Diverse sources of C. difficile infection identified on whole-genome sequencing.
BACKGROUND
It has been thought that Clostridium difficile infection is transmitted predominantly within health care settings. However, endemic spread has hampered identification of precise sources of infection and the assessment of the efficacy of interventions.


METHODS
From September 2007 through March 2011, we performed whole-genome sequencing on isolates obtained from all symptomatic patients with C. difficile infection identified in health care settings or in the community in Oxfordshire, United Kingdom. We compared single-nucleotide variants (SNVs) between the isolates, using C. difficile evolution rates estimated on the basis of the first and last samples obtained from each of 145 patients, with 0 to 2 SNVs expected between transmitted isolates obtained less than 124 days apart, on the basis of a 95% prediction interval. We then identified plausible epidemiologic links among genetically related cases from data on hospital admissions and community location.


RESULTS
Of 1250 C. difficile cases that were evaluated, 1223 (98%) were successfully sequenced. In a comparison of 957 samples obtained from April 2008 through March 2011 with those obtained from September 2007 onward, a total of 333 isolates (35%) had no more than 2 SNVs from at least 1 earlier case, and 428 isolates (45%) had more than 10 SNVs from all previous cases. Reductions in incidence over time were similar in the two groups, a finding that suggests an effect of interventions targeting the transition from exposure to disease. Of the 333 patients with no more than 2 SNVs (consistent with transmission), 126 patients (38%) had close hospital contact with another patient, and 120 patients (36%) had no hospital or community contact with another patient. Distinct subtypes of infection continued to be identified throughout the study, which suggests a considerable reservoir of C. difficile.


CONCLUSIONS
Over a 3-year period, 45% of C. difficile cases in Oxfordshire were genetically distinct from all previous cases. Genetically diverse sources, in addition to symptomatic patients, play a major part in C. difficile transmission. (Funded by the U.K. Clinical Research Collaboration Translational Infection Research Initiative and others.).
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
David W
DW
Eyre
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Madeleine L
ML
Cule
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Daniel J
DJ
Wilson
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
David
D
Griffiths
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Alison
A
Vaughan
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Lily
L
O'Connor
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Camilla L C
CLC
Ip
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Tanya
T
Golubchik
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Elizabeth M
EM
Batty
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
John M
JM
Finney
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
David H
DH
Wyllie
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Xavier
X
Didelot
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Paolo
P
Piazza
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Rory
R
Bowden
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Kate E
KE
Dingle
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Rosalind M
RM
Harding
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Derrick W
DW
Crook
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Mark H
MH
Wilcox
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
Tim E A
TEA
Peto
Nuffield Department of Clinical Medicine (D.W.E., D.J.W., D.G., A.V., L.O., J.M.F., D.H.W., K.E.D., D.W.C., T.E.A.P., A.S.W.), and the Departments of Statistics (M.L.C., C.L.C.I., T.G., X.D., R.B.) and Zoology (R.M.H.), University of Oxford, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital (D.W.E., M.L.C., D.G., A.V., C.L.C.I., T.G., E.M.B., J.M.F., D.H.W., X.D., R.B., K.E.D., R.M.H., D.W.C., T.E.A.P., A.S.W.), Wellcome Trust Centre for Human Genetics (D.J.W., E.M.B., P.P., R.B.), and Oxford University Hospitals National Health Service Trust (L.O., D.W.C., T.E.A.P.), Oxford, the Leeds Teaching Hospitals and University of Leeds, Department of Microbiology, Leeds General Infirmary, Leeds (M.H.W.), and the Medical Research Council, Clinical Trials Unit, London (A.S.W.) - all in the United Kingdom.
A Sarah
AS
Walker
D000368:Aged; D000369:Aged, 80 and over; D016360:Clostridioides difficile / Q000235:genetics* / Q000302:isolation & purification; D003015:Clostridium Infections / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D003428:Cross Infection / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D004269:DNA, Bacterial / Q000032:analysis; D018562:Disease Transmission, Infectious; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D015994:Incidence; D008297:Male; D017422:Sequence Analysis, DNA; D006113:United Kingdom
D004269:DNA, Bacterial