Heather Murdoch

Risk of hospitalisation with fever following MenB vaccination: self-controlled case series analysis

Objective To investigate a possible association between fever admissions and 4 component Meningococcal B (4CMenB). Design 4CMenB is given at 8 and 16 weeks in the first year of life. Self-controlled case series using linked routinely collected healthcare data, where the risk period was the 3 days immediately following receipt of a vaccine dose. Patients Children aged under 1 year in Scotland preintroduction and postintroduction of 4CMenB vaccine (pre—September 2014 to August 2015 and post—September 2015 to June 2016). Main outcome measures Hospitalisations for fever attributable to 4CMenB vaccine. Results The postintroduction model showed an increased risk in the 3 days after dose 1 (relative incidence (RI), 10.78; 95% CI: 8.31 to 14.00) and dose 3 (RI, 9.80; 95% CI: 7.10 to 13.62), with a smaller increased risk after dose 2 (RI, 2.20; 95% CI: 1.27 to 3.82). The magnitude of these effects was greater than in the preintroduction model. The attributable fractions were 90.7%, 54.8% and 89.7%, equating to 162, 14 and 84 vaccine attributable cases per 100 000 doses, respectively. This is equivalent to 102 extra hospitalisations in Scotland annually, based on a birth cohort of 55 100 and extrapolated to 1430 across the UK based on a birth cohort of 777 165. Conclusion There is an increased risk of hospital admission with fever within 3 days of the routine childhood immunisations at 8 and 16 weeks following introduction of 4CMenB vaccine. The results indicate that further understanding of the current use of prophylactic paracetamol is needed. Communication to parents and health professionals may also need to be re-examined, and guidance on the use of prophylactic paracetamol reinforced.

Control of Clostridium difficile infection in the hospital setting

Clostridium difficile infection (CDI) has emerged as a leading challenge in the control of healthcare-associated infection (HCAI). The epidemiology of CDI has changed dramatically, this is associated with emergence of ‘hypervirulent’ strains, particularly PCR ribotype 027. Despite the epidemic spread of these strains, there are recent reports of decreasing incidence from healthcare facilities where multi-facetted targeted control programs have been implemented. We consider these changes in epidemiology and reflect on the tools available to control CDI in the hospital setting. The precise repertoire of measures adopted and emphasis on different interventions will vary, not only between healthcare systems, but also within different institutions within the same healthcare system. Finally, we consider both the sustainability of reductions already achieved, and the potential to reduce CDI further. This takes account of newly emerging data on more recent changes in the epidemiology of CDI, and the potential of novel interventions to decrease the burden of disease.

Active monitoring of potential adverse immunisation events with hospital admission data and linked analysis in Scotland

Abstract Background Maintaining and assuring excellent immunisation safety is essential. Suspected adverse events are passively reported to the UK Medicines and Healthcare Products Regulatory Agency (MHRA). We developed a supplementary system to proactively identify recent potential adverse events resulting in admission to hospital and applied this system to rotavirus vaccine, offered to all infants across Scotland from July, 2013, at age 2 and 3 month visits. Methods All general and acute inpatient and day cases in hospitals across Scotland were included. Records for predefined potential adverse events were extracted with International Classification of Diseases 10 codes. For rotavirus vaccine, inclusion criteria were age less than 2 years, with codes of intussusception, Kawasaki disease, or anaphylaxis; and haematochezia, an intussusception marker. Primary outcome was the number of infants per month meeting inclusion criteria. Historical data were extracted, enabling presentation with Statistical Process Control methodology, with lower and upper control limits. New data points exceeding upper control limits were signals that needed further investigation. These included extracting all associated diagnostic codes, age breakdown to assess plausibility in relation to vaccination age and hospital locations, and, after formal approval, linking admissions to hospital to vaccination and laboratory reports. Findings Every month in Scotland over 9000 rotavirus vaccine doses are administered. Admissions to hospital for intussusception, Kawasaki disease, and anaphylaxis did not exceed upper control limits after vaccination. Admissions for haematochezia exceeded the upper control limit in August, 2013, 1 month after vaccine introduction. Further investigations showed that 45 infants had been admitted with the condition since vaccine implementation, 23 had been vaccinated, but only two had been admitted within 7 days of vaccination, the specific risk period. Neither of these two infants had received the vaccine outside the recommended age period, and both had other compatible reasons for haematochezia. Interpretation We have developed a timely active system for monitoring adverse events potentially associated with vaccination in Scotland. The system is limited to specified events, but it supplements MHRA reporting to provide added assurance of robust monitoring. Signals of interest can be rapidly further investigated, including near-time data linkage to the national childhood immunisation records, leading to formal epidemiological studies, if required. Funding NHS National Services Scotland.

Evidence-Based Medicine applied to the control of communicable disease incidents when evidence is scarce and the time is limited

Control of acute communicable disease incidents demands rapid risk assessment, often with minimal peer-reviewed literature available but conducted in the publics view. This paper explores how methods of evidence-based medicine (EBM) can be applied in this scenario to improve decision making and risk communication. A working group with members from EBM organisations, public health institutions and the European Centre for Disease Prevention and Control used a six-stage framework for rapid risk assessments: preparation, risk detection/verification, risk assessment, development of advice, implementation, and evaluation. It concluded that data from observational studies, surveillance and modelling play a vital role in the evidence base. However, there is a need to further develop protocols and standards, to perform, report and register outbreak investigations more systematically and rigorously, and to allow rapid retrieval of the evidence in emergencies. Lack of evidence for risk assessment and advice (usual for new and emerging diseases) should be made explicit to policy makers and the public. Priorities are to improve templates for reporting and assessing the quality of case and outbreak reports, apply grading systems to evidence generated from field investigations, improve retrieval systems for incident reports internationally, and assess how to communicate uncertainties of scientific evidence more explicitly.

Changing molecular epidemiology of rotavirus infection after introduction of monovalent rotavirus vaccination in Scotland

BACKGROUND Rotaviruses (RV) are the leading cause of gastroenteritis in children less than five years of age worldwide. Rotarix®, a live attenuated monovalent vaccine containing a RV strain of G1P[8] specificity has been included in the childhood immunisation schedule from June 2013 in Scotland. This study aimed to characterise the prevalent RV strains in Scotland before and after the introduction of the RV vaccine. METHODS RV positive faecal samples from Scottish virology laboratories covering the years 2012-2015 were genotyped. Viral RNA was extracted from faecal suspensions. VP7 and VP4 gene specific primers were used for multiplex hemi-nested PCRs and sequencing. Mann-Whitney U test and Chi-square test were used for statistical comparison. RESULTS There was a decrease in RV positive samples from the Scottish virology laboratories from 7409 samples in the pre-vaccination years (2009-2013) to 760 in 2014-2015, with an annual reduction of RV infections by 74.4% (RR-3.95; 95%-CI, 3.53-4.42, p<0.001). 362 samples from the pre-vaccination period and 278 samples from the post-vaccination were genotyped. There was a drop in prevalence of G1P[8] strains (72.1%, 95%-CI, 67.42-76.33 to 15%, 95%-CI, 11.38-19.79) after introduction of the vaccine. In the post-vaccination period G2P[4] was the dominant strain in Scotland (21.9%, 95%-CI, 17.48-27.17) with increase in G9P[8] (12.9%, 95%-CI, 9.50-7.41), G12P[8] (12.2%, 95%-CI, 8.89-16.60) and G3P[8] (11.9%, 95%-CI, 8.58-16.20) infections. Phylogenetic analysis of the VP7 and VP4 genes showed no major differences between the pre and post-vaccination G1P[8] strains. CONCLUSION This laboratory based surveillance study shows significant reduction in reported RV cases and a shift in proportion from G1P[8] to G2P[4] strains after introduction of RV vaccination in Scotland. The genotyping data from a subset of the total reported RV cases will be used to ascertain cross protection against strains and identify vaccine induced RV strain shifts in the years to come.

PTH-228 Genotyping of rotavirus isolates prior to the introduction of the rotavirus vaccine in scotland and early indications of the impact of the vaccine

Introduction Rotaviruses (RV) are the leading cause of severe gastroenteritis in children less than five years of age worldwide. Rotarix®, a live attenuated monovalent vaccine containing a RV strain of G1P[8] specificity has been included in the routine childhood immunisation schedule from June 2013 in Scotland and is offered to infants under the age of four months in two doses. This study aimed to characterise the prevalent rotavirus strains in Scotland prior to the introduction of the vaccine. Method Rotavirus positive faecal samples from various Scottish regional virology laboratories covering the years 2012–2013, before the introduction of the vaccine, were genotyped. Viral RNA was extracted from faecal suspensions using guanidine isothiocyanate – silica gel extraction method. VP7 and VP4 gene specific multiplex hemi-nested PCRs were used for genotyping. Surveillance systems were established by Health Protection Scotland to monitor the impact of the vaccine. Results A total of 387 samples were genotyped from the regional virology laboratories in Aberdeen, Dundee, Inverness, Glasgow and Edinburgh. The commonest strain in Scotland was G1P[8] accounting for 72.1% of cases. The other strains that were identified were G2P[4] in 7.2%, G4P[8] in 6.9%, G9P[8] in 3.4% and G3P[8] in a further 2.3% of cases. Single cases of G12P[8] and G9P[4] were also found (0.26% respectively). Mixed infections were seen in 5.4% of cases. The provisional uptake for the first dose of Rotarix® vaccine in Scotland for children born between 1stof July to 30thSept 2013 was 92.7%% for the completed course by 12 months. The laboratory confirmed cases of RV reported to HPS via ECOSS (The Electronic Communication of Surveillance in Scotland) showed a marked reduction in confirmed reports of RV compared to a three year average of the years 2011–13. Surrogate markers, e.g. calls to NHS24 and GP consultations with childhood diarrhoea and vomiting, have also shown a downward trend. Conclusion The pre-vaccine surveillance of RV strains confirms that G1P[8] is the predominant strain in Scotland. There has been a promising reduction in laboratory confirmed cases of RV in Scotland following the introduction of the vaccine. The baseline genotyping data will be used to ascertain cross protection against strains and also identify vaccine induced RV strain shifts and an overall evaluation of the programme. Disclosure of interest None Declared.