Fig. 1. Map showing the study catchment area in the East of England. The locations of hospitals (n = 3), GP practices (n = 75), and postcode districts are shown for the 1465 study cases. Postcode districts are color-coded to show the number of MRSA-positive cases sampled in each district. A total of 5,012,137 residents lived in the highlighted districts (16,240 km2) according to the 2011 UK Census.
Fig. 2. Pairwise comparison between MRSA relatedness and type of patient contact. For each case, the most closely related MRSA isolate from another case was identified, and the epidemiological contact of each case pair was defined. The number of cases in each epidemiological category is shown as a function of the genetic distance (difference in the number of SNPs in the core genome). (A to D) Genetic distance distribution for cases with hospital contacts alone. Direct contact refers to a link in the same time and place (ward or hospital). Indirect contact refers to a link in the same place but different time. (E) Community contacts (shared residential postcodes or GP practice). (F) Cases with neither hospital nor community contacts. Only cases with MRSA isolates from CCs found in at least one other patient in the population are shown (n = 1459).
Fig. 3. Transmission clusters color-coded on the CC22 phylogeny. Maximum likelihood tree generated from 34,600 SNP sites in the core genome is shown for 1667 CC22 isolates. Colors refer to the type of epidemiological links in clusters of genetically related isolates (maximum 50 SNPs) from multiple cases.
Fig. 4. Exemplars of two patterns of nosocomial MRSA spread. (A) Ward-centric pattern. Eight patients in this transmission cluster had ward contacts in wards B2 and B21, including admission overlaps. Notably, the putative epicenter of transmission was in ward B2 or B21, but the outbreak strain was isolated on later admissions in six of the eight patients, three of which (1090, 727, and 762) were first detected at a different hospital (hospital A) from where they had putatively acquired this strain (that is, in hospital B). (B) Patient-centric pattern. Six patients had stayed in wards visited by patient 388 (that is, A49, A80, and A59) before their MRSA isolation date. Negative MRSA screens before entry to these wards for some patients (1288, 1057, 1488, 1377, and 942) further support hospital acquisition. Isolates from patient 388 were the most basal in the phylogenetic tree, and their diversity enclosed that of isolates from the other patients, providing further indicators for this patient being the potential source for the transmission cluster. Colored blocks other than gray represent ward contacts, which are labeled by a letter to denote the hospital (A or B) and a number that denotes the anonymized ward.
- Table 1. Epidemiological classification of transmission clusters.
Columns are ordered based on decreasing proportion of isolates in each CC. Each cell shows the number of cases and (in parentheses) the number of transmission clusters to which these cases were assigned. The number of transmission clusters in each category is the sum of those of its subcategories. The same applies to the number of cases except for columns “CC22” and “Overall.” A total of seven cases had two different CC22 strains suggestive of mixed colonization or strain replacement that linked them to two different transmission clusters. This explains why the total number of genetically clustered cases (n = 578) is lower than the sum of cases in its subcategories. CCs with genetically unrelated isolates or identified in a single individual from the study population are not shown. “Multiple hospitals” refers to epidemiological contacts from more than one of the three study hospitals (A, B, and C).
Epidemiological classification Overall CC22 CC30 CC5 CC1 CC8 CC45 CC59 CC80 CC15 CC361 Genetically unrelated cases 680 462 36 49 35 42 17 15 6 1 2 Genetically clustered with other cases 785 578 46 30 45 9 34 26 9 8 3 Genetically clustered and epidemiological contacts 598 (173) 449 (127) 36 (8) 20 (9) 33 (13) 4 (2) 24 (8) 21 (3) 2 (1) 8 (1) 3 (1) Only community contacts 72 (27) 50 (17) 3 (1) 3 (1) 6 (3) 4 (2) 4 (2) — 2 (1) — — Different postcode Shared GP practice 14 (3) 10 (1) — — 2 (1) — 2 (1) — — — — Same postcode Shared household 25 (11) 16 (7) 3 (1) — — 4 (2) — — 2 (1) — — Same postcode Shared long-term care facility 22 (8) 20 (7) — — — — 2 (1) — — — — Same postcode Different addresses 2 (1) — — — 2 (1) — — — — — — Same postcode Unresolved 9 (4) 4 (2) — 3 (1) 2 (1) — — — — — — Only hospital contacts 371 (118) 296 (91) 10 (3) 15 (7) 20 (8) — 16 (5) 5 (2) — 8 (1) 3 (1) Ward contact 255 (64) 212 (52) 6 (1) 5 (2) 10 (4) — 9 (2) 3 (1) — 8 (1) 3 (1) Hospital A 125 (41) 101 (35) 6 (1) — 6 (2) — 9 (2) — — — 3 (1) Hospital B 48 (14) 32 (10) — 3 (1) 2 (1) — — 3 (1) — 8 (1) — Hospital C 8 (4) 4 (2) — 2 (1) 2 (1) — — — — — — Multiple hospitals 75 (5) 75 (5) — — — — — — — — — Hospital-wide contact 118 (54) 85 (39) 4 (2) 10 (5) 10 (4) — 7 (3) 2 (1) — — — Hospital A 97 (45) 70 (33) 2 (1) 8 (4) 8 (3) — 7 (3) 2 (1) — — — Hospital B 6 (3) 2 (1) 2 (1) — 2 (1) — — — — — — Hospital C 8 (4) 6 (3) — 2 (1) — — — — — — — Multiple hospitals 8 (2) 8 (2) — — — — — — — — Both hospital and community contacts 156 (28) 104 (19) 23 (4) 2 (1) 7 (2) — 4 (1) 16 (1) — — — Different postcode Shared GP practice 13 (2) 13 (2) — — — — — — — — Same postcode Shared household 37 (9) 17 (3) 11 (3) 2 (1) 3 (1) — 4 (1) — — — — Same postcode Shared long-term care facility 56 (9) 36 (7) — — 4 (1) — — 16 (1) — — — Same postcode Different addresses 17 (3) 5 (2) 12 (1) — — — — — — — — Same postcode Unresolved 33 (5) 33 (5) — — — — — — — — — Neither hospital nor community contacts 193 134 10 10 12 5 10 5 7 — — Total number of cases 1465 1040 82 79 80 51 51 41 15 9 5
Supplementary Materials
www.sciencetranslationalmedicine.org/cgi/content/full/9/413/eaak9745/DC1
Materials and Methods
Fig. S1. Number of isolates sequenced per patient.
Fig. S2. Flowchart summarizing data types and analyses.
Fig. S3. Integration of genomic and epidemiological data to identify transmission clusters.
Fig. S4. Six examples of transmission clusters in different settings.
Fig. S5. Number of heterozygous sites in the core genome per isolate.
Fig. S6. Within-host diversity over time and at a single time point.
Table S1. Proportion of isolates in different CCs.
Table S2. Frequency of epidemiological contacts among genetically unrelated cases.
Table S3. Epidemiological classification of transmission clusters containing five or more cases.
Data file S1. Accession numbers.
References (22–26)
Additional Files
- Supplementary Material for:
Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns in hospitals and the community
Francesc Coll,* Ewan M. Harrison, Michelle S. Toleman, Sandra Reuter, Kathy E. Raven, Beth Blane, Beverley Palmer, A. Ruth M. Kappeler, Nicholas M. Brown, M. Estée Török, Julian Parkhill, Sharon J. Peacock*
*Corresponding author. Email: francesc.coll{at}lshtm.ac.uk (F.C.); sharon.peacock{at}lshtm.ac.uk (S.J.P.)
Published 25 October 2017, Sci. Transl. Med. 9, eaak9745 (2017)
DOI: 10.1126/scitranslmed.aak9745This PDF file includes:
- Materials and Methods
- Fig. S1. Number of isolates sequenced per patient.
- Fig. S2. Flowchart summarizing data types and analyses.
- Fig. S3. Integration of genomic and epidemiological data to identify transmission clusters.
- Fig. S4. Six examples of transmission clusters in different settings.
- Fig. S5. Number of heterozygous sites in the core genome per isolate.
- Fig. S6. Within-host diversity over time and at a single time point.
- Table S1. Proportion of isolates in different CCs.
- Table S2. Frequency of epidemiological contacts among genetically unrelated cases.
- Table S3. Epidemiological classification of transmission clusters containing five or more cases.
- References (22–26)
Other Supplementary Material for this manuscript includes the following:
- Data file S1 (Microsoft Excel format). Accession numbers.
