Canine Parvoviral Enteritis^1,2

Canine parvovirus (CPV) causes canine parvoviral enteritis which first emerged in 1978 as an important cause of severe, often fatal enteritis in dogs. It has remained a leading cause of enteritis in dogs despite the wide availability of effective vaccines. CPV-2a and CPV-2b are the most common virulent strains found worldwide.¹ In 2000, a new CPV-2c strain was discovered in Italy and other countries. In South Africa, CPV-2a and CPV-2b are the only strains identified to date.³ These viruses are hardy, persisting for long periods of time in the environment (5–7 months), and are ubiquitous.

Pathogenesis of CPV¹

The two clinical syndromes described in dogs infected with CPV include enteritis and myocardial failure. Myocardial failure occurs in neonatal puppies infected in utero or shortly after birth and is rarely seen today due to vaccination protocols. Infection with parvovirus in older dogs is acquired by the faecal-oral route of transmission. CPV preferentially targets tissue with rapid turnover. The cells most affected are the intestinal epithelium, lymphoid tissue and bone marrow. Conditions that increase cell turnover, e.g., diet change and change in bacterial flora due to weaning or concurrent endoparasitaemia or corona virus infection, favour viral replication and increase the severity of the resulting lesions and clinical disease. Extensive destruction of lymphoblasts in lymphatic tissue and myeloblasts in bone marrow lead to a lymphopenia and in severe cases a panleukopenia. In the intestinal tract it leads to epithelial necrosis, villus atrophy and collapse of the intestinal epithelium, loss of absorptive capacity and the development of haemorrhagic diarrhoea and vomiting. This clinical syndrome is most commonly seen in pups after weaning and up to 6 months of age.

Clinical Manifestations of CPV Infection¹

Initial signs may be very nonspecific and include anorexia, lethargy and fever.⁴ Vomiting and diarrhoea develop within 12–24 hours. Signs include vomiting and a mucoid to haemorrhagic diarrhoea with marked abdominal pain that can be caused by the acute gastroenteritis or intestinal intussusception. Puppies may also develop a severe, transient lymphopenia.⁴ A more global systemic inflammatory response syndrome (SIRS) can occur in many cases. Mortality is higher in puppies that have evidence of systemic inflammatory response syndrome at the time of admission.⁵ The systemic response is thought to be due to bacterial translocation from the damaged intestinal tract leading to coliform septicaemia.⁴ Endotoxin is a potent stimulus for the inflammatory response through activation of cytokine-mediated procoagulant effect on endothelial cells.⁴ The initial response to endotoxin is activation of coagulation, and then, as inflammation progresses, the hypercoagulable state is followed by a hypocoagulable state and eventually disseminated intravascular coagulation and bleeding.⁶ Puppies with parvoviral enteritis showed thromboelastography (TEG) evidence of hypercoagulability.⁶ Antithrombin (AT) activity was significantly lower and fibrinogen concentrations significantly increased in the parvovirus infected puppies.⁶ Some pups showed clinical thrombosis or phlebitis which was associated with their intravenous catheters.⁶

Diagnosis of CPV^1,4

Definitive diagnostic tests include detection of CPV in the faeces of affected dogs using electron microscopy, virus isolation, faecal haemagglutination, latex agglutination, counterimmunoelectrophoresis, immunochromatography and polymerase chain reaction (PCR), serology and necropsy with histopathology.

Faecal enzyme-linked immunosorbent assay (ELISA) antigen tests are available for in hospital testing for acute CPV. False positive results may occur 3–10 days after vaccination with a modified live CPV vaccine as all the modified live canine parvovirus vaccines are shed in the faeces. False negative results may also occur due to binding of test antigen with serum neutralizing antibodies in bloody diarrhoea or cessation of faecal viral shedding.

Treatment of CPV^1,4

No agent-specific treatment has proven effective, therefore treatment remains symptomatic and supportive. Survival of acute CPV cases is largely dependent on the intensive treatment given when the puppy is hospitalised. Survival of infected puppies ranges from 9% if left untreated to more than 90% in those treated in tertiary veterinary facilities.⁵ The mortality rate for puppies admitted and treated at the Onderstepoort Veterinary Academic Hospital (OVAH) is between 16 and 19%.^1,7

Crystalloids and Electrolytes

Initial treatment consists of an intravenous crystalloid such as lactated Ringer's solution.¹ Initial fluid rates depend on the replacement needs of the patient, and fluid rates are adjusted based on the response of the patient as well as ongoing fluid losses.⁴ In most cases, hypokalaemia develops and supplemental potassium chloride is added to the fluids.⁴ Hypoglycaemia is common and needs to be corrected and monitored.⁴

Synthetic Colloids

In some cases colloidal fluid support may be required.⁴ Addition of synthetic colloids such as hetastarch may be required when total solids decrease to below 40 g/l or if albumin decreases below 20 g/l.⁴ Evidence of third space fluid losses including peripheral edema, conjunctival edema, ascites or pleural effusions are also indications for colloid therapy.⁴ In cases with decreased total solids and albumin, plasma transfusions are not the treatment of choice. To gain a 5 g/l increase in albumin, plasma would need to be given at 22.5 ml/kg. It would result in unwanted fluid overload.

Natural Colloids

Red blood cell transfusions are indicated in patients with severe anaemia and clinical signs resulting from the anaemia (tachycardia, tachypnoea, water hammer pulses).⁴ Fresh frozen plasma has been recommended for potential benefits such as provision of immunoglobulins and serum protease inhibitors which theoretically could play a role in neutralising circulating antigen and aid in limiting the systemic inflammatory response.⁴

Passive Immunity

Passive transfer of immunity has been reported only anecdotally and a recent study has shown no clinical benefits when administering small amounts of plasma to dogs with parvoviral enteritis.⁸ No studies exist that have proven either benefits or severe side effects with the use of plasma products in cases with parvoviral infections. In the author's experience the use of fresh frozen or frozen plasma does have a positive effect on the response to disease as well as outcome. In our teaching hospital, fresh frozen or frozen plasma is administered at the discretion of the attending clinician, and it is administered at a dose of 10–20 ml/kg.

Antimicrobials, Anthelmintics, and Analgesics

Antibiotic recommendations include the use of penicillins, fluoroquinolones and aminoglycosides.⁴ At the OVAH we initially use amoxicillin-clavulanic acid. Because enrofloxacin may lead to cartilage damage in large-breed dogs, this drug is mainly used in small breeds if additional antibiotic cover is indicated. Amikacin is only used once the hydration status is normal and cardiovascular stability is achieved. Metronidazole is used in cases that have concurrent protozoal infections.

Antiemetic drugs include metoclopramide, either intermittently or as a constant rate infusion, ondansetron or maropitant in cases with severe vomiting and prochlorperazine once they are fully hydrated.

Fenbendazole for a period of 5 days is used to eradicate any intestinal helminths.

Opioids such as buprenorphine are used to control severe abdominal pain.

Early enteral nutritional support is also needed as it has been shown to be associated with more rapid clinical improvement.¹

The treatment and convalescent periods in cases with parvoviral enteritis may be prolonged and consequently expensive and the mortality rate relatively high, causing many clients to forego treatment and elect for euthanasia of their pets.

Prognostication in Canine Parvoviral Enteritis²

Some parameters have already been identified as potentially useful in determining the prognosis and/or duration of hospitalisation of an individual patient. These include serum thyroxine, serum cortisol, leukocyte changes, and various biochemical parameters.^{5, 7} Puppies with lymphopaenia and hypoalbuminaemia were hospitalised for more days.⁵ Puppies that survived the disease had significant increases in certain leukocytes, specifically lymphocytes over time.² Monitoring changes in leukocytes during the course of the disease has a high positive predictive value for survival. Elevated serum cortisol and decreased serum thyroxine concentrations as measured at 24 and 48 h after admission were useful as negative predictors of outcome.⁷ C-reactive protein (CRP)was associated with outcome in puppies with canine parvoviral diarrhoea, but even though non-survivors had significantly higher serial CRP concentrations when compared to survivors, CRP was not found to be useful in predicting outcome.² A study examining the lipid profiles in cases with parvoviral enteritis showed that non-survivor puppies had lower levels of total cholesterol and high-density lipoprotein cholesterol and higher levels of triglycerides.² Studies to investigate the prognosis in CPV enteritis are ongoing.

References

1.  Goddard A, Leisewitz A. Canine parvovirus. Vet Clin North Am Small Anim Pract. 2010;40:1041–1053.

2.  Schoeman J, Goddard A, Leisewitz A. Biomarkers in canine parvovirus enteritis. N Z Vet J. 2013;61(4):217–222.

3.  Steinel A, Venter E, van Vuuren M, Parrish C, Truyen U. Antigenic and genetic analysis of canine parvoviruses in Southern Africa. Onderstepoort J Vet Res. 1998;65(4):239–242.

4.  Prittie J. Canine parvoviral enteritis: a review of diagnosis, management and prevention. J Vet Emerg Crit Care. 2004;14(3):167–76.

5.  Kalli I, Leonotides L, Mylonakis M, Adamama-Moraitou K, Rallis T, Koutinas A. Factors affecting occurrence, duration of hospitalization and final outcome in canine parvovirus infection. Res Vet Sci. 2010;89:174–178.

6.  Otto C, Rieser T, Brooks M, Russell M. Evidence of hypercoagulability in dogs with parvoviral enteritis. J Am Vet Med Assoc. 2000;217(10):1500–1504.

7.  Schoeman J, Goddard A, Herrtage M. Serum cortisol and thyroxine concentrations as predictors of death in critically ill puppies with parvoviral diarrhoea. Journal of the American Veterinary Medical Association. 2010;231(10):1534–1539.

8.  Bragg R, Duffy A, DeCecco F, Chung D, Green M, Veir J, et al. Clinical evaluation of a single dose of immune plasma for treatment of canine parvovirus infection. J Am Vet Med Assoc. 2012;240(6):700–704.