Download Canine Distemper Virus and other Infectious Respiratory

July 2010
Diagnostic
Update
Infectious respiratory diseases in dogs
The Canine Distemper Virus and other pathogens
Canine distemper virus (CDV) may cause a constellation of
systemic clinical signs including vomiting, diarrhoea, and/
or respiratory signs. These may be difficult to distinguish
from other infectious and noninfectious diseases in young
dogs. Both acute and chronic progressive neurologic signs
may also be seen in canine distemper. During early systemic infection, having an accurate diagnosis of distemper
infection may better guide appropriate therapy, as well as
prepare the owner for the possibility of future neurologic
consequences. Likewise, the ability to definitively diagnose
distemper virus as the cause of neurologic signs over other
diseases with a better prognosis may help owners and clinicians make informed decisions about continuing therapy
versus euthanasia.
Canine Distemper Virus
Canine distemper virus (CDV) is a single negative-stranded RNA
virus in the genus Morbillivirus of the family Paramyxoviridae.
CDV is the causative agent in canine distemper, one of the most
important infectious diseases in dogs with a worldwide mortality
rate second only to rabies. Canine distemper virus causes significant disease in puppies and unvaccinated dogs, other terrestrial
carnivores, and marine mammals. CDV may result in systemic
infection with gastrointestinal signs and/or respiratory signs,
and can progress to neurologic disease in patients who survive
the initial systemic stage. Mortality and severity of CDV infection
varies greatly with strain, host species, age, immune status, and
vaccination status. The incidence of canine distemper has greatly
decreased since the development of modified live vaccines (MLV)
for CDV. Vaccination with MLV is effective in preventing distemper
although post-vaccinal distemper encephalitis has been rarely
seen. Clinical disease is rare in well-vaccinated adult dogs.
Transmission of CDV to susceptible animals is through exposure to aerosolized respiratory secretions from recently infected
dogs (diseased or nonclinical) or by exposure to infected wildlife.
Shedding of virus begins within seven days of infection and may
continue for up to three months. Because of effective vaccination
programs, canine distemper is most common in areas with a significant unvaccinated canine population or a wildlife reservoir. The
host range has recently widened with interspecies transmission
resulting in several recent epizootics with high mortality.1,2
Early infection with CDV often goes undetected, but may have fever and lymphopenia. The virus then spreads to epithelial tissues
and the central nervous system. Infection may clear, dogs may
become silent carriers (if partial immunity), or may progress to the
systemic stage. Silent carriers may still be infective for other dogs
and may develop hyperkeratosis of the footpads and neurologic
signs later in infection. If inadequate immunity is present, acute
multisystemic illness usually develops about two weeks after
initial exposure. Initial signs include a mild conjunctivitis with clear
to mucopurulent nasal and ocular discharge. Lethargy, fever, and
decreased appetite are often seen. Upper respiratory signs are
followed by a cough, and in severe forms, dyspnoea and bronchopneumonia may develop. Gastrointestinal signs follow with
vomiting, diarrhoea (sometimes bloody), and often severe dehydration. The severity of the multisystemic signs varies with the
degree of immunity. Very mild forms may be confused with kennel
cough. Severe forms may result in acute death. Treatment during
the acute systemic phase is supportive and may also include
antibiotics for treatment of secondary bacterial infections.
Some, but not all, dogs who recover from the systemic stage will
develop neurologic signs. If they occur, neurologic signs most
commonly develop one to two weeks after the systemic illness
has resolved, and can also be seen in dogs that were subclinical
through the initial stages. Dogs infected in utero or shortly after
birth may show peracute neurologic signs without developing
other systemic signs. Neurologic signs can also occur simultaneous with the acute multisystemic signs, or can be delayed by
months or years (Old Dog Encephalitis). The clinical signs seen
vary with the area of the nervous system involved. Myoclonus
(involuntary muscle twitching) is a common sign that has become
almost pathognomic for distemper, but can also rarely be seen
with other inflammatory nervous system diseases. Unusual seizure episodes called “chewing gum fits”, ataxia, para- or tetraparesis, cerebellar and vestibular signs are all common manifestations
of distemper. Optic neuritis, retinal scarring, and uveitis may be
seen. Neurologic signs are generally not reversible. Neurologic
signs may be progressive. Seizures may become more frequent
and refractory to anticonvulsant therapy. Distemper encephalitis
may also progress to coma and death. Post-vaccinal encephalitis
may also rarely be seen following modified live vaccination, and
has a better prognosis with the potential for resolution of neurologic signs.
Diagnostic Tests
The majority of tests currently available for canine distemper virus
infection are hampered by either low sensitivity or specificity.
Virus Isolation for CDV is limited by cost, specialized equipment
required, and low turnaround time. Virus isolation is unable to
detect post-vaccinal or chronic (Old Dog Encephalitis) distemper
encephalitis cases due to defective viral replication. Immunohistochemistry provides a specific, but invasive diagnostic test for
distemper. Sensitivity varies with the stage of disease and site
sampled. Direct Fluorescent Antibody detection of CDV inclusion bodies in conjunctival smears, whole blood and CSF fluid is
a specific diagnostic test for CDV. It is not, however, a sensitive
test, and is primarily useful only in early disease. Vaccination with
a modified live vaccine may result in a false positive in the first
few weeks post-vaccination. Serum antibody titers are difficult
to interpret in dogs that have been vaccinated or late in infection,
which limits their utility.
With IDEXX RealPCR™, CDV RNA is extracted from whole blood,
serum, CSF fluid, fecal, conjunctival or respiratory samples. If
the sample contains CDV RNA, the RNA is converted to complementary DNA (cDNA). The cDNA is then amplified with the PCR
process. In real-time PCR, the reaction mix includes fluorescently
labeled probes that bind only to the unique cDNA of the target organism, releasing fluorescence as the cDNA accumulates. If the
pathogen is present, the resulting fluorescence is detected by the
PCR instrument. This provides both a very specific and sensitive
diagnostic test for canine distemper.3,4
Using the IDEXX RealPCR™ CDV Test in Your Practice
When to use
• Distemper testing via real-time PCR should be performed in
all dogs with signs which may be attributable to distemper, but
particularly in young dogs or dogs that are not fully vaccinated
or for which the vaccine status is unknown.
• Dogs with combinations of conjunctivitis, respiratory and gastrointestinal signs.
• Dogs with only respiratory signs in which standard treatment for
kennel cough has been unrewarding. Note that for these patients, the IDEXX RealPCR™ Canine Respiratory Profile, which
includes real-time PCR for canine distemper virus in addition to
five other infectious canine respiratory agents, may be a more
appropriate choice.
• Dogs with neurologic signs
• Vaccinated dogs suspected of having distemper (for which
other diagnostic tests for distemper would be inaccurate due to
either low sensitivity or vaccine interference).
Limitations
Vaccination with a modified-live canine distemper vaccine may
result in positive PCR results (but not in CSF fluid that is uncontaminated with peripheral blood) for a few weeks immediately
post-vaccination. Killed and vectored-recombinant vaccines do
not interfere with PCR testing.
Sample Guidelines
• For neurological manifestations:
CSF (at least 0.5 ml), EDTA-blood (2 ml).
• For respiratory manifestations
Deep pharyngeal swab* (with visible organic material on swab;
please rub firmly) and a conjunctival swab* (wipe eye clean,
swab inside of eyelid), in the same tube. Please submit swab
dry, without transport media, in a serum tube or an empty,
sterile tube.
• For GI manifestations:
EDTA-blood (2 ml) and fecal sample (fecal cup).
• With no distinct clinical manifestations:
EDTA-blood (2 ml) and conjunctival swab* (wipe eye clean,
swab inside of eyelid). Please submit swab dry, without transport media, in a serum tube or an empty, sterile tube.
IDEXX RealPCR™
Canine Respiratory Profile
Multiple infectious agents can be a cause of respiratory disease
in dogs; the prompt identification and treatment of these may
lead to less severe clinical signs and could even be life-saving as
well as allowing for isolation of infected dogs. The IDEXX RealPCR™ Canine Respiratory Profile provides rapid, sensitive and
specific identification for all six infectious agents at once - Canine
parainfluenza virus type 3, canine adenovirus type 2, canine distemper virus, canine respiratory coronavirus, canine herpesvirus,
and canine influenza virus
Canine Respiratory Disease
Respiratory disease in dogs can be caused by one or more of the
following organisms:
Canine parainfluenzavirus type 3 (CPIV-3) is a highly contagious
paramyxovirus which can cause coughing, nasal discharge and
fever. It is frequently found as one of the infectious agents in ITB
(infectious tracheo-bronchitis, Kennel cough).
Canine adenovirus type 2 (CAV-2) causes infectious laryngotracheitis and may also be an agent of ITB.
Canine distempervirus (CDV) may cause mild to severe, even
fatal, disease, depending on the pathogenicity of the infecting
strain.
*plastic-stemmed swabs are preferred, do not use wooden swabs
Canine respiratory coronavirus (CRCoV) is one of three different
coronaviruses that has been identified in dogs, but is genetically
and antigenically different from the two types of enteric CCoV.
Canine herpesvirus (CHV) may cause mild or no clinical signs in
adults or older puppies; however, this virus can be transmitted
transplacentally or via direct contact and can be fatal in very
young puppies (usually less than two weeks old).
Canine influenzavirus (CIV) has only been noted in dogs since
approximately 2004, when a disease outbreak was identified in
racing greyhounds in Florida. The virus has since been found in
multiple states within the United States. Almost 100 % of animals
that are infected with CIV show illness; most animals present with
the mild form (fever and cough for 10 to 14 days, then recovery),
but approximately 5 % of dogs develop the severe form, exhibiting high fever and tachypnoea, often followed by acute death.
Transmission
Direct contact with respiratory (oronasal) secretions and fomites
and inhalation of aerosolized droplets containing bacteria or virus
particles from infected animals that cough, sneeze, or even simply breathe in close proximity to other animals are thought to be a
mechanism of transmission for each disease. Additionally, some
of these infectious agents may be transmitted transplacentally,
shed in urine, or passed through other bodily secretions (CDV
and CHV).
Diagnostic Tests
Various tests are available to diagnose these infections; however
many are not practical either due to lengthy turnaround times,
poor specificity or sensitivity, or involved and costly diagnostic
methods. Some of these methods include bacterial or viral
culture, virus isolation techniques, and serum antibody measurement (usually requiring “convalescent” testing weeks later to
identify a rise in the titer).
Canine Respiratory Profile (Material: pharyngeal swab and conjunctival swab, turn-around-time 1 – 3 days)
Organisms
Clinical signs
Chronic carriers
Vaccination
Treatment
Canine
parainfluenzavirus
type 3 (CPIV-3)
Dry, hacking cough
Serous nasal discharge
No
· Intranasal
· Injectable
Routine in puppies and
adult dogs
· Supportive
· Antibiotics for
secondary bacterial
infections
Canine adenovirus
type 2 (CAV-2)
Mild (tonsillitis) or none
No
· Intranasal
· Injectable
Routine in puppies and
adult dogs
· Usually none
· Supportive, antibiotics, cough suppressants, etc when part
of the ITB syndrome
Canine
distempervirus
(CDV)
Conjunctivitis, oculonasal
discharge, G.I. signs,
seizures
Yes
(virus shed up to 3
months)
· Injectable
Routine in puppies and
adult dogs
· Supportive
· Antibiotics for secondary bacterial infections
· short-term steroids
· anticonvulsants
Canine
respiratory
coronavirus
(CRCoV)
None, or mild respiratory
signs
Not known
None
· Usually none
· Supportive, antibiotics, cough suppressants, etc when part
of the ITB syndrome
Canine
herpesvirus (CHV)
None, or mild rhinitis or
pharyngitis (only very
young puppies affected)
Yes
(possibly years)
Only available in
Europe, mostly used
for breeding dogs
· Usually none
· Supportive, antibiotics, cough suppressants, etc when part
of the ITB syndrome
Canine
influenzavirus
(CIV)
Mild form: fever, cough,
Not known
+/- nasal discharge
Severe form: rapid respiratory rate, high fever, pulmonary hemorrhage, sudden
death.
None
· Antibiotics
Aggressive supportive
care for severe forms
Diagnostic
Update
IDEXX’s RealPCR™ Canine Respiratory Profile, on the other
hand, offers highly sensitive and specific test results (sensitivity
and specificity are typically greater than 90 % for this diagnostic
panel). Turn-around-time for this test is only 1 to 3 days, allowing
very rapid diagnosis and quick implementation of appropriate
treatment and isolation precautions when necessary.
In addition, we recommend to order a microbiology culture at the
same time to identify involved bacteria (e. g. Bordetella bronchiseptica) and get an antibiogram if neccessary.
Using the Canine Respiratory Profile
in your Practice
When to use
Consider using the Profile with any coughing dog or one that
is presenting with oculonasal discharge. Dogs with a recent
history of being kenneled (humane shelters, boarding facilities,
etc) or hospitalized (with or without an intubation procedure) are
at greater risk for these infections and should be tested if they
have clinical signs. Bitches that give birth to stillborn puppies or
have puppies die within a few weeks of birth should be tested for
CHV (this may be ordered as an individual test; submit a vaginal
swab).
Limitations
Vaccination with a modified-live canine distemper vaccine may
result in positive PCR results (but not in CSF fluid that is uncontaminated with peripheral blood) for a few weeks immediately
post-vaccination. Killed and vectored-recombinant vaccines do
not interfere with PCR testing.
NEW: Updated PCR Test Menu
Available via [email protected]
References:
1. Greene CE, Appel MJ. Canine Distemper. In Greene CE, ed. Infectious Diseases of the Dog and Cat. Philadelphia:Saunders Elsevier;2006: 441-451
2. Lednicky JA, Dubach L, et al. Genetically distant American Canine distempoer virus lineages have recently caused epizootics with somewhat different
characteristics in raccoons living around a large suburban zoo in the USA. Virology J. 2004;1:2
3. Elia G, Decaro N, et al. Detection of canine distemper virus by real-time RT-PCR. J of Virol Methods. 2006;136:171-176
4. Amude AM, Alfieri AA, Alfieri AF. Antemortem diagnosis of CDV infection by RT-PCR in distemper dogs with neurologic deficit without the typical clinical
presentation. Vet Res Commun. 2006;30(6):679-687
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