Tuberculosis In Population Research Articles

Breaking the energy chain: importance of ATP synthase in Mycobacterium tuberculosis and its potential as a drug target.

Unveiling novel pathways for drug discovery forms the foundation of a new era in the combat against tuberculosis. The discovery of a novel drug, bedaquiline, targeting mycobacterial ATP synthase highlighted the targetability of the energy metabolism pathway. The significant potency of bedaquiline against heterogeneous population of Mycobacterium tuberculosis marks ATP synthase as an important complex of the electron transport chain. This review focuses on the importance and unique characteristics of mycobacterial ATP synthase. Understanding these distinctions enables the targeting of ATP synthase subunits for drug discovery, without aiming at the mammalian counterpart. Furthermore, a brief comparison of the structural differences between mycobacterial and mitochondrial ATP synthase is discussed. Being a complex multi-subunit protein, ATP synthase offers multiple sites for potential inhibitors, including the a, c, ε, γ, and δ subunits. Inhibitors targeting these subunits are critically reviewed, providing insight into the design of better and more potent chemical entities with the potential for effective treatment regimens.

Circulation of <i>Mycobacterium tuberculosis</i> strains of the Beijing Central Asian Outbreak genotype in the Kemerovo region — Kuzbass in 2018–2022

Introduction. The Kemerovo region — Kuzbass is characterized by a high prevalence of multidrug-resistant (MDR) tuberculosis (TB), including coinfection with HIV (HIV/TB). A previously unknown in Russia relationship between MDR and the Beijing Central Asian Outbreak (CAO) subtype has been discovered, which updates studies of Mycobacterium tuberculosis taking into account this resistant variant. Objective: to study the molecular genetic structure of the M. tuberculosis population, to assess the prevalence and possible routes of emergence of Beijing CAO strains in the Kemerovo region — Kuzbass. Materials and methods. A total of 325 M. tuberculosis strains were studied in 2018–2022 using spoligotyping, MIRU-VNTR 24 and SNP typing. Whole genome sequencing and bioinformatics analysis were performed for seven Beijing CAO strains. Results. Primary MDR and pre-extensive drug resistance (pre-XDR) were detected in 39.4% and 11.5% of strains, respectively. In the total sample, MDR was 43.4%, pre-XDR — 19.7%. In the structure of the M. tuberculosis population, the Beijing genotype prevailed (78.8%), with its subtypes Central Asian Russian (40.9%) and B0/W148 (32.6%). The Euro-American lineage (27.3%) was represented by the genotypes T (6.5%), LAM (5.8%), Ural (4.9%), H (0.9%); one strain CAS1-Delhi was detected, the genotype of 2.8% of strains was not identified. The proportion of Beijing CAO was 12.6% of the total sample; this subtype was significantly more often detected among HIV/TB (20.6%) than in HIV-negative TB patients (9.1%; p = 0.005). The results of the Beijing CAO genome analysis from the Kemerovo region indicate the absence of a direct chain of transmission between these TB cases. A hypothesis has been put forward about the introduction of Beijing CAO to the Kemerovo region from Central Asia and its endemic circulation in the region. Conclusion. A high level of MDR and pre-XDR was detected in Beijing genotype strains in the M. tuberculosis population of the Kemerovo region — Kuzbass, especially the B0/W148 (97.2%) and CAO (87.5%) subtypes. Beijing CAO strains, detected mainly in newly diagnosed HIV/TB patients, require further monitoring and control of their spreading.

A stochastic model for the bacterial growth exhibiting staged growth, desynchronization, saturation and persistence

We consider a model of population growth based on the stochastic variation of the population size-controlled duplication of bacterial cells. It is shown that the proper choice of the control function allows for reproducing a variety of regimes: a logistic growth with saturation, a hindered growth typical for persistent bacterial systems, and a linear population growth detected for some mycobacterial populations. When supplied with the rectangular function having the width equal to the generation time, this approach represents the solution generalizing Rubinow’s age-maturity model reproducing systems with desynchronization and saturation. The model’s plausibility is confirmed by the direct comparison with real data for the growth of M. tuberculosis populations obtained with the BACTEC MGIT system under different conditions of growth synchronization.

An open-access dashboard to interrogate the genetic diversity of Mycobacterium tuberculosis clinical isolates.

Tuberculosis (TB) remains one of the leading infectious disease killers in the world. The ongoing development of novel anti-TB medications has yielded potent compounds that often target single sites with well-defined mechanisms of action. However, despite the identification of resistance-associated mutations through target deconvolution studies, comparing these findings with the diverse Mycobacterium tuberculosis populations observed in clinical settings is often challenging. To address this gap, we constructed an open-access database encompassing genetic variations from > 50,000 clinical isolates, spanning the entirety of the M. tuberculosis protein-encoding genome. This resource offers a valuable tool for investigating the prevalence of target-based resistance mutations in any drug target within clinical contexts. To demonstrate the practical application of this dataset in drug discovery, we focused on drug targets currently undergoing phase II clinical trials. By juxtaposing genetic variations of these targets with resistance mutations derived from laboratory-adapted strains, we identified multiple positions across three targets harbouring resistance-associated mutations already present in clinical isolates. Furthermore, our analysis revealed a discernible correlation between genetic diversity within each protein and their predicted essentiality. This meta-analysis, openly accessible via a dedicated dashboard, enables comprehensive exploration of genetic diversity pertaining to any drug target or resistance determinant in M. tuberculosis.

Role of DNA Double-Strand Break Formation in Gyrase Inhibitor-Mediated Killing of Nonreplicating Persistent Mycobacterium tuberculosis in Caseum.

Tuberculosis is the leading cause of mortality by infectious agents worldwide. The necrotic debris, known as caseum, which accumulates in the center of pulmonary lesions and cavities is home to nonreplicating drug-tolerant Mycobacterium tuberculosis that presents a significant hurdle to achieving a fast and durable cure. Fluoroquinolones such as moxifloxacin are highly effective at killing this nonreplicating persistent bacterial population and boosting TB lesion sterilization. Fluoroquinolones target bacterial DNA gyrase, which catalyzes the negative supercoiling of DNA and relaxes supercoils ahead of replication forks. In this study, we investigated the potency of several other classes of gyrase inhibitors against M. tuberculosis in different states of replication. In contrast to fluoroquinolones, many other gyrase inhibitors kill only replicating bacterial cultures but produce negligible cidal activity against M. tuberculosis in ex vivo rabbit caseum. We demonstrate that while these inhibitors are capable of inhibiting M. tuberculosis gyrase DNA supercoiling activity, fluoroquinolones are unique in their ability to cleave double-stranded DNA at low micromolar concentrations. We hypothesize that double-strand break formation is an important driver of gyrase inhibitor-mediated bactericidal potency against nonreplicating persistent M. tuberculosis populations in the host. This study provides general insight into the lesion sterilization potential of different gyrase inhibitor classes and informs the development of more effective chemotherapeutic options against persistent mycobacterial infections.

Molecular and microbiological methods for the identification of nonreplicating Mycobacterium tuberculosis.

Chronic tuberculosis (TB) disease, which requires months-long chemotherapy with multiple antibiotics, is defined by diverse pathological manifestations and bacterial phenotypes. Targeting drug-tolerant bacteria in the host is critical to achieving a faster and durable cure for TB. In order to facilitate this field of research, we need to consider the physiology of persistent MTB during infection, which is often associated with the nonreplicating (NR) state. However, the traditional approach to quantifying bacterial burden through colony enumeration alone only informs on the abundance of live bacilli at the time of sampling, and provides an incomplete picture of the replicative state of the pathogen and the extent to which bacterial replication is balanced by ongoing cell death. Modern approaches to profiling bacterial replication status provide a better understanding of inter- and intra-population dynamics under different culture conditions and in distinct host microenvironments. While some methods use molecular markers of DNA replication and cell division, other approaches take advantage of advances in the field of microfluidics and live-cell microscopy. Considerable effort has been made over the past few decades to develop preclinical in vivo models of TB infection and some are recognized for more closely recapitulating clinical disease pathology than others. Unique lesion compartments presenting different environmental conditions produce significant heterogeneity between Mycobacterium tuberculosis populations within the host. While cellular lesion compartments appear to be more permissive of ongoing bacterial replication, caseous foci are associated with the maintenance of M. tuberculosis in a state of static equilibrium. The accurate identification of nonreplicators and where they hide within the host have significant implications for the way novel chemotherapeutic agents and regimens are designed for persistent infections.

Prevalence, treatment, and outcomes of hepatitis C in an MDR/RR-TB trial cohort.

Tuberculosis (TB) and chronic hepatitis C virus infection (HCV) remain significant global health challenges, especially in low- and middle-income countries. In Eastern Europe, a considerable percentage of multi-drug resistant (MDR) and rifampicin resistant (RR) TB populations show high HCV prevalence. Current WHO guidelines do not routinely advise HCV testing during MDR-TB treatment, despite HCV being a risk factor for drug-induced liver complications in TB patients. This study investigates the co-treatment of MDR/RR-TB and HCV, using data from the TB-PRACTECAL trial. Data were collected as part of the TB-PRACTECAL clinical trial. All participants were screened for HCV at baseline. Participants who were HCV antibody positive and those who were treated for hepatitis C with Direct Acting Antivirals (DAAs) were extracted and compared to overall cohort characteristics. The characteristics of participants concomitantly treated with direct-acting antivirals are described including hepatitis treatment outcomes and adverse events. Among 552 participants from Belarus, Uzbekistan, and South Africa, 24 (4.3%) were HCV antibody positive. Unfavourable TB treatment outcomes were noted in 106/523 (22%) of the HCV-negative, 8/18 (44%) of the HCV-seropositive, and 2/7 (29%) of HCV-confirmed participants treated with DAAs. Of the six participants who received concurrent HCV and MDR/RR TB treatment, three were cured of HCV and three had no post-treatment HCV RNA test, five completed TB treatment and one discontinued treatment due to a severe adverse reaction. Concurrent treatment of MDR-TB and HCV, including in HIV patients, showed promising outcomes with no significant adverse events. The findings support the potential benefits of integrating HCV care into MDR-TB management.

An overview of next generation sequencing strategies and genomics tools used for tuberculosis research.

Tuberculosis (TB) is a grave public health concern and is considered the foremost contributor to human mortality resulting from infectious disease. Due to the stringent clonality and extremely restricted genomic diversity, conventional methods prove inefficient for in-depth exploration of minor genomic variations and the evolutionary dynamics operating in Mycobacterium tuberculosis (M.tb) populations. Until now, the majority of reviews have primarily focused on delineating the application of whole-genome sequencing (WGS) in predicting antibiotic resistant genes, surveillance of drug resistance strains, and M.tb lineage classifications. Despite the growing use of next generation sequencing (NGS) and WGS analysis in TB research, there are limited studies that provide a comprehensive summary of there role in studying macroevolution, minor genetic variations, assessing mixed TB infections, and tracking transmission networks at an individual level. This highlights the need for systematic effort to fully explore the potential of WGS and its associated tools in advancing our understanding of TB epidemiology and disease transmission. We delve into the recent bioinformatics pipelines and NGS strategies that leverage various genetic features and simultaneous exploration of host-pathogen protein expression profile to decipher the genetic heterogeneity and host-pathogen interaction dynamics of the M.tb infections. This review highlights the potential benefits and limitations of NGS and bioinformatics tools and discusses their role in TB detection and epidemiology. Overall, this review could be a valuable resource for researchers and clinicians interested in NGS-based approaches in TB research.

Identification of the health education targeted susceptible population of tuberculosis in Ningxia, Northwest China

Knowledge, Attitude, and Practice (KAP) survey, as an effective measure tool, is of practical significance for identifying the susceptible population in high-incidence regions of tuberculosis (TB). We aim to identify the health education targeted susceptible population of TB and discuss the acting pathway of KAP in Ningxia. A multistage random sampling method was used to conduct a face-to-face questionnaire survey for residents. The latent class analysis (LCA) model was used to classify susceptible populations of TB, and the structural equation modeling (SEM) model was also employed to investigate the interaction mechanisms of KAP (mediation analysis). We further applied the ordered logistic regression model to explore the associated factors. A total of 973 residents were enrolled, 70.6% were male, aged from 16 to 89. The LCA analysis demonstrated that 3 categories of susceptible populations of TB ("overall good", "positive attitude" and "overall poor") have optimal goodness of fit (BIC = 7889.5, Entropy = 0.923). SEM model indicated that the attitude plays a significant mediation effect from knowledge to practice toward TB (an indirect effect of 0.038, and a direct effect of 0.138). The ordered logistic regression results found that age, sex, marital status, education level, occupation, family income, self-perceived health status, having a family member or friend with TB, and knowing the DOTS strategy were significantly associated with classifications of KAP level towards TB. Based on the LCA model, we accurately classified the susceptible population of TB into 3 groups with different degrees of KAP. We found that TB attitude plays a mediating role between knowledge and practice. Therefore, we should pay more attention and carry out targeted health education in the community to these populations with overall poor KAP towards TB, and develop effective strategies and measures to realize the End TB Plan.

The Effect of HIV on the Association of Hyperglycaemia and Active Tuberculosis in Zambia, a Case–Control Study

ObjectivesTo determine if HIV modifies the association between hyperglycaemia and active tuberculosis in Lusaka, Zambia.MethodsA case–control study among newly—diagnosed adult tuberculosis cases and population controls in three areas of Lusaka. Hyperglycaemia is determined by random blood glucose (RBG) concentration measured at the time of recruitment; active tuberculosis disease by clinical diagnosis, and HIV status by serological result. Multivariable logistic regression is used to explore the primary association and effect modification by HIV.ResultsThe prevalence of RBG concentration ≥ 11.1 mmol/L among 3843 tuberculosis cases was 1.4% and among 6977 controls was 1.5%. Overall, the adjusted odds ratio of active tuberculosis was 1.60 (95% CI 0.91–2.82) comparing those with RBG concentration ≥ 11.1– < 11.1 mmol/L. The corresponding adjusted odds ratio among those with and without HIV was 5.47 (95% CI 1.29–23.21) and 1.17 (95% CI 0.61–2.27) respectively; p-value for effect modification by HIV = 0.042. On subgroup analysis, the adjusted odds ratio of smear/Xpert-positive tuberculosis was 2.97 (95% CI 1.49–5.90) comparing RBG concentration ≥ 11.1– < 11.1 mmol/L.ConclusionsOverall, no evidence of association between hyperglycaemia and active tuberculosis was found, though among those with HIV and/or smear/Xpert-positive tuberculosis there was evidence of association. Differentiation of hyperglycaemia caused by diabetes mellitus and stress-induced hyperglycaemia secondary to tuberculosis infection is important for a better understanding of these findings.

Seroprevalence of Treponema pallidum infection among high-risk populations from Brazil

Syphilis is a significant public health concern worldwide. According to the 2020 estimates, nearly 7.1 million new cases of syphilis have been reported globally, with over 30 % of these cases reported from American nations, particularly Brazil. Concerns have been raised regarding the susceptibility of specific groups to syphilis due to challenges and vulnerabilities that place these groups at a higher risk of infections or complications in the treatment outcomes. The present study aimed to compare the seroprevalence and the factors associated with syphilis among such high-risk groups. The study was designed as a cross-sectional one and was conducted with pregnant women, people living with HIV (PLHIV), people living with tuberculosis (PLTB), indigenous and healthy populations in Mato Grosso do Sul, Brazil. The study was conducted between June 2019 and August 2022, during which the included patients were subjected to treponemal and non-treponemal serological assays. The study also included a survey conducted through a self-reported questionnaire to collect information regarding the participants' demographics and sexual behaviors. A total of 550 samples were collected, with 110 participants in each of the five groups. The results of the study revealed that the seroprevalence of Treponema pallidum infection in pregnant women, PLHIV, PLTB, indigenous and healthy populations of the study region was 10 % (n = 11/110), 41.81 % (n = 46/110), 17.27 % (n = 19/110), 5.45 % (n = 6/110), and 8.18 % (n = 9/110), respectively. Homosexual orientation (p = 0.04) and a history of sexually transmitted infection (STI) (p = 0.01) were associated with the seroprevalence of T. pallidum infection in PLHIV. However, no such associations were noted in the remaining four groups. The seroprevalence of T. pallidum infection was observed to vary significantly among the different high-risk groups, which highlighted the persistent concern of syphilis, particularly among vulnerable populations. These findings underscore the significance of focused interventions and public health strategies customized to the specific requirements of each of the groups evaluated in the present study to decrease the number of cases of syphilis and thereby prevent future complications in patients with other serious infections.

Subclinical tuberculosis: a meta-analysis of prevalence and scoping review of definitions, prevalence and clinical characteristics.

This scoping review aimed to characterise definitions used to describe subclinical tuberculosis (TB), estimate the prevalence in different populations and describe the clinical characteristics and treatment outcomes in the scientific literature. A systematic literature search was conducted using PubMed. We included studies published in English between January 1990 and August 2022 that defined "subclinical" or "asymptomatic" pulmonary TB disease, regardless of age, HIV status and comorbidities. We estimated the weighted pooled proportions of subclinical TB using a random-effects model by World Health Organization reported TB incidence, populations and settings. We also pooled the proportion of subclinical TB according to definitions described in published prevalence surveys. We identified 29 prevalence surveys and 71 other studies. Prevalence survey data (2002-2022) using "absence of cough of any duration" criteria reported higher subclinical TB prevalence than those using the stricter "completely asymptomatic" threshold. Prevalence estimates overlap in studies using other symptoms and cough duration. Subclinical TB in studies was commonly defined as asymptomatic TB disease. Higher prevalence was reported in high TB burden areas, community settings and immunocompetent populations. People with subclinical TB showed less extensive radiographic abnormalities, higher treatment success rates and lower mortality, although studies were few. A substantial proportion of TB is subclinical. However, prevalence estimates were highly heterogeneous between settings. Most published studies incompletely characterised the phenotype of people with subclinical TB. Standardised definitions and diagnostic criteria are needed to characterise this phenotype. Further research is required to enhance case finding, screening, diagnostics and treatment options for subclinical TB.

Comparative Study of Vitamin D Levels in Newly Diagnosed Tuberculosis and a Normal Population.

Background and Objectives: Tuberculosis (TB) is an ancient disease caused by Mycobacterium tuberculosis, a member of the Mycobacterium tuberculosis complex. It contributes to significant morbidity and mortality. Treatment of TB poses a considerable challenge because of emerging drug resistance and the longer duration of therapy. Various past studies, both in vitro and in vivo, have established the role of vitamin D in the pathogenesis and treatment of TB. Results of in vivo studies are inconsistent, and this study aims to determine vitamin D levels and their association with newly diagnosed TB (pulmonary and extrapulmonary) cases and normal populations. Material and Methods: A Prospective Case-Control study with 116 subjects (58 cases and 58 controls) was conducted over two years. 29 cases of pulmonary TB and 29 cases of extrapulmonary TB constituted 58 cases of TB. Vitamin D levels were measured and compared in both the cases and controls. Data analysis was carried out using SPSS software 22.0. Results: The prevalence of vitamin D deficiency was 68.96% in the cases, while it was 51.72% in the controls. The reported median and quartile of serum vitamin D levels were 14.35 ng/mL (8.65, 25.48) in the TB group and 19.08 ng/mL (13.92, 26.17) in the control group. There was a significant statistical difference between the TB and non-TB populations with a p-value of 0.029 on the Mann-Whitney test. Conclusion: Vitamin D deficiency was more prevalent in individuals with TB than those without TB.

Nutritional status in patients with tuberculosis and diabetes mellitus: A comparative observational study

BackgroundIndia has been estimated to have 14 % of malnourished population and a high TB incidence burden with a 26.9 lakh cases. Malnutrition and diabetes mellitus are major risk factors for tuberculosis infection. Malnutrition in patients with both tuberculosis and diabetes (TB-DM) population worsens the disease severity, treatment outcomes and increases morbidity and mortality risk. ObjectiveTo assess the nutritional status in patients with TB-DM compared with patients with TB and DM alone. MethodRecords from January 2016 to November 2020 for patients admitted to Kasturba Hospital, Manipal were assessed. Data pertaining to glycemic parameters, nutritional parameters, and other relevant laboratory parameters were extracted for assessment. The study population were divided into three groups i.e. patients with TB-DM, TB and DM. The statistical association was carried out with one-way ANOVA method, considering p < 0.05 as statistically significant. ResultsA total of 291 patients were included, with 97 patients in each group; among those, male and female were 86.27 % and 13.73 % respectively. Cardiovascular co-morbidity was predominant in the DM (68.04 %) and TB-DM (26.8 %) group. The mean value of HbA1c (10.47 %) was found to be highest for the TB-DM group. Low levels of albumin were reported by 71.91 % of patients of the TB group, whereas 73.68 % patients in TB-DM group had vitamin D deficiency. Moreover, higher prevalence of low MCV and MCH in the TB-DM group suggest an increased risk of iron-deficiency anemia. ConclusionThe findings of our study reflect the need for implementation of nutritional support in patients with TB-DM.

Compensatory mutations are associated with increased in vitro growth in resistant clinical samples of Mycobacterium tuberculosis.

Mutations in Mycobacterium tuberculosis associated with resistance to antibiotics often come with a fitness cost for the bacteria. Resistance to the first-line drug rifampicin leads to lower competitive fitness of M. tuberculosis populations when compared to susceptible populations. This fitness cost, introduced by resistance mutations in the RNA polymerase, can be alleviated by compensatory mutations (CMs) in other regions of the affected protein. CMs are of particular interest clinically since they could lock in resistance mutations, encouraging the spread of resistant strains worldwide. Here, we report the statistical inference of a comprehensive set of CMs in the RNA polymerase of M. tuberculosis, using over 70 000 M. tuberculosis genomes that were collated as part of the CRyPTIC project. The unprecedented size of this data set gave the statistical tests more power to investigate the association of putative CMs with resistance-conferring mutations. Overall, we propose 51 high-confidence CMs by means of statistical association testing and suggest hypotheses for how they exert their compensatory mechanism by mapping them onto the protein structure. In addition, we were able to show an association of CMs with higher in vitro growth densities, and hence presumably with higher fitness, in resistant samples in the more virulent M. tuberculosis lineage 2. Our results suggest the association of CM presence with significantly higher in vitro growth than for wild-type samples, although this association is confounded with lineage and sub-lineage affiliation. Our findings emphasize the integral role of CMs and lineage affiliation in resistance spread and increases the urgency of antibiotic stewardship, which implies accurate, cheap and widely accessible diagnostics for M. tuberculosis infections to not only improve patient outcomes but also prevent the spread of resistant strains.

Vitamin D, Body Mass Index, and Total Lymphocyte Count in Drug-Sensitive and Drug-Resistant Tuberculosis Patients in Banjarmasin

Introduction: Tuberculosis (TB) remains a global health problem that causes high morbidity and mortality. Based on its classification, TB is divided into drug-sensitive (DS) and drug-resistant (DR). Several risk factors susceptible to TB are malnutrition with low body mass index (BMI), vitamin D deficiency (VDD), and low total lymphocyte count (TLC) related to low immune status. This study aimed to examine the relationship between vitamin D (VD), BMI, and TLC in the TB population in Banjarmasin. Methods: This was an analytic observational study with a cross-sectional design. The total study sample was 42 patients, confirmed by rapid molecular testing, who had not been treated for TB in Banjarmasin from January to May 2023 and met the inclusion and exclusion criteria. Chi-Square and Fisher's exact statistical tests were used to see the relationship between VD, BMI, and TLC in DS TB and DR TB. Results: The median age of DS TB was 38 (24-52) years old, and DR TB was 51 (37-58) years old. Most of the gender was male (24 patients/57.1%). There was a statistically significant difference between VD and BMI in DS TB and DR TB (p = 0.048; p = 0.019). There was a significant relationship between VD and TLC in DS TB and DR TB (p = 0.048). Conclusion: VD and BMI significantly differed in DS TB and DR TB. There was a significant correlation between VD and TLC in TB patients.

The prevalence of pulmonary hypertension in post-tuberculosis and active tuberculosis populations: a systematic review and meta-analysis.

The prevalence of tuberculosis (TB)-associated pulmonary hypertension (PH) has not previously been quantified, resulting in an underappreciated burden of disease. We aimed to estimate the prevalence of PH in post-TB and active TB populations. In this systematic review and meta-analysis, we searched PubMed/Medline, Cochrane Library, EBSCOhost, Scopus, African Journals Online and Google Scholar, with no language restriction, for available literature published after 1950. Eligible studies described adult participants (≥16 years), with documented evidence of active or prior TB, diagnosed with PH. Study quality was assessed using a risk of bias tool specifically developed for prevalence studies. Aggregate prevalence estimates with 95% confidence intervals were synthesised using a random-effects meta-analysis model, incorporating the Freeman-Tukey transformation. Subgroup analysis was conducted to ascertain prevalence estimates in specific patient populations. We identified 1452 unique records, of which 34 met our inclusion criteria. 23 studies, with an acceptable risk of bias and where PH was diagnosed at right heart catheterisation or echocardiography, were included in the meta-analysis. In post-TB studies (14/23), the prevalence of PH was 67.0% (95% CI 50.8-81.4) in patients with chronic respiratory failure, 42.4% (95% CI 31.3-54.0) in hospitalised or symptomatic patients and 6.3% (95% CI 2.3-11.8) in nonhealthcare-seeking outpatients (I2=96%). There was a lower estimated prevalence of PH in studies of populations with active TB (9.4%, 95% CI 6.3-13.0), I2=84%). Our results highlight the significant burden of PH in post-TB and active TB populations. We emphasise the need for increased recognition of TB-associated PH and additional high-quality prevalence data.

Genetic structure and drug resistance of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; strains in the Kemerovo Region — Kuzbass

Background. Kemerovo Region has a high burden of tuberculosis (TB) with incidence rates twice the national average. The circulating variants of Mycobacterium tuberculosis significantly influence the TB epidemic process. Screening of epidemically significant variants of the pathogen in areas with a high burden of TB underlies epidemiological diagnosis and is necessary for the development of effective prevention measures. However, the population structure of M. tuberculosis in the Kemerovo Region — Kuzbass is poorly understood.&#x0D; Aims: to study genetic heterogeneity and phenotypic resistance to anti-tuberculosis drugs of M. tuberculosis strains in the Kemerovo Region.&#x0D; Materials and methods. The MIRU-VNTR genotyping of 163 M. tuberculosis strains isolated from TB patients in the Kemerovo Region in March–October 2022 was carried out. Cultivation of M. tuberculosis, drug susceptibility testing, and isolation of genomic DNA were carried out by standard methods. Genotypic identification was performed using MIRU-VNTR (24 loci) typing. In parallel, express genotyping was carried out: identification of isolates of the Beijing genotype (by RD105/207) and non-Beijing; subtyping Beijing using real-time PCR tests for detection of Central Asian Russian and B0/W148; identification of the non-Beijing group by real-tine PCR RT tests for LAM, S, Ural.&#x0D; Results. The isolates of the Beijing genotype (67.5%) were found to dominate both among newly diagnosed (64.4%) and previously treated patients (88.5%). MIRU-VNTR typing revealed 75 profiles, of which 94-32 (35.3%) and 100-32 (15.7%) were the most abundant and belonged to the Beijing genotype. Overall, 39.9% and 20.9% of isolates, respectively, were assigned to the Beijing Central Asian Russian and B0/W148 epidemic clusters, which differed significantly in MDR levels (50.8% and 85.3%, respectively; p = 0.005). The second most common were strains of the genetic family of the Euro-American lineage (L4) (31.9%): LAM (6.7%) Ural (7.4%) Haarlem (4.9%) and L4-unclassified (12.9%), MDR among of these minor genotypes was significantly lower than among Beijing genotype strains, and amounted to 11.5% (p 0.001). Strains from HIV-TB patients (56.4% of the total sample) carried an MDR profile more often (54.8%) compared to TB cases without HIV infection (35.2%) (p = 0.005), which may be due to higher proportion of Beijing genotype strains in the HIV-TB group (75.0% vs. 57.7%; p = 0.026). Complete comparability of the SNP analysis (in-house tests) to identify the main genotypes and epidemically significant Beijing subtypes was shown, which made it possible to characterize 75.5% of the sample by the express method.&#x0D; Conclusions. The molecular genetic screening carried out in the Kemerovo Region revealed the heterogeneity of the M. tuberculosis population, which was dominated by strains of the Beijing genotype, with the frequency of subtypes comparable with other territories of the Siberian Federal District.

Regional and epidemiological characteristics of tuberculosis and treatment outcomes in West China.

To understand the prevalence and treatment outcome of tuberculosis in a typically regional County from 2016 to 2021, so as to provide reference and basis for the prevention and treatment of tuberculosis in this area. Descriptive epidemiological methods were used to analyze the population, time and location distribution of pulmonary tuberculosis in Dazhu County from 2016 to 2021. The incidence rates were compared by Chi-square test and trend test, time distribution combined with seasonal index analysis, and the test level was α = 0.05. A total of 2,899 cases of pulmonary tuberculosis were reported in Dazhu County from 2016 to 2021, with an average annual incidence rate of 44.29/100,000 and standardized reported incidence rate was 36.77/100,000, showing a downward trend year by year (χ2 trend = 124.629, p < 0.001). A total of 955 cases of pathogen positive were reported, showing an increasing trend year by year (χ2 trend = 59.773, p < 0.001). In terms of time distribution, the incidence rate was high in autumn and winter, and September and December were the peak of the disease in the whole year, and the overall trend increased first, then decreased and once again increased (F = 5.861, p < 0.05). In regional distribution, the highest annual average reported incidence rate was in concentrated population. The incidence rate of male was higher than female in population distribution. After standardization, the overall incidence rate increased from 34 to 45 years old (χ2 trend = 6963.101, p < 0.001), and decreased after 45 years old (χ2 trend = 1104.393, p < 0.001). The occupation distribution is mainly farmers (82.75%). The overall arrival rate and cure rate of patients showed an upward trend year by year (χ2 trend = 4.306, χ2 trend = 5.772, p < 0.001). The incidence rate of pulmonary tuberculosis in this regional county is decreasing year by year. Male patients are higher than female patients and have certain seasonal characteristics. Attention should be paid to male, older adult, farmers and other groups, and corresponding measures should be taken to strengthen the prevention and treatment of tuberculosis in high incidence areas.

The necessity for enhancing awareness of tuberculosis starting from the early college semesters: empirical evidence from a cross-sectional research.

College students, especially those in the lower grades, constitute the main high-risk population for tuberculosis (TB). Insufficient knowledge about TB among college students contributes to an increased risk of TB infection. In Zhejiang Province, China, limited research has been conducted recently on the awareness of TB in schools among college students. Therefore, this study aims to gain insight into TB knowledge among low-grade college students in Zhejiang Province and develop effective strategies for TB education targeted at this specific population. A cross-sectional survey was conducted between 1st and 20th May 2022 in 20 colleges in Zhejiang Province, southeastern China. The survey aimed to assess the level of TB awareness among 1st and 2nd-year college students. Chi-square tests were performed to compare the rates, while multivariate logistic regression was used to identify the factors influencing the overall awareness level of students' regarding key knowledge about TB. A total of 4,414 lower-grade students participated in the study. The total awareness rate and entire awareness rate of key TB knowledge were 81.6 and 25.3%, respectively. Participants who demonstrated a relatively poor understanding of the definition were (51.0%), curable outcomes (75.7%), and preventive measures of TB (76.1%). Female participants [adjusted odds ratio (aOR):1.44; 95% confidence interval (CI):1.25-1.65], medical students (aOR:2.00; 95%CI:1.63-2.64), had a high level of monthly expenditures (aOR:2.50; 95%CI:1.49-4.19), had prior TB health education (aOR:1.95; 95%CI:1.68-2.25) and previous exposure to TB patients (aOR:2.13; 95% CI:1.48-3.08) indicating a better level of awareness of key knowledge about TB. Among the students, 58.5% expressed their willingness to acquire TB knowledge through "broadcasting, television, films, and audiovisual materials." The total awareness rate of key knowledge among low-grade college students in Zhejiang did not meet the national requirements. To effectively prevent TB in schools, it is crucial to develop a comprehensive understanding of the disease among college students. Therefore, it is necessary to enhance TB awareness through theoretical and practical education, starting from the early semesters of college.