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New hope for cats?

Original article on Facebook Medipet Zlín.

Treatment of a fatal disease called FIP.

One of the common and very serious diseases in cats called FIP - feline infectious peritonitis (feline peritonitis), which is considered an incurable disease with high mortality, is experiencing new hope for successful and safe treatment.

FIP is an immune-mediated disease caused by feline coronavirus, which belongs to the group of enveloped RNA viruses (RNA is a type of nucleic acid that encodes the genetic material of several viruses) and has the abbreviation FCoV (feline coronavirus). The transmission of this viral disease takes place via the faecal-oral route (infectious particles are present in the faeces of an infected individual and can enter the digestive tract of another susceptible individual through the oral cavity) and are not transmissible to other animal species, including humans. The common FCoV infects the intestinal cells within which it multiplies, and in the process it can mutate (alter its RNA genetic information) within a particular cat. This new mutation allows FCoV to multiply in cells of the immune system called macrophages, a point that is becoming crucial for the development of FIP. If feline immunity cannot prevent this, a systemic immune response soon occurs, which is fatal for the cat. Factors that increase the likelihood of mutation are the potency of the virus and the weakened immunity of the cat.

FIP is always a diagnostic challenge for veterinarians around the world. Why is that so? This disease has very non-specific and variable clinical symptoms, has no specific changes in routine laboratory diagnostics, and in practice there is no available and sufficiently sensitive and reliable test to detect it.

Diagnosis is a jigsaw puzzle of several hints.

  1. Clinical signs of the disease, which are very often non-specific and present in varying intensity. In practice, 3 forms of the disease are described - wet form, dry form and form transient between wet and dry form. The imaginary is a clean dry and clean wet form at the opposite end of a wide range of symptoms. The development of a specific form of the disease depends on the immune response of the cat and the intensity of the production of antibodies, which, however, do not have a protective effect. The development of the so-called granulomatous inflammation of individual organs (granulomatous inflammation is one of the subtypes of the body's inflammatory response) is the cause of a variety of symptoms, because one specific organ is not always affected, but the whole amount and in different severity. As a result, the dry form of FIP is difficult to distinguish from other diseases by clinical examination. Increased production of antibodies leads to inflammation of the blood vessels, which leads to their disrupted integrity and the formation of effusion in the body cavities or the heart. Commonly observed symptoms include fever that does not respond to antibiotics, drowsiness, decreased food intake, wasting. Depending on the degree of involvement of the internal organs, symptoms of kidney damage (enlargement and pain), vomiting and diarrhea in case of digestive system involvement, enlargement of the lymph nodes in the abdominal cavity, pneumonia accompanied by difficulty breathing, changes in the eyes (changes in the iris) may be added. , blood in the anterior chamber, uneven pupil size, sudden loss of vision), eye examination reveals inflammation of the retina. 10% patients with FIP experience central nervous system disorders, such as gait disorders, convulsions, spontaneous eye movements, increased sensitivity to pain on normal touch, and behavioral changes. Rare symptoms such as inflammatory skin changes have also been reported. When the blood vessels are broken, an inflammatory effusion occurs, which is very important to examine thoroughly. There are transient forms of FIP that combine different dry and wet symptoms.
  2. Presence of inflammatory effusion. According to statistics, only 10% feline cats have FIP disease, so it is extremely important to rule out other causes such as heart disease, lymphoma, biliary tract infections and inflammation of the lining of the body cavities from other causes. It is often stated that the effusion is characteristic, this is not the case, and there are several variants of the effusion in cats with FIP. The most common is a yellowish, viscous effusion rich in protein and fibrin, which contains relatively few cells.
  3. Changes in the image of white blood cells. This can be changed in terms of an increase in the number and types of white blood cells, but also in terms of their decrease.
  4. Serum protein changes. There is an increase in total protein in the blood serum (this may be due to the production of inflammatory proteins and antibodies). The ratio of proteins changes and is accompanied by ratio changes of individual proteins such as albumin to antibodies called globulin. Albumin is one of the proteins in the blood serum and is formed in the liver. The albumin / globulin ratio drops below 0.8. Decreased albumin is aware of its leakage through damaged blood vessels, as well as reduced production in liver damage.
  5. Serum protein electrophoresis. This is a special test that reveals the amount of individual types of protein in the blood serum, which is not determined in a routine test.
  6. Other changes in the blood test called biochemical examination, which tells about the metabolic processes of some organs. This test is not specific, but can help us consider the severity of the patient's condition.
  7. Examination of cerebrospinal fluid in cats with symptoms of central nervous system damage.
  8. However, by determining antibodies whose interpretation has its limitations and pitfalls. The fact that a cat has antibodies against the FCoV virus does not mean that it has been mutated and thus that FIP is behind the symptoms of the disease. Most cats have antibodies to the harmless form of the virus. However, the absence of antibodies does not mean that the cat does not have FIP. Their formation depends very much on the patient's immune status. Sometimes high levels, along with other contexts, can help us diagnose.
  9. Detection of virus particles in tissues or effusions. These more complicated but available immunological laboratory methods also capture mutations in the virus itself and can distinguish the mutated from the harmless form. The problem with this method is that this test is most often performed on the cat's life and it is impossible to detect whether the virus is also present in the blood at a given stage of the disease. There is a so-called false negative result. Cats that have an effusion should always be referred for this examination when considering FIP.

Based on diagnostics, which can be costly but absolutely important, we should take a responsible view in such a serious case as FIP. The prognosis is very unfavorable, cats die on average within 16 days of the disease developing, with an average survival of 8 days. However, longer survival periods have also been described, e.g. several months with mild clinical signs. Adverse conditions include reduced quality of life, wasting, ingestion of food or only small amounts, a reduction in the number of white blood cells and a large amount of effusion. It can be said that if a cat stops eating and starts to wither in FIP, it will soon die.

Efforts have been made for a long time to develop effective vaccinations to prevent the disease, but its suffering is impossible. Vaccination does not protect against individual mutations in the virus and, in addition, dramatically worsens its course. It is not available at all today.
Today, FIP treatment includes several possible treatment protocols using drugs that alter immune responses and supportive drugs. These protocols, however, do not cure the disease.

New hope?

In the February 2019 study, the study of Dr. Niels C. Pedersen in The Highly Journal of Feline Medicine and Surgery, which tested probably the first truly successful therapy for the disease. The development of the drug was inspired by the treatment of Ebola virus and similar diseases, which are caused by viruses also belonging to the group of RNA viruses. So far, this drug is called GS-441524 and it is called nucleoside analog. The nucleoside is one of the building blocks of the genetic information of the RNA virus, this analogue can be included in its construction in exchange for the original building blocks and thus prevent its application and multiplication. It is a very small particle that can freely enter the cells of the body where the virus multiplies. A safe and curative amount of the drug was injected once daily into the cat's subcutaneous tissue for 12 weeks. In the vast majority of treated cats, there was a significant and rapid response to treatment. This treatment test was properly accompanied by regular blood tests and possible effusions, eye examinations and daily clinical examinations. In the dead animals, or animals where euthanasia was necessary due to severe deterioration in the first 2-3 days of treatment, a post-mortem examination was performed in connection with the detection of viral particles by a special examination. The result of this study was more than surprising. The treated animals improved their health and the amount of virus particles in the effluent and their amount decreased within a few hours. All cats that underwent a 12-week treatment, survived and had a good quality of life long after the end of treatment will continue to be carefully monitored for any recurrence of the disease. No systemic toxicity was observed during treatment. So far, this drug is only available in studies, but we hope that it will soon become available to ordinary patients, for whom it means a completely new hope for survival and perhaps a cure for the disease, which is still commonly fatal today.

MVDr. Katarína Novotová
Medipet Veterinary Clinic
Broučkova 5395
Zlín

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Dr. Pedersen about relapses and posttreatments

Original article: Dr. Pedersen on Relapses and Post-GS Treatment; 14.8.2019

Is it possible that GS-441524 will lose its effectiveness, leading to relapses?

In particular, GS-441524 is extremely stable in the highly acidic solution used by its suppliers. We stored it in the fridge for months. The more likely reasons for relapses are inadequate treatment (poor injection, poor medicine), inability to get enough medicine in places with inflammation (such as the brain), or drug resistance (we saw this in 1 cat in both our GC376 and GS studies). -441524).

Are secondary infections such as toxoplasma or infectious anemia associated with relapse?

This is very unlikely for secondary infections that lead to relapse. Cats are the ultimate host for Toxoplasma gondii and the infection is rarely systemic. In fact, the systemic form is so unusual compared to FIP that there is no good clinical reason for its routine testing in cats suspected of having FIP. In addition, toxoplasmosis would be much more likely to occur in outdoor cats that hunt than in shelter or indoor cats that are fed commercial feed. Infectious feline anemia, which is caused by a common and largely overt blood infection with one or more types of hemotropic mycoplasma or hemoplasm, could break into clinical form upon immunosuppression by another infectious agent. However, I cannot recall the case of FIP, which was complicated by these organisms. However, feline leukemia virus, and not coronavirus, is strongly associated with hemotropic mycoplasma. Nevertheless, I suspect that this is one of the reasons why so many veterinarians include doxycycline in the cocktail of drugs they used to "treat" the FIP.

Should cats receive Virbagen omega after GS treatment to strengthen the immune system?

Published double-blind, placebo-controlled studies of feline interferon omega in FIP have shown that it has no therapeutic benefit. I also perceive this with other immunomodulators such as PI.

Should I try to eliminate feline enteric coronavirus (FECV) from my cat's environment after the cat is no longer treated with GS-441524?

This virus is so ubiquitous, difficult to eliminate, and easily reinfected that I have come to the conclusion that attempting to eliminate it will be very costly and largely unproductive. Although it is possible to eliminate FECV in a small group of cats that are kept in strict isolation and by faecal testing, in reality it is easier said than done. In the end, even if you succeed with great effort and cost, what will you do then ?! The only way to maintain the situation is to observe an extremely strict quarantine of cats and people moving in and out of your premises, which greatly complicates the ability to maintain a functional shelter or rescue or kennel.

How useful is the AGP test to find out if my cat is cured?

The AGP test is popular in Europe, but I can't figure out why. The test measures what we call the "phase reactant" and is a measure of inflammation in the body. It is completely non-specific and has no added value compared to routine examinations, such as general health, weight loss, fever, abnormalities in white blood cell parameters, albumin and globulin levels, A: G ratio, etc.

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How to Diagnose and Treat Feline Infectious Peritonitis (FIP)

Original article: How to Diagnose and Treat Feline Infectious Peritonitis (FIP)
8/5/2019, Translation 1/25/2021

Feline peritonitis (FIP) is a relatively rare disease that usually occurs in cats less than two years of age or if they have lived or are living in a group with multiple cats. FIP is caused by an inadequate immune response to a common virus called feline coronavirus. Most cats that get the virus can eliminate it without any lasting consequences, but some cats have a virus mutation that leads to the development of this devastating disease. There are two forms, wet and dry. If a cat develops FIP, it is almost always fatal. Learn to recognize the symptoms of FIP, take your cat to a veterinarian and have it tested. If the diagnosis is confirmed, there is no official treatment, but you can provide supportive care to the cat.

This procedure was written before the GS441524 FIP treatment boom. So one last point could be added here - the real cure and the mention that FIP may not always end in death.

Recognition of FIP symptoms

1. Notice the change in appetite. Cats can stop eating or reduce the amount of food they consume each day. Because of this, the cat may begin to lose weight. In kittens, this may slow their growth. These symptoms are characteristic of wet FIP.

  • Despite poor food intake and weight loss, the abdomen may swell and the cat may look like a balloon.
  • A cat can also have diarrhea.

2. Monitor for breathing problems. Infectious feline peritonitis can affect the cat's respiratory system. The cat may have difficulty breathing and wheezing. He can also sneeze and have a cold. These symptoms are also characteristic of wet FIP.

  • These respiratory symptoms may be associated with the formation of fluids in the chest cavity.

3. Pay attention to the health of the cat. The second type of FIP is the dry (non-effluent) non-effluent form. If the cat has this form, it will be in poor health. Kittens may have slow growth and do not develop as they should. Cats may also show symptoms of jaundice (yellow inner eyelids) and anemia. Matte coat is also common.

  • A cat may have a fever.
  • Cats with FIP may show symptoms of depression or lethargy.

4. Watch for eye problems. The dry version of FIP can affect the eyes. The eye may be inflamed and swollen. You may notice redness in the whites and in some cases the eyes may even bleed. Cats' eyes can change color, usually to a brown hue.

  • The cat can go blind.
  • Eye problems may be the only manifestation of this disease.

5. Watch for neurological symptoms. FIP can affect the nervous system. The cat may have coordination problems, so it may fluctuate, have balance or gait problems. He may also have tremors or seizures.

FIP diagnosis

1. Find out if your cat has been at risk of infection. The disease usually affects cats under 2 years of age. It occurs more often in larger feline communities. The most common mode of infection is contact with infected feces. People can transmit the virus on their clothes. If an infected cat comes in contact with an object, the virus can be transmitted to the object.

  • The virus is often excreted in the faeces. The virus will live up to 36 hours, although in colder climates it may last longer.
  • In most cats, the virus causes diarrhea and then the body gets rid of it itself.
  • Feline coronavirus is not transmissible to humans and dogs.

2. Take the cat to the vet. FIP is difficult to diagnose, so see a veterinarian as soon as you suspect a problem, which can help with diagnosis. Make sure you tell your veterinarian about all the symptoms to help him get all the facts.
Sometimes FIP can only be diagnosed by excluding other diseases.

3. Have blood tested. The first thing a veterinarian is likely to do is a blood test. Anti-coronavirus antibodies are detected. However, these antibodies only mean that the cat has been exposed to the virus, not that it has FIP. The veterinarian can make a diagnosis based on the blood test and the symptoms that the cat has.

  • There may be certain abnormalities in the blood test that may indicate FIP. The veterinarian may also perform a titration test on the FIP.
  • The blood veterinarian will also assess the function of the liver and kidneys.

4. Have the thoracic and abdominal cavities examined. The veterinarian may perform an X-ray to determine if there is fluid in the abdomen or chest. If the X-ray shows fluid, the veterinarian may take a sample for further testing.

  • This is often enough for a diagnosis, but in some cases it is not yet possible to make a definitive diagnosis.

5. Have a biopsy done. Diagnosing the dry form of FIP is difficult because it is not present in the fluid in the organs. If the differential diagnosis does not lead to a diagnosis, the veterinarian may biopsy the affected organs.

FIP Treatment

1. When the FIP is dry, provide support for the cat. There is no cure for both types of FIP. However, dry cats can live for several months if they are still eating, have not developed neurological symptoms and do not have anemia. Providing quality nutritious food to a cat can help survive for several months.

  • If a cat develops anemia, she may need a blood transfusion.

2. When the FIP is wet, you can aspirate some of the liquid. Wet form cats generally do not live as long as dry form ones. To prolong the life of the cat at least a little, you can suck some of the fluid out of your chest and abdomen.

  • Fluid aspiration can cause significant protein loss, which can make the condition worse.

3. Give the cat medication. The veterinarian may give the cat antibiotics if it develops an infection. Immunosuppressants are sometimes given to reduce antibodies. If cats have eye problems, they may be prescribed corticosteroids.

4. Decide when it is time for euthanasia. Almost every case of FIP is fatal and the virus is incurable. Most treatments are only supportive to improve a cat's quality of life for weeks or months. Many veterinarians suggest that cats diagnosed with FIP be killed.

  • If your cat is diagnosed, you and your family must decide on the most humane and appropriate treatment.
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BLACK-MARKET PRODUCTION AND SALE OF GS-441524 AND GC376

Niels C. Pedersen, DVM PhD
Dear Professor Emeritus
School of Veterinary Medicine
University of California, Davis

Original article: BLACK-MARKET PRODUCTION AND SALE OF GS-441524 AND GC376
6/18/2019, Translation 4/23/2021

Many entities, mainly in China, produce GS-441524 (GS) and GC374 (GC) intended mainly for desperate owners of cats with FIP. Some of these products come from non-veterinarians, while some are synthesized with the direct or indirect involvement of people with veterinary or human medical education. People in China have a big problem with FIP because of their growing ability to keep pets. There is a particularly high demand for expensive kittens with pedigrees, which are at increased risk of FIP. Therefore, the Chinese interest in drugs such as GS-441524 (GS) and G376 (GC) is not entirely financial and opportunistic. Although their first efforts were focused on GC, the emphasis of this black market quickly shifted to GS. Although this type of marketing and use of GS and GC is technically illegal, the companies holding the GC and GS patents have no effective means of stopping this black market. Reputable pharmaceutical companies offering GS and GC usually use a disclaimer limiting their use to research purposes only and not to human or veterinary treatment. This disclaimer, if issued, has no legal weight for law enforcement against the owners and is largely ignored. Medicines offered by individuals are often packaged and labeled as nutritional supplements, making it easier for customs to pass through customs in other countries. Fortunately, this mislabeled drug usually contains accurate information about the drug concentration, for example 15 or 16.5 mg / ml. The recommended GS dose for cats with non-neurological FIP is 4 mg / kg, SC once daily, for 12 weeks. Cats with neurological FIP may require a gradually higher dose of 5-10 mg / kg.

Veterinarians, who are more bound by legal and ethical restrictions, may look at the black market in a completely different way than owners of cats suffering from FIP. Some may refuse to participate beyond the initial diagnosis of FIP, others may assist in administering and monitoring treatment if cat owners provide medication, and some may require signing exemptions that relieve them of any legal or ethical obligations. I respect any procedure that veterinarians may use in interpreting their personal oaths to "use their scientific knowledge and skills for the benefit of society through the protection of animal health and welfare, the prevention and alleviation of animal suffering, the protection of animal resources, the promotion of public health and progress. in medicine. "

We already know about the problems of black market drugs in human medicine. Although suppliers declare high purity, biological activities (ie antiviral effect) are not tested. We already know that GC and GS produce more and more individuals and that quality in mg / kg or molar dosage may vary. We also know that the price of GC and GS can also vary widely and that owners can expect to pay thousands of dollars for enough medicine to complete treatment.

Buying enough medicine and fast enough to help you is just the first step. The drug can be purchased in powder form, which requires more than average knowledge for successful conversion to a stable and injectable form. In response to this problem, most suppliers offer GC or GS in pre-form. The oral form GS-441524 has recently started to be produced in China and is starting to appear on the market. Chemical modifications for oral absorption are well known in the development of drugs for HIV / AIDS and HCV. However, owners and veterinarians who buy GS or GC on the black market, usually at a very high price, would normally expect from the supplier some information on biological (antiviral) activity on a molar basis, diluent used and information on storage conditions and shelf life. If the antiviral activity is the same as for the drugs described in the research publications, the published information can be used directly. If this is not the case, the published information will not be applied. Remember to be very careful in such situations.

Information on where and how to get GC376 and GS-441524 can be easily found on social websites. This website was developed from groups of cat owners who have personal experience with the FIP and are familiar with the black market. Although Chinese retailers provide advice on the FIP and how these drugs are used, many claim to have veterinary contacts, and groups of cat owners are much more helpful. We now know that hundreds, if not thousands, of cats around the world are currently being successfully treated with FIP using drugs obtained on the black market. These favorable reactions appear to confirm our own published research on both GC376 and GS-441524. Owning groups have become very adept at identifying the most biologically active and economical GC and GS resources based on personal experience.

It is also very important that the diagnosis of FIP be as accurate as possible, as the disease is still often misdiagnosed. We therefore hope that owners have access to the veterinary expertise needed to properly diagnose FIP and monitor treatment with this level of emotional involvement, duration, cost, and monitoring. Information on how to administer these medicines has been provided in the form of published scientific publications listed in our supplement on "treatment of FIP". There is still a lack of knowledge on how to properly treat cats with neurological and ocular / neurological forms of FIP. GC and GS penetrate the brain with some difficulty, which is explained in the second appendix on neurological FIP. The only way to increase the level of the drug in the brain is to increase the level in the blood using higher and higher dosing regimens. It has been shown that higher doses, especially in GS, can lead to complete or almost complete remission of clinical symptoms. However, it is still uncertain whether every cat with neurological FIP can be cured. For this reason, cats with FIP with neurological disabilities should be treated much more cautiously than other forms of FIP. We are also aware of the potential problem of drug resistance, which is present either at the start of treatment or which develops during treatment. We observed primary drug resistance in 1 of 20 GC376-treated cats and 1 of 31 GS-441524-treated cats. Therefore, drug resistance should always be considered in any cat that does not respond rapidly to initial treatment or has relapsed after a period of positive response. Although this has not been adequately investigated, it is reasonable to assume that resistance to one drug will not apply to other drugs, as their mechanisms of virus inhibition are completely different.

I will continue to give the best possible advice to owners and veterinarians who use or are considering the use of GS and GC from the black market in the treatment of cats with FIP. Fortunately, extremely active and knowledgeable owner groups have emerged in several countries, serving as the main channel between GS and GC owners and suppliers. These groups are active in social media forums and desperate owners have relatively easy access to them and receive timely and critical assistance.

I must make it clear that I would have preferred these medicines to be approved and commercially available in the usual way. I am sure that will happen in the next few years, and if it does, black market demand for drugs like GS and GC will fall. In the meantime, UC Davis will continue to research new antiviral drugs for diseases such as FIP and share our findings in a conventional manner in peer-reviewed scientific publications. It is our sole responsibility to assure owners and veterinarians that our published findings are accurate, reproducible and applicable.

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How to Give a Cat an Injection

Original article on wikihow.com, 15.5.2019

Injections are often a problem for owners. The technical term for the category of injectable medicinal products is subcutaneous medicationwhich means it is applied subcutaneously. Some subcutaneous drugs are simply administered under the skin, while other types of subcutaneous drugs must be administered intramuscularly (intramuscular injection), and the route of administration will depend on the desired injection site. Proper subcutaneous administration can help reduce stress levels and keep your cat happy and healthy.

Preparing the cat for injection

Make sure your cat is hydrated. If you are giving the cat subcutaneous injections, it is essential that the cat is hydrated before and after administration. If your cat is severely dehydrated, the medicines you give may not be completely absorbed. This should not be a problem for most healthy cats, but if you suspect that your cat may be dehydrated, you should consult a veterinarian on how to keep it well hydrated.

Decide where you want to inject. You may want to keep your cat in your lap to calm it down during the injection, but this increases the likelihood that your cat may scratch or injure you, and may cause you to associate staying in your lap with injections. If you decide to keep your cat in your lap, it is best to put on a rough towel to cover your feet. However, it is best to place the cat on a flat surface, such as a tabletop.

Select a suitable injection site. The injection site will vary depending on whether you are giving a single subcutaneous injection or an intramuscular injection. Too many applications in the same place can be a problem for your cat. This is because it takes the cat's body six to eight hours to fully absorb the injected fluids. If you apply too many medicines to one site before they are absorbed, it can cause fluid to build up called edema. This can be annoying for your cat and could prevent many of the medications you give from running in your cat's body.

  • You should be able to give about 10 to 20 ml of medicine per kilogram of body weight before you have to choose a new injection site.
  • Check your cat to make sure the injections are adequately absorbed. The area around the injection site should remain dry.

Wipe the injection site with an alcohol swab. Most cats will not need this step unless they have a compromised immune system. The bactericidal effect is only one of the advantages. By easing the coat, you can see the skin better when injecting.

Use food to distract attention. Just before the injection, give your cat a taste that really tastes good, such as your favorite can or tuna. As soon as it starts to eat, gently pinch the skin at the injection site. After about five seconds, you should stop beasting and take food. Return the food and this time pinch (pinch) more intensely. Repeat this until your cat is tolerant to biting and stays focused on food. This will help her prepare for the injection and reduce the pain and stress she experiences when injecting.

Subcutaneous injection

Find a place with loose skin. In general, the areas between the neck and the back of the cat are the freest and most flexible places. Gently squeeze and stretch the skin where it is loosest, hold it between your thumb and forefinger, and distract the cat with food. The resulting shape resembles a tent.

Insert the needle. When you have the skin fold firmly between your fingers, you should see a narrow strip of skin between your thumb and forefinger. Insert the needle into this area.

  • The needle should be kept parallel to the skin along your cat's back at all times. Tilting the needle could pierce the skin on the other side and the needle could stab you in the finger.
  • Do not hold your thumb over the plunger until you are sure the needle is inserted correctly. Holding the plunger when inserting the needle could cause premature injection if the cat jerks or if you have inserted the needle incorrectly.

Pull out the plunger before injecting. It is important that you pull the plunger slightly before injecting the medicine. This will make sure that you hit the injection site.

  • If blood enters the syringe after pulling the plunger, it means that you have hit a vessel. You will need to pull the needle out and try again in another place.
  • If air bubbles enter the syringe, it means that you have pierced through the skin fold and sucked in air from the other side. You will need to pull the needle out and try again.
  • If no blood or air bubbles have entered the syringe, you have hit an acceptable site and can continue to inject.

Inject the contents of the syringe. Make sure you inject all the medicine. Once the syringe is completely empty, carefully pull the needle out and follow the same path that you used to inject it. 

  • Holding the syringe between your index finger and middle finger and thumb (same hand), push the plunger.

Check for bleeding or leakage. You must check the injection site after the injection. If you find that blood or medicine is leaking from the injection site, apply a clean cotton swab or tissue to the injection site until excretion stops. This should take about a minute, or longer if the cat is too restless.

Dispose of the used needle correctly. Do not dispose of the syringe in the household waste, as needles are considered to be biohazardous waste. Contact your veterinarian to see if they can dispose of needles. Never throw the exposed needle in the trash, as this could cause injury or infection to the waste collector or anyone else handling your waste.

Intramuscular injection

Find the injection site. Your veterinarian should give you specific instructions on where to take intramuscular medication and you should follow them carefully. In general, most veterinarians recommend intramuscular injections into the quadriceps (upper thigh) or lumbar spinal epaxial muscles (dorsal muscles along the spine). 

  • Be sure when giving intramuscular injections extremely careful . A poorly inserted needle could cause serious damage to your cat's nerves. For this reason, it is best to follow all the veterinarian's instructions. If you are unsure about any part of your veterinarian's instructions, or if you do not find a recommended injection site at home, call or visit a veterinarian for more detailed instructions.

Insert the needle. The needle should be inserted at an angle of 45 to 90 degrees, depending on the site chosen for the injection. To prevent the cat from moving and for the needle to enter the muscle correctly, it can help to keep the muscle flat.

  • Make sure you insert the needle at the correct angle as shown by your veterinarian. Inserting the needle at too small an angle can prevent the injection from reaching the required depth and penetrating the muscle. 
  • Do not hold your thumb over the plunger of the syringe until you are sure that the needle is inserted correctly. If you touch the plunger while inserting the needle, it may result in premature injection if the cat moves or you have inserted the needle incorrectly.

Pull the plunger before injecting. As with subcutaneous injection, pull the plunger slightly before injecting. Air bubbles should not be a problem with intramuscular injections, but if you see blood, you must pull the needle out and try again, as this may mean hitting the blood vessel.

Inject the contents of the syringe. It is important to ensure that the full dose of the medicine is given in the syringe. Once the syringe is completely empty, pull the needle out the same way you inserted it. 

  • Holding the syringe between your index finger and middle finger and thumb (same hand), push the plunger down.

Check for bleeding or leakage. Check the injection site after the injection. If you notice signs of blood or leaked medicine, press a clean cotton swab or swab into the injection site. It only takes one minute for the bleeding or leak to stop at the correct pressure.

Dispose of the needle properly. Used syringes are considered to be biohazardous waste and as such should never be disposed of with household waste or left uncovered in waste. Ask your veterinarian if they dispose of used needles.

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Fifty years’ fascination with FIP culminates in a promising new antiviral

3/25/2019, Translation 5/1/2021
Niels C. Pedersen
Original article: Fifty years' fascination with FIP culminates in a promising new antiviral

Feline infectious peritonitis (FIP) has fascinated me for the last 50 years. Although FIP is caused by a virus, it most closely resembles mycobacterial infections, which cause tuberculosis and leprosy in humans and cats. The disease revealed its secrets very reluctantly, and each new discovery led to further questions. As Robert Frost's famous poem puts it: "We dance around the ring and assume, but the secret sits in the middle and knows." I'm lucky to have reached the last milestone of my career when I identified safe and effective FIP treatment. We were able to reach this vase only thanks to hard work and great cooperation with teams of people in the USA from places like Kansas State and Wichita State University or Gilead Sciences.

We know that small molecules targeting specific proteins involved in RNA virus replication are able to safely treat various forms of FIP. These small molecules include the protease inhibitor GC376 and the nucleoside analog GS-441524. Both are based on drugs that are currently used to treat common human diseases, such as hepatitis C and HIV / AIDS, and are tested for exotic infections called MERS (Middle East Respiratory Syndrome), SARS (Severe Acute Respiratory Syndrome). and Ebola.

It is important to note that the small clinical trials we have completed and published are intended primarily to validate the concept, but unfortunately not to be quickly translated into approved and commercially available products. Some investigational drugs may be preferred (and thus delayed for veterinary use) in human medicine, and all will require a lengthy process to obtain final approval, even for animals. Private veterinary pharmaceutical companies will ultimately be responsible for their marketing. Is the demand for such medicines and the willingness of owners to bear the costs a sufficient incentive for these companies?

The FIP relinquished its secrets with great reluctance, and each new discovery led to further questions.

Figure 1. Bubba was originally found as an abandoned 3-week-old kitten by its owner in Florida, USA. He was diagnosed with dry abdominal FIP at the age of 7 and enrolled in treatment study GS-441524.
(a) In May 2017, just before the start of treatment, Bubba weighed 6 kg (13.5 lb). In the first week of the 12-week treatment, his owner stated that he "ate alone, alert, energetic and playful."
(b) Bubba, shown in January 2018, weighing 9.3 kg (20.5 lb).
Acknowledgments: Adel Gastle

Unfortunately, initial reports of successful treatment only stimulated the desperate owners' efforts for immediate access to these drugs and created a growing black market. Therefore, I suspect that we will test our patience and ethics over the next few years. None of this should detract from the fact that, after more than 50 years of research, we have reached this important point. Much more is waiting to be discovered. How does virus replication in macrophages lead to immunity in many cats, while in unfortunate individuals it leads to disease? Can this knowledge finally lead to effective vaccines? What is the best way to care for kittens in kennels, shelters and deposits to minimize FIP losses? Are even better drugs awaiting their discovery? Can small molecule inhibitors act in synergy with each other in a completely different treatment modality?

I will leave these and other questions to my scientific colleagues in the field of FIP.

Niels C Pedersen DVM, PhD
Center for Pet Health,
School of Veterinary Medicine,
University of California, Davis, USA

References

  • Pedersen, NC, Perron, M, Bannasch, M. Efficacy and safety of the nucleoside analog GS-441524 for the treatment of cats with naturally occurring feline infectious peritonitis. J Feline Med Surg 2019; 21: 271–281.
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Ending FIP, Is There Hope? A Summary of Dr. Niels Pedersen’s Presentation at the Winn Feline Foundation Symposium

Original article: Ending FIP, Is There Hope? A Summary of Dr. Niels Pedersen's Presentation at the Winn Feline Foundation Symposium (29.6.2017)

Summary: Carol Johnson DVM, PhD. A Heather Lorimer Ph.D.
For clarification, additional information from literature articles by Dr. Pedersena.

Feline Infectios Peritonitis (FIP) is one of the most complex infectious diseases and is undoubtedly one of the worst diseases imaginable. It is caused by an RNA virus from the coronavirus family Nidovirales. Other RNA viruses that the reader may be familiar with include the Ebola virus, influenza virus, AIDS, and rhinoviruses. Coronaviruses are named after protrusions that look like a crown (or corona) when viewed under an electron microscope. Coronaviruses can cause disease in almost every animal species, but as such, coronaviruses are species-specific: feline coronaviruses do not infect humans, dogs, or other animals.

Feline enteric coronavirus (FECV, also referred to in the literature as FCoV) usually remains in the intestinal tract and infects the upper layer of cells lining the small intestine before settling in the large intestine. FECV can cause mild diarrhea and vomiting, but is not considered a serious pathogen in the intestinal tract.

An FECV-infected cat can shed the virus in large quantities and excretion can continue for months. Cats are obligatory carnivores and, as a result, have a very short digestive tract. This may play a role in high virus shedding. Immunity to FECV is usually temporary and previously immune animals may be reinfected. This is one of the reasons why vaccination prevention is difficult, if not impossible.

FECV specific mutations they allow him to leave the intestinal tract, where he infects cells of the immune system called macrophages, which usually help fight infection. This mutated version of FECV is called FIPV (feline infectious peritonitis virus). Infected macrophages spread the disease in the cat's body in a similar way as tuberculosis (TB) bacteria spread in humans or animals. FIPV-associated mutations occur in three parts of the FECV genome, but a particular mutation may be unique to each cat. As many as 20% FECV infections can lead to subclinical macrophage infection, but relatively few cats develop FIP. Similarly, up to 40% of the world's human population is infected with tuberculosis bacteria, but few people have developed complete tuberculosis. Unlike TB, FIPV is not transmitted to other cats; the transmission takes place via an unmutated FECV.

FIP is a population-related disease high-density cats, where kittens are part of the equation. Kittens are most susceptible to developing FIP and are usually infected with FECV at about 9 weeks of age. In general, FIP can also occur in a dense urban or rural population of free-range cats. In the United States, FIP is more common in cats and kittens from conventional, high-density shelters and feline shelters or rescue stations where kittens may be exposed to large viral loads. Another source of FIP are kennels. Not only are a number of cats concentrated in farms, but there may also be genetic predispositions that may also play a role (up to 50% in some cases). Although the genetic risk is clear, genetic analysis shows that susceptibility to FIP is likely to involve a large number of genes. As a result, inbreeding is associated with susceptibility to FIP, but genetic testing for this susceptibility is not currently possible. Overall, FIP occurs in about 0.3% cats, but can occur in up to 1-5% (or more) cats in high-density sites, such as kennels or rescue stations.

The FIP is on the rise probably due to the increasing number of rescued cats in which kittens can be fed from bottles, weaned prematurely and exposed to large amounts of FECV.

There is a dry and wet form of FIP, but there may be combined forms and it is possible to change from one form to another. In general, the moist form, characterized by effusion, which leads to enlargement of the abdomen or fluid in the lungs, along with other symptoms, has a rapid course and can kill the cat very quickly (in this case, it is often death due to euthanasia). The dry form can last for months to about a year, sometimes longer.

Risk factors for FIP development they include the prevalence of cats that shed FECV, the intensity of virus shedding, the number of cats aged 4 to 29 months (most sensitive) and genetic predisposition (in bred cats). FIP often occurs in young cats after a stressful event, such as castration or sterilization. In these cases, the cat may already have FIPV-infected macrophages in the lymph nodes, and stress allows FIP to break out.

FIP can also develop in older cats. It typically happens that one (or more) cats in a multi-cat household die due to old age and the owner feels that the remaining cat needs a new friend, so he gets the kitten out of the shelter. The older cat has long since lost immunity to FECV and is now susceptible to infection. Due to older age, an older cat may have a worse immune response than a younger animal and is more likely to develop FIP.

Dr. Pedersen is of the opinion that FIP can usually be diagnosed relatively easily. Kittens or young cats with a viscous, slimy, yellow-colored fluid in the abdomen or thoracic cavity are likely to have FIP. The dry form of FIP may be more difficult to diagnose, but in young cats it is usually a combination of symptoms associated with chronic ill health, including weight loss, cyclic fever, characteristic blood count (anemia, decreased albumin, increased globulin, low albumin to globulin ratio, increase in absolute neutrophil count, decrease in absolute lymphocyte count, increase in bilirubin, etc.) and coronavirus titre ≥ 1: 3200, which helps to guide the diagnosis of FIP. Dry FIP may present with neurological symptoms such as convulsions or ocular lesions. Autopsy of most cases confirms characteristic lesions and leads to characteristic histological findings. Tissue or histological specimens can be further tested by various techniques, such as polymerase chain reaction (PCR), immunofluorescence (IFA) (frozen tissue only) or immunohistochemistry (IHC) (formalin-fixed tissue), but Dr. Pedersen considers these tests to be confirmatory. He believes that in almost all cases it is possible to diagnose FIP by routine examination. Some diagnostic tools lead to false negative results. For example, PCR, a commonly used diagnostic test, has about 30% false negative results.

Traditional treatment does not work. Immunosuppressants such as corticosteroids may make the cat feel better, but the course of the disease will not change. Biological agents do not work. Vaccines do not work because the kitten is usually infected with FECV before vaccination and because the immunity is only temporary. The most common cause of death in cats with FIP is euthanasia due to loss of quality of life as the disease progresses relentlessly. Although the wet form of FIP is often very fast, some cats may live longer with supportive care than one might think (weeks or months). Pulmonary fluid should be aspirated, but abdominal fluid should generally not be aspirated. Dry cats can stay alive for months or more. Spontaneous remissions may occur, but usually all cats eventually succumb to FIP.

Hope comes in the form of new antivirals. RNA viruses share many of the same types of genes and therefore present similar goals in drug development. This means that drugs designed to block one type of RNA virus may prove useful in the treatment of another type. Two potential drugs that may be effective in the treatment of FIP are protease inhibitors and nucleoside analogs (NUCs), which specifically target viral enzymes. RNA viruses often form one very large protein, which is cleaved by very specific proteases into the individual viral proteins needed to assemble new viruses. Drugs that inhibit specific proteases have been developed as antiviral drugs for various viruses. NUCs used to prevent HIV genome replication (reverse transcriptase inhibitors) in AIDS patients may also block RNA-dependent RNA polymerases that replicate the coronavirus genome. Cats, like all mammals, do not have an RNA-dependent RNA polymerase, so it is an enzyme specific for a given virus. Protease inhibitors act in the late phase of cell infection, while NUCs act in the early phase.

GC376, a protease inhibitor, was the first drug of its kind to be studied in cats. Dr. Pedersen worked with a team of veterinarians and chemists at Kansas and Wichita State Universities to treat cats experimentally infected with FIP, and later naturally infected cats. The treatment included 20 naturally infected symptomatic cats with FIP. Thirteen eventually died, some relapsing after remission and death due to neurological FIP. Seven cats survived and now appear to be free of disease, one to 1 year after treatment. A study in symptomatic, naturally infected cats determined a safe dose of drugs and determined an optimal treatment time of 12 weeks. However, treatment of cats with neurological symptoms was not successful, probably because the drug does not cross the blood-brain barrier. The drugs had few adverse effects; one of the most pronounced was the inhibition of adult tooth formation, which is a known side effect of this group of drugs. The limiting factor in the study was the final amount of drug produced.

EVO984 is a nucleoside analogue - reverse transcriptase inhibitor developed by Gilead Sciences. NUCs may have some advantage over protease inhibitors because they act in the early stages of virus infection of the cell. Gilead has provided several NUCs for which Dr. Pedersen tested their effectiveness against FIPV in vitro, followed by a pharmacokinetic study and finally a study in cats with artificially induced FIP. UC Davis needed to obtain extensive documentation and knowledge before treatment could be done on client pets with naturally developed FIP, and this study is underway right now. The drug appears to be safe, has been able to reverse the symptoms of FIP, including effusion, and some cats have successfully entered remission. Like GC376, EVO984 is not effective on neurological FIP because it does not cross the blood-brain barrier well. Although this study has only been running for a few months, it looks more promising than GC376. The test has only lasted 12 weeks, but all 24 cats that took part are currently alive.

Translator's note: EVO984 later became known under a new name, which is known to almost everyone who treated a cat with FIP. EVO984 is nothing but GS441524. In addition, GS441524 has been shown to cross the blood-brain barrier at increased doses and thus to treat neurological forms of FIP.

Next steps: While the studies appear promising, many unanswered questions remain. Dr. Pedersen believes that if his study is successful, it will likely need to be confirmed by a second group. It has been pointed out that additional funding may be needed through the Winn Feline Foundation’s Bria Fund, which has invited contributions for future FIP research. Gilead is excited about the preliminary results, but the company develops drugs for human use and does not have an animal health division. Gilead has indicated to Dr. Pedersen that if the results continue to be promising, they may pursue it or seek a partner that specializes in animal health products. However, given the overall prevalence of FIP worldwide, the drug may not be attractive enough for large pharmaceutical companies. However, Dr. Pedersen pointed out that there may be a way to find a way around it using provisions of the FDA’s Minor Use and Minor Species Animal Health Act of 2004.

Questions and Answers:

The question was asked why more cats could not be treated in the study. The drugs are experimental and have limited supplies. Dr. Pedersen feels that he only needs about 20 cats to draw conclusions, as this is usually a deadly disease. He also said that the desperate owners sometimes offered him a large amount of money so that their cat could be included in the study. He said it was very sad, but strict criteria had to be followed to be included in the study and it was not possible to meet everyone.

Asked about the genetic predisposition and whether it is possible to select purebred cats resistant to FIP, Dr. Pedersen shared his experience with randomly selected breeding cats experimentally infected with the highly lethal FIPV laboratory strain. Despite infection, about 20% cats did not develop FIP. When these cats were housed together, their kittens did not develop FIP in only about 10%. When the second generation of surviving cats were bred together, FIP developed in all their offspring. Dr. Pedersen believes that these results support the concept that the most resistant cats are crossbred cats, where many immune system genes are heterozygous (having two different versions of each gene), so that a cat's immune system can respond and attack a wider range of pathogenic targets. He believes that when cats are bred, the cat's immune system becomes more homozygous (they have two copies of the same version of each gene), which reduces the variety of targets to which the immune system can respond. Because mutations that change FECV to FIPV vary, cats with a broader ability to respond to small viral changes are likely to be better protected. Breeders should minimize the use of males that have fathered kittens that have died of FIP. Why males? Because individual breeding males generally produce more offspring than breeding females, they therefore have a greater impact on the next generation of cats.

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DR. PEDERSEN’S AUTOBIOGRAPHY

Original article: DR. PEDERSEN'S AUTOBIOGRAPHY
Published 18.3.2014, Translation 29.1.2021

I was born in 1943. My father was a Danish emigrant and my mother was the daughter of Danish emigrants. However, I learned that I also have Swedish roots after my father's line. I spent the first 14 years of my life in Southern California (Azusa and San Dimas), where my parents rented and then owned several family poultry farms. Although wholesale and retail eggs were their main business, they also raised ducks, geese and turkeys for the holidays. My father liked cats, but not pets. He always kept a large number of them on the farm to keep the rodent population low and their diet was supplemented by blood eggs. I loved all sorts of animals and bred pigeons, pheasants, wild ducks. As a pet, I even had a goat and a rabbit. However, my greatest love was the cats.

My first feline companion was a white, short-haired female with brownish ears, called MoMo (the mother of a cat in my child's tongue). She lived with me for 14 years and regularly and later irregularly gave me kittens. I also befriended many wild cats and one of my tasks was to sit with a box of kittens when customers came to buy eggs. I found homes for many kittens and once in a while I got 25 or 50 cents. I got to know the character and personality of cats more than anyone else. My life changed in 1956, when a huge summer fire in the hills around our San Dimas farm caused the temperature around the chickens to rise to more than 53 ° C and we lost all the water used to cool them. Sixty thousand chickens died within a week as a result of the sunburn. This unfortunate incident was, in fact, a blessing, as small family poultry farms in Southern California were rapidly becoming unprofitable, and this event forced my father to leave poultry after 30 years. He monetized all the property, which had some value, and exchanged it for a small warm spring resort in southern Nevada, and since then my family has been a real middle class. The resort was located in a valley called Upper Muddy, which also housed a large cattle ranch. The high school was 20 miles from Overton and the school started by 6:30. I started high school as a freshman with great tremor and on the first day of school I immediately fell in love with my future wife (Gerie). A small high school and living in a Mormon farming community have given me all sorts of experiences I wouldn't have had if I attended a much larger high school in Southern California. Every capable boy competed in sports and there were many interesting courses and extracurricular activities. Each student had to participate in several activities. My greatest high school experience was with Future Farmers of America, and I eventually became an FFA civil servant.

In 1961, I was accepted to the University of Nevada in Rene for scholarships from the Union Pacific Railroad and the Max E. Fleishman Foundation with the intention of becoming a teacher of professional agriculture. I soon realized that this was probably not the best career choice, but I had no idea about anything else. At the end of the first year, however, I switched to Animal Sciences and in the second year I began to attend much more demanding subjects in preparation for a possible Ph.D. in this field. My life changed again when I enrolled in a veterinary course led by one of the two veterinarians who were responsible for the small veterinary program at UNR. I have never had any direct experience with veterinarians before. Dr. Marble started my interest in veterinary medicine and even allowed me to help him with some of his experimental operations. I was immediately caught up in it and at the last minute I applied to three veterinary schools, UC Davis, WSU and CSU. I was accepted to all three schools, but I decided to go to UC Davis, California, which was closer to my home. I'm a native Californian (and an adapted Nevada). I was also fortunate that my tuition was paid by the state of Nevada under the Western Interstate Compact for Higher Education (WICHE).

I entered veterinary school in September 1963 with the intention of becoming a general practitioner for cattle (my second and third loves are cows and poultry). I worked on several science projects over the weekends and holidays, and I fell even more in love with research. In August 1964, I married my high school love Gerie. In my spare time, I worked with one of the graduate pathology students on a new feline disease called feline peritonitis and co-authored my first scientific article on FIP in 1964. I was horrified by a lack of knowledge about cats and their diseases, but that didn't stop me. After graduating from veterinary school, I graduated in internal medicine for small animals and surgery at Colorado State University, which significantly affected my future life and career. Once again, I realized how little we knew about cat diseases, and I became even more aware of my lifelong affinity and understanding with this species. Prior to my internship in 1967, I was accepted as a graduate student at the John Curtin School of Medical Research (JCSMR), Australian National University, Canberra, ACT, Australia. Australia has fascinated me all my life and JCSMR has given me not only a great research experience, but also my first experience with this vast and beautiful country. After graduating, I worked briefly as a celebrity practitioner in Hollywood to earn money to get my family (I already had a daughter) to Australia. Studying research at the Department of Experimental Pathology at JCSMR was unmatched, but not entirely related to my future career. But I learned about experimental methods. In 1972 I received my Ph.D. from experimental pathology and immunology with honors in. My love for Australia, which I cultivated in books as a child, became a lifelong passion. My hobby is identifying and photographing Western Australian plants. At our house in Winters, California, I have a large collection of photos of the flowering shrubs of Western Australia.

Dr. As longtime director of the Center for Pet Health (CCAH), Pedersen led a team that raised money and designed his current home. The CCAH building was completed in 2006 at a cost of $ 16 million, all of which was obtained from private sources. It is considered one of the most beautiful and functional buildings in the complex and is home to five clinical services and four major research programs.

In early 1972, I returned to the United States for a research position at the School of Veterinary Medicine at UC Davis, where I studied animal cancer associated with retroviruses. This was my first experience with the feline leukemia virus, which we saw during my studies in many cats, but whose cause was unknown at the time. My first year in research did not go well for me and I was considering moving to a postdoctoral position in transplant immunology at the University of Washington. Before formalizing this position, however, the dean of the Veterinary School called me and asked me if I would consider accepting a position at an internal medicine clinic for small animals. Dean Pritchard was tired of hiring doctors with rich clinical experience but weak scientific skills. He decided to try to admit to the clinic people with great research experience and good clinical potential. I became the first of a large number of employees at UC Davis with a professional background of this kind. It turned out to be a very wise decision, as the clinical program at UC Davis soon became world famous not only for its high clinical level but also high level of research.

I have worked at UC Davis since 1972 and retired in October 2013 as Professor Emeritus. I spent the first 17 years in clinics, teaching and working in research. For the rest of my time at Davis, my career was much more about administration and research. After serving as chair of the department, I became the founder and director of the Center for Pet Health and a few years later the director of the Laboratory for Veterinary Genetics. This latter function has rekindled my interest in the role of genetics in disease. Research into infectious and immunological diseases in cats and dogs has accompanied me throughout my career. I am still working and continuing my first love, research. I have no plans to retire if my health allows it, because for me, retirement in research is much better than retirement.

Although I have studied many infectious diseases of cats, FIP remains my first love, if the term can be called a disease that is still so widespread and almost always fatal. I learned to look at the FIP as a "worthy adversary." It is undoubtedly one of the most complex and challenging infectious diseases in existence, and trying to find prevention and treatment is what drives me the most. I realize that the answers don't just come. It's not like researching human diseases that have no problems with funding, whether from individuals or organizations that have a personal interest in discovering treatments. I hope that I will continue to strive to keep the disease at the center of attention, and I can say that I am not alone. I have recently reviewed more than 100 clinical and scientific publications on FIP submitted by research groups around the world since 2008. No other cat disease has received so much attention.

I enclose a more detailed biography of my career with an emphasis on FIP research, which still engulfs me. My biggest career achievements have been in the field of feline infectious diseases such as FeLV, FIV, FCV, FECV and FIPV. My textbook on diseases in a multi-cat environment, which has become a classic today, is perhaps my best creative work. However, my wife, three daughters, a son and 7 (soon to be 8) grandchildren, all successful so far, are my greatest legacy. But I hope that at least for a while, my "paw prints" will remain visible through the literature on cat diseases. And something like pets I've always had cats - always only two and always males.

–Niels C. Pedersen

Note: When Dr. Pedersen mentions a more detailed career CV, meaning mainly a number of published articles that you will find in scientific journals.

This is a 1991 photo when I received the first Jean Holzworth Cat Research Award. Dr. Holzworth was for me the best feline medicine expert he had ever lived. She graduated from DVM at Cornell University and spent her entire life at Angell Memorial Animal Hospital in Boston. She wrote the first modern textbook on cat diseases and I considered her a good friend and inspiration. She convinced me of something I've always believed in - you can't be a great veterinarian for cats without deep and confidential knowledge of this species, including everything from anatomy and physiology to behavior. -DR. P.

Wife of Dr. Pedersen Gerie with the newest members of the SOCK FIP family - recently adopted two brothers Piper (right) and Frodo (left). Frodo and Piper are among the many former experimental cats that the Pedersen have adopted over the past 40 years.

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History of FIP research

Original article: History of FIP research; 19.10.2010; Translation 1.2.2021

Probably the oldest recorded case of FIP (Utrecht State Veterinary School, 1912/13); retrospective diagnosis is likely from the description of chronic exudative peritonitis, dyspnoea (pleurisy?), fever and eye symptoms. (Jacob, 1914).

The sudden occurrence of FIP in the late 1950s has been documented in long-term and thorough autopsy records at the hospital. Angell Memorial Animal Hospital in Boston. Therefore, the existence of FIP as a major disease before this time is questionable. The mention of a cat with a disease reminiscent of the FIP was published half a century earlier (1914 Jakob-Groot and Horzinek), but whether it was really the FIP is uncertain given the absence of reports of a similar disease in the following decades. The incidence of the disease has steadily increased since the 1960s and is currently one of the leading infectious causes of death in young cats from shelters and kennels. The reason for the sudden onset of FIP is unknown, but there are at least three possible explanations. First, coronaviruses may have specialized in cats over the last half century. Remarkably, FIP emerged ten years after the first mentions of porcine gastroenteritis (TGE) in North America. The causative FIP virus is closely related to porcine TGE virus and CCV (Canine Corona Virus), although they are still genetically distinguishable. However, recombinants are known to occur between these three viruses. At least one CCV strain can cause mild enteritis in cats and exacerbate subsequent FIPV infection, suggesting a strong resemblance to feline coronaviruses. Therefore, in this scenario, CCV may be a more likely precursor to FECV. Recombinant events are favored by the ease with which transcription units (RNAs) can be gained or lost during the divergent development of coronaviruses. Second, the FIP mutation may be selective for the FECV variant that emerged in the 1950s. This variant could also arise due to intraspecific and interspecific mutability of coronaviruses in general, and in this case FCoV in particular. The third explanation may include changes in the understanding of cats as pets and their breeding in this modern age. After World War II, there was a dramatic shift when cats began to behave like pets. The numbers of domestic cats have increased significantly, the breeding of purebred animals and cat breeding has become more popular, and more and more cats, especially kittens, have found themselves in shelters. These large, multi-cat enclosures are known to be a breeding ground for feline enteric coronavirus (FECV) and FIP infection. Interestingly, feline leukemia virus infection also spread among domestic cats during this period. FeLV infection was an important cofactor for FIP until it was pushed back into the wild in the 1970s and 1980s by testing, elimination / isolation, and possible vaccination.

Genetic relationships between different genotypes of feline and canine coronaviruses (FCoV and CCoV). Feline sequences are colored blue, canine sequences are colored orange, and porcine sequences are colored purple. Arrows indicate predicted recombination sites. Genes encoding polymerase polyprotein (Pol), structural peak (S), envelope (E), membrane (M) and nucleocapsid (N) proteins are indicated. Genes encoding helper proteins are indicated by numbers.

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