• Embed Doc
  • Copy Link
  • Readcast
  • Collections
  • CommentGo Back
Download
 
Vol. 19, No. 2February 1997Continuing Education Article
FOCAL POINTKEY FACTS
5
The high-titer, low-passagevaccines elicit a more effectiveimmune response in the face ofmaternal antibodies.
Canine Parvovirus.Part I. Pathogenesisand Vaccination
*
 Auburn University 
Saralyn Smith-Carr, DVM, PhDDouglass K. Macintire, DVM, MSLarry J. Swango, DVM, PhD
P
arvoviruses replicate only in cells synthesizing DNA (i.e., rapidly divid-ing cells). This characteristic leads to the clinical signs of hemorrhagicenteritis. In susceptible canine populations, parvovirus infection most of-ten occurs as a severe systemic and even life-threatening illness.Passive immunity from maternal antibodies blocks the immune response inpuppies but does not prevent infection. Puppies younger than 16 weeks aretherefore highly susceptible. Infection leads to hemorrhagic diarrhea and sep-ticemia due to unrestricted viral proliferation and cell destruction in bone mar-row, lymphoid tissue, and intestinal crypts. Newly available vaccines may stim-ulate an adequate immune response in the face of maternal antibody.Parvoviral disease may thus be prevented in this highly susceptible population.Part II of this two-part presentation will discuss diagnosis and treatment of ca-nine parvovirus infection.
PARVOVIRIDAE
Parvoviruses (Parvoviridae) are small, nonenveloped viruses. They are theonly group of mammalian viruses with single-stranded DNA. After enteringthe cell, the parvovirus is carried or travels to the nucleus via endosomes toreplicate.
1
Parvoviruses replicate only in cells synthesizing DNA and use thecell’s machinery to produce viral rather than cellular proteins, thus leading tothe death of the cell. Parvoviruses are hardy, withstanding a wide range of tem-peratures and disinfectants.
2,3
However, they can be inactivated by sodiumhypochlorite, formalin, and sunlight.
3,4
Parvoviruses in Dogs
Defective (adeno-associated) and nondefective (or autonomous) parvovirusesare found in dogs. The adeno-associated parvoviruses were discovered as con-taminants of stock cultures of canine infectious hepatitis virus. These virusescannot replicate or assemble mature viral particles without enzymes produced
s
Two new subtypes of canineparvovirus 2 (CPV-2) haveemerged; these subtypes providecomplete crossprotectiveimmunity.
s
CPV-2a and CPV-2b have anincreased affinity for cats.
s
The highest incidence of CPVinfection continues to occur inexposed puppies with waningmaternal antibody that interfereswith active immunization.
s
Reactions after parvovirusvaccination are rare and shouldbe anticipated and treated assoon as they arise.
*Part II of this presentation appears in the March 1997 (Vol. 19, No. 3) issue of 
Com-  pendium 
.
 
by adenovirus infection of cells. The autonomous par-voviruses can replicate without the adenovirus enzymesand are pathogenic.The first autonomous canine parvovirus (CPV-1) wasisolated in 1967 from the feces of normal dogs.
5
Thisvirus was first named the minute virus of canine(MVC) because of its small size.
6
This virus was diffi-cult to grow in tissue culture. Its growth could not besupported by other canine cell lines or cell lines fromother species. The virus could only be propagated invitro in one continuous cell line called Walter Reed Ca-nine Cell (WRCC).
6
This cell line was developed froma subdermoid cyst of an irradiated dog.Before 1985, MVC or CPV-1 was considered non-pathogenic. Since then, however, it has been reportedto cause transient diarrhea in puppies between the agesof 5 and 21 days.
7
Oronasal exposure of specific-pathogen
–
free neonatal puppies to CPV-1 has beenobserved to cause mild to severe respiratory disease,including bronchitis, interstitial disease, and lym-phadenitis with mild to absent small intestinal le-sions.
8
Experimental inoculation of CPV-1 into pregnantbitches resulted in fetal death, abortion, and respiratory distress and death of puppies born to infected bitches.This finding was significant. Unlike in other species,parvoviruses had not previously been recognized as acause of poor reproductive performance (abortion andfetal death) in dogs.Parvovirus was isolated from the thymus and intesti-nal microvilli tips of puppies infected in utero.
8
TheMVC or CPV-1 differs in its in vitro host cell range,hemagglutination, and antigenic and genomic proper-ties from the parvovirus that causes hemorrhagic diar-rhea.The parvovirus causing hemorrhagic diarrhea wasoriginally named canine parvovirus 2 (CPV-2). Itemerged in 1978 in the United States. The earliest re-port of a detectable titer is from Greece in 1974.
9
Thefirst evidence of infection by CPV-2 was seen in serumcollected from dogs in Belgium in 1976, the Nether-lands in 1977, Denmark, Australia, and United Statesin 1978, and Japan in 1979.
10
The CPV-2 variant is be-lieved to have emerged from feline panleukopenia virus(FPV) or from a parvovirus of another wildlife species(possibly mink enteritis virus [MEV], raccoon par-vovirus [RPV], or fox parvovirus) because it has ge-nomic and antigenic similarities to these viruses.
11,12
Between 1979 and 1982, less of the original strain of CPV-2 was isolated from infected dogs. It was replacedby another strain (CPV-2a), which was consideredmore virulent because it replicated more efficiently indogs and other wild canids.
9
Later, another variant(CPV-2b) evolved. More than 80% of the isolates inthe United States today are CPV-2b.
13
The CPV-2a and CPV-2b subtypes can be distin-guished by their restriction endonuclease patterns andreactivity with specific monoclonal antibodies.
13
Re-striction endonucleases are bacterial enzymes that canbe used to digest viral DNA. The size and number of the digested DNA fragments (digests) vary according tothe particular restriction endonuclease and virus thatare used.Digests are subjected to an electrical field (elec-trophoresis) while placed on polyacrylamide gel thatsupports and allows movement of the ensuing DNA fragments. The viral DNA fragments migrate accordingto size and separate. This is the first step in determiningsequence patterns or maps of viral genomes. The mapor sequence analysis that is generated can be used tocompare closely related organisms.
Parvoviruses in Cats
In addition to the antigenic variation, CPV-2a and-2b are reported to differ from CPV-2 in their affinity for host cells. Whereas CPV-2a and CPV-2b can repli-cate and produce high titers in lymphoid and intestinalcells of inoculated cats, CPV-2 could not. The isolationof CPV-2a and CPV-2b from cats suggested that bothof these variants might cause clinical disease in cats as well as dogs.Ten percent of parvovirus isolates from cats with nat-urally occurring disease are antigenically identical toCPV-2a or -2b.
14
Furthermore, it is postulated that thenewer isolates of CPV may further adapt to cats andeventually replace FPV in the feline population.
14
Therapid emergence of new subtypes of CPV results fromsmall revisions in the viral genome in a region responsi-ble for the virus capsid, where three protein monomersinteract.
14
The capsid is responsible for the changes incell infectivity and the in vivo host range of thevirus.
12
–
14
INCIDENCE AND PREDISPOSING FACTORS
Initial outbreaks of parvovirus in dogs were charac-terized by high morbidity and mortality in all agegroups. Currently, the disease is more commonly en-countered in puppies from 6 weeks to 6 months of age.Most adult dogs have become immune through vacci-nation or natural infection. This immunity is passed onto newborn puppies via maternal antibodies.Puppies become susceptible to viral infection as thematernal antibody titer declines to nonprotective levels;and adequate immunization to parvovirus does not oc-cur during the first year of life. There seems to be a window of time during which the maternal antibodies
Small Animal
The Compendium 
February 1997
CPV-2
s
FPV
s
CPV-2a
s
CPV-2b
 
block the immune response to CPV vaccine but cannotprevent CPV infection.
15,16
Maternal antibody titer in puppies varies withamount of colostrum ingested, the serum titer of themother at whelping, and litter size.
15
The CPV-2 titerprovided by absorbed colostral antibody is 50% to 60%of the mother
’
s.
15,16
This maternal antibody has a half-life of about 10 days.
15,16
How long maternal antibody continues to interfere with CPV vaccines depends on the type of CPV vac-cine the puppy receives. Less maternal antibody isneeded to suppress an immune response to an inacti-vated vaccine than to new-generation, low-passage,high-titer, modified-live virus (MLV) vaccines. Thesevaccines are also better at stimulating an immune re-sponse during the period of maternal antibody interfer-ence than are the low-titer MLV vaccines.The antibody titer that interferes with immunizationby vaccination varies depending on the serologicmethod used to measure the titer.
15
–
18
Serum neutraliza-tion (SN) titers from 1:2 to 1:16 have been reported tointerfere with vaccination, depending on the type of vaccine used.
15,17,19
High-titer MLV vaccines will gener-ate an immune response in most puppies withSN titers of 1:8 and in some with SN titers of 1:16. A protective SN titer over 1:20 will inter-fere with essentially all CPV vaccines.
17,19
Hemagglutination inhibition (HI) titers of 1:80 are usually protective and also interfere with vaccinations.
18
However, HI titers of 1:10have also been reported to interfere with inacti-vated vaccines as well as with low-titer attenuat-ed vaccines.
16
The new-generation high-titerMLV vaccines induce immune responses inpups with HI titers equal to or slightly less than1:80.
20
Serologic titers are not routinely measured be-fore vaccination. Furthermore, there is no evi-dence that any vaccine can com-pletely override interference frommaternal antibody (Table I). Theuse of serial vaccinations or vacci-nation schedules therefore remainsa practical approach for maximizingthe probability that puppies will beimmunized during the normal peri-od of maternal antibody interfer-ence.The predisposing factors for par-vovirus infection in puppies arelack of protective immunity; inter-nal parasites; and overcrowded, un-sanitary, and stressful environmen-tal conditions.
21
In adult dogs, parvovirus infection isusually inapparent, acute, or subacute. Many infectionsare subclinical. Immunity to canine parvovirus causedby infection or attenuated vaccine is reported to belong lived (>20 months) and perhaps lifelong.
22
Certain breeds are reported to be more susceptible tothe development of parvovirus disease despite antibody titers considered protective in other breeds
21
(see Risk Factors for Canine Parvovirus Infection). Rottweilers,Doberman pinschers, and Labrador retrievers are report-ed to be more severely affected by parvoviral infection.
21
In one study, signalments associated with increasedrisk were immature male Doberman pinschers and rott- weilers and mature female springer spaniels.
23
Datafrom the nationwide Veterinary Medical Data Programindicated that Doberman pinschers and rottweilers were at significantly increased risk of CPV enteritis.
23
The prevalence of von Willebrand
’
s disease has beensuggested to be a predisposing factor in the develop-ment of severe bloody diarrhea in some breeds, particu-larly Doberman pinschers and rottweilers.
20
In a West German study, the breeds at increased risk  were German shepherds and Yorkshire terriers. In this
The Compendium 
February 1997Small Animal
SERUM NEUTRALIZATION TITER
s
HEMAGGLUTINATION INHIBITION TITER
s
PARASITES
TABLE IAntibody Titers Capable of Interfering with Active Immunization
Serum Interference by Neutralization Hemagglutination Maternal AntibodyTiterInhibition Titer 
Interferes with low-titer attenuated
≥
1:2
≥
1:10and inactivated vaccinesInterferes with high-titer attenuated
≥
1:16
≥
1:64vaccinesInterferes with all vaccines but 1:201:80provides protective immunity 
Predisposed Breeds
RottweilersDoberman pinschersLabrador retrieversGerman shepherdsSpringer spanielsAmerican pit bull terriersYorkshire terriers
Breeds at Decreased Risk
Cocker spanielsToy poodles
Months with High Incidence
November, December, andJanuary (in Germany)July, August, and September(in Canada)
Risk Factors for Canine Parvovirus Infection
of 00

Leave a Comment

You must be to leave a comment.
Submit
Characters: ...
You must be to leave a comment.
Submit
Characters: ...