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