Calf-Level Factors Associated with Bovine Neonatal Pancytopenia – A Multi-Country Case-Control Study

Abstract

Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A multi-country matched case-control study was conducted in 2011 to identify calf-level risk factors for BNP. 405 BNP cases were recruited from 330 farms in Belgium, France, Germany and the Netherlands by laboratory confirmation of farmer-reported cases. Up to four calves of similar age from the same farm were selected as controls (1154 calves). Risk factor data were collected by questionnaire. Multivariable modelling using conditional logistic regression indicated that PregSure®BVD (PregSure, Pfizer Animal Health) vaccination of the dam was strongly associated with BNP cases (adjusted matched Odds Ratio - amOR 17.8 first lactation dams; 95% confidence interval – ci 2.4, 134.4; p = 0.005), and second or more lactation PregSure-vaccinated dams were more likely to have a case than first lactation vaccinated dams (amOR 2.2 second lactation; ci 1.1, 4.3; p = 0.024; amOR 5.3 third or more lactation; ci 2.9, 9.8; p = <0.001). Feeding colostrum from other cows was strongly associated with BNP if the dam was not PregSure-vaccinated (amOR 30.5; ci 2.1, 440.5; p = 0.012), but the effect was less if the dam was PregSure-vaccinated (amOR 2.1; ci 1.1, 4.0; p = 0.024). Feeding exclusively dam’s milk was a higher risk than other types of milk (amOR 3.4; ci 1.6, 7.5; p = 0.002). The population attributable fractions were 0.84 (ci 0.68, 0.92) for PregSure vaccination, 0.13 (ci 0.06, 0.19) for feeding other cows’ colostrum, and 0.15 (ci 0.08, 0.22) for feeding dam’s milk. No other calf-level factors were identified, suggesting that there are other important factors that are outside the scope of this study, such as genetics, which explain why BNP develops in some PregSure-colostrum-exposed calves but not in others.

Explanation and Elaboration Document for the STROBE‐Vet Statement: Strengthening the Reporting of Observational Studies in Epidemiology—Veterinary Extension

“…The following Pfizer personnel were observers during the study: Jeremy Salt, Michael Pearce, Tony Simon and Marie‐Odile Hendrickx. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, except attendance at project coordination meetings as observers, and commenting on the draft manuscript.119 …”

The risks of using allogeneic cell lines for vaccine production: the example of Bovine Neonatal Pancytopenia

“…Thus these factors will contribute to variability in the likelihood of a calf developing BNP and the extent of alloantibody-induced pathology ( Figure 2) [26].…”

“…Epidemiological studies demonstrated a significant association between BNP and the administration of a specific vaccine (Pregsure© BVD, Pfizer Animal Health) to the mothers of affected calves [26][27][28] and showed that the incidence of BNP was higher in herds that received multiple doses of the vaccine [10]. It was also notable that those European countries that remained free from BNP prohibited the use of this and all other BVD vaccines, due to alternative disease control policies.…”

“…However the alloantibody specificity remains remarkably similar at subsequent pregnancies [11], indicating that the fetus appears only to be boosting existing Pregsure©-induced alloantibodies, rather than stimulating novel alloantibodies. Whether other cattle vaccines, many of which are also produced using MDBK cells, play a role in maintaining or boosting existing BNP alloantibodies has not yet been thoroughly investigated, but vaccines other than Pregsure© have not been identified as risk factors for the occurrence of BNP [26,28].…”

“…Nevertheless, the production of many vaccines requires the use of allogeneic cell lines and, because complete purification to remove all residual cell-line contamination is difficult and costly, this raises the possibility of similar problems occurring with other vaccines. Very low alloantibody titers have been detected in cows and guinea pigs vaccinated with alternative BVD vaccines [8,19] and it could be speculated that such responses might play a role in BNP-like cases that cannot be linked to Pregsure© [26,[41][42][43].…”