Download LECTUER-4 INFECTIOUS DISEASES Week No: 2 L. Dr. Yahia I

October 11,
LECTUER-4
INFECTIOUS DISEASES Week
2016
No: 2
L. Dr. Yahia I. Khudair
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Malignant catarrhal fever (MCF):
Definition: Malignant catarrhal fever is an infectious disease of ruminants. It is also referred to as
malignant catarrh, malignant head catarrh, gangrenous coryza, and catarrhal fever; it is an acute,
sporadic, infectious disease of cattle and some other bovidae and cervidae characterized by low
morbidity and extremely high mortality
Etiology:
Malignant catarrhal fever (MCF) is really two diseases, clinically and pathologically
indistinguishable, but associated with two different infectious agents with different ecologies:
1-
Alcelaphine herpesvirus-1 (AHV-l) in the genus Rhadinovirus of the subfamily
Gammaherpesvirinae. This is the wildebeest-associated MCF virus, transmitted to cattle from blue
wildebeest (Connochaetes taurinus) "
2-
A virus designated ovine herpesvirus-2 (OvHV-2) also a Rhadinovirus of the subfamily
Gammaherpesvirinae. This is the sheep-associated MCF virus transmitted to cattle from sheep. Has
not been isolated, it occurs worldwide in both wild and domestic sheep and goat without causes
disease.
Epidemiology
Occurrence and prevalence
Alcelaphine MCF Wildebeest- associated MCF occurs in most African countries in cattle which
commingle with clinically normal wildebeest and hartebeest. It is epizootic and seasonal.
Sheep associated MCF occurs worldwide. Cases mostly occur when cattle have had contact with
lambing ewes and usually start 1-2 months later. 4-6 Goats can also act as a source of OvHV-2
infection for cattle.
The morbidity rate varies. Usually the disease is sporadic and presents as a single or small number
of cases over a short period but on occasion up to 50% of a herd may be affected in rare but
devastating outbreaks which may be short lived or last for several months.8,9 The disease with both
agents is almost invariably fatal
Methods of transmission
Alcelaphine MCF Infection with AHV-l in wildebeest occurs in the perinatal period by horizontal
and occasional intrauterine transmission, and infected young wildebeest up to the age of about 4
months have viremia and shed virus in ocular and nasal secretions. The disease is transmitted from
wildebeest to cattle by contact or over short distances, by inhalation of aerosol or ingestion of
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October 11,
LECTUER-4
INFECTIOUS DISEASES Week
2016
No: 2
L. Dr. Yahia I. Khudair
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pasture contaminated by virus excreted by young wildebeest in nasal and ocular discharges. In
contrast, infected cattle do not excrete virus in nasal or ocular secretions.
Sheep associated MCF
All domestic sheep raised under natural flock conditions are infected with OvHV-2. the
transmission of OvHV-2 between sheep appears minimal in the perinatal period. There is no
evidence for transplacental, the majority of lambs are not infected until after 2-3 months of age. The
common epidemiological association of diseased cattle having had contact with lambing ewes
suggests that perinatal lambs play a role in transmission similar to that played by wildebeest calves,
however the age at infection of lambs and the excretion patterns of virus do not fit this assumption.
Shedding from ewes does not increase in the lambing period.
Amongst domestic animals, all ages, races and breeds of cattle are equally susceptible but banteng
(Banteng sondaicus), buffalo (Bubalus bubalis), bison (Bison bison) and deer are more susceptible
and suffer a more severe form of the disease than commercial cattle. Sheep-associated MCF virus
does not replicate in tissue culture. It has a close association with lymphoblastoid cells, particularly
large granular lymphocytes, which can be grown in tissue culture, MCF is considered one of the
most important diseases of farmed deer.
PATHOGENESIS
MCF is a fatal, multisystemic disease characterized by lymphoid proliferation and infiltration, and
widespread vascular epithelial and mesothelial lesions, which are morphologically associated with
lymphoid cells. CD8+ T- lymphocytes are the predominant cells associated with the vascular
lesions. Involvement of the vascular adventitia accounts for the development of gross lesions,
including the epithelial erosions and keratoconjunctivitis. The lymph node enlargement is due to
atypical proliferation of sinusoidal cells and the cerebromeningeal changes usually referred to as
encephalitis. There is commonly a synovitis, especially involving tibiotarsal joints and this also is
associated with a lymphoid vasculitis. It is believed that the pathogenesis of this disease is the result
of direct virus-cell interactions or perhaps immune-mediated responses directed against infected
cells
The incubation period varies from 3-8 weeks. MCF is described as occurring in a number of forms:
1. Peracute
2. Alimentary tract form
3. Common 'head and eye' form
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October 11,
LECTUER-4
INFECTIOUS DISEASES Week
2016
No: 2
L. Dr. Yahia I. Khudair
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4. Mild form, but these are all gradations, cases being classified on the predominant clinical signs.
In serial transmissions with one strain of the virus all of these forms may be produced. The most
common manifestation is the head and eye

Head and eye form

There is a sudden onset of the following symptoms:

Extreme dejection

Anorexia

Agalactia

High fever (41-41.5C)

Rapid pulse rate (100-120/bpm)

Profuse mucopurulent nasal discharge

Severe dyspnea with stertor due to obstruction of the nasal cavities with exudate

Ocular discharge with variable degrees of edema of the eyelids and blepharospasm

Congestion of scleral vessels.

Superficial necrosis is evident in the anterior nasal mucosa and on the buccal mucosa. This
begins as a diffuse reddening of the mucosa, and is a consistent finding about day 19 or 20
after infection. Discrete local areas of necrosis appear on the hard palate, gums and
gingivae. The mouth is painful at this time and the animal moves its jaws carefully,
painfully and with a smacking sound. The mucosa as a whole is fragile and splits easily. The
erosive mucosal lesions may be localized or diffuse. They may occur on the: hard palate,
dorsum of the tongue, gums below the incisors commissures of the mouth inside the lips.
The cheek papillae inside the mouth are hemorrhagic, especially at the tips which are later
eroded.

There is excessive salivation with saliva which is ropy and bubbly hanging from the lips.

The skin of the muzzle is extensively involved, commencing with discrete patches of
necrosis at the nostrils to be covered by tenacious scabs. Similar lesions may occur at the
skin-horn junction of the feet, especially at the back of the pastern. The skin of the teats,
vulva and scrotum in acute cases may slough off entirely upon touch or become covered
with dry.

Nervous signs, particularly weakness in one leg, incoordination, a demented appearance and
muscle tremor may develop very early, and nystagmus, head-pushing, paralysis and
convulsions may occur in the final stages.
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October 11,
LECTUER-4
INFECTIOUS DISEASES Week
2016
No: 2
L. Dr. Yahia I. Khudair
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
In natural cases the superficial lymph nodes are often visibly and usually palpably enlarged.
Lymphadenopathy is also one of the earliest.

The consistency of the feces varies, dysentery in some cases there is gross hematuria with
the red coloration most marked at the end of urination.

Opacity of the cornea is always present to some degree, commencing as a narrow, gray ring
at the corneoscleral junction and spreading centripetally with conjunctival and episcleral
hyperemia.

In cases of longer duration, skin changes, including local papule formation with clumping of
the hair into tufts over the loins and withers, may occur. In addition, eczematous weeping
may result in crust formation, particularly on the perineum, around the prepuce, in the
axillae and inside the thighs. Infection of the cranial sinuses may occur with pain on
percussion over the area. The horns and rarely the hooves may be shed.

Persistence of the fever is a characteristic of MCF, even cases that persist for several weeks
with a fluctuating temperature, usually exceeding 39SC.

In the more typical cases the illness lasts for 3-7 days and rarely up to 14 d.
Peracute and alimentary tract forms

In the peracute form the disease runs a short course of 1-3 d and characteristic signs and
lesions of the 'head and eye' form do not appear. There is usually a high fever, dyspnea and
an acute gastroenteritis.

The alimentally tract form resembles the 'head and eye' form, except that there is marked
diarrhea and only minor eye changes consisting of conjunctivitis rather than ophthalmia.
This form of the disease has been encountered in outbreak form in cattle in large dairy herds
in drylots, with only indirect contact with sheep, and in cattle to which transmission was
attempted and fanned deer. A feature of this form of the disease is reported to be a brief
period of slight illness followed by the final fulminating disease which is common in deer.
Mild form

The mild form occurs most commonly in experimental animals but is observed in natural
outbreaks. There is a transient fever and mild erosions appear on the oral and nasal mucosae.
Mild disease may be followed by complete recovery, recovery with recrudescence or
chronic MCF. A

distinctive clinical feature in chronic MCF is persistent bilateral ocular leukomata 26
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October 11,
LECTUER-4
INFECTIOUS DISEASES Week
2016
No: 2
L. Dr. Yahia I. Khudair
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CLINICAL PATHOLOGY

A leukopenia, commencing at first illness and progressing to a level of 3000-6000/pL,
observation the leukopenia recorded was due mainly to an agranulocytosis.

Virus isolation is not practical with either virus because of the instability of cell- associated
AHV- 1 and the fact that OHV-2 does not replicate in cell culture.

Transmission can be used for diagnosis using whole blood, nasal swabs or washings and
preferably lymph node collected by biopsy, with histological lesions in the recipient rabbits
or calves. Detection of viral nucleic acid by PCR has largely replaced transmission
experiments.

A competitive-inhibition ELISA using a monoclonal antibody to a broadly conserved
epitope of the MCF virus can be used for detection of antibody and has largely replaced
other serological tests. It is of particular value for epidemiological studies.

Detection of viral nucleic acid by PCR techniques
NECROPSY FINDINGS
Lesions in the mouth, nasal cavities and pharynx vary from minor degrees of hemorrhage and
erythema, through extensive, severe inflammation to discrete ulcers. These lesions may be shallow
and almost imperceptible or deeper and covered by cheesy diphtheritic deposits. Erosion of the tips
of the cheek papillae, especially at the commissures, is common. Longitudinal, shallow erosions are
present in the esophagus. The mucosa of the fore stomachs may exhibit erythema, or sparse
hemorrhages or erosions. Similar but more extensive lesions occur in the abomasum. Catarrhal
enteritis of moderate degree and swelling and, ulceration of the Peyer's patches are constant. The
feces may be loose and blood stained. Similar lesions to those in the mouth and sometimes in the
bronchi but the lungs are not usually involved except for occasional emphysema or secondary
pneumonia.
The liver is swollen and severe hemorrhage may be visible in the urinary bladder: All lymph nodes
are swollen, edematous and often hemorrhagic. Petechial hemorrhages and congestion may be
visible in brain and meninges.
Histologically,

MCF is characterized by perivascular, mononuclear cell cuffing in most organs and by
degeneration and erosion of affected epithelium. The pathognomonic lesion is a necrotizing
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October 11,
LECTUER-4
INFECTIOUS DISEASES Week
2016
No: 2
L. Dr. Yahia I. Khudair
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vasculitis which features infiltration of the tunica media and adventitia by lymphoblast-like
cells and macrophages.

Acidophilic, intracytoplasmic inclusion bodies in neurons have been described but their
identity as viral inclusions has not been established.

Large numbers of inclusion bodies have been observed in the tissue of artificially infected
rabbits.

The histologic features of the panophthalmitis have been described cattle with chronic MCF
have chronic bilateral central stromal keratitis with or without corneal pigmentation. An
obliterative arteriopathy is characteristic and this vascular lesion is present in all major
organs Results of a competitive inhibition ELISA serologic test suggesting a role for the
virus in the development of

obliterative arterial lesions in cattle have been supported by in situ PCR and
immunohistochemical studies of the disease in bison which demonstrated OHV-2 within the
infiltrating lymphocytes. These lymphoblast-like cells were also shown to be CDS (+) Tcells.

A PCR technique or immunohistochemical stains can be used to confirm the presence of
viral antigen in whole blood or in tissues harvested at necropsy. When transmitted to rabbits,
both the wildebeest and sheep-associated viruses elicit a rapidly fatal lymphoproliferative
disorder. The newer molecular biology-based techniques have made this bioassay method
obsolete.

Samples for confirmation of diagnosis Histology - fixed brain, lymph node, alimentary tract
mucosa including pharynx, esophagus, rumen and Peyer's patch, liver, adrenal gland,
kidney, urinary bladder, salivary gland (IHC, LM); Bouin's-fixed eye (LM)

Virology - lymph node, spleen, lung.
Differential diagnosis
• Mucosal disease
• Infectious bovine rhinotracheitis
• Sporadic bovine encephalomyelitis
• Rinderpest
• Jembrana disease.
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October 11,
LECTUER-4
INFECTIOUS DISEASES Week
2016
No: 2
L. Dr. Yahia I. Khudair
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TREATMENT
Treatment of affected animals is unlikely to influence the course of the disease.
Non-steroidal anti-inflammatories may ease the discomfort.
CONTROL

Isolation of affected cattle is usually recommended but its value is questioned because of the
slow rate of spread and the uncertainty regarding the mode of transmission.

Because of the field observation that sheep are important in the spread of the disease,
separation of cattle and sheep herds is recommended.

The introduction of sheep from areas where the disease has occurred to farms with cattle
should be avoided.

A program to produce sheep free of OVHV-2 infection by separation and isolation of lambs
before they become infected is recommended for sheep used

Attempts to immunize cattle with an inactivated wildebeest-associated MCF virus vaccine
have provided protection against challenge with virulent viruses.
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