Haemophilus influenzae type b reemergence after combination immunization

An increase in Haemophilus influenzae type b (Hib) in British children has been linked to the widespread use of a diphtheria/tetanus/acellular pertussis combination vaccine (DTaP-Hib). We measured anti-polyribosyl-ribitol phos- phate antibody concentration and avidity before and after a Hib booster in 176 children 2–4 years of age who had received 3 doses of DTP-Hib (either DT whole cell pertus- sis-Hib or DTaP-Hib) combination vaccine in infancy. We also measured pharyngeal carriage of Hib. Antibody con- centrations before and avidity indices after vaccination were low (geometric mean concentration 0.46μg/mL, 95% confidence interval [CI] 0.36–0.58; geometric mean avidity index 0.16, 95% CI 0.14–0.18) and inversely related to the number of previous doses of DTaP-Hib (p = 0.02 and p<0.001, respectively). Hib was found in 2.1% (95% CI 0.7%–6.0%) of study participants. Our data support an association between DTaP-Hib vaccine combinations and clinical Hib disease through an effect on antibody concen- tration and avidit

Safety and efficacy of 2% chlorhexidine gluconate aqueous versus 2% chlorhexidine gluconate in 70% isopropyl alcohol for skin disinfection prior to percutaneous central venous catheter insertion in preterm neonates:The ARCTIC randomised-controlled feasibility trial protocol

Introduction Catheter-related sepsis is one of the most dangerous complications of neonatal intensive care and is associated with significant morbidity and mortality. Use of catheter-care € bundles' has reduced the incidence of catheter-related sepsis, although individual components have not been well studied. Better evidence is needed to guide selection of the most appropriate antiseptic solution for skin disinfection in preterm neonates. This study will inform the feasibility and design of the first randomised controlled trial to examine the safety and efficacy of alcohol-based versus aqueous-based chlorhexidine antiseptic formulations for skin disinfection prior to percutaneous central venous catheterisation in preterm neonates. The antiseptics to be compared are 2% chlorhexidine gluconate (CHG) aqueous and 2% CHG in 70% isopropyl alcohol. Methods and analysis The Antiseptic Randomised Controlled Trial for Insertion of Catheters (ARCTIC) is a two-centre randomised-controlled feasibility trial. At least 100 preterm infants born at <34 weeks' gestation and due to undergo percutaneous insertion of a central venous catheter will be randomly allocated to receive prior skin disinfection with one of the two antiseptic solutions. Outcomes include: i) recruitment and retention rates; ii) completeness of data collection; iii) numbers of enrolled infants meeting case definitions for definite catheter-related sepsis, catheter-associated sepsis and catheter colonisation and iv) safety outcomes of skin morbidity scores recorded daily from catheter insertion until 48 hours post removal. The key feasibility metrics will be reported as proportions with 95% CIs. Estimated prevalence of catheter colonisation will allow calculation of sample size for the large-scale trial. The data will inform whether it will be feasible to progress to a large-scale trial. Ethics and dissemination ARCTIC has been approved by the National Health Service Health Research Authority National Research Ethics Service Committee East of England (Cambridge South) (IRAS ID 163868), was adopted onto the National Institute of Health Research Clinical Research Network portfolio (CPMS ID 19899) and is registered with an International Standard Randomised Control Trials Number (ISRCTN: 82571474; Pre-results) and European Clinical Trials Database number 2015-000874-36. Dissemination plans include presentations at scientific conferences, scientific publications and sharing of the findings with parents via the support of Bliss baby charity

Status of vaccine research and development of vaccines for GBS

Streptococcus agalactiae (group B streptococcus (GBS)) is the leading cause of neonatal sepsis and meningitis in many countries. Intrapartum antibiotic strategies have reduced the incidence of early-onset neonatal GBS in a number of countries but have had no impact on late onset GBS infection (LOD). In low/middle income settings, the disease burden remains uncertain although in several countries of Southern Africa appears comparable to or higher than that of high-income countries. As disease may be rapidly fulminating cases can be missed before appropriate samples are obtained and this may lead to underestimation of the true burden. Given the rapid onset and progression within hours of birth as well as the deficiencies in IAP strategies and absence of a solution for preventing LOD, it is clear that administration of a suitable vaccine in pregnancy could provide a better solution in all settings; it should also be cost effective. The current leading vaccine candidates are CPS-protein conjugate vaccines but protein-based vaccines are also in development and one has recently commenced clinical trials

Guidance for the collection of case report form variables to assess safety in clinical trials of vaccines in pregnancy.

Vaccination in pregnancy is an effective strategy to prevent serious infections in mothers and their infants. Safety of this strategy is of principal importance to all stakeholders. As the number of studies assessing safety of vaccines in pregnancy increases, the need to ensure consistent collection and reporting of critical data to allow comparisons and data pooling becomes more important. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project aims to improve data collection and create a shared understanding of maternal, fetal and neonatal outcomes in order to progress the global agenda for vaccination in pregnancy. The guidance in this document has been developed to harmonize the data collected in case report forms used for safety monitoring in clinical trials of vaccination in pregnant women. Data to be collected is prioritized to allow applicability in diverse research settings, including low and middle-income countries. Standardized data will enable the research community to have a common base upon which to conduct meta-analyses, strengthening the applicability of outcomes to different settings

Attitudes of pregnant women and healthcare professionals towards clinical trials and routine implementation of antenatal vaccination against respiratory syncytial virus : a multicenter questionnaire study

Introduction: Respiratory syncytial virus (RSV) is a common cause of infant hospitalization and mortality. With multiple vaccines in development, we aimed to determine: (1) the awareness of RSV among pregnant women and healthcare professionals (HCPs), and (2) attitudes toward clinical trials and routine implementation of antenatal RSV vaccination.Methods: Separate questionnaires for pregnant women and HCPs were distributed within 4 hospitals in South England (July 2017–January 2018).Results: Responses from 314 pregnant women and 204 HCPs (18% obstetricians, 75% midwives, 7% unknown) were analyzed. Most pregnant women (88%) and midwives (66%) had no/very little awareness of RSV, unlike obstetricians (14%). Among pregnant women, 29% and 75% would likely accept RSV vaccination as part of a trial, or if routinely recommended, respectively. Younger women (16–24 years), those of 21–30 weeks’ gestation, and with experience of RSV were significantly more likely to participate in trials [odds ratio (OR): 1.42 (1.72–9.86); OR: 2.29 (1.22–4.31); OR: 9.07 (1.62–50.86), respectively]. White-British women and those of 21–30 weeks’ gestation were more likely to accept routinely recommended vaccination [OR: 2.16 (1.07–4.13); OR: 2.10 (1.07–4.13)]. Obstetricians were more likely than midwives to support clinical trials [92% vs. 68%, OR: 2.50 (1.01–6.16)] and routine RSV vaccination [89% vs. 79%, OR: 4.08 (1.53–9.81)], as were those with prior knowledge of RSV, and who deemed it serious.Conclusions: RSV awareness is low among pregnant women and midwives. Education will be required to support successful implementation of routine antenatal vaccination. Research is needed to understand reasons for vaccine hesitancy among pregnant women and HCPs, particularly midwives.<br/

Isotopic and Compositional Variations in Single Nuclear Fuel Pellet Particles Analyzed by Nanoscale Secondary Ion Mass Spectrometry

Article published under an ACS AuthorChoice LicenseThe Collaborative Materials Exercise (CMX) is organized by the Nuclear Forensics International Technical Working Group, with the aim of advancing the analytical capabilities of the participating organizations and providing feedback on the best approaches to a nuclear forensic investigation. Here, model nuclear fuel materials from the 5th CMX iteration were analyzed using a NanoSIMS 50L (CAMECA) in order to examine inhomogeneities in the U-235/U-238 ratio and trace element abundance within individual, micrometer scale particles. Two fuel pellets were manufactured for the exercise and labelled CMX-5A and CMX-5B. These pellets were created using different processing techniques, but both had a target enrichment value of U-235/U-238 = 0.01. Particles from these pellets were isolated for isotopic and trace element analysis. Fifteen CMX-5A particles and 20 CMX-5B particles were analyzed, with both sample types displaying inhomogeneities in the U isotopic composition at a sub-micrometer scale within individual particles. Typical particle diameters were similar to 1.5 to 41 mu m for CMX-5A and similar to 1 to 61 mu m for CMX-5B. The CMX-5A particles were shown to be more isotopically homogeneous, with a mean U-235/U-238 atom ratio of 0.0130 +/- 0.0066. The CMX-5B particles showed a predominantly depleted mean U-235/U-238 atom ratio of 0.0063 +/- 0.0094, which is significantly different to the target enrichment value of the pellet and highlights the potential variation of U-235/U-238 in U fuel pellets at the micrometer scale. This study details the successful application of the NanoSIMS 50L in a mock nuclear forensic investigation by optimizing high-resolution imaging for uranium isotopics.Peer reviewe

Impact of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial

Background: Meningococcal conjugate vaccines protect individuals directly, but also confer herd protection by interrupting carriage transmission. This Phase III observer-blind, randomised, controlled study evaluated the effects of meningococcal quadrivalent (ACWY) glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in young adults. Methods: University students (aged 18–24 years) from ten sites in England were randomised to receive two vaccinations one month apart: two doses of Japanese Encephalitis vaccine (controls), two doses of 4CMenB (4CMenB), or one dose of MenACWY-CRM then placebo (MenACWY-CRM). Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over one year. Primary analysis was cross-sectional carriage one month after the vaccine course; secondary analyses included comparison of carriage at any time point after primary analysis until study termination. Findings: 2954 subjects were randomised (control, n=987; 4CMenB, n=988; MenACWY-CRM, n=979); approximately one-third of each group was positive for meningococcal carriage at study entry. By one month, there was no significant difference in carriage between controls and 4CMenB (Odds Ratios (OR) [95% CI]; 1·2 [0·8−1·7]) or MenACWY-CRM (OR [95% CI], 0·9 [0·6–1·3]) groups. From three months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (calculated efficacy 18·2% [95% CI: 3·4–30·8]) and capsular groups BCWY (calculated efficacy 26·6% [95% CI: 10·5–39·9]) compared to control vaccination. Significantly lower carriage rates were also observed in the MenACWY-CRM group compared with controls: calculated efficacies 39·0% [95%CI: 17·3-55·0] and 36.2% [95%CI: 15·6-51·7] for serogroups Y and CWY, respectively. Interpretation: MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates over 12 months post-vaccination and, therefore, may affect transmission where widely implemented