Drug resistant Mycobacterium tuberculosis in Oman: resistance-conferring mutations and lineage diversity.

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.

Dynamics of Mycobacterium tuberculosis Lineages in Oman, 2009 to 2018.

Study aim. Effective Tuberculosis (TB) control measures in Oman have reduced the annual incidence of tuberculosis cases by 92% between 1981 and 2016. However, the current incidence remains above the program control target of <1 TB case per 100,000 population. This has been partly attributed to a high influx of migrants from countries with high TB burdens. The present study aimed to elucidate Mycobacterium tuberculosis infection dynamics among nationals and foreigners over a period of 10 years. Methods. The study examined TB cases reported between 2009 and 2018 and examined the spatial heterogeneity of TB cases and the distribution of M. tuberculosis genotypes defined by spoligotypes and MIRU-VNTR among Omanis and foreigners. Results. A total of 484 spoligoprofiles were detected among the examined isolates (n = 1295). These include 943 (72.8%) clustered and 352 (27.2%) unique isolates. Diverse M. tuberculosis lineages exist in all provinces in Oman, with most lineages shared between Omanis and foreigners. The most frequent spoligotypes were found to belong to EAI (318, 30.9%), CAS (310, 30.1%), T (154, 14.9%), and Beijing (88, 8.5%) lineages. However, the frequencies of these lineages differed between Omanis and foreigners. Of the clustered strains, 192 MTB isolates were further analysed via MIRU-VNTR. Each isolate exhibited a unique MIRU-VNTR profile, indicative of absence of ongoing transmission. Conclusions. TB incidence exhibits spatial heterogeneity across Oman, with high levels of diversity of M. tuberculosis lineages among Omanis and foreigners and sub-lineages shared between the two groups. However, MIRU-VNTR analysis ruled out ongoing transmission.

Serotype distribution and antibiotic resistance among invasive Streptococcus pneumoniae from Oman post 13-valent vaccine introduction.

OBJECTIVE: This study was undertaken to determine the serotype distribution and drug susceptibility patterns in pneumococcal isolates recovered from patients with invasive pneumococcal disease (IPD). METHODS: All invasive pneumococcal isolates received between June 2014 and June 2016 were included in the study as part of a national laboratory-based IPD surveillance program. Isolates recovered from clinical specimens of normally sterile body sites were included. RESULTS: A total of 41 different serotypes were identified among the 132 pneumococcal isolates included in this study. The most prevalent serotypes/serogroups were 12 (8.3%), 15 (8.3%), 19F (7.6%), 3 (6.1%), and 19A (6.1%);. It was observed that overall vaccine coverage rates for pneumococcal conjugate vaccines (PCV), PCV7, PCV10 and PCV13 were 15.9%, 24.2% and 37.1% respectively. 56.8% (n=75) of the isolates were non-susceptible to at least one antibiotic and 40.9% (n=54) of the isolates were resistant to PEN (M). 18.9% (n=25) of the isolates were multi-drug resistant (MDR).The case fatality rate was 15.9%. CONCLUSION: Our study results call for broader vaccine coverage, emphasizes the need to introduce the conjugate pneumococcal vaccine for the high risk adult population and stress the importance of continuous surveillance of serotypes and antimicrobial resistance to guide vaccine development and antimicrobial stewardship activities.