96. FIS 2024 part 2: Viruses

HO HO HO, MERRY FISMAS!!!

On the Second Pod of FISmas these ID:IOTS have for you… an all-enveloping, capsidating update on the High Consequence Infectious Diseases, measles, RSV and other viruses that you ‘R naught’ going to want to skip! 

Jame and Callum attended the Federation of Infection Societies 2024 annual meeting in  Liverpool; here they share their reflections on the sessions  they attended on: Viral pathogens

Final episode on fungi etc. coming soon!

Notes for this episode here

Transcript

Jame: 0:18

Okay, back with our viral section, Callum. Do you want to start?

callum_1_11-26-2024_140036: 0:24

So no, no introduction, no pun, nothing. You don't think, I think if we did a really good joke, perhaps it might go viral. So yeah, but we're back to this and, James, so you went to this talk about a measles outbreak in Birmingham.

Jame: 0:41

did you?

callum_1_11-26-2024_140036: 0:43

I didn't actually make it to that one. I wanted to go,

Jame: 0:45

yeah, so This was from Lisa Berry, who works in Birmingham, and she was talking about how they had dealt with a outbreak of measles that they got due to under vaccination in certain deprived areas. And she talked in particular about a couple of schools where the vaccination rates were something like 60 percent and they were able to get them up to 80%. But as, as you're well aware, Callum, if you have less than 90 to 93 percent vaccine uptake in your school, population, then that is enough for measles to spread because it's one of the most infectious, in fact, the most infectious, disease that we've got. So it's R nought number, if people remember R noughts from, the COVID years, it's R nought is about 15. And so it is very easy to catch measles, particularly if you're unvaccinated. and one, one of the, they mentioned that one of the reasons that they were having a bit of difficulty is that The MMR has a porcine component, and so in areas where people don't want to eat, pork, then there was a significant, lack of uptake, and there's a non porcine, variant available, so they started promoting that they had that, and the uptake, got much better, and then they mentioned a couple of things that they did to try and improve measles uptake. One was that they went into schools and sort of said, hey, we've got a non piggy MMR. Why don't you have it? And everyone said, yes, excellent idea. And the other was that the. check the measles IgG, both pre immunosuppression and in pregnant women at the 12 week scan. They either asked about MMR status, or if they said they weren't sure, that they'd had two shots. They then got their measles IgG checked, and if, the IgG was negative, they were then offered, vaccination. And then there was a little bit on, symptomatology.

callum_1_11-26-2024_140036: 2:36

Yeah, so I think one way of remembering, so, measles is something that is increasingly prevalent and we should all have a high degree of suspicion of in people presenting with the four C's they talk about. So cough, carisa, conjunctivitis and. Coplex, which is definitely a spell of a C. and the, there's some useful, summaries of this and also the differential diagnoses that you might think about because, children in particular presenting with fever and rash isn't that uncommon. So the National Measles Guidelines, which were published this year from, the UK health security agency are actually a really useful summary of, measles. And they've got a nice graphic figure one, which tells you the clinical course over the sort of days of illness. So starting with a rising fever, and when you might expect to have these symptoms.

Jame: 3:24

the rash comes on at sort of day three, four. It's not the first thing. The fever's the first thing. And then the chorizon conjunctivitis arrives and then you get the,

callum_1_11-26-2024_140036: 3:35

And you're infectious before the rash comes on and then after the rash is there as it's four days before to four days after the rash onset I think that's the most challenging thing of measles. So locally we've had some cases where it's been missed because it's not been, obvious initially and people haven't thought about it. So I guess one, one main takeaway from this talk would be just You know, having a really good understanding and having a high index of suspicion. They also went on to talk about the diagnostics. and again, in the show notes, I've taken a useful graphic figure 2 from those national guidelines. And they just talk about, when different tests might be positive from time onset of rash. So, initially when you see your viremia. checking on an RNA, can be useful, via PCR, and you can do that oral fluid mouth swabs. And then later on, you can check serum IgM and an IgG. In the Birmingham outbreak, they talked about their experience using different treatments. Now, in measles overall, there's no specific antiviral treatment available. Things like ribavirin and interferon gamma have been used in severe measles. especially in CNS disease, which is a sort of, rare complication, the efficacy of these is unknown, often used in sort of desperation. There is some guidance internationally about vitamin A, which has been shown to reduce morbidity and mortality in measles. And WHO recommends, dosing, based on age of under 12 months, getting lower doses. Again, usually that's in the context of a low middle income country. So how much that applies to the UK setting is unclear. but the mainstay of treatment really is, supportive care plus management of any secondary bacterial infections. So that's treatment. So what about human, normal immunoglobulin? How were they using that in the Birmingham outbreak?

Jame: 5:20

Well, so in the trust it's a controlled drug, and there is a national pathway in the measles guidance for what to do with it, and what they did was they adapted that and implemented it locally. So they were giving it, IM or subcutaneous, and that meant that they didn't have to give a cannula, although if you give it subcutaneously, it is an infusion, and so there are issues doing that in pediatric patients, they need to be trained, and so not all the nurses had that training, so maybe IM was preferred. But those are the two non cannula ways that you can give it. They tried to administer it via their SDEC, so their same day emergency care units and ambulatory care centre, and that meant that the patient didn't have to come in or they didn't have to set up an outpatient clinic. That took a bit of persuading locally that this was something that, should be done in an SDEC, because it's not really what they were set up for, but you can justify it on an admission avoidance. We're trying to, we're trying to combat the world's most infectious disease sort of argument eventually won out.

callum_1_11-26-2024_140036: 6:22

Yeah, I think we've put copies of those in the show notes, the local pathway. We don't have the original image. It's not the best quality, but I think a good example of, taking those national guidance and then implementing them locally like they did in Birmingham. So some lessons to be learned for every center, which I think every reason to be seeing more and more measles as time goes on. Unfortunately,

Jame: 6:42

the main take home message is that I need money to buy a new phone, so any donations to the Idiots Podcast will be gratefully received. let's talk about flu.

callum_1_11-26-2024_140036: 6:54

yeah, so there was a talk in the, there was a session that I think both of us went to about high consequence infectious diseases. So we'll talk through a couple of those The first one was about avian influenza and other emerging influenza viruses. So this is by Catherine Brewer, consultant clinical scientists, in Wales National Influenza Center for the uk. so essentially, the initial part of the talk you just talking about like how, how influenza viruses normally exist. In birds, so she was talking about LPAI, and, HPAI, so low pathogenicity avian influenza and high pathogenicity avian influenza. And usually in, the bird host, you've got this low pathogenicity strain, which is circulating. Usually the birds aren't really sick and maybe asymptomatic. It's present in the sort of respiratory tract, but not really anywhere else. And, it's not causing them any disease. But with, accumulation and mutations, particularly within the hemagglutinin, protein, you end up getting wider cleavage off the virus by different bird cell types, leading to higher pathogenicity, and that leads to it being spread basically throughout the bird, different organ systems and in the gut, and then it is, coming out in the from the cloacae and the sort of bird droppings, and not only can this lead to this sort of high pathogenicity and widespread bird death, which we see in the news, but also contamination of the environment. And she was talking about how does it spread? And while birds passing over, even just, a small amount of droppings can lead to, infection. and then, and in the animal husbandry trade, these birds are often in very close confinement. They're maybe not a very good hygienic settings. So it leads to quite quick spread. Um, so it's just really interesting to understand that, because we talk about, avian influenza and the risks that pose from a sort of high consequence infectious disease. quite a lot.

Jame: 8:45

Yeah, it was interesting. And they also mentioned that it was commoner high pathogenicity variants with H5 or H7 hemagglutinin. So currently there's a H5 and one. outbreak in, cattle in the us. And so the tho those hemagglutinins, in particular are associated with higher pathogenicity, which I thought was quite interesting.

callum_1_11-26-2024_140036: 9:08

There are lots of barriers for these influenza viruses to spread into the sort of mammal host. so things like host cell recognition, cell proteases and genetic factors. so it's not easy for them to switch over, but it's certainly something that we need to be very vigilant, about.

Jame: 9:25

Well, no, but I, I think it must be easy enough

callum_1_11-26-2024_140036: 9:29

yeah, I guess they're pretty different, they just, you need that high level exposure and you see most of the cases where it does cross over that actually the, that primary, mammal infection, they might be unwell, but it's harder for them to spread just because it's not well adapted to the host, but the worry is that you get co infection and so on.

Jame: 9:48

Speaking of which, Callum, the US listeners will probably be aware that there's an outbreak of bovine flu A in cows at the moment, and it's quite interesting what is happening. So the. flu has adapted to infecting the udders of the cow through what alchemy I do not know. And therefore the milk is contaminated with the virus but completely inactivated by pasteurization. So unless you're drinking raw milk from a flu infected cow, the risk is minimal. And apparently when the cows get infected by this, their productivity of milk drops, but then recovers, and then you get stable, infection of the flu. And it doesn't seem to have any, affinity for the cow respiratory tract, but it can affect, humans. So people that are involved with animal husbandry, on cattle farms have been infected. So dairy workers, and farmers, but mostly they're getting mild infection with cow milk. conjunctivitis only and that's because of a particular tropism for a epithelial surface receptor which is on conjunctiva as well as respiratory epithelium. So I thought that was quite interesting, and so the conjunctivitis, I think, comes first, and the mild, flu like symptoms come second.

callum_1_11-26-2024_140036: 11:14

Hmm.

Jame: 11:15

and the other interesting thing, which I don't think has any relevance to us, Calum, is that farm cats have been getting this, and they've been dying of very serious respiratory problems. infection. So the cows are transmitting it, to the cats and the cats are badly affected by this.

callum_1_11-26-2024_140036: 11:31

Well, fought some prayers to the cats, I guess. I, I thought this whole session was quite something that we think about, but I didn't really understand that much about, so it was good to get a bit more understanding. And as always. Don't drink raw milk. Just don't do it. Pasture came up with pasteurization. It's amazing. It stops lots of infectious diseases.

Jame: 11:52

Um, what about RSV, Cal?

callum_1_11-26-2024_140036: 11:55

RSV. So RSV, respiratory syncytiovirus. So I think we've talked before in the pod, maybe after the BIA spring meeting. theRe was some talk about, RSV vaccine

Jame: 12:04

Yeah, we talked about vaccination, the new vaccines coming out. So yeah. so RSV there was a talk about the burden of RSV overall and the introduction of the vaccines. And the, there was data presented on what proportion of seasonal flu like illnesses are caused by RSV, and it's about sort of 13%. And by, by contrast, the influenzas would probably account for something like 50 percent of that. And then coronavirus is about 8%. Obviously, this is, pre pandemic, from 2015 to 2018 in Canada. And then some more local data from, Nottingham, the RSV seems to exhibit a seasonality that we haven't seen yet with COVID, but we do see with influenza. And we see it a little bit with RSV. So the RSV season seems to come in sort of November, December time and flu comes after it, but COVID is not exhibiting that seasonality just yet. And notably it's a cause of care home outbreaks. In terms of transmissibility, it's R0 is between 3 and 9 comparing to flu's R0 of 1. 5 and COVID's 2. So it is the most transmissible of what you would nowadays call the big three. And much higher risk in age extremes, particularly over the age of 75, pre existing chest or chronic respiratory disease, cardiovascular disease and immunocompromised and diabetics. But yeah, the interesting thing is that in the over 75s, the mortality at two months is about 11 to 16%. In contrast with influenza, which has a, 60 day mortality of between 8 and 10%. And there seems to be a more recent, rise in case fatality rates in the over 75s as well. So that's something to worry about. But, luckily, vaccines to the rescue, because the treatment is entirely supportive and so they mentioned the UK rollout of the RSV program. So initially it's going to you. And they mentioned what the UK was doing to roll out the RSV vaccine. So they have purchased a Brisvo from Pfizer for the vaccine. They are initially rolling out the over 75s., And they're using an all year, program, so they're not just doing it in winter like we would do for influenza, say. they're doing it all through the year, and they're going to have a catch up program for, people that aren't just 75, people that are all older than 75. And the interesting thing, that they've got is that they've got a second year efficacy data., And it still seems to be pretty efficacious, about 77%, so that's pretty good. and not much in the way of side effects, so about 10 percent get pain at the site of injection. Fewer than 10 percent get redness and swelling, and 4. 4 people per million doses of RSV vaccine will get Guillain Barré syndrome. That's against a background rate of 0. 5, so in excess of 3. 9. So, rare, but important to know about, I suppose. Yeah,

callum_1_11-26-2024_140036: 15:31

you know, people having RSV and not really thinking about it too closely. But, as you got more data, hopefully they were going to target that and stop it being such an issue. Talking about other viruses, which are potentially much more, scary, moving on to the sort of big boys of the scary infectious diseases. So there was a talk on was two talks on high constant infectious disease, but specifically looking at viral hemorrhagic fevers. So first was by Dr Tom Fletcher, who's pretty well known in the world of viral hemorrhagic fever and has done a lot of important work internationally, particularly around. Trying to improve our knowledge and management of, CCHF, Crimean Congo Hemorrhagic Fever. And he was giving a sort of general overview of the diagnostics, epidemiology and management of viral hemorrhagic fever, which is quite a broad topic because there's a lot of different viruses, within that. He shared some recent experience following the Marburg virus outbreak in Rwanda. and there was a large nosocomial, outbreak involving healthcare workers, and actually they had a very low mortality rate in that outbreak. ICU. Um, and, the health system in Rwanda is, much more established than in other areas where we've seen VHF outbreaks. So it was just a sort of to demonstrate that what you can do, even without, good therapeutics, he was really making a plea. there's been a large scale funding for vaccine development following the, west African Ebola outbreak. but. he was highlighting the need for increased funding for therapeutics because at the moment, really don't have many options. there's some, Mabs that can be used, which they were able to access in Rwanda and Remdesivir was used widely, but there was no randomized, trial evidence base to support that. so, some hypothesis could be formed about that contributing to low mortality that he saw, but not really, proven. and I guess his other point was that not only, is the right thing to get therapeutics, but if you want people. to have faith in your control measures. So he was saying that in the West African Ebola outbreak, because the mortality was so high in treatment centers, that it was difficult to establish people's, in the communities trust within that process, because all they would see is people coming out, in body bags from that. So it'd be hard to convince people to report or be involved in surveillance to try and recognize cases. So without having, therapeutics and lowering the mortality, it would be very hard to actually control. Control outbreaks. And the other main point that he had is a very rapid summary of a very sort of comprehensive and all inspiring talk was the need for rapid near patient diagnostics supported by sort of laboratory services to and really focusing on ruling out. So tests of a high negative predictive value. In order to allow patients that don't have VHF to receive the care they need. So he shared some sort of examples of patients that he'd been involved with where the patient's care for their actual disease causing hemorrhage had been significantly delayed. relating to the query around viral hemorrhagic fever. And you can look at that and even in the UK, a high resource setting because these services are so centralized, sometimes it can take up to 24 hours to get a result back. that kind of leaves you in a limbo and ability to manage the patient appropriately. that sort of hidden harm. It was, yeah, a fantastic talk. really, but very fortunate to be able to hear from that experience and try and learn something from it. and then just following on from that, there was another talk on VHF and it was talking about preparedness and focus on the UK hospital setting, but I think lessons to be learned everywhere. And just a couple of key takeaways from that. So that was presented by Anne Turnbridge, who works in Sheffield, and she was highlighting a couple of resources. So three things have changed recently. So the National Infection Control Manual for England now has an addendum on high consequence infectious diseases, PPE. And that's born out of a lot of work that's been going on over the last several years. So I think the first paper was published in 2018, where there was this need to say, we were a lot, a wide range of PPE has been used, both in Africa and in other healthcare settings. And in UK, there was a very fragmented, approach with lots of different centers using different PPE. And so, there was work undertaken to try and develop an evidence based PPE involving simulation with, ultraviolet, lace, different bodily fluids, examining the different PPEs and finding where the breaches are. And finally, after many years of hard work by many people, that PPE is now published, and the link for that is in the show notes. And along with that, there's a wealth of training resources, including videos and donning and doffing guides, and that's, a lot of that's hosted on the H Kids training website. Site and the HK training, national team were there. And that's again, based out of Sheffield. Link for that there. So if you're listening and you don't really have, joined up PPE or you don't have the educational resources, that's a great thing. And then in the infection control manual, they've got the links, the procurement of all the different equipment that you need as well. Yeah, so just and then just two other things to highlight. So, I think we need to come back and talk about VHS when we get onto viruses eventually, but the advisory council on dangerous pathogens guidance has recently been updated. this in the last, just the last couple of months and an updated risk assessment for VHF, which is really useful. And there's e learning available on H kids on the learning platform for NHS England. So loads of stuff that you can talk about, outside of the sort of guidelines. she also presented two other small things that I think are worth mentioning. One was, just talking about how. Diagnostics for again, non VHF conditions can often be delayed in these patients, even in a high resource setting. And she referenced a paper that was published in 2017, by Shorten et al. And that was looking at the risk of transmission of VHF infections in the laboratory. And basically saying that we can, and certainly locally we do this, you can process samples from these into the sort of normal laboratory area for other tests. And, we know that there's a lot of patients coming back from travel who may be a query VHF, but are actually presenting of something else, for example, severe dengue and she highlighted a paper that was published by the reimported pathogens lab ripple and I've put the graphic from that paper into our notes. Just looking at the different destinations that people were turning from and what conditions that they were eventually diagnosed with and dengue was, very, very common in large parts of the world. And so, just thinking again, just like Tom Fletcher had mentioned, that we need to be able to rule out VHF quickly so that we can manage the condition the patient actually has. Yeah, it's great. Great talks. So that's viruses