Canine parvovirus (CPV) is a highly contagious and relatively common cause of acute, infectious GI illness in young dogs. Although its exact origin is unknown, it is believed to have arisen from feline panleukopenia virus or a related parvovirus of nondomestic animals. It is a nonenveloped, single-stranded DNA virus, resistant to many common detergents and disinfectants, as well as to changes in temperature and pH. Infectious CPV can persist indoors at room temperature for at least 2 mo; outdoors, if protected from sunlight and desiccation, it can persist for many months and possibly years. In North America, clinical disease is largely attributed to CPV-2b; however, infection with a newer and equally virulent strain, CPV-2c, is increasingly common, having been identified in at least 15 states. To date, no association has been identified between CPV strain and severity of clinical disease.
Young (6 wk to 6 mo), unvaccinated or incompletely vaccinated dogs are most susceptible. Rottweilers, Doberman Pinschers, American Pit Bull Terriers, English Springer Spaniels, and German Shepherds have been described to be at increased risk of disease. Assuming sufficient colostrum ingestion, puppies born to a dam with CPV antibodies are protected from infection for the first few weeks of life; however, susceptibility to infection increases as maternally acquired antibody wanes. Stress (eg, from weaning, overcrowding, malnutrition, etc), concurrent intestinal parasitism, or enteric pathogen infection (eg, Clostridium spp, Campylobacter spp, Salmonella spp, Giardia spp, coronavirus) have been associated with more severe clinical illness. Among dogs >6 mo old, intact male dogs are more likely than intact female dogs to develop CPV enteritis.
Virus is shed in the feces of infected dogs within 4–5 days of exposure (often before clinical signs develop), throughout the period of illness, and for ~10 days after clinical recovery. Infection is acquired through direct oral or nasal contact with virus-containing feces or indirectly through contact with virus-contaminated fomites (eg, environment, personnel, equipment). Viral replication occurs initially in the lymphoid tissue of the oropharynx, with systemic illness resulting for subsequent hematogenous dissemination. CPV preferentially infects and destroys rapidly dividing cells of the small-intestinal crypt epithelium, lymphopoietic tissue, and bone marrow. Destruction of the intestinal crypt epithelium results in epithelial necrosis, villous atrophy, impaired absorptive capacity, and disrupted gut barrier function, with the potential for bacterial translocation and bacteremia.
Lymphopenia and neutropenia develop secondary to destruction of hematopoietic progenitor cells in the bone marrow and lymphopoietic tissues (eg, thymus, lymph nodes, etc) and are further exacerbated by an increased systemic demand for leukocytes. Infection in utero or in pups <8 wk old or born to unvaccinated dams without naturally occurring antibodies can result in myocardial infection, necrosis, and myocarditis. Myocarditis, presenting as acute cardiopulmonary failure or delayed, progressive cardiac failure, can be seen with or without signs of enteritis. However, CPV-2 myocarditis is infrequent, because most bitches have CPV antibodies from immunization or natural exposure.
Clinical signs of parvoviral enteritis generally develop within 5–7 days of infection but can range from 2–14 days. Initial clinical signs may be nonspecific (eg, lethargy, anorexia, fever) with progression to vomiting and hemorrhagic small-bowel diarrhea within 24–48 hr. Physical examination findings can include depression, fever, dehydration, and intestinal loops that are dilated and fluid filled. Abdominal pain warrants further investigation to exclude the potential complication of intussusception. Severely affected animals may present collapsed with prolonged capillary refill time, poor pulse quality, tachycardia, and hypothermia—signs potentially consistent with septic shock. Although CPV-associated leukoencephalomalacia has been reported, CNS signs are more commonly attributable to hypoglycemia, sepsis, or acid-base and electrolyte abnormalities. Inapparent or subclinical infection is common.
Gross necropsy lesions can include a thickened and discolored intestinal wall; watery, mucoid, or hemorrhagic intestinal contents; edema and congestion of abdominal and thoracic lymph nodes; thymic atrophy; and, in the case of CPV myocarditis, pale streaks in the myocardium. Histologically, intestinal lesions are characterized by multifocal necrosis of the crypt epithelium, loss of crypt architecture, and villous blunting and sloughing. Depletion of lymphoid tissue and cortical lymphocytes (Peyer's patches, peripheral lymph nodes, mesenteric lymph nodes, thymus, spleen) and bone marrow hypoplasia are also seen. Pulmonary edema, alveolitis, and bacterial colonization of the lungs and liver may be seen in dogs that died of complicating acute respiratory distress syndrome, systemic inflammatory response syndrome, endotoxemia, or septicemia.
CPV enteritis should be suspected in any young, unvaccinated, or incompletely vaccinated dog with relevant clinical signs, especially those living in or newly acquired from a shelter or breeding kennel. During the course of the illness, most dogs develop a moderate to severe leukopenia characterized by lymphopenia and neutropenia. Leukopenia, lymphopenia, and the absence of a band neutrophil response within 24 hr of starting treatment has been associated with a poor prognosis. Prerenal azotemia, hypoalbuminemia (GI protein loss), hyponatremia, hypokalemia, hypochloremia, and hypoglycemia (due to inadequate glycogen stores in young puppies and/or sepsis, potentially a poor prognostic indicator), and increased liver enzyme activities may be noted on the serum biochemical profile. Commercial ELISAs for detection of antigen in feces are widely available and have good to excellent sensitivity and specificity, even for the more recently evolved CPV-2c strain. All animals with relevant clinical signs should be immediately tested, so appropriate isolation procedures can be initiated. Most clinically ill dogs shed large quantities of virus in the feces. However, false-negative results can be seen early in the course of the disease (before peak viral shedding), because of the dilutional effect of large volume diarrhea, or after the rapid decline in viral shedding that tends to occur within 10–12 days of infection. False-positive results can be seen within 4–10 days of vaccination with modified-live CPV vaccine. Alternative ways to detect CPV antigen in feces include PCR testing, electron microscopy, and virus isolation. Serodiagnosis of CPV infection requires demonstration of a 4-fold increase in serum IgG titer throughout a 14-day period or detection of IgM antibodies in the absence of recent (within 4 wk) vaccination.
The main goals of treatment for CPV enteritis include restoration of fluid, electrolyte, and metabolic abnormalities and prevention of secondary bacterial infection. In the absence of significant vomiting, oral electrolyte solutions can be offered. Administration SC of an isotonic balanced electrolyte solution may be sufficient to correct mild fluid deficits (<5%) but is insufficient for dogs with moderate to severe dehydration. Most dogs will benefit from IV fluid therapy with a balanced electrolyte solution. Correcting dehydration, replacing ongoing fluid losses, and providing maintenance fluid needs are essential for effective treatment. Dogs must be monitored for development of hypokalemia and hypoglycemia. If electrolytes and serum blood glucose concentration cannot be routinely monitored, empirical supplementation of IV fluids with potassium (potassium chloride 20–40 mEq/L) and dextrose (2.5%–5%) is appropriate.
If GI protein loss is severe (albumin <20 g/L, total protein <40 g/L, evidence of peripheral edema, ascites, pleural effusion, etc), colloid therapy should be considered. Nonprotein colloids (eg, pentastarch, hetastarch) can be administered in boluses (5 mL/kg, maximum of 20 mL/kg) throughout at least 15 min. The remainder of the maximal dosage of 20 mL/kg can be administered as a constant-rate infusion throughout 24 hr, and the volume of crystalloids administered decreased by 40%–60%. Alternatively, transfusion of fresh frozen plasma may partially replace serum albumin while providing serum protease inhibitors to counter the systemic inflammatory response. There is no evidence to support the use of serum from dogs recovered from CPV-enteritis (convalescent or hyperimmune serum) as a means of passive immunization.
Antibiotics are indicated because of the risk of bacterial translocation across the disrupted intestinal epithelium and the likelihood of concurrent neutropenia. A β-lactam antibiotic (eg, ampicillin or cefazolin [22 mg/kg, IV, tid]) will provide appropriate gram-positive and anaerobic coverage. For severe clinical signs and/or marked neutropenia, additional gram-negative coverage (eg, enrofloxacin [5 mg/kg/day, IM or IV] or gentamicin [6 mg/kg/day, IV]) is indicated. Aminoglycoside antibiotics must not be administered until dehydration has been corrected and fluid therapy established. Enrofloxacin has been associated with articular cartilage damage in rapidly growing dogs 2–8 mo old and should be discontinued if joint pain or swelling develops. Second- or third-generation cephalosporins (eg, cefoxitin, ceftazidime, cefovecin, others) can also be considered for their relatively wide spectrum of activity against gram-positive and gram-negative bacteria.
Antiemetic therapy is indicated if vomiting is protracted, perpetuates dehydration and electrolyte abnormalities, or limits oral administration of medications and nutritional support. α-Adrenergic antagonists (eg, prochlorperazine, 0.1–0.5 mg/kg, SC, tid) can worsen hypotension in hypovolemic animals, whereas prokinetic agents (eg, metoclopramide, 0.3 mg/kg, PO or SC, tid, or 1–2 mg/kg/day as a constant-rate infusion) may increase the risk of intussusception; use of either agent should be restricted to dogs that are rehydrated and being appropriately monitored. In dogs with CPV enteritis, maropitant (1 mg/kg/day, IV) and ondansetron (0.5 mg/kg, IV, tid) appear to be equally effective at controlling vomiting, although maropitant may be associated with an improved ability to maintain body weight during illness. Vomiting may persist despite antiemetic administration. Antidiarrheals are not recommended, because retention of intestinal contents within a compromised gut increases the risk of bacterial translocation and systemic complications. A successful protocol for outpatient treatment of dogs with parvoviral enteritits, consisting of maropitant (1 mg/kg/day, SC), cefovecin (8 mg/kg, SC, every 14 days), and SC crystalloid fluids (tid), has been described.
Previous anecdotal recommendations for nutritional management of CPV enteritis included withholding food and water until cessation of vomiting. However, evidence suggests early enteral nutrition is associated with earlier clinical improvement, weight gain, and improved gut barrier function. For anorectic dogs, placement of a nasoesophageal or nasogastric tube for continual feeding of a prepared liquid diet (eg, Clinicare®, or dilute, blended canned diet) should be instituted within 12 hr of hospital admission. Once vomiting has subsided for 12–24 hr, gradual reintroduction of water and a bland, low-fat, easily digestible commercial or homemade (eg, boiled chicken or low-fat cottage cheese and rice) diet is recommended. Partial or total parenteral nutrition is reserved for dogs with anorexia >3 days that cannot tolerate enteral feeding.
Oseltamivir is an antiviral agent, usually used to treat influenza virus infections in people. In a single published study of naturally occurring CPV enteritis in dogs, treatment with oseltamivir (2 mg/kg, PO, bid for 5 days) did not decrease duration of hospitalization, clinical disease severity, or mortality. However, treated dogs did not experience weight loss or a decrease in WBC count, as were observed in untreated control dogs. The potential for induction of drug resistance to human or avian influenza viruses has led some to question the appropriateness of oseltamivir administration to animals. Other adjunctive treatments such as recombinant human granulocyte colony-stimulating factor, recombinant bactericidal/permeability-increasing protein, and feline interferon-ω have not been shown to be beneficial.
Intussusception, bacterial colonization of IV catheters, thrombosis, urinary tract infection, septicemia, endotoxemia, acute respiratory distress syndrome, and sudden death are potential complications of CPV enteritis. Most puppies that survive the first 3–4 days of illness make a full recovery, usually within 1 wk. With appropriate supportive care, 68%–92% of dogs with CPV enteritis will survive. Dogs that recover develop longterm, possibly lifelong immunity.
To limit environmental contamination and spread to other susceptible animals, dogs with confirmed or suspected CPV enteritis must be handled with strict isolation procedures (eg, isolation housing, gowning and gloving of personnel, frequent and thorough cleaning, footbaths, etc). All surfaces should be cleaned of gross organic matter and then disinfected with a solution of dilute bleach (1:30) or a peroxygen, potassium peroxymonosulfate, or accelerated hydrogen peroxide disinfectant. The same solutions may be used as footbaths to disinfect footwear.
To prevent and control CPV, vaccination with a modified-live vaccine is recommended at 6–8, 10–12, and 14–16 wk of age, followed by a booster administered 1 yr later and then every 3 yr. Because of potential damage by CPV to myocardial or cerebellar cells, inactivated rather than modified-live vaccines are indicated in pregnant dogs or colostrum-deprived puppies vaccinated before 6–8 wk of age. It has been suggested that the presence of maternally acquired CPV antibodies may interfere with the effectiveness of vaccination in puppies <8–10 wk old. However, current modified-live CPV vaccines are sufficiently immunogenic to protect puppies from infection in the presence of low levels of interfering maternal antibody, and vaccination of 4-wk-old puppies with a high antigen titer vaccine results in seroconversion and may decrease the window of susceptibility to infection. Current vaccine products protect similarly well against CPV-2 as against other strains of the virus.
As described above, CPV can remain viable in the environment for an extended period. In a kennel, shelter, or hospital situation, cages and equipment should be cleaned, disinfected, and dried twice before reuse. The same concepts can be applied to a home situation. Removal of contaminated organic material is important in outdoor situations where complete disinfection is not practical. Disinfectants can be applied outdoors with spray hoses, but disinfection will be less effective than when applied to clean, indoor surfaces. In a home situation, only fully vaccinated puppies (at 6, 8, and 12 wk) or fully vaccinated adult dogs should be introduced into the home of a dog recently diagnosed with CPV enteritis. Booster vaccination of in-contact healthy dogs that are up-to-date on parvovirus vaccination is reasonable but potentially unnecessary given the extended duration of immunity to CPV.