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Micro lecture. So this is the second half of the microbiology section. I didn't actually write this section. Um So some bits of it might not quite line up in terms of the content, but I've had a flick through and I sort of pulled out what I think is the most relevant stuff. So what we're gonna talk about is going to start with a little bit of stuff about sort of mycology in the immunocompromised. And then the first big chunk is gonna be about the virology. So influenza and then more generally sort of your viral diseases worth knowing about. Then we're gonna move on to sort of director of unknown origin and then into your causes of fever in the returning traveler and more broadly, some of your sort of your zoona tick infections, which is the second big chunk I think in this half of microbiology and then finally onto fungal infections and then a little bit about prion diseases at the end, like I said, I'd say in general, I think this half of mycology is a little bit less high yield for the exam than the first half. So certainly the virology, the Zoono season, the fungal infections are worth going through. But I definitely, the first half has more content will come up in the exam. Like last time, my standard disclaimer, I'm just a six year medical student. Um I'm definitely no expert in infectious disease. This is not meant to be an exhaustive discussion of it. It's an interesting topic. Um But I'm not going to bore you with all the details all the way through. And if this is something that you're personally interested in MSD manuals is a really nice resource and also sort of Coumadin clerks as you go to for, I mean, everything I'd suggest. So if I just get over to the, actually, we'll get to that in a second. So we're just not briefly, there's not really much, let's examine. It was just a quick talk about microbiology and immunocompromised. So broadly, what causes can people think of that might lead to immune compromise of some form if people want to um you, that's great or otherwise just pop your ideas in the chair? Ok. Fab, you've gone for us a couple of the, the less common is really good. So broadly, the way I think about immuna comprise is you've got your immunodeficiency syndromes, which we're not going to talk about. They come up in the immunology section. Um These are all very, very rare. You don't see very much of the, but in the exams they're quite high yield, then you've got your required systemic immunocompromised. So HIV is sort of your prototypical one. Malnutrition is a really good shout for this diabetes as well. Um And indeed sort of post transplant when we're sort of iatrogenic lee immune suppressing people. And then finally, the one to not miss because people often forget it sort of your organ specific immunocompromised. So this isn't really a true immunocompromised but often presents that way. So for instance, somebody with cystic fibrosis or COPD is specifically going to be at risk of somewhat unusual infections in the lungs. There's a, there's a degree of immunocompromised specifically with running the pulmonary system. Splenectomy is a good, another good example. Um what organisms are people at risk for if they've had a splenectomy? Yes, you're in capitate organisms. NHS. Soma Syria Hum Oculus and strep is the way people often remember your most common ones. So those are you going to be your broad causes of immune suppression? What are your consequences though? So I'd say you're consequences of immune suppression or immune compromise where microbiology specifically concerned is firstly, you're going to get unusual organisms. So, so a couple of examples worth knowing any organisms people, I mean, there's lots of these but any organisms people specifically associate with HIV. So what things can cause infections if you have HIV, that don't really cause infection otherwise PCP. Definitely. So you're certainly at higher risk of TB, but you, you can get TB at a toxin is another really good one. C M V. Again, anybody can get it. But I agree, it certainly presents differently. Yeah. So, the Clancy's are a couple of examples that sort of come to my mind for HIV micros Pyridium, um, causes gi infections. You really don't see that outside of HIV populations and MAC as well. Cystic fibrosis patients specifically at risk of Burkholderia. So, patient infections, one worth knowing for your Pedes exams because that's a contraindications, a lung transplant and then patient's are on all kinds of different immune suppression, but especially monoclonals can be at risk of J C virus which will come to a little bit later. The second thing that can change when you're in a compromised is where the infection is actually set up. And you already mentioned a lot of these. So HIV again, see M V tends to go to some strange places, it can go to your colon, it can go to your eyes and go to your lungs, but it doesn't just present with your classic sort of mononucleosis quite type of picture. And I think somebody mentioned sickle cell disease a little bit earlier. Sickle cell is really worth being aware of that. There's very specifically at risk of salmonella septic arthritis. It's something to do with you get increased translocation across the gut wall, I think because you get a surgery of microvascular occlusion, something like that. Um But it's a very sort of well established risk factor and then the final thing to be aware of where, I mean, a compromise is concerned is prophylaxis. So if a patient has, let's say HIV, that's poorly controlled. What do we sometimes do for them if they're CD four count is low enough in terms of prophylactic management, good co-trimoxazole. So it varies depending on where you're on your precise local guidelines. Normally we say if you've got a CD four count, less than 200 you start considering prophylactic co-trimoxazole, especially if you've got a history of PCP infection. And the other one is if somebody's gonna have a splenectomy before your splenectomy, you'd give them vaccinations certainly against um meningitis and uh pneumococcal. So onto the first of big chunk of examine herbal stuff, which is some of our virology. So we'll start. So if we just bring up the mentee, so if people can join this, let's get a few more in and then we'll start working through it. Okay. But let's get going. Okay. I mean, reset this. I think my trial run is still showing. Um Sorry about this. I'm not going to so bear with me just a second. Yeah, sorry about this. So just bear with me. I think my trial run is still showing rather than starting it again and just do it like this. Um There we go. Sorry about that. I just have a different code if you can just go in this one. Okay. But let's get going So first question that what feature of influenza allows antigenic shift to occur? Ok. Bit of a widespread here. So these are all features of influenza virus. It's actually the multi segmented genome that is relevant to an antigenic shift. So if you just go back to the power point, so this is one of the few, this is one of the parts, it's actually very high yield. I don't really know why, but they always like asking about this. So it's worth having a good handle on. So, influenza is broadly split into influenza A and influenza B, they're technically four different um Sarah vase influenza C and D also exist. They're not really clinically relevant. So A and B are the ones that we normally care about. A is typically worse than B and A is the one we tend to be talking about. Certainly we were talking about sort of pandemic influenza and there are certain things about influenza that predispose it to causing pandemics. And this is a very classic question in the path exam, what features allow it to have sort of pandemic sort of risk? So the the factors that sort of just and just learn these on novel anti Jenness Itty, efficient replication in the airways and efficient transmission between people. Those three features of sort of the features you'd expect to be in common between any of your big sort of pandemic strains. Now, novel anti Jenness ITTY is produced by two different processes. Does anyone know the names of those two processes? Good, just antigenic shift and antigenic drift. And these are two different processes and they actually result in two different things that we're concerned about influenza. So this is a sort of a rough diagrams of hopefully trying to get across the idea of these two processes. So, antigenic drift is just the accumulation of mutations over time. So because you have an, you have an error prone replication process, it's going to change slightly every time. Every however many times it replicates, there's gonna be errors, you're gonna get a slightly different um sort of primary sequence for some of the proteins within the influenza. As this happens, sort of relatively frequently, you get small changes that accumulate. And what these mean is that your preformed antibodies from your last exposure to influenza aren't quite as effective. This antigenic drift is what produces your, your new epidemics strain of influenza every year. It's the reason you get a new influenza vaccine every year because the influenza you get next year is going to be slightly different from the one you have this year. And that's a result of antigenic drift. It's just the slow accumulation of mutations. Antigenic shift is very, very different and it doesn't happen very often. So the viral genome of influenza is made of eight chunks. It's a, it's an RNA virus I believe from ahead and it comes in there. It's not one R N A, it's eight different parts to that RNA genome. Now very, very infrequently, an organism can be infected with two different strains of influenza. And if those two strains of influenza both infect the same cell at the same time, one of those eight strain, one of those eight strands of the RNA might be mixed up from the other virus. So it suddenly gets a whole different section of genome unlike your antigenic drift, which is slowly accumulating small changes. This means that you very suddenly completely change part of the genome and some of the proteins it's expressing this is antigenic shift. Now, a lot of the time when sort of this event occurs, what it produces will just be nonsense. It won't be something that works. But every so often the recombination will produce a virus is not only still functional, but it's actually incredibly effective because it now has a completely different set of antigens which you've never sort of encountered anything like before. So this is an infrequent event that produces an entirely novel strain. Okay. So it's this that tends to reduce your pandemics, your sudden appearance of H five N one, which was swine flu back in, I think 2010 or 2009, that was an antigenic shift effect. But the influenza vaccine you're gonna get this year despite having had one last year, that's because of antigenic drift. Okay. Okay. So that leads us onto neuraminidase and hemagglutinin. So these are the two most important genes in the influenza virus. And because they're so important, this is how we actually name the different strains. So when somebody says H five, N one is swine flu, what they're actually telling you is H five and N one are the specific versions of the hemagglutinin, your arm in a daze genes that, that virus is expressing. Does anybody know what these two genes do is very sort of the M C D. Do we start with hemagglutinin? Any ideas what hemagglutinin does for the virus? So it so it does coagulate. It's not actually the purpose of the drayton but but it's something we noticed and it helps us test for it. Um But yeah, so very good. Yeah, it binds to Salik acid. So, hemagglutinin is a market is, it's a protein on the surface of the influenza virus. It binds to Salik acid where then gets cleaved by tryptase on the surface of certain cells in the lungs and that allows it to enter and humid. So, hemagglutinin facilitates entry to the cell that it's invading. And this gene is especially prone to antigenic drift. So this is very much the uh the protein that you normally targeting with your sort of yearly influenza vaccine. By contrast in your arm under days, which somebody else mentioned, this aids exit of the cells. So it also targets a folic acid, but this facilitates viral release. And this is more prone to sort of an antigenic shift effect because these two proteins, in particular so important. Uh PCR is especially relevant for diagnosing because PCR not only diagnose is the virus, it is there but also tells you what strain you're dealing with, which has ramifications for epidemiology that also has ramifications for certain drugs. So this is sort of a simplified diagram of its life cycle. I don't think this is particularly worth worrying about the thing to realize is that both of these proteins are certain markers on the surface of the influenza virus, which means that they're very good targets for antibodies and they're also very good targets for drugs potentially. And that takes us on to influenza antivirals. Now there's a bunch of these in terms of what's worth knowing anybody name any antivirals we used to treat influenza. So Tamiflu is the brand name. Does anybody know what the actual um oseltamivir? Yeah. So Tamiflu is the same thing I think film and I think that's the brand name for oseltamivir. There's actually a bunch of them but also to move there is the one worth knowing. So oseltamivir um is a neuraminidase inhibitor as it prevents viral release. And so it prevents the virus replicating and and releasing and infecting new cells. There's some other ones someone actually mentioned actually zanamivir and peramivir, they will target the same thing they're not really used very often. Um There's not really been any evidence to show it's any better than oseltamivir. The only real reason to use either of these is if somebody couldn't tolerate oral medications at all. Um, and zanamivir, I think off the top of my head, you can't give this to people with asthma and often they're the people who get bad, um, influenza infection. So the other two drugs exist also to move here is the one to know galaxy via, is another drug that you can use. This targets a slightly different part of the sort of the viral life cycle. Again, not used very often. The main reason this isn't used is because you can only use it within the first two days of infection. After that, there's no sort of evidence that it improves outcomes. So it's not really used very often. And there's also a drug called amantadine. Amantadine was sort of thought to be quite a big breakthrough. It was first discovered is one of the older drugs. Does anybody know the problem with amantadine? So it's actually not side effects normally. That's the right answer. Um And this is the reason why amantadine isn't really used very much anymore because it's actually really easy to become resistant to it. It's only a single nucleotide polymorphism that's required to sort of confer resistance. So almost all influenza is now actually resistance to the. So it's never used at all. Um But it's mentioned in the path guide. So I just thought I'd address that. So loads of different antivirals. The only one I could really imagine coming up with the oseltamivir, that's the one to know. And that's really all the stuff about influenza that is worth talking about. So if you go back to this question, these are all features of influenza virus. However, it's the multi segmented genome that allows the recombination of big sections that produces your antigenic shift, the aero prone genome replication that produces your antigenic drift. And these two enzymes are just, these two proteins are just responsible for it's invading of cells. Um But antigenic shift is specifically because it has this quite strange genomes, listen to different sections. So what we'll talk about now is some of the other viruses. So we'll do a few more of our questions. So which are the following presentations of herpes indicates a potentially uncontrolled HIV infection. So you can certainly see all of these, the one that is specifically would make me think about HIV is particularly herpes office esophagitis. Again, we'll talk a little about why that might be a second JC virus is responsible for which of the following clinical entities. Very good. I I know exactly why people have put those other two options and we'll talk about what causes those things. And everyone's favorite topic. HEP B serology. So what does this HEP B serology imply about the patient? It was taken from? Very good, very, very good. Keep it often struggle with that. So that's a very good sign. Okay. So we'll go back through those soon. But let's talk through the biology. So, the first thing I want to talk about actually is some of the antivirals because I always found this, like, frightfully complicated. Uh, I found it far harder than sort of, um, antibiotics. Antibacterials. I think the best way to think about antivirus is to split it into four chunks. To my mind. You've got your normal antivirals that treats sort of fairly generic viruses. And they work across several different viral infections and you very specifically got HEP B drugs, hep C drugs and HIV drugs, which are very much antivirals for a specific purpose for a specific virus. So what we're gonna talk about first is sort of these sort of what I call normal antivirals. And the first thing to address is the antiviral, this is the antiviral with val in front of it. Okay. So the only real difference this makes is sort of in terms of practicality, they tend to be essentially the same drug and have essentially the same indication, the, the addition of the val, which I don't remember what actual chemical group that represents. But what this, what effect this has is it makes it more bioavailable and it makes it resistant to first pass metabolism. Practically what this means is, you don't need to take it as often to get up to a therapeutic dose. And in particular for some of the drugs and some of the indications you can take it orally when otherwise you couldn't. Um, in particular, Ganciclovir is almost always given IV because it's so extensively metabolized by the liver. Whereas valGANciclovir is a drug you can give orally and it will have the same effect because you can actually get up to a therapeutic dose. So any time that you could give the antiviral, the one with val in front of it is always also going to be totally legitimate. They do the same thing. They are essentially the same drug in um in situ. So when we're treating herpes viruses broadly speaking, you're gonna follow this algorithm. Your first line choice is either gonna be Acyclovir or Ganciclovir to the one that you choose depends on the specific herpes virus will be speaking, if you're treating um HSV, or if you're treating varicella, you're gonna start with Acyclovir to, if you're gonna start with, if you're treating CNV and rarely EBV, you'd start with ganciclovir and then irrespective of what you started with. First line. If it's resistant to that, your next option is then for scar knit and then cidofovir. Okay. So that goes from the vast majority of your sort of your, the herpes virus infections that you're going to treat for non herpes viruses. So for some of your sort of more wrote of things like the adenoviruses and some of the others will talk about, you go straight to sit off of it. You might be wondering on the basis of that, why do we not just treat everyone with Cidofovir? Does anybody know why? Or? Indeed for Scarlett? Because they're definitely more potent drugs than a cycle of your or ganciclovir, which has been around quite a while. I don't really know why we don't go straight for those drugs. Yes. So, the really dirty drugs, um, nephro toxicity is one of the big ones. They've also got quite a lot of ocular toxicity and quite a bone marrow suppression. Um So yes, it off of it is in particular is a really unpleasant drugs. So we try not to use it if, if we can avoid it. Um Yes. So that's why we like to start idea with things like Acyclovir or Ganciclovir. They've got pretty benign side effect profiles. So that's just a little bit on the antiviral side of it. We're not gonna start talking through the virus is that I think are worth knowing. Um Don't get bogged down in all the details here like that. You know, virology is a whole career and of itself focus on the buzzwords. So we're gonna start with the human herpes viruses. So I'm gonna start with H B one and two which are herpes simplex. So how can this present the Epp so cold sauce? Yep. So we can get sort of your classic sort of cause a classic sort of ginger the sir Matitis around your mouth. How else can it present? So it's worth having. So you can get genital herpes as well. And so these are the classics with people go to. It's worth bearing in mind. Herpes can present in a lot of different ways. So HSV one or human herpes virus one, the two names are interchangeable. It's s is specifically associated with herpes labialis, which is called cold source. Um and also HSV and Katha litis. HSV two. It's almost classically associated with genital herpes and HSV, meningitis. Watch out for the encapsulitis versus meningitis. Quite a common questions or what's the most common cause of um of encapsulitis? It's HSV one, not HSV two. These are the sort of the common causes that everybody goes to the herpes can do quite a lot of different things. So these are some of the other presentations to just be aware of. So HSV esophagitis or more rarely colitis and even pneumonitis sometimes is one of your sort of, we don't really use the phrase anymore, but one of your AIDS defining illness is you would very rarely see it sort of um in somebody who didn't have some level of pre existing immuno suppression and especially patient with HIV, you're prone to HSV, esophagitis, um H S B in the mouth, sort of what we call a gingivostomatitis is very often the first presentation of cold sores. So your initial HSV, one of the infection can actually have quite a lot of oral involvement and subsequent reactivation tends to be sort of your isolated vesicles with cold sores, other things that you can present with extra herpetic. Um um So this is sort of something that you'll see in Children normally who have a history of asthma pathetic Whitlow. Somebody actually mentioned this. Does anybody know what herpetic whitlow is? So herpetic Whitlow is herpes on the finger? Um And it's actually the most common presentation of herpes in healthcare workers. So it's one that we should really know about. And in fact, if you were interested in these things, there's a case going through, I think they're still going through the court's at the moment about two pregnant women who died because they think the surgeon had a herpetic whitlow. And during cesarean section, there was some, there was sort of inoculation of the virus into the abdomen and it results in sort of widespread herpes and then multi organ failure. There's one that sort of we should in particularly aware because it's the most common presentation clinicians and then you can get disseminated cutaneous herpes. Now, this again is something you wouldn't really expect to see unless somebody was already immunocompromised. And as we already said, first line treatment is going to be a cyclopia. So this is what herpes looks like. This is what genital herpes often looks like. This is a fairly classic representation of vesicles. This is sort of an example of what we call herpes gingivostomatitis. So this is more likely to be the initial inoculation with H S B one rather than a reactivation. And that's herpes esophagitis. You can see that it's very, very widespread through the esophagus. And this is taken from a patient who I believe had HIV. Um So I said this is considered one of your HIV, defining illness is and this is excellent herpetic. Um So this will almost certainly be a patient with a history of asthma who's been, who's now suffered a herpes virus infection. And this is your herpetic whitlow very easily missed. So people often have these without even realizing it's just something you want to be checking for very closely. So that's herpes what? That's HSV one and two onto H H P three, which is varicella. So how does varicella present? So I can present with shingles? But how does it present initially? Chicken pox? Yes. So chickenpox and shingles. Now, chicken pox, we all know what chicken pox looks like. Um You know, so again, you'll be doing this in peeves, I'm sure. So classically, the rash starts with macular and progresses to pat pills and then progresses to your classic vehicles as often described as starting sort of from the face and then descending onto the trunk. Um notice it can affect of just be aware, it can affect the mucous membranes as well. And when it does, it's pretty indistinguishable from HSV one and two. So you often need to swab it for that. When can, can check it can, what can chicken pox do? That's a little bit more serious. And so who gets more serious chicken pox infections? So, anybody who's immune, suppressed and adults in general, we tend to be a bit worried. Pregnant women, we worry, um, not, well, we worry about it in any adult who's presenting with sort of chicken pox. Um, pregnant women, the specific concerns often for the effects it can have on the developing baby, but they're an adult. So you definitely still be concerned about it. And in adults it can present in lots of other ways. It doesn't, you're not what? It's not the rash you're worried about. It can cause like a really nasty pneumonitis. It can cause in Katha litis, it can called myocarditis. It really prone to causing D I see it's a very, very serious illness in adults. And as somebody else mentioned, it can also cause shingles. So I actually just put it up there. Um So reactivation called the shingles or herpes zoster with sort of your classic dermatomal rash. So I mentioned two specific things there. So we start with the first one. What's ophthalmic herpes zoster? Yeah. So it's so authentic Herpes zoster is um is shingles essentially of V one, the first branch of the trigeminal nerve. And the reason we worry about it is it can cause a lot of damage to the retina. So there's a specific sign to be really aware of called Hutchinson signs. Every you know what Hutchinson sign is good. So Hutchinson side is vehicles on the nose. If somebody has shingles and it's affecting the tip of the nose, it means it's in the right nerve to be affecting the eye. And so those patient that's a medical emergency or sending those patients' straight to the sort of the the ophthalmologist because they need quite sort of complex um, interview secular treatments. The other one I mentioned was Ramsay Hunt. What, what, what, what is Ramsay Hunt syndrome? So, yes, Ramsay Hunt is the facial nerve instead. So classic presentation here is they'll, they'll describe ear pain. They often get facial paralysis like a Bell's palsy picture and what you look, what you want to look for is vehicles in the ear is the only place you might, you is very often the only place you'll actually see the vehicles. And again, this requires prompt treatment in order to sort of recover or get sort of decent recovery of function facial nerve because of how we treat it. We already said that we're gonna treat with acyclovir first line or indeed valet cyclopia a bit of peed revision. Again, what do we definitely not give to people, especially Children with chicken pox. So we don't give them Ibuprofen for bonus points. Why don't we give them ibuprofen? Good. So Ibuprofen has been shown to increase the risk of secondary skin infections where killed Children, scratch at them. And in particularly causes where there's an increased risk of neck fash. You're right. We also wouldn't give them aspirin, but we don't give any child aspirin because of the concerns around. Well Reyes syndrome. So this is a fairly classic sort of description of what sort of chicken pox would look like on a child. And this is sort of your shingles, dermatomal rash. This is a patient with Ramsay Hunt syndrome. So you can see that they've got this sort of facial nerve palsy on the left. And you can also see sort of quite an unpleasant looking rash within the ear. And then this is a patient with, with ophthalmic herpes. So notice it's the rash is coming from the forehead and specifically down onto the tip of the nose. Really concerning sign of one you definitely want to be looking out for also something worth just being aware of is after sort of resolution of shingles, patient's can develop something called post herpetic neuralgia, which is just pain in the distribution of that dermatome is very, very difficult to treat your treating with your sort of your neuropathic pain drugs, your gabapentin, pregabalin, um, amitriptyline, but it's very, very difficult to treat. Um, so something worth being aware of. Ok, onto the fourth herpes virus, Epstein Barr virus. So, how does this present infectious mononucleosis? So your classic fever, sore throat, lymphadenopathy, you can get liver involvement, you get a big painful liver and spleen, the lymphadenopathy, just sort of a little tip again, a bit more peed. See, um you're normally looking for a symmetric lymphadenopathy and it most often affects the posterior cervical chain. In contrast of tonsillitis, which more classically affects the anterior cervical chain. So it can be a useful way to help you differentiate between the two. It's not a hard and fast rule but makes it slightly more likely to be one or the other. Um Other things that can cause infectious mononucleosis are CNV and toxoplasmosis. Both can present with a very, very similar clinical picture, sometimes with a bit less farengitis, but they both often have similar symptoms and one other cause of this constellation of symptoms that people always forget. It's a really important to keep in the back of your mind is HIV syrah conversion. It can look very, very similar to this kind of federal feeling a bit unwell, big lymph node, sore throat, bit of liver and spleen very, very class presentation. One not to miss what things would point us towards a diagnosis of Epstein Barr. Then if we're suspecting glandular fever, what what laboratory findings sort of strengthen that good on mono spot is one of the one I'd say worth having in your mind as an association. So the other one you often come across is what's described as atypical lymphocytes. Um Yes. So high lymphocytes and often what specifically describe atypical atypical lymphocytes on smear and you can also send E B B serology as well. The B B serology is in real life. What is often used a lot more? Now, the first two are very classic findings for E B B. Um So E B V, we normally don't treat it, normally, sort of takes care of itself. There's not much evidence for treated with antivirals. If somebody was really formant, you can try something like um like um ganciclovir or potentially escalating to things like cidofovir, we normally just leave it alone. Um What advice would you give a patient who had glandular fever there, avoid high contact sports because you get this um splenomegaly and it, there are, there are increased risk of splenic rupture. Um You would also probably tell them to avoid alcohol as well. Anybody with a hepatitis probably shouldn't be drinking with Epstein Barr. The thing to remember is like a lot of herpes virus. It can live dormant and Epstein Barr almost always hangs around dormant lee. And for most people, it doesn't cause any problems, but it is associated with a couple of lymphoproliferative syndromes. So, the to to know a Burkitt's lymphoma and I think actually can't see the bottom of presentation and it clear that there we go. Burkitt's lymphoma and post transplant lymphoproliferative disease. So Burkitt's lymphoma, I'm sure you will know quite a lot about. I'm pretty certain it's somewhere else in the path guide as well. Um And relevant Pedes, post transplant, lymphoproliferative disorder is exactly what it sounds like. When patients have had a transplant, you have to immunosuppress them. And once they're immunosuppressed, you lose the surveillance of the EBV and you get this sort of pre lymphoma state and you've often got to play around with the immune suppression at that point. Otherwise, it will come back as a fully blown lymphoma. It's also associated with nasal pharyngeal carcinoma. This date absolutely love this in the path example, I don't, I don't know why it's not very common cancer, but EBV is associate with nasopharyngeal your carcinomas. So on for 1/5 herpes virus and this is C M V. So CMP, as has already been mentioned, it can either present asymptomatically or again, it can present with a mononucleosis type picture. And the buzz word to have a C M V is owls I inclusion bodies. I don't know what they represent. I don't really know what it means, but owls I inclusion bodies is the buzzword to have with it. And as was also mentioned in the chat earlier, CNV hangs around dormant. We after you've cleared it and then in people with who are suffering from some form of immune suppression can reactivate and it can reactivate all over the place. Um really wide range of presentations. These are the ones that I think are most worth being aware of CNV, Newman, Itis, CNV, retinitis, CNV colitis and C M V N, Katha litis. All four of these are, especially things you're looking out for in patients with poorly controlled HIV. Um, oh, yeah. It's a real high, real big cause of morbidity and mortality and can be very hard to treat in patients with HIV. And that was already discussed. Your first line treatment is gonna be ganciclovir or valganciclovir. So, this is a CT of a patient with CNV. Um, CNV, pneumonitis. Notice on the ground glass appearance is what you're looking for and it's very, very multifocal. It's not a pneumonia where you've got this sort of low bar consolidation. It's very, very widespread pneumonitis. This is a picture of CNV retinitis. Um I can't imagine they'd ask you too much about this. I don't think they asked about it in histology in them, the histopathologic shin, but it often looks like cotton wool spots. It got really, really bad, really diffuse cotton wool spots like you'd get with like diabetic disease. And then this is C M V colitis. Um notice as I mentioned the herpes, but when we're talking about herpes simplex, it looks very similar to HSV esophagitis and it can be very difficult to distinguish between the specific herpes virus when it's presenting somewhat unusually. So you're almost always gonna be diagnosing these with serology rather than a spot diagnosis, I think picture. So I think that is an owl's I inclusion body. Like I said, I don't actually know what it physically represents, but it's a buzzword worth having in mind. Okay. So those are the five major ones. So there are three other herpes viruses. So H B six and seven causes roseola. Um, very, very rarely can causing Katha litis. Really not worth worrying about. It does have a bit of a tropism for the brain. Um, what's the cont, what's the significance of roseola having a tropism for the brain in pediatrics? Good. So they think that's why roseola is specifically associated with federal convulsions. They think it's because the virus is quite good at getting into the brain. It very rarely does any damage there. Um Roseola is the only thing you should associate with it and virtually everybody is infected with this. By the time they reach adulthood, the final human herpes virus is H H V eight. Does anybody know what H H V eight causes? Good? Composes sarcoma is the one to know. So you only really see this impatience where municipal, you only see it really impatience where immune suppressed and especially associated with HIV. Um These are the two conditions I've mentioned. Um really not worth knowing about. I've just mentioned because again, I think that in the path guide and it is take Google, it is true. These are so primary effusion lymphoma is a really, really did dismal prognosis form of diffuse large b cell lymphoma and Castle Man's disease is a very strange lymphoproliferative disorder that's not quite a lymphoma, but it kind of acts like a lymphoma, not worth worrying about composing sarcoma is the want to associate it with. So, composes sarcoma is, we don't actually know exactly what it is. The best guess at the moment is it's a proliferation, proliferation of the lymphatic endothelium. And we think that's what the actual sort of the cells are proliferating that produced this malignancy. And people often associate Capozide sarcoma is being a malignancy that doesn't really do very much. You know, people normally say that obviously like the concern with Capozide sarcoma is it implies poorly controlled HIV or sort of significant immune suppression, but the actual lesions themselves can be really problematic. So this is a patient with roseola and then this is a patient with Kaposi's sarcoma. And what you've got here is Capozide sarcoma on the skin. But patient's with Composer sarcoma often get these lesions internally as well. So in particular, the g eye and respiratory tract. So this is a patient with these are Capozide sarcoma lesion's within the bow. And the problem with these is that they can hemorrhage and they can really, really hemorrhage. So patient with Kaposi's sarcoma will sometimes die not because of sort of like your classic malignant cause malignancy causing death, but because they just exsanguinate because they believe so heavily. The way you treat this is normally not a huge amount of chemotherapy or treating the cancer. It's about treating the immune suppression and then the immune system will clear up the cancer ideally. So they are all your herpes viruses. Well, next talk about is just some of us are slightly more random viruses. So the first one we're gonna talk about adding the virus is so what to add in a viruses. Course, yes, they can. Kaiser cause a bit of everything and healthy people. They tend to just cause of coryza or a little bit of a gi infection in people immunocompromised. There are growing concerns. You can do all kinds of stuff, pneumonitis, meningea, encapsulitis, and hemorrhagic cystitis are the big ticket ones that people think about but immune suppressed but they can do all kinds of stuff. It's got really wide set of different serovar which all have different viral tropism. So it can really affect all over the place. Um So one worth being aware of JC virus. JC virus is was actually one of the questions. So JC virus is specifically associated with reactivation in immunosuppressed patient's lots of people are infected with JC virus. It normally does nothing if you have some sort of immune suppression. Um HIV can do it but it's especially associate with monoclonal antibodies. It can reactivate in the brain. Of course, something called progressive multifocal nuclear Keppel opathy, antivirals don't really work for it. The only way you can treat this is by treating the immune suppression. And final one you mention is BK virus definitely know what BK virus causes and who we worry about it in. So you can cause cystitis and what else? Nephropathy? Perfect. So you only, again, it's a virus that lots of people are infected with. It does nothing. For the most part, the people we worry about is people who've had transplants. And there's two specific situations where we tend to see it. Patient's who've had kidney for transplants, get nephropathy. So they get the BK virus infecting the transplanted kidney and it causes a nephropathy and in patient's who've had bone marrow transplants, you see hemorrhagic cystitis. So those are the two presentations we tend to get with BK virus, very difficult to treat. You often have to try and taper down unionist suppression, which is a nightmare because they've had a transplant. So it's very, very difficult to treat. And this is just an MRI of the patient with who had progressive multifocal leukoencephalopathy over time. So you can see that these, these scans are only taken over, I think it was six months to a year. And you can see that you've got lesions of the white matter, but you can also just see that you've got really significant and quite accelerated cortical atrophy over a very short period of time. So it's a, so this used to be a death sentence. Now, we've got some options to treat. It normally involves tapering off the immune suppression. Um But yeah, so it's something to watch out for, especially patient's or monoclonals. So now we're going to move on to our final set of viruses we'll talk about which are, are hepatitis viruses. So which hepatitis viruses cause acute infection? Hep A and HEP B and I highly recommend you think of these two together because not only do they both cause acute infection, they both transmit the same way fetal already. They're both principally seen in travellers and they're virtually indistinguishable. So like I said, they both generally presenting travelers and feet have already transmitted one thing to not missus. This, these can functions S T I S especially in the MSM community to an S B A S. If they tell you sort of travelers, all people have sort of, you know, men who have sex with men worth just being aware that these, those two populations of the groups that are most likely contract. Hep A and HEP E and they both present very, very similarly, you tend to get an incubator in period, sort of about a month or so. They then tend to feel a bit a bit sort of Malaysia, your classic viral prodrome, then you get your hepatitis space, they get drawn this, they'll have sort of right upper quadrant pain. They sometimes get a cola static picture which causes the jaundiced and they feel really rubbish for a month or two. And then they tend to get better for minute. Hepatitis is relatively uncommon with HEP A and HEP A but it does happen HEPA we tend to worry about for minute hepatitis in elderly people who do we worry about Hep Ian, in particular pregnancy, good pregnant women are high risk performance disease um with hepatitis E, because these viruses normally, they normally don't cause liver failure, they normally just fix themselves. The treatment is supportive. There's no antivirals we really use for either of these. Um HEPA is vaccine preventable. And so it is given to people who are traveling in high risk areas. But for the most part, these things will sort of take care of themselves and neither of these produce chronic infection. Now, technically, that's not strictly true. There is a strain of HEP B that can rarely cause a chronic infection. So if you look that up, you will find that don't worry about it for the purpose of the exam, for the purposes of this exam. Hep A and HEP E only cause acute infection and then they fully resolve. And you probably seen a lot of these diagrams. I'm not going to dwell on these. I don't actually think they're terribly helpful. The only reason I include these two here is just to highlight how similar these two are virtually the same time, of course, is virtually the same sort of um incubation period and then symptomatic period and then sort of the slow recovery. So these are virtually indistinguishable. The only way you can pick between them, I would say is formant disease in pregnant women, you're thinking happy. Okay. So now we're gonna move on to our other Hepatitis virus is the one that can cause chronic infection. So we start with hepatitis B. So this is by far the most complex hepatitis virus as when we're going to dwell on a little bit. So how is HEP B transmitted? Good? Just blood borne virus. You're thinking bodily fluids and you're thinking vertical transmission. Hepatitis B will normally present acutely and rarely causes chronic illness. Okay. This is in contrast to HEP C which will move on to it in a second. But I really don't remember that Hep, most people infected with HEP B will develop an acute hepatitis and it's quite a prolonged one. It can last up to six months. Very rarely will this cause for minute disease, but they will normally present with a protracted hepatitis phase. However, it's relatively uncommon that they develop chronic illness. Okay. Only about five to set 5 10% of people will fail to clear the acute HEP B and these are the ones that become chronically infected. The general of thumb is the younger you're infected with HEP B. The higher the risk of it becoming chronic. So in general is about 5 to 10% chance of acute HEP B becoming chronic in infants. So your your classic vertical transmission that can be as high as 90%. But most people, it's very, very unlikely to develop into a chronic infection. Okay. So HEP B, you're expecting an acute infection. Most patient's will recover from that. They won't develop a chronic infection afterwards. And you've seen diagrams like this before often as a way of trying to help you interpret the serology. Like I said, I don't think these are helpful. I think it's far more sensible to just go through the different parts of the serology and just think of what they implied. So we're going to start with the HEP B surface antigen. What does it tell you if a patient has a positive Hep B surface antigen, it tells you that the virus is there okay strictly. It could tell you they've been vaccinated if you took the blood test, like immediately after they vaccinated, but nobody obviously does that. So if somebody has the surface antigen in their blood, they have the virus there. So that's the first question you're always asking yourself is the virus in them at the moment. If there's no surface antigen, there's no virus. So the next thing we look at is the surface antibody. What does it tell you if a patient has the surface antibody? So it tells you that an immune response has occurred. But more importantly, it tells you that you are immune so that the antibodies against the surface antigen on neutralizing antibodies. But definition, if you're, if you're producing these antibodies, you are now immune to Hepatitis B, we don't yet necessarily know is why you're immune, whether it's because of the vaccine or because of the, because of a previous infection. But we know you're immune to them. What tells us whether you've had an infection before is the court antibodies. So the only way you produce core antibody is if at some point you've had HEP B in you and I G M is your acute antibody. So if you've got anti cord and it's I G M that tells you that you've had the virus in you for a short amount of time. If it's I G it tells you've had the virus in your body a long time. Okay. So the anti court antibodies do not confer immunity, but they do tell you you've had the virus in you. So if you have anti surface and anti court antibodies, you know, you've had the virus in you and your immune. So you cleared the infection if you've got anti court antibodies. I'm sorry if you've got anti surface antibodies, but no anti court antibodies, that means you're immune, but you've never had the virus in you. So that must mean you've been vaccinated. Okay. And the final thing we test for is the, the antibody and antigen generally know what the e antigen is. A marker of infectivity tells you how active the infection currently is. So, if you have the e antigen, that means that you're highly infected because the virus is highly active and replicating. If you have the antibody means it's not very active. So from just from sort of what those different things actually mean, you can just in for from there what any different status is and you obviously tables like this. I don't think it's sensible to learn the table. I think it's sensible to learn what each of the things implies. And then the table kind of just works itself out. Right. If we pick, for instance, the acute HEP B patient, well, the acute HEP B patient, they have surface antigen because they have the virus in them. They have antibodies against the court antigen because they have the virus in them and they don't have surface antibodies because they're not yet immune and so on. So if you understand what each of the different components actually tells you is happening, you don't actually need to learn this table. I think that's an easier way to learn your way through the HEP B serology. There are some edge cases. I don't think you'll ever be asked them. Um So one of the edge cases that people sometimes worry about is if you just have the core antibody and nothing else, which can happen, what that normally implies is one of two things, it either implies that you're just finishing an acute infection. So what's happened is you've had an acute infection and you've basically fully cleared it. What that means is you've produced surface antibodies which has cleared the surface aunties, you've wiped out the virus, but you've not produced enough of them yet. To be measuring it. So the surface antibodies are there, you're just not measuring them, but they killed all the virus. So there's no surface antigen left and you have anti court antibodies. So somebody with just anti court antibodies, it might be that they're just clearing the infection. Like as you're testing them, it can also mean that you were infected a long, long time ago because they might have just lost production of the surface antibody because they had HEP B 30 years ago or something. I would expect them to ask you about that. Um At all, I don't think that's a very fair question. So that's how we work out. Somebody's HEP B status. One thing then to do think about is how we treat it. Now, there are a whole load of difference, a load of different anti Hep B drugs. I don't think they can ask you very much about it because it's very, very complicated. Do they really know the names of any drugs that you use for Hep B? So Interferon Alpha is the old drug and it's, it's still used sometimes it was the first treatment that we had for it. It's been replaced by some of the other options. So come back to direct acting antivirals, they're for HEP C. So we're gonna circle back to that in a second. Tenofovir is the only one. If you're going to learn one, I would recommend learning first one option is Tenofovir roughly, but there are other options and entecavir is another option. There are several other ones, lamiVUDine tell, give you Dean really not worth worrying about because the actual indication very much depends on your HEP B and various of the sort of, you know, um, co morbidities. If you're gonna learn one, learn, turn off of it, I wouldn't go any deeper into it than that. The other things you're going to do in terms of management is you're going to regularly screen these patient's for development of have cell carcinoma. So they get ultrasounds, you're gonna measure serum AFP, although it's debated how useful this is and you can also do things like Alaska scans. Um And you can also do, I forget the proper name for it and there's a serum test, you can do that gives you an indication of cirrhosis. But you want to be following these patient's up for possible cirrhosis to sell it carcinoma more important than all of this. Ideally is preventing it because HPV HPV. As a vaccine, this is a table of all the different antivirals that are most commonly used for HEP B. And this is exactly why I say, don't bother learning them. What you can see is that Tenofovir has no real resistance, which is why it's first line. Um But all these other drugs have their places. So don't worry about it. If you're gonna learn one, learn Tenofovir, I don't think anything else is worth going into what sometimes comes with HEP B is HEP D. So HEP D is also transmitted by bodily fluids. But it can only cause infection if you already have Hep B, it's not a complete functioning virus by itself. So times that we suspect Hep B and it's not very common, but the times that we suspect Hep D or either there's been a co infection. And this is basically the main reason that somebody might have HEP B presenting with formant liver failure in that acute phase. So if somebody had acute HEP B and the liver was failing, be worried that they might have been co infected with hepatitis. The second way this can present with super infection. So this is somebody has had an acute flare up of their HEP B when they were initially infected, it then settled into chronic HEP B. And all of a sudden, they've had a second bout of acute hepatitis from their HEP B that makes you wonder, have they now gained a HEP D infection that's causing this second round of acute symptoms. And then the final cause would be if you're trying to treat just a chronic HEP B and it's really not responding to anything. You'd start wondering have they also got HEP D. If you suspect it, you test um anti hefty antibodies, very, very difficult to treat. Interferon alpha is basically the only thing that's shown any efficacy, but it's not very good. And these patient's very often go on to develop cirrhosis or cancer within a couple of years. It's really, really bad prognosis. Luckily it's quite rare. So the final hepatitis viruses, HEP C so like HEP B transmitted by bodily fluids and it's transmitted vertically. Um It actually comes in six different forms. So there are genotypes. One through six, the vast majority of infections are genotype one. Um And the reason we split them into these genotypes is that it has ramifications for the way that you're going to treat it. Different genotypes, respond to different things. This used to be really important. But with the advent of direct acting antivirals, which we'll talk about in a second, the importance of that has decreased somewhat. Um And the thing too about HEP C is it's the complete opposite of HEP B. So HEP C very, very rarely causes an acute hepatitis. When you're acutely infected with this, you do not normally get any symptoms. Sometimes might, you might get a little bit of a prodrome. You would not expect somebody normally to end up jaundiced from HEP C. That's much more Hep B. So it's really unlikely you get acute symptoms. However, it's much more likely than HEP B that you will develop a chronic infection. Okay. As high as 80% of patients who were inoculated with HEP C will develop a chronic infection just exactly the other way around. The problem with this is that you never got the hepatitis. So these patient's often present in cirrhosis or with HCC because they never had the first warning that something was wrong. It can also present in some other ways. I don't think this is very high yield, but just sort of, so you're aware because you get an immune response, you get antibodies. So one way HEP C can sort of present actually quite common. First presentation. Pepsi is glory loan arthritis because they're producing all these antibodies, the complexes deposit in the kidney and you develop a nephrotic nephrotic syndrome. Um I'd be very surprised if they gave you any exam. But in real life, it's something that's reasonably useful to know. And because HEP C is less complicated than head beat. Serology is less important. We can do serology, we can test for antibodies. The viral load tends to be the main market we're using. It also has a graph like this which you've probably seen someone show you somewhere. I don't think it's very useful. Um I wouldn't worry about it very much. And then we've got to think about how we treat Hep C. So Hep C is kind of like HEP B in that I wouldn't worry very much about the treatment. It's very complex. Historically, it was ribavirin and pegylated Interferon alpha. It wasn't very good at treating it. But as I mentioned in the PAP was subsequently developed, were called the direct acting antivirals, which specifically targets various parts of the HEP C genome. This is really not worth learning. If you're gonna learn anything, you could learn the suffixes because the suffixes tell you what class of HEP C drug you're dealing with. I don't think it's worth even learning that I think because the choice of the drugs is very specific to genotyping, the specific HEP C that you've got. So really, I don't think this is very high yield. The way that we judge treatment for HEP C is something called a sustained virological response. And this is at 12 weeks after you finish your treatment course. Do you have a detectable viral load if you're non detectible at 12 weeks? Very, very good prognosis. You've almost certainly cleared it. If you've still got a viral at 12 weeks, it's much worse prognostically. A notes that unlike HEP B HEP C is not vaccine presentable, preventable. Rather, this is just to show you exactly why I don't think you should learn the drugs. Um This is a simplified diagram of how the different parts of the genome of HEP C related to its life cycle and the drugs that we use do not learn this from for the light. And honestly, you'd be mad to try and learn this and that I think is all the sort of virology that is worth going through. Are there any questions about any of that before we move on? So if you just go back to the mentee, so if you're for this question. So all of these things are presentations of herpes and any sort of serious presentation is gonna be more likely in HIV herpes esophagitis in particular, though is very, very uncommon. National, significantly immunosuppressed herpes encapsulitis can happen to anybody. You'd be unlucky, but it happens and ginger. This dermatitis is your classic first presentation of HSV. One, the recurrence is often just a single bicycle, what we call call SOLs. The first presentation is very often sort of more sort of pronounced involvement of the oral cavity. This question, PML is your classic disease to associate with J C your post kidney transplant nephropathy. That's BK virus rather than J C and post transplant, lymphoproliferative disease. You want to be associated with E B B and the serology, you all did this really well. Um So the surface antigen positive. So they must have the virus in them, the surface antibody negative. So they're not immune, they have the virus. So then it's just a question of what stage is the infection, the core antibody they have is I G M. It must be an acute infection and stuff about the E antigen doesn't really paying anything at this stage. Ok. Fab. So we're going to move on now to some of our sort of other causes of fever, some of other infectious causes. So we're going to do a couple of questions before we start going to the power point. Okay. So which of the following is not an indication. The IV A test on it in a patient with malaria. So it is, the parasite immigrated. Um sent I've been a little bit treaty there. So we'll talk about exactly why that one isn't the indication for IV art, isn't it? In a second? So, a 37 year old man presents to a and E with a three day history of fever. Malaise Wriggles. Let's say they returned a couple of weeks ago from South America on examination. That's what they're left. Axilla looks like with a profound lymph node and you aspirated it, you bring out a sort of a dense black fluid which of these organisms is most likely responsible. Yeah. So this is, this is yesenia. And again, we'll talk about what exactly that is and what the other organism have mentioned, their hopes. And then finally, which of these infections isn't transmitted by mosquitoes? Good. So is leishmaniasis? And we'll again, we'll talk about most of these infections and what actually transmits those. So let's go back to the powerpoint. Okay. So direction of unknown origin. So this has a very specific definition and this is a definition to learn. They like asking this soap, erection of unknown origin is defined as repeated pyrexia above 38.3 degrees for more than three weeks without a known cause. Despite having spent at least a week actively trying to find out what's going on. This is your classic definition of pyrexia of unknown origin. There are other definitions for specific circumstances. I don't, I wouldn't learn those definitions. Like word for word, learn that classic definition though. They like asking it. Noticed this has to be an objective fever. It cannot be any of this. I felt a bit hot and sweaty nonsense. Right. It can't be, I felt a bit unwell. You've got to have measured temperatures beyond 38.3. It doesn't have to stay there the whole time, but they have to have objective spikes. These are some of the other definitions. So you have nosocomial perec's of unknown origin, neutropenic correction of unknown origin, high HIV associated. I wouldn't bother learning those they exist. I can't see them asking it. The classic definition though is really worth being aware of the thing about practice of unknown origin is it implies that you ruled out all the obvious causes. So what things can cause a fever other than your obvious infections? Any idea of what things we might be thinking to look out for? So, systemic inflammatory. So, autoimmune is definitely on the list. So I think the first thing to look for is some of your non obvious infection and this can be weird organisms, but it could also be unusual fozie of infection. So wants to always sort of have a like a high index of suspicion for infective endocarditis. So as abscess, an epidural abscess, these infections are very easy to miss autoimmune conditions. So any of your rheumatology, vasculitic diseases and especially still's disease can prevent, present, very, very inflammatory. There's also really, really interesting condition called HLH. I'm not going to bore you with it. It's very, very rare. Only mention it because I found a patient with it a week or two ago. Really, really interesting. I'd recommend looking into it if you're interested in this stuff, but it's definitely not gonna be on the exam. Other thing to really be thinking about is malignancy. Okay. Him on in particular can present very, very acutely inflamed. Um lymphomas can very easily mimic infections. And finally, you've got your rare stuff. You have talked about this elsewhere. I think in, in, you know, you've got your periodic fever syndromes, things like familial mediterranean fever and your immuno deficiencies. Um So we talked about non obvious infections and this leads us quite nicely onto fever in the returning traveler, which is a common cause of some well weird infections. So the first one I think is really worth knowing about is typhoid. Now, for the most part, we're gonna be buzz wording here. It's not worth knowing loads and loads of details. It's about being able to identify them. And just to sort of a top tip in the exam if they ask you how to treat a weird infection and you have no idea what the correct choice of antibiotic is. Plump for Doxycycline more often than not Doxycycline will cover it. So, the first one we're gonna talk about is typhoid fever. What causes typhoid fever, salmonella typhi or salmonella, paratyphoid, not salmonella enteritidis. That's what causes your sort of your classic, um, your classic sort of diarrheal illness. It's a cause of dysentery. It's salmonella, typhi and paratyphoid. Classically, it's going to be certainly an SBA land is going to be somebody who's traveled from India is transmitted by the faecal is classically associate with people traveling from India. And does anybody have any buzz words we associate with the presentation of typhoid fever? What things in a clinical description would point you that way, rose spots, constipation, very, very good. There's one more, I think worth being aware of maybe two more but one of them in particular. So, so it definitely will present with my algia doesn't help you let them sort of narrow it down because lots of things will settle. So classically incubates for a couple of weeks, you start getting symptoms. The things to look out for are rose spots, nosebleeds, constipation, not diarrhea and faggots sign. So fagina sign is what's called a relative bradycardia. Most patients with a fever will have an increase in their heart rate. There is a formula for how much you expect the heart rate to increase if depending on how high your fever is. But in general, if the patient has a fever of 40 they're going to be tachycardic fagina sign is a patient who has a heart rate of about 60 or 70 which is sort of quote unquote normal despite having a raging fever, it's called fagina sign. And you see, in a handful of specific infections on one of those is typhoid. So those are the things I would be thinking. I'd like buzz words to associate with it. We're going to diagnose typhoid for, from sort of culture or serology. Does anybody know what technically is the gold standard test for typhoid fever culture? Of what though? So that is a very sensible thing to be thinking. It's definitely something you would send that. Actually, the gold standard is a bone marrow culture. It's very, very road. I can't imagine this actually happens very much but just be aware that technically and if this does happen sometimes with the gold standard test is definitely not the test you're practically going to be doing. Um But you're gonna, you're gonna diagnose with cultures and something called vigils test, which isn't actually used very much anymore. But it's the classic test for typhoid fever. And this one, I know I said to start by thinking doxy. If you're not sure this one actually doesn't follow the rule. You normally start these patient's on cefTRIAXone. So this is what your rose spots look like because it almost looks a little bit like early chickenpox. Um But yeah, so this is what your rose spots look like. And this is the actual infection inside the gi tract. So pie avoid fever actually lives within the payers patches and it can actually really, really serious. Most patient's recover after sort of their acute illness space, but these payers patches can become really, really congested and one of the complications is massive gi hemorrhage or indeed, um indeed, um perforation like intestinal perforation. Um Yeah, that is a little bit of stuff for interest, not worth worrying about those four things I mentioned. Those are the buzzwords to associate with Typhoid. Uh Yeah, little test is rubbish. It's not really used very much anymore, but it's a, it's a name worth having as an association because it is a very classic test. So that's why we're gonna talk about is Dengue. So, Deng is a mosquito borne. Um There's four different serovar that can cause infection. Um You're normally thinking somebody's been traveling around Southeast Asia. Thailand is normally try under like Cambodia tend to be the country's you'll get in an S B A. Now, what buzzwords do people have for? Dengue fever. So, I'd say there are two buzzwords have here. Good retro orbital headache. So the other one to have is a sunburn rash. Those are the two buzzwords to have these patient's present very, very high fevers. They look really, really unwell, but most of the patients are covered by themselves. So we don't actually treat Dengue fever when it first presents. Normally these supportive treatment and they should normally do get better by themselves. Dengue can present with two very severe syndromes. One is called Dengue shock syndrome and one is called Dengue have Dengue hemorrhagic syndrome. Does anybody know? I think this will be a little bit harsh to ask anybody know why people presenting these more serious infections. Good. So it's previous Dengue. So when you're infected with Dengue for the first time, you don't have any antibodies. Once you develop the antibodies, you clear the infection. If you then get infected with a different serovar, you have an antibody already there, that isn't good enough to completely stop it working. But what that antibody does is it carries the virus to your B and T cells and your macrophages. So all the antibody actually does is it gives the dengue virus a wider range of cells and it's now capable of infecting. So this second infection is much more severe and that's when you see either shock or hemorrhage. Um It's also why there's no dengue vaccine. They tried the Dengue vaccine, but it actually made it much worse for this reason because you have to be infected the second time. Severe illness is very uncommon in travelers because you've not only been there long enough to be exposed twice, far more likely to be in somebody who lived in that country. And a lot of these sort of buzz words are like, let's be honest, most of them are crap, but this one is actually really good. So this is the classic dengue rash. And I'd argue this actually really does look like a sunburn. So sunburn rash is a really good association to have. Okay. The next infection we're gonna talk about is malaria and this is the first one we're gonna into a bit of detail about cause there's some stuff worth knowing here. So there is a parasitic infection. It's caused by various plasmodium species and you find it all over the place is in Africa, it's in South Asia and Southeast Asia is in South America. It can incubate for a variable amount of time and how long it incubates for, depends on the species that you're, you've been infected with. But once you've been infected and once it becomes symptomatic after it's incubated, it typically starts with what we call paroxysms of fever and wriggles. Do people know what I mean by paroxysms? So, what we mean really is this is very episodic. What they'll have is they'll have an episode for several hours where they feel absolutely horrendous. They'll spike a really high fever. They'll be really profoundly recurring and then they won't be quite as ill for the next day or two. And they'll have another episode where they're really profoundly unwell and they tend to cycle backwards and forwards like this. It's very, very classic for malaria. If you have a more serious illness, various other things can go wrong. It has a real propensity for affecting the liver. So you get this jaundiced that practice like megaly, you get humanistic anemia which causes hemoglobinuria. You can get really profound anemia. And if it's really serious, it can kill you in all kinds of different ways. These are the most common, really bad presentations to be aware of. So it can cause shock, it can cause ARDS, it can go to the brain and cause sort of coma. It can cause profound bleeding and it can also cause something called black water fever that people know does anybody know what black water fever is? So black water fever is where you get really really pronounced Hamal icis, which means that you leak loads of hemoglobin into your urine which then trashes your kidney and the the urine it proves is really startling. So it looks like that okay. It's really really, it's so much more than your classic rhabdomyolysis. It's really dark black urine um and very very classic sign to associate with malaria. So as I mentioned, there's a bunch of different species of malaria and the way we diagnose malaria is with thick and thin blood films and strictly if you really know what you're doing a blood film like this will tell you what species of malaria you're dealing with, which is really important to know because it has ramifications of how you treat it. So there are five plasmodium species and these are the five and we're talking a little bit about the life cycle. Not too much. I'm not going to bore you with all the path of physiology, but there's a little bit worth knowing cause it has some of the, some ramifications for how you treat it. So you get malaria from mosquito, mosquito bites you and it releases the sporozoite into your bloodstream where they go straight to your liver and they set up shop. What they do is they infect hepatocyte and that performs what sort of she's on is basically just a big, the cell descend into a big ball of developing malaria parasites. It gets bigger and bigger and bigger and then it ruptures and releases all of these immature parasites into the bloodstream. What these then do is invade red blood cells. Each one of these will go into its own red blood cell and it will mature and as it matures, it turns into a erythrocyte picture, isn't? It turns into another big ball of immature parasites. And as it develops over time, once it's fully developed, it ruptures the red blood cell releases loads of immature parasites that go on and do the same thing and go in a big cycle and keep infecting more red blood cells. The reason this is worth knowing is it tells you two things about the actual malarial infection. The first one is this cycle of developing a red blood cell and then rupturing that cycle is why you get the paroxysms. So where you get the episodes of fever and rivals and feeling really, really unwell. That's because all your red blood cells are rupturing and you're getting an acute inflammation and you feel better while they're invading the new red blood cells and developing. Okay. So I don't think these are worth learning but different malaria species take different amounts of time to develop in the red blood cell. So for false apart and y vaccine avail it takes two days. So you get these spikes every two days for no less. See it's only one day. So you get spikes, everyone 24 hours. And for malaria, it's every three days. So you get a longer period between the episodes of fever. So that's the first reason to mention sort of this life cycle. The second reason is if you look at step three on this diagram, it mentions a hip mastoid. So Viravax and oh valley and only these to produce hypno sides. And what this means is when you infect the liver rather than all of the parasites forming these seasons and rupturing and releasing parasites. Some of them become quiescent, they become a hipness avoid that just sits there asleep essentially. And those ones can reactivate years later, which means that you could have been, you could have been last in an endemic region 678 years ago. But if the infection with one of those two species, you can present 678 years from now with acute malaria having not been exposed to it. Since then, this also has ramifications for treatment because your antimalarials that treat the actual active parasites in the blood don't kill the hip no sides. So when you type the species, if it's vibe box Oravail, it changes the treatment slightly. And it's just just the diagram that shows that if you really know what you're doing, you can actually work out the species from the thick and thin blood film. So when we treat malaria, do you know what do we used to treat malaria? So, Chloroquine is one of the older drugs and we can use that for relatively milder treatment. It's been replaced by a different group of drugs. So, primaquine is a drug that we still use for killing the hip. No. So it's actually, but the actual treating of the malaria is something else we use. Now we use our test on it or are thames in based therapy. So IV artesunate is the strongest drug we have and this is for severe malaria. So any of those previous things that I mentioned that suggest really severe illness or if they have a parasitic burden, greater than 2% low blood sugar there, acidotic or a really severe anemia. The cut off is 70 or 80. Those patient's get IV artesunate, it's not as severe. We use combat are Temer's on combination therapy or we can use Chloroquine or primaquine. Um Primaquine in particular, we will give to anybody with buybacks Oravail alongside the Artemus in because we have to kill the hip besides. Okay. This, now we're now going to talk about a broader group of sort of zoonotic infections. Again, we're gonna be very, very buzz worthy here. Most of these you don't need to know too much detail for. So brucellosis, what buzzwords do people have for brucellosis? Exposure to cattle, so exposed to Castle is a really good one or more importantly, often the products of cattle. So unpasteurized milk, raw dairy is the classic exposure that will give people brucella in terms of her actually presents. I'd say that anybody have any symptoms, they specifically associate with brucella. So it does very good. It does tend classically cause an evening fever. The other name for brucellosis, undulant fever, it could be very harsh if they ask you to get it off of that. I think the two, they tend to give you a bit more often. It can do loads and loads of stuff. The two that I would highlight here are sort of the lower back pain because it can cause epidural abscess, ear's an epididymal walk itis. Those are the two sort of classic symptoms to specifically associate with brucella. We diagnose it with cultures and we treat it with doctor cycling. You can see this a bit of recurring thing that's gonna be a lot of doxy. So we treated the doctor cycling. This is a picture. So what you can see the arrow is pointing out here is the epidural abscess, which is one of your classic presentation to associate the other one. Now, luckily, this is not from a human. I should warn you some of the pictures we're going to have a little bit unpleasant for some of these infections. This is actually from a cattle that was infected with brucella. So when we say epididymo-orchitis, lots of things can cause epididymo-orchitis. Brucella really does cause epididymo-orchitis. So the difference there on the left is your, that's your inflamed one. And you can see it's really, really profound. So those are the two symptoms to associate with brucella. And like we said, the exposure you're looking for is some exposure to raw daring. How about rabies? What do we associate with rabies and all whites, dogs and bats in particular? And what about your symptoms in terms of the presentation, behavioral changes, any specific behaviors you're looking for hydrophobia? So that's going to be your big one. Um You can actually incubate for quite a while. Hydrophobia is the big one to be aware of. Some pay the vast majority of patients present with what's called furious and careful itis where you get the really profound behavior change that become really aggressive. The other 20% present with what's called dumb rabies, which is very paralytic. And then yeah, your excess salivation and hydrophobia is your classic symptoms. Um in terms of diagnosing it. In reality, the diagnosis is very often clinical because you have to diagnose this quickly because does anybody know how we can treat this or when we can treat it? So we can treat it with rabies, immunoglobulin and with the rabies vaccine. But the key thing to re note is you can only treat it really before they're symptomatic. Once they developed symptoms, they're probably dead. Um There's something if you're interested called the Milwaukee protocol, which has saved a couple of people who have developed symptomatic rabies. It's very, very unlikely. I'm talking literally a couple of people in the world have survived it. So if you develop symptoms, you're probably dead. So it's very often diagnosed clinically. Um If there's any doubt, you're going to give the treatment just to be safe. Um You can use a PCR, the CSF. But by that point, it's in the CSF, that's a really bad sign. So the test that people often do actually is they take a biopsy of the skin from the nape of the neck, which can sometimes be early enough before they get to the brain. And the other buzzword to associate with it is something called a negri body, which is something it's pathognomonic. It's something they see on histology. It's an inclusion body in the neurons that are infected. I think obviously this is only ever gonna be postmortem really. So just associate that buzzword with it. And as I said, if bitten, you're gonna give the vaccine and the immunoglobulin this diagram here, this is showing the negative body. So if you look in the middle, you got your neuron in the nucleus in the middle. If you look around the pale center, you can see these black circles, these are your negri bodies. And as I said, that is just something to associate with rabies. It's just another buzzword to have there. So the next one which is the plague, what buzzwords do people have for the plague? What why do they get it from? And what does it present with? So rats and more specifically not rapu fleas for this one, it tends to be fleas that transmit this. You can get it from other rodents as well, but it tends to be from. So rats spread it around, but it's the fleas that actually transmit it. And how does plague present? What buzzwords do we have for plague? So flaky present a few different ways. The want to know is bubonic plague and the buzz word to have isb you bows. So these are massive fat lymph nodes that when you aspirate them are full of a really dense black fluid that is going to be your classic presentation for plague. It can present in other ways depending on where it inoculates and is often crossover between these as the bacteria spreads around. But yeah, buba those the big lymph nodes often auxiliary limit flows or England on inflows. When you aspirate, I feel with a dense black fluid is your classic plague symptom we diagnosed but with microscopy often of the aspirate and how do you think we treat it? It's gonna be doctor cycling. So this is what your bugles like you can see. These are really sort of prominent massive lymph nodes. What what here actually is the other thing that often presents with is peripheral gangrene. He always called dry gangrene. As you can see, here's all the, all the necrotic tissue. Okay. Next, infection talk about is leptospirosis. So same again. What buzzwords do we associate with? Leptospirosis? What spreads it? How do you catch it? What does it present with? So this one is spread by rat urine. Okay. It's a spiral key is spread by rat urine. This can either be direct inoculation but more commonly the way you'll see this present in A, in an S B A is somebody who's been swimming in like a lake or a river or something and they've caught it because there's rats obviously peeing into the water. So exposure to stagnant water, swimming in lakes or something is your classic exposure for leptospirosis. It can present with lots of different things. Plus words to look for are jaundiced. So they often present with the hepatitis and conjunctival suffusion. Very, very classic for leptospirosis. What that means is they've got a conjunctive itis without any exudates. So it's a dry conjunctivitis. We call that conjunctival suffusion. You're gonna diagnose it by the getting cultures or serology and how are we going to treat it? We're gonna give them doctor cycling again. Okay. And this is what your conjunctival suffusion looks like. So you can see it's a really profound inflammation is a really profound conjunctivitis, but there's no extra date there, there's nothing coming out of the eyes which would expect with a really bad bacterial conjunctivitis. Ok. Bartonella, do we have any buzz words for Bartonella, pets? What sort of pets as a specific pet to associate Bartonella with kittens? So cats, so it's called cats. It present a few different ways, but it's called cat scratch fever. When it's most common presentation, any buzz words we associate with it. So it's very prone to causing lymphadenopathy. What you tend to get is a PAP, you're where you were scratched, you then tend to get lymphadenopathy proximal to that. So if you got scratched on your hand, most commonly, you then get lymph nodes in your armpit for instance, in your axilla. And then the pathognomonic syndrome again, just a buzzword to recognize is paranal oculoglandular syndrome. It sounds very fancy. All it is is the combination of conjunctive itis and big lymph nodes in front of your ear. Those two things together are basically diagnostic of Bartonella. We're gonna diagnose it, we can do PCR sor allegedly cultures and how we're gonna treat it. We're gonna give them doctor cycling. So you can see here that you can see here that you've got this papule forming where you are actually scratched. And then this is an example of sort of white. Why I mentioned the parallels oculoglandular syndrome, big lymph nodes and conjunctive isis. Ok, Lyme disease. Same again. What are the buzzwords? What are the things to associate with? Line Outdoors because it's transmitted by ticks. And there's a presentation, one of the things to associate what symptoms are going to be classic your balls. I rush. So it is transmitted by the eggs, odis tick. It's not actually been found in the UK. Um It's certainly, I think Scotland has Lyme disease now. And yeah, it presents in different stages. But the buzzwords to associate are erythema migrants, your bullseye or target rash and the other things that causes our arthralgias and in particular, it can cause heart blocks. Those are the things I'd be associating with. It. Really important actually to be aware of clinically. Lyme disease is a clinical diagnosis. If you have erythema migrants, you can get things like serology. You don't need them erythema migrants in and of itself in. Somebody who has an exposure is reason enough to treat it. How do you think we're gonna treat Lyme disease? You're gonna give them doxycycline honestly, should put it in the water. So this is erythema migrants. This is the classic target shaped rash. If you see that on a patient and they've been anywhere outside in the woods. That is Lyme disease, you can start treating, you don't need to wait for any tests. Ok. Leishmaniasis. Now, this is slightly more niche, but there's a few buzz wordsworth nosing anybody have any association with the leishmaniasis terms of what spreads it or how it presents. So it is spread by sand flies. Very good and anybody have any idea how it presents very good. So, kala-azar is the name of the visceral leishmaniasis presentation. So it can present in two main ways. There's a bunch of different subtypes that I'm not gonna perfect visceral and cutaneous. I'm not going to dwell too much on the different subtypes, not worth worrying about. It can present with cutaneous symptoms and you can either get a really bad lesion at the site of the bite or it can be the skin lesions everywhere or you can get visceral disease. And so this is where this is sort of a prolonged course of sort of just feeling really unwell for participating megaly and gradual Emaciation. And these patients, if you don't treat them invariably die of um secondary infections as they emaciate. If they have visceral infection, we diagnosed by microscopy because we can actually see the leishmania under microscope because it's a parasitic infection or it's a protozoa, I think technically, um and for the first time, this is not doxycycline, we normally treat this with liposomal amphotericin being slightly what you tell them you probably need. This is normally the treatment for visceral. And despite that visceral is the one that kills you. It's actually one that's much easier to treat cutaneous disease of any form is really, really hard to treat. And often we're not very good at it. And like I said, there are some unpleasant pictures here so little and I can cause really destructive skin lesions. So this is an example of localized cutaneous leishmaniasis. As you can see that you get this also that forms and it's quite profound also. And it can take months to heal the other presentation that just worth recognizing because it's so sort of pathognomonic you can get what's called mucocutaneous leishmaniasis. And this is a very destructive leaders. So this is a picture and I said it's quite graphic of somebody who had mucous cutaneous leishmaniasis. And you can see that it's completely destroyed all the mucosal tissue around the mouth and the nose. So, and this is incredibly difficult to treat. This is another sort of cutaneous presentation and this is yet another cutaneous presentation. So lots of different forms, but certainly that sort of destructive mucosal form is very classic for leishmaniasis that sand flies are probably the main association to have with it. Ok. Anthrax, anybody have any associations with anthrax in terms of where you get it from or just buzzwords to have with it. So anthrax normally got from wild animals. And again, it has a few different forms depending on how it inoculates the buzzwords to have for anthrax I would say R S cars and widened mediastinum. So an escarre is if it's inoculated on the skin, which is the most common way that you contract it, it gets in through a wound and you develop what's called eschar, which is basically just a skin lesion, which is painless and it's necrotic. So it goes a really deep dark black necrotic color. That's very classic for anthrax. Wider mediastinum is the classic presentation for a a pulmonary anthrax. But it's very, very uncommon if they give you this, it will probably be via an escarre um that they want you to diagnose it, you know, diagnosed by microscopy or various other options. And how are we going to treat it? We're going to treat it with doctor cycling. So this is what your esseker looks like. You can see that it looks like dead necrotic tissue. And this is just an example of a chest X ray showing a widened media sign in okay. And that is the end of sort of the bacteria and protozoa, all sort of zoona tick infections that I think are worth going through. Um We don't have, that's the second big chunk. There's not a huge amount left for us to go through. So are there any questions about anything we've talked about there? So just while anybody thinks that they have any, um so just go back through these questions. So the reason that this was not the indication for treatment of malaria with IVR Tiziana is that parasite team regret than 1% isn't necessarily considered a high disease burden. 2% is your cut off. That cut off is worth knowing. Hypoglycemia is often more people think. But hypoglycemia is actually a really problematic symptoms in malaria because you have so many parasites. If you have a high disease burden, they just metabolize all your sugar and they can leave you really, really dangerously hypoglycemic. Um This one, this is your senior pestis. So Yersinia pestis is the causative organism for the plague. As we discussed, having this big lymph node with the black aspirate very, very classic buzzwords for plague. And finally, of these so West Nile dengue, yellow fever and malaria are all mosquito borne diseases. Um What leishmaniasis like we just mentioned is transmitted by sand flies. Okay. If there are no questions we will carry on, um there's not a huge amount left. So the end is in sight. So that's we're gonna talk about briefly. It's fungal infections and we can split fungal infections into a superficial infections and are sort of deep more concerning infections. So what organisms can cause superficial fungal infections? Any ideas? So, tin ear infections are your classic, most common form of superficial infections. A few things can cause them. The organism to know is trichophyton rubrum, there's a couple of others, but trichophyton rubrum is the one they will ask you about and it has a different name depending on where it is. Now, does anybody know why I've laid these out with those four at the top? And tinea capitis and tinea hungry, um separate from the other four. So most your dumb ass if it's, which we also call ringworm or tenure infections, most of these can be treated with just topical antifungals and you normally the correct dose will be like a topical antifungal shampoo or topical antifungal cream. The reason we separate out the bottom too isn't because it's a different organism is the same organism. But when it causes those types of infections, it's much harder to clear. So tenure and capitis and 10, you're hungry um are the only tenure infections that you will not clear with topical antifungals alone. Those to require systemic antifungals. Normally this will be an all A's oral antifungal um or it might be to benefit um Griseofulviin I think is the other new one. Um because Aizaz are a bit protocols. Um Hepatic injury, but you have to give some form of all antifungal where you will not clear those the other cause of superficial fungal infection to be aware of is pity. Rice's versicolor. I probably butchered that pronunciation. Um because anybody know what organism causes that infection? Good. So this is Malassezia for, for those are the two main superficial infections. Nobel malice pityriasis is classically described as having sort of multiple brown or tan lesions across the trunk and the abdomen. Notice that this is a description of how it classically presents on people with white skin and in people with darker skin, the classic presentation is actually deep pigmentation. So they have hyperpigmented scaly patches rather than the classic brown patches. So just something worth being aware of. But again, like your simple tinea infections will clear with just topical anti fungals, your sister, you're sort of your more systemic anti fungal infections worth knowing about. First one is Candy Diocese. So, unsurprisingly, it's caused by Candida species. It can present lots of different ways. How can Candida present good? So those are the main ones. So vaginal candidiasis or thrush is going to be the most common presentation of a candida infection. Oral candy Diocese is classically associated with asthmatics because they use steroid inhalers. That's why you should advise them to wash their mouth out with water whenever they use their steroid inhaler, a softer Geul candy Diocese by comparison is associate with severe immune suppression. It's again, very classic for patients with HIV and you can also get disseminated candy Diocese. This tends to be in patient's who've got like central accesses. You get line infections with Candida. Sometimes we diagnosed with cultures specific blood tests you can do are the beta D glucan and galacto manner. And for Candida, the beta D glucan will be positive, the galacto manner will be negative. This is in contrast to the main other one we use these tests for which is Aspergillus, which for which both of them will be positive galacto man. And in particular is very particular, more or less for Aspergillus infections and like most anti, most like most fungal infections. If it's really, really bad, we treat it with amphotericin B. You can also use econo candin. So these are drugs like anidulafungin or I think Casper fungin, I think is the other one but it was really, really bad. Your, your disseminated candy Diocese, you're going to have to use amphotericin B. This is what sort of oral candid isis looks like, like I said, very tight associate with asthmatics and this is your sausage to your candid isis a much more serious presentation. The next thing fungus we're going to talk about is Aspergillus. So how can aspire Galis cause symptoms in people? You can get A BP A. What else can I do? Invasive aspergillosis? And one other one I said worth knowing is Aspergillum Azaz. So asthma Gialamas or a big ball of Aspergillus that forms in a pre existing cavity. So, patient's who've had TB patients who've had squamous cell lung cancer, which is cavity or bronchiectasis, some kind of cavitary lung disease and the Asperger's can move in and set up a big ball of fungus, um invasive aspergillosis. This is something you're going to see mostly in your immunocompromised patient. Sor sort of in a hospital setting with line infections, this can be in the lungs or it can go anywhere. You can get sort of like a okay, I guess fungi Mick picture with just a specialist all over the place. And then a BP A, this is not an infection. So allergic bronchopulmonary, aspergillosis is a complication. You sometimes see in asthmatics and this is not an infection with Aspergillus. This is, there's Aspergillus in your lungs that probably everybody has a little bit of because you have hyperactive airways, you get a profound inflammatory response to the Aspergillus. It's there, it is not infecting you. As I mentioned, if you're infected with astragalus, you're gonna diagnose with cultures again. But this time, the basic D glucan and the galacto manner are both positive and if it's really bad, it's a fungus you're gonna treat without for terracing. Be there's some nuance here. If you have an asthma Aloma, you can't really treat that antifungals. The way you treat that is by pulling out the lump of fungus. And if you have a BP A, that is not an infection, you do not treat with antifungals. They're controversial, but broadly, they don't work. Steroid is how you treat it cause this is more of a hypersensitivity reaction than it is an infection. And I'm afraid there's a few more unpleasant pictures. That's what Aspergillum a looks like. So this is an Aspirin regimen that's actually being read it and being pulled out of a patient's lungs and looks, yeah, pretty horrible. And this is a patient who had TB and you can see where you've got these cavities of the TV is left behind. You can see you've got these balls that are actually fungus forming and then a couple of other random bits of fungal sort of pathology worth knowing just cause they have buzzwords associated with them. First one is sporotrichosis. The only thing to know about this is, it's caused by being, it's caused by, it's carried on roads, storms. So you'll see this in gardeners or farm work is your classic exposure for this. The way it presents is you get uh you get a rash starting from wherever you got um infected and it spreads proximately causing these sort of patchy big necrotic rashes. Um Only thing to know about it is know that is associated with roads, storms or farm workers. And then the other one I'm just going to mention is mucormycosis is something you might have heard of. It can cause it's called by various different species. The reason I've heard of it is there's a big worry about it is that you see it in a lot of patient's had COVID, especially diabetics who had COVID developed it. It causes what's called a rhinocerebral infection which is a really destructive lesion around the face where the fungus just invades everything really hard to treat. You have to sort of surgically debride it and give lots of antifungals, but it's a really dismal prognosis. So this is a classic picture of sporotrichosis. So you can see on the finger, you've got a rash where you've probably stabbed yourself with a rose thorn and these patchy rashes spreading upwards. And again, this is a really unpleasant picture. Afraid. This is a picture. Something with you for Mike Osis. So you can see that you've literally got a fungus growing inside the oral cavity and destroying the tissue. If you look at this patient's nose, you can see where it's eroded upwards and is now growing into the nasal cavity as well. That's eroding straight through the palate, really, really dismal prognosis and that's all the fungal stuff. Now, we're nearly there. The final thing we do is very briefly talk about prion diseases. Now, this is, I'm not going to dwell very long here. There's not much for your worth knowing. So, Priam's are proteins that behaving a bit of a weird way. So we have a PRP, see is the name of the normal protein on neurons in your brain. We don't really know what it does. There's a theory, it's something to do with moving copper around, but we don't really know what it does, but it's a protein that's on the surface of your nose and it has some function we don't know. And the way that protein is set up is it structure is primarily dominated by secondary alpha helix sees that's how it's meant to be shaped. What can happen though is it MS folds and it turns from what we call P R P C two P R P S C and that's the misfolded structure. Now, this doesn't change the primary structure, but the secondary structure changes instead of having a lot of alpha helix sees you have a lot of beta pleated sheets. Now, this has two consequences. The beta pleated sheets aren't very easy to degrade. They're very resistant to protease. So you can't break them down and the very water insoluble compared to the correct form of the protein. So you can't move it. So this protein now is in the wrong shape, which causes it to accumulate because you can't break it down and you can't move it anywhere else. So it forms big lumps of protein. Now, this is kind of like what happens in amyloidosis. It's very similar to what an amyloid protein is. What's a bit weird about Priam's is the misfolded protein. The PRP sc can interact with the correctly folded protein and make it MS fold. So when the PRP S C comes in contact with the normal prion protein, it causes it to miss fold. So what it does is it the heart kind of behaves like an infectious agent. If you contract forms of a better word, the misfolded form, it will make the normal protein MS fold. What this means then is you get a propagation of these big lumps of protein that you can't break down. And a neuro toxic and this is what causes prion disease. Okay. So these all present of the various forms that exist, these all present with a very rapid and urine degeneration. Now, we often don't know what causes the original MS folding because that's really the crux of this matter. Right? It's why does this start happening? And often we don't know, depending on the different form of the different type of prime disease you have, depends on how it started essentially. Okay. So the most common group of prion diseases are Cruise Felt Yacoub disease. And as I said, we give it a different name depending on why it started, why you developed this first MS folding. So the most common cause is sporadic and this means the MS folding happened for some indigenous reason, we don't know. So for some reason, one of your normal prion proteins misfolded itself and then it caused all the other ones to start following its lead and miss forming. Okay. That's the most common cause of critical Yacoub disease. Familial crucial Jakob disease way less common. There's a family history here and that's because there is some mutation, there's some genetic mutation that predisposes to miss folding. So in these cases, the reason why you had the first exposure to the misfolded protein because you had a genetic mutation that made it miss fold. Okay. That's familial cruise felt Jakob disease and the last group is acquired and this is you got your first dose of the misfolded protein from somewhere exogenously. Now, this can be iatrogenic. It happens very rarely, but it does happen as part of why the autoclave procedures for surgical equipment are the way they are. Um So it can happen iatrogenic lee. The place where we've seen this most is specifically something called variant Creutzfeldt Jakob. Does anybody know what variant Creutzfeldt Jakob disease is? So that's where you've acquired it from eating beef that was contaminated with mad cow disease. So mad cow disease or bovine spongiform encephalopathy, that's a prion disease in cows. And if you eat cows that are affected with that, the price runs from the cow can cause your protein to start MS folding. Okay. So variant Creutzfeldt Jakob is a form of acquired Creutzfeldt Jakob where you've gained the prion protein from somewhere externally. These are all diagnosed clinically, you can diagnose it. Biopsy is going to be definitive. But obviously, that's always postmortem. One sort of just little buzz words know for variant Creutzfeldt Jakob is for some reason in variant, the prion protein also is found in your tonsils. So tonsil a biopsy is specific for the variant form of Creutzfeldt Jakob disease. Now, Chris, but Yacoub's, you're by far the most common form of prime disease. There are a couple of others um which are these, I don't think these are worth knowing at all. Fatal familial insomnia is a, is a familiar one. Unsurprisingly, it's dominated early on by disturbance of sleep. Gerstman Strauss Lawyer Shanker disease is another familiar one has slightly better prognosis and not worth worrying about. Kuru is the only other one you might have heard of. This is one of the, I think this was the original one that we found in humans and this was found in tribes in Papua, New Guinea where they performed the ritual cannibalism and eight people's brains. And so then inoculated it. So it's kind of analogous to variant Creutzfeldt Jakob. It's just the variants from cows, whereas cruise from other humans. Okay. And that is the end of it. Um Well done for sticking with me. I know there was a lot there. Um If anybody has any questions, go for it, I'm just share ing the feedback now while people are thinking about questions. Thank you so much for the talk like that was not really, really good. It's a lot, especially this half of my quality is very, very dense. It's just, here's a condition, here's some things about it and I appreciate it very dense. How much do you sort of means about treatments like different fungal treatment and mechanisms, secondary transfer zoona tick infections, I think, I mean, it's hard for me to give a hard and fast answer because technically they could ask anything about anything I think realistically, I wouldn't get too bogged down in it. Um So in terms of the specific questions, I think for fungal fungal mechanisms, I've never seen a question. I let's not say they couldn't ask it. I've never seen a question where they asked you about the different mechanisms of the different antifungals. Um In terms of the different fungal treatments, I think it's probably worth knowing that econo Candance tend to be first line for Candida. Um So things like anidulafungin tends to be your first line for Candida. Worth knowing that amphotericin B is your first line for any serious fungal infection, essentially. Um And worth knowing that superficial fungal infections are treated topically unless it's tinea capitis, which is the scalp or tinea hungry on which is the nails and then they need oral um antifungals. I think any more detail on that is relatively unlikely to come up. Likewise, for secondary treatments for zoonotic infections, I'd be very surprised if they were to give you, I don't know, a patient with typhoid fever who was also allergic to penicillin and I'd be very, very unlikely. Um Is the quiz over the quizzes over? I might well have missed a question. I mean, I can promise you, it probably wasn't very exciting. And yeah, let's say, I think there's a lot of, there's a lot of just lists of organisms for the second half of microbiology. I think the approach to take is very buzz wording. I've included a lot of information there partly cause I just kind of like infectious disease and also sort of, you know, for your own interested you want to read through it. The best approach in terms of just like revising for path is to be very, very buzz worthy. Something like brucella. It's going to be someone who's been exposed to unpasteurized milk is gonna be somebody with floors the symptoms with way of fevers, feeling unwell back pain and epididymo-orchitis. It's not going to be subtle. If a patient has leptospirosis, they're going to tell you in the vignette, they've been swimming in lakes in Venezuela and they've now got a really sort of red inflamed. I and Hepatomegaly, they really won't be subtle with those kind of infections. And yeah, if you're uncertain, give everybody doxy, no problem at all. I hope it was helpful and people managed to stay awake. Um, okay. There's no other questions I will.