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What? Hi Ahmed. Hi Dr. Mark. How are you? Good. Um, hi Mark. You? Dr. Foreign. Good morning. Good morning.
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Foreign.
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Um, can you present your presentation about the European experience about Salmonella control in European countries? Okay, so thanks. I will share my screen. Yes. Okay, so please let me know if you can see my screen. Yes, clear. Okay. I need to find, uh, sorry. You want soon? Just need to. Okay. So, good morning, everybody. I'm glad to be with you. I'm sorry, I cannot do it in Arabic. I'm still learning, but I'm far away of being able to do this kind of presentation in Arabic. Um, so I will, uh, go through this presentation about Salmonella control in EU. And first, I want to invite this of the importance of this disease. But before that, I really want to thank, uh, SFD and Dr. Ahmed El Demerdash to organize this meeting and to make me the owner to be part of this meeting. So I will stop. One comment. One comment before the beginning. Us? Okay, Dr. Mark. Okay. Thanks. And Ahmed, uh, do not hesitate to interrupt me if you want or need to translate things. Okay? Okay. I will provide the Arabic. Okay. Thanks. And so I realized I, I think you presented me. Okay. Um, so I will start by importance of Salmonella because, uh, in Europe, it is the second most important zoonotic disease in humans. As you can see here, Campylobacteriosis is the most important one with more than 246,000 cases. But then you see Salmonellosis with 90,000 cases per year. So that's data from 2017 and didn't change a lot since that time. Interestingly, uh, cases decreased by twice, uh, for the last 15 years. So meaning that the effort that has been done in EU helped to decrease the importance of his zoonosis. And if you see that's all the reported zoonoses for EU, and you see that it's far, far more important than any, uh, other diseases like, for example, Toxoplasmosis is 40 cases, which is very, very low. It was more in the past. So our hope is to decrease again in the coming years. Zoonotics are manila. If we look at the, what we call the couple of pathogen and food vehicle, um, we can see that in the top 10, Salmonella is present five times. So the two most important causative agent, and this is number of human cases, you can see it's Salmonella linked with meat and meat products, and then eggs and egg products. And for meat and meat products, mainly it's from broilers and turkey. Then you can also have some cases of Salmonella linked to bakery products, but because they use eggs. So, but we are not able to to identify eggs in it. But you can see that it's a lot, um, 600. So it's far less than the other cases. And also in mixed foods like salad or things like that, and in other foods. What is important also is a trend. And you see that the trend for the two most important ones is increasing slowly, slightly, until the one is stable. For bakery products, it's increasing a little bit more. More important here is what we call the iceberg. Uh, so ECDC, which is the European Centre for Disease Prevention and Control in EU, made a study based on serology to compare what is actually the real number of cases and and the underlying part, I mean, cases that are not reported but that may exist. And so I will take here only the example of France, which is number nine. I'm sorry, because it's very, very small. So France, you can see this year you had 6,300 cases reported, and the estimate of ECDC is 24 million of people have encountered the disease Salmonella. So maybe it's a little bit too exaggerated in the other way. But what we can say is that reported cases is really the tip of the iceberg, and Salmonellosis is much more important that even, uh, official reports may, uh, show. If we look at the type of Salmonella that are reported in Europe, so that's data from 2018, but 2019 is close to that. And you see that 50% overall of cases, uh, human cases confirmed cases by Salmonella are Enteritidis. And then you see Salmonella Typhimurium, and third is Salmonella monophasic, which is a similarity Typhimurium monophasic, which is growing at the moment in EU, and especially in France. And you see that overall Enteritidis and Typhimurium represent 70% of human Salmonellosis cases in EU. Then you have a lot of different stereotypes. And you see that just for other, you have 18%. So, but mainly it's SE and ST, which explains that, uh, at the moment, EU legislation is really focused on SE and ST. But for breeders, we also look at Infantis. And you see Infantis is very low, it's 2%, but it's growing. And also, uh, we are looking at Salmonella Agona, which is very, very low. But that's the official one. Third point, I want to discuss with you is the resistance to antibiotics. And what you can see, first, uh, slide about resistance is for human cases. But Salmonella spp, meaning every Salmonella, the ones that are really pathogens, and the other one. What we can see is that 50% of isolates are sensitive to antibiotics. Important here to know is that when you go in this kind of EFSA report, it's not resistance as you are not able to treat human disease. It's resistance as an epidemiological value, meaning that you can split a Salmonella population between the one who are sensitive and resistant. But it's an epidemiological cut-off. It's not a clinical breakpoint, meaning that we should not over-interpret this, uh, data on sensitivity and resistance because it doesn't mean that in 50% of the case, you will have issue to treat humans. But it gives you an overview. And more interestingly is, uh, it does, uh, evolve, uh, coming forward. So for Salmonella spp, I would say no issue. If we look at SE, Salmonella Enteritidis, in human cases, we see that 70% of Salmonella Enteritidis isolates are susceptible to all nine antimicrobial tested. And here you see the different countries. For so for sure, there are more resistance in Portugal and Greece than in Austria or Netherlands for SE. And you see the different countries listed here. You have not all EU countries, but you have a lot of them. Um, and so for Salmonella Enteritidis, overall, we can say that there is no issue. If we look at Salmonella ST, Salmonella Typhimurium, then the picture is quite different because we have 41% of Salmonella Typhimurium isolates that are multi-resistant, meaning resistance to more than two antibiotics. And you see that in some countries like in Estonia, um, the situation is is very, very, yes, it's a big concern because resistance, um, to more than five, uh, antibiotics is about, you know, 70%, which is very high. And here, if we look at the, I would say, emerging, uh, serotype, which is Salmonella Typhimurium monophasic, you see that overall 80% of, uh, monophasic ST is the less are multi-resistant. And you see that for example, in Greece, you have almost, in Greece and Ireland, you have no ST monophasic that are sensitive to all the antibiotics, meaning that the population are moving towards racism. So even if it is epidemiological, that means that one day for clinical, it's not a good sign. And so the monitoring of resistance is quite important. And I would say that, uh, that's interesting to see, but that's also one reason to fight Salmonella because resistance to antimicrobial resistance is a growing concern globally. And and one of the way to avoid issues with antimicrobial resistance in humans is to avoid humans to get sick from zoonotic bacteria. And that's one of the reason we should find Salmonella together with antimicrobial resistance. No, I'm going to EU legislation. So there are a lot of pieces of laws that we call regulation. And what you can see here is that the most recent regulation is from 2012, but the big pieces have been set in '06. And I said, Mr. Kelvin, you know, the guy who invented the thermometer, if you want to improve something, you need to measure it. If you don't measure, you cannot improve. So the first things in EU started with a multi-country monitoring studies, uh, prevalence study in every EU countries in 2005. Then they decided to set a target for different kind of flocks. So for example, for breeding hens and breeding turkeys, they decided to set the target at less than 1% of prevalence in each country. So the objective at that time was to have less than 1% of breeding flocks positive every year. And the targeted serovars were SE, ST, and also Infantis, Virchow. And that's for breeding hens. You can see that for breeding turkeys, the target in prevalence is the same, but serovars are different. It's only SE and ST. If we go a little bit further, closer to the customer, we see that laying hens, the target is less than 2% of flocks per year for SE and ST. And for breeders, the target is less than 1%, as it is for fattening turkeys for slaughter. And processing, uh, you can have processing, direct processing, or heat treatment for laying hens products, and for broilers, and for fattening turkeys. But at the end, the objective for trade for eggs is, uh, no SE and ST at all. For eggs, for egg products, is absence in 25 grams for all serovars, meaning Salmonella spp. For egg products, and for fresh meat, it's absence in 25 grams for SE and ST. And for meat preparations, it's absence in 25 grams for SE and ST. I think that in a lot of countries in the world, these targets are the same. But what is quite different is the control and primary production, and to have targets set in flocks. If you look at this graph, and I'm sorry again, because it's very, very small, but you can see that for each box, it's a country. And I will take an example, for example, Estonia. And you see the first line is 1%, and second line is 2%. And here, first row is breeding hens, then it's laying hens, then it's broilers, then breeding turkeys, and fattening turkeys. And so you, for each country, you can say, are they compliant with the required target or not? And you see that for Estonia, in, in '07, they were far away from the target. But most of the country for laying hens are below the 2%. You see, because they all are below 2%. Croatia was upper, Czech Republic was below. So we had some countries like Latvia, Estonia, who joined recently EU, was still, uh, over, uh, the target. Okay, how do we control, uh, Salmonella in flocks? So, uh, what is important is that control, you don't make control on on eggs and and on chicken at farm level. What they do, uh, is that they do sampling with boots, for example, or with, uh, towels on the wall of the farm. And you have two ways to control. You have self-monitoring. It can be done by a vet or by technician or by the farmer under supervision of the vet. So the people have to trust each other. So they will do self-monitoring at one day, four weeks of age, and two weeks before during the rearing phase for breeders. Okay? And for production, they will do self-monitoring every two or three weeks. But if they don't do it seriously, anyway, you have official monitoring done by vets from government. At the beginning, one set of lay, middle of lay, and end of lay, that will be done by an official monitoring. So anyway, you will not be able to hide the fact that you have Salmonella if you are not serious in doing your self-monitoring. So at the beginning, you know, people have to get used to that. But no, that's clear. People respect the self-monitoring in any way, or future monitoring is well known. So for breeders, again, uh, we target five serovars. For layers, uh, at rearing period, it's only self-monitoring at one day when they receive you, they all check, and four weeks before lay, and during the production period, the control in layers is every 15 weeks. And official monitoring happens nine weeks before the end of lay. And the two targeted are SE and ST. And that's the way they do it. Just to give you an example of what has been achieved. And we have no time to go through the UK story. But as you, you may know, uh, in 1985, there's been a big scandal, public scandal, media scandal in in UK, because the military affairs at that time accused egg producers of being all positive for Salmonella and said that if you eat eggs, it's quite dangerous and you may get ill. UK farmers and governments, they made a lot of progress using the standards of monitoring of EU, and also using vaccination, which is mandatory for SE and ST also since 2014. And what they achieve is just wonderful because now the UK Food Standards Agency publicly said in 2017 that even young children, pregnant women, and elderly people, who are the most, you know, susceptible to have, uh, Salmonellas, which is a very bad Salmonella disease, even in some cases, you can, uh, you can be dead due to Salmonella. So even these people, they say that they can safely eat raw or lightly cooked eggs if they are part of the Lion Code. The Lion Code, which is a high private standard that is adopted by 95% of egg producers in UK. So you see between 1989 and after 40 years of fight, and the UK Food Standards Agency recognize big efforts and it says that raw eggs are safe. That's a really a great, great achievement. And what they have done, they have done monitoring for sure, biosecurity, they insist a lot on control of rodents because they have a lot of freedom issues in EU, and also mandatory vaccination against Salmonella Enteritidis and Salmonella Typhimurium. And so egg producers took tough decisions. Um, they invest a lot of money, a lot of time to control, uh, Salmonella. But now they have regained the trust of both consumers and government and and Ministry of Health. And so those eggs that are deemed to be safe are the one with the Lion stamp on on the eggs. And every UK consumer knows that they can safely eat these kind of eggs. So now comes a time for a take-home message. I would say that zoonotic Salmonella is really an amazing disease. And that we really need to to have in mind because zoonotic Salmonella is not a disease for poultry producer. It's not a disease that will decrease the production or make be responsible for losses in poultry farms. Zoonotic Salmonella is just a human disease. But it's really amazing because it's a human disease, but if you want to prevent the disease in humans, you need to work at farm level. And you need the support and expertise of this and poultry farmer to control this disease. And this human disease in many countries is a concern for Ministry of Health, but they sometimes even don't realize that they need to work end in end with Ministry of Agriculture to convince farmers to control the disease at farm level. Otherwise, you will still have issues for human health. It's a zoonotic disease that we monitor at farm level by looking for the bacteria in poultry barns, in the environment, you know, with boots and things like that, not in animals or food products. Um, sometimes for, uh, poultry diseases, you just make a necropsy and you look for the bacteria or the virus all on the poultry. Here, what we do is we try to guarantee that the poultry barn is free of Salmonella, meaning free off. We realize this sampling, 10 samples by per farm, every 15 weeks during the laying, the production period in layers, for example, as I showed. But you cannot say free off. You free of after this kind of control. And you will not look for Salmonella in eggs because excretion is very low. So you will need to control every egg before to find one Salmonella. It's more powerful to monitor in the environment of the farm that what is done for years now in EU. And zoonotic Salmonella is also a threat, especially for children under five. Why you, you still have a lot of children dying all over the world, but also for elderly and immunodepressed people. And it's also a threat because, uh, there is a link with antimicrobial resistance. And and so, as you have seen, uh, Salmonella Typhimurium monophasic variant is really often resistant to most of the antibiotics. What is important is that poultry companies, and I think that some poultry companies in in Saudi, but I can tell you it's not the case in many countries, poultry companies and producers should realize that they are food companies. They are not just farmers, they are food companies because what they produce can bring a disease. So they should have very high standards of biosecurity, like you have in a food company producing milk or a slaughterhouse. That should be the same at farm level. They are food companies, they produce food for humans. And so they are responsible for providing nutritious food, but they should also provide safe food. Salmonella can impact also business and country reputation. And I invite you to type Salmonella holidays, for example, in Google. And you will see that you have some reports of tourists going to foreign countries and going back home being sick and complaining against the country or or the hotel company because of Salmonella. So that's not a good advertising, uh, for countries like, for example, Saudi wants to increase the tourism with a 2030 plan in Saudi. So, last but not least, EU regulation. So ready, you need to have national control plans in each member state for zoonotic Salmonella. And it's at farm level. Um, it's mandatory. What you have to know is that, for example, uh, up to now, it's only for poultry products. For swine, for example, or for beef, there is no mandatory plan for control at farm level in EU. In EU regulation, also vaccination is mandatory in countries where the prevalence percentage of flocks positive is above 10%. And just to conclude, I think, uh, it's really time for action because it's very complex. It must be a progressive approach. And as that's what we have done in EU, we started by breeders, and then we went to laying hens, and then to broilers, you know, every two years, we increase the pressure. Um, but the earlier you start with an official control plan or private, uh, control plan, and the more successful you will be. Because even if you do everything very well, you will need time, years, I would say, I would not say ages because I am optimistic. But you can see that in England, it took almost 30 years to come from a very bad situation to a very good situation. So yes, it's always time for action and and it's urgent to start something. Okay. And I, I think I'm at the end of my presentation.
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Francesco? Yes, that's right. Thank you very much. Are you able to see the screen? Yes, clear. Very good. So, um, first of all, um, good morning, ladies and gentlemen. It is my pleasure to be to be here with you today in the occasion to address this presentation. I would like to thank you very much Dr. Ali for the kind introduction and Dr. Ahmed for the very comprehensive organization for this particular event. And I thank him very much for for all the the inputs that gave me the chance to really be up to date on the current situation in the Saudi poultry industry. So the title of this presentation is similar risk management in poultry vaccination in the frame of the holistic approach. Um, basically, the idea is to cover a different topic. So I will be starting by explaining why the holistic approach is is relevant, is the is the recommended, uh, method or initiative to tackle Salmonella infection in poultry production. And then afterwards, I will be transitioning and how do vaccines help to build this active immunity? And finally, I will be summarizing the what to expect from the Salmonella live vaccines from Elanco. So, um, as you might know already, so the holistic approach is pretty much justified because of the multiple transmission routes when it comes to Salmonella. So, um, we have a number of sources of infection. We do have reservoirs, and we do have rodents, pests, surfaces that are contaminated, and also of course, people that is very typically underestimated and happens to be one of the most important sources of transmission at farm level. Right? So along with these sources of infection, we do have the risk factors. So, uh, in the literature, uh, mentioned has been made about a number of risk factors associated with Salmonella transmission. And here I'm only listing 16 of them associated with the layer, the layer context, but we can also extrapolate this and make it suitable for the for the breeder operation, also the the broiler operation as well. So, uh, because of that, so we need also to be mindful that yeah, the industry because it's integrated, so we need to come up with the customized approaches along every single link in the value chain, right? So, and if we simply say that, okay, biosecurity in primary production will solve all the challenges, this is not really accurate. So we need to find a proper combination of methods. And typically, this is start from the top-down approach, starting with the breeders, of course, in order to prevent this vertical transmission to the to the progeny, right? So, and the idea is, of course, to have integrated outcomes in the processing plant or the egg packing center, so that retailers and the value chain, the restaurant chains, are in the position to provide wholesome food to the consumer. So this is the first, the first reason for that. So we need the holistic approach in order to tackle all the different sources of infection and the risk factors associated to Salmonella. And and for that, of course, we we can refer to specific measures. So we do have, this is for instance, an illustration that we try to illustrate what specific sources of infection here represented in orange can be tackled with certain intervention programs here represented in blue. And of course, each of the programs in blue are supposed to be complemented or composed by different technologies or or tools that are being part of that particular intervention program, right? So this is only an example of what can be done at farm level, primary production, but of course, and there is a a similar consideration when it comes to the processing plant, right? So we need to customize those. Very good. So, so the second reason why the holistic approach is relevant against Salmonella has to do with them with the with the proven concept when it comes to reducing the prevalence not only in in poultry but also in humans. So in this particular graph, you might be familiar with this already. So it is represented here the dynamics in terms of prevalence in the United Kingdom, starting from the early 80s, where there was an important rise of Salmonella cases, not because before there was not a case, but because the fourth day was not monitoring. So the monitoring in principle, with all the robust methodology and surveillance system, starting to happen from the mid-80s. And this is therefore it was documented as an as the rise of the infection. So here you have the the red line representing the cases in humans, the black line is representing the cases in poultry. And what we want to illustrate here is that in the United Kingdom, Dr. Mark was explaining the the Lion Code approach, and this is very much an industry initiative that was triggered, was initiated because of the crisis in the late 80s. So in 1998, with the junior health minister Edwina Currie, gave this famous declaration to the public here, the majority of egg products in this country, namely the United Kingdom, was contaminated with Salmonella. This provoked a huge outrage in the industry and of course led to the fact that the consumer was not interested to consume eggs anymore, right? So it created a crisis. So the industry immediately reacted with a great crisis management approach. And part of that initiative was to come up with this code of practice. And the code of practice, you might be known already, is consisting of multiple measures, yeah, some general and some specific, which include a vaccination of poultry and Salmonella. So they, uh, vaccination of the of the kill vaccines, because it was the only technology available at that time. So it was the first generation vaccine. Then in the early 2000s, the second generation vaccine was introduced, yeah, and there was an immediate switch, yeah, because of the convenience, because of the advantages in terms of the mode of action, the the switch was automatically, yeah, so the live oral vaccination was replacing the inactivated vaccine. And more recently, in the year 2012, the the third generation vaccine, which is the bivalent live combination of Enteritidis and Typhimurium in one vial, it was introduced in order to be part of this, uh, Lion Code approach and also part of the national control program. So the second reason why the holistic approach makes total sense against Salmonella has to do with the fact that is a is a proven concept, very well demonstrated that, uh, that of course leads to these integrated outcomes in the processing plant or egg packing center. And, and the third reason, pretty much summarized here, has to do with many of the concepts that were already mentioned by Dr. Mark, has to do with a multiple connotation when it comes to Salmonella infection, right? So, so we do have three different, uh, dimensions of the impact of Salmonella. So one is the epidemiological dimension, so poultry being the main source for infections in humans, yeah, the fact that, uh, several sources are associated to the transmission across the value chain, and also to highlight the impact in terms of multidrug resistance. So, we do have, uh, established serovars like Typhimurium having this multidrug resistance pattern, but also we do have emerging serovars like Salmonella Infantis, Salmonella Newport, Salmonella Heidelberg, perhaps not relevant for for Saudi Arabia, but for other countries as well. So, a number of emerging serovars having this multitude of resistance pattern that of course are having a a huge impact in the most susceptible population, and we need to be mindful about that. The second connotation is, has, it has to do with immunological factors. So the holistic approach is necessary. Within the holistic approach, the vaccine is the only tool capable to reduce organ colonization and at the same time prevent the excretion and prevent the egg contamination. Of course, not all live vaccines are are capable to do so. Some of them are able to do that. I will refer to this in a minute. Some others don't. And, and also not the case for the kill vaccines. So we, we need to really be conscious about the key differences of one technology compared to the other. And the idea is to decrease prevalence over time based on this systematic approach. In terms of the impact, uh, because of the, of course, the, uh, huge economic connotations, supermarket recalls, condemnations from authorities, trade barriers, damage reputation, in in consumer shifting to other kind of proteins, yeah. And then Saudi's particular relevance to protect the brand, especially taking into consideration that the domestic consumption of poultry meat is not fully satisfied. So the industry is open for poultry products coming from South America that could be cheaper, that could be having a strong brand on them, and this could be a, a competition to be to be aware of. So, keeping strong brands for the Saudi poultry industry is, is something relevant, of course. And this is a summary slide around the connotation. It's very much inspired in the European experience. So it has been demonstrated that biosecurity alone is not enough to prevent the birds to become infected. You need both general and specific prophylaxis. The low prevalence we see across the European Union is the result of continuous vaccination using the recommended vaccination scheme. And in spite of the low prevalence, so the prevalence was reduced from more than 30% 10 years ago to below 2% nowadays, and this has to do with the with this implementation. And in spite of that, the point I want to make is that the scientific community strongly recommends to continue this approach over time in order to prevent the rise of the infection again. So we have some precedence. Three years ago in Poland, there were some disruptions in the intervention programs in some egg farms, and and what happened was that Enteritidis, which was supposed to be a very controlled zero bar, because of the different general and specific measures, happens that this zero bar was re-emerging, right? And this is something that of course should not happen. Very good. Now we transition to the second point of this presentation. So how do vaccines help to build immunity in the frame of the holistic approach? And as I was referring before, we need to address the Salmonella management issue with, um, with a top-down approach. So, so we need to start with the with the elite flocks. This elite flocks needs to be negative of Salmonella. In some countries, this is forbidden to vaccinate the elite flocks because of course, we want them to be fully negative. And, and, and then when it comes to the parent stock and the breeders, of course, they need to be immunized in order to prevent this vertical transmission to the progeny. If one single hatching egg is being contaminated, they could be the case that in the hatchery, there will be a cross-contamination with the remaining, uh, cabinets, and the the flocks that were coming from that particular feeder flock, the the broilers will be spreading the bacteria in the hatchery, therefore contaminated other batches of daily chicks that were coming from a different parent stock. So it would be a, uh, exponential multiplication, uh, because one single daily that was having this vertical transmission from the breeders. So it's very critical to immunize breeders. Typically, they are immunized against multiple serovars, and it could be using the the live vaccine along the two live vaccine or combining with the kill vaccine. So this is very much conditioned to the local epidemiological situation. But the key concept here is to convert as much spectrum as possible when it comes to the multiple serovars established serovars and emerging serovars. So that's the rationale for the parent stock vaccination. Then when it comes to the progeny, so you have two different possibilities. Of course, the the layers, because of the life cycle which tends to be longer, of course, so you need vaccines that are agile, that are versatile enough to confer a robust immunity throughout the whole cycle. So the idea is to to utilize the live vaccine because only the live vaccine is capable to trigger this immunity based on three mechanisms. So the first mechanism is the colonization inhibition effect. The second one is the secretory IgA, and the third one is the stimulated immunity, which cannot be offered by the kill vaccine. And because of this combination, uh, is it possible to also to expect cross-protection against, uh, some endemic serovars for some regions causing more mortality and more morbidity cases like Salmonella Agona. So when it comes to broilers, and perhaps this is a new concept for the most geographies, but in in some key regions in the world, in the United States for instance, in Brazil for instance, some European countries are being open to to this practice because when you immunize the breeder stock and then afterwards you confer active immunity in the broiler, you are having better results at plant level when it comes to the the number of Salmonella positive carcasses, right? So, so the rationale here is that the maternally derived antibodies that were supposed to be coming from the pattern stock that was immunized with the kill vaccine, these are not really protected for long, right? So they are conferred certain systemic immunity in the progeny, in the broiler, but this is only lasting for a few days, and it's only a systemic effect, right? So it has not an impact in the in the gut level, at the gut level, so in the intestine, which is actually the main site of the infection, specifically the ceca. And we need to be aware that the Salmonella infection in broilers mainly happens horizontally with fecal-oral infections. Therefore, you need to make sure that the intestine, the ceca in the broiler is properly protected. In this, of course, better achieved with the live vaccination of the broiler. Having said this, so it's a top-down approach. So we need to start with the breeder, as I say, and then continue with the broiler, or the layer, based on the, uh, on the particular epidemiological situation. And for both cases, for all three cases, the live vaccine represents a very valuable tool. Now, let us address, uh, some differences between the live and inactivated vaccine. So in terms of convenience, and there are important differences. For instance, the age for the first vaccination with the live vaccine is possible from day one, and with the kill vaccine, you need to wait for some weeks, typically between the week, six, seven, eight, the first dose would take place. It depends on the commercial product available. So there are different indications according to the kill vaccine involved. But the point is that it is not possible to cover the gap of infection since the very early age, right? Another important difference is the application method. So with the live vaccine, you deliver the vaccine, uh, either via drinking water or coarse spray, so it's a mass application covering many, many birds with a reduced requirement for labor. While the kill vaccine, you need to inject subcutaneously or intramuscularly, depending on the product, each bird individually. And when it comes to interference with monitoring, with the live vaccine, because you rely on the bacteriological method, there are no risks for you to have interference with the with the flock monitoring you use with serological monitoring. So, um, with the live vaccine, you do not rely on serology, would you rely on bacteriology? And because of that, there is no chance for you to have this particular interference. When it comes to immunity, there are some important differences to be highlighted. So the mode of action, as I said before, with the live vaccine is based on three different immune mechanisms. The first one is the so-called colonization inhibition effect, which confers a protection actually as rapid as 24 hours. So you apply the vaccine to day or six, if you challenge them the next day, you will have a significant protection in front of this challenge serovar. So it's a very rapid effect that happens very rapidly. And, and the point is that if you administer the vaccine following the vaccination scheme, so three doses, so you were not only able to activate this colonization inhibition effect, but also the local immunoglobulins and the secretory IgA, which should be already reaching some important titers after the first week of age. And, and then of course, with the subsequent booster vaccinations, the second dose, and the third dose, specifically, you will be able to establish a cell-mediated response that is that is the one responsible for tackling the intracellular Salmonella. So Salmonella is an intracellular pathogen, and therefore, nature needs to be neutralized, uh, within the cell. And only the live vaccine is capable to do so. The kill vaccine can theoretically trigger some level of cell-mediated response, but it's much, much limited, and this has been vastly documented in the literature. We can share this information with you if you're interested. Very good. So the kill vaccine, in contrast, it's mainly triggering circulating antibodies, starting with the IgM and the IgG. And, and these circulating antibodies are very important to neutralize this Salmonella that is already disseminated systemically across the different organs. But it's not really effective to neutralize Salmonella that is colonizing the the intestine, right? So, so there is some gap there with the kill vaccines. So the onset of immunity, so OOI stands for onset of immunity, and is the ability of each one of the vaccines to neutralize the field bacteria as as fast as possible. This is possible with the live vaccine within a few hours through a non-specific mechanism, the colonization inhibition effect that I was referring before. And with the kill vaccine, you need to wait onto the second vaccination. The duration of immunity is typically longer with the live vaccine because of the combination of the three mechanisms. And then with the kill vaccine, it is typically shorter. So we need to, of course, both case by case and customize the vaccination scheme based on the particular situation. Very good. So, um, in this particular slide, I'm referring to an illustration from an independent group in Brazil. This is a paper from 2012. And, and here what we see is the different immune mechanisms involved after a vaccination against Salmonella. So with the kill vaccine, you trigger, as I say, mainly a systemic response. With a live vaccine that was applied by injection, you trigger this systemic response along with the cell-mediated immunity. And with the live vaccine that was applied orally, you are also capable to trigger this local response, highlighting the secretory IgA, which is not a, was not the case for those vaccines that were injected. So this is a very important difference and should give you a better idea on on why the other live vaccines are supposed to confirm its advantages, uh, in this slide. I would like to refer to the rationale why it's important to continuously vaccinate poultry flocks. So when you immunize a flock and you do that systematically round after round, cycle after cycle, you would expect that the vaccinated birds are less infected. Once they are infected, they can shed in the environment less Salmonella carrier status is being present within the flock. Therefore, the bacteria is less present in the environment. In turn, the flock is having less challenge to get infected. And, and at the end, of course, you will have a systematically a systematic reduction, uh, of Salmonella prevalence over time, right? In some, in some cases, you will expect that the flock reduction happens very quickly, so after only a few cycles. And some other cases, because the challenge pressure is too high, you might wait a little bit more to have this particular status. But but the concept works. It is a proven concept that is showing important results across different geographies. When it comes to oral vaccination, we need to be mindful that the vaccine is a live organism. Therefore, it is susceptible, uh, to a certain factor. So the pH is a very important one. In order to preserve the vaccine, we need to make sure that the water quality is complying with minimum requirements. So the pH should be between five and seven, and not below five because it will be compromised the vaccine strength, not above seven because it will be compromising as well. It should be free of ions. The vaccine water should be free of chlorine, specifically. So the chlorine tends to compromise. And for this, there are some water stabilizers available in the marketplace that can help you to mitigate this particular challenge. Also, the temperature is an important topic. So we need to make sure that the there is a transition between the cold temperature from the fridge to the temperature that is being present in the farm. So, so there will be a a transition period so that the the microorganisms can be, uh, can be adapted to the to the new vaccine solution before this is delivered to the, uh, to the flock, right? Important considerations in order to help you with this consideration. So we do have a different SOPs that, uh, provides some guidance at, uh, at farm level. So these are kind of posters that can be a place across the different facilities, uh, and as a reminder for the vaccination crew, what to consider before vaccination and what to consider during vaccination. So all considerations about hygiene, keeping the right temperature, using the right device in the proper condition, how to dilute the vaccine, and of course, how to make sure that the vaccine solution was properly distributed across the different drinking lines. So this has been properly documented. This is something that you can also leverage. So based on that, so we cover the holistic approach. We also address important differences between the live and the kill boxing. Now I would like to summarize what to expect from Abby Pro live vaccines from Elanco. So here, basically, what we see is a timeline. So starting from 1994, and then, uh, continued throughout the years. And, and just to remind you that, um, uh, Lohmann, at the time, was a pioneer with the Abby Pro vaccines in order to make available this differentiated products to the global poultry industry. So it started in Europe, and then afterwards have been receiving approval by many, many countries. So we started with Vectra, which is now present in 24 countries. This was at that time the first live vaccine attenuated for sickness. Then in 1999, the monovalent Enteritidis vaccine, which is now licensed in more than 50 countries, 57 countries to be more precise. It was at that time the first and only Enteritidis vaccine with data comparing egg protection. And, and then back in the year 2012, which was the first and only bivalent live vaccine against the two most prevalent serovars. Not only was but it's still the the first, the unique vaccine confirmed these particular advantages. It is now being licensed in at least 36 countries. So we are very confident to introduce these technologies to the Saudi poultry industry. These vaccines are coming from Germany, so European GMP production site equipped with the state-of-the-art technologies when it comes to manufacturing and releasing these best-in-class live vaccines. And these particular facilities are exposed to multiple audits coming from regulators and customers from all over the world. And the feedback we receive is that after every single audit, the impression is that the standard being practiced here is is going above and beyond the the what has been established by law, so the European GMP regulations. So we are very confident to share this, uh, state-of-the-art facilities with our our visitors. And the safety profile is another important feature to be aware of. So these vaccines are not genetically modified. It's our natural strains that were developed under the metabolic drift mutation attenuation technology. And, and this is basically an attenuation that takes place at the chromosomal level, not at plasmid level. Therefore, these mutations are very simple and conform to the vaccine trend. Important safety function. So the first function is the shedding of the vaccine strain. It's very limited to a maximum 35 days, um, and this is after the first dose. So after the second dose, the shedding pattern is much shorter, and after the third dose, it's even much shorter. So a very important, uh, to consider. Also, once the vaccine reaches the environment, it's only surviving for a few days. So because of the the the structure has been attenuated so that it triggers the response in the bird, but then afterwards does not survive in the environment. It's not something we want. Uh, and since sensitivity to used for human therapy is of course increased at least by four times when compared to the field strain. And also the reversion to pathogenicity is something that can be discarded. A number of tests has been conducted, and, and after more than two decades using these vaccines, there has not been a single case of reversion to pathogenicity. So a very robust safety profile. And in this paper, it can be made available to you, you can find all the specifics when it comes to the MDM attenuation technology. So the differentiation between vaccinated and infected animals can be achieved by the the antibiotic marker principle. So each vaccine strain is having three markers, one related to antibiotic sensitivity, which is erythromycin, and two markers related to antibiotic resistance, which is rifampicin and streptomycin for the Enteritidis vaccine strain. And, and you have the rifampicin and nalidixic acid for the Typhimurium vaccine strain. So you have, you can see here a picture of how the agar plates enriched with the antibiotic markers look like after the corresponding incubation. So you can see the there is a growth pattern for the vaccine strain when exposed to this particular sensitivity and resistance marker. And the same applies for the Typhimurium vaccine strain. Another important consideration is that both vaccine strains do not grow in the modified semi-solid Rappaport Vassiliadis medium, which is the the official agar plate recommended by the EU framed by the ISO methodology 6579. The field strain will grow in that particular media. Other live vaccine strains will grow in that media, but not ours. That means if you test one positive, it will not be the vaccine strain. It could be a a field strain or could be another vaccine strain. Another important consideration, what to expect from Abby Pro is that.
It is fully consistent with the OIE requirements. So, the OIE established important features in terms of safety and efficacy, uh, for, uh, a vaccine. And the safety part is basically highlighting the fact that the vaccine should not persist in vaccinated animals and not be transmitted to eggs, and also has should have a limited survival in the environment.
In terms of efficacy, of course, you need to be able to increase the threshold for infection, reduce the level of excretion, and also reduce the transmission to eggs. And this is something that you can expect with Abi-Pro, a vaccine. So, in this particular study, it's a study completed in 2019, and we basically, uh, we're comparing the shedding pattern after using the the compliant vaccination scheme, so three doses during the rearing period. This Abi-Pro vaccine strain is another vaccine strain, another entirely different boxing strain. And detection sampling took place during the rearing period after every single vaccination, and also during the production period.
And in this graph, you can see the different dynamics in terms of shedding pattern. So, the, the other entry this boxing stream was having a very intermittent shedding pattern, so it could be not only found during rearing but also during the production period. While the Abi-Pro MDM strength was only found during the rearing period and not during the production period, which is, of course, something very important because you will not expect traces of the vaccine strain on poultry products. And this is, of course, compliant with the OIE standard and should be a the standard of every, every single food operator across the globe.
Another important expectation that should be considered as well is, um, the fact that only Abi-Pro's, I'm going to do is having the the claim to reduce not only reducing production of Salmonella at the intestine but also in internal organs, but on top of that, reduction at egg levels. So, being capable to reduce the number of positive eggs, similar entities, positive eggs, it is something remarkable that was tested under field in controlled conditions. And and the outcome is that after intravenous challenge, which is a very severe challenge model, the vaccine was capable to reduce positivity from more than 40% after the first week post-challenge to below 5%, and after week two and week three to zero percent. So, very, very impactful results.
Beyond that, the the product is also capable to confer protection against not only Group B but also Group D, and on top of that, Group C serovars. So, there has been some research conducted at Kent University in Belgium that demonstrated the ability of the vaccine to confer significant levels of protection not only in the spring but also in the Zika against Salmonella Infantis, which is becoming more a threat for ultramate operations not only in Europe but also in many, many countries across the globe, including Saudi Arabia as well.
Very good. So, with this presentation, I would like to refer to the takeaways. So, the holistic approach has proven to sustainably reduce the Salmonella infection pressure over time. So, the idea is to conduct some customized intervention in primary production, then complement those in the processing plants, so that we have integrated outcomes. Vaccination is as such a fundamental tool to trigger active immunity. All vaccines are able to trigger active immunity against a specific serovar, but only few of them are able to do so by, uh, enabling egg protection and also a coverage against multiple serovars in a safe way. So, we need to be mindful about the key important differences, and we need, we need also to consider the the, the, uh, the differences in terms of mode of action. Is something relevant to take into account. And last but not least, when it comes to Elanco's new vaccines, you may expect important advantages in terms of safety, convenience, robust protection from day one, and also coverage in terms of a spectrum against other serovars.
Thank you very much for your attention. I hope this information was useful, and now I hand over to Dr. Ali and Dr. Ahmed for the Q&A session.
Thank you, Dr. Francesco, for this nice and comprehensive presentation. Dr. Francesco, um, and foreign.
Will vaccination reduce contamination? This question for you, Dr. Francesco.
Yes, thank you, Dr. Ahmed, for the question. And the answer to this is yes. There is evidence that demonstrates that even in in those flocks that are already infected, the vaccine is capable to confer some reduction in the different matrices. So, reduction has been measured by testing the environmental samples and also by doing some necropsy in some sample birds. And and when you, uh, when you, um, apply the vaccine, yeah, you compare the samples before vaccination. So, there is some some differences to to take into account, right? So, there is a concept called therapeutic vaccination that actually refers to that. So, can we expect immunity even though the immune system is already immunocompromised? So, the answer is yes, of course. It cannot be compared with an immunocompetent flock, but of course, the, the protective effect is also expected.
And the second question: An area with high prevalence of Salmonella Enteritidis and Salmonella Typhimurium, will vaccination during production, both 45 weeks, be helpful in broiler breeders? For you, Dr. Francesco.
Yes, thank you, Dr. Ahmed. So, um, the breeder cycle typically is lasting only 65 weeks. So, on average, it could be less, it could be more than that. So, so that the the quality of the hatchability cannot be compromised. But if you have a particular situation where the challenge infection is is really high and and and you, uh, already comply with the strong biosecurity general measures, um, theoretically, the the good delivery of the three doses should be enough to protect during the whole cycle. Yeah, of course, associated with vaccination. If for any reason, yeah, the challenge is beyond the expectation, yeah, of course, it makes sense to to test the the fourth vaccination during late. We have been testing that in layers because of the length of the production cycle. So, we are talking about 80 weeks, 100 weeks, 120 weeks, and the time point for that particular fourth dose was a between 50 and 55 weeks of age, right? So, this is something that could be potentially extrapolated to the breeder, um, in case of very, very exceptional situations of very, very high challenge. But as I said, always combined with general measures. Yeah. And in short, the answer to the question is yes, this is something feasible and it makes sense. It makes sense. The question is, is it justified or not? And this is, of course, to be assessed after having analyzed of the different of the different factors influencing the results. Hopefully, this answers the the question. Okay, sir.
The question: In case of spray vaccination, can we mix other vaccines like IB, ND, or probiotics?
Yes, we do have some data with some commercial IB and ND vaccines that were having some a small concentration of antibiotics in the in the in the composition as a preservative, so gentamicin, for instance. And the result was that there was not a compromising effect. So, there was some compatibility. But this should be taken, the decision should be taken on a case-by-case basis because in the case of coccidia vaccines, for instance, we realized that some preservatives within the coccidia vaccine can be detrimental for the live strain. Live action. So, so the, the answer to the question is generally yes, but we should double-check and inspect, make sure that there is not a a compromising effect by looking at all the ingredients in the preservative of the viral vaccine or coccidia vaccine we are talking about.
Okay. The first question: What is the ideal TDS in water used in vaccination? I, I didn't understand the the term TDS. According to the water quality, what is the parameters of the water quality used for water vaccination of Salmonella live vaccine?
Yeah, there are some considerations when it comes to the the the physical parameters of temperature, for instance, and also chemical parameters. So, we need to make sure that the chemical composition of the water is is stable enough, not compromising. So, I mentioned the pH, I also refer to the chlorine, the ions, I also refer to the importance of not having a detergents treatments for the water acids. Yeah, so it needs to be a a water that it is not overwhelmed with a with mineral ions. So, in terms of water quality, a we need to need to be mindful about this potential risk to compromise the the vaccine strength. Um, we do have some information that can be made available in case you would like to explore more details about what particular components or agents can be compromising to the to the vaccine strain when applied via drinking water.
The next question: What about antimicrobial sensitivity of live Salmonella vaccine with other macrolides, erythromycin, or E. coli antimicrobials? Can we use these antibiotics with the live vaccine?
Yeah, the answer is preferably not because antibiotics, by definition, they are having an effect on the on the Salmonella bacteria, and the same vaccine strain is a very attenuated strain. It's very sensitive. It's a live organism. So, we should be very careful when utilizing these antibiotics. In theory, the those antibiotics having a spectrum against gram-positive only are supposed to have less detrimental effect, but still, we should be very careful. We have data with safety of four, so, third-generation cephalosporins, this is having a compromising effect. We also have data with, um, quinolones and fluoroquinolones, and this is having a compromising effect. So, there should be a waiting period of at least five days between the treatment and the vaccination if you already administer the antibiotic.
Okay, now all questions are answered. Er.
Yes, the answer is yes, you can utilize core spray. Nevertheless, um, experience in the field and also some documented control studies refer to the drinking water vaccination as the as the best, best approach to enable this colonization of the Salmonella live vaccine strain in in the intestine. Because when you deliver the vaccine via core spray, let's speculate, we do it in the hatchery, so the oral intake of the vaccine will also be, uh, by picking the birds. So, the birds are picking the the gel from other birds. So, it is the main route. So, the volumes of the vaccine strain are less compared to the drinking water. So, the drinking water vaccination gives you the chance to deliver more concentration of antigen compared to the spray vaccination. But it's also effective, and we do have also some data that refers to this spray vaccination as an alternative approach in case the drinking water method is not useful for whatever reason. So, so both are possible.
Thank you, Dr. Francesco. Uh.
Thank you, Vermont. Um. Is.