الملخص الإنجليزي
Tuberculosis is a fatal contagious disease caused by Mycobacterium tuberculosis complex (MTBC) resulting in the death of 2 million people worldwide every year. The disease is treatable; however, the emergence of resistant strains to anti-tuberculosis drugs is a major concern. This study examined the distribution of drug resistant tuberculosis in Oman and used spoligotyping to identify the extent of genetic diversity and clustering of MTBC isolates among Omanis and expatriates.
The study examined a total of 748 MTBC isolates collected between 2008 and 2013 in the Central Public Health Laboratories in Oman. The in vitro drug response of these isolates was determined by Drug Susceptibility Testing (DST), the spoligotypes were defined based on amplification of direct repeat (DR) region, while polymerase chain reaction (PCR) and DNA sequencing were used for the detection of mutations associated with resistance to anti-tuberculosis drugs. Chi-square test was performed to evaluate the association between the drug resistance mutations and DST results.
The study showed that CAS and EAI clades were the predominant spoligo patterns in Oman among both Omanis and expatriates. Out of 548 isolates examined by spoligotyping, 67.3% were in clusters. The clusters ranged from 2 to 68 isolates with clustering rate of 41.0%. Clustered MTB isolates among both Omanis and expatriates shared 23 different sub-lineages. Clustering of TB among both Omanis and expatriates suggests ongoing transmission between the two groups, which needs further evaluation. High prevalence of drug resistant strains existed in Oman, out of 693 of examined isolates 33.3% were found to be isoniazid resistant (INH 21.0% were streptomycin resistant (SM) and 17.3% were pyrazinamide resistant (PZ ). 60.3% of the INH MTB isolates carried katG $315T mutation and 23.5% carried the inh -15CT mutation. Similarly, 95% of the RIF MTB strains harbored mutated rpoB gene, out of these 70.0%, 20.0% and 5.0% carried S531L, H526L and D516V, respectively. MDR-TB, defined as strains resistant to at least INH and RIF, represented 2.4% of the exaimned MTB isolates. CA$1_Delhi and Beijing family predominated among MDR strains. Analysis of 12-MIRU-VNTR of the MDR-MTBC isolates indicated that each patient was infected with a unique strain, most likely, as a result of reactivated latent infection acquired earlier.
This study represents a baseline study of the MTBC population structure in Oman, and may serve as a motivation for future molecular epidemiological studies in the region, and help comprehend the global tubercle bacilli genotypic dive is caused by a wide diversity of spoligotypes with predominance of two genotype lineages originate from the Indian subcontinent (CAS & EAI) highlighting the role of expatriates in disseminating the disease. This hypothesis is supported by the high rate of shared clusters of spoligotypes among Omanis and expatriates. Treatment guidelines should consider the widespread of MTB strains carrying drug resistance mutations. This study also gave an insight into the MTBC genetic biodiversity in Oman, the predominant spoligotypes and mutations associated with resistance to anti-TB drugs.
