Remote Sensing Provides a Rapid Epidemiological Context for the Control of African Swine Fever in Germany.

Transboundary disease control, as for African swine fever (ASF), requires rapid understanding of the locally relevant potential risk factors. Here, we show how satellite remote sensing can be applied to the field of animal disease control by providing an epidemiological context for the implementation of measures against the occurrence of ASF in Germany. We find that remotely sensed observations are of the greatest value at a lower jurisdictional level, particularly in support of wild boar carcass search efforts.

The diffusion metrics of African swine fever in wild boar.

To control African swine fever (ASF) efficiently, easily interpretable metrics of the outbreak dynamics are needed to plan and adapt the required measures. We found that the spread pattern of African Swine Fever cases in wild boar follows the mechanics of a diffusion process, at least in the early phase, for the cases that occurred in Germany. Following incursion into a previously unaffected area, infection disseminates locally within a naive and abundant wild boar population. Using real case data for Germany, we derive statistics about the time differences and distances between consecutive case reports. With the use of these statistics, we generate an ensemble of random walkers (continuous time random walks, CTRW) that resemble the properties of the observed outbreak pattern as one possible realization of all possible disease dissemination patterns. The trained random walker ensemble yields the diffusion constant, the affected area, and the outbreak velocity of early ASF spread in wild boar. These methods are easy to interpret, robust, and may be adapted for different regions. Therefore, diffusion metrics can be useful descriptors of early disease dynamics and help facilitate efficient control of African Swine Fever.

Seasonal Occurrence of African Swine Fever in Wild Boar and Domestic Pigs in EU Member States.

Since 2007, African swine fever (ASF) has spread widely within Europe and beyond. Most affected countries recorded outbreaks in domestic pigs and cases in wild boar. Outbreak data from 2014 to 2021 were used to investigate the seasonal pattern of ASF in domestic pigs and wild boar across affected member states of the European Union, since knowledge of seasonal patterns may provide the potential to adapt prevention, surveillance and control during times of increased risk. In domestic pigs, a yearly peak was observed in many European countries in summer (predominantly in July and August). In wild boar, the patterns showed more variability. In many countries, there was a seasonal peak of ASF occurrence in winter (predominantly in January and December), with an additional summer peak in the Baltic States (predominantly in July) and a further spring peak in Poland (predominantly in March). The observed seasonal effects may be related to the abundance and population dynamics of wild boar and to seasonality in pig farming. Moreover, ASF occurrence may also be influenced by human activities in both domestic pigs and wild boar.

Identification of Risk Factors for African Swine Fever: A Systematic Review.

African swine fever (ASF) is an internationally-spreading viral pig disease that severely damages agricultural pork production and trade economy as well as social welfare in disease-affected regions. A comprehensive understanding of ASF risk factors is imperative for efficient disease control. As the absence of effective ASF vaccines limits disease management options, the identification and minimisation of ASF-associated risk factors is critical to preventing ASF outbreaks. Here, we compile currently known potential ASF risk factors identified through a systematic literature review. We found 154 observation-based and 1239 potential ASF risk factors, which we were able to group into the following defined risk categories: 'ASF-virus', 'Biosecurity', 'Disease control', 'Environment', 'Husbandry', 'Movement', 'Network', 'Pig', 'Society' and 'Surveillance'. Throughout the epidemiological history of ASF there have been similar risk categories, such as 'Environment'-related risk factors, predominantly reported in the literature irrespective of the ASF situation at the time. While ASF risk factor reporting has markedly increased since 2010, the majority of identified risk factors overall have referred to domestic pigs. The reporting of risk factors for ASF in wild boar mostly commenced from 2016 onwards. The compendium of ASF risk factors presented herein defines our current knowledge of ASF risk factors, and critically informs ASF-related problem solving.

Review: Vaccines and Vaccination against Lumpy Skin Disease.

The geographical distribution of lumpy skin disease (LSD), an economically important cattle disease caused by a capripoxvirus, has reached an unprecedented extent. Vaccination is the only way to prevent the spread of the infection in endemic and newly affected regions. Yet, in the event of an outbreak, selection of the best vaccine is a major challenge for veterinary authorities and farmers. Decision makers need sound scientific information to support their decisions and subsequent actions. The available vaccine products vary in terms of quality, efficacy, safety, side effects, and price. The pros and cons of different types of live attenuated and inactivated vaccines, vaccination strategies, and associated risks are discussed. Seroconversion, which typically follows vaccination, places specific demands on the tools and methods used to evaluate the effectiveness of the LSD vaccination campaigns in the field. We aimed to give a comprehensive update on available vaccines and vaccination against LSD, to better prepare affected and at-risk countries to control LSD and ensure the safe trade of cattle.

A Review of Environmental Risk Factors for African Swine Fever in European Wild Boar.

A detailed understanding of environmental risk factors for African swine fever (ASF) in wild boar will be not only essential for risk assessments but also for timely and spatially informed allocation of resources in order to manage wild boar-targeted ASF control measures efficiently. Here, we review currently known environmental risk factors that can influence the occurrence of ASF virus infection in wild boar when compared to disease occurrence in wild boar of a non-exposed reference scenario. Accordingly, the exposure of wild boar to environmental risk factors related to (1) climate, (2) land cover, (3) human activity, (4) wild boar and (5) ASF were evaluated. As key environmental risk factors in this review, increased ASF occurrence in wild boar was associated with seasonal patterns, forest coverage, presence of water, human presence, farming activities, wild boar density and ASF nearness. The review highlights inconsistencies in some of these risk factor associations with disease detection in space and time and may provide valuable insights for the investigation of ASF transmission dynamics. The examined risk information was applied to consider potential improvements of the ASF control strategy in wild boar regarding disease surveillance, hunting, wild boar carcass searches and ASF barrier implementation.

Species Detection within the Echinococcus granulosus sensu lato Complex by Novel Probe-Based Real-Time PCRs.

Infections with eggs of Echinococcus granulosus sensu lato (s.l.) can cause cystic echinococcosis in intermediate host animals and humans. Upon ingestion of viable eggs, oncospheres hatch from the eggs and subsequently develop into fluid-filled larval cysts, most frequently in the liver or the lungs. The slowly growing cysts progressively interfere with organ function. The risk of infection is determined by the host range of the parasite, its pathogenicity and other epidemiologically relevant parameters, which differ significantly among the five species within the E. granulosus s.l. complex. It is therefore essential to diagnose the correct species within E. granulosus s.l. to help understand specific disease epidemiology and to facilitate effective implementation of control measures. For this purpose, simple, fast and cost-effective typing techniques are needed. We developed quantitative real-time polymerase chain reactions (qPCRs) to target polymorphic regions in the mitochondrial genome of E. granulosus s.l. In a single-step typing approach, we distinguished E. granulosus s.l. members in four epidemiologically relevant subgroups. These were E. granulosus sensu stricto, E. equinus, E. ortleppi and the E. canadensis cluster. The technique also allowed identification and differentiation of these species from other Echinococcus or Taenia taxa for samples isolated from cysts or faeces.

IgD attenuates the IgM-induced anergy response in transitional and mature B cells.

Self-tolerance by clonal anergy of B cells is marked by an increase in IgD and decrease in IgM antigen receptor surface expression, yet the function of IgD on anergic cells is obscure. Here we define the RNA landscape of the in vivo anergy response, comprising 220 induced sequences including a core set of 97. Failure to co-express IgD with IgM decreases overall expression of receptors for self-antigen, but paradoxically increases the core anergy response, exemplified by increased Sdc1 encoding the cell surface marker syndecan-1. IgD expressed on its own is nevertheless competent to induce calcium signalling and the core anergy mRNA response. Syndecan-1 induction correlates with reduction of surface IgM and is exaggerated without surface IgD in many transitional and mature B cells. These results show that IgD attenuates the response to self-antigen in anergic cells and promotes their accumulation. In this way, IgD minimizes tolerance-induced holes in the pre-immune antibody repertoire.

Zinc-finger protein ZFP318 is essential for expression of IgD, the alternatively spliced Igh product made by mature B lymphocytes.

IgD and IgM are produced by alternative splicing of long primary RNA transcripts from the Ig heavy chain (Igh) locus and serve as the receptors for antigen on naïve mature B lymphocytes. IgM is made selectively in immature B cells, whereas IgD is coexpressed with IgM when the cells mature into follicular or marginal zone B cells, but the transacting factors responsible for this regulated change in splicing have remained elusive. Here, we use a genetic screen in mice to identify ZFP318, a nuclear protein with two U1-type zinc fingers found in RNA-binding proteins and no known role in the immune system, as a critical factor for IgD expression. A point mutation in an evolutionarily conserved lysine-rich domain encoded by the alternatively spliced Zfp318 exon 10 abolished IgD expression on marginal zone B cells, decreased IgD on follicular B cells, and increased IgM, but only slightly decreased the percentage of B cells and did not decrease expression of other maturation markers CD21, CD23, or CD62L. A targeted Zfp318 null allele extinguished IgD expression on mature B cells and increased IgM. Zfp318 mRNA is developmentally regulated in parallel with IgD, with little in pro-B cells, moderate amounts in immature B cells, and high levels selectively in mature follicular B cells. These findings identify ZFP318 as a crucial factor regulating the expression of the two major antibody isotypes on the surface of most mature B cells.

B cell survival, surface BCR and BAFFR expression, CD74 metabolism, and CD8- dendritic cells require the intramembrane endopeptidase SPPL2A.

Druggable proteins required for B lymphocyte survival and immune responses are an emerging source of new treatments for autoimmunity and lymphoid malignancy. In this study, we show that mice with an inactivating mutation in the intramembrane protease signal peptide peptidase-like 2A (SPPL2A) unexpectedly exhibit profound humoral immunodeficiency and lack mature B cell subsets, mirroring deficiency of the cytokine B cell-activating factor (BAFF). Accumulation of Sppl2a-deficient B cells was rescued by overexpression of the BAFF-induced survival protein B cell lymphoma 2 (BCL2) but not BAFF and was distinguished by low surface BAFF receptor and IgM and IgD B cell receptors. CD8-negative dendritic cells were also greatly decreased. SPPL2A deficiency blocked the proteolytic processing of CD74 MHC II invariant chain in both cell types, causing dramatic build-up of the p8 product of Cathepsin S and interfering with earlier steps in CD74 endosomal retention and processing. The findings illuminate an important role for the final step in the CD74-MHC II pathway and a new target for protease inhibitor treatment of B cell diseases.

ZBTB7B (Th-POK) regulates the development of IL-17-producing CD1d-restricted mouse NKT cells.

CD1d-dependent NKT cells represent a heterogeneous family of effector T cells including CD4(+)CD8(-) and CD4(-)CD8(-) subsets that respond to glycolipid Ags with rapid and potent cytokine production. NKT cell development is regulated by a unique combination of factors, however very little is known about factors that control the development of NKT subsets. In this study, we analyze a novel mouse strain (helpless) with a mis-sense mutation in the BTB-POZ domain of ZBTB7B and demonstrate that this mutation has dramatic, intrinsic effects on development of NKT cell subsets. Although NKT cell numbers are similar in Zbtb7b mutant mice, these cells are hyperproliferative and most lack CD4 and instead express CD8. Moreover, the majority of ZBTB7B mutant NKT cells in the thymus are retinoic acid-related orphan receptor γt positive, and a high frequency produce IL-17 while very few produce IFN-γ or other cytokines, sharply contrasting the profile of normal NKT cells. Mice heterozygous for the helpless mutation also have reduced numbers of CD4(+) NKT cells and increased production of IL-17 without an increase in CD8(+) cells, suggesting that ZBTB7B acts at multiple stages of NKT cell development. These results reveal ZBTB7B as a critical factor genetically predetermining the balance of effector subsets within the NKT cell population.

Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes.

BACKGROUND: Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue. METHODS: The present study investigates metabolic responses in two different lines of mice either selected for high body weight (DU6) leading to rapid obesity development, or selected for high treadmill performance (DUhTP) leading to a lean phenotype. At 29 days of age the mice were fed standard chow (7.2% fat, 25.7% protein), or a high-fat diet rich in n-3 PUFA (n-3 HFD, 27.7% fat, 19% protein) or a high-fat diet rich in n-6 PUFA (n-6 HFD, 27.7% fat, 18.6% protein) for 8 weeks. The aim of the study was to determine the effect of these PUFA-rich high-fat diets on the fatty acid profile and on the protein expression of key components of insulin signalling pathways. RESULTS: Plasma concentrations of leptin and insulin were higher in DU6 in comparison with DUhTP mice. The high-fat diets stimulated a strong increase in leptin levels and body fat only in DU6 mice. Muscle and liver fatty acid composition were clearly changed by dietary lipid composition. In both lines of mice n-3 HFD feeding significantly reduced the hepatic insulin receptor ß protein concentration which may explain decreased insulin action in liver. In contrast, protein kinase C ζ expression increased strongly in abdominal fat of n-3 HFD fed DUhTP mice, indicating enhanced insulin sensitivity in adipose tissue. CONCLUSIONS: A diet high in n-3 PUFA may facilitate a shift from fuel deposition in liver to fuel storage as fat in adipose tissue in mice. Tissue specific changes in insulin sensitivity may describe, at least in part, the health improving properties of dietary n-3 PUFA. However, important genotype-diet interactions may explain why such diets have little effect in some population groups.

Comparison of analgesic efficacy of preoperative or postoperative carprofen with or without preincisional mepivacaine epidural anesthesia in canine pelvic or femoral fracture repair.

OBJECTIVE: To compare analgesic efficacy of preoperative versus postoperative administration of carprofen and to determine, if preincisional mepivacaine epidural anesthesia improves postoperative analgesia in dogs treated with carprofen. STUDY DESIGN: Blind, randomized clinical study. ANIMALS: Dogs with femoral (n=18) or pelvic (27) fractures. METHODS: Dogs were grouped by restricted randomization into 4 groups: group 1 = carprofen (4 mg/kg subcutaneously) immediately before induction of anesthesia, no epidural anesthesia; group 2 = carprofen immediately after extubation, no epidural anesthesia; group 3 = carprofen immediately before induction, mepivacaine epidural block 15 minutes before surgical incision; and group 4 = mepivacaine epidural block 15 minutes before surgical incision, carprofen after extubation. All dogs were administered carprofen (4 mg/kg, subcutaneously, once daily) for 4 days after surgery. Physiologic variables, nociceptive threshold, lameness score, pain, and sedation (numerical rating scale [NRS], visual analog scale [VAS]), plasma glucose and cortisol concentration, renal function, and hemostatic variables were measured preoperatively and at various times after surgery. Dogs with VAS pain scores >30 were administered rescue analgesia. RESULTS: Group 3 and 4 dogs had significantly lower pain scores and amount of rescue analgesia compared with groups 1 and 2. VAS and NRS pain scores were not significantly different among groups 1 and 2 or among groups 3 and 4. There was no treatment effect on renal function and hemostatic variables. CONCLUSIONS: Preoperative carprofen combined with mepivacaine epidural anesthesia had superior postoperative analgesia compared with preoperative carprofen alone. When preoperative epidural anesthesia was performed, preoperative administration of carprofen did not improve postoperative analgesia compared with postoperative administration of carprofen. CLINICAL RELEVANCE: Preoperative administration of systemic opioid agonists in combination with regional anesthesia and postoperative administration of carprofen provides safe and effective pain relieve in canine fracture repair.

Effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing surgery for fracture repair.

OBJECTIVE: To evaluate effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing general anesthesia for fracture repair. ANIMALS: 26 client-owned dogs. PROCEDURE: Anesthesia was induced with levomethadone, diazepam, and propofol and maintained by administration of isoflurane in oxygen-nitrous oxide. Carprofen (4 mg/kg, SC) was administered 1 hour before induction to 13 dogs (group 1) and after extubation to the other 13 dogs (group 2). All dogs also received carprofen (4 mg/kg, SC, q 24 h) for the first 4 days after surgery. Renal function (glomerular filtration rate [GFR], urinary protein-to-urinary creatinine ratio [UP:UC], and results of urinalysis and biochemical analysis of plasma), hemostatic variables (bleeding time, platelet aggregation, prothrombin time [PT], activated partial thromboplastin time [APTT], and platelet count), and Hct were assessed before and at various time points after surgery. RESULTS: Analysis of results for renal function tests, most of the hemostatic and plasma biochemical variables, and Hct did not reveal significant differences between treatment groups. Values for GFR, UP:UC, PT, APTT, and platelet aggregation were outside reference ranges in many dogs before surgery and during the first 6 hours after surgery. In most dogs, these trauma-induced pathologic changes returned to within reference ranges during the 4-day period after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen did not cause clinically relevant adverse effects in dogs anesthetized for fracture repair after 5 days of treatment, even when it was administered before surgery or given to patients with trauma-induced alterations in renal function or hemostasis.