Canine Parvovirus (CPV)

• First Described: 1978, worldwide.
• Etiology : CPV-2 variants (family Parvoviridae, subfamily Parvovirinae, genus Protoparvovirus). Monoclonal-antibody studies have tracked antigenic drift in CPV-2, and the CPV-2a, 2b and 2c strains are now recognised; CPV-2c viruses are more virulent and carry a higher mortality. CPV-2 is a close relative of feline panleukopenia virus (FPV).
• Human Health Significance: The virus itself poses no zoonotic risk, but affected puppies may carry Giardia co-infections, which can be zoonotic.
• Characterization: An acute systemic illness marked by fever, lethargy, inappetence, vomiting, hemorrhagic enteritis, dehydration and leukopenia. Sudden death or tachypnea from myocarditis is rare and follows infection of neonatal animals only.
• Affected Hosts: Dogs and other members of the order Carnivora — coyotes, foxes, wolves, raccoons, otters and coatis — with occasional infection of large and small cats.
• Route of Transmission: Direct contact with virus in feces and vomitus, or with contaminated fomites. Feces become infectious 3–4 days after exposure and heavy shedding lasts about 10–14 days. CPV survives in soil for up to 7 months; sunlight and dry conditions shorten its infectivity, while cold weather may prolong it.

Vaccination and good hygiene are the cornerstones of prevention. Young puppies are highly susceptible because the immunity they receive in their mother’s milk can fade before their own immune system is mature enough to fight the virus; a puppy exposed to canine parvovirus during this gap may become ill. Maternal antibody can also blunt the response to vaccination, which is why even vaccinated puppies are occasionally infected and develop disease. To narrow the gap and give the best protection during the first months of life, puppies receive a series of vaccinations, and every puppy should get a dose of canine parvovirus vaccine between 14 and 16 weeks of age — whatever it received earlier — to be adequately protected.

To protect adult dogs, owners should make sure their dog’s parvovirus vaccination stays up-to-date.

• Parvoviruses require actively dividing cells for growth.
• Ingestion of the virus is followed by a 2–4-day period of viremia.
• Early lymphatic infection brings lymphopenia and precedes intestinal infection and clinical signs.
• By post infection (PI) day 3, the rapidly dividing crypt cells of the small intestine are infected.
• Fecal shedding of virus begins ∼3–4 days PI and peaks with the clinical signs.
• Virus is no longer shed in detectable amounts by PI days 8–12.
• Bacterial endotoxins absorbed through the damaged intestinal mucosa contribute to CPV-2 disease.
• Severity of illness relates to viral dose and antigenic type.
• Gross changes include subserosal congestion and hemorrhage, or frank hemorrhage into the small-intestinal lumen, or intestines that are empty or hold yellow or blood-tinged fluid.
• Mesenteric lymph nodes are often enlarged and edematous, with cortical hemorrhages.
• Thymic atrophy in young dogs.
• In dogs with myocarditis and heart failure, pulmonary edema and hydropericardium may be the only gross change.
• Histopathology shows intestinal inflammation and necrosis with severe villus atrophy.

Suspect CPV-2 infection whenever puppies have an enteric illness.

• Sudden onset of bloody diarrhea, anorexia, and vomiting.
• Some dogs collapse in a shock-like state and die without enteric signs.
• In breeding kennels, several littermates may fall ill at the same time or within a short period.
• Occasionally one or two puppies in a litter show minimal signs while littermates die, which may reflect the degree of virus exposure.

• Hypovolemic shock—weak pulse, tachycardia, dull mentation.
• Severe hemorrhagic diarrhea.
• Fluid-filled intestinal loops may be palpated.
• Dehydration, weight loss, abdominal discomfort.
• May have fever or hypothermia.
• Vomiting and diarrhea lead to dehydration. Vital signs reflect systemic inflammation — fever, tachycardia and tachypnea — while severely decompensated dogs may present with bradycardia and hypothermia. Mucous membranes may be injected from sepsis-induced vasodilation, or pale from hypovolemic shock and/or anemia.
• Continuing fluid losses deplete intravascular volume, and the resulting hypovolemia shows in abnormal perfusion parameters (e.g., tachycardia, prolonged capillary refill time, weak or absent peripheral pulses, obtundation, low arterial blood pressure and raised blood lactate).
• Because the enteritis is severe, most dogs have moderate to severe abdominal pain. Palpation provokes nausea, regurgitation and discomfort; the intestinal loops feel distended and fluid-filled, and an intussuscepted segment is sometimes palpable. Rectal examination yields liquid, often hemorrhagic feces.

• Canine coronavirus infection.
• Salmonellosis; colibacillosis; other enteric bacterial infections.
• Gastrointestinal foreign bodies.
• Gastrointestinal parasites.
• Acute hemorrhagic diarrhea syndrome (previously hemorrhagic gastroenteritis).
• Intussusception (may be concurrent).
• Toxin ingestion.

• Lymphopenia—characteristic; commonly occurs PI days 4–6
• Severely affected dogs develop severe neutropenia as intestinal damage begins.
• Leukocytosis during recovery.
• Serum chemistry profiles help assess electrolyte disturbances (especially hypokalemia), azotemia, panhypoproteinemia and hypoglycemia.

• Viral antigen can be detected in stool at the onset of disease and for 2–4 days afterward; many commercial point-of-care ELISA kits are available, as are PCR and quantitative PCR methods, including fecal PCR panels that detect parvovirus. ELISA can detect antibodies or antigens, and the canine parvovirus test is very specific. Virus may not appear in the feces for the first 24 to 48 hours after clinical signs begin, so a negative test should be repeated in 2 to 3 days when parvoviral infection is strongly suspected. Dogs with parvoviral diarrhea shed large amounts of virus at first, but shedding falls sharply over the next 7 to 14 days, so repeatedly negative results do not rule out infection — they call for other acute, febrile gastroenteritides (e.g., salmonellosis) to be considered. The test is especially valuable where epidemiologic factors apply (e.g., a breeding kennel).
• Serologic tests are not diagnostic, because dogs often have high titers from vaccination and/or maternal antibodies.

• Abdominal radiographs—generalized small-intestinal ileus; take care not to misdiagnose intestinal obstruction, although intussusception can produce an obstructive pattern.
• Abdominal ultrasound—fluid-filled, atonic small and large intestines; thinning of the duodenal and jejunal mucosal layer, with or without indistinct wall layering and irregular luminal-mucosal surfaces; extensive hyperechoic mucosal speckling and corrugation of the duodenum and/or jejunum; intussusceptions can be identified.

• Electron microscopy detects fecal virus during early stages of infection.
• Submit samples for virus detection during the acute phase of infection and ship them refrigerated, not frozen. Electron microscopy can reveal viral particles such as parvovirus in feces. Because ELISA usually suffices to detect parvovirus, electron microscopy is rarely needed, but it is a reasonable choice when other results are not diagnostic and epidemiologic factors apply. Collect feces for electron microscopy early in the disease, as fecal viral concentrations can fall dramatically within 7 to 14 days of the onset of signs.

• Symptomatic and supportive (see Acute Vomiting; Acute Diarrhea; Gastroenteritis, Acute Hemorrhagic Diarrhea Syndrome), including IV fluids, antibiotics, antiemetics, and analgesics.
• Intensity depends on the severity of signs; both in- and outpatient protocols exist.
• Goals are to provide intestinal nutrients, restore and maintain fluid and electrolyte balance, and resolve shock, sepsis, and endotoxemia.
• Fecal microbiota transplant may speed resolution of diarrhea.
• Prompt, intensive inpatient care leads to treatment success.
• Proper, strict isolation procedures are essential.
• Take care to prevent spread of CPV-2, a very stable virus.
• Antiviral drugs have not yet been shown to be a critical part of treatment.

• Hospitalize patients and monitor for dehydration and electrolyte imbalance.
• Fluids are usually supplemented with potassium chloride, 5% dextrose and possibly sodium bicarbonate (if bicarbonate loss causes severe metabolic acidosis).

Restrict until symptoms abate.

Puppies given early enteral nutrition through a nasoesophageal tube — compared with puppies given nothing by mouth until vomiting stopped — improved clinically sooner, gained significantly more weight and had better gut-barrier function, which may limit bacterial or endotoxin translocation.

• Explain the need for thorough disinfection, especially if other dogs are on the premises; strict sanitation is essential, and a 1 : 30 dilution of bleach (5% sodium hypochlorite) destroys CPV-2 within a few minutes.
• If possible, isolate puppies until 3 months of age and vaccinate repeatedly; typical protocols vaccinate at 6, 9, and 12 weeks of age.
• Puppies can be infected with virulent virus before any vaccine confers immunity.
• CPV-2 is shed for less than 2 weeks after infection; no carrier state has been substantiated.

• Take care not to misdiagnose intestinal obstruction, especially if vomiting is the only clinical sign.
• Intussusceptions can occur.

Treatment of acute Vomiting; Acute Diarrhea; Gastroenteritis, Acute Hemorrhagic Diarrhea Syndrome*

Further recommended drugs are parenteral antibiotics (ampicillin and gentamicin) and antiemetics (e.g., ondansetron, maropitant).

Gentamicin may cause renal toxicity in dehydrated puppies.

Dogs and cats with viral enteritis but no obvious systemic sepsis may reasonably receive antibiotics when secondary sepsis is likely (e.g., patients that are, or are likely to become, neutropenic); first-generation cephalosporins (e.g., cefazolin) often work well here. When systemic or abdominal sepsis is thought to originate in the alimentary tract (e.g., septicemia from parvoviral enteritis, a perforated intestine), broad-spectrum antimicrobial therapy is indicated. Pairing a drug with strong aerobic gram-positive and anaerobic activity (e.g., ampicillin plus sulbactam [Unasyn] 20 mg/kg IV q8h, or clindamycin 11 mg/kg IV q8h) with one active against most aerobic bacteria (e.g., amikacin 25 mg/kg IV q24h, or enrofloxacin 15 mg/kg IV q24h [5 mg/kg in cats]) is often effective. To widen anaerobic cover — especially when a cephalosporin replaces ampicillin — metronidazole (10 mg/kg IV q8–12h) can be added, or a second-generation cephalosporin (e.g., cefoxitin 30 mg/kg IV q6–8h) used instead. It generally takes at least 48 hours to judge whether therapy is working.

Puppies that have had parvovirus infection show a higher incidence of discospondylitis.

• Both inactivated and live vaccines are available, and they differ in how well they immunize puppies that still carry maternal antibodies.
• A modified live vaccine given at 4 weeks of age to puppies with high maternally derived antibody produced seroconversion in up to 80%, which may shorten the window of susceptibility to CPV and could support control in contaminated environments.
• Controlling CPV-2 requires effective vaccines, isolation of puppies, and strict hygiene.

• Septicemia/endotoxemia.
• Bacterial pneumonia.
• Intussusception.
• Discospondylitis.

• Prognosis is guarded in severely affected puppies.
• Prognosis is good for dogs that receive prompt initial treatment and survive the initial crisis—approximately 80% survival rate.
• Dogs treated promptly and appropriately usually survive, especially once they are past the first 4 days of clinical signs. Intussusception secondary to parvoviral enteritis can cause persistent diarrhea in a pup that is otherwise recovering. Dogs that recover from CPV-2 enteritis develop long-lived, possibly lifelong, immunity.
• The prognosis is poor for purebred and low-bodyweight patients and for those showing, after 24 hours of intensive therapy, severe persistent leuko- and lymphopenia, a persistently high or rising serum cortisol (>8.1 µg/dL), severe hypothyroxinemia (<0.2 µg/dL), hypocholesterolemia (<100 mg/dL) or a persistently high serum C-reactive protein (>97.3 mg/L).
• Conversely, puppies with a good prognosis are of mixed breed, older than 6 months and show a total leukocyte count >4.5 × 10³/µL, a lymphocyte count >1 × 10³/µL and a mature neutrophil count >3 × 10³/µL. A serum cortisol <8.1 µg/dL at 48 hours after admission has been associated with 96% survival, a serum thyroxine >0.2 µg/dL at 24 hours with 100% survival, and an HDL-cholesterol >50.2 mg/dL at admission with 100% survival.

“Sam,” an 8-week-old intact male Hungarian vizsla puppy from northern California.

Sam came from a breeder 6 days earlier and was eating and active on arrival. The following day a local clinic ran a routine fecal examination that found Giardia and Isospora spp., and sulfamethoxazole was started; a day later the puppy developed diarrhea, and lethargy and vomiting followed the next day. Vomiting and diarrhea then recurred every few hours — the diarrhea held fresh blood and the vomitus was clear, frothy fluid — and inappetence with intermittent vomiting continued for another 2 days.

None

Sam had been vaccinated with an attenuated live CDV, CPV-2 and CPIV vaccine at 6 weeks of age. The household had no other dogs, only one adult cat.

Body weight: 4.2 kg. General: quiet, alert and responsive; about 7%–8% dehydrated; T = 103.4°F (39.7°C), HR = 240 beats/minute, RR = 36 breaths/minute; mucous membranes pale pink and tacky, CRT = 2 seconds. Integument: full, shiny haircoat without ectoparasites. Eyes, ears, nose and throat: enophthalmos and a dry nasal planum. Musculoskeletal: BCS 2/9 — ambulatory, but emaciated and weak. Cardiovascular: weak but synchronous femoral pulses; no murmurs or arrhythmias. Respiratory: no clinically significant findings. GI: no pain on abdominal palpation; fluid-filled intestinal tract and a full urinary bladder. Rectal examination: bloody diarrhea on the thermometer; a digital rectal examination was not performed. Lymph nodes: all within normal limits.

CBC: HCT 31.5% (40%–55%), MCV 62.6 fL (65–75 fL), MCHC 35.6 g/dL (33–36 g/dL), WBC 530 cells/μL (6,000–13,000 cells/μL), neutrophils 16 cells/μL (3,000–10,500 cells/μL), lymphocytes 504 cells/μL (1,000–4,000 cells/μL), monocytes 11 cells/μL (150–1,200 cells/μL); platelets clumped but appeared adequate. Serum chemistry: sodium 143 mmol/L (145–154 mmol/L), potassium 3.8 mmol/L (3.6–5.3 mmol/L), chloride 106 mmol/L (108–118 mmol/L), bicarbonate 23 mmol/L (16–26 mmol/L), phosphorus 4.8 mg/dL (3.0–6.2 mg/dL), calcium 10.3 mg/dL (9.7–11.5 mg/dL), BUN 6 mg/dL (5–21 mg/dL), creatinine < 0.2 mg/dL (0.3–1.2 mg/dL), glucose 133 mg/dL (64–123 mg/dL), total protein 4.3 g/dL (5.4–7.6 g/dL), albumin 2.4 g/dL (3.0–4.4 g/dL), globulin 1.9 g/dL (1.8–3.9 g/dL), ALT 22 U/L (19–67 U/L), AST 15 U/L (19–42 U/L), ALP 179 U/L (21–170 U/L), creatine kinase 274 U/L (51–399 U/L), GGT < 3 U/L (0–6 U/L), cholesterol 278 mg/dL (135–361 mg/dL), total bilirubin 0.1 mg/dL (0–0.2 mg/dL), magnesium 2.0 mg/dL (1.5–2.6 mg/dL).

Abdominal radiographs: the gastric wall looked thickened. A loop of intestine in the right cranial abdomen held numerous round gas opacities, thought to be gas in the ascending colon or duodenum, and further gas opacities lay in a loop in the mid-right abdomen at the level of the fourth lumbar vertebra. Serosal detail was reduced, as expected for the puppy’s age. The changes were considered consistent with gastroenterocolitis.

Fecal parvovirus antigen ELISA: negative. Fecal enteric real-time PCR panel: positive for CPV; negative for Clostridium difficile toxin A and B genes and for Cryptosporidium, Salmonella and Giardia DNA. Fecal zinc sulfate centrifugal flotation: no parasite ova.

Enteritis and leukopenia secondary to CPV infection.

Sam was admitted to isolation and treated aggressively with IV lactated Ringer’s solution supplemented with 20 mEq KCl/L, famotidine (0.5 mg/kg IV q12h), ondansetron (0.5 mg/kg IV q12h), ampicillin (22 mg/kg IV q6h) and enrofloxacin (5 mg/kg IV q24h); persistent vomiting led to maropitant citrate (1 mg/kg IV q24h) being added as a second antiemetic. Blood glucose was checked three times a day but dextrose supplementation was never needed. For the first 24 hours he passed bloody diarrhea containing sloughed mucosa every few hours. His neutrophil count was 9 cells/μL the next day and 261 cells/μL by day 4 — with 241 moderately toxic bands/μL and 1,226 lymphocytes/μL — as he gradually improved; he began eating small amounts of cottage cheese and rice on day 4 and went home on day 5.

Although the fecal antigen ELISA was negative, CPV enteritis was suspected from the history, the clinical signs and the severe leukopenia. Leukopenia with diarrhea is not by itself diagnostic of parvoviral enteritis, since other severe enteritides such as salmonellosis can cause it. The positive fecal real-time PCR supported the diagnosis, but because some assays are positive in healthy dogs and after vaccination, the PCR result alone could not confirm it — the diagnosis rested on the combination of findings. The dog’s neutropenia was profound, and because diarrhea began only 2 days after purchase, infection most likely happened before the owner acquired the puppy.

• CPV = canine parvovirus.
• FPV = feline panleukopenia virus.
• PI = postinfection.

• Acute Diarrhea.
• Acute Vomiting.
• Canine Coronavirus Infections.
• Gastroenteritis, Acute Hemorrhagic Diarrhea Syndrome.
• Sepsis and Bacteremia.
• Shock, Septic.

Mohr AJ, Leisewitz AL, Jacobson LS, et al. Effect of early enteral nutrition on intestinal permeability, intestinal protein loss, and outcome in dogs with severe parvoviral enteritis. J Vet Intern Med 2003, 17:791–798.

Schoeman JP, Goddard A, Herrtage ME. Serum cortisol and thyroxine concentrations as predictors of death in critically ill puppies with parvoviral diarrhea. J Am Vet Med Assoc 2007, 231:1534–1539.

Venn EC, Preisner K, Boscan PL, et al. Evaluation of an outpatient protocol in the treatment of canine parvoviral enteritis. J Vet Emerg Crit Care 2017, 27:52–65.

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