Jean-Philippe Leroy

From tailor-made to ready-to-wear meningococcal B vaccines: longitudinal study of a clonal meningococcal B outbreak

BACKGROUND Outer-membrane-vesicle vaccines for meningococcal B outbreaks are complex and time consuming to develop. We studied the use of already available vaccine to control an outbreak caused by a genetically close strain. METHODS From 2006 to 2009, all individuals younger than 20 years living in the region of Normandy, France, in which an outbreak caused by a B:14:P1.7,16 strain occurred, were eligible to receive MenBvac, a Norwegian vaccine designed 20 years earlier against a strain sharing the same serosubtype (B:15:P1.7,16). The immunogenicity (in a randomly selected cohort of 400 children aged 1-5 years), safety, and epidemiological effect of the vaccination were assessed. FINDINGS 26,014 individuals were eligible to receive the vaccine. Shortage of vaccine production prompted start of the campaign in the highest incidence groups (1-5 years). 16,709 (64%) received a complete vaccination schedule of whom 13,589 (81%) received a 2+1 dose schedule (week 0, week 6, and month 8). At 6 weeks after the third dose, of 235 vaccinees for whom samples were available, 206 (88%) had a seroresponse, and 108 (56 %) of 193 had a seroresponse at 15 months. These results were similar to those described for tailor-made vaccines and their homologous strain. Only previously described adverse effects occurred. The incidence of B:14:P1.7,16 cases decreased significantly in the vaccine targeted population after the primary vaccination period (from 31·6 per 100,000 to 5·9 per 100,000; p=0·001). INTERPRETATION The ready-to-wear approach is reliable if epidemic and vaccine strains are genetically close. Other meningococcal B clonal outbreaks might benefit from this strategy; and previously described outer-membrane-vesicle vaccines can be effective against various strains. FUNDING French Ministry of Health.

Impact of MenBvac, an outer membrane vesicle (OMV) vaccine, on the meningococcal carriage.

The aim of the study was to analyze the impact of MenBvac, an outer membrane vesicle (OMV) vaccine against P1.7,16 strains, on meningococcal carriage. During a B:14:P1.7,16/ST-32 outbreak in Normandy (France), children aged 1-7 years were randomly selected to participate in the study. Among the 1082 volunteers, there were 17 Neisseria meningitidis carriers (carriage rate of 1.57%). MenBvac vaccination appeared associated with lower carriage rate, i.e., 0.31% among the vaccinated children versus 2.10% among the non-vaccinated (p=0.03). The beneficial effect on carriage was observed regardless of the strain serogroup. OMV-vaccinated mice also showed reduction of bacterial acquisition of OMV-homolog and hererolog strains in respiratory pathways after intranasal challenge. These results suggest that meningococcal OMV-based vaccines reduce meningococcal carriage and may hence confer herd immunity.

Evolution of immune response against Neisseria meningitidis B:14:P1.7,16 before and after the outer membrane vesicle vaccine MenBvac

A meningococcal B:14:P1.7,16 outbreak in Normandy (France) was recently controlled using MenBvac, an outer membrane vesicle vaccine previously designed against the B:15:P1.7,16 strain. The further emergence of a new B:14:P1.7,16 outbreak in another district in Normandy led us to explore immunity against B:14:P1.7,16 before and after the MenBvac campaign using a 2+1 (day 0, week 6, month 8) schedule. Children (1-5 years) were sampled before, during and up to one year after vaccination. Serum bactericidal activity against B:14:P1.7,16 was titrated using human complement (hSBA) and immune response was defined by hSBA titer ≥4 as a surrogate for protection. The percentage of hSBA titer ≥4 was 10.8% before vaccination, raised to 84.1% 6 weeks after the completion of the schedule, but declined to 39.7% one year later. This level is lower than the targeted 60% level and suggests only short-term persistence of response against B:14:P1.7,16 using this schedule.

Physician satisfaction with transition from CPOE to paper-based prescription

INTRODUCTION In January 2015, Rouen University Hospitals information system experienced serious issues. It was necessary to rapidly switch from the computerized provider order entry (CPOE) system towards a paper-based order entry (PBOE) system. This was an opportunity to evaluate prescriber opinion on the two provider order entry (POE) systems. METHODS All residents were asked to fill an augmented version of the POE satisfaction and usage survey for both POE systems. The results were compared to identify the strengths and weaknesses of each system. RESULTS Fifty-one respondents had used the CPOE system and the PBOE system. Overall, satisfaction was higher with PBOE than CPOE (odds ratio (OR)=3.74; p<0.001). Usability (OR=4.00; p<0.001), reliability (OR=8.54; p<0.001), time consumption (OR=0.50; p<0.05 - survey statement was formulated negatively), and communication with nurses (OR=14.27; p<0.0001) reached statistically better agreement. The more experience with CPOE the more residents were disillusioned with the reliability (OR=6.55; p<0.01), the usability (OR=5.68; p<0.01) and the patient safety (OR=0.27; p<0.05 - survey statement was formulated negatively) of CPOE. Although safety issues were reported for both systems, the causes were different; PBOE imposed frequent rewriting of the order while CPOE lack of usability might be unsafe. Another important issue with both POE systems was time consumption. CONCLUSION Residents did not report any increase in safety issues with the rapid switch from CPOE to PBOE. They even seemed more satisfied with the rollback to paper, which remains a possible degraded mode in case of health information technology collapse.

SETH: A toxicological expert system in adult drugs poisoning

The aim of SETH is to give end-users specific advice concerning treatment and monitoring of adult drug poisoning. SETH is developed with an off the shelf expert system shell (KBMS) and runs on a microcomputer. No errors were detected in final conclusions in the internal evaluation.