# Targeted genome sequencing for tuberculosis drug susceptibility testing in South Africa: a proposed diagnostic pipeline

## TL;DR

This paper proposes a feasible diagnostic pipeline for tuberculosis drug resistance testing in South Africa using existing and emerging sequencing technologies.

## Contribution

The novel contribution is a stratified diagnostic pipeline tailored to South Africa’s context, integrating existing GeneXpert tools with potential tNGS adoption.

## Key findings

- South Africa's adoption of the GeneXpert XDR cartridge supports second-line drug resistance detection.
- Implementing tNGS faces economic and infrastructural challenges in South Africa.
- A stratified pipeline is recommended to reduce tNGS implementation costs.

## Abstract

In July 2023, the World Health Organization (WHO) began recommending targeted next-generation sequencing (tNGS), due to its ability to detect resistance to many drugs with a single test. In March 2023, South Africa further adopted the GeneXpert XDR cartridge, which detects mutations associated with resistance to second-line injectable drugs. Here, we consider the feasibility for implementing tNGS in South Africa, what such a facility might look like and the specific context of this upper-middle-income country. Whilst the WHO now recommends tNGS for TB diagnostics and DST, there are many economic and infrastructural challenges opposing its deployment. In lieu of this, we instead recommend a stratified diagnostic pipeline that utilizes South Africa’s existing GeneXpert technologies, attempting to reduce the costs associated with implementation of tNGS.