A single subcutaneous dose of eprinomectin (Eprecis®) is effective against common gastrointestinal nematodes and lungworms in experimentally infected lactating goats.

BACKGROUND: The health and productivity of dairy goats continue to be impacted by gastrointestinal nematodes (GIN) and lungworms (LW). Eprinomectin (EPN) is frequently selected for treatment because it is generally effective and does not require a milk withdrawal period. However, some factors, such as lactation, can have an impact on EPN pharmacokinetics and potentially its efficacy. To evaluate whether this can alter the efficacy of Eprecis® 2%, an eprinomectin injectable solution, a study was performed in lactating goats using the dose currently registered in cattle, sheep and goats (0.2 mg/kg). METHODS: This study was a blinded, randomized, controlled trial performed according to the VICH guidelines. Eighteen (18) worm-free lactating goats were included and experimentally challenged on day 28 with a mixed culture of infective gastrointestinal and lung nematode larvae (Haemonchus contortus, Trichostrongylus colubriformis, Teladorsagia circumcincta, Dictyocaulus filaria). At D-1, fecal samples were collected to confirm patent infection in all animals. On D0, the goats were randomly allocated into two groups of nine goats; group 1 was treated with Eprecis® 2% at 0.2 mg/kg BW by subcutaneous injection, while group 2 remained untreated. Fecal samples for egg counts were collected from all animals on days 3, 5, 7, 9, 11 and 14. On D14, all goats were killed, and the abomasum, small intestine and lungs were removed, processed and subsampled to record the number and species of worms. RESULTS: The treatment was well tolerated. After treatment, the arithmetic mean FEC decreased in the treated group and remained < 5 EPG until the end of the study, while the arithmetic mean FEC in the control group remained > 849.0 EPG. At D14, goats in the treated group had very limited or zero total worm counts, whereas all animals from the control group had a high worm burden. The measured efficacy was 100.0% against H. contortus and T. colubriformis, 99.9% against T. circumcincta and 98.0% against D. filaria. CONCLUSIONS: Eprinomectin (Eprecis®, 20 mg/ml), administered at the label dose (0.2 mg/kg), is highly effective against gastrointestinal nematodes and lungworms in lactating goats.

Effects of a water-soluble formulation of tylvalosin on disease caused by porcine reproductive and respiratory syndrome virus alone in sows or in combination with Mycoplasma hyopneumoniae in piglets.

BACKGROUND: The effect of a water-soluble formulation of tylvalosin (Aivlosin® 625 mg/g granules) on disease caused by porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (Mhyop) was investigated in two animal studies. In a PRRSV challenge model in pregnant sows (n = 18), six sows received water medicated at target dose of 5 mg tylvalosin/kg body weight/day from 3 days prior to challenge until the end of gestation. Six sows were left untreated, with a third group remaining untreated and unchallenged. Sows were challenged with PRRSV-2 at approximately 85 days of gestation. Cytokines, viremia, viral shedding, sow reproductive parameters and piglet performance to weaning were evaluated. In a dual infection study (n = 16), piglets were challenged with Mhyop on days 0, 1 and 2, and with PRRSV-1 on day 14 and euthanized on day 24. From day 10 to 20, eight piglets received water medicated at target dose of 20 mg tylvalosin/kg body weight/day and eight piglets were left untreated. Cytokines, viremia, bacteriology and lung lesions were evaluated. RESULTS: In the PRRSV challenge study in pregnant sows, tylvalosin significantly reduced the levels of serum IL-8 (P < 0.001), IL-12 (P = 0.032), TNFα (P < 0.001) and GM-CSF (P = 0.001). IL-8 (P = 0.100) tended to be lower in uterus of tylvalosin sows. All piglets from tylvalosin sows surviving to weaning were PRRSV negative in faecal swabs at weaning compared to 33.3% PRRSV positive piglets from untreated sows (P = 0.08). In the dual challenge study in piglet, tylvalosin reduced serum IL1ß, IL-4, IL-6, IL-8, IL-10, IL-12, IL-1α, IL-13, IL-17A, IL-18, GM-CSF, TGFß1, TNFα, CCL3L1, MIG, PEPCAM-1 (P < 0.001) and increased serum IFNα, IL-1ra and MIP-1b (P < 0.001). In the lungs, tylvalosin reduced IL-8, IL-10 and IL-12 compared to untreated pigs (P < 0.001) and tended to reduce TNFα (P = 0.082). Lung lavage samples from all tylvalosin treated piglets were negative for Mhyop (0 cfu/mL) compared to the untreated piglets which had mean Mhyop counts of 2.68 × 104 cfu/mL (P = 0.023). CONCLUSION: Overall, tylvalosin reduced both local and systemic proinflammatory cytokines after challenge with respiratory pathogens in sows and in piglets. Tylvalosin was effective in reducing Mhyop recovery from the lungs and may reduce virus shedding in piglets following transplacental PRRSV infection in sows.

Named Data Networking for Genomics Data Management and Integrated Workflows.

Advanced imaging and DNA sequencing technologies now enable the diverse biology community to routinely generate and analyze terabytes of high resolution biological data. The community is rapidly heading toward the petascale in single investigator laboratory settings. As evidence, the single NCBI SRA central DNA sequence repository contains over 45 petabytes of biological data. Given the geometric growth of this and other genomics repositories, an exabyte of mineable biological data is imminent. The challenges of effectively utilizing these datasets are enormous as they are not only large in the size but also stored in geographically distributed repositories in various repositories such as National Center for Biotechnology Information (NCBI), DNA Data Bank of Japan (DDBJ), European Bioinformatics Institute (EBI), and NASA's GeneLab. In this work, we first systematically point out the data-management challenges of the genomics community. We then introduce Named Data Networking (NDN), a novel but well-researched Internet architecture, is capable of solving these challenges at the network layer. NDN performs all operations such as forwarding requests to data sources, content discovery, access, and retrieval using content names (that are similar to traditional filenames or filepaths) and eliminates the need for a location layer (the IP address) for data management. Utilizing NDN for genomics workflows simplifies data discovery, speeds up data retrieval using in-network caching of popular datasets, and allows the community to create infrastructure that supports operations such as creating federation of content repositories, retrieval from multiple sources, remote data subsetting, and others. Named based operations also streamlines deployment and integration of workflows with various cloud platforms. Our contributions in this work are as follows 1) we enumerate the cyberinfrastructure challenges of the genomics community that NDN can alleviate, and 2) we describe our efforts in applying NDN for a contemporary genomics workflow (GEMmaker) and quantify the improvements. The preliminary evaluation shows a sixfold speed up in data insertion into the workflow. 3) As a pilot, we have used an NDN naming scheme (agreed upon by the community and discussed in Section 4) to publish data from broadly used data repositories including the NCBI SRA. We have loaded the NDN testbed with these pre-processed genomes that can be accessed over NDN and used by anyone interested in those datasets. Finally, we discuss our continued effort in integrating NDN with cloud computing platforms, such as the Pacific Research Platform (PRP). The reader should note that the goal of this paper is to introduce NDN to the genomics community and discuss NDN's properties that can benefit the genomics community. We do not present an extensive performance evaluation of NDN-we are working on extending and evaluating our pilot deployment and will present systematic results in a future work.

Treatment of experimentally induced bovine respiratory disease in young calves with a single administration of a combination of florfenicol and meloxicam.

This study was designed to evaluate the efficacy of a new florfenicol/meloxicam combination (FMC) in calves with bovine respiratory disease. A total of 90 young calves were challenged via intratracheal deposition of 108 colony-forming units of Mannheimia haemolytica Data for 84 calves demonstrating a rectal temperature (RT) above 39.5°C and a combined total clinical score (TCS) greater than or equal to 3 were included. Calves were then randomly allocated to one of the three study groups (FMC; florfenicol/flunixin combination (FFC); or saline) and promptly treated. RT and TCS of calves treated with an FMC or FFC were consistently lower than RT and TCS of calves belonging to the control group (P<0.001). Moreover, at the end of the study, a high clinical cure rate was observed in calves treated with FMC (100 per cent) or FFC (96.6 per cent) whereas cure was limited for calves receiving saline (29.6 per cent). Interestingly, calves treated with FMC were cured without relapse more rapidly compared with calves treated with FFC (HR=1.76, P<0.05) and with a lower percentage of clinical relapse due to fever (P=0.05). These results underline the high efficacy of the FMC and are in line with the pharmacokinetic properties of florfenicol and meloxicam.

Comparative efficacy of tulathromycin and tildipirosin for the treatment of experimental Mycoplasma bovis infection in calves.

The objective of this negative controlled, blinded, randomised, parallel group study was to compare the efficacy of two injectable macrolide antimicrobials, tulathromycin and tildipirosin, administered by single subcutaneous injection at dose rates of 2.5 and 4.0 mg kg-1 bodyweight, respectively, in the treatment of an experimentally induced Mycoplasma bovis infection in calves. A total of 238 M. bovis-negative calves were challenged on three consecutive days with M. bovis by endobronchial deposition. Post-challenge, a total of 126 animals fulfilled the inclusion criteria and were randomly allocated to three treatment groups: tulathromycin, tildipirosin and saline. Clinical observations for signs of respiratory disease and injection site assessments were conducted daily for 14 days post-treatment. The animals were then killed, the lungs were examined for evidence of lesions, and samples collected for bacterial isolation. Calves treated with tulathromycin had a lower percentage of lung with lesions (P = 0.0079), lower mortality (P = 0.0477), fewer days with depressed demeanour (P = 0.0486) and higher body weight (P = 0.0112) than calves administered tildipirosin.

Are US jurisdictions prepared to dispense medical countermeasures through open points of dispensing? Findings from a national study.

Communities will rely on open points of dispensing (PODs) for mass dispensing of medical countermeasures following a bioterrorism attack or a pandemic. US Cities Readiness Initiative (CRI) open POD preparedness is assessed using the Technical Assistance Review (TAR) but focuses on oral prophylaxis dispensing; mass vaccination readiness is not well measured. Non-CRI preparedness had not been studied. In 2013 an online questionnaire was sent to all 456 CRIs and a random sample of 500 non-CRIs to measure open POD preparedness and exercise participation. Hierarchical linear regression was used to describe factors associated with higher POD preparedness and exercise participation scores. In total, 257 subjects participated, for a 41% response rate. Almost all open PODs have existing written plans and/or a layout for each site (93.4%, n=240, and 87.0%, n=220). Only half (46.7%, n=120) have an alternative dispensing modality in place, and even fewer (42.6%, n=104) report having adequate staffing. Determinants of open POD preparedness were perceived preparedness, participation in more POD exercises, and more closed POD coverage. Most jurisdictions conducted a full-scale exercise and a staff notification drill (83.7%, n=215 for both). Fewer than half (40.5%, n=104) have conducted a vaccination clinic exercise. Determinants of increased POD exercises were perceived preparedness, years of work experience, community type (nontribal), and larger population. Because successful open POD deployment is critical, jurisdictions need to plan for mass vaccination, use of alternative dispensing modalities, and recruitment strategies to increase POD staffing.

A national study examining closed points of dispensing (PODs): existence, preparedness, exercise participation, and training provided.

The Centers for Disease Control and Prevention recommends using open points of dispensing (PODs) and alternative modalities, such as closed PODs, for mass dispensing of medical countermeasures. However, closed POD existence has not been assessed. In 2013 we sent an online questionnaire to US Cities Readiness Initiative (CRI) and non-CRI public health disaster planners. Chi-square tests were used to determine differences between CRIs and non-CRIs when comparing having at least 1 closed POD, and to compare having a closed POD and perceived mass dispensing preparedness. A total of 301 disaster planners participated. Almost all (89.3%, n=218) jurisdictions have considered establishing a closed POD, and three-quarters (74.2%, n=181) currently have at least one. CRIs were more likely than non-CRIs to have a closed POD (85.0% vs 58.5%, X(2)=21.3, p<.001). Those with 1 or more closed PODs were more likely to believe their jurisdiction could distribute medical countermeasures within 48 hours compared to those without a closed POD (78.5% vs 21.5%; X(2)=10.8, p=.001). Half had a written plan and/or written standing orders (59.1% and 52.5%, respectively). Almost half (42%, n=72) have done no preevent training for POD staff in the past 2 years; almost 20% (18%, n=32) do not plan to offer any just-in-time training. Nearly 40% (n=70) have conducted no exercises in the past year. Closed PODs contribute to community preparedness; their establishment should be followed by development of written plans, worker training, and exercises.

US school morbidity and mortality, mandatory vaccination, institution closure, and interventions implemented during the 2009 influenza A H1N1 pandemic.

The 2009 H1N1 pandemic disproportionately affected school-aged children, but only school-based outbreak case studies have been conducted. The purposes of this study were to evaluate US academic institutions' experiences during the 2009 H1N1 pandemic in terms of infection prevention interventions implemented and to examine factors associated with school closure during the pandemic. An online survey was sent to school nurses in May through July 2011. Hierarchical logistic regressions were used to determine predictive models for having a mandatory H1N1 vaccination policy for school nurses and school closure. In all, 1,997 nurses from 26 states participated. Very few nurses (3.3%, n=65) reported having a mandatory H1N1 influenza vaccination policy; nurses were more likely than all other school employees (p<.001) to be mandated to receive vaccine. Determinants of having a mandatory H1N1 vaccination policy were being employed by a hospital or public health agency, and the school being located in a western or northeastern state. Factors related to school closure included being in a western or northeastern state, having higher H1N1-related morbidity/mortality, being a school nurse employed by a public health agency or hospital, and being a private school. The most commonly implemented interventions included encouraging staff and students to exercise hand hygiene and increasing classroom cleaning; least commonly implemented interventions included discouraging face-to-face meetings, training staff on H1N1 influenza and/or respiratory hygiene, and discouraging handshaking. Schools should develop and continue to improve their pandemic plans, including collaborating with community response agencies.

Health care versus non-health care businesses' experiences during the 2009 H1N1 pandemic: financial impact, vaccination policies, and control measures implemented.

BACKGROUND: Only limited data are available on businesses' experiences related to the 2009 H1N1 pandemic in terms of interventions implemented, staffing shortages, employees working while ill, and H1N1 vaccination policy. METHODS: A questionnaire was administered to human resource professionals during May-July 2011 to assess US businesses' experiences related to the 2009 pandemic. Logistic regressions were used to describe factors associated with providing H1N1 and respiratory hygiene training and offering H1N1 vaccine to staff. Linear regression was used to describe factors associated with higher infection prevention intervention scores (ie, number of interventions implemented). RESULTS: In all, 471 human resource professionals participated. Most (85.1%, n = 401) did not work while ill. Twelve percent (n = 57) reported staffing shortages, 2.1% (n = 10) needed to hire temporary staff, and fewer than 1% (0.8%, n = 4) reduced workload or closed during the pandemic. From logistic and linear regressions, determinants of providing employees H1N1 influenza training, respiratory hygiene education, offering H1N1 vaccine to employees, and higher infection prevention intervention scores were size of the business (with larger businesses implementing more interventions, such as providing education and vaccine, than smaller businesses) and being a health care agency. CONCLUSION: Businesses should continue to improve business continuity and pandemic plans to prepare for the next biologic event (ie, pandemic, bioterrorism attack, or emerging infectious disease outbreak).

Business continuity and pandemic preparedness: US health care versus non-health care agencies.

BACKGROUND: Only limited data are available on US business continuity activities related to biologic events. METHODS: A questionnaire was administered to human resource professionals during May-July 2011 to assess business continuity related to biologic events, incentives businesses are providing to maximize worker surge capacity, and seasonal influenza vaccination policy. Linear regressions were used to describe factors associated with higher business continuity and pandemic preparedness scores. The χ(2) and Fisher exact tests compared health care versus non-health care businesses on preparedness indicators. RESULTS: Possible business continuity and pandemic preparedness scores ranged from 0.5 to 27 and 0 to 15, with average resulting scores among participants at 13.2 and 7.3, respectively. Determinants of business continuity and pandemic preparedness were (1) business size (larger businesses were more prepared), (2) type of business (health care more prepared), (3) having human resource professional as company disaster planning committee member, and (4) risk perception of a pandemic in the next year. Most businesses (63.3%, n = 298) encourage staff influenza vaccination; 2.1% (n = 10) mandate it. Only 10% of businesses (11.0%, n = 52) provide employee incentives, and fewer than half (41.0%, n = 193) stockpile personal protective equipment. CONCLUSION: Despite the recent H1N1 pandemic, many US businesses lack adequate pandemic plans. It is critical that businesses of all sizes and types become better prepared for a biologic event.