Direct on Sputum Sequencing to Interrupt Transmission of Rifampicin Resistant Tuberculosis

Descripción del proyecto

Utilizar la genómica para adelantarse a la tuberculosis farmacorresistente

La tuberculosis (TB) farmacorresistente es una grave amenaza para la salud mundial. Algunas cepas de TB ya no responden a la rifampicina, uno de los principales fármacos utilizados para tratar la tuberculosis, y se están extendiendo en zonas de alta carga. Al mismo tiempo, los primeros signos de resistencia a la bedaquilina, un tratamiento más nuevo y crucial, están suscitando preocupación. El equipo del proyecto DiSrupT RR-TB, financiado por el Consejo Europeo de Investigación, lleva la precisión genómica directamente a la atención de primera línea para hacer frente a esta amenaza creciente. En KwaZulu-Natal (Sudáfrica), los investigadores están probando un sistema que secuencia los genomas de la tuberculosis a partir del esputo y entrega automáticamente los resultados a los médicos. El objetivo es tratar a los pacientes e interrumpir las cadenas de transmisión. En DiSrupT RR-TB se podría redefinir el uso de la genómica en el control de la tuberculosis.

Objetivo

The DiSrupT RR-TB pragmatic cluster randomized trial (CRT) will tackle the ongoing public health threat of rifampicin-resistant tuberculosis (RR-TB) and prevent the emergence of bedaquiline-resistant tuberculosis (BDQR-TB) as a new public health crisis. The trial aims to evaluate an innovative all-in-1 solution for whole genome sequencing (WGS): the recently launched QIAseq xHYB Mtb assay for WGS directly on sputum (dWGS) in combination with Illumina sequencing and the novel digital MAGMA-MICK platform for automated analysis, interpretation, and communication of dWGS results to health care workers. The intervention aims to provide optimal treatment for all patients (precision medicine) and to reduce transmission of RR-TB in high-burden settings by breaking transmission chains in hotspots and superspreading events (precision public health). The trial will take place in KwaZulu-Natal, South Africa, and address four objectives to provide a holistic evaluation of the intervention's impact: (1) reduction in the recent transmission rate of RR-TB, (2) prevention of a rise in the proportion of cases of BDQR-TB that are due to transmission versus acquisition, (3) increase in timely initiation of effective treatment regimens for patients with BDQR-TB and (4) improved treatment outcomes of BDQR-TB. Data analysis will employ causal inference methodologies, including the difference-in-difference method for the cluster-level analyses (objectives 1 and 2), and inverse probability weighting for the individual-level analyses (objectives 3 and 4). The methodological rigor of the pragmatic CRT design will generate results with high internal and external validity, which is needed to inform policy and practice. If the intervention is shown to be effective and feasible, the trial will represent a paradigm shift in how genomic data can be utilised in public health interventions in low-resource countries and make a transformative contribution to infectious disease control efforts.