Information regarding diagnosis and testing for Malignant Catarrhal Fever
(MCF)
January, 2005
Brief review of MCF
Malignant catarrhal fever (MCF) is a frequently fatal
disease syndrome primarily of certain ruminant species (e.g. cattle, bison,
deer), caused by one of several herpesviruses. The disease is characterized
by inflammation, ulceration, and exudation of the oral and upper respiratory
mucous membranes, and sometimes eye lesions and nervous system disturbances.
The causative viruses exist in nature as subclinical infections in other
ruminant species (e. g. sheep, goats) that serve as carriers. The disease is
emerging as a significant source of economic loss in several ruminant
species, particularly in confined bison. Two major epidemiologic types of
MCF exist, being defined by the reservoir ruminant species from which the
causative virus arises. One is commonly known as the African form or
‘wildebeest-associated’ MCF (WA-MCF) caused by alcelaphine herpesvirus-1
(AlHV-1). The other is referred to as ‘sheep-associated’ MCF (SA-MCF).
Virtually all cases of MCF in the U.S. are SA-MCF, caused by the sheep virus
or ovine herpesvirus 2 (OvHV-2), which exists as a ubiquitous subclinical
infection in domestic sheep. although several more members of MCF virus
group have recently been recognized, only two reportedly cause clinical
disease in nature. One, tentatively termed MCF virus in white-tailed deer (MCFV-WTD),
was found causing the classic MCF syndrome in white-tailed deer in North
America. The carrier species for this virus has not yet been identified. The
other, provisionally called caprine herpesvirus 2 (CpHV-2), is endemic in
domestic goats and was associated with alopecia, chronic weight loss and
dermatitis in two species of deer.
Samples
Antibody testing by cELISA may be done with either
serum or plasma. Antemortem detection of viral DNA by PCR may be done on
whole blood in EDTA. Preferred postmortem samples for detection of viral DNA
by PCR are lymph node or spleen, but other acceptable tissues include lung,
kidney, and intestine
Available tests
Detection of MCF antibody in clinically susceptible
species (e.g. cattle, bison, and deer) indicates infection, but is not
diagnostic of disease since a significant percentage of these species can be
latently infected with the virus. PCR should be used to confirm suspected
cases of clinical MCF in all clinically susceptible species. PCR detection
of viral DNA in leukocytes or tissues correlates better with clinical
disease since in most latently infected animals viral DNA is below the
threshold of detection.
Although rarely necessary, detection of MCF antibody
can be used to document infection (but not disease) in MCF susceptible
species (e.g. cattle, bison and deer) and MCF virus carrier species (e.g.
sheep, goats and wildebeest).
Effect of age of kids or lambs on antibody or PCR
results
Uninfected lambs or kids under 4 months of age may be
antibody positive due to the presence of maternal antibody. Conversely,
between about 3 and 12 months of age, infected lambs may test antibody
negative since in about 30% of lambs exposed under natural circumstances the
development of antibody can be delayed up to 1 year of age. Consequently, in
lambs or kids less than 1 year of age, serology is unreliable for
determining if these animals are infected. After about 1 year of age,
serology is reliable for determining infection status.
Although generally infected early in life, viral DNA
as detected by PCR does become detectable in leukocytes until 1-4 weeks post
infection. Epidemiologically, most infected lambs and kids do not become PCR
positive until about 3 months of age. Therefore, if MCF testing is being
done to confirm that lambs or kid are not infected, it is necessary to test
after they are at least 4 months of age. Although false negatives may occur,
PCR for viral DNA in leukocytes is the optimal test for determining
infection status in animals between 3 and 12 months of age.
Requests for PCR testing of sheep
and goats with suspected MCF disease
Since virtually all sheep and goats are naturally
infected with, and carriers of, their respective MCF viruses, a positive PCR
test is of little diagnostic value. Although recent research suggests that
clinical MCF in sheep may be induced experimentally with very high doses of
virus, this is extremely unlikely to be seen with natural transmission and
clinical MCF in sheep is exceedingly rare. It may be possible that MCF may
occur only in those individuals with genetic or acquired immune
deficiencies. However, antibody or PCR testing in sheep is not diagnostic,
and verification of suspected cases of MCF in the carrier species will
require additional laboratory data (e.g. compatible histologic lesions,
ruling out other differential diagnoses).
Requests for PCR testing of normal sheep and goats
PCR testing for the presence of MCF virus is not
routinely performed on normal adult sheep and goats. In those instances
where it is necessary to document that these animals are MCF-free, the
cELISA is the optimal test for this type of screening. In the carrier
species, the cELISA is very sensitive and will detect over 95% of infected
animals. In addition, serology is much more economical than PCR.
Negative antibody results in adult, clinically normal
sheep or goats
It is unusual for adult sheep or goats to be
seronegative since these animals are endemically infected with OvHV-2 or
CpHV-2 respectively. The occasional negative animals usually originate from
specially-designed programs intended to produce MCF-free sheep or goats, or
from zoos, small operations or other conditions which restrict exposure to
other members of the species.
Antibody testing of
clinically-ill, PCR-negative susceptible species
The presence of MCF-group antibody in clinically
susceptible species (e.g. cattle, bison, deer) cannot be used to verify
clinical MCF. Up to 30% of normal cattle and bison are seropositive but
latently infected. In addition, acute cases of MCF may occur before
seroconversion and thus test antibody negative. Therefore, antibody testing
is of limited value for diagnosis of MCF in clinically susceptible species.
Animals that are seropositive and PCR negative, especially if they lack the
characteristic clinical signs of MCF, are most likely latently infected.
Antibody testing of Oryx (Gemsbok), Ibex and Muskox
Most Oryx, Ibex and Muskox are seropositive in MCF
cELISA antibody test being performed by WADDL due to infection with their
respective MCF-group viruses. Similar to sheep, the prevalence of infection
in these animals is very high. These viruses are distinct from the
Alcelaphine (AlHV-1) or Ovine (OvHV-2) MCF viruses, and they have not been
reported to cause disease in any species to date.
Positive antibody results in other
exotic species
The cELISA detects antibody against an epitope which
is present against all known members of the closely related MCF group of
ruminant rhadinoviruses. Currently more than 8 members of this group have
been identified, and it is likely that most ungulates have similar viruses.
Thus a positive antibody test in an exotic species means only that it is
infected by a member of this virus group. The test is not specific for ovine
herpesvirus 2, and no inference about virus identity can be made. If
necessary, the identity of these viruses can be determined by PCR and DNA
sequence analysis from leukocytes or lymphoid tissue.
When OvHV-2 PCR is negative on a case with strong
clinical suspicion of MCF
When epidemiologic, clinical, histologic and other
laboratory evidence strongly suggests MCF, and PCR testing does not detect
sheep-associated MCF virus (OvHV-2), then it is possible that another MCF
virus may be involved. It is possible that other combinations of viruses
from carrier (especially members of the Caprinae or Alcelaphinae) and
susceptible ungulates may result in MCF. If an adequate level of suspicion
and the possibility of exposure to other ungulates exists, this possibility
can be pursued with other PCR tests.
Additional information
If there are questions about MCF biology, sampling,
testing, interpretation of results or MCF testing in general, please contact:
Dr. Hong Li
509-335-6002
hli@vetmed.wsu.edu
or
Dr. Lindsay Oaks
509-335-9696
loaks@vetmed.wsu.edu
Last Edited: Nov 05, 2008 2:38 PM
