Drug resistant Mycobacterium tuberculosis 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 105 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 Mycobacterium tuberculosis collected from Omanis and expatriates to recognise possible causes of disease transmission. Methods We examined M. tuberculosis cultured positive samples, collected from Omanis (n = 1,344) and expatriates (n = 1,203) between 2009 and 2018. These isolates had a known in vitro 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 (katG, inhA, ahpc, rpoB, rpsL, rrs, embB, embC, pncA) and their phenotypic relationship were analysed. Results In total, 341/2192 (13.4%), M. tuberculosis 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 PZAR were significantly higher among Omanis, while INHR was greater among expatriates. Mutations rpsL K43R and rpoB S450L were linked to Streptomycin (SMR) and Rifampicin resistance (RIFR) respectively. Whereas, katG S315T and inhA –C15T/G–17T were associated with Isoniazid resistance (INHR). The resistance patterns (mono-resistant, poly-resistant and MDR) and drug resistance-conferring mutations were found in different spoligo-lineages. rpsL K43R, katG S315T and rpoB S450L mutations were significantly higher in Beijing strains. Conclusions Diverse drug resistant M. tuberculosis strains exist in Oman, with drug resistance-conferring mutations widespread in multiple spoligo-lineages, indicative of a large resistance reservoir. Beijing’s M. tuberculosis 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.

Mycobacterium tuberculosis epidemiology in Oman: whole-genome sequencing uncovers transmission pathways

“…Whereas the other lineages, T, LAM, and H (27.9%) are prevalent in East Africa, which has a historical link with Oman ( 41 ). These findings are consistent with a recent analysis of 1,295 M. tuberculosis isolates in different provinces in Oman, where no differences were seen among MTB lineages infecting nationals and expatriates ( 13 ). Such a pattern has also been reported in other GCC countries, with a similar demographic structure of a high proportion of expatriates, such as Saudi Arabia and Kuwait ( 6 , 42 ).…”

“…The laboratory performs confirmation of TB diagnosis using standard microbiological procedures for the identification of the M. tuberculosis complex and in vitro drug-susceptibility test for all first-line anti-TB drugs ( 13 ). Isolates resistant to a single drug were classified as mono-resistant.…”

Mutations inembB406 are associated with low-level ethambutol resistance in CanadianMycobacterium tuberculosisisolates

“…The adaptation of critical concentrations from agar proportion methods to the MGIT™ 460 system, which were shortly modified in the shift to the MGIT™ 960 system has been criticized for poor concordance and standardization (15, 41). Again, several describe ethambutol susceptible strains with emb B406 mutations (15, 16, 21, 42). Further, Bwalya et al .…”