Rubarth's Disease: Symptoms and Treatment of Infectious Canine Hepatitis

Rubarth's disease in a dog

Rubarth's disease, otherwise canine infectious hepatitis (ICH - Infectious Canine Hepatitis) is an infectious, dangerous and often fatal disease caused by Canine adenovirus type 1.

The disease was first identified in 1925 in North American silver foxes, and first described in 1947 by Swedish veterinarian Carl Sven Rubarth.

In addition to red and silver foxes and other canids such as dogs, wolves, coyotes and jackals, the virus can also infect representatives of bear families (e.g. black bear, polar bear), as well as skunks, otters and raccoons.

Psi adenovirus type 1 it is not dangerous to humans.

• The causes of Rubarth's disease
  • Which dogs are most at risk of being infected?
  • How does virus infection and disease develop??
• Rubarth's disease symptoms in a dog
  • Rubarth's disease is more acute
  • Acute form of Rubarth's disease
  • Mild or asymptomatic form of Rubarth's disease
• Diagnosis of Rubarth's disease
  • Differential diagnosis
• Treatment of Rubarth's disease in a dog
  • Treatment of DIC
  • Management of coma
  • Antibiotic therapy
• Prognosis
• How to prevent disease?

The causes of Rubarth's disease

Canine infectious hepatitis is caused by canine adenovirus type 1 (CAV-1 Canine adenovirus 1) related to adenovirus type 2 (CAV-2), which is one of the causative agents of infectious canine tracheobronchitis.

This strong antigenic relationship between CAV-1 and CAV-2 is very important from a clinical point of view as vaccines containing CAV-2 protect against CAV-1 infection and vice versa.

Type 1 adenovirus is resistant to environmental factors:

at room temperature, it is able to survive on objects soiled with soil several days, and at temperatures below 4 ° C, it even survives couple months.

Withstands a pH in the range of 6-8.5.

This germ can also withstand disinfection with various chemicals, such as:

• chloroform,
• ether,
• acids,
• formalin.

It is resistant to exposure to certain frequencies of UV radiation.

However, there are ways to inactivate the virus:

good methods of disinfection are steam treatments, because at higher temperatures (approx. 50-60 ° C for a minimum of 5 minutes) these microorganisms are rendered harmless.

Chemical disinfection with substances such as iodine, phenol or sodium hydroxide (NaOH) is also effective in combating the virus in the environment.

Adenovirus is quickly inactivated by 1-3% sodium hypochlorite and 2% caustic soda.

Which dogs are most at risk of being infected?

Which dogs are most at risk of being infected?

Type 1 adenovirus. causes clinical symptoms of the disease in dogs, coyotes, foxes and other canines, as well as in bears.

Among dogs, they are most at risk juveniles, unvaccinated, as well as animals with a weakened immune system (e.g. older dogs suffering from serious systemic diseases, but also young dogs, subjected to high stress).

Dogs, host glucocorticosteroids are also at risk.

Rubarth's disease occurs worldwide and most commonly affects individuals younger than 1 year, however, in unvaccinated dogs it can occur at any age.

In puppies up to 2. During the first week of life, the disease is at its most severe and usually fatal.

Older dogs are less sensitive.

How does virus infection and disease develop??

Infectious hepatitis is highly contagious and the virus spreads fairly easily.

The source of the disease are sick animals, convalescents and asymptomatic carriers.

During the acute phase of the disease, the sower can infect through all secretions - thus:

• urine,
• feces,
• vomit,
• saliva.

For 10-14 days after infection, the virus is detected only in the kidneys, and it is the urine of sowers and convalescents that is the main source of infection for at least 6-9 months.

The virus can spread by direct contact with contaminated surfaces or objects, it can also be spread, for example, by. on hands.

Also, external parasites (such as e.g. fleas or ticks) can be potential carriers of the virus.

The virus enters the body through the pathway:

• nasopharynx,
• conjunctiva,
• oropharyngeal.

So it is enough for the dogs to lick their faces on a walk, or to lick their urine, saliva or eat the feces of an infected individual for the virus to enter, which initially locates in the tonsils of the new host.

From here it begins to spread to the regional lymph nodes and vessels and then into the bloodstream (via the thoracic duct).

In phase viremia (this is the condition where the virus is present in the blood) for usually 4-8 days from infection, there is a massive spread of germs to various tissues and secretions of the body (including saliva, urine and feces).

The target organs for the virus where it causes significant damage are:

• liver,
• kidneys,
• spleen and lungs,
• brain,
• eye and other organs.

Type 1 adenovirus. has a strong affinity for the liver parenchyma and the endothelium of blood vessels in many organs (including the kidneys and eyes), causing cell damage in them.

As germs multiply in the endothelium of the vessels, their walls are damaged, which results in the appearance of petechiae and haemorrhages.

However, the body is not completely defenseless and activates the rapid reaction forces - approx 7th day Following infection, the virus is removed from the blood and liver by a humoral immune response.

In dogs that survive this phase of the disease, their liver has a chance to regenerate. However, it all depends on the level of anti-adenovirus antibodies.

In dogs with low titre (less than 1: 4), it may occur acute liver necrosis.

Dogs with an antibody titre greater than 1:16 but less than 1: 500 (and thus antibody levels are sufficient to partially neutralize the virus) may develop chronic active disease within 4-5 days after infection hepatitis and her fibrosis.

Animals with adequate antibody levels (titer above 1: 500) show mild disease symptoms.

The kidneys are also damaged by virus activity.

During viraemia, the germ primarily locates in the glomerular endothelium.

In response to the organism, there is a gradual increase in the level of neutralizing antibodies. As a result, approximately week transient appears after infection proteinuria, resulting from the build-up of immune complexes (around 7. one day after infection).

After 14 days the virus still remains in the renal tubular epithelium, although it is no longer detected in the glomeruli. The presence of the virus in the kidneys can make it mild interstitial nephritis.

About 20% of infected dogs the virus locates in the eyeball causing ophthalmological symptoms.

Already during viremia, i.e. approx 4-6 days the infection causes damage to the eyeball due to the penetration of the virus into the aqueous humor and its replication in the corneal endothelial cells.

In effect, it comes to severe uveitis and corneal swelling. This happens not only as a result of the damaging effect of the virus itself, but also as a result of the increasing level of neutralizing antibodies and the formation of immune complexes, which results in drawing more inflammatory cells to the anterior chamber of the eye.

This causes extensive damage to the corneal endothelium and the accumulation of edema fluid in the corneal parenchyma.

Corneal endothelial damage is an important prognostic factor. Unless there is significant damage, the uveitis and edema usually resolve on their own.

After approx 3 weeks from infection, recovery of clinical symptoms of the eyeball is usually noticeable.

However, if the inflammation is severe enough to block the angle of infiltration, it may occur glaucoma and hydrocephalus (due to increasing intraocular pressure) and also keratoconus, and even atrophy of the eyeball.

Virus replication can also take place in the endothelium of other organs, such as the brain, lungs, and lymph nodes.

Then the disease leads to the impairment of their functions and develops DIC (intravascular coagulation syndrome), and in severe cases, the animal may even die.

As a result of damage to the endothelium of the blood vessels of the central nervous system, neurological symptoms may manifest, but this is rare in dogs.

The virus that multiplies in these organs causes the formation of necrotic foci in them.

It happens so from the fifth day after infection. The immune response also develops during this time, giving most infected dogs a chance to recover.

The presence and action of adenovirus in the body, however, is associated with the emergence of a number of complications complicating the course of the disease.

These include:

1. Pyelonephritis as a result of virus damage and the emergence of immune complexes.
2. Inflammation of the iris and ciliary body and swelling of the cornea, giving the symptom of the so-called "blue eye ".
3. The syndrome of disseminated intravascular coagulation (DIC) is relatively common. Its development occurs in the early stages of viremia. Endothelial cell damage, along with activation of clotting mechanisms, may be at the root of DIC. A failing liver may also contribute to the pathogenesis of DIC - it does not produce enough clotting factors, which predisposes to the appearance of this condition.
4. Hypoglycaemia, hypoalbuminaemia, drop in oncotic pressure and appearance of edema. These conditions are the result of liver damage.
5. Hepatic encephalopathy can result in the development of semi-coma and even death, but death is usually caused by damage to the brain, lungs, and other organs, or from the development of intravascular coagulation syndrome.

Rubarth's disease symptoms in a dog

Rubarth's disease symptoms in a dog

The incubation period of the disease is 2-9 days.

Depending on the immune status and the general clinical condition of the patient, the course of the disease may vary:

• from mild discomfort with a fever of 1-2 days and leukopenia, which are often not even recognized,
• through common illnesses (of milder or more severe severity), after which, however, dogs recover quickly,
• up to a severe course, which is fatal at a different time than the onset of clinical symptoms.

Thus, canine infectious hepatitis has a varied course and describes three overlapping syndromes.

Rubarth's disease is more acute

The first syndrome is an acute form of the disease with cardiovascular collapse, coma and death after a short illness that lasts less than 24-48 hours.

The course of hyperacute is characterized by high mortality.

Severely sick dogs die within hours of the first clinical signs appearing.

It looks as if the animal has been poisoned.

The main clinical symptoms of hyperacute Rubarth's disease are:

• fever,
• central nervous system symptoms,
• circulatory collapse,
• intravascular coagulation syndrome,
• death within hours.

Acute form of Rubarth's disease

The most frequently described syndrome in the course of canine infectious hepatitis is the acute form of the disease, which is associated with high morbidity.

The mortality rate is 10-30%.

In the beginning, the symptoms are non-specific in the early stages of infection.

It all starts with a fever (transient or biphasic) that usually exceeds 40 ° C (ranges from 39.4 to 41.1 ° C).

She is accompanied by:

• accelerated heart rate and breathing,
• apathy,
• strong thirst,
• lack of appetite.

The temperature usually returns to normal after 1-2 days.

At this stage of the disease, the tonsils also become inflamed, visible as their enlargement and redness.

The inflammatory process may also affect the pharynx and larynx mucosa.

There is congestion of the oral mucosa, and the appearance of ecchymoses on mucous membranes is also possible.

Usually, you will notice tenderness in the abdominal cavity when palpating, as well as palpable enlargement of the liver. Due to enlargement and severe soreness of the liver, animals become more lethargic, squeaky and reluctant to move.

In the acute form of the disease, vomiting and diarrhea (often haemorrhagic) are usually present, resulting in noticeable dehydration.

It is also visible conjunctivitis with serous outflow from the conjunctival sacs, photophobia and squinting.

The mucous membranes become hyperemic. Hemorrhagic diathesis is possible with small, punctured petechiae or haemorrhage, bruises, nosebleeds, as well as prolonged bleeding from puncture sites (e.g. after blood collection).

Petechiae can also be seen on the skin, especially in poorly hairy areas, such as:

• belly,
• medial surface of the thighs,
• groin.

Swollen lymph nodes in the neck, often together with swelling of the subcutaneous tissue of the head, neck, forechest and various parts of the trunk (such swellings usually appear in the subacute course of the disease).

It is also possible to develop respiratory symptoms as a result of the damaging effect of the virus on the lung tissue and the formation of inflammatory foci. However, symptoms of pneumonia, including coughing and shortness of breath, are rare.

In this form of the disease, it rarely develops jaundice, however, it can occur in dogs that have survived a very acute, fulminant phase of the disease.

Enlargement of the abdominal wall as a result of the accumulation of fluid (serous-blood) or even blood (due to internal hemorrhage).

Central nervous system symptoms appear very rarely and include:

• depression,
• confusion,
• seizures,
• tonic-clonic contractions,
• coma.

On the other hand, muscle tremors caused by hypoglycaemia are observed more frequently.

These symptoms can appear at any time after infection.

If pregnant bitches are affected by the disease, the infection may result abortion.

The characteristic "blue eye" - corneal edema and uveitis of the front part of the eye are symptoms typical of the recovery phase, but may also be the only symptoms of the disease in dogs with asymptomatic infection.

Blepharospasm, sore eyeball, corneal opacity, photophobia, and serous discharge from the eye may also occur in animals suffering from this form of Rubarth's disease.

About 5-10% dogs develop a corneal opacity (unilateral or bilateral) within 1-3 weeks after onset, which usually resolves spontaneously within 1-2 weeks.

If the deeper structures of the eyeball have not become inflamed, the cornea regains its translucency and the patient's ability to see.

Mild or asymptomatic form of Rubarth's disease

Symptoms of the mild form of Rubarth's disease are usually poorly expressed and nonspecific:

• apathy,
• lack of appetite,
• transient fever,
• inflammation of tonsils,
• vomiting,
• diarrhea,
• enlargement of the lymph nodes,
• enlarged liver,
• abdominal pain.

In uncomplicated canine infectious hepatitis, clinical signs usually last 5-7 days.

Animals who develop chronic hepatitis or other infections may experience longer symptoms.

Diagnosis of Rubarth's disease

Diagnosis of Rubarth's disease

Diagnosing Rubarth's disease in the early stages of infection is quite difficult.

In many cases, the disease is mild and the clinical symptoms are non-specific.

Often the diagnosis is made only when other characteristic symptoms, such as symptoms of decreased blood clotting or also corneal clouding.

Therefore, the diagnosis should always take into account all factors that may raise the suspicion of infectious hepatitis, especially if the patient is a young, unvaccinated dog.

In the interview, we often get information that the animal is not vaccinated or - in the case of adopted dogs, we do not know about possible previous vaccinations.

Even if vaccination is postponed (for various reasons), infection and the development of the disease may occur.

It also happens that the dog has previously been in a crowded environment (e.g. hotel for animals, pseudo-breeding, etc.). Dogs that have been in contact with an infected or convalescent animal are at risk.

Clinical symptoms such as fever, abdominal pain, reluctance to move, lethargy, sadness and vomiting with retained thirst in a young dog should prompt considering Rubarth's disease as the cause of the poor clinical condition of the patient.

Epizootiological situation

Information on the number of cases in the dog population in a given region is important, but even in the absence of reports on current cases of infectious hepatitis, the veterinarian should consider this unit in the differential diagnosis.

Clinical examination

Enlargement of the liver, pain in the abdominal wall, dehydration, the presence of ecchymoses and haemorrhages on the mucous membranes and skin, and ultimately the ophthalmological symptoms (blue eye symptom) make a serious suspicion of Rubarth's disease.

The symptoms of the nervous system are relatively rare, but they are clinically important not only in the diagnosis of the disease, but also in further therapeutic management.

Laboratory tests

Their results are key diagnostic methods in the diagnosis of canine infectious hepatitis:

• initially there is leukopenia with lymphopenia and neutropenia;
  thereafter, dogs that recover without complications usually develop neutrophilia and lymphocytosis;
• changes in serum proteins (detectable thanks to protein electrophoresis) - a transient increase in the level of α2 globulins up to 7 days after infection and a delayed increase in the level of γ globulin, which reaches the peak of approx. 21. the day after infection;
• the presence of bilirubin in the urine;
  Due to the low renal threshold for conjugated bilirubin, a slight degree of bilirubinuria is often present;
• hypoglycaemia, which may be end-stage of the disease;
• increase in the activity of liver enzymes, the degree of which depends on the time of taking the sample for testing and the extent of liver necrosis;
  the activity of ALT, AST and AP increases continuously to 14. the day after infection and then declines;
• coagulation disorders related to the intravascular coagulation syndrome are clearly visible in the viremia phase; is observed:
  • thrombocytopenia, often with altered platelet function,
  • increase in prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT),
  • decrease in the activity of coagulation factor VIII,
  • increase in the amount of fibrin breakdown products or fibrinogen (FDPs),
  • early prolongation of partial thromboplastin time (PTT) due to the consumption of coagulation factor VIII;
• if you have kidney problems:
  • proteinuria (mainly albuminuria) - protein concentration is usually above 50 mg / dl,
  • increase in the level of urea and creatinine in the blood serum;
• during illness, dogs may develop semi-coma, possibly caused by hepatic encephalopathy or encephalitis;
  in order to distinguish the cause of neurological disorders, it is important to test the level of glucose and ammonia in the blood;
• examination of the fluid obtained from the puncture of the abdominal cavity; It can be of different color: from yellow through bright red to blood-red (depending on the blood content);
  usually, however, it is an exudative fluid with a protein content of 5.29-9.3 g / dl and a specific weight of 1.020-1.03;
• examination of the cerebrospinal fluid;
  in the presence of neurological symptoms caused by hepatic encephalopathy, the cerebrospinal fluid is unchanged;
  otherwise it is the case with non-inflammatory encephalitis, which is the result of localization of the virus in the brain structures, then an increase in the concentration of proteins is observed (> 30 mg / dl), and their level increases with the increase in the number of mononuclear cells (> 10 cells / mm3);
• with uveitis in the anterior part of the eye, the aqueous humor increases the amount of protein and the number of cells.

Serological tests used to confirm the presence of the virus

For this purpose, indirect hemagglutination, complement fixation, immunodiffusion and ELISA tests are used.

Virus isolation from blood, urine and cell culture or PCR identification.

Still in viremia, around 5. the day after infection, the virus can be isolated from any tissue or body secretion:

• virus can be isolated from the anterior chamber of the eye during the mild phase of uveitis (but before antibodies penetrate and immune complexes form);
• isolation from the liver of dogs is often difficult, and after 10 weeks of age. the day after infection may be impossible (most likely due to the virus becoming latent);
• the virus is most easily isolated from urine - adenovirus type 1. stays in the kidneys for the longest time, therefore its isolation from urine is possible for 6-9 months after infection.
• post-mortem: demonstration of inclusion bodies by IF in liver and kidney sections.

Differential diagnosis

The differential diagnosis should include:

• Other systemic viral diseases such as:
  • Parvoviral enteritis.
    When infected with parvovirus, the animal refuses to drink, unlike Rubarth's disease, in which thirst is maintained (or even increased).
    There is also no pain in the liver;
  • Nasal - here mainly respiratory symptoms are dominant, but later are joined by neurological symptoms;
  • Leptospirosis, which is associated with jaundice and uremia more often than infectious hepatitis;
  • Viral and bacterial intestinal infections;
• Hepatotoxicosis (after ingestion of toxins, poisoning, etc.);
• Foreign bodies in the digestive tract;
• Food intolerance;
• Portal systemic anastomoses with hepatic encephalopathy;
• Disseminated fungal infections (especially systemic candidiasis);
• Systemic protozoal infections (e.g. toxoplasmosis);
• Tumors (especially lymphoma) - less common in young animals.

Treatment of Rubarth's disease in a dog

Treatment of Rubarth's disease in a dog

The causal treatment is difficult due to the lack of an effective anti-adenovirus drug.

Therefore, the initial management of a patient with infectious hepatitis is symptomatic and supportive.

Treatment of Rubarth's disease in a dog typical of acute hepatitis

1. At the beginning, fasting and intravenous infusions of large amounts of 20% glucose (up to 0.5 g / kg m.c.).
   For this purpose, the use of a cannula is necessary, especially in seriously ill dogs. However, it should be done very carefully (due to coexisting coagulation disorders);
2. Intravenous administration of multi-electrolyte fluids:
   • isotonic fluids, e.g. Ringer's fluid. Due to liver damage, administration of lactate is not recommended;
   • infusions also help lower the fever;
   • in dogs that do not drink or who persist vomiting or diarrhea, it is necessary to replenish daily losses in the amount of 45 ml / kg m.c.;
3. Administration of painkillers;
4. After stabilizing the condition, introduce a diet that protects the liver (ready-made feeds such as "hepatic " or a diet based on wholesome and easily digestible protein, such as lean white cheese, carbohydrates such as rice, groats and a small amount of fat in the form of vegetable oils).

Treatment of DIC

• Blood transfusion replenishes clotting factors.
• Blood transfusion is indicated in cases where the hematocrit drops below 25%.
  Donor selection: clinically healthy dog, preferably of the same breed.
  Dogs that lack DEA 1.1 and DEA 1.2 blood cell antigens are the best.
  You can download about 20 ml of blood / kg m.c. every 3 weeks.
• Transfusion plan: 2 g of sodium citrate mixed with 100 ml of 5% glucose or dextrose.
  Mix the blood for transfusion with the fluid in a ratio of 2/3 blood and 1/3 fluid.
  The mixture is administered intravenously at the rate of 1-2 drops / second twice every 48 hours (5-20 ml / kg m.c.).

Management of coma

• Since one of the causes of coma may be too low blood sugar, it is necessary to control the glucose level and correct it if necessary.
  In this situation, an intravenous bolus dose of 50% glucose (0.5 ml / kg) is administered over 5 minutes.
  The infusion of hypertonic glucose solution should not exceed 0.5-0.9 g / kg / h.;
• Lowering blood ammonia levels:
  • reduction of ammonia production as a result of protein catabolism by colon bacteria:
    • low-protein diet,
    • inhibition of bleeding into the lumen of the gastrointestinal tract;
    • colon emptying by using cleansing and acidifying rectal enemas;
    • oral antibiotics, non-absorbable from the gastrointestinal tract to reduce the amount of bacteria that produce ammonia (e.g. neomycin);
    • oral administration of lactulose (only to dogs that do not vomit) to acidify the contents of the colon;
  • reduction of ammonia resorption in the renal tubules:
    • oral or parenteral administration of potassium (and, as a result, correction of metabolic alkalosis);
    • acidification of the urine significantly reduces the ammonia reabsorption in the kidneys. For this purpose, vitamin C is used.

Antibiotic therapy

Although bacterial complications in canine infectious hepatitis are rare, administration of low-hepatotoxic antibiotics (amoxicillin with clavulanic acid, cephalosporins) is indicated.

• Antiemetic drugs (metoclopramide, cerenia).
• H2 receptor antagonists, e.g. famotidine.
• Protective drugs - sucralfate for gastrointestinal bleeding.
• Ursodeoxycholic acid as a choleretic and hepatoprotective agent.
• Antioxidants: vitamin E and S-adenosylmethionine.
• Treatment of ophthalmic disorders is also symptomatic and consists of topical anti-inflammatory drugs and atropine. With severe corneal edema, hypertonic solutions and ointments can be administered.

During treatment, the following are routinely monitored:

• electrolytes,
• acid-base balance,
• coagulation state,
• hematological and biochemical parameters of blood.

Prognosis

There is a prognosis in a hyperacute course badly - death occurs within hours.

In the acute course, the prognosis is cautious to good.

Chronic hepatitis may develop with a weak antibody response (titer 1:16 - 1:50).

With a good antibody response (titer above 1: 500), complete recovery is possible within 5-7 days.

It happens that chronic patients develop in cured patients liver or kidney disease.

How to prevent disease?

How to prevent disease?

Significant reduction or even elimination of the disease caused by CAV-1 from the population of domestic dogs is possible thanks to regular vaccinations.

Cases of Rubarth's disease that occur in animals primarily concern those dogs that were not vaccinated at the age of puppies.

However, since the virus is still present in the wild animal population and, in addition, it is resistant to the conditions of the external environment, it is necessary to continue an appropriate prophylactic program in all dogs.

The available vaccines against this disease are usually combination preparations that also contain the antigens of the virus:

• distemper,
• parvovirosis,
• kennel cough,
• leptospirosis,
• coronavirus.

In the first year of life, it is recommended to vaccinate at least twice with an interval of 3-4 weeks: that is, at the age of 8-10 weeks, and then 12-14 weeks.

Subsequent vaccinations should be repeated annually or according to the manufacturer's instructions.

In justified cases, the preventive program is corrected by a veterinarian. After contracting the disease, dogs develop lifelong immunity to recurrence.

Summary

Rubarth's disease it affects dogs, especially unvaccinated puppies.

Fortunately - thanks to effective vaccinations - it has become less common, although still diagnosed in veterinary offices.

Among its many features, the three most important should be noted:

1. First, it is a highly contagious disease.
2. Secondly, it is very dangerous (even fatal) especially for puppies.
3. Third: it can be effectively prevented by applying an appropriate preventive program.

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