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Determining the situation of drug-resistance Tuberculosis in the South of Mozambique by using whole genome sequencing for the first time

C Mariner-Llicer(1) B Saavedra-Cervera(2,3) E Mambuque(3) S Munguambe(3) N Gomes(3) I Cancino-Muñoz(5) L Villamayor(4) M Torres-Puente(1) D Nguenha(3,6) D Respeito(3) G Tembe(3) M G López(1) I Comas(1,7) A García-Basteiro(2,3,8)

1:Instituto de Biomedicina de Valencia (CSIC); 2:ISGlobal, Hospital Clínic - Universitat de Barcelona; 3:Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique; 4:FISABIO Public Health, Valencia, Spain; 5:Universitat de València, Valencia, Spain; 6:Amsterdam Institute for Global Health & Development (AIGHD). Amsterdam, The Netherlands; 7:CIBER in Epidemiology and Public Health, Madrid, Spain; 8:Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Barcelona, Spain

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 harboring the rpoB_I491F mutation not detected by XpertUltra/RIF. Due to the concerning MDR-TB situation in Southern Africa, it is crucial to review the current resistance status in Mozambique. Our aim is to depict the current evolution of drug-resistance prevalence to first and second-line drugs compared to 2008. We analyzed 275 and 337 genomes from two population-based surveys conducted in Manhiça in 2014 and 2018 and looked for drug-resistance mutations included in the recently published WHO catalog. We found that the overall resistance increased slightly from 10.78% to 14.42%. 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 neighboring countries. Importantly, we detected a high isoniazid (INH) prevalence not associated with MDR-TB (4.20% and 7.61% in 2008 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 Manhiça 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.

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