Clinical and pathologic features of parvoviral diarrhea in pound-source dogs

From June 1980 through May 1982, 161 pound-source dogs that developed diarrhea while being used in research were evaluated to determine whether canine parvovirus (CPV) type 2 was the etiologic agent. Evaluation included notation of clinical signs, determination of serum CPV-specific immunoglobulin (Ig) M and IgG titers, virus isolation attempts, and histologic examination of tissues. Criteria for diagnosis of canine parvoviral enteritis were serum CPV-specific IgM antibodies, isolation of CPV from feces, and histologic evidence of intestinal crypt cell necrosis. Upon arrival, 67 clinically normal pound-source dogs were evaluated to determine the prevalence of fecal shedding of CPV and to determine their antibody titers to CPV. Parvovirus was not isolated from any of these dogs, although 76% had IgG antibodies and 3% had IgM antibodies. Of the 161 dogs with diarrhea, 40 (25%) had parvoviral enteritis. Of dogs with parvoviral enteritis, 71% had IgG antibodies and 68% had IgM antibodies. Canine parvovirus was isolated from 18 dogs. Serum IgG antibodies were found in 85% of dogs with diarrhea due to other causes. The geometric mean titer of IgG antibodies to CPV was not significantly different among the 3 groups. Clinical signs that appeared significantly (P less than 0.05) more often in dogs with parvoviral enteritis included bloody diarrhea, anorexia, fever (greater than or equal to 39.4 C), and leukopenia (WBC less than 6,000/mm3). Cases occurred throughout the year, without apparent seasonal variation. The duration between arrival and onset of diarrhea was significantly (P less than 0.05) shorter for dogs with parvoviral enteritis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of parvoviral enteritis on plasma citrulline concentration in dogs

Background: Plasma citrulline concentration is a reliable marker of global enterocyte mass in humans and is markedly decreased in diffuse small intestinal diseases. However, the relationship between acute intestinal damage and plasma citrulline concentration in dogs has never been documented. Hypothesis: That dogs with parvoviral enteritis have a lower plasma citrulline concentration than healthy dogs and that plasma citrulline concentration is a predictor of death in puppies with parvoviral enteritis. Animals: Sixty‐one dogs with spontaneous parvoviral enteritis and 14 healthy age‐matched control dogs. Methods: Observational cohort study. Plasma citrulline concentration was measured by liquid chromatography and tandem mass spectrometry in blood samples collected at admission and each day until death or discharge from the hospital. Parvovirus enteritis was confirmed by electron microscopy on a fecal sample. Results: Median (interquartile range) plasma citrulline concentrations at admission were 2.8 μmol/L (range: 0.3, 49.0; P < .001 versus controls) in survivors (n = 49), 2.1 μmol/L (range: 0.5, 6.4, P < .001 versus controls) in nonsurvivors (n = 12) and 38.6 μmol/L (range: 11.4, 96.1) in controls (n = 14), respectively. There was no significant difference in plasma citrulline concentration between survivors and nonsurvivors within the parvovirus‐infected puppies, and plasma citrulline concentration was not significantly associated with outcome in parvoviral enteritis. There were no significant changes in plasma citrulline concentration over the 8‐day follow‐up period. Conclusion and Clinical Importance: Parvovirus enteritis is associated with a severe decrease in plasma citrulline concentration that does not appear to have any significant prognostic value.     

Canine parvoviral enteritis: a review of diagnosis, management, and prevention

Objective: To review and summarize current information regarding epidemiology, risk factors, and pathophysiology associated with canine parvoviral infection, and to outline diagnostic and treatment modalities for this disease. Preventative and vaccination strategies will also be discussed, as serologic documentation of immunocompetence and adoption of safe and effective vaccination protocols are crucial in limiting infection and spread of canine parvoviral enteritis. Etiology: Parvoviruses (Parvoviridae) are small, nonenveloped, single‐stranded DNA viruses that replicate in rapidly dividing cells. Canine parvovirus 2 (CPV‐2) remains a significant worldwide canine pathogen and the most common cause of viral enteritis in this species. Diagnosis: Classic presentation of CPV infection includes acute‐onset enteritis, fever, and leukopenia. Definitive diagnostic tests include detection of CPV in the feces of affected dogs, serology, and necropsy with histopathology. Therapy: Standard therapeutic practices for both mildly and severely affected puppies will be discussed. The ability of this virus to incite not only local gastrointestinal injury, but also a significant systemic inflammatory response has recently been reviewed in the literature, and novel innovative experimental and clinical therapeutic strategies, such as antagonism of proinflammatory cytokines and immunostimulation, are introduced in this article. Prognosis: CPV remains a significant worldwide canine pathogen. In experimentally affected dogs, mortality without treatment has been reported as high as 91%. However, with prompt recognition of dogs infected with CPV‐2, and aggressive in‐hospital supportive therapy of severely affected puppies, survival rates may approach 80–95%.     

Prognostic value of serum acute-phase proteins in dogs with parvoviral enteritis

Objective : To evaluate the acute-phase protein response in dogs with parvoviral enteritis as predictor of the clinical outcome. Methods : Canine parvovirus infection was diagnosed based on the compatible clinical findings and confirmed by the canine parvovirus antigen test in 43 dogs of less than six months of age. Blood samples for complete blood cell count and acute-phase proteins (C-reactive protein, haptoglobin, ceruloplasmin and albumin) were collected before treatment. Twenty-three dogs died during or after treatment (non-survival) and the rest recovered (survival). Five healthy dogs were enrolled as control. Results : Serum C-reactive protein, ceruloplasmin and haptoglobin levels in dogs with parvoviral enteritis were higher (P<0·001, P<0·01 and P<0·001, respectively), but serum albumin was lower (P<0·001) than those in controls. Mean C-reactive protein and ceruloplasmin values in non-survival were higher (P<0·01) than those for survival dogs. C-reactive protein was found to be superior to ceruloplasmin, haptoglobin and albumin for distinguishing survival from non-survival dogs. Values higher than 92·4 mg/l for C-reactive protein had a sensitivity of 91% to predict mortality. Clinical Significance : The magnitude of the increase in serum acute-phase proteins in dogs with parvoviral enteritis could be a useful indicator of the prognosis of the disease. In acute-phase proteins, C-reactive protein is a potent predictor of mortality in dogs with parvoviral enteritis.     

Serum cortisol and thyroxine concentrations as predictors of death in critically ill puppies with parvoviral diarrhea

OBJECTIVE: To evaluate the role of adrenal and thyroid hormones in the prediction of death in a population of critically ill puppies with parvoviral diarrhea by measuring serial daily serum concentrations of cortisol and thyroxine. DESIGN: Prospective case-control study. ANIMALS: 57 critically ill puppies with parvoviral diarrhea admitted to the hospital and 17 clinically normal control puppies. PROCEDURES: Basal serum cortisol and thyroxine concentrations were measured for each dog with parvoviral diarrhea at admission (prior to treatment) and daily until death, euthanasia, or discharge. RESULTS: Median time between admission and death was 48 hours (ie, on day 3). Median serum cortisol concentration on day 1 (admission) in all dogs with parvoviral diarrhea (248 nmol/L) was significantly higher than in control dogs (77 nmol/L). No significant difference was found in the day 1 median serum cortisol concentration of 11 dogs that died (302 nmol/L) and 46 dogs that survived (238 nmol/L). A significantly higher median serum cortisol concentration was, however, found in nonsurvivor group dogs, compared with survivor group dogs, on days 2 and 3. Median serum thyroxine concentration on day 1 in dogs with parvoviral diarrhea was significantly lower than in control dogs (8.12 nmol/L vs 35 nmol/L, respectively). Median serum thyroxine concentration of nonsurvivor group dogs (4.4 nmol/L) was significantly lower than that of survivor group dogs (9.2 nmol/L) at admission and became even lower on days 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE: High serum cortisol and low serum thyroxine concentrations at 24 and 48 hours after admission were associated with death in dogs with parvoviral diarrhea.     

ULTRASONOGRAPHIC APPEARANCE OF CANINE PARVOVIRAL ENTERITIS IN PUPPIES

The ultrasonographic appearance of the gastrointestinal tract of puppies suffering from parvoviral enteritis was characterized. Forty puppies between 6 and 24 weeks of age with confirmed canine parvoviral enteritis were examined ultrasonographically within 24 h of admission. Sonographic findings included fluid‐filled small intestines in 92.5% of subjects, and stomach and colon in 80% and 62.5% of subjects, respectively. Generalized atony was present in 30 subjects and weak peristaltic contractions indicative of functional ileus observed in the remaining 10 subjects. The duodenal and jejunal mucosal layer thicknesses were significantly reduced when compared with normal puppies with mean duodenal mucosal layer measuring 1.7 mm and jejunal mucosal layer 1.0 mm. Additionally, a mucosal layer with diffuse hyperechoic speckles was seen in the duodenum (15% of subjects) and the jejunum (50% of subjects). The luminal surface of the duodenal mucosa was irregular in 22.5% of subjects and the jejunal mucosa in 42.5% of subjects. In all of these subjects, changes were accompanied by generalized indistinct wall layering. Small intestinal corrugations were seen within the duodenum in 35% of subjects and within the jejunum in 7.5%. A mild amount of anechoic free peritoneal fluid was observed in 26 subjects and was considered within normal limits and a moderate amount of anechoic free peritoneal fluid was observed in six subjects. The jejunal lymph node size was within normal limits. None of the above changes are pathognomonic for canine parvoviral enteritis but finding them in combination is highly suggestive.     

Seroconversion of puppies to canine parvovirus and canine distemper virus: a comparison of two combination vaccines

Sixty puppies were randomly assigned to receive one of two commercially available combination vaccines, and responses to the canine parvovirus and canine distemper virus components of the vaccines were determined by measuring serum antibody titers. The percentage of puppies that seroconverted to canine parvovirus was significantly higher and the mean time for seroconversion was significantly shorter for puppies that received one of the vaccines than for puppies that received the other vaccine. Percentages of puppies that seroconverted to canine distemper virus were not significantly different.     

An investigation of ewe to lamb transfer of the itch mite Psorergates ovis

Five outbreaks of acute enteritis and one of myocarditis in 5 to 12-week-old puppies are reported. In cases of enteritis the initial clinical finding of slight malaise was followed within 24 hours by severe vomiting, diarrhoea, dehydration and death in most cases. The lesions of acute necrotizing enteritis and widespread lymphoid depletion were identical to those of feline panleucopaenia. In the outbreak of myocarditis, 3 puppies were founddead and a fourth developed congestive heart failure.

Parvoviral-like particles were found in the faeces of 5 cases of enteritis by electron microscopy and virus was isolated from 2 dogs, using a feline kidney cell line. The isolates demonstrated the physicochemical characteristics of a parvovirus and haemagglutinated porcine red blood cells at 4°C and 22°C but not 37°C. The isolates were antigenically related to feline panleucopaenia virus by immune aggregation, haemagglutination inhibition and immunofluorescence.

Fourteen of 48 sera from local dogs had significant haemagglutination inhibition titres to the virus. The diseases reported here are identical to overseas reports of parvoviral enteritis and myocarditis.     

Sudden death in young dogs with myocarditis caused by parvovirus.

Sudden death of pups in the 4- to 6-week age range has recently been occurring in western Canada as a result of severe, primary, nonsuppurative myocarditis. At necropsy, the prominent macroscopic lesion was pulmonary edema, and microscopically, characteristic intranuclear inclusion bodies were found within cardiac myofibers in association with myocarditis. Ultrastructurally, numerous small particles resembling parvoviruses were found within the intranuclear inclusion bodies, which were positive by direct fluorescent antibody test for canine parvovirus. Of three pups inoculated with homogenate from affected myocardium, one developed lesions resembling canine parvoviral enteritis.     

Characterisation of lipid profiles in dogs with parvoviral enteritis

OBJECTIVE: To characterise the lipid profiles in dogs with parvoviral enteritis. METHODS: Blood was collected before treatment from 30 dogs that fulfilled the criteria for severe sepsis including hypo- or hyperthermia, hypotension, leucopenia, thrombocytopenia and evidences of organ dysfunction. Canine parvovirus was detected by haemagglutination and indirect fluorescence antibody tests in the faeces. Twenty control dogs were also enrolled on the basis of normal physical examination results, complete blood count and serum biochemistry profiles. RESULTS: Tachycardia, tachypnoea, hypotension, leucopenia, thrombocytopenia and increased serum markers of tissue injury (alanine aminotransferase, creatinine kinase myocardial isoenzyme [CK-MB], blood urea nitrogen and creatinine) were observed in dogs with parvoviral enteritis. Serum total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were lower, but serum triglyceride level was higher in dogs with parvoviral enteritis than those in control dogs (P<0.001). Circulating tumour necrosis factor alpha correlated negatively with total cholesterol (r=-0.979; P<0.001) but positively with triglyceride (r=0.953; P<0.001) in dogs with parvoviral enteritis. Serum total cholesterol and high-density lipoprotein cholesterol levels were lower in non-survival (n=9) dogs than in survival dogs (n=21, P<0.001). CLINICAL SIGNIFICANCE: Serum total cholesterol and high-density lipoprotein cholesterol levels decreased, but serum triglyceride level increased in dogs with parvoviral enteritis. Low serum total cholesterol and high-density lipoprotein cholesterol levels may be used as an index of the severity of parvoviral enteritis.     

Development of hypertrophic osteodystrophy and antibody response in a litter of vaccinated Weimaraner puppies

Two different vaccination protocols were compared with regard to the development of hypertrophic osteodystrophy (HOD) (also termed metaphyseal osteopathy) and effectiveness of immunisation in a litter of 10 Weimaraner puppies. Five puppies (group 1) were vaccinated with a modified live canine parvovirus vaccine (CPV) and then two weeks later with a trivalent vaccine containing modified live canine distemper virus and adenovirus type 2 combined with a Leptospira bacterin (DHL). The CPV and DHL vaccine protocols were administered a further two times, at two-week intervals. Group 2 was vaccinated with three consecutive multivalent vaccines containing modified live canine distemper virus, canine parvovirus, parainfluenza and adenovirus type 2 combined with a Leptospira bacterin, at four-week intervals. All puppies were first vaccinated at the age of eight weeks. Three dogs in group 1 developed HOD, while all five dogs in group 2 developed HOD during the study period. Dogs in group 2 had more episodes of HOD than those in group 1. Dogs in group 1 developed higher antibody titres to canine distemper virus and parvovirus compared with those in group 2. Only two out of the 10 dogs developed protective antibody titres to parvovirus. The results of this study suggest that the two different vaccination protocols affected the pattern of appearance of HOD and immunisation in this litter of Weimaraner puppies. The results obtained and the previously reported data suggest that a larger controlled study is needed to further elucidate the effect of different vaccination protocols on HOD and immunisation in Weimaraner puppies.     

Canine viral enteritis: Prevalence of parvo-, corona- and rotavirus infections in dogs in the Netherlands

Summary After a brief review of the present knowledge about canine viral enteritis, the role played by parvoviral, coronaviral and rotaviral infections in contagious diarrhoea in dogs in the Netherlands is discussed. For this purpose a serologic survey, pathologic findings in dogs, and the demonstration of parvoviral antigen with an immunofluorescence test and with a newly developed haemadsorption-elution-haemagglutination assay (HEHA) are presented. It is concluded that infections with canine parvovirus, coronavirus and rotavirus appear widespread among dog populations in the Netherlands.     

Serum protein electrophoresis in canine parvovirus enteritis

The serum protein concentrations of dogs with confirmed canine parvovirus enteritis were determined by agarose gel electrophoresis before treatment. A significant decrease was detected in the mean concentration and percentage of albumin and gammaglobulin and the percentage of alpha-1-globulin. The mean concentration and percentage of alpha-2-globulin were significantly increased.     

Factors affecting the occurrence, duration of hospitalization and final outcome in canine parvovirus infection

The objectives of this matched case-control study in a veterinary teaching hospital were to investigate the influence of signalment and historical data on the odds of occurrence of canine parvovirus (CPV) enteritis and the potential usefulness of the clinical signs and clinicopathologic abnormalities recorded on admission as prognostic indicators of mean duration of hospitalization (DOH) and outcome of the disease. Ninety-four puppies with natural CPV enteritis and 188 age-matched controls were studied. The odds to develop CPV enteritis were higher in purebreds compared to mixed-breed puppies. Vomiting and depression at the time of admission were associated with a prolongation of DOH by 2 and 1.75 days, respectively. The lymphopenic and hypoalbuminemic dogs were hospitalized for 1.9 and 2.5 more days, respectively, compared to those without these abnormalities. The odds of non-survival were higher in those puppies with evidence of systemic inflammatory response syndrome (SIRS) at the time of admission.     

Endotoxemia and Tumor Necrosis Factor Activity in Dogs With Naturally Occurring Parvoviral Enteritis

A prospective, nonrandomized study was performed to evaluate the role of endotoxin and tumor necrosis factor (TNF) in dogs with parvoviral enteritis. Seventeen dogs with naturally occurring parvoviral enteritis were enrolled in the study. Plasma samples were obtained for quantification of endotoxin and TNF on presentation and at 3 and 6 hours after therapy with either fluids prior to antibiotics, or fluids concurrently with antibiotics. All dogs received standard supportive therapy. Fourteen of 17 dogs had endotoxin in their plasma during the study period; 7 of 17 dogs had measurable TNF. No endotoxin or TNF was detectable in plasma from normal puppies. An increase in TNF activity was pre dictive of mortality ( P = .041). There was a trend for increasing endotoxin activity to predict mortality ( P = .0769). Animals that received antibiotics with fluids were significantly older than those that received fluids prior to antibiotics, and there was a trend for animals that received antibiotics with fluids to have a decrease in endotoxin activity after treatment ( P = .054). Endotoxin and activation of the cytokine cascade are integral to the pathophysiology of parvoviral enteritis. Measures to limit endotoxemia and the systemic inflammatory response may improve survival.     

A longitudinal serological survey of parvovirus infection in dogs

Serum samples collected from dogs routinely presented at a clinic between June 1974 and October 1980 were tested for the presence of haemagglutination inhibition (HI) titres to canine parvovirus. The first positive titre (>1:320) was demonstrated in serum collected in October 1979. The first confirmed clinical case of canine parvovirus enteritis was diagnosed by the authors in July 1979. In addition, between 1st December 1980 and 1st March 1981, serum samples were collected from 106 healthy dogs which were presented for canine parvovirus vaccination for the first time. Twenty-four dogs (approx. 23%) showed HI titres >1:320 indicating probable previous canine parvovirus infection. Therefore approx. 80% of dogs in the clinic area were at risk at that time and vaccination should have protected them from infection.     

Recombinant bactericidal/permeability-increasing protein (rBPI21) for treatment of parvovirus enteritis: a randomized, double-blinded, placebo-controlled trial

We evaluated the ability of an antimicrobial and endotoxin-neutralizing agent, the recombinant amino terminal fragment of bactericidal permeability-increasing protein (rBPI21), to decrease plasma endotoxin concentration and severity of clinical signs of canine parvovirus and to improve survival. This randomized, double-blinded, placebo-controlled clinical trial included 40 client-owned dogs and 9 normal puppies from a closed research colony. Dogs weighing >5 kg (11 lb) with fecal antigen-confirmed parvovirus and clinical signs of vomiting and diarrhea were randomly assigned to receive placebo or rBPI21 infusion over 6 hours. Plasma endotoxin concentration was measured at 0, 3, and 6 hours of infusion. Owners chose continued medical care with either the Veterinary Hospital of the University of Pennsylvania Internal Medicine Service or a local veterinarian. Telephone follow-up was conducted at 14 days. Surviving dogs were reevaluated at >30 days (recovered group), at which time plasma samples for measurement of endotoxin concentration were obtained. Plasma endotoxin concentrations were significantly higher in dogs with parvovirus than in normal or recovered dogs. Despite 90% survival, the rBPI21 treatment did not have a significant effect on outcome, duration of hospitalization, or plasma endotoxin concentrations. Treatment in a tertiary care hospital, however, significantly improved survival but resulted in a significantly increased duration of hospitalization. Endotoxemia occurs in dogs with parvovirus enteritis, but rBPI21 is not associated with improved survival.     

The effect of staphylococcal antigen on the output of cells from the popliteal lymph node of immunized sheep

Serum samples collected from dogs routinely presented at a clinic between June 1974 and October 1980 were tested for the presence of haemagglutination inhibition (HI) titres to canine parvovirus. The first positive titre (> 1:320) was demonstrated in serum collected in October 1979. The first confirmed clinical case of canine parvovirus enteritis was diagnosed by the authors in July 1979.

In addition, between 1st December 1980 and 1st March 1981, serum samples were collected from 106 healthy dogs which were presented for canine parvovirus vaccination for the first time. Twenty-four dogs (approx. 23%) showed HI titres > 1:320 indicating probable previous canine parvovirus infection. Therefore approx. 80% of dogs in the clinic area were at risk at that time and vaccination should have protected them from infection.     

Hemagglutination by canine parvovirus: serologic studies and diagnostic applications

Conditions for canine parvoviral hemagglutination (HA) and hemagglutination-inhibition (HI) reactions were defined. The HA phenomena were used to differentiate canine parvovirus (CPV) from feline panleukopenia virus (FPV), mink enteritis virus (MEV), and minute virus of canines. Serologic comparisons of the CPV, FPV, and MEV by HA-HI and serum-neutralization tests indicated that CPV, FPV, and MEV were antigenically similar but were different from minute virus of canines. Diagnostic application of HA tests to fecal samples from acute cases of enteritis was discussed. Combinating HA tests with HI tests on fecal samples provided a rapid and specific diagnostic method for CPV infection. Secular seroprevalence studies indicated the emergence of CPV infeciton in the United States dog population-at-large in 1978.     

Canine coronavirus-associated puppy mortality without evidence of concurrent canine parvovirus infection.

This report presents 2 cases in which puppy fatalities were associated with canine coronavirus (CCV), but no evidence of concurrent canine parvovirus (CPV-2) disease was observed. Case 1 involved a 7-week-old, male short-haired Chihuahua, which had become lethargic 24 hours after purchase from a pet store. Within 72 hours, the puppy began to vomit, had diarrhea, and was admitted to the veterinary clinic, where it was placed on IV fluids. The parvovirus Cite test was negative. The puppy died within 12 hours of admission and was submitted for diagnostic workup. Gross pathology revealed an enteritis suggestive of CPV-2. Histopathology on intestines showed scattered dilated crypts with necrotic cellular debris and neutrophils. There was moderate depletion and necrosis of lymphoid follicles. Electron microscopy (EM) on intestinal contents was positive for coronavirus and negative for parvovirus. Immunohistochemistry (IHC) on gut sections was positive for CCV and negative for CPV-2. Case 2 was an 8-week-old, male Shih Tzu, which was admitted to the veterinary clinic exhibiting symptoms of severe gastroenteritis with abdominal pain. The referring veterinarian euthanized the puppy, and the entire body was submitted for diagnostic evaluation. Necropsy revealed a severe ileo-cecal intussusception and segmental necrotic enteritis of the small intestine. Electron microscopy of the intestinal contents was positive for coronavirus and negative for parvovirus. Immunohistochemistry on sections of affected gut were positive for CCV and negative for CPV-2. These cases emphasize the importance of pursuing a diagnosis of CCV in young puppies when CPV-2 disease has been ruled out by IHC.