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Daily milk production and reproductive performance of cows vaccinated with a live double-deleted Bovine Viral Diarrhoea Virus (BVDV) vaccine were compared to those of non-vaccinated cows, cohabitating in endemic BVDV herds. All animals in the treatment group were vaccinated on study day 0 irrespective of lactation or gestation status, while control animals did not receive any treatment. 1463 animals were enrolled in the study from four different farms in three different countries (UK, Italy, France). Endemic presence of BVDV in study herds was demonstrated by the detection of BVDV in the bulk tank milk, and seroconversion was evaluated at the beginning of the study. For individual animals, the day of calving was taken to be the start of lactation for the calculation of days in milk (DIM). The standard lactation period of 305 days was divided into three periods: early lactation (EL, from DIM 8 to DIM 102), mid lactation (ML, from DIM 103 to DIM 204 and late lactation (LL, from DIM 205 to DIM 305). For each farm and each lactation period, a mixed model statistical analysis was performed with daily milk production as response, and group, day as well as the interaction between those two factors as fixed factors. Chi-square test was used to compare abortion rate and prolonged inter-oestrous interval rate between treatment and control groups. A significant increase in milk production in the vaccinated group was observed in farms 1 (1.023 L/day) and 3 (0.611 L/day) during EL (p<0.001) and in farm 2 (1.799 L/day) during ML (P<0.001). In addition, at farm 2, vaccinated cows produced more milk than non-vaccinated cows starting from 80 DIM. No differences were found between groups in abortion rates or prolonged inter-oestrous interval rates. Data demonstrate that cows in herds endemically infected with BVDV and vaccinated with live double-deleted BVDV vaccine produce more milk; the difference in milk production occurs during early lactation., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Lucy Metcalfe and Christian Guidarini are both employees of Boehringer Ingelheim Vetmedica GmbH. The funder provided support in form of salaries for 2 of the authors (CG and LM) and in sponsoring of the study, but this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Paratuberculosis, a chronic disease affecting ruminant livestock, is caused by Mycobacterium avium subsp. paratuberculosis (MAP). It has direct and indirect economic costs, impacts animal welfare and arouses public health concerns. In a survey of 48 countries we found paratuberculosis to be very common in livestock. In about half the countries more than 20% of herds and flocks were infected with MAP. Most countries had large ruminant populations (millions), several types of farmed ruminants, multiple husbandry systems and tens of thousands of individual farms, creating challenges for disease control. In addition, numerous species of free-living wildlife were infected. Paratuberculosis was notifiable in most countries, but formal control programs were present in only 22 countries. Generally, these were the more highly developed countries with advanced veterinary services. Of the countries without a formal control program for paratuberculosis, 76% were in South and Central America, Asia and Africa while 20% were in Europe. Control programs were justified most commonly on animal health grounds, but protecting market access and public health were other factors. Prevalence reduction was the major objective in most countries, but Norway and Sweden aimed to eradicate the disease, so surveillance and response were their major objectives. Government funding was involved in about two thirds of countries, but operations tended to be funded by farmers and their organizations and not by government alone. The majority of countries (60%) had voluntary control programs. Generally, programs were supported by incentives for joining, financial compensation and/or penalties for non-participation. Performance indicators, structure, leadership, practices and tools used in control programs are also presented. Securing funding for long-term control activities was a widespread problem. Control programs were reported to be successful in 16 (73%) of the 22 countries. Recommendations are made for future control programs, including a primary goal of establishing an international code for paratuberculosis, leading to universal acknowledgment of the principles and methods of control in relation to endemic and transboundary disease. An holistic approach across all ruminant livestock industries and long-term commitment is required for control of paratuberculosis.

Johne's disease (JD), is a fatal enteritis of animals caused by infection with Mycobacterium avium subspecies paratuberculosis (Map). Diagnosis of subclinical JD is problematic as test sensitivity is limited. Th1 responses to Map are activated early, thus detection of a cell-mediated response, indicated by measuring interferon gamma (IFN-γ) stimulated by mycobacterial antigens, may give the first indication of sub-clinical infection. Crude extracts of Map (PPDJ) have been used to detect the cell-mediated response in infected cattle. More specific, quantifiable antigens may improve test specificity and reproducibility. Map-specific proteins, MAP&#95;3651c and MAP&#95;0268c, raised a cell-mediated immune response in sub-clinically infected sheep. Results presented in this manuscript demonstrate these proteins elicit a cell-mediated response in experimental and natural infections of cattle. Individual ranked IFN-γ responses of experimentally infected calves to PPDJ showed a high, statistically significant association with ranked responses of recombinant Map antigens. Responses of infected animals were higher than the control group. Threshold values determined using data from an experimental infection were applied to naturally infected animals. Some animals exhibited responses above these threshold values. Responses to MAP&#95;3651c on a farm categorised as high-risk for JD showed strong evidence (P<0.001) that responses were significantly different to lower-risk farms. The IGRA test may prove to be an additional tool for the diagnosis of JD, and inclusion of specific antigens a refinement however, understanding and interpretation of IGRA results remain challenging and further investigation will be required to determine whether the IGRA test can detect exposure and hence predict clinical JD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)