Description

It is proposed that the webinar will follow this outline:
• Neonatal calf diarrhoea – the big players
• The important role of colostral antibodies
• The resecretion of antibodies and the important role played in protection at a gut level
• Vaccination – why vaccines might fail and what does that mean for your farmers
• Existing ways of boosting neonatal calf defenses
• Understand the interaction between the various pathogens that are responsible for neonatal calf diarrhoea
• Have an understanding of what makes up the various IgG components in colostrum
• What is meant by the resecretion of antibodies?
• Identify how resecretion of antibodies plays a key role in protecting the neonate at the level of the gut
• Understand the reasons why a vaccination programme may be ineffective
• What steps may be taken following the identification of a problem to alleviate the situation and lessen the impact on neonates
 
With thanks to Forte Healthcare for sponsoring.
NB: For those veterinary surgeons practising in Ireland this webinar is approved by the Veterinary Council of Ireland for 1 CVE point live and on demand (until 31st December 2023). Approved course no: 22-23-09
VCI compliant CPD certs for Irish attendees are available on request please email: [email protected]

Transcription

OK, so, yeah, welcome everybody. Thank you for attending tonight's webinar, today's webinar, depending where you are. My name is Silveyansky.
I'll be your chair for tonight, and, yep, thank you very much for attending. Thank you, to Forte Healthcare for sponsoring this talk. If I can just ask, all of you listening in, if you can write your questions into the Q&A box rather than into the chat, that'd be useful.
Thank you. And thank you, Nicola for being with us here today. Nicola Gladden, she graduated from Royal Dick School of Veterinary Studies in Edinburgh in 2006.
Since graduating, she worked in a mixed animal practises in England and Wales, and then later in 2014, she returned to Scotland to further specialise in cattle health and production, and to and study for the European diploma in bovine Health Management. And Nicola has joined the European College of Ban Health Health Management as a diplomat in 2019. And has completed a PhD studying peripatrian welfare in of cows and calves in 2021.
So wow, lot lot's going on there. We're very, very, pleased you can join us and give us this talk tonight, and tonight's talk is titled Fresh Ideas on Neonatal Passive Transfer in Calves and the Implications for scars prophylaxis. So thank you very much again and over to you, Nicola.
Thank you very much. So for that, that really nice introduction and thank you, everybody for joining us this evening. Welcome, welcome to the webinar.
So yes, I've just been asked to talk about, neonatal passive transfer and some implications for scour prophylaxis there. So, We're going to start off just talking a little bit about neonatal immunity of calves. And of course, we can't miss out lustrum and, and passive transfer.
So there's a little bit on that. We're going to move on to neonatal calf diarrhoea, and then at the end, have a little bit of a think about how we can maybe optimise and harness the calf's immunity to aid in our management of, of scour problems on the farm. So if we sort of start at the beginning and, and think about the immunity of our neonatal calves.
So neonatal calves would be calves within the first month of life. And the immune system starts developing actually quite early in gestation at around about 100 days after conception. And, calves are actually, they're born with a fully developed immune system, but it is quite immature.
And we also know that, birth stress can have a negative effect on that very early and immature immune system. We can see here, if we look at this graph that, the cytokine responses, they actually steadily decline after birth, but then by about 5 days of age, they're back up to birth level. And the reason for this is because cortisol concentrations in newborn ruminants are quite high because that's normal for ruminants, because, parttuition is initiated by a rise in foetal cortisol.
However, cortisol also, as you'll know, has an immunosuppressive effect. So this is, this is sort of a side effect of this. And this happens in, in all calves, but we do know that calves who have, difficult births, who maybe are assisted at birth, they typically have an even higher cortisol concentration when plasma or blood cortisol is measured.
At birth. And so it's reasonable to assume, I think there's not really been any studies specifically looking at those calves, I think it's reasonable to assume that probably the immunosuppressive effect is even greater in those calves. So those calves probably need a bit more help in the first few days to weeks of life.
And the calf immune system, once the calf is born, interactions between the mucosal immunity, which we're going to go into in a bit more detail in a minute, interactions with various microorganisms initiates the maturation of the calf immune system. So think about the mucosal immunity, the largest immune organ in the body. And in actual fact, About 90% of pathogens, will meet the mucosal immune system in the, in, in the first instance.
And the microbiome, the microbiota of this mucosal, system is really vital for maintaining, a healthy, mucosal immunity. And colonisation of this starts at birth with exposure to bacteria of the dam, and then is it fairly closely followed. By, exposure to, bacteria within colostrum, particularly there's lots of sort of inverted commas, good bacteria in Colostrum.
And that helps to also, start to colonise the, the microbiota of the mucosal immunity, and particularly with colostrum, as you might expect, because it's ingested, that's particularly important for the gastrointestinal immune mucosal immunity. So if we think more about the enteric or the gastrointestinal mucosal immunity, it's really very important first line immune defence for our calves. We know an awful lot of, of, pathogens are ingested, and it might be the first line of defence for, for these.
Pathogens. It has extremely high concentration of lymphocytes in the gut mucosal immune system, and really high numbers of antibodies as well. In actual fact, there's a greater antibody concentration in the enteric mucosal immunity than there is anywhere else in the body.
And the first line, I suppose, is, is there's a physical barrier, which is a combination of the commensal bacteria that are present and other microorganisms. Also mucus secretions as well. So, mucus is a fairly unpleasant, material for, for pathogens, and they get all stuck in it.
And also paras lysis as well, actually has a really important thing. Obviously, peristalsis is important for passing ingestor through the gastrointestinal tract. But also, if the guts are continuously moving, that makes it more difficult for pathogens to adhere to the mucosa.
So peristalsis is an important immune defence as well as, for its role in digestion. And that barrier then is also complemented, by the innate immunity and acquired immunity of the enteric, mucosal system. And, all of these three components are integrated, to create a pretty quite effective, actually, immune defence, in the gastrointestinal tract.
So if we just think about this sort of schematic diagram of, of some intestines here, and we think about it, the immune response to enteric pathogens, these are pathogens that are ingested. This immune response all occurs at the mucosal level. So it's very localised immune response.
And this means that, because there's no blood vessels level. Immune, proteins and immunoglobulins, etc. That are circulating, actually do not have a very important role in, this localised immune system.
This is, all happening at this level. And it's just worth bearing that in mind for some of the future things that we chat about moving forwards. So if we think about this mucosal barrier, and it's primarily comprised of a mucous barrier, mucus is really, really important, for this.
There's enterocytes, which is epithelial cells. So obviously, if we're not in the gastrointestinal tract, it won't be in terocytes, it will. Other epithelial cells.
And then also immune cells that are secreted from the laminopropria into this layer. And overall mucosal health is dependent on good health of each of these three structures. Together they form what's called a kill zone within the mucosa.
And the kill zone comprises of the inner mucus layer, and also within this mucus are, bactericidal sort of defensive proteins, and also, IGA immunoglobulin, as well. So this is just in a more sort of close up diagram of, of the mucosal barrier. And if you look here, this sort of inner mucus layer, this comprises sort of primary aspect of the kill zone.
And then this outer mucus layer, this is colonised by the microbiome. So that's also contributing to the local immune response, in the, in the gut or on any mucosal surface. Now, if we think about enteric immunity a bit more specifically, this is quite a specialised, immune site, because not only does immunity in this area need to protect the animal, the body against pathogenic organisms.
In the intestines, that also needs to be tolerant to commensal bacteria, but also to dietary antigens as well, so that the animal does not mount an immune response to, to food and to milk and, and things that, might be ingested that we don't want an immune response to. And This is a particular field of interest in the human field because there are a number of autoimmune conditions in that we see in people. That, where this sort of balance becomes unbalanced.
So this is a very specialised feature of the enteric immune system. And this is largely driven by the microbiome. So the microbiome and the microbiota, in the outer mucus layer, that, helps to maintain this balance.
And so this is really vitally important for healthy mucosal immune defences. And this is established, in the pre-weaning period, in the very first days or so of life, actually. Thought that colonisation of the mucosal layer, starts at birth with exposure to dam bacteria.
And for calves that are born with a sort of her vaginal birth, that is from the dam's vaginal mucosal layer, and mucosal microbiota there. However, there is some more recent evidence that suggests that possibly, colonisation may even start in utero, and there's some in utero exposure, but this is still currently a little bit unclear. But this sort of research is starting to challenge the, the paradigm that, colonisation starts at birth, and, and the mucosal defences are, are maybe, almost sterile at birth.
That may not be the case, but, but the work is still currently ongoing. And then, as you might expect, after birth, continued, development and establishment of this healthy, microbial, layer and commensal microbes, continues with colostrum ingestion and also environmental exposure as well. So, as I said, this is a vital, layer for development and maintain maintenance of enteric immunity, and particularly in the first few days of life, it's quite a dynamic population of bacteria that are found.
And initially, you start with faculty of anaerobes in the intestines there, but as oxygen gets used up, because the Intestinal surfaces, within just a few days of life become anaerobic sites. The, population of, of bacteria changes from faculty of anaerobes to strict anaerobes. And in the older animals and in adults, the population there is a more anaerobic population of bacteria.
But, as you might expect, alterations to this microbiome, they can negatively affect enteric immunity, because it's so important for healthy immune defences in the gastrointestinal tract that, any alterations will have a negative effect on the ability, the localised immunity to defend the animal from any ingested pathogens. And that's not just because of the loss of good bacteria, but Also, because we know the kill zone becomes depleted. You see that diagram there, I've just almost completely removed the, the kill zone because a very narrow, kill zone.
And then that in itself means that you've got reduced barrier defences. You've got less mucus, you've got fewer, or lower concentration of immunoglobulin, particularly IGA, and also these defensive bactericidal proteins present as well. And we do know that the faecal microbiome, which is often what's tested because you can, you can test that in live animals without having to remove parts of the gut.
If you compare calves with diarrhoea to healthy calves with no diarrhoea, the, the, Bacterial populations there are quite different. And, it, we, it's seen that commensal bacteria are replaced with pathogenic bacteria that are not always bacteria that are considered classic scour bacteria. And it's possible that these, sort of Extra pathogens, so to speak, possibly contribute to the presentation of diarrhoea in these calves, and maybe even be making this condition worse for them.
And we, it has been found that diarrhoea, calves with diarrhoea, Fusobacterium is more prevalent, in the bacterial populations isolated from diarrhoea, and that has been linked with cryptosporidium infections, and also in cars with rotavirus infections, Clostridial bacteria have been found to be more prevalent in the diarrhoea of those carbs, it's possible that these are having sort of multifactorial and contributing to the more wider scour syndrome that we're seeing. And, maybe to, to labour the point slightly, I suppose, but if we think about the neonatal microbiome, this is affected by both internal or host factors, and also external or environmental factors. We've mentioned already about establishment of those, commensal bacteria, by the calf being exposed to the dam, and also to colostrum.
And also to the environment, but also within the calf, the maturity, the gastrointestinal, tract affects the populations of bacteria that are present. And as also the maturity the immune system does as well. So, for example, a ruminating calf will have a different, population.
Of commensal bacteria, slightly different to a pre-ruminant calf. And if we think about our newborn calf again here, this calf initially has been, because that calf was, was born to a normal calving, been exposed to the dam's genital tract and vaginal, commensal bacteria. She's licking the calf in this picture, too.
So bacteria that are on the oral mucous membranes and from the tongue. That calf is, is being exposed to those as well. And then also, if the calf suckles, she'll be exposed to bacteria that are on the skin.
Primarily the teats, but as we know, calves, they do tend to try and suckle from the legs and from the underneath, the ventral abdomen and, and other, other areas until they find the teeth as well. So all of those, bact. Populations that are on the dam are being transferred in the, even during part tuition and immediately after birth to this calf.
And those populations are further influenced by the populations of bacteria that are present in other cows, because they're contributing to the environment. And of course, the, the environment itself, so the straw and, and the shed. If we think a little bit more about colostrum, as I said, it really does play an essential part in the development of this microbiome.
And we do know that colostrum deprived calves, when their, commensal enteric bacteria are, analysed, more, more pathogens are isolated. There seems to be more prevalence or higher prevalence of pathogenic bacteria. In the enteric microbiome of colostrum deprived calves.
Conversely, heat-treated colostrum does also seem to have an effect. And actually, a study has found that if the calf, lostrum was pasteurised, and in this study it was pasteurised. For an hour for 60 minutes at 60 degrees, which is what's, recommended for balancing that, not deatturing the proteins with, hopefully removing or reducing the concentration of, of pathogenic bacteria.
And that study found that actually, there was a higher proportion or more a higher prevalence of beneficial bacteria, in the microbiome of these calves that had been fed pasteurised colostrum, compared to calves that were fed unpasteurized colostrum. It's also worth noting as well, that actually, the carbohydrates that are in lostrum are, really great for bacterial growth. They're a great substrate for bacterial growth, which, of course, does mean that storage of colostrum can sometimes be, be tricky, particularly in, in hot weather.
But when the colostrum is inside the calf, it's really helpful because it helps to promote micro the growth of the microorganisms in the gastrointestinal tract. So we can't really mention colostrum without talking about passive transfer. But this webinar is, is not really, focused on passive transfer, and this is something that I think we're probably all quite familiar with.
But just briefly, calves and also other ruminants as well are born practically a gamma globu anaemic, due to the quite specialised coilleddenary. Placenta that's present, which, prevents the transfer of immunoglobulins across the placenta. So because of this, they have to ingest immunoglobulins shortly after birth, and they are transferred passively, through the tight junctions in the gastrointestinal tract.
Of course, Colostrum is the primary source of these immunoglobulins, but Also, it's a source of glucose and growth factors and other important factors as well. The glucose, in particular, is really quite important because calves are usually born, fairly hypoglycemic. And, and so they do need to ingest lostrum, for, to return to a normal glycemic level, pretty soon after birth.
So if we think about the immunoglobulins in just a little bit more detail, so the primary immunoglobulin in lostrum is IgG, and that is mostly IgG one. And that's really important for early life immunity. There are also smaller concentrations of IgGA, which is important for intestinal immunity, and it helps to prevent attachment of pathogens, to the small intestine and protect that mucosal barrier.
IGM is also present as well, and the role of IGM is to sort of identify and destroy bacteria that are, in the bloodstream. So hematogenous bacteria. And because of that, IGM is quite an important mechanism of defence, for its contributing to the defence of septicemia.
If we think a little bit more about IgG, the IgG is quite interesting in the newborn calf, because, IGA, although IGA is the primary immunoglobulin for enteric immunity in very newborn calves, the concentration in that kill zone is not as high as it is in older calves and, adult animals with a more mature mucosal barrier. And so, IGG is really important for contributing to that localised, immune response to enteric pathogens. What happens is circulating IgG one is re-secreed from the circulation into the intestinal lumen.
And, for every 100 grammes of IgG1 ingested, about 2 to 4 will be grammes, will be re-secreed each day for the 1st 2 weeks or so of life. Interestingly, IgG 2 is not re-secreted, and it's possible that this is why IGG1 predominates, in cow colostrum, although it's still a little unclear. That's slightly speculative.
How does this affect us though? Well, it sort of affects us because intestinal IgG one and serum IgG one concentrations are very closely related. So, We can't directly measure intestinal IgG1, but our normal sort of measures of quantifying passive transfer, so whichever you choose, your ZST tests or your total protein, or even your IG, elizers, whatever you choose, they tend to, although they are not specific for IgG, or even IGG1, because the prevalence, or the concentration of IgG, and particularly IGG1, is so much higher than IGIA or IGM.
They do offer those tests do offer a reasonable proxy of, of the, likely concentrations, of IGG1 that's, And the calf has, has gained through passive transfer. And so, if we measure serum total protein, or even, directly IgG, and that is quite high, then we can make a reasonable assumption that the, local effects and the re-secretion into the enteric mucosa is also Going to be quite high and provide good, local immunity for that calf in the first two weeks of life, while the immune system is maturing. Conversely, of course, if the calf has poor or failure of passive transfer, then we can assume that that's also going to be having a negative effect at local mucosa level as well.
And here's just a, a little diagram, if you remember again about our kill zone, and these, epithelial cells here, and IgG from the bloodstream, is re-secreed from the bloodstream, probably through reverse pena cytosis. The exact mechanisms are still a little unclear, but, re-secreted into this inner mucosal layer to provide support for this localised immunity until the IGA defences have become more mature. And this is probably the primary, excretion method as well of, of IgG, because it's re-secreted, and then it's not reabsorbed again.
It's excreted in the faeces. So, just for completeness, if we think about other important immunological factors contained in Colostrum, contains factors such as cytokines, maternal white blood cells. These are viable white blood cells, although, and it's thought that, they're certainly important for development of, the calf's immune system, although that most of them are not, no longer present after about a week of life.
So they're exact, mechanisms are currently unclear. And there's also some iron binding proteins as well, which again, are thought to be important for the development and selection of commensal bacteria. So.
Again, we're going back to this microbiome and the importance of that. There of course other nutritional and non immunological factors as well. And the one thing that probably is worth noting there, just as a, as almost as a side point is there are a num a number of enzymes and enzyme inhibitors included in Colostrum, but one of them is gamma glutamyl transferase so GGT.
And it's always worth just remembering that, because if for any reason you were to blood sample a calf to do a routine biochemistry on a calf in this sort of, you know, 12 or 3 weeks of age, GGT will, if that calf has had adequate passive transfer, invariably, exceed the upper limit of the reference interval for adult animals that's often provided, by the laboratories. And that's completely normal. That's not indicative of liver or bile duct, disease.
And in actual fact, GGT can be used as a proxy measure of, passive transfer as well. So, having thought about the immunity, if we, move on to sort of neonatal calf diarrhoea, which is more the, the sort of focus of, of this webinar, and this is diarrhoea. It's generally defined as diarrhoea occurring in calves under 30 days of age.
And there are a number of different types of diarrhoea that we can see in animals of which these top 3, so maabsorptive osmotic and secretory diarrhoea are. Ones that we're really thinking about in this first month of life. And essentially, what happens is they all result in increased fluid in the gut lumen, and decreased solid solidity of, faecal output.
So just briefly, if we remind ourselves, neonatal calf diarrhoea is really very common. I'm sure we're all aware of that. And there's a prevalence of about 20% in most studies.
Obviously, that's quite variable, but that would suggest that globally, about 1 in 5 calves has diarrhoea. And in calves under 1 month of age is the leading cause of death. And actually week two of life is when death tends to peak.
So that's when the calves are most likely to die, scar related reasons. And it can be causes, as I'm sure we all know, by both infectious and non-infectious causes. And these top 4 would be sort of the big 4 when it comes to infectious causes of neonatal calf diarrhoea.
Giardia, we sometimes see and it's more prevalent in some countries than others. Salmonella, is something that doesn't really have that much of an age distribution. So it's always worth considering, particularly because of its zoonotic potential for some types of salmonella.
And if we think about the scar pathogens, I've just put coccidiosis at the bottom for completeness, but we don't consider that to be a neonatal calf diarrhoea pathogen, because we're usually seeing it in calves over a month of age. But I don't know about any of you when you're in vet school, but I can recall when I was in vet school, having a very clear list, E. Coli, cars of this age, cars of this age, we rotor in coronavirus, and cars of this age.
Will be crypto. And it was very, clear cut in a very sort of black and white situation. As we can see, actually, the typical age at which calves are infected with these conditions, really is quite overlapping, and it's not quite as clear cut as as I was certainly, led to believe in, in vet school.
And this means that you can get, Multifactorial infections and multiple, kind of co-infections with, with more than one of these conditions. The only one that I would say is, is quite age-specific is E. Coli.
So, the upper end of the age range of E. Coli, there's overlap. But in these very young calves that get E E.
Coli, if they're sort of less than 4 days of age, that is usually quite specific for E. Coli. I'll explain that on this slide.
So the E. Coli diarrhoea that we see in cars of this age is an enterotoxigenic E. Coli.
There are other types of pathogenic E. Coli that can cause diarrhoea at other ages in older animals, and also, of course, in people. But they're less common.
And it causes a secretory diarrhoea, usually in calves under 4 days of age, although not always. And it's pathogenicity is particularly driven by these virulence factors. It's got a fimbral antigen, and then it produces a heat stable toxin as well.
And if the calves ingest eate, often it's at or very shortly after birth, and it's from the environment. The antigens bind to the small intestine, and that allows E-tech to proliferate and establish itself in the cast small intestine. And then it can produce a heat stable toxin.
Which stimulates chloride secretion into the intestinal lumen of the calf. Because the chloride concentration in the lumen, therefore increases, you get water moving due to osmosis. That's why it's called secretory diarrhoea, because you've got secretion of chloride irons.
And then, of course, that results in diarrhoea. Now, the reason that, ETech is quite age-specific is because the expression of, Proteins that allow, the antigen binding at this stage, that expression declines with age. And after calves are approximately a week of age, they don't express those factors.
So at that stage and older, these antigens can no longer bind to the small. Intestine. So the rest of the, of the pathogenesis story also can't occur.
And any e-tech that are ingested by calves that are maybe 2 weeks of age or adult animals will just pass through because they're not able to adhere to the small intestinal epithelium. So a second one to consider is crypto. And cryptosporidium is very, very common, and it can be quite challenging to manage, actually, because, controlling the ecy concentration in the environment can be very difficult.
They're very resistant, Eoys are very resistant. To a lot of our measures. And also the amount of shedding of these calves, particularly dairy calves.
There's some studies that suggest that beef breeds may be shared a little bit less than dairy breeds. But they shared an awful lot per gramme of osis per gramme of faeces, which means they become a very significant source of infection to all of, all of their peers, in the same pen or or even in in the next door pen. Now, crypto actually causes direct effects on the villi of the intestines and results in villous atrophy, which has traditionally been thought to be due to a cytotoxic effect.
So, a toxic effect on the enterocytes. However, More recent research is suggesting that maybe crypto actually induces apoptosis, which reduces, the, the amount of vili present. But again, it's a little unclear.
But the upshot is that we get a malasorptive diarrhoea with cryptosporidium. Think about rotavirus. This is a very, very common cause of diarrhoea.
And actually one study found that almost 100% of calves, it was isolated from, just because, a pathogen is isolated, though, doesn't necessarily mean it's the cause of the diarrhoea and a lot of calves, where rotavirus is isolated from actually have healthy faeces. However, very commonly coinfects calves, there's a common co-infection found with other scour pathogens, and it is definitely very possible that infection with rotavirus, Also contributes to, sort of, again, the scour sort of syndrome. So if a calf becomes also infected with cryptosporidium, as well as rotavirus, then the outcome of that is likely to be more severe diarrhoea than if the calf was only infected with, with one of those two pathogens.
It also causes both a malasorptive and a secretory diarrhoea rotavirus. So it can be quite unpleasant. Finally, if we think about coronavirus, again, also very high prevalence, similar to rotavirus can be isolated from high numbers of calves in the herd, and also from calves that are apparently healthy and healthy faeces as well as calves with with diarrhoea.
Coronavirus is also a common coinfection in these cases. Now, interestingly, coronavirus, also has a direct effect on the cells and it actually results in loss of enterocytes. And so because of that, that often means that The calves take longer to recover from Coronavirus, because to achieve full recovery, those enterocytes, need to be replaced, which takes a little while in comparison to some of the other conditions where there's no cell loss.
And so, the, the animal can show apparent recovery more quickly. And so if we have coronavirus here, and we get lost, you can imagine if those, and sites were lost, then they need to be, replaced, before the, before the casts, local immunity in the gut, is restored to sort of it's, it's full function. And that's because these enterocytes, these epithelial cells are really important, for producing, or sort of re-secreting the IGA and also the other, bactericidal proteins and defence proteins, that are found in the kill zones.
So if you get enterocyte loss, you also get reduction of function of this local, localised mucosal immunity here. So, what can we do to maximise the calf's own enteric immunity to manage or hopefully even prevent scour in our newborn calves in their first month of life? Firstly, we need to optimise colostrum management, and although this webinar is not focused on lum management, I don't want anybody to leave here thinking that's because it's not important.
It's just because that's well covered elsewhere. Colostrum management is the keystone in, the key factor in maximising the enteric immunity. And, I think we discussed quite a lot about the factors of colostrum outwith immunoglobulin that support the enteric immunity.
So, it's important for the microbiome. It is important. For the immunoglobulins.
It's important for all of the cytokines that it brings with it and and the immune defence cells and etc. Etc. That are produced from the from the cow.
So, The importance of colostrum, although we are typically very focused on immunoglobulins, the importance of colostrum is actually much wider than that. And so it really is vital that colostrum management is optimised. And of course, as we all know, by that, we mean ensuring adequate quantity of colostrum.
Of good quality colostrum provided quickly also needs to be harvested quickly as well. And also calves should be fed first milking colostrum, because every time that a cow is milked and colostrum is harvested, The IgG concentration of that harvested colossum or transition milk is reduced with each milking. So the IgG or immunoglobulin and more generally concentration.
Is always highest in that first milking, and that would what we would consider to be true colostrum, and that's what should be fed to calves. The transition milk and the later feeds, of course, do have importance, but it's this 1st, 1st feed and first harvest that is most important from an immunological point of view. Clossum needs to be quite clean as well.
As I said earlier, we don't want it absolutely sterile, because we do want, some of these good bacteria to be present in the colostrum, for the calves, mucose development and establishment of the calves mucosal immunity. And then, of course, it is important to quantify our passive transfer and our cluster management, because if we're not quantifying, by measuring passive transfer and monitoring this, it's quite difficult actually to assess how well the rest of of the cluster management is going. And if we can maximise and optimise our lustre management, then that maximises the serum IgG, and particularly IGG1 present, which then maximises the availability of IgG one for re-secretion into that kill zone, the gut.
And then that means you've got a nice high concentration of I. GG1 in that kill zone, in those first two weeks of life, to maximise and optimise that casts local enteric defences against, the scour pathogens. I think there's not a lot more than we can ask for than a nice, functional, strong, local immune defence there.
But what else can we do? Because we know that sometimes the cluster management is very, very good, but we still have some problems, or maybe we want to just augment that colostrum management. Firstly, I think it's worth thinking about vaccination.
Vaccination would be the, primary sort of augmentation of, of cluster management with regard to scour management in this country, and probably between 25% and 3 of, certainly of dairy herds use vaccination, to, to maximise, their colostrum management with the intention of, aiding scour management on farm. And how vaccination works, the idea and is typical, the typical protocols that are used currently is that the dam is vaccinated, usually sort of 3 to 12 weeks before the expected, time of calving. So that's around the time that they're There is cholostrogenesis.
And, the idea is that it might be ro for coronavirus, that's quite a common one, or E. Coli is another one that's available. And the idea is that you're trying to maximise, the antibody fraction that is specific to these pathogens.
And it can really be important, but it is worth remembering that it does rely on adequate passive transfer, because in order for the calf to be protected, they need to ingest enough colostrum that they receive those antibodies that that have been produced from, as a result of dam vaccination. And of course, also the calf needs to be fed colostrum from vaccinated dams as well. So, so if there's been any issues with dam vaccination, and that can be that can be, have an effect.
And sometimes, there are vaccine failures. It is worthwhile thinking why, there might be some failure of a, neonatal calf diarrhoea vaccination protocol. Firstly, poor vaccine compliance.
And this is, often a reason for failure of any vaccination protocol, actually, you know, maybe the cold chain wasn't, maintained or Maybe not enough vaccine was, was injected or, you know, the dosing guns weren't, calibrated, that kind of thing. So poor vaccine compliance would always be sort of the first thing to, to investigate as to why, vaccine protocol has maybe failed. As I've mentioned as well, these neonatal calf vaccines, they rely on adequate passive transfer because that's how the calf becomes protected.
And so if any reason is poor passive transfer, either because generally, lustre management and passive transfer on farm is suboptimal. Or maybe an individual level, because maybe a calf, was, born sick or, maybe unable to stand that kind of thing, or maybe just didn't get colostrum quickly enough. So that can happen.
That can be an issue just for those individual calves as well. There might be an incomplete immune response as well, that can be either from the cow or from the calf. For example, if the, cow, for example, is maybe sick in the transition or the close up period, then she might not mount an adequate immune response.
That might also happen as well if, the cow calves. Too close to when the vaccine was, was produced. Although she might mount an immune response, it might not be enough, because there's not enough time for an adequate enough immune response to expand the fraction of, of antibodies that are specific for these pathogens.
The pathogen itself and the antigenic complexity of the pathogen can sometimes mean that the vaccine is, is, do everything right, but the vaccine still might fail. And that's particularly the case for E. Coli and salmonella.
There's a lot of, quite complex antigens, and a number of quite a lot of antigenic differences in some of these pathogens, and vaccines sometimes don't manage to capture that. Of course, you might be dealing with a pathogen that that that is not vaccinated, and cryptosporidium arum is is a very classic example of that. We don't vaccinate, no vaccine for that.
And yet it is a very common scour pathogen. And so even if Have received adequate colostrum from vaccinated dams will protect them against these coinfections, and therefore, the diarrhoea may be not as severe as it would have been if they were not vaccinated, but they're still going to get some diarrhoea because they've been infected with crypto. Or you might find that the field strain that the calf is exposed to is different to the vaccine strain, and that has been reported with, with rotavirus, although, because rotavirus.
In the field, the cow often, has that her own antibody response to the field strain. So even if there is a mismatch there, you often find that, the calf is still protected because of the, the damned own immune response, to the field strain, that's in the environment that she's living in. So another, another possibility that is available to us for maximising the enteric immunity and supporting our callosum management, is oral passive immune therapy.
This operates on a, in some ways, in a similar idea to, to vaccination in that the calf ingests, pathogens specific antibodies. However, the that is provided orally, in a, in a liquid, and it's not rely on, colostrum. Ingestion.
And so this can be quite useful for use, for example, if you've had cows who, have maybe caught early, they've had twins, for example. So you think that, possibly the, antibody, fraction specific to these, pathogens in, in the colostrum is, is inadequate. This can be a useful sort of support there.
It can be useful in sort of individual calves who maybe don't get adequate colostrum for whatever reason. This can be quite helpful. Also, if you have, say, scour outbreak on farms where maybe they weren't vaccinating and you had some animals that were too close to calving for vaccine to be effective, then you could use this to, optimise the carciteric responses.
Of those calves that were born to those dams, to sort of tide you over until you were able to, to get vaccinated and, sort of bridge that gap really between the scour outbreak and the time taken for, the vaccines to be effective and, and the cows to mount an immune response and, and then also contribute to, to the Colostrum. And it is thought that these work, by contributing to the, IgG concentration that's in that kill zone and sort of directly supplementing, directly supplementing those. And they've been around for quite some time, actually, this oral passive immune therapy.
But, but actually, the studies are fairly few, and there's certainly some more recent studies that have found that, calves who, had this at birth were, although they might still have got diarrhoea, it was of reduced duration and reduced severity compared to calves, who were on the same choloster management protocol, but did not receive, these types of products. Finally, there is increasing interest in the use of pro and prebiotics. Most of the calf work or cattle work is looking at these for, maintenance and of a healthy microbiome.
Within the room and actually in ruminating animals, but there is increasing interest in pre-ruminant calves as well. And it's thought that, these pro and prebiotics, they can have an anti-inflammatory effect, and they contribute to the homeostasis of a healthy microbiome as well, which, in turn, leads to improved mucosal immunity and low. Level, because that microbiome is, is, the health of that is optimised.
But research is, still quite in the, in the early stages. This is a very big field of research in, in the human field, whereas in calves and in cattle, research into the microbiome is really just sort of exploded in in the last decade. And, And, and the research into these pro and prebiotics, is fairly swiftly following as well.
So I think in the next sort of 10 to 15 years, we'll probably get a lot more information on this. I know there are products that are available, but their, their benefits are, as yet, a little bit unknown, but there is a lot of, of interest in this. So, so what's this space, I guess.
So, this is all very well and good. But how does this affect you as, as a practising vet? And I think the key thing to remember is really optimisation of cluster management.
It's crucial, and it's the most important factor when it comes to neonatal calf diarrhoea. So if you have farms where neonatal calf diarrhoea is a problem, look into the cluster management first, because particularly, from a long-term point of view, optimising that will optimise the local enteric defences, because it'll also, of course, have wider benefits, because, there are other non-enteric, diseases of calves that also cluster management, optimising choloster management will help with that as well. But from a diarrhoea perspective, if we can maximise that IgG that's being ingested through colostrum, we can maximise the amount that's being re-secreted into the kill zone.
And, make a nice high concentration of IgG in the kill zone there to defend the, calf from any ingested enteric pathogens. But What happens if colostrum management is optimal, or if we want, you know, we need to do something in in the more short term, whilst we're getting the choloster management a bit more optimised. And there are some options to do that.
So there are options to help, bridge the gap until we've got the colostrum management and particularly the, the sort of passive mucosal immunity can be pretty helpful there, because it's a quite a short, a short term sort of immediate. Thing that we can do, but also colostrum management and colostrum protocols, even if they're already optimised, can be further augmented, by, factors such as, maintaining the or optimising the microbiome, for example, maybe with pre and probiotics. Like I said, the evidence for that is still, still a bit undecided, but also vaccination as well.
And vaccination is a really good way of, augmenting, the Colostrum protocols, particularly if you're working on farms where you know there are, diarrhoea issues, and, you want to have a longer term, management plan for this. In summary, neonatal calf is very, very common. And although there are 4 main pathogens that are implicated, mixed infections are really common.
And actually, it's quite rare that you will sample a calf and have, just, a single isolated pathogen or pure growth of a pathogen. And changes in the microbiome may exacerbate this. So, increased prevalence of pathogenic bacteria, such as Fusive bacterium, may well exacerbate these mixed infections and the scour, these scour outbreaks, particularly at the individual level.
Cluster management is key. And although I've suggested a lot of things, to do as well as cluster management, I don't want to detract from the, the real importance of cluster management, and that is really the most important factor when it comes to scour management and prevention. But even if that's optimised, you might still get scour outbreaks, and they There are options available to augment a colostrum management protocol that's already very good, or to help you, reduce the number of sick calves and the number of dying calves, whilst you manage to get, the colostrum protocols on farm, a bit more optimised, or you manage to get a vaccine protocol, in place.
So you just a few of the references that have informed this, this presentation. And thank you everybody for listening. I think if you've got any questions, hopefully you put them in the Q&A.
Thank you very much. Fantastic. Thank you, Nico.
That was a very, very interesting. Thank you for sharing all on all your knowledge. I'm sure all of the attenders have found it extremely useful, and we do have plenty of questions, so I'll try, try to go through some of them obviously where I I don't want to overrun too much, but so if I just shoot you a few questions now, so the first one we have from I asking what strategies are available to enhance the protective mucus layer.
So, so yes, I'd say to enhance the protective mucus layer, with regard to the immunoglobulin concentration, the passive, mucosal immunity is a really good way of enhancing that. And, with the point of sort of enhancing the specificity, specificity, I suppose, of the immunoglobulins that are within that layer for some of these enteric pathogens, notably not crypto, though, because we, we don't have vaccinations for crypto, but. Vaccination can be helpful there.
However, really, it's getting good quality, clean colostrum on board is the best way to do that, because that will, optimise your microbiome and your microbiome. If that's healthy, that drives a healthy mucosal layer. If your microbiome becomes unhealthy, for whatever reason, either the calf has had Limited or poor choloster management, or actually antibiotic usage as well.
So we need to minimise our unnecessary antibiotic usage, and reduce the diversity of that microbiome, then that has a knock-on effect on the mucosal layers. So, we're limited with what we can do directly for that mucosal defences, but it's, it's really all sort of spins around the microbiome and having a healthy microbiome, really. So, so yeah, and you get that from having a healthy cat.
They kind of work 2 and 2. If you have good cholester management and a healthy calf, you'll have a healthy enteric mucosal immunity. If you have healthy enteric mucosal immunity, you'll have a healthy calf.
So the two sort of almost spin round, round, round the axis of the microbiome, I suppose. Yeah, yeah. No, absolutely brilliant.
Thank you. And then another question is about the binding receptors for the coli F5 disappear with age, but do they reappear on juvenile enterocytes that appear when a calf is recovering from rota or coronavirus? No.
So, so it's not really the binding sites. It's sort of the expression of, of those within the gut, and that's very age-related. So once calves are over about a week of age, they just don't have them.
And they, it doesn't, to my knowledge, at least, they don't reform. Again, that expression doesn't redevelop. So, so other types of E.
Coli that's not Etech, have a different pathogenesis. They can still cause diarrhoea, though, in Cattle and calves of, of any age. But this EEC, which is the enterotoxigenic E.
Coli that causes, very, very sick calves, and sometimes even per acute infections will result in, in calves that are just sort of found dead. That's the one that's, that requires the expression of these, These binding sites to facilitate the antigen adhesions. And after the calf is, is about sort of 5 to 7 days of age, that expression becomes lost.
And so ETech enterotoxinogenic E. Coli only affects these, these very, very young calves. Like I say, other E.
Coli that are a bit out with the discussions. They can affect other calves, but they are, fortunately, much less common. Fantastic.
Thank you. Another question is around, all right, here we go. So as, as faecal microbiota transplantation is gaining popularity in companion animals, is there any evidence supporting or evaluating this in calves?
Yeah, I was actually thinking about that, not very long ago, because, Roman, Roman trans, for nation is, is something that's also gaining increasing popularity. To my knowledge, the use of that in cars has not really been studied. But I would imagine, because I'm aware of sort of the wider, interest.
I think in people, it's being studied more as well. So I'd imagine that if studies are not currently ongoing, they, they will be in the very near future. So I think probably, that is something that we'll find out in the, in the future, but I, I certainly when I was studying for this webinar, I didn't see a great deal about that.
Brilliant, thank you. And we've got an anonymous question here from somebody asking if there are any percentages available on inadequate immune response. I suppose it depends a little bit on, on what inadequate immune response is.
I think sort of at local level, that's very difficult to, assess. If we look at generalised failure of passive transfer, we do know that globally, the prevalence of failure of passive transfer, would be, around about 30%. Inadequate immune response in, In reaction, in response to vaccination, I'm not sure actually, I can look that up though, .
Brilliant. OK, thank you. And I'm I'm sure there will be, I, I don't think we'll manage to go through all of the questions, but, I, I, I think you can, you'll have them emails too, so if you can answer them and then that'd be fine thank you.
But, we've got maybe a couple more that I can ask now, somebody here is asking about. Are we saying that they are trying very hard to wrestle oral antibiotics from the grasp of some of the very demanding farm clients, and what do you think about the pro and prebiotics available? I wonder if offering an alternative might help coax them away more effectively, although also worry about the hygiene of the pump dozers going from cough to cough, etc.
Yeah, I think that's a really common challenge that, that we've all sort of had to deal with. My view on, pre and probiotics is, there's certainly no evidence that they're harmful. And sort of evidence extrapolated from other species and other studies would suggest that they probably are beneficial.
But, we don't have a lot of studies looking at neonatal calves, exactly. So they might do nothing. But I think, it is laudable to try and reduce the amount of antibiotics, and it is very, very difficult.
I have found on farms, to get farmers, even on farms where I know everything is spotless. They have excellent cluster management, and there's really no need for, for antibiotics in, in the milk, because the, it's a very human nature thing, isn't it? People say, Well, actually, things are working because we're putting this in the milk, and actually think probably if you take it away, it's not gonna make any difference at all.
I would say, yes, I think, If you are looking to move on to something else, it is worth a try with the pre and probiotics and and yeah, it can, it can only help or do nothing. Having said that, I, I agree with you. I'm If On the farming question, the calves are being dosed with, an unhealthy concentration of potentially pathogenic bacteria through, you know, equipment, whatever, then that hygiene does need to be improved.
And I would say that, the use of antibiotics, for example, in the milk prophylactic antibiotics, it shouldn't really be used to cover poor hygiene. However, If calves are ingesting, for example, a lot of faecal matter on a regular basis, that is going to be proved quite a challenge to their localised mucosal immunity. So, so I can fully understand why, why farmers might be reluctant to, to move away from, From prophylactic antibiotics, but it is something that we do as an industry need to be moving away from.
And, and I think I think possibly in the future, the pre and probiotics might be the way things go, And I think this is worth a try, but it is a bit of a watch this space sort of situation at the moment. Sorry, I can give you a very, very absolute answer to that. I hope that answers your question.
That's, thank you. And we've got Bethany from New Zealand saying, Thank you so much. I was wondering, what the References for the cytokine graph.
Here in New Zealand, it's common to transport calves younger than in Europe, 4 years, 4 days old, and they do struggle with stress of transport. I'm thinking that this is part of the reason why I wonder if you have any further comments on this. Yeah, so, so the cytokine graph that actually came from a review in the vet clinics of North America, and I think the data is, is actually from a PhD study.
But yes, the stress, Any stress is going to, have some level of immunosuppressive effect. And I think if calves are being moved in those first sort of 4 or 5 days of age, then that level of stress will, lead to increased cortisol concentration. And I think it is reasonable to assume that's probably going to have a, an additional immunosuppressive effect over and above what is, Sort of, physiological.
I suppose it happens in all calves, irrespective of, of how they're being managed. It's also worth noting as well, that stress, has been found to affect the microbiome, in calves of all ages. And of course, at that age, that's a really important stage for that microbiome development.
And so stress at that age is, is also going to be, probably going to have a negative effect on that as well, which will contribute, further contribute to, to suppression of, of the local mucosal immunity. I mean, in, in Europe and in the UK we're not allowed to transport calves, certainly any distance, while they still got a wet navel. So for us, I guess this is less of a bit less of an issue because the legislation sort of helps us out a bit there.
And I suppose if, if cars do need to be moved, there are methods that you can do to try and reduce the stress involved in that sort of shorter distances as possible, try not to overstock the lorries. careful driving, those, those sorts of things. So, so, so, yeah, I would, I would say probably minimising, transport at that early age, if possible, but if it needs to be done, then try and do it in a, in a fairly stress, reduced stress manner, if possible.
And of course, yeah. And of course, if, if other management things are going on, if possible, maybe not doing it on the same day as the transport as well. So like air tagging, for example, maybe don't do it on the same day as the transport because that's additional stress as well.
Perfect, thank you. Let's see what's the time. So let's do a couple more then, just some quick ones here.
Would oral IgG given to orphaned calves be a good supplement alongside powdered milk to provide sufficient protection? Yes, yeah, that is definitely an option for that is to give the oral IgG, because it's very concentrated. And also, some of these products are sort of specific to enteric pathogens as well, whereas your powdered lustrum, isn't.
Powder loss is also worth noting as well that, a lot of the sachets don't actually contain enough IGG for one sachet to provide 150 grammes, which is what's needed. So sometimes you need more than one sachet there as well, which I think is, is not always realised. And, and also they don't always contain all of the other factors as well, although, your mucosal immunity doesn't either.
But, but yeah, it definitely, for those orphan calves, particularly if they're high value orphan calves, that can be, a very useful adjunct to, to your powdered colostrum. Perfect, thank you. And just a a last one.
Do you think that heat treatment of cholesterol is always a must since it can decrease beneficial bacteria as well? Yeah, no, it doesn't decrease beneficial bacteria increases, or it's been associated with an increased prevalence of, of beneficial bacteria. I think pasteurisation or heat treatment of colostrum definitely has a place.
I wouldn't go so far to say it's always a must, because, I've worked on lots of farms that don't do it. And, But still have excellent calf health. So, but there is some evidence that, I mean, it's quite a lot of evidence that it definitely reduces the risk of pathogenic bacteria, particularly Yoni's disease.
Calves fed, heat tree colostrum have in some studies, been found to have, better, efficient. Of absorption of IgGs. And in that study that I mentioned, they actually found that the prevalence of, beneficial bacteria was actually higher in the calves, fed, the heat-treated colostrum.
So, so not lower. So, you would think it might be lower because, because you're potentially, Decreasing the concentration of all the bacteria. But actually, I think what happened, was that the, the level of concentrations of pathogenic bacteria would decreased.
So that led to, so they weren't competing with, with these sort of good bacteria in inverted commas. So, so yes, so heat treating or pasteurisation of, colostrum, is a good thing, even with respect to, to the microbiome. But, it's not something that Necessarily every farm needs to be doing.
And, and you can have very good calf health, very good entire community, and very good coloster management without it. But it is, it is a really useful thing to do, if you've got farmers that are keen to do it, as long as it's done properly, of course, and it's also not used, again, as, as, as a way of saying, oh, well, my, my colostrum is is pasteurised, so I don't need to worry about cleanliness and, and hygiene and those sorts of things. It's not a magic bullet, but it is very useful for, for, calf health.
And, and yeah, no, it's, it was associated with the increased prevalence of, of beneficial bacteria. Yeah, brilliant, fantastic. Thank you very much.
For any questions that haven't been answered, watch the space. We'll get some answers back to you all. But, yeah, no, thank you very much, Nicola, for talking to us, tonight.
Thank you thank you for coming. Yeah, thank you, webinar but for having us and thank you to Forte for obviously sponsoring the talk. Yeah, thank you and thank you to you, Sylvia as well for for sharing.
Absolutely, you're welcome. All right, take care. OK, thank you, bye bye.

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