Meera Chand

Insidious risk of severe mycobacterium chimaera infection in cardiac surgery patients

Background. An urgent UK investigation was launched to assess risk of invasive Mycobacterium chimaera infection in cardiothoracic surgery and a possible association with cardiopulmonary bypass heater-cooler units following alerts in Switzerland and The Netherlands. Methods. Parallel investigations were pursued: (1) identification of cardiopulmonary bypass–associated M. chimaera infection through national laboratory and hospital admissions data linkage; (2) cohort study to assess patient risk; (3) microbiological and aerobiological investigations of heater-coolers in situ and under controlled laboratory conditions; and (4) whole-genome sequencing of clinical and environmental isolates. Results. Eighteen probable cases of cardiopulmonary bypass–associated M. chimaera infection were identified; all except one occurred in adults. Patients had undergone valve replacement in 11 hospitals between 2007 and 2015, a median of 19 months prior to onset (range, 3 months to 5 years). Risk to patients increased after 2010 from <0.2 to 1.65 per 10000 person-years in 2013, a 9-fold rise for infections within 2 years of surgery (rate ratio, 9.08 [95% CI, 1.81–87.76]). Endocarditis was the most common presentation (n = 11). To date, 9 patients have died. Investigations identified aerosol release through breaches in heater-cooler tanks. Mycobacterium chimaera and other pathogens were recovered from water and air samples. Phylogenetic analysis found close clustering of strains from probable cases. Conclusions. We identified low but escalating risk of severe M. chimaera infection associated with heater-coolers with cases in a quarter of cardiothoracic centers. Our investigations strengthen etiological evidence for the role of heater-coolers in transmission and raise the possibility of an ongoing, international point-source outbreak. Active management of heater-coolers and heightened clinical awareness are imperative given the consequences of infection.

Increase in scarlet fever notifications in the United Kingdom, 2013/2014.

Increases in scarlet fever above usual seasonal levels are currently being seen across the United Kingdom. Medical practitioners have been alerted to the exceptional increase in incidence. Given the potential for this to signal a population increase in invasive group A streptococcal disease, close monitoring of invasive disease is essential.

Resurgence of scarlet fever in England, 2014–16: a population-based surveillance study

BACKGROUND After decades of decreasing scarlet fever incidence, a dramatic increase was seen in England beginning in 2014. Investigations were launched to assess clinical and epidemiological patterns and identify potential causes. METHODS In this population-based surveillance study, we analysed statutory scarlet fever notifications held by Public Health England from 1911 to 2016 in England and Wales to identify periods of sudden escalation of scarlet fever. Characteristics of cases and outbreaks in England including frequency of complications and hospital admissions were assessed and compared with the pre-upsurge period. Isolates from throat swabs were obtained and were emm typed. FINDINGS Data were retrieved for our analysis between Jan 1, 1911, and Dec 31, 2016. Population rates of scarlet fever increased by a factor of three between 2013 and 2014 from 8·2 to 27·2 per 100 000 (rate ratio [RR] 3·34, 95% CI 3·23-3·45; p<0·0001); further increases were observed in 2015 (30·6 per 100 000) and in 2016 (33·2 per 100 000), which reached the highest number of cases (19 206) and rate of scarlet fever notifcation since 1967. The median age of cases in 2014 was 4 years (IQR 3-7) with an incidence of 186 per 100 000 children under age 10 years. All parts of England saw an increase in incidence, with 620 outbreaks reported in 2016. Hospital admissions for scarlet fever increased by 97% between 2013 and 2016; one in 40 cases were admitted for management of the condition or potential complications. Analysis of strains (n=303) identified a diversity of emm types with emm3 (43%), emm12 (15%), emm1 (11%), and emm4 (9%) being the most common. Longitudinal analysis identified 4-yearly periodicity in population incidence of scarlet fever but of consistently lower magnitude than the current escalation. INTERPRETATION England is experiencing an unprecedented rise in scarlet fever with the highest incidence for nearly 50 years. Reasons for this escalation are unclear and identifying these remains a public health priority. FUNDING None.

Genome analysis following a national increase in Scarlet Fever in England 2014

BackgroundDuring a substantial elevation in scarlet fever (SF) notifications in 2014 a national genomic study was undertaken of Streptococcus pyogenes (Group A Streptococci, GAS) isolates from patients with SF with comparison to isolates from patients with invasive disease (iGAS) to test the hypotheses that the increase in SF was due to either the introduction of one or more new/emerging strains in the population in England or the transmission of a known genetic element through the population of GAS by horizontal gene transfer (HGT) resulting in infections with an increased likelihood of causing SF. Isolates were collected to provide geographical representation, for approximately 5% SF isolates from each region from 1st April 2014 to 18th June 2014. Contemporaneous iGAS isolates for which genomic data were available were included for comparison. Data were analysed in order to determine emm gene sequence type, phylogenetic lineage and genomic clade representation, the presence of known prophage elements and the presence of genes known to confer pathogenicity and resistance to antibiotics.Results555 isolates were analysed, 303 from patients with SF and 252 from patients with iGAS. Isolates from patients with SF were of multiple distinct emm sequence types and phylogenetic lineages. Prior to data normalisation, emm3 was the predominant type (accounting for 42.9% of SF isolates, 130/303 95%CI 37.5–48.5; 14.7% higher than the percentage of emm3 isolates found in the iGAS isolates). Post-normalisation emm types, 4 and 12, were found to be over-represented in patients with SF versus iGAS (p < 0.001). A single gene, ssa, was over-represented in isolates from patients with SF. No single phage was found to be over represented in SF vs iGAS. However, a “meta-ssa” phage defined by the presence of :315.2, SPsP6, MGAS10750.3 or HK360ssa, was found to be over represented. The HKU360.vir phage was not detected yet the HKU360.ssa phage was present in 43/63 emm12 isolates but not found to be over-represented in isolates from patients with SF.ConclusionsThere is no evidence that the increased number of SF cases was a strain-specific or known mobile element specific phenomenon, as the increase in SF cases was associated with multiple lineages of GAS.

Cross-sectional study of Ebola virus disease preparedness among National Health Service hospital trusts in England.

BACKGROUND The largest outbreak of Ebola virus disease (EVD) is ongoing in West Africa. Air-travel data indicate that outside Africa, the UK is among the countries at greatest risk of importing a case of EVD. Hospitals in England were therefore instructed to prepare for the assessment and early management of suspected cases. However, the response of hospitals across England is undetermined. AIM To evaluate the readiness of acute hospitals in England, and to describe the challenges experienced in preparing for suspected cases of EVD. METHODS A cross-sectional study using semi-structured telephone interviews and online surveys of all acute National Health Service (NHS) hospital trusts in England (hospital trusts are the vehicle by which one or more NHS hospitals in a geographical area are managed). FINDINGS In total, 112 hospital trusts completed the survey. All interviewed hospital trusts reported undertaking preparedness activities for suspected cases of EVD, and 97% reported that they were ready to assess suspected cases. Most hospital trusts had considered scenarios in accident & emergency (97%). However, fewer hospital trusts had considered specific obstetric (61%) and paediatric scenarios (79%), the provision of ventilatory and renal support (75%), or resuscitation in the event of cardiorespiratory arrest (56%). Thirty-four hospital trusts reported issues with timely access to category A couriers for sample transportation. Challenges included the choice, use and procurement of personal protective equipment (71%), national guidance interpretation (62%) and resource allocation/management support (38%). CONCLUSION English hospital trusts have engaged well with EVD preparedness. Although subsequent national guidance has addressed some issues identified in this study, there remains further scope for improvement, particularly in a practical direction, for acute care services encountering suspected cases of EVD.

The UK’s multidisciplinary response to an Ebola epidemic

The West African Ebola virus disease (EVD) epidemic was the largest and most devastating outbreak of EVD the world has ever seen. Its impact was felt far from the shores of Guinea, Liberia and Sierra Leone, with public health systems and clinicians across the globe confronted with an international response both in the affected region and within their own borders. The UK had a prominent role in response efforts, particularly in Sierra Leone. This article highlights how UK academic, health service, military, commercial and public health professionals all played a significant role both at home and abroad.

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.

Characteristics and mortality of severe influenza cases treated with parenteral aqueous zanamivir, United Kingdom, October 2009 to January 2011

Aqueous zanamivir solution, an investigational product, was provided by the manufacturer on compassionate grounds for parenteral administration to severe H1N1pdm09 influenza cases during the 2009 pandemic.