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Parvoviruses (canine parvovirus -2)

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Department of Pathobiological Sciences, School of Veterinary Medicine ... * see figures from vaccine efficacy * * * Haemagglutination Dilution 2 4 8 16 ... – PowerPoint PPT presentation

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Title: Parvoviruses (canine parvovirus -2)


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. 54593.
1978
Canine gastroenteritis associated with a
parvovirus-like agent. G.W. Thompson and A.N.
Gagnon. Can. Vet Jn. 19346. 1978
3
W.R. Kelly. 1978. An enteric disease of dogs
resembling feline panleucopenia. A.V.J. 54593
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 5536. 1979
Sudden death in puppies associated with a
suspected viral myocarditis R.B. Atwell et al.
Aust. Vet Jn 5537. 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 31254
10
Kennedy et al 95
11
American Jn of Inf. Control 2006, 34269-273
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
Pathogenesis
  • infection
  • fecal-oral route
  • Virus extremely stable (gt 6 months)
  • Inactivated by 4 solution of bleach
  • Most virucidal disinfectants not effective
  • access to lymphatic nodules in tonsils or gut
    (M-cells)

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
Peyers patches
21
Damage to the gut
collapsed crypts
depleted Peyers 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
Response to infection - asymptomatic -gtdeath
Depends on
  • immune status of dog
  • Immune or able to make antibodies
  • individual variation
  • Intestinal and lymphoid cell turn-over
  • genetic susceptibility
  • variation among virus strains

26
Risk factors for parvovirus enteritis
  • 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 associated with parvovirus enteritis
in dogs283 cases - D. M. Houston et al. JAVMA
208542-546. 1996
27
Most likely clinico-path findings
  • lethargy and vomiting - 84-87
  • diarrhoea - 60
  • leukopenia (at some time) - 45
  • neutropenia (at some time) - 51
  • fever (gt39.5) - 24

Risk factors associated with parvovirus enteritis
in dogs283 cases - D. M. Houston et al. JAVMA
208542-546. 1996
28
 Vet Rec. 2010 Aug 7167(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 (lt30 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
Some infectious causes of enteritis in dogs
  • Parvovirus
  • Distemper virus
  • Coronavirus
  • Rotavirus (lt2weeks)
  • Salmonella
  • Campylobacter
  • Clostridium
  • Yersinia
  • Neorickettsia
  • Histoplasmosis

32
Virus isolation
  • fecal suspension treated with chloroform
  • inoculate feline kidney cells
  • incubate 3-5 days
  • 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
Haemagglutination inhibition (HAI)
  • heat to inactivate complement in serum
  • adsorb to RBC, then remove
  • dilute (1/20, 1/40 etc)
  • add virus
  • incubate
  • add RBC
  • incubate

38
HAI
Serum dilution
Virus HA
1 wk
8 wks
1/20
1/40
1/80
1/160
1/320
1/640
1/1280
-ve control
39
Protection of animals (vaccination)
  • by itself or as component of combined vaccine
    (DA2PPv)
  • attenuated or inactivated

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
May47(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
Strategies for reducing/overcoming risk of
maternal interference
  • biweekly vaccinations
  • low passage, high titre vaccines

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

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 Fall5(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 25152(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 Aug33(4)352-6. Hemato
logic 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
Other parvoviruses of veterinary importance
  • feline panleukopenia virus (related carnivore
    parvoviruses)
  • porcine parvovirus
  • aleutian mink diseases
  • human parvovirus B19

50
Feline parvovirus
normal
cerebellar hypoplasia
from Veterinary Virology Murphy et al.
51
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52
Czar
Mr. S brought Czar, a 7 month old Rottweiler, to
the WCVM clinic on August 30. Czar had had severe
vomiting and diarrhea for the previous two days.
He had vomited two or three times on the previous
evening and once that morning. The diarrhea was
watery with no blood. Czar had not eaten in the
two days prior to presentation. Czar did not
have a history of raiding garbage cans and Mr. S
thought it unlikely that Czar had eaten anything
unusual. The dog was fed a commercial puppy chow
and there had been no change in his diet. Czars
vaccinations were up to date with extra
parvovirus boosters up to 20 weeks of age.
According to the WCVM records Czar had been
vaccinated at 8, 12, 16 and 20 weeks with a
vaccine containing distemper virus, parvovirus
and adenovirus-2. The attending veterinarian
found Czar to be listless and quiet. The dog was
anorexic and slightly dehydrated. There appeared
to be no discomfort on palpation. His
temperature was 39oC (N 37.2 39.2), pulse was
116 (N 70 160) and respiration was 32 (N 10
-30).
53
  • You suspect that Czar has parvovirus enteritis.
    What tests would you request to confirm (or
    refute) your suspicions?
  • What are your reasons for requesting these tests?
    What would you expect the tests to show?
  • Would you treat Czar with antibiotics? Why?
  • If you requested a complete blood count (CBC) for
    Czar, what might the CBC pattern be? How might
    you expect the pattern to change over the next
    few days?
  • Which tissues is the parvovirus most likely to
    affect? What changes would you expect in these
    tissues?
  • Assume that Czar has parvovirus enteritis. Why do
    you think he became sick despite your having
    vaccinated him against parvovirus?
  • Are any of Mr. Ss family members likely to be
    infected by Czars virus? Is there a human
    parvovirus? How is it related to canine
    parvovirus 2?
  • Can Czar pass parvovirus on to the family cat?
  • What advise would you give Czars owner about
    disinfecting areas contaminated with Czars
    feces?
  • Czar was hospitalized but a week later he had
    recovered and was sent home. Would you expect
    Czar to be contagious at that time?

54
Questions 1 and 2 Liz Andree Colleen
Chan Questions 3 and 4 Sydney Chow Shannon
Gruen Questions 5 and 6 Amber Hamilton Angela
Le Questions 7 and 8 Ellen Littley Janine
Regehr Questions 9 and 10 Dane Richardson
Anita Yee
55
What happened
Blood was taken for CBC, a faecal sample was
submitted for bacteriological analysis and a
ParvoCITE test was performed. On the basis of the
ParvoCITE test, which was strongly positive, a
diagnosis of parvovirus enteritis was made.
Czar was put in an isolation ward and started
immediately on IV fluids. Ampicillin as well as
gentamicin were administered. Over the next 3
days Czar's condition deteriorated. Diarrhea
became bloody. The IV fluids and antibiotics were
continued. On the fourth day after admitting, the
diarrhea appeared to stop. Although weak, Czar
seemed willing to walk around. The dog's
condition improved steadily over the next few
days. By day 6 Czar was able to drink without
vomiting and a day later he ate small amount of
Hill's I/D diet. Once it was established that
he could maintain his body's fluid levels he was
weaned off the I.V. fluids. Eight days after
being admitted to hospital he was sent home.
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