Diagnosis and testing for malignant catarrhal fever (MCF)

What is malignant catarrhal fever?

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 U.S. 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 oryx, roan antelope, muskox, and aoudad; however, so far none of these viruses has been reported in association with clinical cases in nature. 

How is malignant catarrhal fever diagnosed?

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.

For questions about MCF biology, sampling, testing, interpretation of results, or MCF testing in general, please contact Dr. Cristina Cunha at cwcunha@wsu.edu or 509-335-6072, or the consulting microbiologist at WADDL at 509-335-9696.

Additional information

Available tests

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.

  • MCF-cELISA: 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, 10 viruses have been identified within this group, and it is likely most ungulates have similar viruses. Thus, a positive antibody test means 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: 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. Clinically 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 the identification of new MCF viruses. d

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 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, the 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 associated 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 an unknown MCF virus is involved. If an adequate 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

If there are questions about MCF biology, sampling, testing, interpretation of results or MCF testing in general, please contact:

Dr. Cristina Cunha

Page revised June 2019

Categories: Cattle