Research and analysis

HPR volume 11 issue 8: news (24 February)

Updated 15 December 2017

1. Group A streptococcal infections: update on seasonal activity during the 2016 to 2017 season

Public Health England continues to monitor notifications of scarlet fever cases in England following the high levels recorded last spring.

According to the second report on group A Streptococcus activity for the current 2016/17 season [1], typical seasonal increases in scarlet fever activity are being reported across England and, as of early-February 2017, activity remains elevated suggesting this may be the fourth year in a row with high levels of scarlet fever incidence.

Invasive disease rates are above average, but remain within the upper bounds of normal seasonal levels for this time of year.

1.1 Reference

1. Group A streptococcal infections: update on seasonal activity, 2016/17.

2. Investigation of Mycobacterium chimaera infection associated with cardiopulmonary bypass: updated guidance published

New guidance published this month provides an updated risk assessment following the identification of further patients with invasive Mycobacterium chimaera infection associated with contaminated heater cooler units (HCUs) used in open-heart surgery. The guidance includes a new requirement for NHS and independent sector cardiothoracic centres across the UK to prospectively inform all patients undergoing open-heart surgery of the potential risk of M. chimaera infection and to contact patients who underwent heart valve surgery since 2013 to inform them of their potential exposure to this organism such that they can seek medical attention if they develop potential signs and symptoms of infection [1]. This exercise will seek to improve early diagnosis in patients who may not otherwise have clinical specimens tested for mycobacterial infection in the wake of continued delays in diagnosing such infections, with potentially severe consequences for patients.

Results of the UK-wide investigations launched in 2015 in response to the M. chimaera threat identified 18 initial cases with heater-cooler associated infections, revealed widespread contamination of water circuits in the implicated heater coolers, demonstrated aerosolisation from the units and identified limited genetic diversity across patient isolates suggestive of a point-source outbreak [2-4]. Ongoing surveillance has identified further cases bringing the total to 26 to date, 25 of whom had undergone repair or replacement of cardiac valves and one a coronary artery bypass graft. Patients had their surgery in 13 NHS Trusts and one private provider between 2007 and 2015. The interval between infection and diagnosis was long, a median 18 months, with most patients diagnosed within two years of surgery (maximum five years). Clinical presentations include endocarditis, sternal wound infection, and disseminated infection; 15 of the cases are known to have died.

As a result of the additional cases identified, the risk to patients undergoing cardiac surgery on cardiopulmonary bypass has been re-assessed. The overall risk across the years during which cases had surgery (2007-2015) remains little changed with one in 5000 patients undergoing heart valve surgery developing infection. However, the annual risk estimates increased after 2007 to reach one in 2000 in 2014 with individual cardiothoracic centres’ risks very heterogeneous. These estimates are likely to under-estimate the true risk to patients given that mycobacterial cultures would not have been routinely performed in patients with endocarditis prior to this outbreak being known.

Clinicians are reminded to consider M. chimaera aetiology in patients with a prior history of open-heart surgery or ECMO presenting with signs and symptoms consistent with endocarditis or other organ/space and deep incisional surgical site or disseminated infection. Any suspected cases (patients with non-tuberculous mycobacterial infection following cardiopulmonary bypass or ECMO) should be reported to local health protection teams. Hospitals should be mindful of the potential for transmission of other pathogens from contaminated heater cooler water circuits during cardiac surgery.

Updated guidelines on the management of heater cooler devices, clinical guidance for secondary care providers, reporting requirements and protocols for environmental sampling of heater coolers are available on the PHE website: Mycobacterial infections linked with heater cooler units.

2.1 References

1. PHE, NHS England, MHRA, HSE, Society for Cardiothoracic Surgery, Association for Cardiothoracic Anaesthesia and Critical Care, et al (February 2017). Infections associated with heater cooler units used in cardiopulmonary bypass and ECMO. Information for healthcare providers in the UK.
2. PHE (2015). Investigation of Mycobacterium chimaera infection associated with cardiopulmonary bypass, HPR 9(15)
3. PHE (2015). Investigation of Mycobacterium chimaera infection associated with cardiopulmonary bypass: an update, HPR 9(18).
4. Chand M, Lamagni T, Kranzer K, Hedge J, Moore G, Parks S et al (2017). Insidious risk of severe Mycobacterium chimaera Infection in cardiac surgery patients, Clin Infect Dis 64: 335-342.

3. Further steps in sequencing pathogens taken by PHE

PHE’s Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit is set to harness whole-genome sequencing (WGS) for Staphylococcus aureus national reference services and enhanced surveillance of MRSA bacteraemia.

A growing literature attests to how WGS is revolutionising the way public health microbiology services are delivered in PHE for gastrointestinal and respiratory pathogens such as Salmonellae and Mycobacterium tuberculosis complex [1,2].

Following extensive validation of its public health utility [3-6], AMRHAI Reference Unit will be formally implementing WGS for the identification and characterisation of Staphylococcus aureus isolates (including MRSA) from April 2017.

The results of reference tests – including (i) lineage determination (typing) based on Multi-Locus Sequence Typing (MLST), (ii) antimicrobial resistance gene detection and (iii) toxin gene profiling – will be derived from WGS.

At this stage, WGS will not be used for outbreak investigations, but during autumn of 2017 current methods (spa typing and pulsed-field gel electrophoresis) will be supplanted by phylogenetic analysis of WGS data providing improvements in outbreak characterisation [6,7]. Similarly, WGS-based inference will not replace phenotypic antibiotic susceptibility testing of S. aureus suspected to have unusual or exceptional resistance at the present time, but this possibility will continue to be explored [8].

Of particular note is the plan to focus on areas where WGS will enhance national public health surveillance. In recent years, as MRSA bacteraemia rates have declined, a marked change has been noted in the molecular epidemiology [9]. To monitor this change more closely, AMRHAI plans to perform WGS on all MRSA bacteraemia isolates from England from April 2017 to March 2019. This work will lead to better understanding of changes in molecular epidemiology and how MRSA clones emerge and spread, both locally and nationally. Linking of WGS data outputs with the demographic, clinical and geographic information from the national Mandatory Bacteraemia Surveillance Programme is planned; also dissemination of the findings via an annual report. It is hoped that increased understanding of the epidemiology of MRSA may inform interventions aimed at further reducing rates of MRSA infection.

Accordingly, with effect from 1 April 2017, AMRHAI invites referral of a single MRSA isolate from each episode of MRSA bacteraemia in England using a standard referral form. As at present, referrals to support national surveillance will be free of charge. For each isolate referred, a strain characterisation report – detailing the MLST of the isolate alongside the presence/absence of a panel of AMR and virulence genes – will be provided. All sequence data will subsequently be deposited in an open access database. For further information, please contact [Angela Kearns][email protected] or [Russell Hope][email protected].

Further information about WGS, including how genomics can be applied to support public health, is available from the e­learning module at: http://public-health-genomics.phe.org.uk/.

3.1 References

1. Ashton PM, Nair S, Peters TM, et al (2016). Identification of Salmonella for public health surveillance using whole genome sequencing, PeerJ (online), 5 April.
2. Pankhurst LJ, del Ojo Elias C, Votintseva AA, et al (2016). Rapid, comprehensive, and affordable mycobacterial diagnosis with whole-genome sequencing: a prospective study, Lancet Respir Med 4:49-58.
3. Sharma M, Nunez-Garcia J, Kearns AM, Doumith M, Butaye P, Argudín MA, et al (2016). Livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA) CC398 isolated from UK animals belong to European lineages Front Microbiol 7:1741.
4. Lahuerta-Marin A, Guelbenzu-Gonzalo M, Pichon B, Allen A, Doumith M, Lavery JF, et al (2016). First report of lukM-positive livestock-associated methicillin-resistant Staphylococcus aureus CC30 from fattening pigs in Northern Ireland, Veterinary Microbiology 182:131-134.
5. Garvey MI, Pichon B, Bradley CW, Moiemen NS, Oppenheim B, Kearns AM (2016). Improved understanding of an outbreak of meticillin resistant Staphylococcus aureus in a regional burns centre via Whole-Genome Sequencing, J Hosp Infect 94: 401-404.
6. Price JR, Golubchik T, Cole K, et al (2014). Whole-Genome Sequencing Shows That Patient-to-Patient Transmission Rarely Accounts for Acquisition of Staphylococcus aureus in an Intensive Care Unit, Clinical Infectious Diseases 58(5): 609-618.
7. Ellington MJ, Ekelund O, Aarestrup FM, et al (2017). The role of whole genome sequencing in antimicrobial susceptibility testing of bacteria: report from the EUCAST Subcommittee, Clin Microbiol Infect 23:2-22.
8. Kearns A, Bou-Antoun S, Pichon B, Yacoub M, Gow I, Ganner M, et al (2015). The changing epidemiology of MRSA bacteraemia in England – PVL on the increase?, ESCMID eLibrary (online) 25 April.

4. Vaccine coverage and vaccine-preventable disease reports in this issue of HPR

The following three immunisation reports are published in this issue of HPR. The links below are to the relevant webpage collections.

4.1 Vaccine coverage (England) report

• Pertussis vaccination programme for pregnant women update: vaccine coverage in England, October to December 2016

4.2 Routine infection reports

• Laboratory confirmed cases of measles, mumps and rubella, England: October to December 2016
• Laboratory confirmed reports of invasive meningococcal disease in England: October to December 2016.