Population-based surveillance of drug-resistant tuberculosis in Southern Mozambique based on whole genome sequencing

Mozambique is considered a high multidrug-resistant (MDR-TB) country by the World Health Organization (WHO) (3.7% new MDR-TB cases). The last national WHO survey was performed in 2008. Nowadays, South Africa and Eswatini are reporting an increase in MDR-TB cases heightened, in Eswatini, by the spread of a MDR-TB strain harbouring the rpoB_I491F mutation not detected by XpertUltra/RIF. Due to the concerning MDR-TB situation in its neighbouring countries, it is crucial to review the current resistance status in Mozambique. Our aim is to depict the current prevalence of drug-resistance to first and second-line drugs and track its trends since 2008. We analysed 312 Mycobacterium tuberculosis genomes from a population-based survey conducted in Manhica in 2018 and looked for drug-resistance mutations included in the recently published WHO catalogue and compared with the prevalences reported in 2014 and 2008. We found that the overall resistance increased in 2014 (15.9%) and 2018 (14.4%) was slightly higher than the one reported in 2008. Although, new multidrug/rifampicin resistance cases remained consistent with the 2008 prevalence study (3.5%) indicating that MDR-TB is not spreading as rapidly as in neighbouring countries. Importantly, we detected a high isoniazid (INH) prevalence not associated with MDR-TB (4.2%, 5.5% and 7.6% in 2008, 2014 and 2018, p-value=0.03) suggesting that a sizeable number of cases are INH-resistant before starting treatment and not detected by XpertUltra/RIF. Fortunately, no mutations associated with second-line drug-resistance were found in the dataset. Our results show a stable drug-resistance situation in Manhica with the need to monitor isoniazid resistance, and highlight the potential of WGS to be used in national surveys to expand our knowledge of drug-resistance prevalence throughout all Mozambican provinces.