Tuberculous Spondylitis in Russia and Prominent Role of Multidrug-Resistant Clone Mycobacterium tuberculosis Beijing B0/W148

Abstract

Extrapulmonary and, in particular, spinal tuberculosis (TB) constitutes a minor but significant part of the total TB incidence. In spite of this, almost no studies on the genetic diversity and drug resistance of Mycobacterium tuberculosis isolates from spinal TB patients have been published to date. Here, we report results of the first Russian and globally largest molecular study of M. tuberculosis isolates recovered from patients with tuberculous spondylitis (TBS). The majority of 107 isolates were assigned to the Beijing genotype (n ‫؍‬ 80); the other main families were T (n ‫؍‬ 11), Ural (n ‫؍‬ 7), and LAM (n ‫؍‬ 4). Multidrug resistance (MDR) was more frequently found among Beijing (90.5%) and, intriguingly, Ural (71.4%) isolates than other genotypes (5%; P < 0.001). The extremely drug-resistant (XDR) phenotype was exclusively found in the Beijing isolates (n ‫؍‬ 7). A notable prevalence of the rpoB531 and katG315 mutations in Beijing strains that were similarly high in both TBS (this study) and published pulmonary TB ( Extrapulmonary tuberculosis (EPTB) remains a major health problem due to a significantly high rate of morbidity and mortality in both developing and developed countries and constitutes a significant part of the total TB incidence (1, 2). In Russia, the rate of EPTB decreased from 9.4% in 1992 to 3.4% in 2011, and the EPTB incidence constituted 2.4/100,000 in 2011 (3, 4). At the same time, the rate of tuberculous spondylitis (TBS) among all new EPTB cases increased in Russia from 23% in 2006 to 33% in 2010, which is higher than TB rate for of all other sites of the disease (3, 5).Tuberculous spondylitis constitutes about half of bone and joint TB cases and thus represents the most severe orthopedic disease, frequently leading to irreversible neurological disorders and disability and constituting a serious social and economic problem (6-8). TBS is developed as a result of blood-born dissemination of Mycobacterium tuberculosis. Bacteriological diagnosis of bone and joint TB is a most challenging task, and findings of drug resistance in these isolates may be crucial for adequate management of such cases. Delayed initial diagnosis and confirmation (from 3 months to 10 years after onset of the disease) and the increasing incidence of the multidrug-resistant TBS with spondyloarthropathy in adults require improvement of the etiological diagnostics, taking into account biological and molecular properties of the pathogen (4, 6, 7).M. tuberculosis has a clonal population structure, and it has been demonstrated that not only its large genetic families but also their variants or subgenotypes may play a special role in the disease progression. Russian strain Beijing B0/W148, initially defined by IS6110-restriction fragment length polymorphism (RFLP) analysis (9), presents a remarkable example of a successful clone highly associated with multidrug resistance (MDR) (10). Correlating different typing schemes, 24-locus mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) type 1...

Acid-Fast Bacilli Conversion of Beijing and Non-Beijing Strain of Pulmonary Tuberculosis in South Sulawesi

“…Vyazovaya's research was showed mutations in rpoB531 were most commonly found among Beijing isolates (60 of 72 isolates with rpoB mutations), five isolates (four of which were Beijing) were showed multiple or triple mutations in rpoB. INH resistance mutations, the katG315 mutation is also the most common in Beijing isolates 30 . Studies from Estonia, China, Korea and Taiwan were showed a significantly higher MDR frequency among Beijing descendants 31 .…”

Characterization of Mycobacterium Tuberculosis Strains (A 15-Year Survey in Leningrad Region, Russia)

“…у ранее леченных больных ту-беркулезом легких [1]. При этом ранее доказана клиническая значимость и преимущественно эпидемический путь распространения МЛУ штаммов M. tuberculosis генотипа Beijing на тер-ритории России [2,4,6,12,15]. Штаммы дан-ного генотипа характеризует наличие, по мень-шей мере, трех спейсеров 35-43 и отсутствие 1-34 спейсеров в профиле сполиготипирова-ния (табл.…”

“…Нами впервые показано, что среди штаммов M. tuberculosis, выделенных от больных хрони-ческим туберкулезом легких в Ленинградской области, также превалируют представители генетического семейства Beijing, причем их доля возросла с 56, [3,6,9,11,15].…”

Molecular Characteristics of Mycobacterium tuberculosis Strains Isolated from Cutaneous Tuberculosis Patients in China

“…Nevertheless, some common and distinctive observations can be made based on recent genotyping studies on EPTB in different countries. For example, in Russia, a study of spinal TB (TBS) found that 75% of strains were of the Beijing type, a proportion greater than that of the national prevalence of pure PTBs (50). More-over, 95% of these Beijing TBS were multidrug resistant, bearing mutations katG315 and rpoB531 commonly found in PTBs.…”