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Direct on Sputum Sequencing to Interrupt Transmission of Rifampicin Resistant Tuberculosis

Project description

Using genomics to stay ahead of drug-resistant TB

Drug-resistant tuberculosis (TB) is a major global health threat. Some TB strains no longer respond to rifampicin, one of the main drugs used to treat tuberculosis, and are spreading in high-burden areas. At the same time, early signs of resistance to bedaquiline, a newer and crucial treatment, are raising concerns. The ERC-funded DiSrupT RR-TB project brings genomic precision directly into frontline care to confront this growing threat. In KwaZulu-Natal, South Africa, researchers are testing a system that sequences TB genomes from sputum and delivers automated results to clinicians. The goal is to treat patients and interrupt transmission chains. DiSrupT RR-TB could redefine how genomics is used in TB control.

Objective

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.

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HORIZON-ERC - HORIZON ERC Grants

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(opens in new window) ERC-2024-ADG

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Host institution

UNIVERSITEIT ANTWERPEN
Net EU contribution

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€ 2 499 855,00
Address
PRINSSTRAAT 13
2000 Antwerpen
Belgium

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Region
Vlaams Gewest Prov. Antwerpen Arr. Antwerpen
Activity type
Higher or Secondary Education Establishments
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Total cost

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