Impact of pathobiological diversity of Mycobacterium tuberculosis on clinical features and lethal outcome of tuberculosis.

BACKGROUND: Mycobacterium tuberculosis population in Russia is dominated by the notorious Beijing genotype whose major variants are characterized by contrasting resistance and virulence properties. Here we studied how these strain features could impact the progression of pulmonary tuberculosis (TB) concerning clinical manifestation and lethal outcome. RESULTS: The study sample included 548 M. tuberculosis isolates from 548 patients with newly diagnosed pulmonary TB in Omsk, West Siberia, Russia. Strains were subjected to drug susceptibility testing and genotyping to detect lineages, sublineages, and subtypes (within Beijing genotype). The Beijing genotype was detected in 370 (67.5%) of the studied strains. The strongest association with multidrug resistance (MDR) was found for epidemic cluster Beijing B0/W148 (modern sublineage) and two recently discovered MDR clusters 1071-32 and 14717-15 of the ancient Beijing sublineage. The group of patients infected with hypervirulent and highly lethal (in a mouse model) Beijing 14717-15 showed the highest rate of lethal outcome (58.3%) compared to Beijing B0/W148 (31.4%; P = 0.06), Beijing Central Asian/Russian (29.7%, P = 0.037), and non-Beijing (15.2%, P = 0.001). The 14717-15 cluster mostly included isolates from patients with infiltrative but not with fibrous-cavernous and disseminated TB. In contrast, a group infected with low virulent 1071-32-cluster had the highest rate of fibrous-cavernous TB, possibly reflecting the capacity of these strains for prolonged survival and chronicity of the TB process. CONCLUSIONS: The group of patients infected with hypervirulent and highly lethal in murine model 14717-15 cluster had the highest proportion of the lethal outcome (58.3%) compared to the groups infected with Beijing B0/W148 (31.4%) and non-Beijing (15.2%) isolates. This study carried out in the TB high-burden area highlights that not only drug resistance but also strain virulence should be considered in the implementation of personalized TB treatment.

Molecular & genetic characteristics of Mycobacterium tuberculosis strains circulating in the southern part of West Siberia.

BACKGROUND & OBJECTIVES: A complicated epidemiological situation characterized by significantly high tuberculosis (TB) morbidity is observed in West Siberia. This study was aimed to investigate the genetic characteristics of Mycobacterium tuberculosis circulating in the southern part of West Siberia (in the Omsk region). METHODS: From March 2013 to January 2015, 100 isolates of M. tuberculosis were obtained from patients with pulmonary TB living in the Omsk region. Drug susceptibility testing was performed on Lowenstein-Jensen medium (absolute concentration method). Genetic typing of isolates was carried out by variable number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) typing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The genetic types and characteristics of cluster strains were determined using 15 MIRU-VNTR loci. RESULTS: Thirty six VNTR types were found. Twenty six (26.0%) isolates had a unique profile, and the remaining 74 were grouped in 10 clusters containing from 2 to 23 isolates. The Beijing genotype was found in 72 isolates, 61 (85.0%) of which were part of five clusters that included two large clusters containing 23 isolates. Other genetic families, such as Latin-American Mediterranean (LAM, 11.0%), S family (2.0%) and Haarlem (4.0%), were also detected. The genetic family of 11 isolates could not be determined. Six different VNTR profiles were found in these non-classified isolates. Only 16 per cent of isolates were sensitive to anti-TB drugs. The katG315 (94.8%) and rpoB531 (92.2%) mutations were identified in 77 multidrug-resistant M. tuberculosis isolates. INTERPRETATION & CONCLUSIONS: This study showed that the M. tuberculosis population in the Omsk region was heterogeneous. The Beijing genotype predominated and was actively spreading. The findings obtained point to the need for the implementation of more effective preventive measures to stop the spread of drug-resistant M. tuberculosis strains.

Prevalence and Spectrum of HIV-1 Resistance Mutations in the Siberian Federal District.

The Siberian Federal District is among the most affected regions with a high prevalence of HIV-infection and is characterized by high HIV-infection incidence rate and high mortality among the HIV-infected population. HIV drug resistance poses a major threat to public health and is associated with increased mortality, HIV incidence, and cost of epidemic control programs. A total of 1281 samples from HIV-infected patients were sequenced and analyzed with the DEONA and HIVdb Program to assess the prevalence of drug resistance mutations in patients in the Siberian Federal District in 2016-2018. The federal surveillance data obtained from 0.5% of HIV-infected patients during the long-term follow-up care in 2021 were also used. The incidence rate of HIV infection in the Siberian Federal District has declined since 2016: from 135.8 per 100 thousand population to 81.1 per 100 thousand population in 2021. Mutations associated with resistance to NRTI and NNRTI were found in 10.3% of the samples in 2016-2018 and in 28.4% of the samples in 2020. The rising prevalence of drug resistance in HIV-infected patients indicates that it is increasingly important to continuously monitor and improve the approaches to the use of effective treatment regimens.

Correction: Prevalence and spatiotemporal dynamics of HIV-1 Circulating Recombinant Form 03_AB (CRF03_AB) in the Former Soviet Union countries.

[This corrects the article DOI: 10.1371/journal.pone.0241269.].

Prevalence and spatiotemporal dynamics of HIV-1 Circulating Recombinant Form 03_AB (CRF03_AB) in the Former Soviet Union countries.

BACKGROUND: HIV-1 circulating recombinant forms (CRFs) infections has been increasing in Former Soviet Union (FSU) countries in the recent decade. One is the CRF03_AB, which circulated in the region since late 1990s and probably became widespread in northwestern FSU countries. However, there is not much information provided about the dissemination of this recombinant. Here, we examine the prevalence, evolutionary dynamics and dispersion pattern of HIV-1 CRF03_AB recombinant. METHODS: We analyzed 32 independent studies and 151 HIV-1 CRF03_AB pol sequences isolated from different FSU countries over a period of 22 years. Pooled prevalence was estimated using a random effects model. Bayesian coalescent-based method was used to estimate the evolutionary, phylogeographic and demographic parameters. RESULTS: Our meta-analysis showed that the pooled prevalence of CRF03_AB infection in northwestern FSU region was 5.9% [95%CI: 4.1-7.8]. Lithuania (11.6%), Russia (5.9%) and Belarus (2.9%) were the most affected by CRF03_AB. We found that early region wide spread of HIV-1 CRF03_AB originated from one viral clade that arose in the city of Kaliningrad in 1992 [95%HPD: 1990-1995]. Fourteen migration route of this variant were found. The city of Kaliningrad is involved in most of these, confirming its leading role in CRF03_AB spread within FSU. Demographic reconstruction point to this is that CRF03_AB clade seems to have experienced an exponential growth until the mid-2000s and a decrease in recent years. CONCLUSION: These data provide new insights into the molecular epidemiology of CRF03_AB as well as contributing to the fundamental understanding of HIV epidemic in FSU.

Major genotype families and epidemic clones of Mycobacterium tuberculosis in Omsk region, Western Siberia, Russia, marked by a high burden of tuberculosis-HIV coinfection.

This population-based study characterized Mycobacterium tuberculosis isolates from HIV-positive and HIV-negative tuberculosis (TB) patients in the Omsk region in Western Siberia, Russia. We sought to gain insight into the major genotype families and epidemic and endemic clones of M. tuberculosis in the area with a high burden and adverse trend of TB/HIV coinfection. The study collection included M. tuberculosis isolates from 207 newly-diagnosed patients with pulmonary TB; 55 (26.5%) of patients were HIV-infected. The M. tuberculosis isolates were subjected to drug susceptibility testing and molecular typing based on spoligotyping and analysis of the robust genotype and cluster-specific markers. Patients with disseminated TB disease were more prevalent in the HIV-positive (34.5%) than in the HIV-negative group (4.6%) (P < .001). The Beijing genotype was predominant (62.3% of isolates), and its major subtypes were 94-32-cluster (Central Asian/Russian strain, n = 80) and B0/W148-cluster (successful Russian strain, n = 28). The main non-Beijing families were represented by Latin-American Mediterranean (14.5%), T family (11.1%), Ural (5.8%), and Haarlem (3.9%). Under multivariate logistic regression analysis, MDR was associated with Beijing genotype and not associated with HIV coinfection status (P < .001). Beijing genotype isolates were found more frequently in TB/HIV patients than in TB HIV-negative patients (74.5% versus 57.9%, respectively; P = .031). The non-Beijing genotypes were mainly drug susceptible except for the drug-resistant Ural SIT262 isolates. To summarize, the alarming situation in the Omsk region in Siberia regarding TB/HIV coinfection is seriously influenced by the active circulation of M. tuberculosis isolates of MDR-associated Beijing genotype. Among the non-Beijing families, emergence of the drug-resistant Ural family strains of spoligotype SIT262 warrants attention.