XDR-TB transmission in London: Case management and contact tracing investigation assisted by early whole genome sequencing

Abstract

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.