85. Bordetella and the Cough of 100 Days

You'll be whooping with knowledge after listening to this one. Come hear all about Bordetella species. From pertussis to kennel cough you'll hear it all.

Show notes for this episode here

Transcript

Jame: 0:18

Callum, how you doing?

Callum: 0:19

I, you know what, James? I am, I'm good. Sitting down the other day, James, and as, after the Euros have finished and all, the football is done, I was gonna watch some TV, or you might say the teller, and I thought, I'm bored of the teller.

Jame: 0:40

Oh. Do you know Callum, sometimes I get tired of these puns and I think to myself, I just want to become a farmer. A farmer on a variable. At the point where Scotland ends and England begins. That's a lovely part of the country. I'd like to be a border tiller. And that reminds me Callum, what are we talking about today?

Callum: 1:00

I'm whooping with laughter at that one, James.

Jame: 1:04

All right, thank you very much.

Callum: 1:06

Whooping.

Jame: 1:08

Yes, we're we're back to the bug episodes. We need to finish these gram negatives.

Callum: 1:11

bugs are back in town!

Jame: 1:12

finish us. The bugs are back in town.

Callum: 1:15

Na. But if you buy us enough copies, then you can hear our new jingle, which is The Bugs Are Back In Town.

Jame: 1:21

Absolutely do not promise that. That is not going up on buymeacoffee. com. Although donations of coffee are gratefully received. Yeah, we're talking about Bordetella in general and Bordetella pertussis in particular, Callum.

Callum: 1:35

Yes. So border teller. So we're back to the bugs. So just a recap to where we were. We were making a way for the gram negatives in the very logical order that we created and we cannot deviate from which strange, I guess in some ways, but there is a plan, dear listener just stick with the program

Jame: 1:53

the plan is we'll finish the bacteria if it kills us, which it just might.

Callum: 1:57

It might just kill us because man, there's a lot of

Jame: 1:59

Yeah, I mean, I've only got 20 years left in my career, Callum. I need to get a wriggle on.

Callum: 2:04

Yeah, you do need to hurry up with this. Maybe we need to release an episode every day and we probably still wouldn't,

Jame: 2:10

stop promising the loyal listeners stuff I can't deliver.

Callum: 2:15

I can't lift that either, unless this became a full-time job.

Jame: 2:18

Yeah and so we're gonna do our say, what we always do, an overview of the species in general and then significant diseases in particular. Callum, what do you know of Bordetella genus?

Callum: 2:31

well, Borella named for the Belgium Bacteriologist, Jules Borday.

Jame: 2:36

Oh, this is good.

Callum: 2:37

not sure how to pronounce

Jame: 2:38

Oh no, this is good knowledge because I didn't actually look that up.

Callum: 2:41

Yeah, 1906 Drs. Bordet and Octave Gengu, so they named the bacteria Bordetella, and Pertussis this is the bacteria responsible for whooping cough, a deadly disease of young children. And Pertussis comes from the Latin per, which means Intensive or thorough. I'm not really sure exactly what it means, but it seems to be like bad. And then tussus, which is cough. So when you're examining someone's chest, and they've got crackles, if you get them to cough and the crackle's clear, you call it tussable. So like coughable. Don't know if you ever come

Jame: 3:20

No, I didn't know that. No.

Callum: 3:21

So I remember a professor once was like, are the crackles tussable? And I had no idea what they were talking about.

Jame: 3:26

It's funny, professors have that peculiar knack of being able to dive deep into the medical literature and produce something that you have never heard of. But,

Callum: 3:34

Yeah, just to make you look

Jame: 3:36

And then you look like a complete idiot, yeah. Yeah. How many species are there?

Callum: 3:40

Of Bordetella, there are 16 species,

Jame: 3:44

And how many of them cause disease in humans, Callum? And how many are classical, Callum?

Callum: 3:49

3

Jame: 3:50

you name them, Callum?

Callum: 3:51

I can try. The first one is Pertussis, which is the one we're going to talk about a lot. Bordetella pertussis. That's the one that everyone knows. Then there's Parabertussis. And finally, bronchiseptica, otherwise known as the cause of kennel

Jame: 4:06

Exactly, yeah. This is much more of a problem for vets, but humans can get it.

Callum: 4:11

I have seen two cases of people with kennel cough.

Jame: 4:15

That's interesting.

Callum: 4:16

When I say see them, I've seen the agar plate with the bug on

Jame: 4:20

That's the same as seeing the patient and treating them and diagnosing them and getting them home. Everybody knows the Microbiology Lab is the actual linchpin of the whole hospital. Isn't that

Callum: 4:28

yeah, of course. Yeah, of course, yeah.

Jame: 4:29

And then the non classical species. Let's do a good old fashioned alternating nomenclature list off, Callum. Ansorpii. Bronchialis. Hinzii. Ansorpii.

Callum: 4:46

Bye.

Jame: 4:46

Petriae,

Callum: 4:48

Sputagena.

Jame: 4:49

And Trematum, and four other species not associated with human infection. And then the ones which are this will be of relevance later most of these are aerobic because most of them are infecting the upper respiratory tract. There are a few that aren't aerobic, and in the PrEP notes, we've underlined them. Galen. But they are Bronchialis, Flabulus, Pertreii and Sputagena. No. No, me neither.

Callum: 5:14

James, you're a bit of a history buff. What do you know about the history of pertussis?

Jame: 5:18

So yeah, pertussis also known as the violent cough, also known as whooping cough, also known as the cough of 100 days. They really had good names for diseases in the past. It was first described in 1578 during an outbreak in Paris. And so the disease was known about before the cause of organism, the cause of organism was isolated in 1906, as you said. And then in the 1940s, we developed a vaccine against it. And we revised that to a cellular form of the vaccine in sort of the 90s. But before then, actually, it was a major cause of infant morbidity and mortality. So Callum, talk to us about Pertussis in general. Where would you find it, and who are the kind of people that get it?

Callum: 6:04

Really this is a disease primarily of the very young. We worry about this most in, very young babies, less than one year. Also children, adolescents to a lesser extent. And then those who are unvaccinated. In the, high income countries this is with, adequate vaccination coverage. Is really not a significant disease, vaccine doesn't, really prevent you getting the disease, but it certainly prevents this or more serious end of the illness, but it can still cause problems in parts of the world where there isn't a robust immunization program,

Jame: 6:37

Yeah, so this is part of the UK. We'll talk about it in a second, but it's part of the UK vaccination programme, and most high income countries will have it as well. Where do you find it? In the human.

Callum: 6:48

We are the only reservoir, humans, are the only reservoir for Bordetellar pertussis. And it, it lives in the upper respiratory tract. As James said earlier on, it's strictly aerobic, so it cannot survive without oxygen present. And that makes sense. And yeah, the other organisms Brongiceptica is a disease of sort of other mammals as well, which can be transmitted to human, but it's pretty small print. And parapertosis is similar to pertussis in many ways, apart from it's just not as bad.

Jame: 7:15

Yeah, and the remainder are very little. You'll be lucky to encounter any of those in your career. Although we've both taken care of a B home SEI, endocarditis, haven't we Callum?

Callum: 7:28

Oh

Jame: 7:29

Back in the day. Very odd. Environmental exposure. And a metal valve. And just an unlucky patient. And had to stay on Meropenem for six weeks if I remember.

Callum: 7:38

Yeah, I think yeah, the message there is that there are many bacteria that don't normally cause problems until you've got prosthetic material or immune compromised patients, at which point you look them up and you don't memorize the stuff about them. You get them all the ID and you think, What is this? And then you go and look at the literature.

Jame: 7:54

One hundred percent.

Callum: 7:56

this is not the podcast for the weird and wonderful tiny little bugs. We only cover the main culprits,

Jame: 8:02

Yeah. The meat and potatoes. Fine. Will I go through the clinical syndromes?

Callum: 8:06

Yes, please do.

Jame: 8:08

So the just to say, in the UK at least, this is

Callum2: 8:10

A notifiable.

Jame: 8:12

condition, if you get it. The incubation is a week to 10 days, but that range extends up to about 20 days. But, beyond 10 days, you are unlikely to be acquiring it if you've had a contact. And the sort of main features are the cough, which is quite considerable, and the main clinical diagnostic criteria are a cough lasting more than two weeks, and one of paroxysmal coughing, post cough vomiting, So you cough so much that you throw up, and the inspiratory whoop that gives the disease its name, and that's a forceful inspiration after coughing fit, which you see mostly in children and the illnesses is described in sort of three phases. One is a catarrhal phase, which will be very difficult to tell from a normal upper respiratory tract infection. So the main features there are choriza, fever. a cough and conjunctival injection, and that will last between one and two weeks. And then you've got the paroxysmal phase, where you've got the paroxysmal cough and the whoop. Usually the patient defervesces at that point. The coughing is particularly worse at night. And then the convalescent phase, where the cough is the only thing that persists, but it slow resolves over a period of weeks to months. It can be very annoying for the patient, but I mean, there's literally nothing you can do in that phase. And then potential complications of that are pneumonia and that can either be the Bordetella or another colonizing organism. And very uncommonly, because of certain virulence factors the Bordetella can lead to the development of encephalopathy and seizure secondary to that.

Callum: 9:54

I've never encountered that. And to be honest, I don't know if I would ever have thought about it, but I guess, it's quite a classic clinical syndrome. Like when you see some of pertussis, when it's developed, you're more than 14 days in, it's pretty path economic, these These these coughing fits. Maybe not as classic and in your serving in the vaccinated host, but it's not I guess the other thing to say here is it is primarily a disease that will be dealt with by, community primary care physicians like general practitioner. Not something that often makes it to secondary care.

Jame: 10:25

No. Although we do, we are considering it more an ambulatory care so patients will, not necessarily need to be admitted, but they may make it to ambulatory care units as a sort of diagnostic dilemma. And so sometimes in, in the kind of work that I'm currently doing, we'll, it will be considered and there, particularly because of the effects of the pandemic, there's been. Reduced vaccination. And you might see this being considered at least in the, in England or sorry, in, in restarting in the UK, there's been a recent uptick in pertussis cases. That's mostly because the cases went through the floor because all of the stuff that you have to do to stop you getting COVID also stops you getting pertussis. So the they've still not reached pre pandemic levels, but they're getting close to it And so they've noticed this recent uptick and that's really, I think, why the UK HSA decided to update their guidance.

Callum: 11:23

Okay. That's what it can cause. And I guess we talk about the incubation period. So it's between seven to 10 days between being exposed and sent to onset. The infectious period is slightly different. It's generally considered that a person is infectious for 21 days after your symptom onset. So having both of those numbers is quite a useful thing to remember because then you can tie up, This person, they had symptoms on since this day, they're infected for 21 days, incubation period 7 to 10 days. Public health would be looking at that sort of thing if they're managing an outbreak. Talking of whom you mentioned UKHSA, the UK Health Security Agency, who, of course, are not anything to do with Scotland, so misleadingly named, but

Jame: 12:11

the UKHSA only managed public health in England and somewhat frustratingly, Health Protection Scotland only just changed their name to Public Health Scotland to align with Public Health England shortly before Public Health England changed their name to the UKHSA.

Callum: 12:27

Yeah, it's a public health body. I guess they, they had, they were taking a bit of flak, I think somewhat unfairly post Covid. So the, there was a name change, because as we all know if you change the name of something,

Jame: 12:38

Then everything changes completely. Yes, that's

Callum: 12:41

We're looking at you, Hermes.

Jame: 12:43

Yeah they, so they've got some definitions which are interesting to know about. I'm not sure that they're worth memorizing, but yeah so they've got suspected, confirmed and epidemiologically linked cases.

Callum: 12:55

Yeah, so suspected is new cough, obviously, plus one or more of, paroxysms of coughing, post tussive vomiting, so after coughing, vomiting inspiratory whoop, cough of duration 14 days or more. Those are the people that you'd be thinking about testing and then confirm to be the symptoms of pertussis as described, plus one of either a positive respiratory sample, so a nasal pharyngeal aspirate, or a nasal pharyngeal swab, a positive respiratory sample for culture, or a positive respiratory sample for PCR which is quite a commonly done test, or an antipertussin toxin IgG titer greater than 70 international units per mL serum, yeah and that's in the absence of vaccination in the last year. So basically you've got an antibody response without vaccination. So that's your confirmed. So basically as you'd suspect symptoms of pertussis and a positive test for pertussis, pretty straightforward, and then epidemiologically linked. So that's people who've got the symptoms of pertussis and you were in close contact of a confirmed case within 21 days or infectious period onset of their cough. And then close contacts in this context are defined as either household contacts or overnight stay in the same room. So that's your case definitions. But really, as we talked about earlier on, who do we worry about and UKHSA lists that into two groups. Jayme, take us through group one.

Jame: 14:23

Alright, group 1 are vulnerable infants. And so there's four categories. The first is unimmunised infants born at less than 32 weeks, that are less than 2 months old. Group 2 is unimmunised infants born at more than 32 weeks that are less than 2 months old, whose mothers did not receive Pertussis vaccine after 16 weeks and more than 2 weeks before delivery. The third group are infants between 2 and 5 months old. regardless of maternal vaccination status or gestational age and delivery. And the fourth group are infants between 5 and 12 months old who have not been fully vaccinated. So the reason that those last two groups are considered at risk is, of course, between two and five months, you're meant to be getting your pertussis vaccine. in the UK vaccination schedule. And so if you've not completed vaccination, or between five and 12 months, you haven't had all three shots of acellular pertussis, then you are at risk of getting the disease. And then group two is individuals who could transmit to group one and haven't been vaccinated in the previous five years. And more than seven days ago. Yeah, if and so they are Pregnant women over 32 weeks, because they should have received some testis vaccine. Healthcare workers who provide close personal care to group 1 infants and pregnant women. People whose work involves regular, close, and prolonged contact with Group 1 infants. So the example is nursery nurses that are working in the infant room. And the last group is people who share a household with a Group 1 infant. So anybody who is living I'm just going to say it. People who share a household with a Group 1 infant. So they will become more relevant when we talk about the UK HSA's guidance that they've recently updated in June 2024 for the UK.

Callum: 16:27

Yeah I always find it very confusing between these different guidances because they always talk about risk groups and its criteria. I find it very hard to remember, so I basically always look it up. If you're advising for an exam, then that might be something to

Jame: 16:40

This is something that the UK HSA can update you on as and when an uptick in cases as they have done.

Callum: 16:48

So that's our sort of risk groups and definitions and so on. So why is it, Jayme, that borotella pertussis is such a problem? And what is it that we're, how are we, how's the vaccine working?

Jame: 16:59

Yeah, so like the The interesting thing about Bordetella is that it's got a bunch of different pathogenic mechanisms, all of which need to be there in order for it to cause significant disease. Most of them are in B. pertussis, some of them are also in Parapertussis and Bronchoceptica, and the other ones, as far as I can tell, just basically don't have these mechanisms. So mostly they're toxins. So we'll start with pertussis toxin, which is seen in B pertussis. And it's an AB toxin. Do you remember your AB toxins, Cal?

Callum: 17:32

Yeah, so A B toxins is where there's like a two part to the toxin and one of the parts of the toxin is that the B part is the one that gets it into the cell and then the A toxin is the one that has the effect.

Jame: 17:43

they're also more commonly called EB5 toxins because there's five B components and they form a ring and form a pore basically and into that pore goes the A component of the toxin and usually, so cholera toxin works this way as well, pertussis toxin does too, usually what they do is in their target cell they'll increase intracellular cyclic AMP. Okay. And that will alter signaling. Pertussis toxin also does the thing where it inhibits G protein chemokine receptors in the cell. And what effect that has, is it reduces phagocyte chemotaxis. Because fewer chemokines are being produced by the respiratory epithelium, which is the target cell. And they also reduce phagocyte recruitment. And chemotaxis directly as well. So that's quite interesting. Tell me about adenylate cyclase toxin, Callum.

Callum: 18:35

So adenylate cyclase toxin. So that's commonly seen in pertussis, parapertussis and broncho optica. It's an RTX toxin and it binds complement receptor free and phagocytes, and that leads to cytotoxic pores and that leads to calcium influx and potassium e flux, which damages the cells. So it's basically trying to. Knock out your phagocytes. It also has intracellular adenylate cyclase activity, which leads to increased intracellular cyclic a MP which all again alters signaling. So it's similar in some ways to pertussis toxin.

Jame: 19:11

And then we've got filamentous hemagglutinin which is seen in pertussis. And then that has an attachment factor which promotes adherence to the host cell and biofilm formation.

Callum: 19:21

We've got perin, which is in pertussis and broncho optica, and that leads to adhesion to epithelial cells.

Jame: 19:27

And then Fimbria, which is more commonly known as an attachment pylus. So pyle are the thread like protrusions from,

Callum: 19:35

Yeah, I think it comes from the la Latin versus spear, is that

Jame: 19:38

Yeah from the gram negative cell wall, mostly. And they are important for adhering to cells and the formation of biofilm. In fact, they are essential for biofilm formation. Actually, fimbria. The cells latch onto each other and form a sort of web. And lastly, Callum, we have

Callum: 19:55

Tra cytotoxic, which is in pertussis. It's also in. Mysterio Gonorrhea, and Vibrio

Jame: 20:03

Yes, which I've never heard of. But yeah, so the, these also have tracheal the same one. As far

Callum: 20:10

And the tracheal cytotoxin is a soluble peptidoglycan, which is an important part of the cell wall, and it damages ciliated cells. So those cells that are sitting in your airways, getting all the gunk out. And that leads to impaired mucous removal from the upper respiratory tract. And I think my understanding is that leads to the paroxysmal cough.

Jame: 20:32

Yes, that's right.

Callum: 20:33

Because you don't have the reduced pathogen removal, your cilia aren't working so well, so then you're more, you're getting much more mucus and then leading to your coughing

Jame: 20:40

Yeah, it's like an acquired Cartagena syndrome. Really interesting.

Callum: 20:44

So there's some pathogenic mechanisms for you. Lab. Oh, should we do the thing?

Jame: 20:49

What thing? Oh. Okay. Micromode engaged. Yeah. What is this bug, Callum, that is causing us so much mischief?

Callum: 20:58

Yeah, it's it's gram negative. It's a coccobacillus, somewhere between round and oval. It's fairly small, I guess, in the realm of things. The size varies between 0. 2 to 0. 5 times 0. 5 to 2 micrometers. Micrometers. Micrometers. they are usually on the gram seen singly and they can also be in pairs and they're rarely seen in chains. They exhibit bipolar staining. And then they're usually motile or they can be non motile as well. And Jane mentioned earlier, they are strictly aerobic apart from those sort of small print species that we mentioned earlier on. So agar. So there is a selective agar for Bordetella. Known as often called Bordetella medium, and it consists of charcoal agar with kephalexin. And that's because Bordetella is intrinsically resistant to kephalexin. Bordetella pertussis generally grows poorly or not along at all on your Makonke, which is your sort of selective gram negative. And you might see it growing on nutrients or blood agar. If you on your request details put that you're suspecting pertussis or they have got paroxysmal cough, then the laboratory would put that up as a potential thing to look for. It grows at normal temperature, 35 to 37 degrees. It's quite slow growing, so it can take up to 5 to 7 days to grow. And. Yeah, essentially, when it looks on the plate, it's a sort of glistening greyish white colony. And then you do your Gram stain. The other thing that's useful to differentiate is an oxidase test. The things that we'll be looking for are Pertussis is oxidase positive, as is Bronchiseptica. And then, Parapertussis is negative.

Jame: 22:41

rest, just look it up. Yeah.

Callum: 22:43

Yeah, I think that's quite a useful differentiator, if there's an oxidase positive coccobacillus that's growing on a charcoal acre of keflalexin, you're probably looking at Bordetella pertussis. If you were feeling really mean in an exam, you might mention the history of a dog with kennel cough or something like that. There's a glutination that can be done and the specific antisere that can do that. But if you're growing on a culture plate, you're probably. You're probably going to mold it off it, aren't you being realistic, but you can do the agglutination tests and then refer on to the reference lab for confirmation.

Jame: 23:14

Yeah. Yeah.

Callum: 23:15

yeah,

Jame: 23:16

I'm not sure the hallucination, like how, what difference it makes in terms of like, how are you going to treat it? But, it's part of the SMI for identification. So I suppose that's interesting to know.

Callum: 23:29

other thing to say is, the, there's a classic appearance of the colony. So I mentioned there really is, but it's meant to be nearly transparent. So it's like a mercury drop. That's what it's called. Now, people might less and less likely see mercury. So

Jame: 23:41

Which is not transparent, by the way.

Callum: 23:43

blood pressure and like we measure so much things in millimeters of mercury. It's just, it's such like an interesting little historical thing every time you look at blood pressure I think about mercury. The other thing that's classic on the blood ag in the blood agar, I guess, would be a zone of hemolysis without a definitive periphery. So often see, when you see like beta hemolysis on a blood agar, it's quite defined edge.

Jame: 24:04

Yeah, but this just fades in

Callum: 24:06

yeah so yeah, and I guess we would refer these on to if you're growing them onto a reference lab and to confirm ID

Jame: 24:13

Yeah particularly pertussis and parabertussis, I don't know if you do it for the rest of them. Although, I'm sure the reference lab would be happy to help. But yes, we would usually send them down to Colindale and they will confirm the identification and they will confirm the serotype as well, which I think is, actually I think that's good for epidemiological purposes.

Callum: 24:35

I guess the other thing to say is that it's quite slow growing and It's not something that we're going to do sensitivity testing on, which we'll come on to, I

Jame: 24:42

no, the reference lab might, but I think most of the time, diagnosis is done by PCR these days.

Callum: 24:48

But you can grow it. And sometimes it comes up as a bit of a surprise. The people that I'd been involved with the Bordetella bronchiseptica, it was a, what's this weird organism? Oh, the molotov ID is this. It was not expected, but then when you read through the patient history, it was like, they have a dog. The dog has not been vaccinated against kennel cough. There you go. And I guess just the other thing to mention about testing, I guess, is when to test. Because it is a bit confusing and I think it's worth maybe just spelling this out. James put this in a really useful table about when to test.

Jame: 25:19

Cam, this is straight from the mouth of the UK HSA. They've got a brilliant sort of one page, everything a GP needs to know about testing. And so it's taken from that. And I've actually linked to it in the show notes.

Callum: 25:31

go read that guidance. But if you don't have time, then essentially you divide up the testing by the weeks from onset of cough. So if it's less than two weeks from onset of the cough, the patient's symptomatic, you can do the PCR tests, you can do a culture. On the upper respiratory samples that we mentioned earlier on. But you can't do serology because it'll be negative. Two to three weeks, you can do all three. And then if it's more than three weeks from onset of cough, you're not meant to do the PCR culture, but you can do the serology. So yeah, that's testing. Treatment! James favourite.

Jame: 26:05

Yep, let's kill these bugs. Although, killing them is not as fun as the other ones. There's basically only two options. Macrolides or cotrimoxazole. And that's it. So there's no UCAS breakpoints, Cal. There's just clinical use. Historical usage. And in terms of when to treat you need to do it within two weeks of the onset of the cough. So if you're seeing a patient after that, it's not really worth doing. There's not enough bug left at that point really. It's all symptoms. And in terms of close contacts, again, you're not usually going to be doing that after two weeks. of the onset of the case's cough. So it's whoever they've had contact with. The only exception is in between two to three weeks because they're still potentially able to transmit it. If the contact, not the case, was a pregnant woman or they were in risk group one, so one of those infants that we discussed then you might consider doing it. What would you use? You would use the appropriate dose of clarithromycin, azithromycin, erythromycin, or cotramoxazole. For pregnant patients, they prefer firstly in the UK erythro, And then azithro, and then clari, and then lastly cotrimoxazole. Of course there are concerns about using cotrim in the first trimester because trimethrin is an antifolate and the neural tube is not closed yet before the end of the first trimester. And then in the third trimester, of course, there's worries about the sulfamethoxazole causing Issues with, G6PD deficient infants etc. So macrolides are preferred overall. The other options that we've got, there's some limited human data for the use of piperacillin, and also kefiperazone sulbactam, which I'm not sure we've got access to in the UK, but I suppose if you have enough time and money you can get access to anything, can't you Callum? And the other thing to talk about, which is the main treatment, if it can be considered treatment, is exclusion from community settings. Now this is something that, isn't unlikely, and a lot of the time that's handled by the health protection local health protection team. But the main way that you stop, Bordasella having an effect is you stop it spreading. To other people. And so, for, we've got a table, I'm not sure it's worth going through in intense detail, but we'll just talk about children and healthcare workers, say so from children, you would exclude them from school, either two days after starting antibiotics, because then you're considered to be non infectious, or two weeks from cough onset, And then the same applies to healthcare workers that are working in a healthcare setting caring for group 1 infants or pregnant patients. And then lastly, an inpatient would be placed in respiratory isolation until 2 days after starting antibiotics or 21 days. from onset of the cough. So for some reason you can't give them a macrolide and you can't give them a cotrim, you're placing them in respiratory isolation, and you're doing that for three weeks or until discharge, whichever comes soonest. In terms of chemoprophylaxis, for close contacts, you would give them chemoprophylaxis and the same sort of antibiotics that we mentioned. If the case had an onset of cough in the previous two weeks, or the close contact is in a group one or group two, as defined by the HSA, so either an infant or somebody who's at risk of giving it to an infant. And if the case is a healthcare worker, you would give chemoprophylaxis to pregnant patients over the age of 32 weeks who have not had a vaccination in the past five years and more than a week ago. Group one infants, Or a health care worker, as in the contact is a health care worker providing care to a group one infant who haven't received a vaccine more than one week, but less than five years ago. This makes a lot more sense of you if you read it in the UK HSA document, which we have linked to at the bottom of the show notes. And of course, if you are listening from outside of the UK, It's all good advice, but none of it will apply in your local setting. And you will have different advice to go by. Sorry about that.

Callum: 30:30

Yeah,

Jame: 30:31

But what about resistance, Callum?

Callum: 30:33

Resistance is a concern globally and the reports were coming up from China. So I've heard people talk about this locally where people have been worried about macrolide resistance. And, to date we've not seen it in the UK. Okay. Immediately, it's not something that we are seeing and, hasn't been confirmed. It may be here, I guess, but you would expect it to be picked up. But the places that has been reported is China, so I think there was a, was it a publication? Is that where it's come from? Where They looked at an outbreak and they said that 60 to 92% of cases had macrolide resistance. And that was through a single nucleotide polymorphism and it was a 2 0 4 7 G. So that was the sort of an a has, has been placed into a G at location 2 0 4 7 and the 20 and the gene that sort of, codes for the 23 s RRNA gene. And that's also been reported in Iran. There's been some other literature studies, I think in Finland they reported it and basically had, they had zero

Jame: 31:41

All over the EU, there have been very sporadic reports of this mutation. But this seems to be the only stated mutation. That's the one that they check for in the reference lab. And the, what does it do? It alters the binding site for macrolides in the ribosome RNA. That's seems a bit strange to me that there's only one SNP to worry about. And so they do. Look for others, but they haven't found any as far as I can tell in the document I looked at. And then when it comes to code remarks is all I couldn't find any resistance data. For Bordetella. I think the main problem will be tolerance or appropriateness in the risk group. But I mean, fortunately, for Bordetella, we have a vaccine. So let's talk about that. So we used to have a cellular vaccine, but that tended to cause encephalopathy and seizures. Not in many people, but in enough people that we wanted a replacement. And so in 1991, an acellular pertussis vaccine was implemented. And so that's the one that now people people get. Yeah but yeah, so the main vaccine that's used in the UK paediatric schedule is the DTAP IPV HIB, which is Diphtheria Tetanus Acellular Pertussis

Callum: 33:03

that is basically poliovirus.

Jame: 33:05

poliovirus and Haemophilus influenzae type B. And those are all given at 16 weeks. And by about 5 months, you would expect your kid to be immune to all of those, including pertussis. It's about 95 percent effective. Contraindications would include anaphylaxis to previous pertussis containing vaccine. Polymyxin B and neomycin those two are

Callum: 33:33

I think they're used in the preparation

Jame: 33:36

In the prep for the, yeah, fair enough and yeah the sort of advice for any patient that gets pertussis, if they are unvaccinated or partially immunised, is to complete immunisation after recovery. For pregnant patients, you meant to offer it 16 to 32 weeks. So usually that's given at the 20 week scan that, that is relative routine. But if they present late, like over 32 weeks, carl yeah. So if they present more than 32 weeks give it anyway. And the reason is that this is going to give passive immunity to the child. Both transplacentally and in breast milk as well. And in terms of close contacts, would you offer vaccination? You might do if the patient was under 10 years old and unvaccinated or partially immunized. Uh, if they're pregnant over 20 weeks who haven't received any vaccine in the pregnancy. You might do that. You would want to do that routinely anyway. And finally, if they're a healthcare worker providing care to pregnant patients or group one infants and they've not been vaccinated in the previous five years. And that Callum, is that.

Callum: 34:45

Yeah. That's vaccination. And so just to summarize what we've gone through there very briefly at the end. So we talked a little bit about the history of Bartitella pertussis, a violent cough or the cough of a hundred days, which I think is my new favorite way of talking about it. The cause of whooping cough. I was just thinking there that the symptoms can last up to three months, which is almost a hundred days. So that's going to help me memorise that. We talked about, it's a sort of usually, Bordetail pertussis is a strictly aerobic pathogen. It's in the upper respiratory tract. It's mainly a risk for children under one, particularly those who are unvaccinated. And it causes this paroxysmal coughing. Talked through the case definitions and risk groups. Group one, vulnerable infants. And group two, people that can transmit to group one. Pathogenic mechanisms, mainly around affecting how your immune response goes. Lab diagnosis. Gram negative coccobacillus, it's oxidase positive, it's aerobic. The testing schedule, depending on how long you've had symptoms. Treatment with macrolides, cotrim and then exclusion. And finally, talked a bit about vaccination. And we've got some links to the UK HSA guidance, which is really useful. The UK SMI on the diagnostics and also the final thing that we didn't mention was the green book on pertussis which is also published by the UK health security agency and has some really useful information on the vaccine. If you're interested in the integrity of the other vaccine.

Jame: 36:11

Lovely.

Callum: 36:12

If just to wrap up, if you were if you didn't find this very interesting I would say if you were bored, don't tell us. Bored to tell us.

Jame: 36:21

Yeah. Board, don't tell us. See you later. Bye.

Callum: 36:24

Bye.