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An Outbreak of Streptococcus pyogenes in a Mental Health Facility: Advantage of Well-Timed Whole-Genome Sequencing Over emm Typing

Published online by Cambridge University Press:  09 May 2018

Sarah M. Bergin ,
Balamurugan Periaswamy ,
Timothy Barkham ,
Hong Choon Chua ,
Yee Ming Mok ,
Daniel Shuen Sheng Fung ,
Alex Hsin Chuan Su ,
Yen Ling Lee ,
Ming Lai Ivan Chua  and
Poh Yong Ng
...Show all authors
Sarah M. Bergin
Affiliation:
Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore
Balamurugan Periaswamy
Affiliation:
Genome Institute of Singapore, Singapore
Timothy Barkham
Affiliation:
Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Hong Choon Chua
Affiliation:
Institute of Mental Health, Singapore
Yee Ming Mok
Affiliation:
Institute of Mental Health, Singapore
Daniel Shuen Sheng Fung
Affiliation:
Institute of Mental Health, Singapore
Alex Hsin Chuan Su
Affiliation:
Institute of Mental Health, Singapore
Yen Ling Lee
Affiliation:
Genome Institute of Singapore, Singapore
Ming Lai Ivan Chua
Affiliation:
Genome Institute of Singapore, Singapore
Poh Yong Ng
Affiliation:
Genome Institute of Singapore, Singapore
Wei Jia Wendy Soon
Affiliation:
Genome Institute of Singapore, Singapore
Collins Wenhan Chu
Affiliation:
Genome Institute of Singapore, Singapore
Siyun Lucinda Tan
Affiliation:
National Skin Center, Singapore
Mary Meehan
Affiliation:
Irish Meningitis and Sepsis Reference Laboratory, Temple Street Children’s University Hospital, Dublin, Ireland
Brenda Sze Peng Ang
Affiliation:
Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore Lee Kong Chien School of Medicine, Nanyang Technological University, Singapore
Yee Sin Leo
Affiliation:
Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore Lee Kong Chien School of Medicine, Nanyang Technological University, Singapore Saw Swee Hock School of Public Health, National University of Singapore, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Matthew T. G. Holden
Affiliation:
University of St Andrews, St Andrews, Scotland
Partha De
Affiliation:
Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore Lee Kong Chien School of Medicine, Nanyang Technological University, Singapore
Li Yang Hsu
Affiliation:
Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore Saw Swee Hock School of Public Health, National University of Singapore, Singapore
Swaine L. Chen
Affiliation:
Genome Institute of Singapore, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Paola Florez de Sessions
Affiliation:
Genome Institute of Singapore, Singapore
Kalisvar Marimuthu*
Affiliation:
Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore
*
Address correspondence to Kalisvar Marimuthu, 11 Jalan Tan Tock Seng, 308433 Singapore (Kalisvar_marimuthu@ttsh.com.sg).
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Abstract

OBJECTIVE

We report the utility of whole-genome sequencing (WGS) conducted in a clinically relevant time frame (ie, sufficient for guiding management decision), in managing a Streptococcus pyogenes outbreak, and present a comparison of its performance with emm typing.

SETTING

A 2,000-bed tertiary-care psychiatric hospital.

METHODS

Active surveillance was conducted to identify new cases of S. pyogenes. WGS guided targeted epidemiological investigations, and infection control measures were implemented. Single-nucleotide polymorphism (SNP)–based genome phylogeny, emm typing, and multilocus sequence typing (MLST) were performed. We compared the ability of WGS and emm typing to correctly identify person-to-person transmission and to guide the management of the outbreak.

RESULTS

The study included 204 patients and 152 staff. We identified 35 patients and 2 staff members with S. pyogenes. WGS revealed polyclonal S. pyogenes infections with 3 genetically distinct phylogenetic clusters (C1–C3). Cluster C1 isolates were all emm type 4, sequence type 915 and had pairwise SNP differences of 0–5, which suggested recent person-to-person transmissions. Epidemiological investigation revealed that cluster C1 was mediated by dermal colonization and transmission of S. pyogenes in a male residential ward. Clusters C2 and C3 were genomically diverse, with pairwise SNP differences of 21–45 and 26–58, and emm 11 and mostly emm120, respectively. Clusters C2 and C3, which may have been considered person-to-person transmissions by emm typing, were shown by WGS to be unlikely by integrating pairwise SNP differences with epidemiology.

CONCLUSIONS

WGS had higher resolution than emm typing in identifying clusters with recent and ongoing person-to-person transmissions, which allowed implementation of targeted intervention to control the outbreak.

Infect Control Hosp Epidemiol 2018;852–860

Information

Type
Original Article
Information
Infection Control & Hospital Epidemiology , Volume 39 , Issue 7 , July 2018 , pp. 852 - 860
Copyright
© 2018 by The Society for Healthcare Epidemiology of America. All rights reserved. 

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Footnotes

a

First authors of equal contribution.

b

Authors of equal contribution.

References

REFERENCES

1. Lamagni, TL, Darenberg, J, Luca-Harari, B, et al. Epidemiology of severe Streptococcus pyogenes disease in Europe. J Clin Microbiol 2008;46:2359–2367.Google Scholar
2. Walker, MJ, Barnett, TC, McArthur, JD, et al. Disease manifestations and pathogenic mechanisms of Group A Streptococcus. Clin Microbiol Rev 2014;27:264–301.Google Scholar
3. Daneman, N, McGeer, A, Low, DE, et al. Hospital-acquired invasive group a streptococcal infections in Ontario, Canada, 1992–2000. Clin Infect Dis 2005;41:334–342.Google Scholar
4. Kakis, A, Gibbs, L, Eguia, J, et al. An outbreak of group A streptococcal infection among health care workers. Clin Infect Dis 2002;35:1353–1359.Google Scholar
5. Steer, JA, Lamagni, T, Healy, B, et al. Guidelines for prevention and control of group A streptococcal infection in acute healthcare and maternity settings in the UK. J Infect 2012;64:1–18.Google Scholar
6. Auerbach, SB, Schwartz, B, Williams, D, et al. Outbreak of invasive group A streptococcal infections in a nursing home. Lessons on prevention and control. Arch Intern Med 1992;152:1017–1022.Google Scholar
7. Davies, HD, McGeer, A, Schwartz, B, et al. Invasive group A streptococcal infections in Ontario, Canada. Ontario Group A Streptococcal Study Group. New Engl J Med 1996;335:547–554.Google Scholar
8. Harkness, GA, Bentley, DW, Mottley, M, Lee, J. Streptococcus pyogenes outbreak in a long-term care facility. Am J Infect Control 1992;20:142–148.Google Scholar
9. Ruben, FL, Norden, CW, Heisler, B, Korica, Y. An outbreak of Streptococcus pyogenes infections in a nursing home. Ann Intern Med 1984;101:494–496.Google Scholar
10. Schwartz, B, Elliott, JA, Butler, JC, et al. Clusters of invasive group A streptococcal infections in family, hospital, and nursing home settings. Clin Infect Dis 1992;15:277–284.Google Scholar
11. Smith, A, Li, A, Tolomeo, O, Tyrrell, GJ, Jamieson, F, Fisman, D. Mass antibiotic treatment for group A streptococcus outbreaks in two long-term care facilities. Emerg Infect Dis 2003;9:1260–1265.Google Scholar
12. Thigpen, MC, Richards, CL Jr, Lynfield, R, et al. Invasive group A streptococcal infection in older adults in long-term care facilities and the community, United States, 1998–2003. Emerg Infect Dis 2007;13:1852–1859.Google Scholar
13. Clinical and Laboratory Standards Institute (M100-S25). Performance Standards for Antimicrobial Susceptibility Testing: Twenty-Fifth Informational Supplement. January 2015.Google Scholar
14. Harris, SR, Feil, EJ, Holden, MT, et al. Evolution of MRSA during hospital transmission and intercontinental spread. Science 2010;327:469–474.Google Scholar
15. Holt, KE, Baker, S, Weill, FX, et al. Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe. Nat Genet 2012;44:1056–1059.Google Scholar
16. Athey, TB, Teatero, S, Li, A, Marchand-Austin, A, Beall, BW, Fittipaldi, N. Deriving group A Streptococcus typing information from short-read whole-genome sequencing data. J Clin Microbiol 2014;52:1871–1876.Google Scholar
17. Kapatai, G, Coelho, J, Platt, S, Chalker, VJ. Whole genome sequencing of group A Streptococcus: development and evaluation of an automated pipeline for emmgene typing. PeerJ 2017;5:e3226.Google Scholar
18. Inouye, M, Dashnow, H, Raven, LA, et al. SRST2: rapid genomic surveillance for public health and hospital microbiology labs. Genome Med 2014;6:90.Google Scholar
19. Steer, AC, Law, I, Matatolu, L, Beall, BW, Carapetis, JR. Global emm type distribution of group A streptococci: systematic review and implications for vaccine development. Lancet Infect Dis 2009;9:611–616.Google Scholar
20. McGregor, KF, Spratt, BG, Kalia, A, et al. Multilocus sequence typing of Streptococcus pyogenes representing most known emm types and distinctions among subpopulation genetic structures. J Bacteriol 2004;186:4285–4294.Google Scholar
21. Tewodros, W, Kronvall, G. M protein gene (emm type) analysis of group A beta-hemolytic streptococci from Ethiopia reveals unique patterns. J Clin Microbiol 2005;43:4369–4376.Google Scholar
22. Jordan, HT, Richards, CL Jr, Burton, DC, Thigpen, MC, Van Beneden, CA. Group a streptococcal disease in long-term care facilities: descriptive epidemiology and potential control measures. Clin Infect Dis 2007;45:742–752.Google Scholar
23. Facklam, R, Beall, B, Efstratiou, A, et al. emm typing and validation of provisional M types for group A streptococci. Emerg Infect Dis 1999;5:247–253.Google Scholar
24. Turner, CE, Dryden, M, Holden, MT, et al. Molecular analysis of an outbreak of lethal postpartum sepsis caused by Streptococcus pyogenes . J Clin Microbiol 2013;51:2089–2095.Google Scholar
25. Chalker, VJ, Smith, A, Al-Shahib, A, et al. Integration of genomic and other epidemiologic data to investigate and control a cross-institutional outbreak of Streptococcus pyogenes . Emerg Infect Dis 2016;22:973–980.Google Scholar
26. Engelthaler, DM, Valentine, M, Bowers, J, et al. Hypervirulent emm59 clone in invasive group A Streptococcus outbreak, southwestern United States. Emerg Infect Dis 2016;22:734–738.Google Scholar
27. Beres, SB, Carroll, RK, Shea, PR, et al. Molecular complexity of successive bacterial epidemics deconvoluted by comparative pathogenomics. Proc Natl Acad Sci U S A 2010;107:4371–4376.Google Scholar
28. Nasser, W, Beres, SB, Olsen, RJ, et al. Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences. Proc Natl Acad Sci U S A 2014;111:E1768–E1776.Google Scholar
29. Turner, CE, Abbott, J, Lamagni, T, et al. Emergence of a new highly successful acapsular group A Streptococcus clade of genotype emm89 in the United Kingdom. mBio 2015;6:e00622.Google Scholar
30. Koser, CU, Holden, MT, Ellington, MJ, et al. Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. New Engl J Med 2012;366:2267–2275.Google Scholar
31. Fittipaldi, N, Beres, SB, Olsen, RJ, et al. Full-genome dissection of an epidemic of severe invasive disease caused by a hypervirulent, recently emerged clone of group A Streptococcus . Am J Pathol 2012;180:1522–1534.Google Scholar
32. Feil, EJ, Holmes, EC, Bessen, DE, et al. Recombination within natural populations of pathogenic bacteria: short-term empirical estimates and long-term phylogenetic consequences. Proc Natl Acad Sci U S A 2001;98:182–187.Google Scholar
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