2016 National tuberculosis drug resistance survey of DRC: Targeted next generation sequencing performed directly from sputum using Deeplex MycTB assay (Genoscreen, France). human sputum metagenome

The surveillance of drug resistance among tuberculosis (TB) patients is central to preventing the spread of antimicrobial resistance. The Democratic Republic of the Congo (DR Congo) is classified by WHO as a high TB and high multidrug-resistant TB (MDR-TB) burden country, but there are no nationally representative data on the burden of drug-resistant TB. In 2016-2017, a national survey of TB patients was conducted in 108 microscopy centres across all 11 provinces of the country. Sputum samples were collected from 1545 new and 163 previously treated patients. These were tested by the Xpert MTB/RIF assay, followed by targeted next generation sequencing directly on sputum. The prevalence of rifampicin resistance was low, at 1.7% (95%CI: 1.1-2.6) among new and 17.7% (95%CI: 11.7-26.0) among previously treated patients. Resistance to pyrazinamide, fluoroquinolones and second-line injectables was also low. The prevalence of resistance to isoniazid among rifampicin-susceptible patients was more concerning, at 6.6% (95%CI: 4.4-9.8) among new and 8.7% (95%CI: 3.2-21.2) among previously treated patients. Diagnosing and treating isoniazid-resistant patients remains a challenge, given that many will be missed by the current national diagnostic algorithm that is driven by Xpert MTB/RIF testing. The innovative integration of molecular tools into this survey serves as a proof-of-concept for other settings that do yet have capacity for rapid sputum transport and culture.