136. RIPL - VHF

What could be more Rare Imported or Pathogenic than the Viral Haemorrhagic fevers?!

Callum is joined again by Drs Claire Gordon and Amy Bellfield to talk all things VHF and HCID from the clinical lab perspective.

We're sure you'll all be Very Happy Fans by the end of this one...

Transcript

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Callum 0:18

Hello, Amy and Claire.

Amy 0:21

hi.

claire ripl 2 0:21

Hi.

Callum 0:23

Hi. We are once again honored to be joined by Dr. Amy Bellfield, a Ripple Clinical fellow, and Dr. Claire Garden, who's head of the ripple Clinical Services. And if you haven't already done it at this point, you should go back and listen to our previous episode all about Ripple because it gives you a wonderful overview of what Ripple is and what they provide. We're here today to put out an episode to all of the very huge fans out there, the VFS all about. VHF.

claire ripl 2 0:59

Well done.

Callum 1:01

So yeah, that was a difficult one. So I guess my first question is going to be, what on earth is A-V-H-F-A viral hemorrhagic fever?

claire ripl 2 1:13

So the first thing to say is probably it's not the greatest name for them in that hemorrhage is not necessarily always a feature. So it's basically the sort of the catchall name for a group of evil viruses that where the sort of common. Pathway may well. be hemorrhage but isn't always. And the viruses that cause viral hemorrhagic fevers, are actually varying groups. So the sort of four main, groups of virus that. these fall into. And you'll see in the show notes the sort of very long list of things that are classified as viral hemorrhagic fevers. So it's not a great name for them actually, but I didn't come up with it. And that's, it's just how we refer to a group of viruses that may be associated with severe infection plus or minus hemorrhage.

Callum 2:05

So what maybe would be a better term, something to implicate that they are an infectious disease that have consequences that are quite. you know?

Amy 2:14

consequence.

claire ripl 2 2:15

I see where you've gone There. So one of the classifications of infectious disease is high consequence infectious disease? That's a UK term that we've come up with. And I don't mean we as in we at Ripple, that's a, an A-C-D-P-I think, categorization to identify diseases that need a particular public health response and that need particular, management, containment of the patient. So, not all of the viral hemorrhagic fevers are actually high consequence infectious diseases. And the ones that are, are the ones where there's a high risk of person to person transmission. So technically dengue. Maybe a viral hemorrhagic fever. If you get severe dengue with hemorrhagic fevers. It's a virus. It causes a fever, which can be hemorrhagic. And it is on the list of viral hemorrhagic fevers, but it's not a high consequence infectious disease because we don't see person to person transmission. So it doesn't need all that sort of specialist public health response or specialist management of the patient.

Callum 3:13

So there's a Venn diagram of, these, you've got one circle, which is viral, hemorrhagic fever, and you've got another circle, which is high consequence infectious diseases. And they overlap, but they'll, they're not completely overlapping. And there's obviously lots of other high consequence infectious diseases that cause things aren't viral, hemorrhage, fevers, severe acute respiratory infections, for example, being another main one. That some VFS are H kids. not sure if you, are you meant to say H kids or

claire ripl 2 3:40

I like you saying H kids. I think that sounds amazing. Everyone. We say Hsid, but that's rubbish. Or HCID. Yeah. I'm gonna start that.

Callum 3:51

is that the ke born debate all over again. Don't email about that. So, So how is it decided? Like what's the kind of definition, 'cause you've just defined what A VHF is, what's the sort of definition or how do you decide if something is a high consequence infectious disease? And also it changes, doesn't it? People remember that COVID was initially a HH kid and or h said I no, I'm getting self-conscious about that, but and OC was as well how is that defined?

claire ripl 2 4:22

So a CDP the Advisory Council on Dangerous Pathogens. So, they've come up with the criteria for an hsid. An HCD doesn't have to meet all the criteria, But these are the things that. That will factor into the decision about whether it's an or not. So that's. It obviously has to be an acute infectious disease. One that typically has a high case fatality rate where there usually isn't an effective prophylaxis or treatment. And where there's the ability to spread quickly within a community or within a healthcare setting, and particularly if there's a high risk of person to person trans transmission. And there's a clear risk to healthcare workers and. the, sort of uniting factor is going to be that they, they require an enhanced individual response. so they require high level isolation unit and specialist clinical and nursing management. and then there will also need to be a specialist public health response to do things like, contact tracing to decontaminate, for example, to notify Other countries if if it's been an imported case. So those are the criteria. and the sort of overarching thing is that this is a, an acute, severe infectious disease with A high risk of transmission within the UK that needs to be contained by specialist measure. That definition, I think is will change. That's a sort of an ongoing piece of work by A CDP. So that will evolve over time. But that's where it currently, isn't it? There is a webpage on Gov uk that I presume we can link to. It might even be there already. Is it Amy? There you go. She's good.

Callum 6:03

Thanks again to Amy for preparing the show notes for this episode. So we just talked about what they are. So maybe I could ask you, amy We already talked about Arboviruses in the last episode and how that isn't a category of viruses and just means or insect born viruses. what are the different sort of, I say groups, is that right? Or is it families? I'm gotten myself confused.

claire ripl 2 6:30

It's alright. Virus classification, nobody understands it and it changes. By the time this episode goes out, they'll have renamed something. It'll be fine. And if they haven't, sometime in the future we will be correct, whatever we say now.

Callum 6:43

So what are the different types of viruses that cause VHF? There you go. I haven't used a word that's in the classification system.

Amy 6:51

So we split them into four different groups. So there's the Arenaviridae the filoviridae, the Bunyaviridae, flaviviridae groups.

Callum 7:03

And could you give us some key examples of those viruses? And just as a sidebar in the show notes for this episode, Amy has put together a table, which is color coded, which we don't normally get in the show. So that's even extra special By the different types of viruses And the primary vector whether's, a human to human transmission documented and the country's affected, which is just like such a great reference. What are some key examples from each type?

Amy 7:30

For the Arenaviridae, probably the most commonly thought about one in everyday infectious diseases is lasso virus. Found in West Africa. And then there's also the south American, viral hemorrhagic fevers, which often come under that group as well. And then in the filoviridae there's the Ebola viruses, so Ebola virus and Sudan virus and so on. And Marburg virus as well. In the Bunya Vera Day, it's crime and Congo Hemorrhagic fever, so CCHF and the So both the old world and New world Hanta viruses, and RIF Valley Fever actually. So there's a fair few in there. And then for the Flavi Vir Day, it's, as we mentioned previously dengue virus yellow fever virus. And then a few others as well.

Callum 8:29

Yeah, there's certainly quite a few on this list that I'm familiar with and have thought about. And there's some that I have definitely read before But then I guess it's like all knowledge, if you don't use it, it disappears, isn't it? There's a lot more than you would think, but also, these are rare. Thankfully it's the name of your lab. And there's some maps here as well, which give us risk areas.. So when we talk about the epidemiology, how do you decide, what is or isn't a risk area? We're gonna come onto the risk assessment shortly, but there's some maps available on the UKHS HSA websites, which are really helpful in terms of, highlighting the areas, particularly in Africa where they're endemic. How is that decided?

claire ripl 2 9:15

It varies very much between the viruses. So some of them are actually quite widespread, so, lasso fever, lots of different countries in West Africa are endemic for lasso fever. And we don't know exactly what the spread is. So actually we're quite we're quite generous with our testing and we are not looking at, oh it's never been reported in this country. We feel that if it's in the general area, borders a country where it's been reported there's likely to be under ascertainment and a lack of testing in many of those areas. so If the symptoms fit. If the exposure fits, we, will test. And probably the same with CCHF actually. So CCHF is very widespread throughout Asia and the African continent. Whereas particularly the South American arena viruses, they're actually very geographically limited because for some reason they're very limited to particular species. So if your corn mouse is your reservoir, you're only going to find this in the bit where that particular species of corn mouse lives. So it's very geographically focused. In terms of the risk assessment, we are looking at the geographic location. we are looking at the activities that people are doing if they've got, particularly risky exposures. We are looking at whether there's been reports of the disease in that area, So, either an outbreak reported or a country with end ethnicity. And then we're also looking at the So we take a sort of a slightly different approach at Ripple compared to the same services in other countries. In that I think we do a lot more testing and we're very generous with the testing. And so rather than having a big confab about the specific risk factors, we are like, meh. Can't rule it out on the basis of what you've told me. so let's test. It's just A PCR test. It is just PCR testing. There's nothing terribly exciting about that and as I've said, our lab teams do this routinely. We are doing this once or twice a week. They go in, they do the test, it's a PCR, we get the results. and so we try and normalize it and take the drama out. So we work through the risk assessment, we There's absolutely nothing in this history. That allows us to exclude A VHF, then we'll just, we'll be cautious and we'll go ahead and test. The problem is that with that is, is just the way the patient is managed because once you say we're going to have to do VHF testing on this patient everyone's oh my gosh. and the poor patient, doesn't even get a sandwich. So there is that sort of risk balance to factor into it. But again, we try and get the testing done as quickly as possible, and that's why we have the lab team on standby So that, patients aren't. Forgotten about for 24 48 hours waiting for a negative last of fever result. And in the meantime, they haven't had their basic treatment. They haven't had antibiotics, they haven't had their lunch.

Callum 12:07

No, that only too well these maps are really useful and I guess that feeds into the updated as of I'm gonna say it's listed here on the link as October, 2024. Is that right? It doesn't feel like that long ago. Oh man. So

claire ripl 2 12:25

It's very new.

Callum 12:27

July, 2025. And that's just telling me that the last eight months ago passed very quickly. So yes, I was, it was really exciting, I think when the new protocol came out because we got the email and opened it up and it's something that I guess most infectious disease doctors in the UK will be looking at over a regular basis. So maybe now we could just I guess firstly highlight the protocol that's available, which you can find. We've got the link in the show notes as I think really helpful and I think that the new version in particular is a bit easier to follow than it was before, which I guess is one of the aims of updating it. So maybe I can just ask you to maybe Amy, you could take us through what the, risk assessment

Amy 13:05

sure. The algorithm that we've put in the show notes is part of a bigger document, but I think we probably use the chart more commonly. So the, it's was curated by the advisory committee on dangerous pathogens, so A CDP that we've been, referring to quite a fair bit. and essentially the first part is a link to the high consequence infectious diseases, country specific risk. And I think this is a really useful link and I use it every day at work at the moment, at Ripple. And that has every country and every high consequence infectious disease that has been, there. So whether that's a case or whether it's serology or whether there's been imported cases. So that's the first bit which I think is important and worth having a look at. And then there's the additional questions, which again, a key to your VHF risk assessment. So has your patient traveled to an area where there's a current VHF outbreak and there's a few links on the algorithm to where you might find out about outbreaks. And then have they worked in areas where there's potentially lasso fever? So rural, basic rural conditions. So what kind of accommodation were they staying in, if it was aela endemic area and were there any rat exposures? Then any caves and mines, any primates, antelopes, or bats. So that's fear Marburg and Ebola areas. Then, have they traveled to somewhere where Crime and Congo hemorrhagic fever, so CCHF is endemic and in the area did they sustain a tick bite or crush a tick or have any involvement with animal slaughter? And that's in case they had contact with an animal who obviously was infected with CCHF. and so I guess within all of this, all your infectious diseases history is key for saying where did you go? What did you do there? sometimes why and yes, what have you eaten? Have you had any exposures? It's just a nice and concise additional questions of that. And then obviously someone has to have a fever or in the case of the algorithm, feverishness,

Callum 15:24

Yeah, really interesting. We wrote a local protocol on assessment of the fever in the training traveler. had a bit of debate when we were writing that before this algorithm was updated. And one of my colleagues suggested changing it from fever documented to history of Feverishness, which we actually ended up doing. And then this protocol came out and we were like, that was good timing. 'cause that's exactly what we just did. Is that just to increase the sensitivity of the protocol, and picking these people up so you don't miss people where we've missed the fever?

claire ripl 2 15:57

The feverishness, I just don't like that word. I think history of fever is fine. It's like I didn't but I think the reason and it. It wasn't us, it was a CDP that developed the algorithm. But I think the reason for that word is because it's not always a documented fever, who's traveling on a plane with a thermometer. So it's to capture the, I felt feverish or had chills or something on the plane. And just because I, you haven't written down a temperature of 38, you can still get into the algorithm without actually documenting the temperature. So yeah, it increases the sensitivity of it.

Amy 16:33

And I guess the other big part of the algorithm is has malaria been tested for? And often when people ring us to discuss VHF risk assessments, we that, one of the first things we say is, have you tested for malaria? Because of how similar the syndromes are and the presentations can be. So it's really important that malaria is considered and tested so that people can get the right treatment sooner rather than later.

Callum 17:03

So I guess we won't walk through the whole protocol because we don't want to spoil it for you. And as of some things it's better probably experienced looking at image rather than, us talking through it. But you go to that and it also has some useful links in it. It gives you some content information. So how to contact the imported fever service that we spoke about last episode, and it has linked to the the new H Kid, PPE, Section in the National Infection Prevention Control manual, which I have to say is just so brilliant. The, new PPE. Take a look at that as well. Maybe we'll talk about that in more detail in a future episode. So Amy, you mentioned there that the syndrome between malaria and VHF is similar. So I guess that leads nicely into the next question, which is, when should we consider VHF what I guess might be worth saying briefly what is a compatible illness?

claire ripl 2 17:57

The sad thing about VHS is there isn't anything particularly distinguishing. And like I, said earlier the hemorrhage bit is. Bit of a, it's not a misnomer, but it's a bit distracting. So most of these syndromes present with a non-specific febrile flu malaise. There's nothing, I'm trying to think if any of them have any sort of specific pathognomonic features and they don't think they really do. Sore throat features, I suppose a fair bit. So in the early stages, These just look like. Malaria, dengue, et cetera, et cetera. And then once they progress to more severe stage, again, there's nothing particularly path monic, the three main features of severe or advanced VHF would be yes. Some of them do bleed, But, it's not major hemorrhage. It's more sort of the. The DIC type picture, the oozing, sort of bleeding, they're not, bleeding from everywhere. You very occasionally might see a major GI hemorrhage if they've already got a preexisting gastritis. So they're not bleeding everywhere. They're just super sick patients. It's like a viral septicemia. That, is the main feature. And the other bit that I think people don't think about is the neurological. Aspect of it. so many of these will present with neurological features, usually because of some sort of cerebral edema or hypo hypoperfusion. So altered level of consciousness, confusion, agitation, that thing. So there's, again, that could fit with the cerebral malaria. So there's nothing really specific. And even the bleeding, they might be bleeding for. some other reason, or because they've got, low platelets from their other non VHF. Viral infection because that's a feature of many of the non VHS as well. So that's the difficult thing about these is that there isn't anything specific really in the clinical picture. Early on you've got a vaguely sick patient late on, you've got a very sick patient, but there's nothing path. Monica, I don't think it's really about the exposure history, suspecting it. And. Being quite detailed about your history taking, if you can, to see if there's anything at all in that history that is flagging this. I think what the algorithm is, focused on actually is the high consequence infection, infectious diseases category of viral hemorrhagic fevers. This doesn't really capture the, non HD ones and particularly the other non Lassa arenaviruses. So it's not, going to capture all VHS actually, the risks are very much focused on the main VHS that are also high consequence.

Callum 20:31

But then I guess that should be captured when they send a geographical panel test to ripple hopefully,

claire ripl 2 20:37

Some of, so Yeah. Again, if you've got enough, if there's enough information on the thing that some of those are they're so rare, I can't pronounce them. Equ, reovirus is only in very specific areas, with very specific exposures. It's like farmers, in particular parts of South America that get that. So we, we don't test that. Routinely on everybody. We might test it if everything else is negative and they go, actually he visited this part of wherever and had contact handled this particular type of rodent. It's, yeah.

Callum 21:14

a patient who was a zoologist and they did, they were able to give that level of detail if they'd been to the Amazon and they would, knew the diagnosis before I

claire ripl 2 21:21

Brilliant.

Callum 21:21

to be honest. But yeah. It was, that was quite an interesting interaction.

Amy 21:24

One thing to mention, in the risk assessment for Lasser in particular in Nigeria, the Nigerian CDC website, I've put it in the show notes, is such an invaluable resource. They do weekly epidemiology, basically of all the different states in Nigeria.

Callum 21:42

Yeah. Yeah.

Amy 21:43

so it's really helpful for assessing risk for that.

Callum 21:46

Yeah, I think that's been our, in locally, our most of our queer VFS have come back from Nigeria and I certainly use that. I've feel like I'm more familiar with the states of Nigeria than I am with the counties in England, which is slightly strange, but it's a struggle with the counties in England, but yeah, that's, I found that really helpful as well. So I guess to summarize the answer to that, so when to consider VHF, it's, when you've got a febrile illness, there's no path omic features they present, with general symptoms. So you really think for. History of fever travel to the endemic countries listed. And I guess a key thing we haven't mentioned is a symptom onset within 21 days of return, which I'm going to ask a follow up question on, but I'll just finish this spot. The exposure history, which were those questions that Amy read out in the protocol? My follow up question is, although we say within 21 days of return be, my understanding is that basically that's the maximum incubation period for any of the, vhf. So we can, after 21 days, we can say we're off the hook, but what's the sort of typical incubation period? Because I think my understanding is it depends. Virus to virus,

claire ripl 2 22:55

it, is, virus to virus. So the range is usually three to 21 days. So some of them are very rapid onset, but about a, I'm just gonna say about a week for most of them actually would be standard. But yeah, varies a little bit. Virus to virus.

Callum 23:09

You know, because, 21 days you're at risk, 22, you're not, obviously this is

claire ripl 2 23:12

There's n yeah. It's difficult, especially this with de isolation. There's nothing magic that happens at midnight, on the 21st day. And I think that comes down to being very careful about your history taking and your onset and your exposure dates. and like I say. Our instinct at Ripple is to test if there's a level of uncertainty. So the bit of the algorithm that is really important is the phone, the IFS comes into it. but if you're uncertain, if you think it's, if you're not sure or you think it's an unusual. VHF that might not be captured by the algorithm, then phone us. We're friendly, we're happy to talk. There's, you don't need to follow it too rigidly. If you are if It's not making sense or you're getting confused or you just don't feel happy with how it's going, give us a call. We'll talk you through it and we'll help you.

Callum 24:03

So that's beautifully covered when we should call you. Which is which is good. So maybe I can ask you, Amy, what happens when, so say I call IFS and you answer the phone. What's the sort of steps that happen after that?

Amy 24:18

So first I guess we'll go through the history and what you're concerned about. Where has the travel history as we've previously mentioned, then making sure that a malaria test has been done and a result has been obtained. then we will point people in the direction of the PPE guidance that you. Mentioned before. So assessment, PPE, if we think that there's a risk of VHF. For example, if they've been to a lasser endemic area and the malaria negative, but have fever. As everyone will get to hear in the additional bonus content, we'll discuss about category of packaging. So category B packaging is usually okay for if we're considering VHF, but it's not confirmed. So category B couriers and category B packaging to send samples to us. normally ask for serum and EDTA and urine to allow us to do the PCRs and then we can do serology testing thereafter if negative for the non VHF testing. And then we'll determine the timing of testing depending on how the patient is clinically. So we can either bring in the lab team overnight because they're wonderful and often do come in overnight to do testing if it's urgent. Or sometimes we'll say we'll get it on first thing in the morning so that we to have a resort by lunchtime the next day. And then we'll get, yeah.

Callum 26:01

So I guess if it's positive then I'm just reminded of dad's army which don't panic, but I guess you. Would be scheduling our instant management team locally and the, I presume there'd be a national one. The H Kid Network would be activated and then transferred to a H Kidd Center via your HAART ambulance. Unless you're working in a h Kidd center, obviously, then you, will continue managing them. and if it's negative, then I guess the key point that Amy's written here is don't forget the rest of the travel killers. So your malaria, which you've already done one test for, but you would've ruled out salmonella, typhi Ian, more standard organisms. So the hard work isn't over. It's just begun, i've called and I hope I've done a good job, but, what are some of the common issues that you experience with Cal? Or I guess what would, if the loyal listener is going to call, what would you suggest they do to make it a really excellent and useful discussion with yourselves?

claire ripl 2 26:58

We haven't talked about who can call, and the truth is we'll just answer the phone and we'll talk to whoever's calling us. But actually, strictly speaking, it should really be infection doctors. So Id, microbiology, virology, whatever your flavor is locally. That's really because we think that if somebody in your hospital thinks they have a patient with A-A-V-H-F or another hsid. The infection, people should know about it and they should be, actively helping, teams deal with what are likely to be complicated patients. So we very often get, general medicine or Ed phoning us directly and it's fine we'll talk to them, we'll talk them through it, but we feel it's polite for them to at least go through their local infection services first. And also this is. Stuff that we hope that infection doctors are interested in. And we hope that if people have a case in the hospital, they're gonna take an interest and they're going to work with the hospital team to get all the information. We appreciate it's not always possible, particularly if the services are remote and sometimes whoever's with the patient has better information. But really the landing message will always ask that it's an infection. Doctor. So yeah, there's that bit of it as well.

Callum 28:09

Maybe amy, you can answer the common issues then

Amy 28:11

so as we mentioned in the previous episode with regards to the request forms it's often inadequate history that trips us up. So often people would just say, oh, there's been travel to Asia or travel to Africa. So it's really important to get that travel history. Where, when and what were they doing? Other issues. So phoning before there's any routine bloods and before there's a malaria film because we're inevitably gonna say, please may that before we discuss or before we can give a plan. We're happy to discuss, but it's hard for us a, so phoning us before you've got a malaria resort or blood results is often that or not often, but sometimes local labs can be unhappy to do malaria films and routine bloods. So I think it's important to that in the guidance

Callum 29:16

Hmm.

Amy 29:17

films in safety cabinets are considered safe and routine bloods in auto analyzers are considered safe. And so referring to the testing guidance if the LABA and happy, so referring them to that can be quite helpful.

Callum 29:34

Yeah. We've certainly had issues sometimes locally with that, but I think it's usually smoothed out after a discussion and some reassurance that it's safe.

Amy 29:42

I think it's just a good chat and pointing them in the right direction, but

Callum 29:45

Yeah.

Amy 29:45

yeah. I think if people haven't done things regularly, it can be quite anxiety provoking. So often where there's been laboratory acquisitions, it's almost always been research labs where they're working with viral cultures or infected animals. and So, standard good laboratory practices often um, effective in minimizing the of labor.

Callum 30:09

Yeah, so we're saying there's minimal risk, but also do tell the laboratory if someone's traveled, that's a key thing. But not just for VHF, but for things like typhoid and so on. So biomedical scientists are at the front line of the lab tests, so we did need to tell them, if we're concerned about something, pick up the phone and say, if you're worried about VHF,

Amy 30:29

Definitely, and we're always happy to discuss if there's any concerns pre or post testing. Yeah. and the other thing that we've alluded to already is courier delays. So often if you use category A couriers is much more of a delay 'cause they're much harder to come by. As we've mentioned before, category B for most things is okay, but we'll advise on that on the case by case basis. And then often people ring about being concerned about risk to staff and so we'll point people in the right direction for A PPE moving forward. But also I guess it's quite reassuring as we mentioned earlier, that from the 2012, the 2022 and the 2025 incidences of Lassa there's been no secondary cases. Obviously it depends between the vhs, the various risks, but, we're happy to advise on risk to staff and that forms part of the incident management as well moving forwards.

Callum 31:38

I guess it's a really important phone call to get, right? So preparing as you would for any other discussion, but, having that key information available is really important. So to summarize, and again, would point people towards the show notes if you want to get a bit more information. But there, we've talked through what a A VHF is and also what a H kid is, or HID and some of the types of virus that are included within that classification. We've talked about the risk assessment algorithm by the A CDP and some of the key points in your history that you need to be taking in order to do an adequate risk assessment when to consider VHF. And there's no necess necessity for them to have hemorrhage, and there's not really any path omic signs. So we need to have a highend suspicion and when to call the imported fever service, what happens when you call some common pitfalls. And we'll be releasing a bonus as alluded to there, which is a deep dive into the biosafety and biosecurity and the confusing world of containment levels, A, CDB, pathogens, transportation, you name it, which confused me for a very long time. And cleared as an excellent job of summarizing that down into digestible chunk. All that remains to be said is thank you so much to Amy for suggesting the idea of these episodes, for preparing all the content and coming on the show with your boss and having only nice things to say. So I dunno what that says, but it sounds like a lovely place to work. And thank you so much, Claire, for all your hard work at Ripple, but also for coming on the show. So thank you.

Amy 33:20

Thank you for having us.