Evaluation of the Immunogenicity of an Experimental Subunit Vaccine That Allows Differentiation between Infected and Vaccinated Animals against Bluetongue Virus Serotype 8 in Cattle

Bluetongue virus (BTV), the causative agent of bluetongue in ruminants, is an emerging virus in northern Europe. The 2006 outbreak of BTV serotype 8 (BTV-8) in Europe was marked by an unusual teratogenic effect and a high frequency of clinical signs in cattle. Conventional control strategies targeting small ruminants were therefore extended to include cattle. Since cattle were not routinely vaccinated before 2006, the immune responses to BTV have not been studied extensively in this species. With the aims of developing a subunit vaccine against BTV-8 for differentiation between infected and vaccinated animals based on viral protein 7 (VP7) antibody detection and of improving the current understanding of the immunogenicity of BTV proteins in cattle, the immune responses induced by recombinant VP2 (BTV-8) and nonstructural protein 1 (NS1) and NS2 (BTV-2) were studied. Cows were immunized twice (with a 3-week interval) with the experimental vaccine, a commercial inactivated vaccine, or a placebo. The two vaccines induced similar neutralizing antibody responses to BTV-8. Furthermore, the antibody responses detected against VP2, NS1, and NS2 were strongest in the animals immunized with the experimental vaccine, and for the first time, a serotype cross-reactive antibody response to NS2 was shown in cattle vaccinated with the commercial vaccine. The two vaccines evoked measurable T cell responses against NS1, thereby supporting a bovine cross-reactive T cell response. Finally, VP7 seroconversion was observed after vaccination with the commercial vaccine, as in natural infections, but not after vaccination with the experimental vaccine, indicating that the experimental vaccine may allow the differentiation of vaccinated animals from infected animals regardless of BTV serotype. The experimental vaccine will be further evaluated during a virulent challenge in a high-containment facility.     

What lessons can be learned from γδ T cell-based cancer immunotherapy trials?

During the last several years, research has produced a significant amount of knowledge concerning the characteristics of human γδ T lymphocytes. Findings regarding the immune functions of these cells, particularly their natural killer cell-like lytic activity against tumor cells, have raised expectations for the therapeutic applications of these cells for cancer. Pharmaceutical companies have produced selective agonists for these lymphocytes, and several teams have launched clinical trials of γδ T cell-based cancer therapies. The findings from these studies include hematological malignancies (follicular lymphoma, multiple myeloma, acute and chronic myeloid leukemia), as well as solid tumors (renal cell, breast and prostate carcinomas), consisting of samples from more than 250 patients from Europe, Japan and the United States. The results of these pioneering studies are now available, and this short review summarizes the lessons learned and the role of γδ T cell-based strategies in the current landscape of cancer immunotherapies.     

Complications of pelvic organ prolapse surgery and methods of prevention

Introduction and hypothesis

The aim was to review complications associated with pelvic organ prolapse surgery.

Methods

Every 4 years and as part of the Fifth International Collaboration on Incontinence we reviewed the English-language scientific literature after searching PubMed, Medline, Cochrane library and Cochrane database of systematic reviews, published up to January 2012. Publications were classified as level 1 evidence (randomised controlled trials [RCT] or systematic reviews), level 2 (poor quality RCT, prospective cohort studies), level 3 (case series or retrospective studies) and level 4 (case reports). The highest level of evidence was utilised by the committee to make evidence-based recommendations based upon the Oxford grading system. Grade A recommendation usually depends on consistent level 1 evidence. Grade B recommendation usually depends on consistent level 2 and/or 3 studies, or “majority evidence” from RCTs. Grade C recommendation usually depends on level 4 studies or “majority evidence? from level 2/3 studies or Delphi processed expert opinion. Grade D “no recommendation possible” would be used where the evidence is inadequate or conflicting and when expert opinion is delivered without a formal analytical process, such as by Delphi.

Results and conclusions

Transvaginal mesh has a higher re-operation rate than native tissue vaginal repairs (grade A). If a synthetic mesh is placed via the vaginal route, it is recommended that a macroporous polypropylene monofilament mesh should be used. At sacral colpopexy mesh should not be introduced or sutured via the vaginal route and silicone-coated polyester, porcine dermis, fascia lata and polytetrafluoroethylene meshes are not recommended as grafts. Hysterectomy should also be avoided (grade B). There is no evidence to recommend routine local or systemic oestrogen therapy before or after prolapse surgery using mesh. The first cases should be undertaken with the guidance of an experienced surgeon in the relevant technique (grade C). Expert opinion suggests that by whatever the surgical route pre-operative urinary tract infections are treated, smoking is ceased and antibiotic prophylaxis is undertaken. It is recommended that a non-absorbable synthetic mesh should not be inserted into the rectovaginal septum when a rectal injury occurs. The placement of a non-absorbable synthetic mesh into the vesicovaginal septum may be considered after a bladder injury has been repaired, if the repair is considered to be satisfactory. It is possible to perform a hysterectomy in association with the introduction of a non-absorbable synthetic mesh inserted vaginally, but this is not recommended routinely.     

The effect of a cognitive task on the postural control of dyslexic children

We explore the influence of a secondary cognitive task on concurrent postural control in dyslexic children. Seventeen children with dyslexia (DYS) were compared with thirteen non-dyslexic children (NDYS). Postural control was recorded in Standard Romberg (SR) and Tandem Romberg (TR) conditions while children, in separate sessions, have to fixate on a target and name simple objects appearing consecutively on a computer screen. The surface, the length and the mean speed of the center of pressure were analyzed; the percentage of correct responses to the cognitive task was also measured. DYS are significantly more unstable than NDYS. The secondary cognitive task significantly decreases the postural stability in DYS only. For both children postural performances in the TR condition is significantly worse than in the SR condition. The percentage of wrong responses to the cognitive task is significantly higher in DYS. Postural instability observed in DYS supports the hypothesis that there is a deficit of automatic integration of visual information and postural control in these children. This result is in line with the U-shaped non linear model showing that a secondary task performed during a postural task leads to an impaired postural stability probably due to focus attention on the cognitive task.     

Survival Benefit of Hyperthermic Intraperitoneal Chemotherapy for Recurrent Ovarian Cancer: A Multi-institutional Case Control Study

Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) and complete surgical removal of the tumor, in relapsing patients may provide a clinical benefit. There is no consensus considering the place of HIPEC for patients who had first ovarian cancer relapse. To assess for possible efficacy of HIPEC on overall survival (OS) rates in this situation, we performed a multi-institutional study.

Methods

The current study was a retrospective case control multi-institutional study comparing a group of patients treated with HIPEC to a group of patients treated without HIPEC. Inclusion criteria were first relapse of a serous ovarian carcinoma and >6 months after the end of initial treatment. Exclusion criteria were another pathological subtype of ovarian cancer, a relapse at <6 months after initial treatment, and a second relapse or more. We aimed to assess OS, morbidity, and mortality rates and prognostic factors.

Results

From June 1997–July 2011, 42 patients were included, 23 in the HIPEC group and 19 in the control group. Each patient from the two groups had a complete secondary surgery at the time of the first relapse. At 4 years OS was 75.6 % in the HIPEC group and 19.4 % in the control group (p = 0.013). In a multivariate analysis, HIPEC and interval-free before the end of initial treatment were both independent prognostic factors.

Conclusion

When compared to the control group, complete secondary surgery and HIPEC appear to afford a better OS rate than complete secondary surgery alone, in case of first ovarian cancer relapse. Further randomized trials are warranted to confirm these results.     

Complete cervical spinal cord injury above C6 predicts the need for tracheostomy

Background

Failed extubation and delayed tracheostomy contribute to poor outcomes in patients with a traumatic spinal cord injury (SCI). We determined if the level and completeness of SCI predict the need for tracheostomy.

Methods

Data from 256 patients with SCI between C1 and T3 with or without tracheostomy were retrospectively analyzed. Logistic regression identified predictors for tracheostomy. Data are presented as raw percentage or odds ratio (OR) with 95% confidence interval. P < .05 indicates significance.

Results

Complete spinal cord injuries were common in patients requiring tracheostomy (55% vs 18%, P < .05), and predicted the need for tracheostomy (OR: 6.4 (3.1 to 13.5), P < .05). An injury above C6 predicted the need for tracheostomy in patients with complete injury (OR: 3.7 (1 to 11.9), P < .05), but not incomplete injury (OR: .7 (.3 to 1.9); P = .53).

Conclusion

Tracheostomy is unlikely in patients with incomplete SCI, regardless of the level of injury. Patients with complete SCI above C6 are likely to require tracheostomy.     

Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle

Bluetongue virus (BTV) infections in ruminants pose a permanent agricultural threat since new serotypes are constantly emerging in new locations. Clinical disease is mainly observed in sheep, but cattle were unusually affected during an outbreak of BTV seroype 8 (BTV-8) in Europe. We previously developed an experimental vaccine based on recombinant viral protein 2 (VP2) of BTV-8 and non-structural proteins 1 (NS1) and NS2 of BTV-2, mixed with an immunostimulating complex (ISCOM)–matrix adjuvant. We demonstrated that bovine immune responses induced by this vaccine were as good or superior to those induced by a classic commercial inactivated vaccine. In this study, we evaluated the protective efficacy of the experimental vaccine in cattle and, based on the detection of VP7 antibodies, assessed its DIVA compliancy following virus challenge. Two groups of BTV-seronegative calves were subcutaneously immunized twice at a 3-week interval with the subunit vaccine (n = 6) or with adjuvant alone (n = 6). Following BTV-8 challenge 3 weeks after second immunization, controls developed viremia and fever associated with other mild clinical signs of bluetongue disease, whereas vaccinated animals were clinically and virologically protected. The vaccine-induced protection was likely mediated by high virus-neutralizing antibody titers directed against VP2 and perhaps by cellular responses to NS1 and NS2. T lymphocyte responses were cross-reactive between BTV-2 and BTV-8, suggesting that NS1 and NS2 may provide the basis of an adaptable vaccine that can be varied by using VP2 of different serotypes. The detection of different levels of VP7 antibodies in vaccinated animals and controls after challenge suggested a compliancy between the vaccine and the DIVA companion test. This BTV subunit vaccine is a promising candidate that should be further evaluated and developed to protect against different serotypes.     

Feasibility of azithromycin prophylaxis during a pertussis outbreak among healthcare workers in a university hospital in Paris.

The objective of the present study was to evaluate the feasibility of azithromycin prophylaxis with respect to tolerability and compliance during a pertussis outbreak among healthcare workers in a university hospital ward. Compliance with the prophylaxis regimen was 89%; compliance was 75% from intent-to-treat perspective. The rate of adverse events was 33%. Female sex was associated with reporting of adverse events. Nonstudents and healthcare workers who reported adverse events were less compliant with the prophylaxis regimen.