Etiology

• Ingestion of colostrum containing vaccine-induced maternal alloantibodies specific for major histocompatibility complex class I (MHC I). These alloantibodies are found in the colostrum from some cows vaccinated with a vaccine that contains residual cell-line material that generates alloantibodies specific for MHC I.
• Development of clinical signs in the calf depends on the dose of alloantibody consumed by the calf, which depends on the alloantibody titer of the cow. The genotype of the calf MHC I also determines if the individual calf develops the syndrome.
• Pregsure© BVD (Pfizer Animal Health) vaccine was identified as the cause of the initial outbreak of this syndrome which was first seen in 2006/2007. This vaccine was subsequently withdrawn from the market.

Predisposing factors

General

• Vaccination of the dam with a vaccine that contains residual cell-line material that generates alloantibodies to MHC I.
• Cow and calf MHC I genotype.

Specific

• Consumption of colostrum containing alloantibodies to MHC I by calves with a susceptible MHC I genotype. The MHC I genotype of the cow is not generally known so risk cannot be predicted.

Pathophysiology

• In some cows vaccinated with certain vaccines, alloreactive antibodies are produced that target the MHC I complex on bovine cells.
• These alloantibodies are passed from the cow to the calf in colostrum, and absorbed via the gut in the first 24-32 hours of life.
• The alloantibodies bind to white blood cells and platelets in the circulation, as well as to cells in the bone marrow.
• Platelets and white blood cells in the circulation are destroyed first, followed by destruction of the hematopoietic precursors in the bone marrow. This is demonstrated diagnostically by a thrombocytopenia and leukocytopenia on hematology, and replacement of hematopoietic tissue by abnormal tissue in the bone marrow on histology (panmyelophthisis/ trilineage hypoplasia).
• Circulating red blood cells are not damaged, but a normochromic, normocytic, nonregenerative Anemia Anemia: overview can develop in response to the loss of precursors in the bone marrow.

Timecourse

• A reduction in the number of circulating white blood cells and platelets can be seen as early as four hours after ingestion of colostrum containing alloantibodies.
• Most calves die within 24-48 h of the onset of clinical signs.

Epidemiology

• Affects neonatal calves, <4 weeks of age.
• Generally, has a low incidence with only a few cases reported per farm, occasional larger outbreaks may be seen with up to 5-10% of calves affected. Incidence is reported to be higher in herds that have received multiple doses of the vaccine.
• Dams which have had an affected calf will not necessarily have affected calves at their next calving.