Epidemiology of bovine malignant catarrhal fevers,a review

The mode of transmission of malignant catarrhal fever virus (MCFV) from wildebeest to cattle has been obscure for some time. Recent studies on the virus shedding patterns of wildebeest have revealed that MCFV occurs in nasal and ocular secretions of young wildebeest in a stable, cell-free state. Such cell-free virus is not found in the secretions of MCFV infected cattle.The findings indicate that MCFV is transmitted from wildebeest to cattle as cell-free virus shed in the secretions of young wildebeest calves and may explain the non-contagious nature of the disease in cattle.The mode of transmission of sheep-associated MCF has not been determined because the causative agent of this condition has not been isolated from either carrier sheep or sick cattle.     

Malignant catarrhal fever virus specific secretory IgA in nasal secretions of wildebeest calves

Wildebeest IgA was isolated from nasal secretions and precolostrum. It was indentified by cross-reaction with anti-human and anti-bovine IgA sera.

Nasal secretions collected from wildebeest calves over 3 months old had malignant catarrhal fever virus neutralizing antibody activity. They also contained specific IgA to the virus as detected by indirect immunofluorescence. It is suggested that production of malignant catarrhal fever virus specific IgA in the nasal cavity, contributes to the elimination and cassation of the virus shed in the nasal secretions of wildebeest calves over 3 months. old.     

Epizootology of wildebeest-derived malignant catarrhal fever in an outbreak in the north-western Transvaal: indications of an intermediate host

The investigation involved 37 herds of cattle numbering 6,280 animals and 5 groups of blue wildebeest (Connochaetes taurinus), consisting of 30-330 wildebeest per group. All the cases of wildebeest-derived malignant catarrhal fever encountered were associated with wildebeest and not with other game animals. Six per cent of the cases were encountered in late summer when the wildebeest calves were 3-4 months old, whereas 73% occurred in spring, when the wildebeest calves were 8-11 months old and did not excrete virus. The incidence of the disease among cattle born and reared in the vicinity of wildebeest was less than 0.5%. Among intermittently and directly exposed cattle the incidence was 5.2%, but the highest incidence was encountered in cattle kept in camps separated from wildebeest by a distance of approximately 100 m. Alcelaphine herpesvirus-1 (AHV-1), the causal agent of malignant catarrhal fever (MCF) was isolated from the tears, blood and nasal mucus of 8 out of 14 wildebeest calves during their 4th-6th month (April-June), but not subsequently. No sampling was possible before the age of 3 months. The occurrence of the disease from September-November, when wildebeest calves could not be incriminated because they no longer excreted virus, suggests the involvement of another host or an intermediate host capable of acquiring the infection from young wildebest calves, harbouring the infection until August-September, and then transferring it to cattle.     

Maasai perception of the impact and incidence of malignant catarrhal fever (MCF) in southern Kenya

We investigated the perceived impact of malignant catarrhal fever (MCF) to pastoralists in Isinya Division, a wildlife dispersal area of Nairobi National Park, and used a range of participatory epidemiology methodologies. We compared the relative importance, incidence and impact of MCF compared to other locally defined important diseases with a total of 158 respondents in 11 group meetings and 21 household meetings in July 2004. Direct losses due to disease were investigated through lowered prices as a result of the emergency sale of disease-infected animals.

Overall, Maasai in Isinya Division perceived east coast fever (ECF) to be the most important cattle disease and to have the highest incidence. Anthrax was considered to have the largest impact. In areas within or adjacent to the wildebeest calving zone, MCF was perceived to be the most important cattle disease and also to have the largest impact. Outside the calving zone, MCF was considered the fourth-most important disease with the fourth largest impact, and these were areas where wildebeest were less common. MCF was also the fourth-most common disease, and across the Division incidence was estimated at 5% in calves and 10% in adults. However, MCF incidence varied greatly throughout the study area, from 3% to 12%, and the highest incidence risks were found in areas where wildebeest came to calve. The percent drop in sale price per animal infected with MCF was estimated at 50% for MCF for the year 2003–2004.

Forced avoidance movements away from wildebeest calves were reported to decrease livestock production due to loss of access to prime grazing sites. As suggested by pastoralists in this study, the development of compensation schemes or incentives from wildlife would reduce the conflict between livestock keeping and wildlife conservation.     

Characteristics of the herpesvirus of malignant catarrhal fever isolated from captive wildebeest calves

A herpesvirus was isolated from buffy coat cells from a newborn wildebeest (Connochaetes gnou) and from tissues of a 12-day-old wildebeest during the 1982 calving season of a captive, inbred herd maintained in a zoologic collection. Both wildebeests were clinically healthy, and there was no herd record that malignant catarrhal fever (MCF) existed. Each viral isolate produced cytopathologic changes in bovine kidney cell cultures (intranuclear inclusions and massive syncytia). The viral-infected cell cultures contained antigens of MCF virus detected by immunofluorescence. The morphology of each viral isolate as determined by electron microscopy was that of a herpesvirus. Suspensions of 4 to 5 ml of disrupted cell culture material which contained virus from each wildebeest were inoculated (IV) into white-tailed deer (Odocoileus virginianus). Each deer became clinically ill within 28 days. Both deer had mucoid catarrh and a febrile response (40.5 to 41 C). Each also seroconverted to MCF virus. The histopathologic change in the tissues from the 2 inoculated deer was vasculitis. At 16 to 17 days after the deer were inoculated, a syncytial-forming virus was isolated from each deer from buffy coat cells fused with polyethylene glycol (1000) to bovine fetal kidney cells. The virus was identified as MCF virus by immunofluorescence and production of antibody to MCF virus. The presence of virus in the inbred wildebeest herd established this species as a reservoir or latent carrier of African MCF virus at the zoologic park.     

Immunisation of cattle against the herpesvirus of malignant catarrhal fever: failure of inactivated culture vaccines with adjuvant.

Attempts were made to immunise cattle against the herpesvirus of malignant catarrhal fever by inoculating living or formalinised preparations of the agent, propagated in cell cultures and combined with Freund's incomplete adjuvant. High and persistent levels of virus-neutralising antibody were regularly demonstrable, especially following two intramuscular inoculations at an interval of six to eight weeks. In spite of this no protection was demonstrable against parenteral challenge with virulent virus, whether in cell-free or cell-associated form. In a controlled field trial vaccinated cattle showed no evidence of protection against natural challenge by exposure to wildebeest herds. It was concluded that humoral mechanisms are probably not important in determining resistance to infection with virulent MCFV.     

Wildebeest-derived malignant catarrhal fever: unusual epidemiology in South Africa

The epidemiology of wildebeest-derived malignant catarrhal fever in South Africa differs from the worldwide accepted pattern. Here the occurrence of the disease is often not related to close contact between cattle and wildebeest, and most cases are observed during late winter and spring, when wildebeest calves are 8-10 months old. This is in contrast to the situation in Kenya and Tanzania, where most cases are encountered during autumn, when wildebeest calves are 3-4 months old.     

Derivation of a DNA clone corresponding to the viral agent of sheep-associated malignant catarrhal fever

Malignant catarrhal fever is a fatal lymphoproliferative and degenerative disease of ruminants. One causative agent is the gammaherpesvirus alcelaphine herpesvirus 1 (AHV-1), which produces no disease in its natural host, the wildebeest (Connochaetes species). Epidemiological evidence implicates sheep as the carrier of a similar virus. However, attempts to culture this virus from sheep or from animals affected with sheep-associated malignant catarrhal fever (SA-MCF) have failed. Lymphoblastoid cells have been propagated from cattle, deer and rabbits with SA-MCF. Although these cells show no evidence of viral particles or antigens, hybridisation experiments now show that they contain DNA sequences homologous to those of AHV-1. A genomic library was constructed from one of these lymphoblastoid cell lines and a clone identified which hybridised to cloned AHV-1 DNA. The authors believe that this clone contains part of the SA-MCF viral genome, and that the SA-MCF virus and AHV-1 are closely related gammaherpesviruses.     

Malignant catarrhal fever. I. Response of American cattle to malignant catarrhal virus isolated in Kenya.

Fifty-three American cattle were inoculated with malignant catarrhal fever virus isolated from a wildebeest in Kenya. Three animals showed the mild form of the disease and recovered, and 47 showed the severe form of the disease. The other three did not react. Of the 47 cattle, 28 died, 16 were killed for the collection of specimens and three recovered. The incubation period for the 47 cattle ranged from 16 to 29 days and the course of the fatal disease for 28 cattle averaged three to 23 days. Virus titration of specimens from nine infected steers yielded a mean titer of 10(4)/TCID50 per gm for lymph nodes, 10(3) TCID50 per mL for buffy coats and 10(2.3) TCID50 per gm for spleens. Smaller amounts of virus were found in the liver, kidneys, adrenals and thyroids. Malignant catarrhal fever virus was also found in nasal secretions and saliva of viremic cattle. Viral infectivity was shown in bovine buffy coat cells stored at 4 degrees C for two days but was immediately destroyed upon freezing even when glycerine or dimethylsulfoxide was added. Viral particles were not found in infected animal tissues by electron microscopy. The disease was successfully transmitted in steers by intratracheal intubation and by aerosol inhalation but not by contact.     

Epizootology of wildebeest-derived malignant catarrhal fever: possible transmission among cows and their calves in the north-western Transvaal

The investigation involved 52 cases of wildebeest-derived malignant catarrhal fever in 1986 and 1989 in a herd of cattle kept in camps adjacent to a game farm harbouring a herd of approximately 330 blue wildebeest (Connochaetes taurinus). In the outbreaks, 34 cows and 18 calves died as result of the disease. The exceptionally high incidence of the disease in both cows and their calves, the low incidence in calves of unaffected cows, the relatively short period between the death of cows and their calves as well as the occurrence of the disease in 2 calves born after their mothers had been moved away from wildebeest, are indicative of transmission among cows and calves. The death of at least 6 calves within 6 weeks of birth is ascribed to intra-uterine infection while some calves that survived longer may have acquired the infection from other cattle or from wildebeest.     

A Plaque Assay for Malignant Catarrhal Fever Virus and Virus Neutralizing Activity

A cell-free strain of malignant catarrhal fever virus which produced a readily recognizable cytopathic effect was obtained by serial passage of the virus in a rabbit kidney cell line. Plaque assay of the virus was more rapid and gave higher titres 11 days postinoculation than tube titration, but the latter advantage decreased with a longer incubation period. Plaques were clear with sharp edges and measured 0.5 to 2 mm in diameter after 15 days. A plaque neutralization test was developed and successfully employed for the titration of malignant catarrhal fever virus neutralizing activity in the sera and nasal secretions of blue wildebeest.     

Concurrent malignant catarrhal fever and bovine virus diarrhoea virus infection in a dairy herd

An account is given of an outbreak of malignant catarrhal fever which occurred in a 98-cow dairy herd. Ten animals died or were slaughtered and the disease was confirmed by clinical and histological examination. Serological tests for malignant catarrhal fever virus were positive in three of four animals. The diagnosis of malignant catarrhal fever was complicated by the presence of bovine virus diarrhoea virus infection in three of the early cases. The initial cases of malignant catarrhal fever occurred in a group of nine-month-old calves which were housed in an old milking parlour with 19 pedigree Suffolk ewes at lambing time. Later cases occurred in two adult cows and in two heifers. Investigations of the remainder of the herd for evidence of bovine virus diarrhoea virus did not reveal the presence of any persistently infected cattle. Serological examinations for antibody to malignant catarrhal fever and bovine virus diarrhoea virus were carried out on the 19 Suffolk ewes. Six of them had neutralising antibody titres to malignant catarrhal fever virus and three were positive in the indirect immunofluorescence test. The possible roles of bovine virus     

Excretion of alcelaphine herpesvirus-1 by captive and free-living wildebeest (Connochaetes taurinus)

Excretion of alcelaphine herpesvirus-1 (AHV-1) is for all practical purposes limited to wildebeest calves under the age of 4 months. Sixty-one per cent of calves 1-2 months of age excreted virus with a mean titre of 9.8 X 10(4) cytopathic-forming foci/ml in their ocular fluid. The incidence declined sharply to less than 2% in wildebeest older than 6 months. No difference in age-related excretion of virus could be detected between free-living and captive wildebeest and no virus could be isolated from free-living pregnant wildebeest cows or from captive cows and their calves during the first 4 weeks after birth. The occurrence of wildebeest-derived malignant catarrhal fever (WD MCF) during spring, when wildebeest do not excrete virus, is a strong indication of the existence of an alternative host or an intermediate host capable of biological transfer of AHV-1.     

Immunoblotting analysis of the reaction of wildebeest, sheep and cattle sera with the structural antigens of alcelaphine herpesvirus-1 (malignant catarrhal fever virus)

Malignant catarrhal fever (MCF) is a disease of cattle and some other ruminants caused by alcelaphine herpesvirus-1 (AHV-1), a virus of wildebeest. The disease also occurs in the absence of wildebeest and is then thought to be caused by a viral agent harboured by the sheep. The structural proteins of AHV-1 have been used as antigens for the immunoblotting analysis of sera from wildebeest, sheep and cattle infected by either AHV-1 or the "sheep-associated" form of the disease. Wildebeest sera showed a uniform response reacting strongly with six polypeptides. Sheep sera also gave positive results but individual sera reacted with varying subsets of the antigens recognized by wildebeest. These results support the earlier suggestion that sheep harbour a herpesvirus related to AHV-1. A bovine serum from a case of MCF caused by AHV-1 also reacted only with a subset of the six wildebeest-reactive polypeptides. Sera from cattle affected with the "sheep-associated" form of the disease gave reactions in only two of the eight cases tested; both positive sera reacted to a few polypeptides only.     

Prevalence of antibodies to alcelaphine herpesvirus-1 and nucleic acid hybridization analysis of viruses isolated from captive exotic ruminants

A serologic survey was conducted to determine the prevalence of antibodies to alcelaphine herpesvirus-1 (AHV-1) in captive exotic ruminants within the United States. Forty-six percent of the members of the subfamily Alcelaphinae (wildebeest, topi, hartebeest) in the family Bovidae had virus-neutralizing antibody to AHV-1. Other subfamilies of Bovidae with high prevalence of virus-neutralizing antibodies to AHV-1 included Hippotraginae (oryx and addax) and Caprinae (sheep and goats), with prevalence of 45% and 29%, respectively. Herpesviruses that have been isolated from captive exotic ruminant species, including healthy animals and those with clinical malignant catarrhal fever at the Oklahoma City Zoo and the San Diego Zoo/Wild Animal Park, were analyzed by DNA restriction enzyme analysis and blot hybridization. Variation has been detected among the genomes of several malignant catarrhal fever virus isolates obtained from various exotic species of ruminants, using the DNA restriction enzymes BamHI and HindIII. The DNA of these virus isolates is distinct from that of bovine herpesviruses 1, 2, and 4, as demonstrated by restriction enzyme analysis and nucleic acid hybridization. On the basis of restriction enzyme analysis and nucleic acid hybridization data, the DNA from each of the putative alcelaphine herpesvirus isolates examined, except for the topi virus isolate, had a high degree of DNA sequence similarity with the original AHV-1 isolate, WC-11, from a blue wildebeest.     

Antibodies to malignant catarrhal fever virus antigens in the sera of normal and naturally infected cattle in Kenya

Six different serological tests were used to examine Kenyan cattle sera for antibodies to the herpesvirus of malignant catarrhal fever. Significantly higher levels of indirect immunofluorescent antibody to early and late virus antigens and of complement fixing antibody were found in the sera of 13 naturally infected cattle than in 482 sera collected from four different groups of normal cattle. Virus neutralising and immunoprecipitating antibodies were also found in some infected cattle sera but not in normal cattle sera. Many non-specific reactions occurred using counterimmunoelectrophoresis. These preliminary results indicate that the serological diagnosis of wildebeest-associated malignant catarrhal fever may be possible.     

Antibodies in carrier wildebeest to the lymphoproliferative herpesvirus of malignant catarrhal fever

Six types of antibody to malignant catarrhal fever virus (MCFV) were measured in 132 sera collected from Wildebeest in Kenya Masailand. The titre of all types of antibody declined slowly with increasing age of the wildebeest. A significantly greater proportion of wildebeest calves had higher titres of antibodies to MCFV early antigens, IgM antibodies to MCFV late antigens and complement-fixing antibodies, than did older animals. One seronegative calf, reared in isolation without colostrum, became seropositive 4 1/2 weeks after birth but did not show any clinical signs indicative of MCFV infection. Similarities between MCFV infection of wildebeest calves and other inapparent infections with lymphoproliferative herpesviruses are discussed.     

Antibody to alcelaphine herpesvirus-1 (AHV-1) in hamsters experimentally infected with AHV-1 and the 'sheep-associated' agent of malignant catarrhal fever

Malignant catarrhal fever was induced in four groups of hamsters by the inoculation of cells infected with either the C/500 isolate of alcelaphine herpes-virus-1 (AHV-1) or the sheep-associated agent derived from cattle, red deer or Père David's deer. Using an indirect immunofluorescence assay, antibody to AHV-1 was detected in sera of clinically affected animals of all four groups. The reaction of sera from hamsters affected with malignant catarrhal fever induced by AHV-1 caused diffuse cytoplasmic staining while that from sera of hamsters with the sheep-associated form of the disease stained particulate nuclear antigens. Tests employing three other bovid herpesviruses were negative and no reaction was found with sera from normal hamsters. These studies provide convincing evidence that a virus antigenically related to AHV-1 is the cause of sheep-associated malignant catarrhal fever and that the same virus probably causes this form of the disease in both cattle and deer.     

Shedding of malignant catarrhal fever virus by wildebeest calves

Malignant catarrhal fever virus (MCFV) was isolated from nasal and ocular secretions of wildebeest calves up to 3 months old. The virus was also isolated from explant cultures of cornea and nasal turbinates. It is suggested that MCFV replicates in the cornea and turbinates of young wildebeest calves less than 4 months old.MCFV was not isolated from secretions of calves older than 3 months, but virus neutralizing antibodies were found in their nasal secretions. The appearance of antibodies in the nasal secretions coincided with the cessation of virus shedding. The failure of calves over 3 months old to shed MCFV might explain the seasonal nature of bovine MCFV infection.     

Failure of sheep to respond to repeated inoculations with an alcelaphine herpesvirus-1-like virus, isolated from a case of malignant catarrhal fever in American cattle.

The replication of an alcelaphine herpesvirus-1-like virus (707K), isolated from a clinical case of malignant catarrhal fever in American cattle, was studied in sheep. Viraemia was not observed in any of the six sheep repeatedly inoculated with the 707K virus or in four steers susceptible to malignant catarrhal fever which were housed together with these sheep for one year. None of the four steers seroconverted and only two of the six inoculated sheep showed a negligible and short-lived seroconversion. The inability of the sheep to seroconvert adequately after repeated inoculations with the 707K virus, and the failure to recover the agent from them suggests that this agent does not replicate in sheep.