Implementing a toolkit for the prevention, management and control of carbapenemase-producing Enterobacteriaceae in English acute hospitals trusts: a qualitative evaluation.

BACKGROUND: Antimicrobial resistance is an increasing problem in hospitals world-wide. Following other countries, English hospitals experienced outbreaks of carbapenemase-producing Enterobacteriaceae (CPE), a bacterial infection commonly resistant to last resort antibiotics. One way to improve CPE prevention, management and control is the production of guidelines, such as the CPE toolkit published by Public Health England in December 2013. The aim of this research was to investigate the implementation of the CPE toolkit and to identify barriers and facilitators to inform future policies. METHODS: Acute hospital trusts (N = 12) were purposively sampled based on their self-assessed CPE colonisation rates and time point of introducing local CPE action plans. Following maximum variation sampling, 44 interviews with hospital staff were conducted between April and August 2017 using a semi-structured topic guide based on the Capability, Opportunity, Motivation and Behaviour Model and the Theoretical Domains Framework, covering areas of influences on behaviour. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: The national CPE toolkit was widely disseminated within infection prevention and control teams (IPCT), but awareness was rare among other hospital staff. Local plans, developed by IPCTs referring to the CPE toolkit while considering local circumstances, were in place in all hospitals. Implementation barriers included: shortage of isolation facilities for CPE patients, time pressures, and competing demands. Facilitators were within hospital and across-hospital collaborations and knowledge sharing, availability of dedicated IPCTs, leadership support and prioritisation of CPE as an important concern. Participants using the CPE toolkit had mixed views, appreciating its readability and clarity about patient management, but voicing concerns about the lack of transparency on the level of evidence and the practicality of implementation. They recommended regular updates, additional clarifications, tailored information and implementation guidance. CONCLUSIONS: There were problems with the awareness and implementation of the CPE toolkit and frontline staff saw room for improvement, identifying implementation barriers and facilitators. An updated CPE toolkit version should provide comprehensive and instructive guidance on evidence-based CPE prevention, management and control procedures and their implementation in a modular format with sections tailored to hospitals' CPE status and to different staff groups.

Expansion of the 'Antibiotic Guardian' one health behavioural campaign across Europe to tackle antibiotic resistance: pilot phase and analysis of AMR knowledge.

Antimicrobial resistance (AMR) is a major public health threat. The UK Antibiotic Guardian (AG) behavioural change campaign developed to tackle AMR was expanded across Europe through translation into Russian, Dutch and French. Demographics and knowledge of AGs were analyzed between 01 November 2016 and 31 December 2016. A total of 367 pledges were received with the majority from the public and health care professionals. The pilot has significantly increased the proportion of pledges from Europe (excluding UK) (χ2 = 108.7, P < 0.001). AMR knowledge was greater in AGs (including the public) compared to the EU Eurobarometer survey. Further promotion across Europe is required to measure an impact on tackling AMR.

National outbreak of Pseudomonas aeruginosa associated with an aftercare solution following piercings, July to September 2016, England.

We report a national Pseudomonas aeruginosa outbreak from a common source following piercings between July and September 2016 in England. The multi-agency outbreak investigation included active case finding, microbiological testing of environmental samples and case specimens including Variable Number Tandem Repeat (VNTR) typing and a retrospective cohort study. Overall, 162 outbreak cases (29 confirmed, 14 probable and 119 possible) and 14 non-outbreak cases were identified; all confirmed cases had ear piercings (93% cartilage). Outbreak cases were predominantly female (95%) and had a median age of 18 years (interquartile range: 13-56 years). Nineteen outbreak cases required surgery under general anaesthetic The same outbreak VNTR type (11,3,5,3,3,3,6,4,7) was isolated from bottles of an aftercare solution from a single manufacturer and in specimens from confirmed cases who attended eight different piercing studios supplied with this product. In the cohort study, use of aftercare solution was associated with becoming a case (aOR: 4.60, 95% confidence interval: 1.65-12.90). Environmental, microbiological and epidemiological investigations confirmed that contamination during production of aftercare solution was the source of this national outbreak; highlighting challenges in the regulation of a cosmetic products used in the piercing industry and that guidance on piercing aftercare may need to be reviewed.

Electronic prescribing system design priorities for antimicrobial stewardship: a cross-sectional survey of 142 UK infection specialists.

Background: The implementation of electronic prescribing and medication administration (EPMA) systems is a priority for hospitals and a potential component of antimicrobial stewardship (AMS). Objectives: To identify software features within EPMA systems that could potentially facilitate AMS and to survey practising UK infection specialist healthcare professionals in order to assign priority to these software features. Methods: A questionnaire was developed using nominal group technique and transmitted via email links through professional networks. The questionnaire collected demographic data, information on priority areas and anticipated impact of EPMA. Responses from different respondent groups were compared using the Mann-Whitney U -test. Results: Responses were received from 164 individuals (142 analysable). Respondents were predominantly specialist infection pharmacists (48%) or medical microbiologists (37%). Of the pharmacists, 59% had experience of EPMA in their hospitals compared with 35% of microbiologists. Pharmacists assigned higher priority to indication prompt ( P < 0.001), allergy checker ( P = 0.003), treatment protocols ( P = 0.003), drug-indication mismatch alerts ( P = 0.031) and prolonged course alerts ( P = 0.041) and lower priority to a dose checker for adults ( P = 0.02) and an interaction checker ( P < 0.05) than microbiologists. A 'soft stop' functionality was rated essential or high priority by 89% of respondents. Potential EPMA software features were expected to have the greatest impact on stewardship, treatment efficacy and patient safety outcomes with lowest impact on Clostridium difficile infection, antimicrobial resistance and drug expenditure. Conclusions: The survey demonstrates key differences in health professionals' opinions of potential healthcare benefits of EPMA, but a consensus of anticipated positive impact on patient safety and AMS.

Improving feedback of surveillance data on antimicrobial consumption, resistance and stewardship in England: putting the data at your Fingertips.

The provision of better access to and use of surveillance data is a key component of the UK 5 Year Antimicrobial Resistance (AMR) Strategy. Since April 2016, PHE has made data on practice (infection prevention and control; antimicrobial stewardship) and outcome (prevalence of AMR, antibiotic use and healthcare-associated infections) available through Fingertips, a publicly accessible web tool (https://fingertips.phe.org.uk/profile/amr-local-indicators). Fingertips provides access to a wide range of public health data presented as thematic profiles, with the above data being available through the 'AMR local indicators' profile. Local data on a range of indicators can be viewed at the level of National Health Service acute trusts, Clinical Commissioning Groups or general practitioner practices, all of which can be compared with the corresponding aggregate values for England to allow benchmarking. The data can be viewed in a range of formats including an overview showing counts and rates, interactive maps, spine charts and graphs that show temporal trends over a range of time scales or allow correlations between pairs of indicators. The aim of the AMR local indicators profile on Fingertips is to support the development of local action plans to optimize antibiotic prescribing and reduce AMR and healthcare-associated infections. Provision of access to relevant information in an easy to use format will help local stakeholders, including healthcare staff, commissioners, Directors of Public Health, academics and the public, to benchmark relevant local AMR data and to monitor the impact of local initiatives to tackle AMR over time.

Investigation using whole genome sequencing of a prolonged restaurant outbreak of Salmonella Typhimurium linked to the building drainage system, England, February 2015 to March 2016.

Following notification of a Salmonella enterica serovar Typhimurium gastroenteritis outbreak, we identified 82 cases linked to a restaurant with symptom onset from 12 February 2015 to 8 March 2016. Seventy-two cases had an isolate matching the nationally unique whole genome sequencing profile (single nucleotide polymorphism (SNP) address: 1.1.1.124.395.395). Interviews established exposure to the restaurant and subsequent case-control analysis identified an association with eating carvery buffet food (adjusted odds ratios (AOR): 20.9; 95% confidence interval (CI): 2.2 - ∞). Environmental inspections, food/water testing, and a food trace-back investigation were inconclusive. Repeated cycles of cleaning were undertaken, including hydrogen peroxide fogging, however, transmission continued. After 7 months of investigation, environmental swabbing identified 106 isolates from kitchen surfaces and restaurant drains matching the outbreak profile. We found structural faults with the drainage system and hypothesised that a reservoir of bacteria in drain biofilm and underfloor flooded areas may have sustained this outbreak. Ineffective drain water-traps (U-bends) may have also contributed by allowing transmission of contaminated aerosols into the kitchen environment. These findings suggest that routine swabbing of sink drain points and inspection of drainage systems should be considered in future outbreak scenarios.

Two Linked Enteroinvasive Escherichia coli Outbreaks, Nottingham, UK, June 2014.

Enteroinvasive Escherichia coli (EIEC) outbreaks are uncommon in Europe. In June 2014, two EIEC outbreaks occurred in Nottingham, UK, within 2 days; outbreak A was linked to a takeaway restaurant and outbreak B to a wedding party. We conducted 2 analytical studies: a case-control study for outbreak A and a cohort study for outbreak B. We tested microbiological and environmental samples, including by using whole-genome sequencing. For both outbreaks combined, we identified 157 probable case-patients; 27 were laboratory-confirmed as EIEC O96:H19-positive. Combined epidemiologic, microbiological, and environmental findings implicated lettuce as the vehicle of infection in outbreak A, but the source of the organism remained unknown. Whole-genome sequencing identified the same organism in cases from both outbreaks, but no epidemiologic link was confirmed. These outbreaks highlight that EIEC has the capacity to cause large and severe gastrointestinal disease outbreaks and should be considered as a potential pathogen in foodborne outbreaks in Europe.

The first recorded outbreak of cryptosporidiosis due to Cryptosporidium cuniculus (formerly rabbit genotype), following a water quality incident.

We report the first identified outbreak of cryptosporidiosis with Cryptosporidium cuniculus following a water quality incident in Northamptonshire, UK. A standardised, enhanced Cryptosporidium exposure questionnaire was administered to all cases of cryptosporidiosis after the incident. Stool samples, water testing, microscopy slides and rabbit gut contents positive for Cryptosporidium were typed at the Cryptosporidium Reference Unit, Singleton Hospital, Swansea. Twenty-three people were microbiologically linked to the incident although other evidence suggests an excess of 422 cases of cryptosporidiosis above baseline. Most were adult females; unusually for cryptosporidiosis there were no affected children identified under the age of 5 years. Water consumption was possibly higher than in national drinking water consumption patterns. Diarrhoea duration was negatively correlated to distance from the water treatment works where the contamination occurred. Oocyst counts were highest in water storage facilities. This outbreak is the first caused by C. cuniculus infection to have been noted and it has conclusively demonstrated that this species can be a human pathogen. Although symptomatically similar to cryptosporidiosis from C. parvum or C. hominis, this outbreak has revealed some differences, in particular no children under 5 were identified and females were over-represented. These dissimilarities are unexplained although we postulate possible explanations.

Emergence of a multidrug-resistant (ASSuTTm) strain of Salmonella enterica serovar Typhimurium DT120 in England in 2011 and the use of multiple-locus variable-number tandem-repeat analysis in supporting outbreak investigations.

In summer 2011, two outbreaks of a unique, multidrug-resistant strain of Salmonella enterica serovar Typhimurium phage type 120 (DT120) occurred mainly in the Midlands, England. The first outbreak occurred among guests attending a wedding in July 2011 ('Wedding outbreak'), followed by a more geographically dispersed outbreak in August and September 2011 ('Midlands outbreak'). Fifty-one cases were confirmed. Detailed epidemiological and environmental health investigations suggested that pork was the most likely source of both outbreaks. All human samples and one pork sample showed the specific multiple-locus variable-number tandem-repeat analysis (MLVA) profile 3-11-12-NA-0211, with at most two loci variations. Trace-back investigations suggested a link to a butcher's shop and a pig farm in the East Midlands. The investigations highlight the utility of molecular analysis (MLVA) in supporting epidemiological investigations of outbreaks caused by S. Typhimurium DT120. Safe handling and cooking of pork by food business operators and consumers are key interventions to prevent future outbreaks.

Determining the impact of professional body recommendations on the screening of acquired carbapenemase-producing Enterobacterales in England.

Introduction: Acquired carbapenemase-producing Gram-negative bacteria are an increasing public health concern globally and have been mandatory to report in England since October 2020. However, in light of the COVID-19 (SARS-CoV-2) pandemic, the Royal College of Pathologists (RCPath) released new guidance "for reducing the need for screening of CRE (carbapenem-resistant Enterobacterales) […] in low-risk areas", without defining "low risk". Methods: To assess the impact of the RCPath recommendations on screening of carbapenemase-producing Enterobacterales (CPE), an online Select Survey was sent to all NHS acute hospitals in England. The initial survey distribution was between March and April 2021 and the survey was relaunched between November 2021 and March 2022. Results: In total, 54 hospitals completed the survey, representing 39.1% of 138 eligible Trusts. All hospitals had a CPE screening policy in place, and the majority of these reflect UKHSA's Framework of actions to contain CPE. Of the 23 hospitals who reported a reduction in CPE screening, only three (13.0%) indicated that this was due to the RCPath recommendations, with 21 (91.3%) indicating that there had been a natural reduction in the number of patients admitted to the Trust who would have previously been screened due to the COVID-19 pandemic. Conclusion: For most surveyed hospitals, CPE screening was not reduced due to the RCPath recommendations. However, the results highlighted that there is a large amount of individual variation in CPE screening practices and diagnostic testing between hospitals.

Epidemiology of carbapenemase-producing Enterobacterales in England, May 2015-March 2019: national enhanced surveillance findings and approach.

BACKGROUND: In response to increasing numbers of carbapenemase-producing Enterobacterales (CPE) in England, Public Health England (PHE) launched an electronic reporting system (ERS) for the enhanced surveillance of carbapenemase-producing Gram-negative bacteria. Our study aimed to describe system engagement and the epidemiology of CPE in England. METHODS: Engagement with the ERS was assessed by calculating the proportion of referrals submitted this system. ERS data were extracted and cases defined as patients with CPE isolated from a screening or clinical specimen in England between 1st May 2015 to 31st March 2019. Descriptive summary statistics for each variable were prepared. RESULTS: The ERS processed 12,656 suspected CPE reports. Uptake of the ERS by local microbiology laboratories varied, with approximately 70% of referrals made via the ERS by April 2016; this steadily decreased after March 2018. Six-thousand eight-hundred and fifty-seven cases were included in the analysis. Most cases were from colonised patients (80.6%) rather than infected, and the majority were inpatients in acute hospital settings (87.3%). Carbapenemases were most frequently detected in Klebsiella pneumoniae (39.1%) and Escherichia coli (30.3%). The most frequently identified carbapenemase families were OXA-48-like (45.1%) and KPC (26.4%). Enhanced data variables were poorly completed. CONCLUSIONS: The ERS has provided some insight into the epidemiology of CPE in England. An increasing number of routine diagnostic laboratories have introduced methods to routinely identify acquired carbapenemases and PHE has modified its approach to ensure robust surveillance, which is an essential aspect of an effective response to prevent and control the spread of CPE.

Demographic, Knowledge and Impact Analysis of 57,627 Antibiotic Guardians Who Have Pledged to Contribute to Tackling Antimicrobial Resistance.

In 2014, Public Health England (PHE) developed the behavioural change Antibiotic Guardian (AG) campaign to tackle antimicrobial resistance (AMR). This included an online pledge system aimed at healthcare professionals (HCP) and the public. Demographics of AGs were collected when pledging online and analysed by pledge group, type, geography, and source of hearing of the campaign between 24/07/2014⁻31/12/2017. Website visitors and acquisition routes were described using Google analytics data. From November 2016, five questions assessed AMR knowledge which was compared to published Eurobarometer AMR survey results for UK. Behaviour change of AGs was also assessed through an impact questionnaire, evaluating the effect of the campaign on self-reported behaviour around AMR. Overall there were 231,460 unique website visitors from 202 countries resulting in 57,627 English and 652 foreign language pledges. Website visitors increased each year with peaks during European Antibiotic Awareness Day and (EAAD) World Antibiotic Awareness Week (WAAW). Self-direction was the largest acquisition route (55%) with pledges more likely via this route than social media (OR 2.6, 95% CI 2.5⁻2.6). AGs (including the public) were more likely to answer questions correctly than the Eurobarometer UK group (OR 8.5, 95% CI 7.4⁻9.9). AG campaign engagement has increased over the four years with particular increases in the student group. AGs had greater knowledge compared to the Eurobarometer UK population. The latest impact evaluation of the online pledge scheme highlights that it continues to be an effective and inexpensive way to engage people with the problem of AMR especially among those with prior awareness of the topic.

An outbreak of Shigella boydii serotype 20 in January 2015 amongst United Kingdom healthcare workers involved in the Ebola response in Sierra Leone.

In January 2015, Public Health England and the United Kingdom (UK) Ministry of Defence investigated cases of diarrhoea and fever in military personnel recently returned to the UK after supporting the response to the Ebola epidemic in Sierra Leone. Tests for Ebola virus infection were negative. PCR tests detected the ipaH gene in 10/12 faecal specimens, and Shigella boydii serotype 20 was isolated from 7 patients. A case control study was undertaken and analysed using multivariable logistic regression. Consumption of a coronation chicken lunch at the transit camp in Sierra Leone (SL) 24-48 h prior to departure for the UK was significantly associated with disease [adjusted odds ratio (OR) 28.15, 95 % CI: 1.87-422.65]. In the context of heightened concern during the Ebola epidemic, this outbreak highlights the importance of rapid and effective microbiological and epidemiological investigations to identify the aetiological agent in patients presenting with fever and diarrhoea.

Public health professionals' perceptions toward provision of health protection in England: a survey of expectations of Primary Care Trusts and Health Protection Units in the delivery of health protection.

BACKGROUND: Effective health protection requires systematised responses with clear accountabilities. In England, Primary Care Trusts and the Health Protection Agency both have statutory responsibilities for health protection. A Memorandum of Understanding identifies responsibilities of both parties, but there is a potential lack of clarity about responsibility for specific health protection functions. We aimed to investigate professionals' perceptions of responsibility for different health protection functions, to inform future guidance for, and organisation of, health protection in England. METHODS: We sent a postal questionnaire to all health protection professionals in England from the following groups: (a) Directors of Public Health in Primary Care Trusts; (b) Directors of Health Protection Units within the Health Protection Agency; (c) Directors of Public Health in Strategic Health Authorities and; (d) Regional Directors of the Health Protection Agency RESULTS: The response rate exceeded 70%. Variations in perceptions of who should be, and who is, delivering health protection functions were observed within, and between, the professional groups (a)-(d). Concordance in views of which organisation should, and which does deliver was high (> or =90%) for 6 of 18 health protection functions, but much lower (< or =80%) for 6 other functions, including managing the implications of a case of meningitis out of hours, of landfill environmental contamination, vaccination in response to mumps outbreaks, nursing home infection control, monitoring sexually transmitted infections and immunisation training for primary care staff. The proportion of respondents reporting that they felt confident most or all of the time in the safe delivery of a health protection function was strongly correlated with the concordance (r = 0.65, P = 0.0038). CONCLUSION: Whilst we studied professionals' perceptions, rather than actual responses to incidents, our study suggests that there are important areas of health protection where consistent understanding of responsibility for delivery is lacking. There are opportunities to clarify the responsibility for health protection in England, perhaps learning from the approaches used for those health protection functions where we found consistent perceptions of accountability.

An audit of neonatal and infant hepatitis B immunisation and serological testing in two counties of England, 2007-12.

We audited adherence to national hepatitis B virus (HBV) immunisation policy for neonates and infants born to HBV positive mothers in two counties of England during 2007/08 to 2011/12 (n=112 in County X, n=190 in County Y). Over the five year period, 29.9% of at risk neonates in County X and 23.5% in County Y required hepatitis B immunoglobulin (HBIG) at birth. The annual median age of HBIG administration was 0.0-0.5 days. The annual median coverage and timeliness of the first (coverage range 92.3-100.0%; age of administration range 0.0-0.0 days), second (83.8-100.0%; 32.0-42.0 days), third (81.1-100.0%; 62.0-81.0 days) and fourth dose HBV immunisations (44.4-91.9%; 378.0-443.0 days) and serological testing (8.6-81.0%; 450.0-707.0 days) were calculated. Statistically significant variation was found in the coverage of third and fourth dose immunisations in County Y, age of fourth dose immunisation in County X, and the coverage and timeliness of serological testing in both counties (p < 0.05). HBIG and the first three HBV immunisations were commonly administered according to the national schedule. Fourth dose immunisations and serological tests showed poor adherence. We advocate public health interventions to improve immunisation programme outcomes and hepatitis B surface antigen testing.

Maternal obesity and infant mortality: a meta-analysis.

BACKGROUND AND OBJECTIVES: Despite numerous studies reporting an elevated risk of infant mortality among women who are obese, the magnitude of the association is unclear. A systematic review and meta-analysis was undertaken to assess the association between maternal overweight or obesity and infant mortality. METHODS: Four health care databases and gray literature sources were searched and screened against the protocol eligibility criteria. Observational studies reporting on the relationship between maternal overweight and obesity and infant mortality were included. Data extraction and risk of bias assessments were performed. RESULTS: Twenty-four records were included from 783 screened. Obese mothers (BMI ≥30) had greater odds of having an infant death (odds ratio 1.42; 95% confidence interval, 1.24-1.63; P < .001; 11 studies); these odds were greatest for the most obese (BMI >35) (odds ratio 2.03; 95% confidence interval, 1.61-2.56; P < .001; 3 studies). CONCLUSIONS: Our results suggest that the odds of having an infant death are greater for obese mothers and that this risk may increase with greater maternal BMI or weight; however, residual confounding may explain these findings. Given the rising prevalence of maternal obesity, additional high-quality epidemiologic studies to elucidate the actual influence of elevated maternal mass or weight on infant mortality are needed. If a causal link is determined and the biological basis explained, public health strategies to address the issue of maternal obesity will be needed.

Neuraminidase inhibitors for influenza: a review and public health perspective in the aftermath of the 2009 pandemic.

OBJECTIVES: The objectives of this study were to: (1) reflect on key stages in the discovery, development and pre-pandemic use of neuraminidase inhibitors (NAIs), (2) summarise the evidence of NAI effectiveness for treatment and prophylaxis of seasonal influenza prior to the 2009 pandemic, and (3) summarise the evidence base generated during the 2009 pandemic period. DESIGN: A rapid systematic review of evidence published to June 2010 was conducted where existing high-quality systematic reviews formed a baseline and were supplemented with data from other reviews, randomised controlled trials (RCTs) and observational studies. MAIN OUTCOME MEASURES: Severity and duration of symptoms; rates of severe illness, complications and death following treatment for influenza or influenza-like illness; rates of influenza and influenza-like illness following long-term prophylaxis or post-exposure prophylaxis of household contacts. RESULTS: Prior to the 2009 pandemic, evidence from RCTs conducted in seasonal influenza epidemics indicated that NAIs used to treat laboratory-confirmed influenza in healthy adults reduced the duration of illness by one day. NAIs provide high levels of protective efficacy in adults when given long-term or in household-based post-exposure prophylaxis for seasonal influenza. Several 2009 pandemic period observational studies suggest that early treatment may reduce rates of hospitalisation and in-hospital mortality, but data from that period do not substantially increase the evidence base on prophylaxis, although they confirm effectiveness. CONCLUSIONS: NAIs should be deployed during a future pandemic for either post-exposure prophylaxis or treatment depending on national policy considerations and logistics. The existing evidence base on effectiveness against severe outcomes requires supplementation.

Multi-centre observational study of transplacental transmission of influenza antibodies following vaccination with AS03(A)-adjuvanted H1N1 2009 vaccine.

INTRODUCTION: Illness and death from influenza increase during pregnancy. In the United Kingdom pregnant women were targeted in a national programme for vaccination during the H1N1 2009-10 pandemic. METHODS: In this study, pregnant women were recruited in labour from November 9, 2009 to March 10, 2010. Pandemic vaccination status was determined. Venous cord blood collected at delivery was evaluated for transplacental transfer of antibodies by measurement of haemagglutination inhibition and microneutralization titres. RESULTS: Samples were collected from 77 vaccinated and 27 unvaccinated women. Seroprotection (HI titre ≥1:40) was detected in 58 (75.3%, 95% CI 64.2-84.4) cord blood samples from vaccinated women and 5 (18.5%, 95% CI 6.3-38.1) from unvaccinated women (P<0.0001). There was evidence of transplacental seroprotection 8 days after maternal immunization (77.9%, 95 CI 66.2-87.1), maintained in most cases for at least 16 weeks. DISCUSSION: Immunization of pregnant women with AS03(A)-adjuvanted vaccine is followed by transplacental transfer of passive immunity at titres consistent with clinical protection in three-quarters of new-born infants. The findings support national and international pandemic H1N1 2009 recommendations for immunization during pregnancy.

Parameters for the mathematical modelling of Clostridium difficile acquisition and transmission: a systematic review.

INTRODUCTION: Mathematical modelling of Clostridium difficile infection dynamics could contribute to the optimisation of strategies for its prevention and control. The objective of this systematic review was to summarise the available literature specifically identifying the quantitative parameters required for a compartmental mathematical model of Clostridium difficile transmission. METHODS: Six electronic healthcare databases were searched and all screening, data extraction and study quality assessments were undertaken in duplicate. Results were synthesised using a narrative approach. RESULTS: Fifty-four studies met the inclusion criteria. Reproduction numbers for hospital based epidemics were described in two studies with a range from 0.55 to 7. Two studies provided consistent data on incubation periods. For 62% of cases, symptoms occurred in less than 4 weeks (3-28 days) after infection. Evidence on contact patterns was identified in four studies but with limited data reported for populating a mathematical model. Two studies, including one without clinically apparent donor-recipient pairs, provided information on serial intervals for household or ward contacts, showing transmission intervals of <1 week in ward based contacts compared to up to 2 months for household contacts. Eight studies reported recovery rates of between 75%-100% for patients who had been treated with either metronidazole or vancomycin. Forty-nine studies gave recurrence rates of between 3% and 49% but were limited by varying definitions of recurrence. No study was found which specifically reported force of infection or net reproduction numbers. CONCLUSIONS: There is currently scant literature overtly citing estimates of the parameters required to inform the quantitative modelling of Clostridium difficile transmission. Further high quality studies to investigate transmission parameters are required, including through review of published epidemiological studies where these quantitative estimates may not have been explicitly estimated, but that nonetheless contain the relevant data to allow their calculation.

Influenza vaccination for immunocompromised patients: summary of a systematic review and meta-analysis.

Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta-analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta-analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta-analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.