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.

An attenuated herpesvirus vectored vaccine candidate induces T-cell responses against highly conserved porcine reproductive and respiratory syndrome virus M and NSP5 proteins that are unable to control infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a leading cause of economic loss in pig farming worldwide. Existing commercial vaccines, all based on modified live or inactivated PRRSV, fail to provide effective immunity against the highly diverse circulating strains of both PRRSV-1 and PRRSV-2. Therefore, there is an urgent need to develop more effective and broadly active PRRSV vaccines. In the absence of neutralizing antibodies, T cells are thought to play a central role in controlling PRRSV infection. Herpesvirus-based vectors are novel vaccine platforms capable of inducing high levels of T cells against encoded heterologous antigens. Therefore, the aim of this study was to assess the immunogenicity and efficacy of an attenuated herpesvirus-based vector (bovine herpesvirus-4; BoHV-4) expressing a fusion protein comprising two well-characterized PRRSV-1 T-cell antigens (M and NSP5). Prime-boost immunization of pigs with BoHV-4 expressing the M and NSP5 fusion protein (vector designated BoHV-4-M-NSP5) induced strong IFN-γ responses, as assessed by ELISpot assays of peripheral blood mononuclear cells (PBMC) stimulated with a pool of peptides representing PRRSV-1 M and NSP5. The responses were closely mirrored by spontaneous IFN-γ release from unstimulated cells, albeit at lower levels. A lower frequency of M and NSP5 specific IFN-γ responding cells was induced following a single dose of BoHV-4-M-NSP5 vector. Restimulation using M and NSP5 peptides from PRRSV-2 demonstrated a high level of cross-reactivity. Vaccination with BoHV-4-M-NSP5 did not affect viral loads in either the blood or lungs following challenge with the two heterologous PRRSV-1 strains. However, the BoHV-4-M-NSP5 prime-boost vaccination showed a marked trend toward reduced lung pathology following PRRSV-1 challenge. The limited effect of T cells on PRRSV-1 viral load was further examined by analyzing local and circulating T-cell responses using intracellular cytokine staining and proliferation assays. The results from this study suggest that vaccine-primed T-cell responses may have helped in the control of PRRSV-1 associated tissue damage, but had a minimal, if any, effect on controlling PRRSV-1 viral loads. Together, these results indicate that future efforts to develop effective PRRSV vaccines should focus on achieving a balanced T-cell and antibody response.

Genome Sequence of Streptomyces aureofaciens ATCC Strain 10762.

Streptomyces aureofaciens is a Gram-positive actinomycete that produces the antibiotics tetracycline and chlortetracycline. Here, we report the assembly and initial annotation of the draft genome sequence of S. aureofaciens ATCC strain 10762.

The cutaneous surgery experience of multiple specialties in the Medicare population.

BACKGROUND: There has been tremendous growth in the performance of ambulatory surgical procedures. Traditional forms of peer review, commonplace for hospital-based procedures, are not typically performed in the office-based setting. Hospital credentialing of physicians has been suggested to be a means of assuring patient safety. Credentialing committees may be unaware of the level of experience of typical office-based physicians who perform cutaneous surgery. PURPOSE: To compare the levels of cutaneous surgery experience of dermatologists and other surgical specialists. METHODS: Medicare claims data on number of cutaneous surgery procedures performed by various medical disciplines, including dermatologists, plastic surgeons, general surgeons, and others, were obtained from the 1998-1999 Medicare Current Beneficiary Survey (MCBS) and analyzed. The number of physicians in each specialty was used to normalize the data to a per physician basis. RESULTS: Dermatologists performed half (50%) of the complex repairs and most of the excisions (58%) and intermediate repairs (62%). Dermatologists performed more flaps (40% of all flaps) than any other specialty, while plastic surgeons performed more total grafts (38%) than any other specialty. Dermatologists and plastic surgeons performed similar numbers of full-thickness skin grafts, while plastic surgeons performed more split-thickness skin grafts. CONCLUSION: As dermatologists seek hospital credentials for performing cutaneous surgery procedures, these data should help surgical colleagues understand the typical level of experience of their dermatologist colleagues.

Clindamycin for intraincisional antibiotic prophylaxis in dermatologic surgery.

OBJECTIVE: To assess the efficacy of intraincisional clindamycin therapy as an alternative to nafcillin treatment in decreasing the risk of postoperative wound infections in dermatologic surgery. DESIGN: Prospective, double-blinded, randomized, placebo-controlled trial conducted over a 7-month period. SETTING: Three private practice Mohs micrographic surgery referral centers. PATIENTS: A total of 1030 consecutive patients who underwent Mohs micrographic surgery with subsequent reconstruction. INTERVENTIONS: Prior to reconstruction, patients were randomly assigned to receive either intraincisional buffered lidocaine with epinephrine containing clindamycin or buffered lidocaine with epinephrine without clindamycin. Nurses and physicians who scored the wound at follow-up were blinded to the treatment conditions. MAIN OUTCOME MEASURES: Surgical wounds evaluated at the time of suture removal were scored according to a standardized assessment based on erythema, edema, and the presence of purulent discharge. Wounds scored 4 or higher were considered to be infected. Bacterial cultures obtained when indicated were also compared. RESULTS: Of the 1172 surgical wounds included in the study, 29 had wound scores of 4 or higher, 6 in the study group and 23 in the control group (P =.001, Fisher exact test). Of these 29, 18 had culture-positive infections. Four of these occurred in the study group, and 14 occurred in the control group (P =.02, Fisher exact test). CONCLUSIONS: The results of this study further support the efficacy of single-dose preoperative intraincisional antibiotic treatment for dermatologic surgery. With the relatively high prevalence of patient-reported penicillin allergies, buffered lidocaine containing clindamycin offers an inexpensive, safe, convenient, and effective alternative.