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Resurgence of Old Viruses: Vaccine-Preventable Inf ...
Resurgence of Old Viruses: Vaccine-Preventable Infections in the Critically Ill
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Well thank you very much. So I'm Ryan Mabes. I'm a faculty at Wake Forest and thank you again for that kind invitation. It occurs to me this is my first live meeting since getting out of the Navy, so I'm like wearing like regular clothes. It's kind of novel. These are my disclaimers. Research funding for my institution from a curious sound pharmaceuticals and actually now Pfizer as well, unrelated to any of the topics we'll be talking about. I was the site PI for the AstraZeneca COVID vaccine back in the day and I have some consulting fees for clinical trial support. So none of that has anything to do with this talk from a financial, should I say source of bias, but I do have a very strong intellectual bias here. So the bottom line, right, so you can all just like read this slide and go because this is it, okay. Vaccinate yourself, vaccinate your family, vaccinate your colleagues and staff members, vaccinate your patients and advocate for vaccines, right. That's basically it and enjoy the rest of Congress. All right, so you know it's been interesting the last few years to see how the kind of the politics of vaccine refusal has shifted in the time of the pandemic, but it is not a new problem and so we're going to talk about vaccine preventable diseases and I got to admit I kind of skimped on reading some of the fine print here because I'm not going to talk exclusively about viruses, we will talk about some relevant vaccine preventable bacterial infections as well. But if you look at the big like highly contagious infections that tend to get involved in critical care, we're looking at measles, varicella, meningococcal infections, influenza and COVID-19 of course are addressed elsewhere. There are some other diseases that are clearly of interest to us, pneumococcus, pertussis, tetanus, mumps, rabies and others, but just for purposes of focusing on these this big group, we're going to talk about mainly measles and varicella and then I'm going to cheat a little bit and talk about meninge and pneumococcus. Oops, there we go. All right, so any discussion of vaccines and viral diseases has to talk at least briefly about smallpox and we all had a little reminder with the monkeypox outbreak last year. I have to say I was very excited to give tecovirimat to someone, a drug I'd been writing about since I was an ID fellow. So these are the last three humans to get smallpox, right? So the child on the left is Rahima Banu Begum, who's a child in Bangladesh who has the last known person of naturally occurring variola major. Ali Malmaline is the last known person with naturally occurring smallpox, actually died in 2013 of malaria. He, after surviving smallpox, became a great public health advocate and public health worker in the Horn of Africa. And then Ms. Janet Parker was a medical photographer who is the last human to die of smallpox, the tragic result of a laboratory accident. So if you look at the crude death rate due to infectious diseases, you see a fairly steady decline. Obviously if you put in 2020, 2021, there's this in the map there, much like the big spike you see there with the influenza pandemic. Not all of this decline is obviously due to vaccination. Some of this is due to improvements in sanitation. Some of it is due to the development of antibiotics. But vaccination clearly played a strong role. You can see the introduction of the Salk vaccine against polio there in the middle. And if you look at the death rate due to infectious diseases globally, so the top curves there are the population adjusted death rate for infectious diseases, referring to principally to sub-Saharan Africa there. The very bottom of this list, which goes up to 2019, one of the lowest death rates due to infections in the world is the United States. Obviously 2020 data, it's going to, you know, again be a little askew. But in general, this has been an area of strength for public health in the United States, at least historically. Now if you look to see who dies of COVID, and I said I wasn't going to talk about COVID, but I, you know, lied. You know, you can see overwhelmingly, and this is in the last year, you know, that the, and we all know this, right? We all know this. But like who's dying in the unit of COVID, right? It's not the guy who's gotten four boosters. And this lays it out, I think, in a nice graphical manner. And of course, we have to fight against some folks who, you know, I don't wish to make assumptions about everyone's politics, but I do hope there's a broad consensus in this organization about the value of vaccination. We are one of the relatively few groups in the world, professions in the world, who try to keep people out, you know, away from our places of business if we can. But, you know, Robert Kennedy Jr., who solely is the proud name of his family. Andrew Wakefield, who was licensed to practice medicine, was revoked by the United Kingdom and sadly found a home in the United States. And then the protesters against various COVID vaccine mandates. I cover their faces because I do not consider them entirely at fault for being the, in some ways, final victims of a broad campaign of misinformation. But this is not a new problem, right? This is not a new problem. You see some of these, these are, some of these are from 1902, right? In the upper right-hand corner there, you see people encouraging mask use during the 1918 influenza pandemic. The upper left, the anti-vaccinator, the fake polio vaccine may kill your child. I mean, that could, you know, change one word and that could have come out on Twitter yesterday. And so what does this lead to? This has led to a reemergence of diseases that were largely of historical interest for a long time. So this is the estimated coverage by state from 2016 of having gotten at least one or more doses of the MMR vaccine in children by the age of 24 months. So generally to prevent, measles is super duper duper contagious, right? It is the, the R naught of measles is like 15. It's incredibly contagious. You need about 93 to 95% community vaccination rates to block measles transmission. Right now, kindergarten entrance in the United States by the most recent CDC data is 94%. So we're like right there. And obviously there's some variability in communities and it's interesting in light of the COVID pandemic, what some of the most highly vaccinated areas are like Alabama, like Maryland, way to go Alabama, right? You know, it is quite interesting. My home state of Washington where I grew up is sadly a bit on the low side. We've had measles outbreaks there near the Washington Oregon border as a result. So generally this is a requirement, but it's a requirement with the option for a personal belief exemption or a religious exemption in many, if not most of the states in the United States, California, New York, Maine, West Virginia, interestingly in Mississippi being being standouts in that regard. All right. What does this mean? This means that only about two thirds of U. S. Children have received all recommended vaccines. Now, you know, that's again, that's a fairly binary response, right? If you count like they get all three doses of HPV, you know, that does throw the numbers off of it, but it's not as good as it could be. And look at adults. Fewer than 70% of U. S. Adults have received recommended tetanus, pertussis or pneumococcal vaccines. Slightly more than half of us get a flu shot every year. I mean, not like us in this room, us, but like other us, like my brother. Now he's a good guy. He probably gets his flu shot. I haven't really asked him. Okay, so reported measles cases in globally has, you know, has gone up in 2019. There were actually a large number of measles outbreaks because of these low levels. Now, obviously this is purely numerical. This is not population weighted. So like greater than 1000 cases of measles in the United States is not the same thing as greater than 1000 cases of measles in Portugal, for example, just based on size. But there was a fairly widespread outbreak in many parts of the world. And actually the European Union really got shellacked with this. There were 13,000 cases of measles and 13 deaths in the EU. And I think some people say, well, that's only 13 deaths. I'm like, yeah, it's 13 dead kids. Like, is there a correct number of pediatric deaths we should be aiming for? I'm pretty sure it's like not 13. Alright, so what does measles actually look like? Has anyone here seen measles like clinically? Like I have, but not in the United States. Anyone else? Okay. So this is one of those things that, you know, our older pediatricians knew and older family physicians knew intimately. The complications of measles are, it's actually a much more severe disease in many cases than we fully appreciate, even though it was a universal childhood illness not terribly long ago. 10% of kids will have diarrhea, 5% will progress to pneumonia, and about one in 1000 will progress to encephalitis. And actually, interestingly, mumps and measles were the major causes of asymptotic meningitis in children prior to vaccination. Between one to three kids per 1000 who get measles will die, right? So these lesions here you see on the left, that's coplix spots. That is a kind of classic finding around the onset of fever and cariza that predates the eruption of the rash. So you'd meet older pediatricians who'd see a kid's got a fever, look in the mouth, see coplix spots, says you've got measles, the rash will come tomorrow. And then cariza, the kind of in conjunctival injection is also a classic feature. From an adult, and I'm an adult intensivist, I'm not a pediatrician, from an adult standpoint, the big thing that one would worry about is something called subacute sclerosing panencephalitis, or SSPE, and I have seen a couple cases of this over the course of my career. This is a delayed late manifestation of measles that occurs seven to 10 years after primary infection. About 10 cases per year in the US, about 20 cases per million per year in the US. And this is a delayed late manifestation. About 20 cases per million person years in India, which has a higher, a relatively higher incidence. This is an almost invariably fatal disease within one to three years of diagnosis. Yeah, this is a real deal. And there is a small subset, like 5% of people, who will remit spontaneously, and there have been studies looking at high dose ribavirin as a therapy, interferon alpha has been tried as a therapy with relatively limited success. But there are ongoing efforts, many of them led by NIAID, to try to find some effective therapy for this, thankfully very rare disease. But much more common, not too long ago. So how do you diagnose measles? RT-PCR, nasopharyngeal swab, just like you diagnose flu or COVID or what have you. You can do it based on anti-rubiola IgM from serum. That is not commonly done, but it can be. Therapy is pretty limited. If you are working in a global health setting, if you're working in a resource limited setting, WHO guidelines recommend the administration of vitamin A to kids, and that does show a reduction in many of the acute complications of measles, particularly diarrhea and pneumonia. That study was attempted to be replicated in Western Europe and did not show a benefit. Vitamin A doesn't hurt, but in a child growing up in a relatively well resourced setting, it's unclear that vitamin A helps. Ribavirin has been used. I'll say that no viral infection is truly untreatable until we've thrown ribavirin at it, so take it for what it's worth, but that is one of the recommendations. Isoprenosine is an oral investigational agent with activity against RNA viruses. This is being studied for SSPE, and then obviously secondary bacterial pneumonias. We would typically give antibacterial drugs. These people need to be in respiratory isolation, right? Negative pressure rooms, PAPRs, N95s, the whole shebang. You can use MMR vaccine as post-exposure prophylaxis within 72 hours, which is helpful. You can also give intramuscular IG direct against the rubeola virus. That can be done within six days or if MMR is contraindicated for some reason. Now how about varicella? So this is a guy I took care of when I was in Afghanistan. Sort of an interesting case in that he was a gentleman with undiagnosed HIV infection, which we diagnosed, came in with disseminated varicella. So the features of varicella to look for are centripetal rash, which is concentrated on the face and trunk and decreases on the extremities. Pox viruses tend to be the other way around. Just remember pox viruses tends to be less on the trunk, more on the extremities. Other way around with varicella. And the vesicular lesions of varicella are in varying stages of development. And I think just about every military ID fellow when I was in active duty had some story about a time they get called for suspected smallpox to the emergency department. And it was always chickenpox every time, obviously, because there's no more smallpox. All right, so the diagnosis is obviously history and physical. It has a classic clinical appearance, but we do confirm it with a varicella PCR. The therapy, there is good data on the use of oral, high-dose oral acyclovir and by extension valacyclovir for the treatment of adult varicella in stable patients, and that is the standard of care. Intravenous acyclovir for more severe disease. And then suspected superinfection is relatively common, particularly in patients with signs of sepsis. Staph and streptococci get into those things pretty easily. These people also need to be in respiratory and contact isolation until all lesions are crusted over. This is an example of varicella pneumonia for that patient, and that's obviously a severe case. But that goes to show that varicella complications in adults are much more severe than they are in children. The risk of death in kids up to the age of 14 is 1 in 100,000. In adults, it's 21 in 100,000. So this is a potentially life-threatening disease, and why immunity, if you're non-immune by adulthood, vaccination is clearly indicated. The varicella vaccine, by the way, it's a live virus, but it is like the most attenuated live virus in the world. Like you can give the varicella vaccine to kids who have recovered from leukemia, right? So it is indicated in people who are living with HIV on antiretroviral therapy. It is quite safe. Certainly someone with active AML or on immunosuppression for solid organ transplant is not someone to whom I would administer it, but the threshold is pretty low for administering it. So you can give post-exposure prophylaxis. We try to remove non-immune staph from patient care areas between 8 to 21 days after the last exposure. You can give vaccine within five days of exposure. Varizig is a varicella hyperimmune globulin, which can be used as post-exposure prophylaxis. We occasionally use that in non-immune pregnant women who are exposed to varicella. And there isn't a ton of data on oral prophylaxis with Valtrex, with valicyclovir, or acyclovir. It probably works if dosed appropriately. I would give it the one gram TID dose just to kind of power you through that period. I'll say when I was taking care of this guy in Afghanistan, what we didn't have a lot of was negative pressure or the ability to isolate. And I also had a hospital full of presumably non-immune or uncertain immunity Afghan patients, and so that got very complex from an infection control standpoint. I put all of the Afghan patients on valicyclovir and moved the guys far back away from the rest of the ICU as I could. All right, so meninge, not a virus. Meningococcus is a gram-negative diplococcus. It occurs sporadically and in pandemics. This is a picture of kind of classic purpura fulminans, purpura fulminans due to meninge. Very high mortality despite appropriate therapy, and is really one of those things on the very, very short list of causing life-threatening overwhelming sepsis in immunocompetent hosts, right? It's not a terribly long list. Risks are travel, congregate housing, asplenia, and then terminal complement deficiency, which actually in the U.S. in people who present with meninge is actually relatively common. I would say that probably about half the people I've taken care of with meningococcus, once they're recovered, turn out to have a terminal complement deficiency. That's entirely anecdotal, but probably true. So annual epidemics in Africa, this is really where it's in, this map is what we call the meningitis belt, kind of this strip across central, the central part of the African continent. College students in dorms, about 3.6 relative risk compared to the general, compared to age match controls. Okay, that's surprising. Ah, there we go, thanks. Okay, and then the hajj, actually sort of interesting, the Saudi government requires proof of meningococcal vaccination to go on the hajj every year, to Mecca, because you have people from all around the world packing into a very tight place, and so they have large meningococcal outbreaks in the absence of vaccination. Yeah, so what do we do with these guys? Drop of precautions in hospitalized patients until they've gotten 24 hours of ceftriaxone or equivalent therapy. Post-exposure prophylaxis for close contacts, and this is one of those sort of stop the madness things, where like the person who checked their vital signs three days ago wants to be put on post-exposure prophylaxis. It is really more for people who are involved in direct contact with airway secretion, so if you intubated them, if you did CPR on them, if you bronced them, or household contacts, if you resided with the person, if you lived in the dorm with them and all of that. Just a quick thing on pneumococcal disease, I'm not going to talk about how to take care of pneumococcus, I'm pretty sure we all know that, but just pointing out that the impact of vaccination on the incidence of pneumococcal disease in the United States is extraordinary. These arrows are when different pneumococcal vaccines were introduced and the effect that had on pediatric invasive pneumococcal disease. But the other interesting thing, and another reason to push vaccination, is this is what pediatric vaccination did to adult pneumococcal disease, because it turns out that children are filthy reservoirs of disease, and they give grandma and grandpa pneumococcal infections. And so the incidence, the decreased incidence of pneumococcal disease in older adults and in RICUs, if you're an adult intensivist, is largely driven by pediatric vaccination. Adult vaccination matters as well, of course. So these are the old, decrepit recommendations for pneumococcal vaccination, all right? You give like Prevnar, and then you wait a few months, and then you give Pneumovax, then maybe five years later you give it another. Okay, these are the new recommendations. Give a single dose of PCV20 to people who need pneumococcal vaccination. That's it. That's all of that. All right, we have to set the example. I'm sure a lot of us have these like selfies of us getting our COVID vaccine. And to say this is again not a new problem. This is the order that George Washington wrote to mandate variolation, the predecessor of vaccination, of the Continental Army during the Revolutionary War. It was actually quite controversial at the time, and they had to do it in secret because of mass protests. This is not a new problem we face. We've been through it before. We beat it before. We'll beat it again. Thank you all.
Video Summary
Dr. Ryan Mabes, faculty at Wake Forest, emphasized the importance of vaccines in his presentation. He urged everyone to vaccinate themselves, their families, colleagues, staff members, and patients, and to advocate for vaccines. Dr. Mabes discussed vaccine-preventable diseases, including measles, varicella, and meningococcal infections. He highlighted the decline in death rates due to infectious diseases, largely attributed to vaccination. He also touched on the politics of vaccine refusal and the reemergence of diseases due to low vaccination rates. Dr. Mabes provided insights into measles, its severe complications, and the potential for subacute sclerosing panencephalitis. He also discussed the diagnosis and treatment of varicella in adults, noting its higher mortality rate compared to children. Additionally, he spoke about meningococcus and the importance of post-exposure prophylaxis. Dr. Mabes concluded by emphasizing the impact of pediatric vaccination on adult pneumococcal disease and the need for adult vaccination. He urged healthcare professionals to set an example by getting vaccinated and reminded the audience that vaccine hesitancy is not a new problem.
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Infection, 2023
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Type: one-hour concurrent | Viruses R0 Our Friends (SessionID 1118826)
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2023
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vaccines
vaccine-preventable diseases
measles
varicella
meningococcal infections
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