Malignant catarrhal fever (MCF) is a fatal lymphoproliferative condition affecting ruminants, including at least 13 species of deer, and may present as a peracute to chronic illness (Foyle et al. 2009; Li et al. 2014; Russell et al. 2009). In deer, the disease tends to be acute or peracute, with animals succumbing before the development of more florid lesions, which are characteristic of protracted cases. Features of this enigmatic disease remain poorly understood, although the application of molecular biological methodologies is now shedding new light on the subject (reviewed in Bianchessi et al. 2022).

MCF as a disease was recognised in Europe over 80 years ago as a generally fatal, dramatic, clinical and pathological disease of cattle following contact with sheep. Shortly afterwards the condition was described in Africa, although the wildebeest-associated form of the disease there was distinct from the sheep-associated form (Russell et al. 2009). Some 30 years later, the devastating effect of MCF on Père David’s deer was reported, although it was not until interest in the farming of deer developed that the marked susceptibility of other species of deer was realised.

MCF is caused by herpesviruses of the genus Macavirus, subfamily gammaherpesvirus, of which the best known are Alcelaphine herpesvirus 1 (AlHV-1), which normally infects wildebeest (Connochaetes spp.) without causing clinical disease but causes wildebeest-associated MCF on transmission to susceptible species, and ovine herpesvirus 2 (OvHV-2) the agent of sheep-associated MCF. Within deer species, OvHV-2 appears to be responsible for most cases, while multiple reports have also identified caprine herpesvirus 2 (CpHV-2, with goats as the reservoir host) as a potential cause of MCF in deer (Frolich et al. 1998; Keel et al. 2003; Vikoren et al. 2006; Zhu et al. 2018).

An additional virus associated with MCF in white-tailed deer has also been characterised by limited sequencing (MCFV-WTD; Li et al. 2000). This virus resembles other Macaviruses and was also detected in goats, leading to speculation that goats could be the reservoir species (Li et al. 2005).

Of the MCF viruses, only AlHV-1 can be propagated in culture and has therefore been the subject of significant research efforts, while OvHV-2, the most widespread of the MCF viruses, has also been studied in some detail (reviewed in Gong et al. 2023; Li et al. 2014; Russell et al. 2009). The remaining MCF viruses have generally been characterised on the basis of MCF-like clinical and pathological signs and the detection of antigenic or sequence similarity in serum or tissues from affected animals.

MCF viruses, like all herpesviruses, are fragile, enveloped DNA viruses that characteristically infect most individuals of their natural host species without obvious clinical signs. However, rare cases of MCF-like signs associated with OvHV-2 infection have been reported in sheep (Pesavento et al. 2019) and goats (Makoni et al. 2024). In addition, ulcerative balanitis and vulvitis have been associated with the presence of OvHV-2 (detected in peripheral blood samples) in some affected sheep (Pritchard et al. 2008).

Within natural hosts infection normally occurs within three to six months of birth, and the virus establishes latent infection in lymphoid cells. Infection is established for life, although infectious virus is only shed periodically, possibly following stress or immunosuppression. MCF in susceptible hosts has been observed to show some seasonality and can be associated with calving/lambing in the natural hosts, possibly as a result of increased virus shedding during this period.

When the virus is transmitted to animals susceptible to MCF, only limited viral replication occurs and the virus remains in a strictly cell-associated form. In vivo spread and MCF pathogenesis appear to be due to the expansion and infiltration of these infected lymphocytes in multiple tissues (Gong et al. 2023). The lack of shedding of infectious virus means that no further transmission occurs and affected animals may be regarded as truly dead-end hosts. The generally fatal nature of MCF in susceptible species, together with the rapid clinical course (especially in deer), means that seropositivity in susceptible species is generally restricted to MCF-affected individuals that survive for several weeks.

Typically, affected animals are first seen as inappetent, standing away from the herd, with rectal temperatures above 40 °C. In some, dysentery rapidly develops and death can occur within 12 hours of first signs. In other cases, mainly in less susceptible species, the disease can run a longer course of two to four weeks: peripheral lymph nodes are enlarged, while ocular and nasal secretions initially serous become mucopurulent; and bilateral corneal opacity characteristically affects the periphery initially before spreading centripetally. Erosions of the buccal cavity, particularly of the tips of the papillae, and ulceration of the skin, especially the perineum, may be present. Although cattle may occasionally recover, death would appear to be the inevitable outcome for affected deer. A range of presentations has been reported in deer, including acute, with potentially haemorrhagic diarrhoea; a head and eye form similar to cattle; also a cutaneous form, featuring skin lesions (Foyle et al. 2009; Keel et al. 2003; Li et al. 2000).

At postmortem examination, the lesions reflect the nature of the clinical response, including hyperplasia of lymphoid organs and accumulation of lymphoid cells in many non-lymphoid tissues resulting in grossly visible small, white, multifocal lesions most easily seen on the surfaces of the kidneys, epithelial and lymphoid degeneration, with vasculitis affecting a variety of tissues. The organs and structures that show the most specific changes are the kidney, brain, cornea and epithelial surfaces such as the buccal cavity, urinary bladder and turbinates.

Presumptive diagnoses of the more florid cases may be reached on clinical and postmortem findings, although in general, particularly when the disease is peracute (given that there may be limited macroscopic/gross changes), laboratory confirmation is necessary. The finding of characteristic histopathological lesions has, in the past, been the basis for formal diagnosis of MCF. Examination of multiple cases of MCF in cattle, bison and buffalo revealed vasculitis caused by vascular and perivascular lymphoid cell infiltration and accumulations, respectively, in all cases (Saura et al. 2021).

MCF viruses spread very efficiently amongst their natural hosts, all individuals apparently becoming infected by three to six months of age. Some animals appear to become infected in utero, close to parturition, while most others become infected before six months of age (Lankester et al. 2015). Shedding of the virus by infected wildebeest calves or lambs, also sporadically by adults, is the likely source of infection for MCF-susceptible animals. Infectious virus is probably shed primarily in droplets and aerosols.

Stay updated, free articles. Join our Telegram channel

Join