Chimeric yellow fever 17D/DENV-1-4 viruses (CYD-1-4) have been developed as a tetravalent dengue vaccine candidate which is currently being evaluated in efficacy trials in Asia and America. While YF 17D and DENV are mosquito-borne flaviviruses, it has been shown that CYD-1-4 do not replicate after oral infection in mosquitoes and are not transmitted to new hosts. To further document the risk of environmental dissemination of these viruses, we evaluated the replication of CYD-1-4 in ticks, the vector of tick-borne encephalitis virus (TBEV), another member of the flavivirus family. Females of two hard tick species, Ixodes ricinus and Rhipicephalus appendiculatus, were inoculated intracoelomically with CYD-1-4 viruses and parent viruses (DENV-1-4 and YF 17D). Virus persistence and replication was assessed 2, 16, and 44 days post-inoculation by plaque titration and qRT-PCR. CYD-1-4 viruses were detected in I. ricinus ticks at early time points post-inoculation, but with infectious titers at least 100-fold lower than those observed in TBEV-infected ticks. Unlike TBEV, complete viral clearance occurred by day 44 in most ticks except for CYD-2, which had a tendency to decline. In addition, while about 70% of TBEV-infected I. ricinus nymphs acquired infection by co-feeding with infected tick females on non-viremic hosts, no co-feeding transmission of CYD-2 virus was detected. Based on these results, we conclude that the risk of dissemination of the candidate vaccine viruses by tick bite is highly unlikely.
IntroductionExternal Quality Assessment (EQA) schemes are designed to provide a snapshot of laboratory proficiency, identifying issues and providing feedback to improve laboratory performance and inter-laboratory agreement in testing. Currently there are no international EQA schemes for seasonal influenza serology testing. Here we present a feasibility study for conducting an EQA scheme for influenza serology methods.MethodsWe invited participant laboratories from industry, contract research organizations (CROs), academia and public health institutions who regularly conduct hemagglutination inhibition (HAI) and microneutralization (MN) assays and have an interest in serology standardization. In total 16 laboratories returned data including 19 data sets for HAI assays and 9 data sets for MN assays.ResultsWithin run analysis demonstrated good laboratory performance for HAI, with intrinsically higher levels of intra-assay variation for MN assays. Between run analysis showed laboratory and strain specific issues, particularly with B strains for HAI, whilst MN testing was consistently good across labs and strains. Inter-laboratory variability was higher for MN assays than HAI, however both assays showed a significant reduction in inter-laboratory variation when a human sera pool is used as a standard for normalization.DiscussionThis study has received positive feedback from participants, highlighting the benefit such an EQA scheme would have on improving laboratory performance, reducing inter laboratory variation and raising awareness of both harmonized protocol use and the benefit of biological standards for seasonal influenza serology testing.
Risk-taking behaviors of adult bedridden patients in neurosurgery are frequent, however little analyzed. We aimed to estimate from the literature and our clinical experience the incidence of the different clinical pictures. Risk-taking behaviors seem to be more frequent than reported. They are often minor, but they can lead to death, irrespective of the prescription of physical or chemical constraints. We also aimed to contextualize the risks, and to describe the means reducing the consequences for the patients. Two main conditions were identified, the loss of awareness of risk-taking behaviors by the patient, and uncontrolled body motions. Besides, current experience feedback analyses and new non-exclusive technological solutions could limit the complications, while improving prevention with wearable systems, neighborhood sensors, or room monitoring and service robots. Further research is mandatory to develop efficient and reliable systems avoiding complications and saving lives. Ethical and legal issues must also be accounted for, notably concerning the privacy of patients and caregivers.
A122Eur J Hosp Pharm 2013;20(Suppl 1):A1-A238 treatment after the failure of oxaliplatin and irinotecan-based treatment.Purpose To verify the relevance of cetuximab prescription to the local protocol and cheque the label indications for cetuximab in our hospital. Materials and Methods A retrospective study of patients diagnosed with metastatic colorectal cancer between 2006-2012 with available KRAS status. Patients were followed up for a minimum of three months after diagnosis.Results Twenty-six patients were collected (mean age: 62.2 ± 12.6 years; 53.8% male). KRAS mutation was negative in 42.3% (11/26) patients and therefore they were eligible for treatment with cetuximab. Five out of those 11 patients underwent cetuximab treatment (5/11; 45.5%): three associated with oxaliplatin in first-line treatment, one associated with irinotecan in second-line treatment and one as monotherapy in second-line treatment. Four out of these 5 prescriptions of cetuximab were in accordance to our local protocol and label (4/5; 80.0%). One prescription was not in accordance with either the local protocol or the cetuximab label; due to this the patient was treated with oral capecitabine as first-line and cetuximab monotherapy as second-line treatment.Three KRAS-negative patients (3/11; 27.3%) are currently in treatment with irinotecan as second-line therapy.Three KRAS-negative patients were lost to follow-up after undergoing second-line treatment not known to contain a cetuximab prescription (3/11; 27.3%).Fifteen patients positive for KRAS mutation (15/26; 57.7%) were not treated with cetuximab. Background Linezolid (LNZ) is an antibiotic indicated for the treatment of methicillin-resistant Gram-positive infections. Following recent unavailability of fosfomycin in France, local standards for the treatment of nosocomial meningitis and nosocomial brain abscesses (NM-NBA) have temporarily changed. Indeed, in Toulouse's Teaching Hospital, the Anti-infectious Committee has decided to modify its recommendations, changing fosfomycin to LNZ. At the same time, the use of LNZ is strictly controlled in our hospital, in order to preserve antimicrobial activity as long as possible. Purpose To present an overview of the use of LNZ in a neurosurgery ward, in Toulouse's teaching hospital. Materials and Methods We analysed the prescriptions for LNZ between 1 January 2011 and 1 August 2012, collecting data on: type of infection, germ and antibiotic sensitivity, treatment duration, total cost of antibiotic treatment. Results When fosfomycin was still available, LNZ was only prescribed to six patients, none of whom was treated for NM-NBA. When fosfomycin became unavailable, 72 prescriptions were written for LNZ, of which 59 (82%) were for NM-NBA. Of these 59 prescriptions, 54 (92%) were initially empirical; 45 (76%) were revaluated at day 3 with advice from a senior infectious disease specialist, which resulted in 19 treatment discontinuations (42%). Moreover, 29% (17/59) of identified germs were multi-resistant and DGI-072Materials and Methods This...
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