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, nervous system disturbances, and dermatitis. 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. The vast majority of MCF cases in the US are caused by ovine herpesvirus 2 (OvHV-2), which exists as a ubiquitous subclinical infection in sheep. However, five other MCF viruses have been associated with clinical disease: alcelaphine herpesvirus 1 (AIHV-1) alcelaphine herpesvirus 2(AIHV-2), caprine herpesvirus-2 (CpHV-2), caprine herpesvirus-3 (CpHV-3, previously called MCFV-WTD), and ibex-MCF virus. AIHV-1 is carried by wildebeest and is the predominant cause of MCF in Africa. An AIHV-2 carried by topi or hartebeest was able to cause disease in bison following experimental infection, while an AIHV-2 like MCF virus from Jackson's hartebeest caused MCF in Barbary red deer under natural conditions. CpHV-2 is transmitted by goats and causes disease in deer, moose, and certain antelopes. CpHV-3 is also carried by goats and has been reported as causing MCF in deer in North America. The MCF virus carried by ibex is responsible for cases of MCF in anoa and antelopes, including bongos, pronghorns, and duikers. Other viruses in the MCF-group have also been identified, including the viruses harbored by oryhx, roan antelope, muskox, and aoudad; however, so far none of these viruses have been reported in association with clinical cases in nature.
Diagnosis of MCF is based on epidemiology, clinical signs, pathology and detection of viral DNA in tissues. Serology is recommended for screening of subclinically infected carrier animals.
Serology, using a MCF virus specific competitive ELISA (MCF cELISA) and direct detection of viral DNA using a variety of PCR assays are available through WADDL. The choice of the test to be used depends on species, age, and disease-infection status of the animal.
The assay is broadly used for detection of antibodies to all viruses in the MCF-group, since it is based on an epitope present on all members of the MCF virus group. Currently ten viruses have been identified within this group, and it is likely that most ungulates have similar viruses. Thus a positive antibody test means that the animal is infected by a member of the MCF virus group, but no inference about virus identity can be made. If necessary, the identity of these viruses can be determined by PCR or PCR followed by DNA sequence analysis.
The MCF-cELISA is not used for diagnosis of MCF disease but can be used to document latent infections in both clinically susceptible species (e.g. cattle, bison and deer) and carrier hosts( e.g. sheep, goats and wildebeest).
PCR assays are generally specific for the virus strain for which they were designed. PCR should be used to confirm suspected cases of MCF disease in all clinically susceptible species. Cinically affected animals present high levels of viral DNA in leukocytes and tissues, while latently infected animals show either low or undetectable levels of viral DNA.
Specific PCR assays are available for all CMF viruses known to cause disease. Quantitative assays can be done for OvHV-2, AIHV-1 and CpHV-2. A broad spectrum herpesviral PCR is also available for identification of new MCF viruses. A broad spectrum herpesviral PCR is also available for identification of new MCF viruses.
Samples to be Tested
For antibody testing by MCF-cELISA:
Either serum (RRT, SST) or plasma (PTT) can be used in MCF-cELISA
For detection of viral DNA by PCR:
Whole blood in EDTA (PTT) can be used as an antemortem sample. Preferred postmortem samples are fresh or fresh frozen lymph node and lung, but other tissues including spleen, liver, and intestine are also acceptable.
Testing MCF-Affected Animals
MCF in clinically susceptible hosts:
PCR is the test of choice to confirm disease in clinically susceptible hosts. Clinically affected animals have a higher viral load in tissues, which can be detected and quantified using standard and quantitative PCR assays, respectively.
The presence of antibodies to MCF viruses in clinically susceptible species (e.g. cattle, bison, or deer) cannot be used to confirm the diagnosis of clinical MCF or as differential diagnosis. One of the reasons for that is that in acute cases of MCF, serconversion may not occur before the animal is dead. In contrast, about 30% of cattle and bison in certain populations have been found seropositive, probably due to a latent infection with a MCF virus. Animals that are MCF-cELISA positive and PCR negative, especially if they lack the characteristic clinical signs or lesions of MCF, are most likely latently infected and have a level of virus in the blood that is below the detection threshold of the assays.
MCF in carrier species:
Although clinical MCF in carrier hosts is uncommon, it has been reported in sheep. In cases where MCF is suspected in a carrier species, the detection of the virus by PCR is of little diagnostic value, since most carrier hosts are infected with their respective MCF viruses. However, identification of high levels of MCF viral DNA in tissues can be used to corroborate the diagnosis. In addition, detection of OvHV-2 nucleic acids assocaited with lesions in tissues using an OvHV-2 specific in situ hybridization assay is of diagnostic value when sheep-associated MCF is suspected.
Negative MCF virus-specific PCR in a case with strong clinical suspicion of MCF:
When epidemiologic, clinical, histologic and other laboratory evidence strongly suggest MCF, and the most common MCF virus specific PCRs are negative (OvHV-2, AIHV-1 or CpHV-2), it is possible that an unknown MCF virus is involved. If an adequat level of suspicion exists, this possibility can be pursued with additional PCR tests that have more broad specificity, such as the MCF multiplex PCR of the herpesvirus consensus primer PCR, followed by sequencing.
Prepared by Dr. Cristina Cunha, USDA
Contact the Consulting Microbiologist at WADDL if any questions arise at 509-335-9696
Page revised June 2019
Cunha, C. W., Otto, L., Taus, N.S., Knowles, D.P. & Li, H. (2009). Development of a multiplex real-time PCR for detection and differentiation of malignant catarrhal fever viruses in clinical samples. Journal of Clinical Microbiology 47, 2586-2589.
Li, H., Cunha, C. W., Taus, N.S. & Knowles, D.P. (2011). Malignant Catarrhal Fever: Understanding Molecular Diagnostics in Context of Epidemiology. International Journal of Molecular Sicences 12, 6881-6893
Li, H. Cunha, C.W., Taus, N.S. & Knowles, D.P. (2014). Malignant Catarrhal Fever: inching toward understanding. Annual Review of Animal Biosciences 2, 209-233
O'Toole, D. & Li, H. (2014). The pathology of malignant catarrhal fever, with an emphasis on ovine herpesvirus 2. Veterinary Pathology 51, 437-452