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Drug Resistant in Oman: Resistance-conferring Mutations and Lineage Diversity

Abstract

Background: The Sultanate of Oman is country a low TB-incidence, with less than seven cases per 10 population detected in 2020. Recent years have witnessed a persistence in TB cases, with sustained incidence rate among expatriates and limited reduction among Omanis. This pattern suggests transmission from the migrant population. The present study examined the genetic profile and drug resistance-conferring mutations in collected from Omanis and expatriates to recognise possible causes of disease transmission.

Methods: We examined cultured positive samples, collected from Omanis ( = 1,344) and expatriates ( = 1,203) between 2009 and 2018. These isolates had a known susceptibility profile to first line anti-TB, Streptomycin (SM), Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB) and Pyrazinamide (PZA). The diversity of the isolates was assessed by spacer oligo-typing (spoligotyping). Drug resistance-conferring mutations resulted from full-length sequence of nine genes () and their phenotypic relationship were analysed.

Results: In total, 341/2192 (13.4%), strains showed resistance to any drug, comprising mono-resistance (MR) (242, 71%), poly-resistance (PR) (40, 11.7%) and multi-drug resistance (MDR) (59, 17.3%). The overall rate of resistance among Omanis and expatriates was similar; however, MDR and PZA were significantly higher among Omanis, while INH was greater among expatriates. Mutations K43R and S450L were linked to Streptomycin (SM) and Rifampicin resistance (RIF) respectively. Whereas, katG S315T and -C15T/G-17T were associated with Isoniazid resistance (INH). The resistance patterns (mono-resistant, poly-resistant and MDR) and drug resistance-conferring mutations were found in different spoligo-lineages. K43R, S315T and S450L mutations were significantly higher in Beijing strains.

Conclusions: Diverse drug resistant strains exist in Oman, with drug resistance-conferring mutations widespread in multiple spoligo-lineages, indicative of a large resistance reservoir. Beijing's lineage was associated with MDR, and multiple drug resistance-conferring mutations, favouring the hypothesis of migration as a possible source of resistant lineages in Oman.

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