M. tuberculosis Beijing Genotype Clusters: Impact on Tuberculosis Drug Resistance in Kazakhstan.

The Beijing genotype is the main component of the M. tuberculosis population in Kazakhstan. In this study, we investigated the association of drug resistance (including MDR) and clinical forms of tuberculosis with the Beijing genotype and its dominant clusters, and compared obtained results among new, recurrent and all TB cases. In total, 759 M. tuberculosis isolates were collected from new (n = 540) and recurrent TB cases (n = 219). Drug susceptibility testing was performed on the BACTEC-MGIT 960 system; 24 MIRU-VNTR analysis was carried out to identify M. tuberculosis genotypes. The Beijing genotype was detected in 65.2% (495/759) of all TB cases and was associated with recurrent TB compared with new cases (78% vs. 60%, p < 0.0001). Among both new and recurrent TB cases, the Beijing genotype was associated with drug resistance (p < 0.0001 and p < 0.0001), including MDR (p < 0.0001 and p = 0.0118). Central Asian/Russian cluster 94-32 was the most widespread Beijing cluster in Kazakhstan (52.5%; 260/495). Association of cluster 94-32 with drug-resistant TB in general was confirmed across all cases (p = 0.010) and recurrent TB cases (p = 0.0191; OR = 4.8958; 95%CI: 1.2965-18.4883), while individuals with new TB cases were more likely to be diagnosed with MDR-TB specifically (p = 0.021). Among clinical forms of TB, a significant association was detected between fibrous-cavernous tuberculosis and drug resistance (p = 0.0019; OR = 3.3801; 95%CI: 1.5692-7.2807), including MDR (p = 0.0054; OR = 3.2453; 95%CI: 1.4167-7.4345), among all TB cases. TB patients with Beijing cluster 94-15 mostly had drug-susceptible TB among all TB cases and recurrent cases (p < 0.05). Drug-susceptible tuberculosis was observed among patients with focal TB among new cases (p = 0.0254; OR = 0.1723; 95%CI: 0.0369-0.8050). Tuberculous pleurisy was more commonly diagnosed in individuals with non-Beijing genotypes among all TB cases (p = 0.0430; OR = 0.3643; 95%CI: 0.1371-0.9686). The M. tuberculosis Beijing genotype, particularly the Central Asian cluster 94-32, plays a significant role in the distribution of drug-resistant TB among all TB cases and recurrent cases, including MDR-TB among new TB cases in Kazakhstan. On the contrary, the Beijing cluster 94-15 may contribute to the spread of drug-susceptible TB among all TB cases and recurrent TB cases.