Pathogenesis of canine parvovirus-2 in dogs: haematology, serology and virus recovery

The pathogenesis of canine parvovirus-2 (CPV-2) was studied in orally inoculated conventional dogs using haematological, serological and virological techniques. Virus was first isolated from mesenteric lymph nodes on day 2 after exposure, tonsil on day 3 and small intestine on day 3. Viraemia occurred subsequently and was present in most dogs on days 4 and 5 after exposure. CPV-2 could be isolated from all tissues during viraemia. Relative pyrexia, lymphopenia and neutropenia occurred on days 5, 6 and 7 after exposure, respectively. Virus excretion in faeces began in most dogs on day 4 and continued despite the appearance of neutralising serum antibody. Specific serum antibody, detected in some dogs as early as day 3 and in all dogs by day 7 after exposure, eliminated viraemia and inhibited virus isolation from tissues in cell culture.     

Successful experimental challenge of dogs with canine parvovirus-2.

Withholding food from dogs for 24 hours prior to, and for 48 hours following oral challenge with a gut mucosal homogenate of canine parvovirus-2, was a successful means of reproducing gastroenteric signs of canine parvovirus-2 infection. Twenty-one of 24 dogs, which had previously received various vaccine preparations of mink enteritis virus or were unvaccinated, and which were starved at challenge, developed soft or liquid feces with large or without large clots of mucus. Altered feces were most frequent on postexposure day 11. Seven dogs passed frank blood in their stools on one or more occasions and seven dogs vomited sporadically. Pyrexia was noted in 71.6% of the dogs on postexposure day 6 and lymphopenia was detected on postexposure day 5 or 6 in 50% of the dogs monitored. In contrast, four dogs not starved at the time of challenge remained free of gastrointestinal signs apart from one dog which passed a soft stool with scant mucus on one day, postexposure day 6. Also four dogs vaccinated with a killed canine parvovirus-2 vaccine preparation and subsequently starved at the time of challenge, remained clinically healthy. Apart from these last mentioned four dogs, all others shed canine parvovirus-2 in their feces following challenge.     

The seroprevalence of canine parvovirus-2 in a selected sample of the canine population in ontario

Canine sera, collected from dogs presented to the Ontario Veterinary College between 1976 and 1980, were assessed for canine parvovirus-2 antibody using a microtitre hemagglutination-inhibition test. Special emphasis was made on the period from September 1979 to October 1980 (2892 samples). No antibody was detected in samples collected in 1976 or 1977. The first positive sera were obtained in January 1978. By the end of 1978 antibodies to canine parvovirus-2 were widespread in Ontario dogs and in 1980, 683 of 2191 dogs (31.2%) had antibody. This was before widespread vaccination was being practised and indicates canine parvovirus-2 infection occurred frequently. Evaluation of clinical records of these dogs suggested that most infections had been subclinical.     

犬细小病毒2型变异株对高母源抗体犬的致病性

为了探究CPV-2变异株的致病性,用CPV-2a和CPV-2b野毒株,分别攻击犬细小病毒(CPV-2)高母源抗体(MDA)幼犬,根据犬临床症状,组织病理学,粪便排毒和血清抗体应答等指标,评价高母源抗体(HI滴度≥1∶160)对不同CPV病毒变异株的保护作用。结果表明, CPV-2a和CPV-2b攻毒后引起明显临床症状,攻毒后3～6 d粪便中CPV排毒。感染犬的组织样品经PCR检测表明,CPV-2a/2b病毒广泛分布。组织病理学分析表明,CPV-2a/2b感染引起肠道黏膜出血。研究表明,CPV-2高母源抗体对CPV-2a/2b变异株攻击不能提供有效保护,有必要开发CPV变异株的新型疫苗。     

犬瘟热自然病例脱髓性脑病发生的机理

为了进一步调查脑组织的髓鞘脱失与神经胶质细胞等成份的关系,用12只犬瘟热自然病例通过病理组织学和免疫组织化学染色法进行了本试验.结果表明:髓鞘脱失部位的脑组织伴有明显的血液循环障碍,即淤血、水肿、血栓形成和弥漫性血管内凝血;少突胶质细胞发生代谢紊乱和凋亡;用抗犬瘟热病毒(CDV)抗体染色,星状胶质细胞呈现强阳性反应;用抗GFAP染色,纤维性星状胶质细胞在脱髓区呈较强阳性反应,用TUNEL染色可检出发生凋亡的星状胶质细胞;一些室管膜细胞也被CDV感染,许多含有包涵体币口凋亡的室管膜细胞在脑室壁被发现;少数神经元变性和皱缩,其核发生浓缩.据此认为,脑组织的髓鞘脱失主要与血液循环障碍和少突胶质细胞的代谢紊乱及凋亡有关;脑组织的髓鞘脱失是许多病因共同作用的结果,并非是一种病因所致.     

The failure of an inactivated mink enteritis virus vaccine in four preparations to provide protection to dogs against challenge with canine parvovirus-2.

Four experimental vaccine preparations comprising a strain of mink enteritis virus inactivated by either formalin or beta-propiolactone, and either adjuvanted or nonadjuvanted, failed to stimulate a consistent serum antibody response in 20 vaccinated dogs and failed to protect all but one of these dogs against oral challenge with canine parvovirus-2.     

Renal allograft histopathology in dog leukocyte antigen mismatched dogs after renal transplantation

OBJECTIVE: To evaluate allograft histopathology in dog leukocyte antigen (DLA)-mismatched dogs undergoing renal transplantation, with transient immunosuppression. STUDY DESIGN: Prospective study. ANIMALS: Ten healthy adult mongrel dogs. METHODS: Reciprocal renal transplantation and bilateral nephrectomy were performed. Immune conditioning consisted of nonmyeloablative (200 cGy), total body irradiation (TBI), bone marrow transplantation (BMT; 7 dogs), cyclosporine (CSA; 15 mg/kg every 12 hours), mycophenolate mofetil (MMF; 10 mg/kg every 12 hours) and intermittent prednisone (1 mg/kg every 12-24 hours). Biopsies were collected at transplantation, during full immunosuppression (44-90 days), and once medications were reduced or discontinued (228-580 days). Biopsies were evaluated for interstitial, tubular, vascular, and glomerular lesions. Blood urea nitrogen, creatinine, serum CSA concentrations, and clinical score were determined at each biopsy. RESULTS: Seven dogs survived >200 days (mean, 380 days). Transient CSA toxicity was suspected in 6 dogs. Lymphocytic, plasmacytic interstitial inflammation, and tubulitis progressed when immunosuppressive medications were decreased. All 7 dogs had histologic lesions consistent with some degree of allograft rejection at study end. CONCLUSION: Nonmyeloablative TBI, BMT, and short-term immunosuppression with CSA, MMF, and prednisone allowed renal allograft function and dog survival for >200 days. It appears unlikely that total drug withdrawal will be possible in unrelated DLA-mismatched dogs using this protocol. CLINICAL RELEVANCE: Transient immunosuppression with MMF, CSA, and prednisone along with BMT and nonmyeloablative TBI may make kidney transplantation a clinical reality for treatment of kidney failure in dogs. Initiating both MMF and CSA at lower dosages may potentially eliminate early renal allograft injury.     

Comparison of the viral proteins of canine parvovirus-2, mink enteritis virus and feline panleukopenia virus

Canine parvovirus-2 (CPV-2), Mink enteritis virus (MEV) and feline panleukopenia virus (FPV) were produced using identical cell culture and purification techniques. The distributions of the haemagglutinating activity of the three different parvoviruses in a CsCl gradient were similar with haemagglutinating peaks identified at 1.48–1.49, 1.42, 1.36 and 1.30–1.31 g cm^?3. The number and distribution of the viral proteins and the equivalent protein molecular weights are similar for all three viruses in SDS-polyacrylamide gels (10%). Four viral proteins were identified and their molecular weights were determined: protein A (77 500–79 500), protein B (63 000–63 500), protein C (61 500–63 000) and protein D (50 000–55 000). The viral protein D although reported for some other parvoviruses has not previously been demonstrated in CPV-2, MEV or FPV.     

Comparison of canine distemper virus strains in gnotobiotic dogs: effects on lymphoid tissues.

The effects of infection on various aspects of lymphoid function in gnotobiotic dogs with 2 virulent strains of canine distemper virus (CDV), Snyder-Hill CDV and R252-CDV, were compared. Both infections resulted in a viremia-related lymphopenia which was nonselective in that the percentages of B and T cells remained unchanged throughout the observation period. Nonfatal Snyder-Hill-CDV infection resulted in a transient depression of in vitro lymphocyte responses to phytohemagglutinin-P, whereas R252-CDV produced prolonged in vitro suppression of phytohemagglutinin-P stimulation. The differences observed are of minor significance and do not explain the differences in central nervous system demyelinating potential between these 1 strains of CVD.     

Distribution of inclusion bodies in tissues from 100 dogs infected with canine distemper virus

One hundred dogs that were positive for canine distemper virus antigen and inclusion bodies in the tonsils were examined for the distribution of inclusion bodies in various tissues. Inclusion bodies were found in the lungs (70 dogs), brains (20 dogs), urinary bladders (73 dogs), stomachs (78 dogs), spleens (77 dogs), and lymph nodes (81 dogs) of the dogs. Based on these results, the tonsils may be the most suitable tissue for detection of inclusion bodies in canine distemper.     

Cytology and histopathology of canine leproid granuloma syndrome

OBJECTIVE: To describe the histopathology of canine leproid granuloma syndrome. DESIGN: Histological examination of biopsy specimens taken from dogs with leproid granuloma syndrome. Biopsies were acquired from four veterinary pathology practices after initial examination showed acid-fast bacilli or lesions suggestive of a mycobacterial aetiology. Tissue from 30 cases formed part of a retrospective survey while a further 7 cases were obtained prospectively. PROCEDURE: Tissue samples were fixed in formalin and paraffin embedded. Sections were stained with haematoxylin and eosin and Ziehl-Neelsen stains. Slides were evaluated for the type of inflammatory response and the number of bacteria. In a few cases smears made from crush preparations and needle aspirates were stained with DiffQuik and acid-fast stains. RESULTS: The common cytological feature seen in DiffQuik stained smears was numerous, often spindle-shaped, macrophages with variable numbers of lymphocytes and plasma cells and lower numbers of neutrophils. Usually few to moderate numbers of medium length bacilli were detected within macrophages or extracellularly. Histologically, lesions were chiefly pyogranulomatous within the subcutis and dermis. Pyogranulomas were composed chiefly of epithelioid macrophages and neutrophils but plasma cells and small lymphocytes were scattered throughout the lesions in which giant cells were seen. Lesions were pyogranulomatous in 36 cases and granulomatous with small suppurative foci in one. The numbers of acid-fast bacilli present were very low to low in 22 cases, moderate in 6 and regionally numerous to numerous in 9. Bacteria were pleomorphic, ranging from long, slender filaments in parallel sheaves to short and variably-beaded bacilli or highly beaded to coccoid organisms. The morphology was more uniform in DiffQuik stained smears than in fixed tissue sections. CONCLUSION: The pathology of canine leproid granuloma syndrome is highly uniform and is suggestive of saprophytic mycobacterial involvement. The morphological diversity of acid-fast bacilli probably results from differences in staining characteristics rather than indicating different species of Mycobacterium. While approximately half of the cases had only few organisms present, the veterinary practitioner using a Romanovsky stain such as DiffQuik on aspirated material might expect to obtain a rapid diagnosis in many cases. This would allow differentiation of the syndrome from neoplastic and other diseases of the skin and direct appropriate treatment at the initial presentation.     

Three-year serologic immunity against canine parvovirus type 2 and canine adenovirus type 2 in dogs vaccinated with a canine combination vaccine

A group of client-owned dogs and a group of dogs at a commercial kennel were evaluated for duration of antibody responses against canine parvovirus type 2 (CPV-2) and canine adenovirus type 1 (CAV-1) after receiving a combination vaccine containing recombinant canarypox-vectored canine distemper virus (CDV) and modified-live CPV-2, CAV-2, and canine parainfluenza virus, with (C6) or without (C4) two serovars of Leptospira (Recombitek C4 or C6, Merial). Duration of antibody, which correlates with protective immunity, was found to be at least 36 months in both groups. Recombitek combination vaccines can confidently be given every 3 years with assurance of protection in immunocompetent dogs against CPV-2 and CAV-1 as well as CDV. This allows this combination vaccine, like other, similar modified- live virus combination products containing CDV, CAV-2, and CPV-2, to be administered in accordance with the recommendations of the American Animal Hospital Association Canine Vaccine Task Force.