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

Tuberculosis (TB) originating from expatriates that hail from high TB-burden countries is hypothesized to play a role in continued TB transmission in Oman. Here, we used whole-genome sequencing (WGS) to assess national TB transmission dynamics. The annual incidence per 100,000 population per year was calculated for nationals and expatriates. A convenience sample of Mycobacterium tuberculosis (MTB) isolates from 2018 to 2019 was sequenced and analyzed with publicly available TB sequences from Bangladesh, Tanzania, the Philippines, India, and Pakistan. Relatedness was assessed by generating core-genome single nucleotide polymorphism (SNP) distances. The incidence of TB was five cases per 100,000 persons in 2018 and seven cases per 100,000 persons in 2020 (R2 = 0.34, P = 0.60). Incidence among nationals was 3.9 per 100,000 persons in 2018 and 3.5 per 100,000 persons in 2020 (R2 = 0.20, P = 0.70), and incidence among expatriates was 7.2 per 100,000 persons in 2018 and 12.7 per 100,000 persons in 2020 (R2 = 0.74, P = 0.34). Sixty-eight local MTB isolates were sequenced and analyzed with 393 global isolates. Isolates belonged to nine distinct spoligotypes. Two isolates, originating from an expatriate and an Omani national, were grouped into a WGS-based cluster (SNP distance < 12), which was corroborated by an epidemiological investigation. Relatedness of local and global isolates (SNP distance < 100) was also seen. The relatedness between MTB strains in Oman and those in expatriate countries of origin can aid inform TB control policy. Our results provide evidence that WGS can complement epidemiological analysis to achieve the End TB strategy goal in Oman. IMPORTANCE Tuberculosis (TB) incidence in Oman remains above national program control targets. TB transmission originating from expatriates from high TB-burden countries has been hypothesized to play a role. We used whole-genome sequencing (WGS) to assess TB transmission dynamics between expatriates and Omani nationals to inform TB control efforts. Available Mycobacterium tuberculosis isolates from 2018 to 2019 underwent WGS and analysis with publicly available TB sequences from Bangladesh, the Philippines, India, and Pakistan to assess for genetic relatedness. Our analysis revealed evidence of previously unrecognized transmission between an expatriate and an Omani national, which was corroborated by epidemiological investigation. Analysis of local and global isolates revealed evidence of distant relatedness between local and global isolates. Our results provide evidence that WGS can complement classic public health surveillance to inform targeted interventions to achieve the End TB strategy goal in Oman.

Genomic and geospatial epidemiology of Mycobacterium tuberculosis in Oman: first national insight using whole genome sequencing.

OBJECTIVES: Mycobacterium tuberculosis (MTB) is a global public health issue. Although Oman reduced the burden of tuberculosis (TB) by 85% in under 25 years, the annual incidence rate remains stagnant. Whole genome sequencing (WGS) is used to investigate the transmission dynamics of MTB complex. This study aimed to resolve traditional genotype clusters and exploring the geospatial distribution to understand the epidemiology of TB in Oman. METHODS: Confirmed cases with spoligotyping clusters were randomly selected. WGS of 70 isolates were selected for final analysis. Correlation of epidemiological and geospatial data was conducted. RESULTS: A total of 233 cases were registered in 2021; 169 had confirmed growth, with an incidence rate of 5.2/100,000 population for 2021. A total of 70 genomes were analyzed, and five large clusters and three medium clusters were identified. The lineages L1, L2, L3, and L4 and several sublineages belonging to the Indo-Oceanic family and East African Indian family were identified as predominant in Oman. There were no multidrug-resistant cases identified. CONCLUSION: There is a considerable genetic variation among the strains in Oman. This predominance could be linked with the high percentage of non-national population, which represents different countries and frequent traveling to high TB burden countries. WGS combined with geospatial investigations of MTB are required to better understand the disease transmission in Oman, which will support TB elimination efforts.

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.

Screening migrants from tuberculosis high-endemic countries for latent tuberculosis in Oman: A cross sectional cohort analysis.

To fulfil the World Health Organization (WHO) End TB strategy, screening for tuberculosis (TB) in immigrants is an important component of the strategy to reduce the TB burden in low-incidence countries. Oman has an annual TB incidence rate of 5.7 per 100000 and transmission from migrants with activated latent TB infection (LTBI) to nationals is a concern. The aim of this study was to determine the proportion of migrants to the Sultanate of Oman with LTBI. The study used an interferon-gamma release assay (IGRA) to assess previous exposure to TB, defining LTBI and a positive IGRA with a normal chest X-ray. 1049 subjects were surveyed. Six participants were excluded from the analysis as they had been recently vaccinated and 1 had an indeterminate result, thus 1042 subjects were included. The overall IGRA-positive rate was 22.4% (234/1042), 30.9% and 21.2% of African and Asian migrants, respectively, were IGRA-positive. Fifty-eight of the participants had a strong IGRA reactivity defined as more than 4 IU/ml. The study shows the proportion of migrants from Asia and Africa with LTBI and 24.7% (58/234) of IGRA-positive migrants had an IGRA of >4 IU/ml, defining a subpopulation with a high risk of developing active TB in the first two years of arrival to the country.

Clinical relevance of nontuberculous Mycobacteria, Oman.

Little is known about the clinical relevance of nontuberculous mycobacteria (NTM) in the Arabian Peninsula. We assessed the prevalence and studied a random sample of isolates at a reference laboratory in Muscat, Oman. NTM cause disease in this region, and their prevalence has increased.