Jeremy Hawker

Rapid draft sequencing and real-time nanopore sequencing in a hospital outbreak of Salmonella

BackgroundFoodborne outbreaks of Salmonella remain a pressing public health concern. We recently detected a large outbreak of Salmonella enterica serovar Enteritidis phage type 14b affecting more than 30 patients in our hospital. This outbreak was linked to community, national and European-wide cases. Hospital patients with Salmonella are at high risk, and require a rapid response. We initially investigated this outbreak by whole-genome sequencing using a novel rapid protocol on the Illumina MiSeq; we then integrated these data with whole-genome data from surveillance sequencing, thereby placing the outbreak in a national context. Additionally, we investigated the potential of a newly released sequencing technology, the MinION from Oxford Nanopore Technologies, in the management of a hospital outbreak of Salmonella.ResultsWe demonstrate that rapid MiSeq sequencing can reduce the time to answer compared to the standard sequencing protocol with no impact on the results. We show, for the first time, that the MinION can acquire clinically relevant information in real time and within minutes of a DNA library being loaded. MinION sequencing permits confident assignment to species level within 20xa0min. Using a novel streaming phylogenetic placement method samples can be assigned to a serotype in 40xa0min and determined to be part of the outbreak in less than 2xa0h.ConclusionsBoth approaches yielded reliable and actionable clinical information on the Salmonella outbreak in less than half a day. The rapid availability of such information may facilitate more informed epidemiological investigations and influence infection control practices.

Trends in antibiotic prescribing in primary care for clinical syndromes subject to national recommendations to reduce antibiotic resistance, UK 1995–2011: analysis of a large database of primary care consultations

OBJECTIVESnTo measure trends in antibiotic prescribing in UK primary care in relation to nationally recommended best practice.nnnPATIENTS AND METHODSnA descriptive study linking individual patient data on diagnosis and prescription in a large primary care database, covering 537 UK general practices during 1995-2011.nnnRESULTSnThe proportion of cough/cold episodes for which antibiotics were prescribed decreased from 47% in 1995 to 36% in 1999, before increasing to 51% in 2011. There was marked variation by primary care practice in 2011 [10th-90th percentile range (TNPR) 32%-65%]. Antibiotic prescribing for sore throats fell from 77% in 1995 to 62% in 1999 and then stayed broadly stable (TNPR 45%-78%). Where antibiotics were prescribed for sore throat, recommended antibiotics were used in 69% of cases in 2011 (64% in 1995). The use of recommended short-course trimethoprim for urinary tract infection (UTI) in women aged 16-74 years increased from 8% in 1995 to 50% in 2011; however, a quarter of practices prescribed short courses in ≤16% of episodes in 2011. For otitis media, 85% of prescriptions were for recommended antibiotics in 2011, increasing from 77% in 1995. All these changes in annual prescribing were highly statistically significant (P < 0.001).nnnCONCLUSIONSnThe implementation of national guidelines in UK primary care has had mixed success, with prescribing for coughs/colds, both in total and as a proportion of consultations, now being greater than before recommendations were made to reduce it. Extensive variation by practice suggests that there is significant scope to improve prescribing, particularly for coughs/colds and for UTIs.

A multi-country Salmonella Enteritidis phage type 14b outbreak associated with eggs from a German producer: 'near real-time' application of whole genome sequencing and food chain investigations, United Kingdom, May to September 2014.

We report an outbreak of Salmonella Enteritidis phage type 14b (PT14b) in the United Kingdom (UK) between May and September 2014 where Public Health England launched an investigation to identify the source of infection and implement control measures. During the same period, outbreaks caused by a Salmonella Enteritidis strain with a specific multilocus variable-number tandem repeat analysis (MLVA) profile occurred in other European Union Member States. Isolates from a number of persons affected by the UK outbreak, who had initially been tested by MLVA also shared this particular profile. Cases were defined as any person infected with S. Enteritidis PT14b, resident in England or Wales and without history of travel outside of this geographical area during the incubation period, reported from 1 June 2014 onwards, with a MLVA profile of 2–11–9-7–4-3–2-8–9 or a single locus variant thereof. In total, 287 cases met the definition. Food traceback investigations in the UK and other affected European countries linked the outbreaks to chicken eggs from a German company. We undertook whole genome sequencing of isolates from UK and European cases, implicated UK premises, and German eggs: isolates were highly similar. Combined with food traceback information, this confirmed that the UK outbreak was also linked to a German producer.

The effects of school closures on influenza outbreaks and pandemics: systematic review of simulation studies.

Background School closure is a potential intervention during an influenza pandemic and has been investigated in many modelling studies. Objectives To systematically review the effects of school closure on influenza outbreaks as predicted by simulation studies. Methods We searched Medline and Embase for relevant modelling studies published by the end of October 2012, and handsearched key journals. We summarised the predicted effects of school closure on the peak and cumulative attack rates and the duration of the epidemic. We investigated how these predictions depended on the basic reproduction number, the timing and duration of closure and the assumed effects of school closures on contact patterns. Results School closures were usually predicted to be most effective if they caused large reductions in contact, if transmissibility was low (e.g. a basic reproduction number <2), and if attack rates were higher in children than in adults. The cumulative attack rate was expected to change less than the peak, but quantitative predictions varied (e.g. reductions in the peak were frequently 20–60% but some studies predicted >90% reductions or even increases under certain assumptions). This partly reflected differences in model assumptions, such as those regarding population contact patterns. Conclusions Simulation studies suggest that school closure can be a useful control measure during an influenza pandemic, particularly for reducing peak demand on health services. However, it is difficult to accurately quantify the likely benefits. Further studies of the effects of reactive school closures on contact patterns are needed to improve the accuracy of model predictions.

Four-month outbreak of invasive meningococcal disease caused by a rare serogroup B strain, identified through the use of molecular PorA subtyping, England, 2013

Molecular PorA subtyping provides information that increasingly requires the adaptation of standard public health approaches to outbreak management. We report an outbreak of a rare subtype of meningococcal infection not previously identified in the United Kingdom (UK). The outbreak occurred in the Warwickshire area in England between February and June 2013. Molecular subtyping allowed the identification of additional cases, prompting an enhanced public health response that included efforts to identify potential social networks that might benefit from chemoprophylaxis. It also prompted swabbing to define nasopharyngeal carriage in the focal nursery and helped explain the unusual epidemiological pattern. Without subtyping to identify a link, the additional cases would have been managed as sporadic cases in accordance with current UK guidance.

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

These outbreaks highlight the necessity to consider this bacterium as a potential pathogen in foodborne outbreaks.

Cyclospora infection linked to travel to Mexico, June to September 2015

Cyclospora cayetanensis was identified in 176 returned travellers from the Riviera Maya region of Mexico between 1 June and 22 September 2015; 79 in the United Kingdom (UK) and 97 in Canada. UK cases completed a food exposure questionnaire. This increase in reported Cyclospora cases highlights risks of gastrointestinal infections through travelling, limitations in Cyclospora surveillance and the need for improved hygiene in the production of food consumed in holiday resorts.

Whole genome sequencing reveals an outbreak of Salmonella Enteritidis associated with reptile feeder mice in the United Kingdom, 2012-2015

Analysis of whole genome sequencing data uncovered a previously undetected outbreak of Salmonella Enteritidis that had been on-going for four years. Cases were resident in all countries of the United Kingdom and 40% of the cases were aged less than 11 years old. Initial investigations revealed that 30% of cases reported exposure to pet snakes. A case-control study was designed to test the hypothesis that exposure to reptiles or their feed were risk factors. A robust case-definition, based on the single nucleotide polymorphism (SNP) profile, increased the power of the analytical study. Following univariable and multivariable analysis, exposure to snakes was the only variable independently associated with infection (Odds ratio 810 95% CI (85-7715) pxa0<xa00.001). Isolates of S. Enteritidis belonging to the outbreak profile were recovered from reptile feeder mice sampled at the retail and wholesale level. Control measures included improved public health messaging at point of sale, press releases and engagement with public health and veterinary counterparts across Europe. Mice destined to be fed to reptiles are not regarded as pet food and are not routinely tested for pathogenic bacteria. Routine microbiological testing to ensure feeder mice are free from Salmonella is recommended.

Relationship between socioeconomic status and gastrointestinal infections in developed countries: A systematic review protocol

BackgroundThe association between low socioeconomic status (SES) and poor health is well documented in the existing literature. Nonetheless, evidence on the relationship between SES and gastrointestinal (GI) infections is limited, and the mechanisms underlying this relationship are not well understood with published studies pointing to conflicting results. This review aims to identify studies that investigate the relationship between SES and GI infections in developed countries, in order to assess the direction of the association and explore possible explanations for any differences in the risk, incidence or prevalence of GI infections across socioeconomic groups.MethodsThree systematic methods will be used to identify relevant literature: electronic database, reference list and grey literature searching. The databases MEDLINE, Scopus and Web of Science Core Collection will be searched using a broad range of search terms. Screening of the results will be performed by two reviewers using pre-defined inclusion and exclusion criteria. The reference lists of included studies will be searched, and Google will be used to identify grey literature. Observational studies reporting quantitative results on the prevalence or incidence of any symptomatic GI infections by SES, in a representative population sample from a member country of the Organisation for Economic Co-operation and Development (OECD), will be included. Data will be extracted using a standardised form. Study quality will be assessed using the Liverpool University Quality Assessment Tools (LQAT). A narrative synthesis will be performed including tabulation of studies for comparison.DiscussionThis systematic review will consolidate the existing knowledge on the relationship between SES and GI infections. The results will help to identify gaps in the literature and will therefore provide an evidence base for future empirical studies to deepen the understanding of the relationship, including effective study design and appropriate data analysis methods. Ultimately, gaining insight into this relationship will help to inform policies to reduce any health inequalities identified.Systematic review registrationPROSPERO CRD42015027231

Novel public health risk assessment process developed to support syndromic surveillance for the 2012 Olympic and Paralympic Games

Background Syndromic surveillance aims to provide early warning and real time estimates of the extent of incidents; and reassurance about lack of impact of mass gatherings. We describe a novel public health risk assessment process to ensure those leading the response to the 2012 Olympic Games were alerted to unusual activity that was of potential public health importance, and not inundated with multiple statistical ‘alarms’. Methods Statistical alarms were assessed to identify those which needed to result in ‘alerts’ as reliably as possible. There was no previously developed method for this. We identified factors that increased our concern about an alarm suggesting that an ‘alert’ should be made. Results Between 2 July and 12 September 2012, 350 674 signals were analysed resulting in 4118 statistical alarms. Using the risk assessment process, 122 ‘alerts’ were communicated to Olympic incident directors. Conclusions Use of a novel risk assessment process enabled the interpretation of large number of statistical alarms in a manageable way for the period of a sustained mass gathering. This risk assessment process guided the prioritization and could be readily adapted to other surveillance systems. The process, which is novel to our knowledge, continues as a legacy of the Games.