XDR-TB transmission in London: Case management and contact tracing investigation assisted by early whole genome sequencing.
We describe the first published cluster of extensively drug resistant Tuberculosis (XDR-TB) in the UK and show how early whole genome sequencing (WGS) of Mtb can assist in case management and contact investigations.



We describe the contact tracing investigation undertaken after the presentation of an adult with XDR-TB. Active cases were treated with an XDR-TB drug regimen and contacts underwent a programme of follow-up for 2 years. All isolates of Mycobacterium tuberculosis (Mtb) were assessed early using whole genome sequencing (WGS) as well as routine drug susceptibility testing (DST).



Thirty-three contacts were screened. In the first year one confirmed and one probable case were identified through contact tracing. A further possible case was identified through epidemiological links. Two confirmed cases were identified through WGS 2 years later. Twenty-five (80%) contacts without evidence of tuberculosis were adherent to 1 year of follow-up and 14 (45%) were adherent to 2 years of follow-up. WGS of Mtb was used to guide drug choices, rapidly identify transmission events, and alter public health management.



WGS of Mtb enabled rapid effective individualized treatment and facilitated public health interventions by early identification of transmission events.
Institute for Infection and Immunity, St. George's University of London, London, SW17 0RE, United Kingdom; Infection Care Group, St George's Healthcare NHS Trust, London, United Kingdom. Electronic address: amber.arnold@doctors.org.uk.
Amber
A
Arnold
Institute for Infection and Immunity, St. George's University of London, London, SW17 0RE, United Kingdom. Electronic address: awitney@sgul.ac.uk.
Adam A
AA
Witney
Institute for Infection and Immunity, St. George's University of London, London, SW17 0RE, United Kingdom. Electronic address: stev@doctors.org.uk.
Stephania
S
Vergnano
Public Health England, London, United Kingdom. Electronic address: anita.roche@phe.gov.uk.
Anita
A
Roche
Institute for Infection and Immunity, St. George's University of London, London, SW17 0RE, United Kingdom; Infection Care Group, St George's Healthcare NHS Trust, London, United Kingdom. Electronic address: ccosgrov@sgul.ac.uk.
Catherine A
CA
Cosgrove
Infection Care Group, St George's Healthcare NHS Trust, London, United Kingdom. Electronic address: angela.houston@stgeorges.nhs.uk.
Angela
A
Houston
Institute for Infection and Immunity, St. George's University of London, London, SW17 0RE, United Kingdom. Electronic address: kgould@sgul.ac.uk.
Katherine A
KA
Gould
Institute for Infection and Immunity, St. George's University of London, London, SW17 0RE, United Kingdom. Electronic address: jhinds@sgul.ac.uk.
Jason
J
Hinds
Infection Care Group, St George's Healthcare NHS Trust, London, United Kingdom. Electronic address: peter.riley@stgeorges.nhs.uk.
Peter
P
Riley
Institute for Infection and Immunity, St. George's University of London, London, SW17 0RE, United Kingdom; Infection Care Group, St George's Healthcare NHS Trust, London, United Kingdom. Electronic address: macallan@sgul.ac.uk.
Derek
D
Macallan
Institute for Infection and Immunity, St. George's University of London, London, SW17 0RE, United Kingdom. Electronic address: butercherp@sgul.ac.uk.
Philip D
PD
Butcher
Institute for Infection and Immunity, St. George's University of London, London, SW17 0RE, United Kingdom; Infection Care Group, St George's Healthcare NHS Trust, London, United Kingdom. Electronic address: tharriso@sgul.ac.uk.
Tom S
TS
Harrison
D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D019090:Case Management; D002648:Child; D016358:Contact Tracing; D004196:Disease Outbreaks; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy / Q000453:epidemiology* / Q000517:prevention & control / Q000635:transmission*; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D008131:London / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA
D000995:Antitubercular Agents
Contact tracing; Disease outbreaks; Drug resistance; Pathology, molecular; Tuberculosis