Good morning to everyone who is connecting to this webinar. Thank you very much for attending and trusting that this update I will do about diagnosing and controlling canine leishmaniosis will be useful for everyone. Well, to begin, this is a complex disease, and we all know the clinical management of this disease involves making a series of decisions to succeed.
And of course the key pieces are perhaps the size of this figure that I represent very clear. The most important thing is the diagnosis. To make a good diagnosis so that we can make decisions about the treatment that we're going to use and the follow up that we're going to take with our patients.
I have developed this talk on the aspects of the clinical management of Canine Leishmaniasis in a question and answer format, and we will try to answer these 10 questions that I consider basic and fundamental to control this disease or to handle it properly. Over the course of 1 hour with 10 questions, the first will be, how do I clinically classify my patients? What diagnostic tests do I need to do?
How do I establish a good prognosis? When do I start the treatment, and when do I finish it? Or when can I consider that we should not continue to use drugs?
What do we do if this clinic. Response is not favourable. What else do we have besides leishmannis or what else can we do, including complementary treatments, and when can we use them, when to do clinical checks and both sick and healthy animals and finally with regard to control measures of preventing measures that are effective, which are really effective and whether we vaccinate or not.
Plus we'll take a little bit about the responsible uses of passings. Well then, starting with the first question, when we talk about clinically classifying a patients, we have to take into account or remember all the concepts associated with immunopathology of this disease. And so we divide or classify patients into clinically healthy infected patients who will be the patients on the left.
A dog is infected but has not developed any clinical signs or pathological clinical alterations that are noticeable. It is performing an adequate immune response, a response type TH1. While the patient on the right is a dog that is sick because in this case we see skin lesions but it might not have them.
It could simply be a dog that was having some systemic clinical sign noncutaneous, and that in addition it may or may not have the illness or laboratory alterations that we could detect by the relevant analysis. In this case we call it sick, and we know that the immune response has not been adequate is a type of TH2 response, and the parasite has managed to evade this immune response and has been distributed throughout its organism and is actively multiplying, producing that impact that is translating into clinical signs or laboratory alterations. Well, the key to diagnosis is that we can see the differences well between these two types of patients.
That is the key. We can also consider that it is a dynamic effect that we can have clinically healthy infected animals. That end up developing disease or vice versa, we may have a sick animal that comes after treatment evolves favourably and becomes a patient on the left, becomes a clinical healthy infected patient.
Therefore, it will be all linked to the first approach that is properly classified. And so if we put on the table all aspects related to diagnosis in a healthy dog. We will not have to say that it will obviously have to be a dog without clinical signs, that its physical gesture is completely perfect or normal, that it does not present any laboratory alteration, that the quantitative serology is negative, meaning it is a zero negative dog.
That is therapidos are not positive and in addition that we do not find the parasite in any possible way, meaning there isn't one and molecular diagnosis is also negative. However, if we are talking about a clinically healthy infected dog, if it is healthy, we will not see clinical signs or laboratory alterations. But if on the other hand, We can consider that we can find obvious signs that the parasite is infecting it, that is, we can detect antibodies and titrates normally in clinically healthy animals.
These stritters are usually rather low or not elevated levels, and in terrapidos we might find according to their sensitivity positive or negative sterrapidos, but in In addition to molecular diagnosis, if we talk about appropriate techniques we could find a reactional pea. Finally, if we talk about a sick animal, we're going to find that it may or may not present obvious clinical signs that is, we can find seemingly healthy animals, but that instead they are later have laboratory alterations or vice versa. Animals that for example only present skin forms with their analysis are still mostly normal without obvious alterations in terms of serology, both qualitative and quantitative will be positive and in general, if we quantify antibodies which is appropriate, we will find higher tritters.
Than in clinical healthy infected animals, finally, also in molecular diagnosis, we will be able to consider that we will be able to detect the parasite by different mythologies and of course we will be able to detect or extract DNA from the parasite of some of the samples which we have taken. Therefore, if we look closely between clinically healthy infected dogs and sick dogs, in both of them, the molecular diagnosis is positive. That is why in this disease this diagnosis is not a primer.
It is not to the approach that we have to make or in the first instance we have to use. But going on the second question that we have asked ourselves what diagnostic tests we would need to do, obviously to be able to answer or to be able to classify this patient according to the previous scheme that you will have in mind, we will have to do a physical examination we would. To do a series of laboratory tests which include of course a blood count and a biochemical profile that allowed us to detect alterations in these parameters and we would also need to do a good full urine analysis and of course a serology.
Serology will allow us to detect if these animals have been exposed and have antibodies, but qualitative serology does not really tell us what level of antibodies are being produced, and that is why we need to have the result of a quantitative serology either by the indirect immunofluorescence method. Or by the quantitative Elisa method to quantify those antibodies and assess whether the moral response that it is producing in these individuals is elevated enough to consider that it is causing alterations. As for the PCR, as we just said, the PCR does not discriminate against us.
Of course we have to take it from a suitable target organ, mainly bone or lymph nodule, which are the most sensitive samples that will enhance this sensitivity of this technique and are the pros and cons of these techniques. This is undeniable a technique of great sensitivity as long as we use techniques that are based on the DNA detection of the parasite quinioplast, but as I said, the main con we have regarding this technique is that it does not discriminate between clinically healthy infected animals and sick animals because in both cases it would be test positive. It can serve us.
It is very interesting to define the infection in vaccinated dogs as we will see later in healthy dogs. We can find problems because we can find specially when we talk about quantitative. PCR, we can find that we detect loads that we can quantify and that this technique does not allow us to interpret well if we are seeing high loads in infected animals or in very sick animals.
These are not really well validated today to use them in this regard. That is why quantitative serology and haematological test, as well as bio analysis, are much more important to be able to establish a good diagnosis. Of course it is also very important to look for this parasite.
Try to detect the parasite where, as I said from the start, looking for the target organs, organs where it's multiplying, where it is multiplying. If there are skin lesions, we can use the skin. We can make skin imprints, and we are seeing here on a lip.
We're putting an object carrier on the ulcerative lesion. With a biopsy punch we can do a sampling on a dog that has skin lesions. We can do, as we said, a ganglion aspiration.
In this case, a popilial ganglion which has an evident increase in size. It presents augmented palpable ganglions or reactive ganglions. We can make a joint in cachondral union in the.
5th, 6th coschondrial union, a bone marrow aspiration and in all of them, in all of these cases what we try to show is the parasite which, as we see here in the centre of the slide infecting macrophagal here we see leishmaniasis and must the goats in a macrophag of an infected dog and in this case it is a bone marrow aspiration. Therefore, the bone marrow, the lymph nodule, the vessel, the skin are all target organs where the sensitivity of the technique will increase because it is easy that we find the parasite in these places we are less likely to find it in the conjunctiva. We can also use techniques from this that we have obtained these aspirations or these samples we can also perform.
Histopathology, high monohato chemistry, PCR, and the samples that we consider less which are going to greatly reduce the sensitivity of the technique are bloodbasico, or urine and that's why when we're trying to demonstrate the parasite we don't recommend them we don't recommend doing a blood PCR nor. Doing a urine PCR, but it is much more interesting to use the samples that we have already described that are in the box on the left regarding how we classify patients from the IS bead group from Iceland that are published in different languages in 7 languages currently and which are based on classifying patients from different stages from 1 to 4. Depending on the results of the analysis that we're talking about so far, which are quantitative serology, clinical signs, clinical pathological alterations, and based on these parameters we will be able to establish a prognosis and we will be able to determine or make recommendations on the most appropriate treatments.
As we well known in Canning leishmaniasis, it is very important to understand that the prognosis will be much more reserved in those animals in which we are already having an alteration or kidney disease established. In these cases, the guidelines of the ice bead recommend or we also recommend following the recommendations of the Iris Group, which is the group or scientific society of renal interest that develops a series of guidelines or recommendations to follow depending on the renal disorders that patients present, and that is. Why we're going to classify our Leishmania patients too, making an Irish classification as soon as we have an asotemic or proteoric animal, and this classification will be very useful.
So from this moment I recommend the two Galen to be able to complete the follow up on these patients. Speaking of prognosis as we have just seen in the Gallens, in order to make a good prognosis, first we have to classify the patient. It will be interesting that we evince the parasite and that we use the biomarkers that we deem appropriate to complete the diagnosis according to each of our patients.
As we well know, this disease is very different in every patient and therefore we should take into account the appropriate bio makers for each occasions. If we talk about clinical leishmaniasis, we know that the main clinical signs we're going to find may be abstinence, weight loss, lymphadenomegaly, skin lesions, and also other clinical. Signs associated with the deposit of monocomplexes in this case we are going to find we may find polyarthritis.
We can find vasculitis, histasis, eye injuries, nephritis, and we are very clear, of course, that not all these clinical signs will appear in all animals. Combinations of them may. Or simply a single clinical signs of all of them, but it is true that the prognosis and the laboratory alterations that may occur, which the most common are hyperpetanemia, hypobulinemia, non regenerative anaemia, leukopenia, sometimes leukocytosis, and elevated antibody titers.
I insist that not all these laboratory alterations have to appear in our patients, but they are the most common and to establish a prognosis. We know we are clear that we represent in red the disease by deposit of in monocomplexes. Which is to say that when we find patients with one of these 4 groups of clinical signs we can conclude that the prognosis is much more reserved.
In addition to this alteration or these clinical signs, also the laboratory alterations associated with monoclonal gammapecia, hypobulinemia, aleucopemia, proteinuric and asodemic dogs, we consider that the prognosis is much more reserved. Moving on to the treatment, we will have to review well that there are pelotic tools we have. We do not have many.
It is really worrying that even today we can count them with the fingers of one hand. The therapeutic tools that we have today to treat canning leishmaniosis starting with understanding that of course not all are equal so we can say that we have antimonials and benfuine as unique leishmanicids with proven therapeutic effectiveness. And allopurinol, which can be considered a leishmania static.
Today we use these three tools in combination. We combine the antimonials or the mindful scene with allopur. And then we can use the immunomodulators or immuno stimulants such as doperone or nucleotides which we will go on to explain later.
When do we start a specific treatment? Well, we repeat that we have to make a good clinical classification. If we do not have the patient classified, we will not be able to make decisions about it.
And so again, we review the I be guidelines, and these guides we established according to the stages we have already commented. We have a mild disease that will be a stage one in which regarding treatment we talk about using the treatments in short periods. We can use allopurinol, domperidone, nucleotides depending on the clinical situations that arise for stages 2 and 3 we use combinations of la.
Ses with leishmanostatics meaning combinations of antimonials with allopurinol or mindhoine with allopurinol and of course knowing for sure that if we talk about animals which already have alterations or there is proven kidney disease we will have to make a parallel with the recommendations that you make to assess. What are the possibilities of treatment and regarding stage 4, which is very serious disease asotemic and proteinuric animals with elevated UPC in these animals we will follow the Irish recommendations to manage the chronic kidney disease and perform very individualised treatments. At the beginning of this table we see a zero stage that will be the animals of which we started talking about first, which are 0 positive dogs that have no clinical signs or laboratory alteration.
Today we recommend not treating these dogs. Do not treat them with the le main treatments that are available. We recommend tracking them.
Regarding dogs in stages 1 to 4, the question following treatment. Once we have decided to use one treatment or another, we will have to assess when we seize the treatment, and it really is to talk about diagnosis. That is why we have to value that we have a dog that we have treated because it was sick and we have managed to make the clinical signs that is presented disappear because there has been a good favourable clinical evolution which is normalised in all the laboratory alterations that is initially presented and of course we get the antibody titers to descend to limits close to the cutoff point.
Which is to say that we have antibody titers almost reaching normality. Therefore, we ask the question again, when do we stop treatment? When we manage to convert a sick dog into a clinical healthy infected dog.
This is critical and it is the cornerstone of decision making regarding the management of this disease. With regard to whether or not we should treat clinically healthy infected dogs, the leishbit groups and other experts in leishmaniosis current recommendation in the clinical management of this disease is that it's not recommended to treat these patients, but what is recommended is to continue follow. If these patients are 0 positive, we will do a follow up every 3 or 6 months with the usual test that is doing a good physical exam, doing relevant laboratory tests and doing a quantitative serology and what we have to do with our patients is to have extreme preventive measures.
Maintain adequate treatments which are of course to avoid the transmission of leishmaniasis by biting vector insects which are phlebotomous and therefore the use of repellents with proven effectiveness. We will use these repellents properly in the periods of. Risk and if we have animals that result zero negative, we also have to follow up every 6 or 12 months we can space these follow ups and we'll have to use repellents or basins always combined in all animals that are sero negative.
Well, if the clinical response of our treatments are not as favourable as we wish, that is, we find dogs in which we still have clinical signs and laboratory alterations, we will have to keep in mind that we may have an incorrect diagnosis. We have to think about reconsider. The diagnosis or considering whether there may be underlying diseases, other systemic diseases which are prevented and 100% favourable clinical response.
And of course if they are animals exposed to phlebotomine bites, they may also be exposed. To other bites from other vectors and therefore we will have to bear in mind that they might be parasitized or may present other coinfections from diseases transmitted by ticks or transmitted by fleas or by other arthropods, and it is essential to make a better diagnosis. If on the contrary we have considered that all these options have disappeared, we can have dogs with disease with chronicle clinical leishmaniasis, that is, dogs in which relapses occur because they are animals that do not have a good immune.
And in these cases we could increase the treatment time from 4 to 6 weeks and talk about leishmaniacids. We can even increase the doses of leishmaniccids, but as I say in these cases we have to individualise. We have other things in addition of the leishmaniacids which are fundamentally allopurinol, lomperidona, and nulotidose.
These three drugs are being used right now in combination with the leishmaniacids in different clinical situations. We have to understand that they are very different. Allopurinol is a leishmaniastatic, meaning it will inhibit or prevent the multiplication.
Of the parasite while the lumperidona and necloids are immunomodulators, this means they act in a different way. We're going to review its mechanism of action with regard to the lumperidona, but it has a direct impact on the pituitary gland because it has a prolactin trend efficacy while the nucleotids are going to. Act on the immune response.
What I mean by this is that they act differently and therefore we can't put them on the same group. We're not always going to use them, nor in the same way. So if we start by speaking for allopurinol, it's a structural analogue of the eposantina.
What it does is prevent the growth of leishmania by inhibiting protein synthesis. They're not used of. For long periods between 6 and 12 months, as long as they do not produce adverse effects, the side effects associated with allopurinol are mainly xantinuria, that is, we need to do a bioanalysis follow up whenever we're using it 30 days or 60 days after treatment because we should do a complete bioanalysis to evaluate and as long as we use it for a long period we should perform abdominal ultrasound to be.
Visualise if there are any mineralization problems in the renal pelvis that will end up translating into nephrolithiasis, which are really serious problems that we could be using with the use of this drug without control and therefore we should withdraw these treatments if these patients only have antinuria, we can reduce dosage or increase frequency, convert these treatments instead. Of every 12 hours do it every 6 or every 8 hours but with reduced doses and if there's mineralization or nephrolithiasis, we have to suspend and avoid its use. Additionally, the misuse of this drug is already causing resistances which are published by important research groups in this case by a research group in Israel at the University of Tel Aviv.
We have as alternatives to this drug allopurinol we can use immunomodulators knowing that this is an immuno-mediated disease, very important, and there is different scientific evidence that demonstrate this dysfunction in dogs with leishmaniasis. The immunomodulators that we have now. Available are the lumperidona and neolotids which are unspecified in mono modulators but which may be useful in the clinical management of this disease.
There is a research in human medicine different types of cytokines are applied to live receptors which can act directly by modifying these. Immunised response but at this time they are extremely expensive for veterinary medicinal uses and are the subject of research by different groups but we do not have them available commercially nor are there enough studies to support their recommendation at this time. Well, with regard to those that if we have today already available or market in some countries in Europe, peridone is established that Loperidone is good initially we use it in internal medicine as a blocker of dopamine receptors.
And we use it as anti-hermetic and prosynaptic and it is a very old anti-hermetic from 1985, but it has been assessed that it might have an interested as an immunomodulator of Lomania. Because it works by increasing the prolactin levels in the blood by hypophhysis secretion, meaning it acts on the pituitary gland inducing prolactin production. That is why we say that is a BOGO prolactin.
If we use daily repeated doses in dogs, there are proven studies by researchers like Pablo Gomez Ochoa in 2012. And subsequent studies by the same groups in 2015 showed that this prolactin could have an effect. It could act as a cytokine producing a stimulating effect of the cells-based immune.
Responds essentially stimulating phagocytic function of the macrophagga and neutrophils and therefore having a beneficial effect in patients with leishmaniasis. Actually, the lumperidone may be considered to be of interest in its use, but may also have an organic impact, especially in patients with other disjunctions such as endocrinopathies. Continued levels or repeated doses of this prolactin bogus could actually have an unwanted effect on the pituitary gland and therefore more studies are needed to be able to recommend it indiscriminately.
And that is why I insist that it must be used conveniently and knowing which patients are adequate regarding the necloids that we have available right now on the market, specific necloids which in combination with fungus extract, that is the lupine's eludes, we can say that it can. Become an immunomodulator that has been shown to boost cell-based immune response. Also that it can increase this phagocytic ability of the macrophagga.
And also because it promotes or is a good promoter of the proliferation of the Tylder lymphocytes. Which can create a good TH1 response. We also have studies by Cigarra and collaborators from 2017, studies in which I have actively participated, clinical studies in which we compare two study groups with animals to which we administered to one group allopurinol masloan time.
And in the other group allopurinol massim promune and the results we got were that we find a similar response or clinical efficacy in these patients and even in patients. That didn't take allopurinol there was no presence of santinuria, which we know is an adverse and unwanted effect that can occur in patients who take it. In a second more extended study in which this drug was used for 12 months, which we published in 2018 comparing 64 animals clinically healthy infected animals using the leishmanicid treatment which impromune plus the leishmanicid treatment or using leishmanis.
Treatment with placebo treatment we were able to see that giving the same medication for 6 months we could obtain a lower progression in the disease meaning we achieved a preventive effect on clinically healthy infected patients. Leishmany treatment had to be used on 23% of the patients. This means that over the course of a year of these healthy patients, we were rating out of 64.
Animals we found that in 23% of them we had to use the leishmany treatment because of the immunomodulatory treatment wasn't enough by itself. Continuing with the treatment, we can say we have other complementary, fully complementary organisms that can be used and that can be very useful. Of course they have to be associated with what is needed depending on the clinical picture.
So when we have animals that have skin infections or urinary bacterial infections, always with previous cultures, obviously or urine cultures depending on the situations, antibiotics can help improve the clinical picture. Cortico therapy may be indicated in some cases of disease caused by immunocomplex deposits, but it has strictly controlled and in short periods of time all of the dermatological cosmetic. Currently available on the market, topical treatments based on anti-saics, antiseptics, shampoos, etc.
Will help or contribute to a skin sanitation. And an improvement of all these aspects or alterations that create sevorea and they can be very useful. It is also very important to assess the diet of our patients with leishmaniasis.
The main and most important thing for us is that the dog eats. We need them to get him a palatable diet. It's fun to make.
This diet has to be low in proteins as long as we have a patient with kidney disease. If that's not the case, if we do not have a patient who already presents proteinuria or aotemia, the dogs can eat normal diets because they can eat maintenance diets. We do not have to use hypoprotein diets in.
Patients who do not have renal affectations, we can use normal maintenance diets or we can use specific diets. We have a specific diet for dogs with leishmaniasis which gives good results, although cost must be assessed, especially on large dogs, and we can also use home diets. As I mentioned, we need to use palatable diets.
We need to whet these patients' appetite. We need them to eat properly. If they don't eat and we have them in our hospital, we need to evaluate and make them start eating, or if we need to medicate them appropriately and they are hospitalised for some time, as we may consider the application of nasogastric tube.
To try to get them to start eating and get them to have an appetite again so that we consider that their overall condition improves and after that we can start using more aggressive treatments once we have treated these patients and their clinical evolution is favourable, we have to do clinical monitoring with periodicity which must be bearable according to times as a rule. We can say that sick animals, dogs that we have treated, we monitor them one month after treatment that should include a haematology with biochemistry profile and urine analysis. It is very important to do urinary follow up at this point because we are already saying that allopurinol can have an organic effect and therefore it is essential.
To know in these cases in these patients whether they are already producing chantinuria or not 4 months after treatment we can do or repeat the quantitative serology and make proteon onogram which will be very useful to start assessing whether there is a febrile response, whether that humeral response starts to descend, and if we have a good response, then after. After 8 months we repeat the biochemistry emogram again and ure analysis and after 12 months we repeat the proteogram quantitative serology at this point it will be interesting to do an abdomen ultrasound to assess renal morphology, mineralization, presence or not of masses or other alteration which may be of great use to us. What do we do with healthy animals?
Healthy animals, if they are sero positive, we should repeat the serology at least once a year, making a physical examination, and whenever possible, we should take into account making an annual monitoring on these healthy animals, always monitoring 3 or 4 months after the end of the risk season of presence of the vector of phlebotomes. Why? Because we know why we are slow to detect antibodies in infected dogs, in experimental infection, we have been able to show that they have antibodies between 45 and 90 days post infection.
Therefore, it is highly recommended that we do the serology in healthy dogs after the seasons of risk when these minimums have passed for 2 to 3 months. In our terms all over the south of Europe we could say in endemic areas of Leishmaniasis it will be indicated to do these annual checkups in January February, meaning wait. After the summer and fall to wait for these animals to have detected antibodies finally we move on to the prevention we have very little time left, so let's talk about prevention.
In regards to the measures which preventive measures are effective, well, we know that we have repellents on one side in pipet forms, colours, or sprays, and we have the vaccines as well as immonomodulators. We have already explained the immunomodulators and really in the prevention of our healthy animals we need to talk about the combination of repellents with vaccines and certainly if the only way to avoid transmission is the use of repellents. When we use repellents in colour or in pipette form, pipettes normally have a determined action start of 24 to 48 hours.
Colours can take a little more time. It is very important to take into account the duration of the repellency, that is when we have to repeat the use of these medications or the administrations of these drugs. In function of the duration of its repellency, this is essential in terms of basins.
We need to know, or we have to remember that basins do not prevent infection and therefore, the only way to avoid infection is to avoid transmission and avoid the sting of phlebotomes. But if we use vaccines for another purpose which is in monomodulate or create a good. Immune response in healthy dogs we have to consider those which are not essential vaccines.
The vaccins that call core basins are what we consider essential and should be used in all animals during the first year of life, such as vaccines against the distemper virus or parbo virus or well, depending on the situations laptop series or anti rabbi's vaccine if we talk about. Leishmaniasis, we have to consider which dogs are susceptible to being vaccinated. To begin with, they must be healthy dogs, er negative dogs.
It is more likely that we will apply it on young dogs using it on old dogs doesn't make much sense because they can have other diseases, so we are not establishing for healthy animals, but in any case we will have to individualise. We will have to. Consider what is the risk benefit that these vaccines have if we use them with a justification in vaccinated dogs that can become infected by whatever reasons, be that the repellent hasn't been 100% effective or because it has not been used properly or because these dogs are more susceptible if they're healthy dogs that have been vaccinated, the disease that occurs is going to be.
Moderate, this is really the goal of a vaccine against leishmaniasis to promote an adequate immune response in these dogs when they become infected and thus avoid a progression towards a serious illness that is really the goal of the vaccines. In addition, there are studies that show that these vaccines can reduce the effectiveness of these animals once vaccinated. When should we use them?
We always need to know when dogs develop immunity to these vaccines. We have two types of vaccines today on the market. If we use the vaccine market under the name of Canylace, which is an excerpt from Leishmania in phantum, a protein of secretion expression, the immunity is going to occur within 3 weeks of the last injection.
There are 3 doses while we let the. Is a protein recombining the Q protein immunity is going to occur a month after vaccination. Therefore, we have to take into account this moment of acquiring the immunity to use them according to the risk period to occur and therefore always 1 to 3 months before the start of the risk period so that these talks may be prepared.
This leishmaniasis prevention plan has to be tailor made. We must individualise the cases and therefore we will have to take into account the state of health, the age, the type of life, whether they are working animals, their attitude, whether or not they travel to endemic areas, and the owner's characteristics. We have to take into account if the owners to whom we're going to recommend these preventive measures are responsible owners or forgetful owners that you tell them that they have to use a pipette every 3 weeks and they.
Forget and apply it every 5 or every 6. Maybe with these less responsible owners it is advisable the use of a necklace which you know has an effectiveness of 0 to 12 months depending which one we use. We cannot put in the hands of the owner the decision of what to use, which preventive measures to use.
We are the veterinarians, the health educators, and we are responsible of doing this properly according to the kind of honour we have in front of us of their social economic situation, we can't propose to them, well, these cuts so these costs. Yes, it is our responsibility as clinical veterinarians to offer the best option according to the type of owner they are. Therefore, we can't ask them to make the decision of using repellents or vaccines.
If we tell them to use both, they have to use both. If they cannot use both of them due to the economic restrictions, we have. To do without vaccines and we'll have to recommend only the responsible use of repellents with regard to vaccines comparing these two vaccines, well, here we have the comparison of the two vaccines.
Mainly both are indicated in several negative animals of 6 months or older, a previous serology to detect antibodies in presence of leishmania. Should be done in both cases. In the case of Canillas, a qualitative serology is recommended.
While for epicent a quantitative is recommended, you have to follow the information left let on each of them, and I recommend that you read them properly. It seems that there are more adverse reactions in the former rather than in the later, but. It is likely that it may also be an individual response, and it has to be evaluated.
Immunity, as I have mentioned, occurs after 30 days in the case of Canillase and 30 days after the only dose of EpiPen that is administered. The duration of immunity in both cases is 12 months, meaning we have to re-vaccinate after. 12 months if patients remain zero negative, it has been shown it reduces the infecting capacity of dogs if they are infected throughout the year vaccinated with cannulase.
There are no studies with EpiPen yet. As for cannulase, we have an interference with the diagnosis. We're going to see it now.
The animals vaccinated with cannulase develop post vaccine antibodies, therefore. There may be an interference with the diagnosis, and we may not be able to discriminate between infected healthy animals and infected vaccinated animals while Epiphan is a live vaccine in which it is very clear to discriminate between infected and vaccinated animals because dogs with Epien do not produce post vaccine antibodies. Finally we can see.
What are the antibody kinetics in these dogs vaccinated with cannulase, and I show them here on this last slide. We can see antibodies vaccinated with Epiphen developing a maximum elevation of antibodies after 14 days to 21 days of vaccinate administration, but these antibodies persist for 4 to 6 months. These studies.
We conducted in 2013 and 2014, but we, our research group, studied a high number of dogs up to 90 dogs in which we can see in this graphic that we found several positive dogs even 12 months post vaccination. Therefore we have to keep this in mind when we vaccinate with which type of vaccines we are vaccinating. To summarise and finish this seminar, let us talk about integrated control, understanding the differences there are.
If we're talking about an endemic area, we know that we only see the tip of the iceberg, which are sick animals, which would be a very small percentage with respect to the rest of the population. We have, we can say 5% to 10% of sick animals. We have 50 to 60% of clinically healthy infected animals.
And finally we have a percentage of 0 negative healthy animals. In all cases sick clinically infected and healthy animals, we have to recommend the use of repellents in endemic areas. Additionally, in the event that we have sick animals, we will carry out the treatments we have already seen and the proper follow up in clinically healthy infected dogs, we will always have to monitor all developing cases.
We will be able to use some immonomodulators if we deem it appropriate and in the exclusive case of sero negative healthy animals we will be able to administer vaccines in combination with the repellents. This is the integrated control scheme for individual animals in endemic areas. If we talk about controlling this disease in communities or in dogs that travel to.
Endemic areas we will have to do dogs that live in non endemic areas but are going to travel. Excuse me, dogs living in endemic areas that are going to travel to non-endemic areas, as are all the dogs imported from south of Europe to non-endemic areas since other families will adopt them, we will have to do adequate veterinary checkups before their departure with their. Quantitative serology and they have to be negative when we talk about dogs going the other way, meaning they live in non-endemic areas living in Germany for example and they're going to travel with their owners to an endemic area for a short period of vacation, we recommend the use of repellents exclusively if there are short stays if we're talking about long stays of 3 months, for example.
We recommend the use of repellents associated with the use of vaccines, and we recommend checking on these animals using a quantitative serology 3 or 6 months after returning from that endemic area and not before. Always do it with a quantitative serology and not performing a PCR because as we have already seen, it will prove nothing to us. Finally, if we're talking about collectives, especially in breeding centres, if we detect infected animals, either male or female, the recommendation is that we do not use them.
The fundamental preventive measure is not to use them as breeders since the vertical transmission of the Leishmania infection has been proven from mothers to children or between breeding males and females. We recommend sterilising infected animals and of course not importing reproductive material because the presence of leishmania in phantom in breeding male semen has been proven and therefore this is contraindicated. I will finish establishing a series of messages or conclusions that I would like to leave as key pieces of this seminar I just gave.
A good diagnosis is essential before you act, before you start making decisions. We know now it is a challenge to control the disease by immunocomplex deposits and that the animals that have the. Worse prognosis are when these diseases are associated with immunocomplex deposits such as polyarthritis, vasculitis, or Uveitis.
We know today that the trend in the treatment of cunning leishmaniasis is a combination of leishmanicids and leishmaniostatics such as immuno potentiating molecules. And finally that vaccines do not prevent infection. It is essential to always combine them with the use of repellents and use them only and exclusively on healthy sero negative animals and with this I'm done.
Thank you very much for your attention and I hope this helps you to formulate many questions and to continue studying as well as following all the recommendations we have established here. Thank you very much for your attention.
