41 research outputs found

    Herd-level animal management factors associated with the occurrence of bovine neonatal pancytopenia in calves in a multicountry study

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    Since 2007, mortality associated with a previously unreported haemorrhagic disease has been observed in young calves in several European countries. The syndrome, which has been named ‘bovine neonatal pancytopenia’ (BNP), is characterised by thrombocytopenia, leukocytopenia and a panmyelophthisis. A herd-level case-control study was conducted in four BNP affected countries (Belgium, France, Germany and the Netherlands) to identify herd management risk factors for BNP occurrence. Data were collected using structured face-to-face and telephone interviews of farm managers and their local veterinarians. In total, 363 case farms and 887 control farms were included in a matched multivariable conditional logistic regression analysis. Case-control status was strongly associated with the odds of herd level use of the vaccine PregSure® BVD (PregSure, Pfizer Animal Health) (matched adjusted odds ratio (OR) 107.2; 95% CI: 41.0–280.1). This was also the case for the practices of feeding calves colostrum from the calf’s own dam (OR 2.0; 95% CI: 1.1–3.4) or feeding pooled colostrum (OR 4.1; 95% CI: 1.9–8.8). Given that the study had relatively high statistical power and represented a variety of cattle production and husbandry systems, it can be concluded with some confidence that no other herd level management factors are competent causes for a sufficient cause of BNP occurrence on herd level. It is suggested that genetic characteristics of the dams and BNP calves should be the focus of further investigations aimed at identifying the currently missing component causes that together with PregSure vaccination and colostrum feeding represent a sufficient cause for occurrence of BNP in calves

    Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium

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    BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18. METHODS: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity. FINDINGS: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%-73% for 28 years until 2010-18, when it increased to 87% (95% CI 82·1-90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8-96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5-87·0] and 85·4% [71·8-92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56-3·72; p\u3c0·0001), age 3·5 months or older at HCT (2·12, 1·38-3·24; p=0·001), Black or African-American race (2·33, 1·56-3·46; p\u3c0·0001), and certain SCID genotypes to be associated with lower overall survival during all time intervals. Moreover, after adjusting for several factors in this multivariable analysis, HCT after 2010 no longer conveyed a survival advantage over earlier time intervals studied (HR 0·73, 95% CI 0·43-1·26; p=0·097). This indicated that younger age and freedom from infections at HCT, both directly driven by newborn screening, were the main drivers for recent improvement in overall survival. INTERPRETATION: Population-based newborn screening has facilitated the identification of infants with SCID early in life, in turn leading to prompt HCT while avoiding infections. Public health programmes worldwide can benefit from this definitive demonstration of the value of newborn screening for SCID. FUNDING: National Institute of Allergy and Infectious Diseases, Office of Rare Diseases Research, and National Center for Advancing Translational Sciences
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