Successful Management Strategies for Canine Parvovirus

Successful Management Strategies for Canine Parvovirus
Indiana Veterinary Medical Association Annual Meeting, 2014
Karen M. Tefft, DVM, MVSc, DACVIM (SAIM)
Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH
Introduction
Canine parvovirus (CPV)-2 is one of the most common infectious diseases of dogs and the
most prevalent viral cause of diarrhea in dogs. CPV-2 initially emerged in 1978 to a naive
canine population and spread rapidly with high morbidity and mortality.1 It is postulated to
have arisen either from feline panleukopenia virus or a wild carnivore parvovirus. Over
time, genetic mutations have led to different strains. Strains CPV-2b and CPV-2c are
currently the most commonly identified strains in North America.2 Fortunately, strains
differ in only a single amino acid substitution, so ELISA tests are cross-reactive and
vaccination provides cross-protection.3,4
Most affected dogs are under 6 months of age. Ten to twelve weeks of age is particularly
vulnerable due to the waning protective effect of maternally-derived antibodies. Studies
have reported a summer seasonality and increased prevalence in Rottweilers, Doberman
pinschers, pit bulls, and German shepherds.5 While genetics appear to play a role in the
breed-associated risk for Rottweilers and Doberman pinschers, other factors such as breed
popularity and socioeconomic factors likely also contribute to breed associations.
Diagnosis
Sudden onset of hemorrhagic diarrhea, fever, and leukopenia in a young, unvaccinated dog
is often considered indicative of CPV infection. However, not all dogs with CPV have bloody
diarrhea or leukopenia, and other diseases such as parasitic or enteropathogenic bacterial
infection can also cause these symptoms. Therefore, definitive diagnosis should be
pursued.
Fortunately, practitioners have at their disposal a readily available, easy to use, in-office
ELISA test to detect CPV in the feces of infected dogs. These tests are specific, but poorly
sensitive for detecting CPV.2 Viral particles are readily detectable at the peak of shedding
(4-7 days post-infection). False negative results may occur if tested early in the disease
course, secondary to binding of serum-neutralizing antibodies with antigen in diarrhea or
with decline of fecal viral shed (10-12 days post-infection). False positive results may occur
after vaccination (3-10 days post-vaccination) with a modified live CPV vaccine.
While the ELISA test is sufficient for the majority of patients, fecal PCR for viral DNA may
be performed in a dog with clinical signs and a negative ELISA test. The CPV PCR has a
higher sensitivity and specificity than other methods of viral antigen determination in
feces.2 Quantitative assays (real-time PCR) using blood can also provide an estimation of
viral load, which can help distinguish vaccination from natural infection.6
CPV-2b and 2c pose similar health risks for dogs; therefore, genetic sequencing of CPV to
determine strain is not necessary for the clinical management of patients.3
Prognostic Indicators
Treatment for CPV infection can be quite costly. This often places the practitioner and the
owner in a difficult situation. The mostly likely reason the dog developed CPV infection was
due to lack of vaccination. There was no vaccination likely due to financial constraints.
Several biomarkers have been investigated to try to give some prognostic information, to
help the practitioner and owner decide which patients are most likely to survive. Mortality
without treatment is reportedly as high as 91%.7 However, survival rates with aggressive
care can be as high as 64-92%.8 While some studies have identified leukocyte changes and
signs of systemic inflammatory response syndrome (SIRS) at admission correlated with
odds of survival, a number of more recent studies have suggested that the optimal time to
prognosticate is at the 24 hour mark post-admission.
Hematology
The leukocyte count during CPV infection is classically depressed. This is attributable to
destruction of hematopoetic precursor cells within the bone marrow and other
lymphoproliferative tissue. This results in inadequate supply for the massive demand of
leukocytes (specifically neutrophils) from the inflamed gastrointestinal tract. A lack of
leukopenia, specifically the total leukocyte and lymphocyte counts, had a positive
predictive value of 100% for survival 24 hours post admission in one study.9
Biochemistry
Serum total cholesterol levels were lower in non-survival dogs than in survival dogs in one
study evaluating CPV infected dogs with concurrent signs of severe sepsis.10
Total and ionized magnesium concentrations were not associated with outcome in CPV
infection.11 This relationship was investigated since total magnesium concentration has
been found to be a prognostic indicator in critically ill humans.
Acute Phase Proteins
Acute phase proteins are considered a sensitive biomarker of inflammation. C-reactive
protein (CRP) is a major positive acute phase protein, which means its levels increase with
inflammation. One study found that serum CRP concentrations greater than 92.4 mg/L at
admission had a sensitivity of 91% to predict mortality.12 A second study evaluated the
association of serum CRP concentrations over the course of hospitalization. Their results
indicated that higher serum CRP concentrations at 12 and 24 hours after admission were
associated with shorter survival times. A CRP concentration cutoff value of 97.3 mg/L at 24
hours after admission had a sensitivity of 86.7% and a specificity of 78.7% to predict
death.13
Endocrinology
The response of the adrenal and thyroid glands to critical illness is essential for survival.
Cortisol is the signature hormone involved in the body’s response to inflammation. High
serum cortisol and low serum thyroxine concentrations at 24 and 48 hours after admission
were associated with death in CPV infection in one study.14
Treatment
There is no antiviral treatment specific for CPV, therefore the mainstay of treatment is
supportive care. The primary goals of supportive care are to restore of fluid and electrolyte
balance, prevent secondary bacterial infections, and palliate the symptoms of infection.
Fluid Therapy
The vast majority of dogs with symptomatic CPV infection are dehydrated. Accurately
assessing the degree of dehydration in puppies can be challenging, due to their elastic skin.
Intravenous or intraosseous routes for rehydration are most effective. Subcutaneous fluids
are only appropriate for the mildest of cases. Subcutaneous fluids are contraindicated in
the face of shock as there is inadequate distribution secondary to peripheral
vasoconstriction.
A balanced electrolyte solution such as Plasmalyte-148 or Normosol-R is the best initial
fluid choice. The rate of administration depends on the status of patient. Patients
presenting in shock should receive “shock dosages” of fluids (i.e. 90 ml/kg/hr). Patients not
in shock should have their dehydration corrected over the initial 6-12 hours of
hospitalization. After dehydration is corrected, ongoing fluid therapy should be calculated
based on maintenance rates plus replacement of ongoing losses due to diarrhea or
vomiting. Because of their skewed body surface area to body mass ratio compared to adult
dogs and their immature nephrons, the maintenance rate fluid for young puppies is greater
than that for older puppies or adult dogs. A minimum of 60 ml/kg/day should be
considered maintenance in a young puppy; values can exceed 100 ml/kg/day for
maintenance in neonates.15
Place the intravenous catheter aseptically and practice good catheter care, examining the
catheterization site daily for phlebitis and changing the bandaging as frequently as needed
to keep it clean of vomitus and feces. One study found bacteria colonized 22% of catheters
placed in young dogs suspected of having CPV.16 Most of the bacteria was enteric in origin.
Bacterial colonization of indwelling IV catheters is considered a potential precursor of
catheter-related infection. Only 1 of the dogs in the study was suspected to have a catheterrelated infection. However, given the profound immunosuppression of CPV infected dogs,
fastidious catheter care appears to be prudent.
If the patient is anorexic or if hypokalemia is present, potassium chloride should be added
to the balanced electrolyte solution after the initial dehydration has been corrected. The
following chart gives suggested potassium chloride supplementation rates based on the
degree of hypokalemia:
Serum K+
< 2.0
2.1 – 2.5 2.6 – 3.0 3.1 – 3.5 3.6 – 5.0
mEq/L KCl 80
60
40
30
20
Since fluid rates can be quite high in these patients, ensure that the rate of potassium
supplementation does not exceed 0.5 mEq/kg/hr, as rates in excess of this may negatively
affect cardiac function.
Hypoglycemia, secondary to sepsis, hypermetabolism, and/or decreased glycogen stores, is
commonly observed with CPV infection. After rehydration, 2.5–5% dextrose may be added
to the balanced electrolyte solution. Supplementation of concentrations greater than 5%
will require placement of a central line, as delivering such a hyperosmolar solution
peripherally will lead to phlebitis. Practitioners should be aware of the fact the
administration of dextrose supplementation in intravenous fluids does not constitute
nutritional support. See discussion of “Nutritional Support” below.
Puppies suffering from CPV often develop a severe protein-losing enteropathy due to the
destruction of intestinal villi. Colloidal support (e.g. Hetastarch, Dextrans) should be
considered when total protein drops below 35 g/L or if the patient shows evidence of third
space loss of fluid (e.g. ascites, edema). Overzealous colloidal therapy should be avoided to
prevent blunting of endogenous hepatic albumin production. Dosage of colloidal fluids is
10-20 mL/kg/day. Boluses of 5 mL/kg may be used to treat shock refractory to crystalloid
boluses. When administering colloids, the rate of crystalloids administered should be
decreased by 30-40%.
Fresh frozen plasma (FFP) transfusion has been recommended in the treatment of CPV for
its ability to provide albumin, immunoglobulins, and serum protease inhibitors, which may
help to neutralize circulating virus and control the systemic inflammatory response.
However, FFP alone is a poor means of supporting patient albumin concentrations; very
large volumes of plasma are required to achieve a small increase in plasma albumin. See
“Controversial Therapies” below for more discussion regarding the use of FFP in CPV.
Antimicrobial Therapy
CPV disrupts the gastrointestinal mucosal barrier, allowing for increased translocation of
enteric bacteria. Coupled with the neutropenia experienced by patients with severe CPV
infection, the risk of sepsis is high. Mildly affected, afebrile dogs with normal white blood
cell counts do not require aggressive combination antibiotic therapy, but dogs with
evidence of sepsis should receive bacteriocidal coverage for gram-negative and anaerobic
bacteria. The parenteral route is preferred over enteral as CPV-2 infection is often
associated with vomiting and delayed gastric emptying which may result in poor
absorption of oral medications. A combination of a β-lactam antibiotic (e.g. ampicillin 20
mg/kg IV q 8 hr) with an aminoglycoside antibiotic (e.g. amikacin 20 mg/kg IV q 24 hr) or
flouroquinolone antibiotic (e.g. enrofloxacin 5 mg/kg IV q 24 hr) would cover this
spectrum. If using an aminoglycoside, do not begin its use until the patient is rehydrated
because of the risk of nephrotoxicity with this class of antibiotics. Enrofloxacin has been
associated with cartilage abnormalities in growing dogs, so it should be avoided in large
and giant breed puppies and owners should be warned of the risk.
Antiemetic Therapy
Persistent vomiting leads to fluid and electrolyte loss, interferes with nutritional support,
precludes oral administration of medications, and puts the patient at risk for the
development of pneumonia and esophagitis. The most commonly used classes of
antiemetics for CPV infection are α2-adrenergic antagonists (e.g. chlorpromazine,
prochlorperazine), D2-dopaminergic antagonist (e.g. metoclopramide), 5-HT3-serotonergic
antagonists (dolasetron, ondansetron) and NK1 receptor antagonist (e.g. maropitant). It is
not uncommon for multimodal antiemetic therapy to be required for severe cases of CPV
enteritis.
The α2-adrenergic antagonists (Chlorpromazine: 0.2–0.4 mg/kg SQ, IM q 6-8 hr;
Prochlorperazine: 0.1–0.5 mg/kg SQ, IM q 6-8 hr) are phenothiazine derivatives. They limit
stimulation of the chemoreceptor trigger zone and emetic center. Their antiemetic effect is
potent, however they also can cause sedation and hypotension. They should not be used in
dehydrated patients.
Metoclopramide (0.2-0.4 kg/kg SQ, IM q 6-8 hr; 1–2 mg/kg/day IV CRI) blocks the
chemoreceptor trigger zone, stimulates and coordinates motility of the upper intestinal
tract, and increases pressure in the lower esophageal sphincter. The motility effects of
metoclopramide are beneficial to counteract the gastroparesis frequently found in CPV
infection; however, it does increase the risk of intussusception. It can also cause
extrapyramidal signs (e.g. involuntary muscle spasms, restlessness, aggression). The
antiemetic effect of metoclopramide is relatively weak compared to other antiemetics
although it appears to perform better as a CRI rather than intermittent injections.
The 5-HT3-serotonergic antagonists (dolasetron: 0.5-0.6 mg/kg IV q 24 hr; ondansetron:
0.1–0.3 mg/kg IV q 8-12 hr) limit stimulation of the chemoreceptor trigger zone and vagal
afferents. Their antiemetic effect is potent. They appear to be fairly well tolerated by dogs,
however they are more expensive than the α2-adrenergic antagonists and metoclopramide.
Maropitant (1 mg/kg SQ, IV q 24 hr) limits stimulation of the chemoreceptor trigger zone
and emetic center. In addition, it may have some visceral analgesic effects. Its antiemetic
effect is potent. It is labeled for dogs older than 8 weeks of age. Other than stinging on SQ
injection (which can be decreased by keeping the drug refrigerated), it appears to be fairly
well tolerated by dogs. While off label, it can be diluted and given slowly IV. In a study
comparing maropitant to ondansteron in dogs infected with CPV, maropitant appeared to
be equally as effective in controlling vomiting as compared to ondansetron. In addition,
dogs treated with maropitant demonstrated improved ability to maintain body weight.17
Gastroprotectant Therapy
Antacids and sucralfate (0.25-0.5 g PO q 8 hr) can be used to treat the gastritis and
esophagitis that occurs secondary to CPV infection. While H2-receptor antagonists (e.g.
famotidine 0.5-1 mg/kg PO, SQ, IV q 12 hr) are less expensive than proton pump inhibitors
(e.g. pantoprazole: 0.7–1 mg/kg IV q 24 hr; omeprazole: 0.7–1 mg/kg PO q 24 hr), they are
less efficacious. Enteral gastroprotectants should only be used once vomiting is under
control.
Analgesic Therapy
Ileus can cause significant visceral pain in CPV patients. NSAIDs are contraindicated for
pain management in CPV patients because of their ulcerogenic potential. Also, using
NSAIDs in a dehydrated patient increases the risk of acute renal injury. Opioids (e.g.
buprenorphine: 0.005–0.02 mg/kg IV q6–12hr; butorphanol: 0.1–0.4 mg/kg/hr IV CRI) are
the preferred class of analgesic, but remain mindful that higher doses may worsen ileus
and cause sedation.
Anthelminthic Therapy
The presence of intestinal parasites can worsen the disease process by enhancing intestinal
cell turnover.18 Therefore once the patient can tolerate oral medications, deworming (e.g.
fenbendazole: 50 mg/kg PO q24hr for 3 doses) is recommended.
Nutrition
Early enteral feeding has been shown to help maintain mucosal integrity, which decreases
the risk of bacterial translocation.19 In turn, this leads to faster clinical improvement in
patients, significant weight gain, and decreased hospitalization times. Therefore, the old
recommendations to keep a CPV patient NPO for 24-48 hours beyond the last instance of
vomiting are no longer recommended. Administration of dextrose supplementation in
intravenous fluids does not constitute nutritional support. Total or partial parenteral
nutrition may be used if a patient absolutely does not tolerate enteral feeding, but
meticulous catheter care and monitoring should be performed because of the high risk of
sepsis in CPV patients.
To perform enteral nutrition, a nasoesophageal (NE) and nasogastric (NG) tube can be
placed with minimal sedation. The benefit of NE tubes is that they do not cross the lower
esophageal sphincter, so may cause less gastroesophageal reflux. The benefit of NG tubes is
that they allow the practitioner to intermittently measure gastric residual volume. If large
residual gastric volumes are consistently measured, a promotility agent (e.g.
metoclopramide) should be started. Large residual volumes are defined as greater than
50% of the last volume fed if intermittent bolus feeding or volumes greater than twice what
is fed in an hour of CRI feeding. The removal of large residual gastric volumes will also
improve patient comfort and nausea.
As the patient recovers, there may be temporary intestinal malabsorption and proteinlosing enteropathy until intestinal villi are repaired. Initial feeding should consist of small
amounts of an easily digestible low fat diet fed frequently. The normal diet is gradually reintroduced after appetite and stool have returned to normal.
Controversial Therapies
Granulocyte colony-stimulating factor (G-CSF) is a cytokine produced by the bone marrow,
whose actions include release of granulocytes from the storage pool of the bone marrow,
shortened neutrophil maturation time, and enhanced granulopoiesis. Recombinant human
G-CSF (rhG-CSF) has been investigated in the treatment of severe neutropenia associated
with CPV infection. Results have been mixed. One study demonstrated an increase in the
neutrophil count in puppies treated with rhG-CSF during hospitalization.20 Other
investigators have found neither an increase in white blood cell count nor improved
survival.21,22
In addition to lack of proven efficacy, one complication associated with the rhG-CSF is the
development of neutralizing antibodies, resulting in a decline in leukocyte counts within 3
weeks of treatment.23 To avoid this issue, a recombinant canine G-CSF (rcG-CSF) has been
developed, but it is not commercially available. One study investigating rcG-CSF in CPV
patients found significantly higher neutrophil counts in treated dogs and decreased
hospitalization time. However, survival times were also decreased in treated dogs.24 Given
the conflicting efficacy reports, expense, and sometimes difficulty in obtaining G-CSF, the
speaker does not recommend the use of rhG-CSF or rcG-CSF in the treatment of CPV.
Equine-origin anti-endotoxin serum has also been suggested for treatment of the
endotoxemia associated with CPV infection. Because this product is of equine origin, it can
cause anaphylaxis. Studies investigating its use are conflicting. One study showed a
decrease in the mortality rate by 31%.11 However, another study found an increase in
mortality rate when puppies 16 weeks of age or younger were treated with anti-endotoxin
serum.25 Given the conflicting efficacy reports, the speaker does not recommend the use of
anti-endotoxin in the treatment of CPV.
Oseltamivir (Tamiflu®) is a neuraminidase (NA) inhibitor originally designed to treat
human influenza virus. NA is necessary for liberation of newly formed virions from the host
cell and allows virus penetration through the mucin layer covering the respiratory
epithelium. Unlike the influenza virus, CPV does not rely on NA for replication. Any
beneficial effects oseltamivir may have in CPV infection would not be due to a direct antiviral effect. Some have proposed that NA inhibition could block bacterial penetration
through the mucin layer covering the gut endothelium, thus decreasing bacterial
translocation. One study did not find a significant improvement in the days hospitalized or
outcome; however the oseltamivir treated group did not lose as much weight or have as
significant neutropenia as the control group.26 Given the lack of improvement in outcome,
expense, and shortages of the drug during influenza season, the speaker does not
recommend the use of oseltamivir in the treatment of CPV.
Plasma from dogs who recovered from CPV infection has been recommended anecdotally
to provide passive immunization in affected dogs.27 In theory, the infused antibodies would
neutralize free virus in plasma, impede viral spread by blocking entry into new target cells,
and suppress the release of new infectious virions from infected cells. One study did show
that passive immunotherapy, performed 24 hours after experimental inoculation with CPV
protected from the development of clinical disease.28 However, a recent study, which
evaluated a fixed dose of immune plasma in dogs with naturally occurring CPV infection did
not find that it improved clinical signs, reduced viremia or improved hematologic
recovery.29 However, this study had a small sample size, the dose of plasma may have been
too low, and the dose may have been administered too late in the disease process. Plasma
administration is certainly indicated in CPV puppies with documented hypocoagulability
associated with disseminated intravascular coagulation. While the role of plasma for
immunoglobulin delivery and serum protease inhibitor replenishment is less well defined,
the speaker prefers to use FFP in moderate-to-severe cases of CPV enteritis if finances
allow.
Emerging Therapies
Interferons modulate immune function and have antiviral affects. In 2 experimental models
of CPV infection, administration of recombinant feline interferon-ω (rFeIFN-ω), for 3
successive days after inoculation with CPV, resulted in a significant reduction in the
severity of clinical signs in affected dogs and decreased morbidity and mortality.30,31 More
recently, administration of rFeIFN-ω (2.5 MU/kg intravenously for 3 consecutive days) to a
group of dogs with naturally acquired CPV enteritis resulted in a 4.4-fold overall reduction
in mortality.32 Unfortunately, this promising treatment is not licensed for use in the United
States.
Monitoring
Monitoring should be performed frequently and treatments (e.g. fluid rate) constantly reevaluated in light of changing parameters. Complications to be vigilant for in CPV infected
patients include intussusception, esophagitis, and aspiration pneumonia. Until the patient
begins eating on their own, it is recommended to monitor the following on at least a daily
basis: body weight, abdominal palpation, packed cell volume and total solids, white blood
cell count (or review of a blood smear for a subjective quantification of leukocyte
numbers), blood glucose, serum potassium, and urine specific gravity (which should range
from 1.015-1.020 if euhydrated). In small patients such as young toy breeds, you may want
to consider using pediatric sampling tubes (aka “avian tubes”) for blood sampling so as to
not iatrogenically contribute to anemia.
Infection Control
CPV is a non-enveloped virus, which makes it hardy in the environment and resistant to
many disinfectants. It can survive in the environment for at least 6 months at room
temperature and even longer in the cold. 5% bleach diluted 1:32 or a quaternary
ammonium disinfectant (e.g. Parvosol®, Roccal-D®) are effective disinfectants. Soiling
with bodily fluids should be cleaned prior to disinfecting a cage or exam table as the
presence of organic material diminishes the effectiveness of disinfectants. Disinfectants
should have contact for a minimum of 10 minutes to properly kill CPV.
In your hospital, patients with CPV should be isolated and barrier procedures employed.
This is to both prevent the spread of CPV in your hospital, but to also protect the patient
who is immune-compromised. If you do not have a separate isolation room, tape an
isolation perimeter around the cage. Keep a separate trash and laundry stream for the
patient. Wear disposable protective clothing (e.g. gloves, apron, overshoes) whenever
working with the patient. Remove soiled bedding promptly from the patient’s cage to
minimizing the presence of infectious agents and keeping the patient clean, warm and
comfortable. Use an antiseptic hand wash and a footbath as you leave the isolation area.
Bathe the patient immediately prior to discharge.
References
1.
2.
Shackelton LA, Parrish CR, Truyen U, Holmes EC. High rate of viral evolution associated with the
emergence of carnivore parvovirus. Proc Natl Acad Sci USA 2005;102:379-384.
Greene CE, Decaro N. Canine viral enteritis. In: Greene CE, editor. Infectious diseases of the dog and
cat. 4th ed. St. Louis: Elsevier; 2012. p. 67-80.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
Markovitch JE, Stucker KM, Carr AH, Harbison CE, Scarlett JM, Parrish CR. Effects of canine parvovirus
strain variation on diagnostic test results and clinical management of enteritis in dogs. J Am Vet Med
Assoc 2012;241:66-72.
Wilson S, Stirling C, Borowski S, Thomas A, King V, Salt J. Vaccination of dogs with Duramune
DAPPi_LC protects against pathogenic canine parvovirus type 2c challenge. Vet Rec 2013;172:662664.
Houston DM, Ribble CS, Head LL. Risk factors associated with parvovirus enteritis in dogs: 283 cases
(1982–1991). J Am Vet Med Assoc 1996;208:542-546.
Veir JK, Duffy AL, Dow SW, et al. Comparison of quantitative PCR and conventional endpoint PCR for
amplification of parvovirus DNA in blood from naturally infected and recently vaccinated dogs
[abstract]. J Vet Intern Med 2009;23:769.
Prittie J. Canine parvoviral enteritis: a review of diagnosis, management, and prevention. J Vet Emerg
Crit Care 2004;14:167-176.
Humm KR, Hughes D. Canine parvovirus infection. In: Silverstein DC, Hopper K, editors. Small animal
critical care medicine. St. Louis: Saunders, 2009. p. 482-485.
Goddard A, Leisewitz AL, Christopher MM, et al. Prognostic usefulness of blood leukocyte changes in
canine parvoviral enteritis. J Vet Intern Med 2008;22: 309–16.
Yilmaz Z, Senturk S. Characterization of lipid profiles in dogs with parvoviral enteritis. J Small Anim
Pract 2007;48:643-650.
Mann FA, Boon GD, Wagner-Mann C, et al. Ionized and total magnesium concentrations in blood from
dogs with naturally acquired parvoviral enteritis. J Am Vet Med Assoc 1998;212:1398–401.
Kocaturk M, Martinez S, Eralp O, Tvarijonaviciute A, Ceron J, Yilmaz Z. Prognostic value of serum
acute-phase proteins in dogs with parvoviral enteritis. J Sm Anim Pract. 2010;51:478-483.
McClure V, van Schoor M, Thompson PN, Kjelgaard-Hansen M, Goddard A. Evaluation of the use of
serum C-reactive protein concentration to predict outcome in puppies infected with canine
parvovirus. J Am Vet Med 2013;243:361-266.
Schoeman JP, Goddard A, Herrtage ME. Serum cortisol and thyroxine concentra- tions as predictors of
death in critically ill puppies with parvoviral diarrhea. J Am Vet Med Assoc 2007;231:1534–1539.
Boothe DM, Bucheler J. Drug and blood component therapy and neonatal isoerythrolysis. In: Hoskins
JD, editor. Veterinary pediatrics dogs and cats from birth to six months. 3rd ed. Philadelphia:
Saunders, 2001. p. 35-56.
Lobetti RG, Joubert KE, Picard J, Carstens J, Pretorius E. Bacterial colonization of intravenous
catheters in young dogs suspected to have parvoviral enteritis. J Am Vet Med Assoc 2002;220:13211324.
Lenberg J, Sullivan L, Boscan P, Hackett T, Twedt D. Maropitant versus ondansetron on the clinical
recovery of dogs with parvoviral gastroenteritis [abstract]. J Vet Intern Med 2012;26:795.
Brunner CJ, Swango LJ. Canine parvovirus infection: effects on the immune
system and factors that predispose to severe disease. Compend Contin Educ Pract Vet 1985;7:979–
88.
Mohr AJ, Leisewitz AL, Jacobson LS, Steiner JM, Ruaux CG, Williams DA. 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.
Kraft W, Kuffer M. Treatment of severe neutropenias in the dog and cat with Filgrastim. Tierarztl
Prax 1995; 23:609–613.
Rewerts JM, McCaw DL, Cohn LA, et al. Recombinant human granulocyte colony-stimulating factor for
treat- ment of puppies with neutropenia secondary to canine parvovirus infection. J Am Vet Med
Assoc 1998; 213: 991–992.
Mischke R, Barth T, Wohlsein P, et al. Effect of recombinant human granulocyte colony-stimulating
factor (rhG- CSF) on leukocyte count and survival rate of dogs with parvoviral enteritis. Res Vet Sci
2001; 70:221–225.
Henry CJ, Buss MS, Lothrop CD. Veterinary uses of recombinant human granulocyte colonystimulating factor. Part 1. Oncology. Comp Cont Ed Pract Vet 1998;20:728–735.
Duffy A, Dow S, Ogilvie G, Rao S, Hackett T. Hematologic improvement in dogs with parvovirus
infection treated with recombinant canine granulocyte-solony stimulating factor. J Vet Pharmacol
Therap 2010;33:352-356.
25. Dimmit R. Clinical experience with cross-protective antiendotoxin antiserum in dogs with parvoviral
enteritis. Canine Pract 1991; 16:23–26.
26. Savigny MR, Macintire DK. Use of oseltamivir in the treatment of canine parvoviral enteritis. J Vet
Emerg Crit Care 2010;20:132-142.
27. Macintire DK, Smith-Carr S. Canine parvovirus. Part II. Clinical signs, diagnosis, and treatment.
Compend Contin Educ Pract Vet 1997;19:291–302.
28. Meunier PC, Cooper BJ, Appel MJ, Lanieu ME, Slauson DO. Pathogenesis of canine parvovirus
enteritis: sequential virus distribution and passive immunization studies. Vet Path 1985;22:617-624.
29. Bragg R, Duffy AL, DeCecco FA, et al. Clinical evaluation of a single dose of immune plasma for
treatment of canine parvovirus infection. J Am Vet Med Assoc 2012;240:700-704.
30. Ishiwata K, Minagawa T, Kajimoto T. Clinical effects of the recombinant feline interferon-ω on
experimental parvovirus infection in beagle dogs. J Vet Med Sci 1998;60:911–917.
31. Martin V, Najbar W, Gueguen S, et al. Treatment of canine parvoviral enteritis with interferon-omega
in a placebo-controlled challenge trial. Vet Microbiol 2002;89:115–127.
32. de Mari K, Maynard L, Eun HM, et al. Treatment of canine parvoviral enteritis with interferon-omega
in a placebo-controlled field trial. Vet Rec 2003;152:105–108.
`