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Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns in hospitals and the community

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Science Translational Medicine  25 Oct 2017:
Vol. 9, Issue 413, eaak9745
DOI: 10.1126/scitranslmed.aak9745
  • 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 classificationOverallCC22CC30CC5CC1CC8CC45CC59CC80CC15CC361
    Genetically unrelated cases680462364935421715612
    Genetically clustered with other cases78557846304593426983
      Genetically clustered and epidemiological contacts598 (173)449 (127)36 (8)20 (9)33 (13)4 (2)24 (8)21 (3)2 (1)8 (1)3 (1)
        Only community contacts72 (27)50 (17)3 (1)3 (1)6 (3)4 (2)4 (2)2 (1)
          Different postcode Shared GP practice14 (3)10 (1)2 (1)2 (1)
          Same postcode Shared household25 (11)16 (7)3 (1)4 (2)2 (1)
          Same postcode Shared long-term care facility22 (8)20 (7)2 (1)
          Same postcode Different addresses2 (1)2 (1)
          Same postcode Unresolved9 (4)4 (2)3 (1)2 (1)
        Only hospital contacts371 (118)296 (91)10 (3)15 (7)20 (8)16 (5)5 (2)8 (1)3 (1)
          Ward contact255 (64)212 (52)6 (1)5 (2)10 (4)9 (2)3 (1)8 (1)3 (1)
            Hospital A125 (41)101 (35)6 (1)6 (2)9 (2)3 (1)
            Hospital B48 (14)32 (10)3 (1)2 (1)3 (1)8 (1)
            Hospital C8 (4)4 (2)2 (1)2 (1)
            Multiple hospitals75 (5)75 (5)
          Hospital-wide contact118 (54)85 (39)4 (2)10 (5)10 (4)7 (3)2 (1)
            Hospital A97 (45)70 (33)2 (1)8 (4)8 (3)7 (3)2 (1)
            Hospital B6 (3)2 (1)2 (1)2 (1)
            Hospital C8 (4)6 (3)2 (1)
            Multiple hospitals8 (2)8 (2)
        Both hospital and community contacts156 (28)104 (19)23 (4)2 (1)7 (2)4 (1)16 (1)
          Different postcode Shared GP practice13 (2)13 (2)
          Same postcode Shared household37 (9)17 (3)11 (3)2 (1)3 (1)4 (1)
          Same postcode Shared long-term care facility56 (9)36 (7)4 (1)16 (1)
          Same postcode Different addresses17 (3)5 (2)12 (1)
          Same postcode Unresolved33 (5)33 (5)
      Neither hospital nor community contacts19313410101251057
    Total number of cases146510408279805151411595

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 (2226)

  • 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.aak9745

    This 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 (2226)

    [Download PDF]

    Other Supplementary Material for this manuscript includes the following:

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