A protracted iGAS outbreak in a long-term care facility 2014-2015: control measures and the use of whole-genome sequencing.

BACKGROUND: In 2014, two residents of a long-term care facility (LTCF) developed invasive group A streptococcal (iGAS) infections with identical typing (emm 11), resulting in one death. The second resident recovered but had a subsequent episode of emm 11 iGAS infection 10 months later. This second episode was linked to a third case, within 12 days, leading to a further outbreak investigation. AIM: To combine different techniques to establish whether this was a protracted outbreak, understand transmission pathways and inform appropriate control measures. METHODS: Following a routine response to the first cluster, the second investigation included a care record review. This informed network analysis of case interactions with staff and visitors during 10 days prior to infection. These data were combined with post-outbreak whole-genome sequencing (WGS) using isolates from cases, and staff and resident screening (44 GAS isolates: 11 outbreak-related and 33 sporadic isolates). FINDINGS: Two of the three confirmed iGAS cases died (one suffered two episodes). All iGAS cases, and six non-invasive isolates from 2015, were emm 11 (monophylogenetic WGS clade). Network analysis highlighted only indirect contact through staff-visitor interactions between iGAS cases in 2015. This suggested a common source and transmission propagation through carriage and/or environmental contamination over an 11-month period. CONCLUSIONS: This outbreak highlighted benefits of staff/resident screening and typing as part of routine response. Network analysis and highly discriminatory WGS clarified the protracted nature of the outbreak, supporting findings of hygiene and infection control issues and adding to our understanding of the epidemiology.

Recommendations for detection and rapid management of carbapenemase-producing Enterobacterales outbreaks.

There is large heterogeneity in approaches to tackling nosocomial outbreaks caused by carbapenemase-producing Enterobacterales (CPE), however there is limited guidance on how to approach their management. Rapid and robust infection prevention and control interventions can be effective in preventing and reducing the impact of outbreaks in healthcare environments. We present a stepwise approach to aspects of CPE outbreak management, including the development of an action plan, engagement and communication with key stakeholders, developing a dynamic risk assessment, and staff education. These can provide a blueprint for organisations to create templates and checklists to inform their own outbreak response.

An evaluation of the electronic reporting system for the enhanced surveillance of carbapenemase-producing Gram-negative bacteria in England.

BACKGROUND: An electronic reporting system (ERS) for the enhanced surveillance of carbapenemase-producing Gram-negative bacteria (CPGNB) was launched by Public Health England in May 2015. AIM: This evaluation aimed to assess uptake, timeliness and completeness of data provided and explore potential barriers and facilitators to adopting the system. METHODS: The evaluation comprised a retrospective analysis of surveillance data and semi-structured interviews with ERS users. FINDINGS: The proportion of organisms referred for investigation of carbapenem resistance via ERS increased over the first 12 months post-implementation from 35% to 73%; uptake varied widely across regions of England. Completeness of enhanced data fields was poor in 78% of submitted isolates. The median number of days to report confirmatory test results via ERS was 1 day for the regional service and nine days for the national reference laboratory, which additionally conducts phenotypic testing to confirm carbapenemase negativity. Hindrances to ERS utility included: a lack of designated, ongoing resource for system maintenance, technical support and development; uncertainty about how and when to use ERS and workload. Incomplete data prevented gaining a better understanding of important risk factors and transmission routes of CPGNB in England. CONCLUSION: The ERS is the only surveillance system in England with the potential to gather intelligence on important risk factors for CPGNB to inform public health measures to control their spread. Although the ERS captures more information on CPGNB than other surveillance systems, timeliness and completeness of the enhanced data require substantial improvements in order to deliver the desired health benefits.

Whole-genome sequencing in the investigation of recurrent invasive group A streptococcus outbreaks in a maternity unit.

BACKGROUND: The clinical manifestations of group A streptococcus (GAS) (Streptococcus pyogenes) are diverse, ranging from asymptomatic colonization to devastating invasive disease. Maternity-related clusters of invasive GAS (iGAS) infection are complex to investigate and control, especially if recurrent. AIM: To investigate three episodes of emm 75 GAS/iGAS infection in maternity patients at one hospital site over a four-year period (two with monophyletic ancestry). METHODS: The episodes are described, together with whole-genome sequence (WGS) isolate analyses. Single nucleotide polymorphism differences were compared with contemporaneous emm 75 genomes. FINDINGS: Over the four-year study period, seven mothers had emm 75 GAS/iGAS and one mother had emm 3 iGAS (in year 4) (subsequently discounted as linked). Three (clinical/screening samples) of the seven babies of emm-75-positive mothers and three screened healthcare workers were positive for emm 75 GAS. WGS similarity suggested a shared ancestral lineage and a common source transmission, but directionality of transmission cannot be inferred. However, the findings indicate that persistence of a particular clone in a given setting may be long term. CONCLUSIONS: Occupational health procedures were enhanced, staff were screened, and antibiotic therapy was provided to GAS-positive staff and patients. The definitive source of infection could not be identified, although staff-patient transmission was the most likely route. The pattern of clonal GAS transmission over the four-year study period suggests that long-term persistence of GAS may have occurred.

An outbreak of multidrug-resistant Pseudomonas aeruginosa in a burns service in the North of England: challenges of infection prevention and control in a complex setting.

BACKGROUND: Burns patients are at high risk of nosocomial infection, and Pseudomonas aeruginosa is one of the most common causes of wound and systemic infections resulting in significant morbidity and mortality in burns patients. AIM: To describe an outbreak of multidrug-resistant P. aeruginosa (MDR-Pa) at a specialist burns service and highlight the challenges in identifying the reservoir of infection despite extensive epidemiological, microbiological, and environmental investigations. METHODS: Multi-disciplinary outbreak control investigation. FINDINGS: Following an inter-hospital transfer of a burns patient from another country, an admission screen revealed that the patient was colonized with MDR-Pa. Subsequently nine more patients contracted MDR-Pa in the period from November 2015 to September 2017. Given the relatively long gap between confirmation of the index and subsequent cases, it was not possible to identify with certainty the reservoirs and mechanisms of spread of infection, although contamination of the burns service environment and equipment are likely to be contributory factors. CONCLUSION: Preventing infection transmission in specialist burns services is highly challenging, and it may not always be possible to identify and eradicate the reservoirs of infection for P. aeruginosa outbreaks. Our study supports the literature, providing additional evidence that inanimate, common contact surfaces play an important role in nosocomial transmission of P. aeruginosa. These surfaces should either be decontaminated efficiently between patient contacts or be single patient use. Enhanced vigilance is crucial, and, with strict adherence to infection prevention and control procedures, it is possible to reduce the risk of acquisition and spread of infection in patients.

Nosocomial outbreak of staphyloccocal scalded skin syndrome in neonates in England, December 2012 to March 2013.

Staphylococcal scalded skin syndrome (SSSS) is a blistering skin condition caused by exfoliative toxin-producing strains of Staphylococcus aureus. Outbreaks of SSSS in maternity settings are rarely reported. We describe an outbreak of SSSS that occurred among neonates born at a maternity unit in England during December 2012 to March 2013. Detailed epidemiological and microbiological investigations were undertaken. Eight neonates were found to be infected with the outbreak strain of S. aureus, of spa type t346, representing a single pulsotype. All eight isolates contained genes encoding exfoliative toxin A (eta) and six of them contained genes encoding toxin B (etb). Nasal swabs taken during targeted staff screening yielded a staphylococcal carriage rate of 21% (17/80), but none contained the outbreak strain. Mass screening involving multi-site swabbing and pooled, enrichment culture identified a healthcare worker (HCW) with the outbreak strain. This HCW was known to have a chronic skin condition and their initial nasal screen was negative. The outbreak ended when they were excluded from work. This outbreak highlights the need for implementing robust swabbing and culture methodswhen conventional techniques are unsuccessful in identifying staff carrier(s). This study adds to the growing body of evidence on the role of HCWs in nosocomial transmission of S. aureus.

Observational study to investigate vertically acquired passive immunity in babies of mothers vaccinated against H1N1v during pregnancy.

OBJECTIVE: The primary objective was to determine the proportion of babies who acquired passive immunity to A/H1N1v, born to mothers who accepted vaccination as part of the national vaccination programme while pregnant (during the second and/or third trimesters) against the novel A/H1N1v influenza virus (exposed group) compared with unvaccinated (unexposed) mothers. DESIGN: An observational study at three sites in the UK. The purpose was to determine if mothers immunised against A/H1N1v during the pandemic vaccination period transferred that immunity to their child in utero. SETTING: Three sites in the UK [Queen's Medical Centre, Nottingham; City Hospital, Nottingham (both forming University Hospitals Nottingham), and Leicester Royal Infirmary (part of University Hospitals Leicester)]. PARTICIPANTS: All pregnant women in the second and third trimester presenting at the NHS hospitals above to deliver were eligible to participate in the study. Women were included regardless of age, social class, ethnicity, gravida and parity status, past and current medical history (including current medications), ethnicity, mode of delivery and pregnancy outcome (live/stillbirth). INTERVENTIONS: At enrolment, participants provided written consent and completed a questionnaire. At parturition, venous cord blood was obtained for serological antibody analysis. Serological analysis was undertaken by the Respiratory Virus Unit (RVU), Health Protection Agency (HPA) Centre for Infections, London. MAIN OUTCOME MEASURES: The primary end point in the study was the serological results of the cord blood samples for immunity to A/H1N1v. Regarding a suitable threshold for the determination of a serological response consistent with clinical protection, this issue is somewhat complex for pandemic influenza. The European Medicines Agency (EMEA) Committee for Human Medicinal Products (CHMP) judges that a haemagglutination inhibition (HI) titre of 1 : 40 is an acceptable threshold. However, this level was set in the context of licensing plain trivalent seasonal vaccine, where a titre of 1 : 40 is but one of several related immunogenicity criteria, and supported by paired sera capable of demonstrating a fourfold rise in antibody titre in response to vaccination. The current study mainly investigated the effects of an AS03-adjuvanted monovalent vaccine, and it was not possible to obtain paired sera where the initial sample was taken before vaccination (in vaccinated subjects). Of possibly greater relevance is the fact that it has been established from the study of early outbreaks of pandemic influenza in secondary schools in the UK (HPA, unpublished observations) that an HI antibody titre of 1 : 32 seems to be the threshold for a humoral response to 'wild-type' A/H1N1v infection. On that basis, a threshold of 1 : 32 is at least as appropriate as one of 1 : 40, especially in unvaccinated individuals. Given the difficulties that would accrue by applying thresholds of 1 : 32 in unvaccinated patients and 1 : 40 in vaccinated patients, we have therefore applied a threshold of 1 : 32 and 1 : 40, to increase the robustness of our findings. Differences arising are described. A microneutralisation (MN) titre of 1 : 40 may be also used, although it is not part of the CHMP criteria for vaccine licensure. Nonetheless, we utilised this analysis as a secondary end point, based on a conservative threshold of 1 : 60. RESULTS: Reverse cumulative distribution percentage curves for haemagglutinin dilution and MN titres demonstrate background immunity in babies of unvaccinated mothers of 25%-30%. Humoral immunity in babies of vaccinated mothers was present in 80% of the group. The difference in positive immunity between the babies of unvaccinated and vaccinated mothers was statistically significant (chi-squared test, p < 0.001). CONCLUSIONS: Our findings reveal a highly significant difference in HI titres between babies born to mothers vaccinated with pandemic-specific vaccine against A/H1N1v during the 2009-10 pandemic period. The subjects recruited were comparable from a baseline perspective and thus do not represent different groups that otherwise could have introduced bias into the study. Continued circulation of 2009 A/H1N1-like viruses is uncertain, but is possible as seasonal influenza in years to come. It is possible that future seasonal waves may display increased virulence. Given the adverse outcomes experienced for a small proportion of pregnant women during the influenza pandemic of 2009-10, this study provides useful evidence to support vaccination in pregnancy to protect both the mother and baby. FUNDING: The National Institute for Health Research Health Technology Assessment programme.