Comparison of calf weaning weight and associated economic variables between beef cows with and without serum antibodies against or isolation from feces of Mycobacterium avium subsp paratuberculosis

OBJECTIVE—To compare calf weaning weight and associated economic variables for beef cows with serum antibodies against Mycobacterium avium subsp paratuberculosis (MAP) or from which MAP was isolated from feces with those for cows that were seronegative for antibodies against or culture negative for MAP. DESIGN—Retrospective study. ANIMALS—4,842 beef cows from 3 herds enrolled in the USDA National Johne’s Disease Demonstration Herd Project. PROCEDURES—Individual cow ELISA and culture results were obtained from the project database. During each parity evaluated for each cow, the 205-day adjusted weaning weight (AWW) of its calf was calculated. The AWW was compared between test-positive and testnegative cows by use of multilevel mixed-effect models. The median value for feeder calves from 2007 to 2011 was used to estimate the economic losses associated with MAP test– positive cows. RESULTS—The AWW of calves from cows with strongly positive ELISA results was 21.48 kg (47.26 lb) less than that of calves from cows with negative ELISA results. The AWW of calves from cows classified as heavy or moderate MAP shedders was 58.51 kg (128.72 lb) and 40.81 kg (89.78 lb) less, respectively, than that of calves from MAP culture–negative cows. Associated economic losses were estimated as $57.49/calf for cows with strongly positive ELISA results and$156.60/calf and $109.23/calf for cows classified as heavy and moderate MAP shedders, respectively. CONCLUSIONS AND CLINICAL RELEVANCE—Calves from cows with MAP-positive test results had significantly lower AWWs than did calves from cows with MAP-negative test results, which translated into economic losses for MAP-infected beef herds. (J Am Vet Med Assoc 2013;243:1609–1615)http://avmajournals.avma.org/loi/javmaam2014ab201

Perceptions of veterinarians in bovine practice and producers with beef cow-calf operations enrolled in the US voluntary bovine Johne's disease control program concerning economic losses associated with Johne's disease

This study compares the perceptions of producers and veterinarians on the economicimpacts of Mycobacterium avium subspecies paratuberculosis (MAP) infection in cow-calfherds. Questionnaires were mailed to beef producers through the Designated Johne’sCoordinators and to veterinarians belonging to a nationwide professional organization.Important components of losses associated with MAP infected cows were used to estimatetotal loss per infected cow-year using an iterative approach based on collected survey data.Veterinarians were more likely to perceive a lower calving percentage in MAP infectedcows compared to producers (P = 0.02). Income lost due to the presence of Johne’s disease(JD) in an infected cattle herd was perceived to be higher by veterinarians (P < 0.01). Com-pared to veterinarians without JD certification, seedstock producers were more likely toperceive genetic losses due to culling cows positive for MAP (P < 0.01). There were mixedopinions regarding the magnitude of lowered weaning weight in calves from infected cowsand perceived differences in risk of other diseases or conditions in infected cows. An annualloss of $235 (95$89–$457) for each infected animal was estimated based on infor-mation from the producer survey. The analogous estimate using information inputs fromveterinarians was$250 ($82–$486). Mean annual loss due to JD in a 100 cow herd with a7% true prevalence was $1644 ($625–$3250) based on information provided by producers.Similarly, mean annual loss based on information collected from veterinarians was$1747($575–$3375).Program for the Study of Johne’s Disease in Texas and by a cooperative agreement with USDA-APHIS-VS.http://ww w.elsevier.com/locate/prevetmedhb2014ab201

Intraspecies Variation in the Emergence of Hyperinfectious Bacterial Strains in Nature

Salmonella is a principal health concern because of its endemic prevalence in food and water supplies, the rise in incidence of multi-drug resistant strains, and the emergence of new strains associated with increased disease severity. Insights into pathogen emergence have come from animal-passage studies wherein virulence is often increased during infection. However, these studies did not address the prospect that a select subset of strains undergo a pronounced increase in virulence during the infective process- a prospect that has significant implications for human and animal health. Our findings indicate that the capacity to become hypervirulent (100-fold decreased LD50) was much more evident in certain S. enterica strains than others. Hyperinfectious salmonellae were among the most virulent of this species; restricted to certain serotypes; and more capable of killing vaccinated animals. Such strains exhibited rapid (and rapidly reversible) switching to a less-virulent state accompanied by more competitive growth ex vivo that may contribute to maintenance in nature. The hypervirulent phenotype was associated with increased microbial pathogenicity (colonization; cytotoxin production; cytocidal activity), coupled with an altered innate immune cytokine response within infected cells (IFN-β; IL-1β; IL-6; IL-10). Gene expression analysis revealed that hyperinfectious strains display altered transcription of genes within the PhoP/PhoQ, PhoR/PhoB and ArgR regulons, conferring changes in the expression of classical virulence functions (e.g., SPI-1; SPI-2 effectors) and those involved in cellular physiology/metabolism (nutrient/acid stress). As hyperinfectious strains pose a potential risk to human and animal health, efforts toward mitigation of these potential food-borne contaminants may avert negative public health impacts and industry-associated losses

Useful pharmacodynamic endpoints in children: selection, measurement, and next steps.

Pharmacodynamic (PD) endpoints are essential for establishing the benefit-to-risk ratio for therapeutic interventions in children and neonates. This article discusses the selection of an appropriate measure of response, the PD endpoint, which is a critical methodological step in designing pediatric efficacy and safety studies. We provide an overview of existing guidance on the choice of PD endpoints in pediatric clinical research. We identified several considerations relevant to the selection and measurement of PD endpoints in pediatric clinical trials, including the use of biomarkers, modeling, compliance, scoring systems, and validated measurement tools. To be useful, PD endpoints in children need to be clinically relevant, responsive to both treatment and/or disease progression, reproducible, and reliable. In most pediatric disease areas, this requires significant validation efforts. We propose a minimal set of criteria for useful PD endpoint selection and measurement. We conclude that, given the current heterogeneity of pediatric PD endpoint definitions and measurements, both across and within defined disease areas, there is an acute need for internationally agreed, validated, and condition-specific pediatric PD endpoints that consider the needs of all stakeholders, including healthcare providers, policy makers, patients, and families.Pediatric Research advance online publication, 11 April 2018; doi:10.1038/pr.2018.38