot view really just scares me because I think this is going to be the first case of many that happens. But just to directly address what to do for this particular patient, you really first of all, you really just want to confirm that this is measles, given the amount of effort and time that infection control and public health goes into managing these cases and any kind of subsequent exposures and post-exposure prophylaxis, etc. To add on to what I said earlier, you know, in addition to serology, you're getting a PCR, but I just want to take a moment to say that where you send the PCR, it really does matter because a lot of places you may be able to send it to a commercial lab, but it really is probably best to send it to a state reference lab, you know, send it to a commercial lab could give you a slower turnaround time, could delay result forwarding to the local health department, that would then delay all the critical activities that they need to do, like, you know, contact tracing, notification, post exposure, etc. So really sending to a designated state reference lab is crucial. And that also gives you the added benefit of, you know, perhaps doing any kind of genotyping or measles vaccine assays that can also yield, you know, further useful downstream information. So if you do have this case confirmed, of course I forgot to mention, you know, but this patient should have been isolated from the get go when there is a concern. But let's say you do have that and you've made a diagnosis. What do you actually do for these kids? Unfortunately, there's no directly acting antiviral medication that's available or I should say FDA approved, which is, you know, true for most viruses. The World Health Organization does recommend giving vitamin A to all children and adults with measles, which actually differs a little bit from what the CDC says in that they're saying that to give vitamin A to those who are hospitalized with severe measles. The difference really lies in the fact that there's just a higher likelihood of, you know, malnutrition in underdeveloped countries where measles is, you know, potentially high in incidence as compared t, developed countries. You know, most of the studies on vitamin A are really in resource limited settings. We do know that vitamin A deficiency, you know, contributes to delayed recovery and a higher rate of complications. And that, you know, giving vitamin A to children is associated with decreased rate of complications and improvement in both morbidity and mortality. And that especially is true for the younger population in kids less than two years of age. So I think that's all to say that, you know, most of us would agree it's just giving vitamin A for anyone with any kind of measles infection, regardless of the age group.

Sometimes it's hard to get vitamin A. There is not a lot of available liquid vitamin A for little babies who can't swallow pills. And while there's a ton of it, it turns out on Amazon.com that you can order it, you can't give that in the hospital. And so we ended up having to like, suck it out of Vitamin A capsules from adults and compound it into vitamin A that you can give to babies. So this is not like none of this is easy. Just to be clear, if you find yourself in this situation in your hospital, you are not alone.

So at this point, you're starting to lose your voice, run screaming into the pillow. Your drums are broken, and CDPH calls you again. They tell you they're sending three more children from the shelter and your IPs let you know that we're out of negative pressure room. So what do you do now?

Yeah. There's a lot of things I could say, but they may not be appropriate. Before I say anything else, I just want to make the point that, you know, measles in and of itself isn't a condition that directly requires hospital level care. It's really the complications that do. You know those complications include things like diarrhea, or dehydration from diarrhea, otitis media, and pneumonia. Those are the most common complications. There are some rare complications as well, which includes encephalitis and subsclerosing panencephalitis, which is generally fatal within years if it starts. And that one's a little bit scary because it can happen, you know, a decade after you contract the acute measles infection. These complications are more common in two distinct age groups: our younger population, less than five and then adults actually greater than 20 years of age. But just to just to make the point that in this particular case, you know, here in the city of Chicago, this is where you talk with your public health officials. You know, at the time of this, there really was no viable alternative to isolating these migrants safely. That wouldn't put the community at greater risk. And so, you know, we've had discussions with the public health departments and, as children's hospitals around the city, including us, really were tasked with helping to admit these kids for strictly isolation purposes, which I will say did help protect the general public from any further exposures and potential transmission. So this really was just a very unique situation that we found ourselves in.

But what a disaster, right? I mean, what hospital has like 20 airborne isolation rooms for children? I mean, this is crazy. So the need was so high because you have all these kids, they're ruling out for measles. Then there's all the kids with measles that can't go back to the shelter yet. It's it became an absolute logjam, people with measles. Even though they all did great and most cases didn't have any real complications, figuring out how to manage airflow so that the people who were at risk of measles didn't breathe in the air that the measles people were breathing out is a big issue. And so airflow really matters and the gold standard is to use what's called AIIR or an airborne isolation room, which is one of those rooms that has an ante room and the air actually comes in from a HEPA filter into the anteroom and it contains - there's like this air curtain that contains the isolated individual in the room because fresh air comes into that anteroom, goes into the patient's room and out of the door into the hallway. So you have really good separation between the negative pressure room that you have the patient in and the hallway. Second choice is just a plain old negative pressure room that doesn't have that anteroom where the airflow is only exhaust in the patient room and all the supply is in the hallway. And I promise you, they didn't teach me HVAC in medical school. I had to learn all of this in this job. So those rooms are good because the air is predominantly flowing into the room. But you can have some backwash of air when you open doors or when you're moving stuff in or out of the room. And so they're less good than the sort of overall AIIR or containment isolation rooms. Then there's - what you can do if you do not have that, you can make an entire unit, a quarantine or isolation unit, and you can have the exhaust changed to sort of the airflow, the HVAC management, your plant department can change things around to make an entire unit negative. But then anybody that goes in there, the whole place is contaminated with measles all the time. And so that's not awesome, but it's not bad and it's an option. Another option is to sort of wall off using plastic sheeting and those zippers like you see in construction areas, in hospitals. The reason they do that is because they need to keep the dusty air from the construction outside, out of the hallways and out of patients lungs, because it's basically mold powder. And so you can do the same thing with airborne isolation. So you can create these negative pressures, but it doesn't work well if you don't have HEPA filtered return into your building, because then you could end up just exhausting more measles into other parts of your building. But many hospitals have this now. So what we did is what we did during COVID, which is we created a lot of extra negative pressure rooms using these really fancy schmancy sort of you could even create ante rooms with this. And then you could direct the supply into them and you can have these HEPA filters that are direct and supply into them and make them sort of about as good as you can do. And so that's what we did. We had them make a bunch of extra isolation rooms in the emergency department and a bunch of extra isolation rooms, a couple extra isolation rooms upstairs on the peds units where we could fit them in. But they take up space. They're really annoying. They're kind of loud. You can't really see what's going on inside the room. There's definite downsides. And if you don't have HEPA filter return, then you're not going to be a super viable option. But the key here is that this is the time when you need to start thinking about something you know nothing about, which is a HVAC. And you need to call on people that do know about that for your hospital. And I find myself in this situation multiple times where I'm really encouraging people to be as creative as possible. Like we cannot do this the way that we did it yesterday. We're going to need to think of a creative solution. This is the time to go back to your like I built it with Legos brain and figure out how to do something that is going to work and solve this problem. And that's not always the way that everybody is thinking, but it is the way that you need to think when you have a novel, unusual situation that your hospital is built for, you need to start thinking how you're going to make it work. And that's going to require some creative thinking on the part of people that know a lot more about HVAC than me.

And so you really also need to just talk to your public health department to in determining how many potential cases may be in the future. And that's going to inform your discussions with, you know, plans, as Emily had said, in terms of like, what should we do in terms of, you know, constructing more rooms? How many should we, you know, be constructing, how much should we be converting units, etc. You really need to ask your public health departments, you know, how many were exposed, how many of them were not immune? And where are they at in their incubation period? You know, the incubation period can be a couple of weeks. And so if several of them or a lot of them are, you know, close or a week, are we going to have into the incubation period, then you really should start seeing an influx of cases at any moment. And you also kind of have to ask your public health department like have there been efforts undertaken to vaccinate, you know, after one case you really should start thinking about, okay, who's not immune and who needs to be vaccinated? and this is where the public health department gets a ton of credit for this and for remarkably, just vaccinating all of them or almost all of them in a very limited amount of time. And that's that that's actually what happened here in the city of Chicago. And you also have to talk to other colleagues at other children's hospitals around the city to see where they stand in regards to availability of negative pressure rooms. Because, you know, if you're truly out of negative pressure rooms and there's patients coming that that are going to be at your doorstep in 5 minutes, then it may not make sense for them to, you know, come out of the ambulance bay and just to hold them there while we figure out where the best place may be, whether it is someone here, if we can move patients in and around in the hospital to accommodate or if we really can't, then you really just have to talk to the leaders of other children's hospitals just to see where they're at in terms of their airborne isolation rooms or negative pressure rooms, and that they may or may not have available available.

So despite our best efforts to be prepared, as David mentioned, the outbreak is spreading, cases are rising, and we're now getting a lot of children who are arriving at the hospital without enough notice beforehand. As hospital epidemiologist, you get paged that a healthcare worker with a recent renal transplant has been exposed. How do we deal with that?

Well, hopefully you're knowing about this as quickly as possible because post-exposure prophylaxis is more useful the earlier that you give it. individuals that are unvaccinated and are exposed, if they are healthy, they can get the vaccine. I think the cutoff. David, would you remember the cutoff point, 72 hours, maybe it's four days, three days, four days?

Yeah, three days.

Yeah, 72 hours after the exposure. After that, your option is to give IVIG. And for individuals who are immunocompromised and can't receive live virus vaccines, which is this person with a renal transplant, you're going to need to give that IVIG or IM Ig. And the faster you do it, the better. But you can give it any time you want. If the person was exposed to weeks ago and hasn't developed symptoms, it's hard with immunocompromised individuals, you can't always - they can be sick without you realizing it. And the best thing to do is that. There's no downside to giving it, and you should just do it. In this case, you have to look at the risk benefit. So you want to think about how bad the exposure was. And it really comes down to which is the bigger risk for the individual: measles infection or IM Ig or IVIG, and in this case you're probably going to give them a dose of IVIg and you are going to cross your fingers and watch really closely? You are also probably going to furlough them from work. Although IM Ig and IVIG do have a really good data them for preventing measles if given within a timely within I think six days they can be up to 90% effective. That's still not great for a health care worker who may be taking care of patients with leukemia and things like that. So you're going to definitely furlough them from work during the time period when they could get sick. And you're going to keep a close eye on them. But you can usually prevent measles as long as you know, that you need to be doing something extra to prevent it.

So as the cases continue to rise more and more health care workers are becoming increasingly worried about their own exposure. We touched on this a little bit before, but should all healthcare workers get their measles titers checked?

Yeah. This is a common question. You know, titers really aren't representative of the entire immune system. You know, there's definitely cellular aspects of the immune system like T-cell memory that really aren't being tested. And so, you know, also titers are usually checked by enzyme amino acids. And you know, with any sort of enzyme amino acid that's done in the commercial setting, there's, you know, different performance characteristics for each one. A negative titer doesn't really mean that you're not immune if you've had two doses of MMR. And as Emily said, there likely is some level of immunity if you are fully vaccinated, even if you don't have detectable levels of antibodies. You know, there was a study many, many years ago that looked at health care workers with measles who got measles from the health care setting. I think there were like a handful of cases, like almost 30 cases from a 15 year period. I think over 60, 65% of them did have evidence of measles immunity. So in other words, that's defined by either getting fully vaccinated or having lab evidence of measles immunity or measles detectable in measles titer I should say, or those who have lab evidence of measles infection in the past or those who are born before 1957. But, you know, really, I would say I think the most important thing, at least from a health care worker standpoint, is that you have access to good PPE. And we know, you know, good PPE works if it is worn. And number two, if it is worn correctly. The level of exposure for those health care workers, you know, I think I think if you were to do a deep dive, my hypothesis would be that a lot of them probably weren't wearing great PPE. So I think the emphasis really should just be on wearing good personal protective gear, in addition, really having good triaging upfront so that you can promptly isolate those where there clinically is a concern for measles. And so I think that's really the best bang for your buck

Yeah, worried well are the rule in every single cluster or outbreak investigation. As soon as you're done screaming into the pillow and you have a chance to take a deep breath, you should probably start thinking about what you're going to do with the worried well. People get really concerned about stuff. They see the hubbub and they want to take care of it. So they are going to come, you want to get answers to these questions. If you just ask most risk averse infection preventionist, they will usually be able to tell you exactly what questions worried well are going to have. And you can make a plan in advance. This is where communication matters so much in outbreak management. So we talk a lot in the beginning of this about figuring out if it's real, making sure you have a case definition, confirming your diagnosis, isolating people up front and having protocols for identifying who's at risk and who's not at risk for frontline clinicians. But the really the important thing for you to do at every step of the way if you're the hospital epidemiologist, is to communicate clearly with your staff, with the patients coming to facility, with the leaders that you're reporting up to, about exactly what's going on and trying to anticipate and answer questions in advance. Because when people feel like their questions are answered, they don't like panicking. And when people feel like panicking, they do stuff that you didn't recommend. They make stuff up that may not be the right thing to do, and so the more you can be proactive about communication, sending out all those emails that no one's really reading, but they're going to read them when there's something emergency happening in your hospital, those messages, those you got to send those out. You've got to take the time to write them, even though it's the last thing you're going to do at night after you've handled all the stuff that happened that day, It is really going to make the next day easier if you put a little bit of time into communicating both up, down and to everyone in your institution and the patients that are coming to

Before we wrap up, Emily, would you mind giving us your key takeaway points for investigating an outbreak?

Yeah, I think following the steps and making sure you're deliberate about the details of defining what your case is, making that communication sheets, making the pathway for clinicians to follow. The idea of what you're going to do and what's going to happen, it's going to formulate and then come together in your own head a lot faster than it is for everybody else. So the main takeaway point is to be really deliberate about defining those things and communicating it out to everybody that needs to know, because the biggest mistake we make is probably thinking that other people understand it as well as we do

David, would you like to add anything?

Yeah. Just to add on to what Emily said, you know, the communication aspect is really important. This is this is such a team effort. And when I say team effort, I mean, like it's a citywide effort. It’s your public health officials. It's us, you know, hospital physicians and microbiologists who are sending out these diagnostics. It's up to the pediatricians as well to really make sure that everyone is getting vaccinated. And so if there's something extra, I can add, it's really just to get vaccinated. You know, humans are the only hosts for measles. There's no other reservoir for measles. And so you can really just stop it. We can stop it. We can theoretically eradicate measles if everyone just gets vaccinated. So that's the last thing I wanted to say.

Thanks again to Palak, Emily and David for joining Febrile today. In case you want to hear a little bit more about the steps in an outbreak investigation, I definitely encourage you to check out the prior Febrile episode # 71, also entitled Outbreak Investigation. Febrile is produced with support from the IDSA (Infectious Diseases Society of America). Don’t forget to check out our website febrilepodcast.com, where you can find the Consult Notes, which are written supplements to the show with links to references, our library of ID infographics, and a link to our merch store. Please reach out if you have any suggestions for future shows or want to be more involved with Febrile. Stay safe, and I’ll see you next time.