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Parvoviruses (canine parvovirus -2)

Parvoviruses (canine parvovirus -2). September 7-8, 2010. First reports of CPV enteritis. An enteric disease of dogs resembling feline panleucopenia. W.R. Kelly, Aust. Vet Jn. 54:593. 1978. Canine gastroenteritis associated with a parvovirus-like agent.

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Parvoviruses (canine parvovirus -2)

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  1. Parvoviruses(canine parvovirus -2) September 7-8, 2010

  2. First reports of CPV enteritis An enteric disease of dogs resembling feline panleucopenia. W.R. Kelly, Aust. Vet Jn. 54:593. 1978 Canine gastroenteritis associated with a parvovirus-like agent. G.W. Thompson and A.N. Gagnon. Can. Vet Jn. 19:346. 1978

  3. W.R. Kelly. 1978. An enteric disease of dogs resembling feline panleucopenia. A.V.J. 54:593

  4. Kelly, 1978 suspected viral enteritis normal intestinal crypts bone marrow

  5. First reports of CPV myocarditis Diffuse subacute myocarditis of possible viral aetiology: A cause of sudden death in pups. W.R. Kelly.Aust. Vet Jn 55:36. 1979 Sudden death in puppies associated with a suspected viral myocarditis R.B. Atwell et al. Aust. Vet Jn 55:37. 1979

  6. Kelly,1979

  7. The evolution of CPV ? ~1900 Feline parvovirus ? Fox parvovirus ? 1979 1987 2004 CPV-2 CPV-2a CPV-2b CPV-2c ? Raccoon parvovirus 1970,74-76 cats ? Carnivore (?) parvovirus (10-20% of cats with parvo enteritis)

  8. The virus neutralizing epitopes, host-range mutations dimple canyon

  9. Kennedy et al. 1995. Virucidal efficacy of the newer quarternary ammonium compounds. JAAHA 31:254

  10. Kennedy et al ‘95

  11. American Jn of Inf. Control 2006, 34:269-273 1000 ppm is equivalent to approx. 2% solution of household bleach

  12. Parvovirus in the scheme of things Viruses with single stranded DNA porcine circovirus Circoviridae canine parvovirus-2 feline panleukopenia virus Parvoviridae porcine parvovirus (SMEDI)

  13. Replicative cycle • Attachment • Requirement for dividing cells • Intranuclear inclusion bodies • Release by lysis - death of cell

  14. CPV attaches to cells using transferrin receptor (host tropism) The natural host-range shift and subsequent evolution of canine parvovirus resulted from virus-specific binding to the canine transferrin receptor. Hueffer et al. 2003 J. Virol 77; 1718-1726 transferrin receptor

  15. infection fecal-oral route Virus extremely stable (> 6 months) Inactivated by 4% solution of bleach Most “virucidal” disinfectants not effective access to lymphatic nodules in tonsils or gut (M-cells) Pathogenesis

  16. Entry at mucosal surfaces (M cells) M cell

  17. Entry at mucosal surfaces (M cells) M cell Transport across M cell

  18. Entry at mucosal surfaces (M cells) Infected Lymphoid cell spread

  19. Spread of virus in the body virus in feces mesenteric, systemic lymph nodes, bone marrow (lymphoid and myeloid precursors) crypt cells no epithelial replacement, collapse of lamina propria

  20. Actively dividing cells in gut crypt cells Peyer’s patches

  21. Damage to the gut collapsed crypts depleted Peyer’s patches

  22. Incubation period and duration of shedding virus shedding 4-14 days incubation period clinical signs infection day 0

  23. After challenge incubation period vaccination does not provide “sterile immunity” Ron D. Schultz

  24. What happens to the sick dog • depression • diarrhoea and vomiting • fever • leukopenia, neutropenia • secondary bacterial infections • dehydration, shock • long term sequelae

  25. immune status of dog Immune or able to make antibodies individual variation Intestinal and lymphoid cell turn-over genetic susceptibility variation among virus strains Response to infection - asymptomatic ->death Depends on:

  26. season - 3 times more likely - July to Sept breeds - Rottweilers, Dobermans, Shepherds sex - intact dogs four times more likely no vaccination - 13 times more likely Risk factors for parvovirus enteritis Risk factors associated with parvovirus enteritis in dogs:283 cases - D. M. Houston et al. JAVMA 208:542-546. 1996

  27. lethargy and vomiting - 84-87% diarrhoea - 60% leukopenia (at some time) - 45% neutropenia (at some time) - 51% fever (>39.5) - 24% Most likely clinico-path findings Risk factors associated with parvovirus enteritis in dogs:283 cases - D. M. Houston et al. JAVMA 208:542-546. 1996

  28. Vet Rec. 2010 Aug 7;167(6):196-201.Epidemiology of canine parvovirus and coronavirus in dogs presented with severe diarrhoea to PDSA PetAid hospitals.Godsall SA, Clegg SR, Stavisky JH, Radford AD, Pinchbeck G. • Correlates with detectable CPV2 in feces of dogs with diarrhoea: • Lack of vaccination in young dogs (<30 months) • Vomiting, depression and diarrhoea • No correlation with: • Vaccination status in older dogs • Breed • Severity of diarrhoea, heamorrhage • Mortality

  29. Myocarditis

  30. Diagnosis of parvovirus enteritis • Clinical signs and clinico-pathological parameters • why are these not sufficient to make a definitive diagnosis

  31. Parvovirus Distemper virus Coronavirus Rotavirus (<2weeks) Salmonella Campylobacter Clostridium Yersinia Neorickettsia Histoplasmosis Some infectious causes of enteritis in dogs

  32. fecal suspension treated with chloroform inoculate feline kidney cells incubate 3-5 days Virus isolation • stain with parvo- • virus antibody+ • fluoroscene

  33. Haemagglutination (HA) No virus virus

  34. Haemagglutination Dilution No virus 2 4 8 16 32 64 128 256 512 1024 titre prozone

  35. Comparison of sensitivity dilution 0 1/10 1/100 1/1000 ..…….. 10-7 IDEXX Virus isolation (HA titre during peak clinical signs is 1,000 -10,000) HA 1/8192

  36. Incubation period and duration of shedding virus shedding 4-14 days incubation period clinical signs infection day 0

  37. heat to inactivate complement in serum adsorb to RBC, then remove dilute (1/20, 1/40 etc) add virus incubate add RBC incubate Haemagglutination inhibition (HAI)

  38. HAI Serum dilution Virus HA 8 wks 1 wk 1/20 1/40 1/80 1/160 1/320 1/640 1/1280 -ve control

  39. by itself or as component of combined vaccine (DA2PPv) attenuated or inactivated Protection of animals (vaccination)

  40. Interference by maternal antibodies minimum level needed for protection * window of susceptibility interferes with vaccination * * passive antibody HAI - 80 * HAI - 10 to 20 * Puppies can Only be Vaccinated Below this level * 2 4 6 8 10 12 weeks after birth

  41. Passive antibody decreases vaccine efficacy J Vet Med B Infect Dis Vet Public Health. 2000 May;47(4):273-6. Immunization of pups with maternally derived antibodies to canine parvovirus (CPV) using a modified-live variant (CPV-2b). Pratelli A, Cavalli A, Normanno G, De Palma MG, Pastorelli G, Martella V, Buonavoglia C.

  42. biweekly vaccinations low passage, high titre vaccines Strategies for reducing/overcoming risk of maternal interference

  43. Pfizer - Vanguard puppy Schering-Plough - Galaxy Merial - Canine Parvo XL Low-passage, high-titre vaccines

  44. Vaccines should contain CPV2a and CPV2b CPV vaccination: comparison of neutralizing antibody responses in pups after inoculation with CPV2 or CPV2b modified live vaccines. Pratelli et al. 2001. Clin. Diag. Lab. Immunol. 8: 612-615

  45. Debate on frequency of vaccination

  46. How long does antibody last? Vet Ther. 2004 Fall;5(3):173-86. Evaluation of the efficacy and duration of immunity of a canine combination vaccine against virulent parvovirus, infectious canine hepatitis virus, and distemper virus experimental challenges. Abdelmagid OY, Larson L, Payne L, Tubbs A, Wasmoen T, Schultz R.

  47. Parvovirus vaccines licensed in Canada • modified-live alone or in various combinations CFIA

  48. Potential antiviral therapy Vet Rec. 2003 Jan 25;152(4):105-8. Treatment of canine parvoviral enteritis with interferon-omega in a placebo-controlled field trial. de Mari K, Maynard L, Eun HM, Lebreux B. J Vet Pharmacol Ther. 2010 Aug;33(4):352-6. Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte-colony stimulating factor. Duffy, A, Dow S, Ogilvie G, Rao S, Hackett T.

  49. feline panleukopenia virus (related carnivore parvoviruses) porcine parvovirus aleutian mink diseases human parvovirus B19 Other parvoviruses of veterinary importance

  50. Feline parvovirus normal cerebellar hypoplasia from: Veterinary Virology Murphy et al.

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