Whole Genome Sequencing For The Rapid Prediction Of Drug Susceptibility In Patients With Suspected Multi-Drug Resistant (MOST)

This is a prospective observational cohort study of patients with Mtb and rifampicin resistance detected by MTB/RIF Xpert.


Current standard laboratory methods to identify multi-drug resistance (MDR) TB is phenotypic (culture-based) drug susceptibility testing, which requires specialist laboratories and takes 8-12 weeks. Only two laboratories in Vietnam perform full DST. Inadequate diagnosis leads to missed cases, onward transmission, morbidity and mortality, and increased costs. There is a clear need for fast, accurate DST that guides appropriate treatment.

Our proposal addresses one overarching question: can Whole Genome Sequencing (WGS) replace current methods for the DST of MDR-TB in Vietnam’s tuberculosis National Reference Laboratory (NRL)?


This study aims to demonstrate that:

  • WGS from Mtb cultured from patients with suspected MDR lung TB can provide accurate and rapid 2nd line drug susceptibility predictions.
  • WGS from sputum samples can provide the same information at a much earlier time point in treatment compared to WGS from culture isolations (for the same individual).
  • WGS offers economic benefits by providing earlier diagnosis and supporting treatment decisions for MDR-TB.

As a result, we will develop Mtb WGS’s expertise and capacity within the Hanoi TB NRL. Then, it would be possible to introduce WGS into routine laboratory work once the project ends.

Study design

We will conduct a prospective observational cohort study of patients with Mtb and rifampicin resistance detected by MTB/RIF Xpert, presenting to the National Lung Hospital, Hanoi Lung Hospital, and other participating sites around Hanoi between October 2020 and December 2022.

Recruited patients will have their specimens and isolates analyzed (DNA extraction and WGS) in parallel to routine diagnostic procedures (smear microscopy, MTB/RIF Xpert and DST).

A health economic analysis will be undertaken in parallel to assess the costs of each workflow; routine, WGS from culture, and WGS directly from a clinical sample.




Hanoi Lung Hospital


National Lung Hospital

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University of Oxford

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