Malignant catarrhal fever

Malignant catarrhal fever (MCF) is an infectious systemic disease that presents as a variable complex of lesions affecting mainly ruminants and rarely swine. It is principally a disease of domestic cattle, water buffalo, Bali cattle (banteng), American bison, and deer. In addition to these farmed animals, MCF has been described in a variety of captive ruminants in mixed zoologic collections.MCF results from infection by one of several members of a group of closely related ruminant gammaherpesviruses of the Rhadinovirus genus.

1. Malignant Catarrhal Fever Malignant Catarrh, Malignant Head Catarrh, Gangrenous Coryza , Catarrhal Fever, Snotsiekte

2. S poradic F atal P ansystemic Low morbidity High mortality Infectious high fever catarrhal inflammation of the upper respiratory tract and the digestive tract dehydration, conjunctivitis, generalized lymphadenopathy and epithelial lesions

3. Wildebeest MCF -African continent for many centuries. In the United States there have been reports of a disease resembling Malignant catarrhal fever since the 1920’s ( South Dakota) The first bison case in the US was reported in 1973. Now cases are reported worldwide in many species especially in zoos or wildlife theme parks. For this reason many zoos no longer keep wildebeest

4. ETIOLOGY Family Herpesviridae Subfamily Gammaherpesvirinae Genus Rhadinovirus  Macavirus

5. ETIOLOGY Wildebeest-derived Occurs wherever wildebeest live Alcelaphine herpesvirus-1 (AHV-1). AHV-2 non pathogenic Sheep-associated Endemic, worldwide; sheep and goat are the natural reservoir host Ovine herpesvirus-2 (OVH-2). Goat-derived Goats are the natural reservoir host. Caprine herpesvirus-2 (CpHV-2) Seen in deer as alopecia, weight loss syndrome All are Lymphotropic Cell-associated Gamma family herpesviruses

6. All varieties of domestic sheep in North America are carriers of ovine herpesvirus-2 (OVH-2). Malignant Catarrhal fever in these natural hosts does not produce clinical disease. Likewise, goats are endemically infected with caprine herpesvirus-2 (CpHV-2) which apparently only causes clinical disease in deer The disease expression in “sheep-associated” MCF and “wildebeest-derived” MCF is very similar .

7. HOST RANGE The disease can occur in cattle domesticated buffaloes, wide range of captive antelopes free-living deer.

8. HOST RANGE Under natural conditions only domestic cattle and deer develop clinical signs MCF has never been reported in free-living wild animals in Africa In zoological collections a wide variety of ruminant species have been reported to develop clinical signs Rabbits can be infected experimentally It was recently confirmed in pigs in Scandinavia

9. Reservoir ruminant species Blue wildebeest Black wildebeest Domestic sheep Goats

10. Blue Wildebeest Black Wildebeest

11. Morbidity/Mortality Carrier species asymptomatic Wildebeest, hartebeest, topi , sheep , goats Low morbidity in other species U.S. outbreaks 30 to 40% < 1% in water buffalo, deer Mortality 100% Domestic cattle, white-tail, axis , Pere David’s deer

12. TRANSMISSION Neonatal and adolescent wildebeest shed the virus

13. Transmission from reservoir animals to domestic cattle, deer Primarily the virus is cell associated. Cell-free virus is shed in nasal secretions by neonatal and adolescent sheep. Neonatal wildebeest may shed cell-free virus in lacrimal and nasal secretions and in feces up to 4 months of age. contact with calving wildebeest contact with lambing sheep

14. Cattle are more susceptible to Wildebeest derived MCF than to the sheep or goat MCF

15. Transmission of the virus is associated with lambing time of sheep or calving season of wildebeest when the virus can be shed from nasal secretions. After this period the virus occurs only as cell-associated, not free virus Droplets and aerosol dispersal of free virus may contaminate feed and water sources Transmission to cattle mostly occurs by inhalation of droplets shed from ewes that are lambing Cattle to cattle transmission does not happen

16. Congenital Transmission Because the virus is usually intracellular there is no cow to cow transmission. Cattle are considered the dead end host . Cow will die then later calf

17. AHV-1 Wildebeest calves In utero Contact with nasal and ocular secretions Aerosols during close contact Adult wildebeest Cell-associated form Rarely transmitted OHV-2 Respiratory (aerosol) Transplacental rare Contact with nasal secretions Animal-to-animal rare Dead end hosts

18. The MCF-susceptible species are thought to be dead-end hosts that do not shed virus and are therefore not infectious

19. PATHOGENESIS MCF is a fatal, multisystemic disease characterize 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 a result of atypical proliferation of sinusoidal cells. The cerebromeningeal changes , usually referred to as encephalitis , are in fact a form of vasculitis . There is commonly synovitis , especially involving tibiotarsal joints, and this also is associated with a lymphoid vasculitis . It is thought that the pathogenesis of this disease is the result of direct virus–cell interactions or perhaps immune-mediated responses directed against infected cells

20. Virus infects “natural killer” lymphocytes and transforms them. Transformed cells then replicate as if they were neoplastic and attack host . Terminal necrotizing lesions are believed to be the result of an autoimmune type phenomenon. Vessels and stratified squamous mucosal surfaces are attacked.

21. CLINICAL SIGNS The incubation period in natural infection varies from 3 to 8 weeks. Some animals are subclinically infected and only demonstrate symptoms when stressed. Experimentally incubation periods may be from 7 to 77 days Peracute Alimentary tract form Common “head-and-eye” form Mild form

22. HEAD AND EYE FORM Extreme dejection Anorexia Agalactia High fever (41° to 41.5° C [106–107° F]) Rapid pulse rate (100 to 120/bpm) Profuse mucopurulent nasal discharge Discrete local areas of necrosis appear on the hard palate, gums , and gingivae painful jaw smacking sound Severe dyspnea with stertor as a result of obstruction of the nasal cavities with exudate Ocular discharge with variable degrees Corneal edema Blepharospasm and uveitis Congestion of scleral vessels

23. CLINICAL SIGNS Depressed and VERY SICK Stertorous respiration Enlarged lymph nodes

24. CLINICAL SIGNS Breathing difficulty

25. CLINICAL SIGNS Ocular and nasal discharge

26. Malignant Catarrhal Fever “snotsiekte” CLINICAL SIGNS

27. Mucopurulent discharge, crusting occludes the nostril; animal begins open mouth breathing .

28. Progresses to total opacity Early corneal opacity begins at the limbus CHARATERISTIC OF MCF

29. SEVERE OCULAR LESIONS Painful Conjunctivitis

30. SEVERE OCULAR LESIONS Progresses to corneal opacity beginning at Limbus

31. SEVERE OCULAR LESIONS

32. ORAL LESIONS Erosions near the teeth

33. ORAL LESIONS Necrosis of papillae

34. Erosions of papillae ORAL LESIONS

35. Erosions in squamous (anterior) portion of nasal cavity

36. Enlarged and edematous lymph nodes

37. Moist necrotic dermatitis with exudation and encrustations Skin lesions associated with both sheep form and wildebeest derived .

38. In terminal stages CNS symptoms: falling, circling, head pressing, high stepping convulsions, then death

39. In case of persistent infection skin changes , including local papule formation with clumping of the hair into tufts over the loins and withers, may occur . crust formation, particularly on the perineum, around the prepuce , in the axillae, and on the inside of the thighs.

40. PERACUTE H igh fever, Dyspnea , A cute gastroenteritis . 1-3 days duration

41. ALIMENTARY TRACT FORM R esembles the head-and-eye form , except that there is marked diarrhea O nly minor eye changes consisting of conjunctivitis rather than ophthalmia

42. Mild diarrhea sometimes seen which is black and tarry, but not effusive

43. MILD FORM Transient fever , and mild erosions appear on the oral and nasal mucosae. Mild disease may be followed by complete recovery A distinctive clinical feature in chronic MCF is persistent bilateral ocular leukomata .

44. DIAGNOSIS Virus isolation is not practical with either virus because of the instability of cellassociated AlHV1 and the fact that OvHV2 does not replicate in cell culture . Transmission was taken as a criterion for the diagnosis Replaced by detection of viral antigen by PCR SEROLOGICAL TESTS Little value- antibody titer is low, and there is cross reaction with other herpes viruses . 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 serologic tests.

45. Development of antibody following infection is delayed in a significant proportion of young animals, and serology is unreliable for determining infection status until after 1 year of age. Uninfected lambs or kids under 4 months of age may test positive because of the presence of maternal antibody.

46. NECROPSY FINDINGS Erosions on the tongue and soft and hard palate

47. Necrotic areas in the omasal epithelium Multiple erosions of intestinal epithelium

48. Greatly enlarged lymph node compared to normal Necrotic areas in the larynx Diptheritic membrane often present

49. Urinary bladder mucosa hyperemic and edematous Kidney often has raised white foci on the cortex

50. Focally disseminated erosions and ulcerations in the GIT

51. “ button ulcers” 5-10 cm erosions

52. Frequently see erosions in the bladder mucosa

53. Multifocal lymphoid infiltration

54. Enlarged lymph nodes Tonsils bulge

55. HISTOPATHOLOGY T lymphocyte hyperplasia,cell necrosis Perivascular lymphoid infiltration

56. Perivascular lymphoid infiltration of arterioles

57. DIFFERENTIAL DIAGNOSIS Mucosal disease • Infectious bovine rhinotracheitis (IBR) • Bluetongue • Sporadic bovine encephalomyelitis • Rinderpest (included for historic reasons)

58. CLINICAL DIAGNOSIS Any susceptible animal with sudden death, fever, erosions of the mucosa, nasal/lacrimal discharge, or bilateral corneal opacity should be tested for MCF Particularly with a history of exposure to sheep, goats, antelope, or wildebeest during parturition

59. SAMPLES Histology— fixed brain, lymph node, alimentary tract mucosa including pharynx , esophagus, rumen and Peyer’s patch , liver, adrenal gland, kidney, urinary bladder, salivary gland Bouin’s -fixed eye ( light microscopy ) • Virology— lymph node, spleen, lung (PCR) Blood in EDTA tube for virus isolation Fresh tissue collected and refrigerated immediately after death Spleen, lung, lymp nodes , adrenal glands PCR on peripheral blood, fresh tissues, Paired serum samples

60. TREATMENT Survival is rare if clinically ill Mortality reaches 100% Supportive therapy, antibiotics for secondary bacterial infection Recovered animals will remain virus carriers

61. PREVENTION & CONTROL Separate infected and carrier animals from susceptible species Carriers: sheep and goats Keep cattle away, especially during parturition Zoological parks Introduce seronegative animals only No vaccine available