Information regarding diagnosis and testing for
Malignant Catarrhal Fever (MCF)
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.
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
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 goatsPCR 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.