1. What are the common clinical signs in dogs with canine parvovirus (CPV)?
• Acute-onset diarrhea
• Profound neutropenia (white blood cells < 1000/mm3)
Puppies between the ages of 6 weeks to 6 months are most commonly affected. In a Canadian study, sexually intact dogs had a 4-fold greater risk than spayed or neutered dogs, and the months of July, August, and September had a 3-fold increase in cases of canine parvovirus.
2. What systems other than the GI tract are involved with canine parvovirus?
In a study of dogs with the GI form of canine parvovirus, arrhythmia was diagnosed in 21 of 148 cases, including supraventricular arrhythmias and conduction disturbances. Some dogs developed significant enlargement of the cardiac silhouette and other radiographic cardiac abnormalities. CPV can replicate in bone marrow, heart, and endothelial cells; replication in endothelial cells of the brain produces neurologic disease.
3. What other infectious diseases may be mistaken for canine parvovirus infection?
Infection with Salmonella sp., Campylobacter sp., or Escherichia coli may mimic canine parvovirus symptoms and also cause the shift in white blood cells. CPV infection also may be confused with hemorrhagic gastroenteritis (HGE), although HGE is seen most commonly in smaller breeds and usually resolves in 24 hours. Coronavirus often presents with GI signs, but neutropenia tends to resolve more rapidly than with canine parvovirus infection. Clinical signs of infection with coronavirus are usually seen only in dogs also infected with parvovirus.
4. What is the primary mode of transmission of canine parvovirus?
The number of viral particles in the feces is quite high; the fecal-oral route is the most likely means of transmission. No studies of vomitus have been done, but it probably contains viral particles.
5. How does canine parvovirus infect the intestines?
Viral replication occurs in the oropharynx during the first 2 days of infection, spreading to other organ systems via the blood. By the third to fifth day a marked viremia develops. The virus reaches the intestinal mucosa from the blood rather than from the intestinal lumen. Clinical signs are seen 4-5 days after exposure, and the incubation period ranges from 3-8 days, with shedding of the virus on day 3.
6. Where does canine parvovirus replicate in the body?
The virus replicates in rapidly dividing cells, which include lymph nodes, spleen, bone marrow, and intestines. In the intestines, viral replication kills the germinal epithelium of the intestinal crypts, leading to epithelial loss, shortening of the intestinal villi, vomiting, and diarrhea. Lymphoid necrosis and destruction of myeloproliferative cells result in lymphopenia and, in severe cases, panleukopenia. Only about one-third of canine parvovirus cases have defined neutropenia or lymphopenia.
7. How has the clinical presentation of CPV infection changed since the 1970s?
There are several strains of canine parvovirus, including the original strain, CPV-1; the minute virus; and the most severe strain, CPV-2 (with subtypes 2a and 2b). CPV-2b is now the most common strain in the United States. CPV-1, which dominated in the 1970s, caused a milder disease associated with fever and a larger window for treatment. CPV-2b causes a more explosive acute syndrome that affects young dogs 6-12 weeks of age, making the window between the first signs of GI upset and treatment much narrower and more critical. There have been no major changes in presentation in the past 6 years; lethargy, listlessness, and bloody diarrhea are the most common presenting signs. Other diseases associated with or mistaken for canine parvovirus are canine distemper virus, coccidial or giardial infection, hookworms, roundworms, or a combination of these.
8. When and how does one diagnose canine parvovirus?
CPV is most easily diagnosed with a fecal enzyme-linked immunosorbent assay (ELIS A). If the test is negative but canine parvovirus is still suspected, isolate the animal and run the test again in 48 hours. The virus is not usually shed until day 3, and conscientious clients may bring the animal to the hospital at the first sign of illness. The period during which canine parvovirus is shed in the feces is brief, and the virus is not usually detectable until day 10-12 after infection. Usually the acute phase of illness has passed by this time. Modified live canine parvovirus vaccines shed in the feces may give a false-positive ELISA result 4-10 days after vaccination.
One also may use a combination of ELISA, complete blood count, and radiographs to diagnose canine parvovirus. Radiographs may help to rule out the possibility of an intestinal foreign body, and detection of generalized ileus with fluid-filled loops of intestines supports the diagnosis of canine parvovirus. Be sure to have enough antigen in the fecal sample when running the ELISA; watery stools may dilute the antigen and give a false-negative result.
Conclusive proof of canine parvovirus infection is made with electron microscope identification of the virus.
9. What are the recommendations for inpatient care of dogs with CPV?
1. Aggressive fluid therapy. Correct dehydration and provide intravenous maintenance fluid volumes of a balanced crystalloid solution. Make every attempt to replace continuing losses (vomitus and diarrhea) with equal volumes of crystalloid fluids. The easiest method is simply to estimate the volume lost and double your estimate. Continuing losses need to be replaced at the time that they occur. Use Normosol with at least 20 mEq/L of potassium chloride supplementation. Monitor glucose level. If necessary, add 2.5-5% dextrose to intravenous fluids. A 5% dextrose solution creates an osmotic diuresis, but it also allows assessment of progress in dealing with a septic case (glucose increases when the animal receives 5% dextrose if the sepsis is resolving). Low levels of magnesium chloride may be added to fluids to help correct unresponsive hypokalemia.
2. Antibiotic therapy. Broad-spectrum parenteral antibiotics are recommended because of disruption of the mucosal barrier and potential sepsis. Bacteremia is identified in 25% of dogs infected with parvovirus. A combination of ampicillin and gentamicin is recommended. Most veterinarians use only a first-generation cephalosporin in dogs without neutropenia or fever and reserve ampicillin and gentamicin or amikacin for dogs with signs of sepsis. One should be cautious about using an aminoglycoside because of renal toxicity.
3. Endotoxin-neutralizing products. Endotoxin-neutralizing products may be administered along with antibiotic therapy. The rationale for their use is based on the large population of gram-negative bacteria; by killing the bacteria, antibiotic therapy may shower the body with en-dotoxin, thus exacerbating the canine parvovirus condition. Studies have shown that endotoxin-neutralizing products decrease the incidence of septic shock. They may be diluted (4 ml/kg) with an equal volume of saline and administered intravenously over 30-60 minutes. Dogs who have recovered from parvovirus infections can be a good source for serum. Serum should be collected within 4 months of infection.
4. Antiemetics. Metoclopramide is the drug of choice. Phenothiazine derivatives should be used with caution and only after adequate volume replacement is initiated to avoid severe hypotension. Antiemetics are especially useful when continued vomiting makes it difficult to maintain hydration or electrolyte balance.
5. Motility modifiers. The use of motility modifiers is controversial. Anticholinergic anti-diarrheal medications may suppress segmental contractions and actually hasten transit time. Narcotic analgesics and synthetic opiates are better choices but should be reserved for severe or prolonged cases because slowing the flow through the intestine may increase toxin absorption.
6. Nothing per os (NPO). Begin a slow return to water 24 hours after the animal stops vomiting, and slowly progress to gruel made from a bland diet.
10. What is granulocyte colony-stimulating factor (GCSF)? What role does it have in treating dogs with CPV?
Granulocyte colony-stimulating factor selectively stimulates release of granulocytes form the bone marrow. Preliminary studies have shown that it reduces morbidity and mortality due to canine parvovirus. Unfortunately, it is available only as a human drug and is expensive, but when the positive benefits are considered, its use may be justified.
11. Does interferon benefit a dog with parvovirus infection?
Interferon given parenterally has been shown to be beneficial. The suggested dosage of human recombinant interferon is 1.3 million units/m2 subcutaneously 3 times/week.
12. How is a dog with canine parvovirus monitored?
Monitor respiration and central venous pressure (CVP) to prevent overhydration. With osmotic diarrhea the animal loses protein. If abdominal or extremity swelling is observed or if the total solids drop by 50% from admission values or go below 2.0 gm/dl, the animal should be supplemented with either 6% hetastarch or plasma to maintain colloid oncotic pressures. Blood glucose should be monitored at least 4 times/day on the first two days. Glucose level may drop precipitously and suddenly. Most importantly, weigh the dog at least twice each day. If adequate crystalloid replacement is provided, body weight does not decrease from initial values. Ideally body weight should increase at a rate comparable to the degree of dehydration originally assessed. Dogs that can hold down water for 12 hours may be offered a gruel made from bland foods. Most dogs force-fed by hand will vomit. This response may be physical or psychological (association of food with vomiting). Nasogastric tubes seem to help this problem. Metoclopramide speeds gastric emptying, acts as an antiemetic, and decreases gastric distention when added to the liquid diet. Dogs that are not vomiting should be offered food even if the diarrhea has not totally stopped. A low-fat, high-fiber diet is a good choice to stimulate intestinal motility.
13. How do you know when to send a dog home?
The dog should stay in the hospital for 12 hours after it has ingested solid food with no vomiting. Clients should report immediately any vomiting in the next 7 days or refusal to eat for 24 hours. A high-fiber diet is recommended for reducing diarrhea. A recheck appointment in 1 week with a stool sample helps the clinician to assess progress.
14. What recommendations do you offer to clients who have had a CPV-infected animal in their household and now want a new pet?
Prevention involves a proper vaccination regimen, limited exposure to other animals (especially in puppies less than 12 weeks of age), cleaning contaminated areas with bleach (allowing prolonged contact time), and vacuuming all surfaces with which the previous pet came into contact (rugs, carpet, walls, furniture). Newer higher-titer vaccines (some of which may be started as early as 4 weeks) are helpful. Generally, one should wait at least 1 month before bringing the new pet into the home. It is doubtful that the environment (especially outdoors) will ever be completely free of the virus. Canine parvovirus is a hardy and ubiquitous organism.
15. How long can a dog with CPV be expected to retain immunity?
A dog that has recovered from canine parvovirus can maintain life-long immunity.
16. What is the recommended vaccination schedule for dogs? Is it the same for every breed?
Some breeds are more susceptible to canine parvovirus than others. Rottweilers, American pitbull terriers, Doberman pinschers, and German shepherds are the most susceptible, whereas toy poodles and Cocker spaniels are less susceptible. The new higher-titer vaccines have a higher antigen level and a more virulent vaccine strain that can overcome maternal antibodies, unlike the older lower-titer vaccines. These vaccines narrow the window of infection, especially for susceptible breeds. The vaccination protocol for the new high-titer vaccines is 6, 9, and 12 weeks. Susceptible breeds should be vaccinated only with the high-titer canine parvovirus vaccine and then with a combination vaccine at 6-8, 12, and 16 weeks. For less susceptible breeds, the combination vaccines at 6-8, 12, and 16 weeks should be adequate. Some parvovirus vaccines are approved for use as early as 4 weeks of age.
17. How do you manage a sick puppy when the client is unwilling to pursue hospital treatment for CPV?
Canine parvovirus can be treated on an outpatient basis. A combination of dietary restriction, subcutaneous fluids, and, in some cases, GI medications may be used with a follow-up appointment in 1-3 days. Outpatient recommendations include the following:
• Small, frequent amounts of fluid
• Bland food
• Oral antibiotics
• Strong recommendation to have the pet reexamined and admitted for therapy if vomiting returns or anorexia persists
Nine of ten clients bring the dog back for inpatient care shortly after taking it home. Before treating an outpatient, remember that mildly depressed dogs may have a rectal temperature of 106° F and a blood glucose of 30 mg/dl in 12 hours or less.
18. Should a dog with suspected CPV be hospitalized and placed in isolation?
Undoubtedly hospitalization provides the best chance for survival. Isolation is more controversial. In most veterinary hospitals, isolation means that the animal is housed in a section of the hospital that is not staffed at all times. The adage “out of sight, out of mind” has led to the demise of many CPV-infected dogs. Experience with housing dogs with canine parvovirus in the critical care unit at the Veterinary Teaching Hospital of Colorado State University has shown that nosocomial infections can be avoided with a common-sense approach to patient management. The animal is placed in the least traveled area and has its own cleaning supplies; gowns and gloves are worn each time the animal is handled; and the animal’s cage is kept as clean as humanly possible. These procedures are no different from those in an isolation area. By being housed in an area where constant attention can be given, the animal receives adequate fluid replacement therapy and is monitored for changes, which occur rapidly.
19. How is nutrition provided for vomiting dogs?
Tough question! Dogs that have not eaten for 3-5 days are probably in a negative nitrogen balance, and certainly intestinal villi have undergone atrophy if not already destroyed by the canine parvovirus. The sooner patients begin receiving oral nutrition, the more rapidly they will recover. In addition, micronutrient therapy for the intestinal mucosa is required for maintenance of the mucosal barrier. Without this barrier, sepsis and bacteremia are more likely. Unfortunately, the only means to provide micronutrients is the oral route.
Glucose therapy does not provide nutritional support. It is best to think of dextrose as simply a source of water. One liter of 5% dextrose solution contains a mere 170 kcal. Increasing dextrose concentrations beyond 5% usually results in glycosuria and osmotic diuresis.
Patients that have not eaten for several days are primed for fat metabolism; thus, Intralipid (20%) may be added to fluids. It should be administered through a central IV catheter and requires strict aseptic management, which may be difficult if the patient is in an isolation area of the hospital.
For dogs that retain water without vomiting, glutamine may be added directly to the water bowl. Often placing electrolyte solutions in the water bowl is a good way to start the animal drinking. Placing dextrose in these fluids or even using commercial solutions such as Ensure-Plus in the bowl helps to provide intestinal nutrients.
20. Should parvovirus antibody levels be measured to check the immune status of the puppy?
Although antibodies to parvovirus can be measured, a negative titer does not necessarily mean that the dog is susceptible to canine parvovirus. Repeated revaccination of antibody-negative dogs usually does not result in significant titers.