Tuberculosis Susceptibility Research Articles

Association of NOS2A Gene Polymorphisms with Susceptibility to Tuberculosis in Manipuri Population of Northeast India.

Single nucleotide polymorphisms (SNPs) have been reported to influence the activity of specific genes involved with the innate immune response to Mycobacterium; hence, they are crucial in tuberculosis (TB) susceptibility studies. The study aimed to investigate the polymorphism in the NOS2A (Nitric oxide synthase 2A)geneand its association with susceptibility to TB in the Manipuri population of northeast India. This case-control study includes 495 subjects- 220TB patients and 275 control individuals. TaqMan allelic discrimination assay was used to study the gene polymorphism, and Griess's test was employed to determine the serum nitric oxide (NO) levels. Serum NO levels were analysed to correlate with the functional changes associated with the polymorphisms. Two SNPs of the gene,NOS2A(rs8078340 and rs2274894), were studied. For the SNP-rs8078340, a significant difference in the genotypic and allelic frequencies was observed between the cases and control groups (p = 0.001; AA genotype OR = 30.288, 95% CI: 1.703-538.44 and A allele OR = 2.937, 95%CI: 1.762-4.896). However, for the SNP-rs2274894, only the T allele (with OR = 1.464; 95%CI: 1.080-1.983, p = 0.014) was associated with susceptibility to TB. Serum levels of NO were significantly different between the cases and control groups (p < 0.05). Significant associations of both homozygous AA genotype and allele A of the NOS2A (rs8078340) and minor allele T of NOS2A (rs2274894) were observed with susceptibility to TB. Patients with the AA genotype of NOS2A show a higher NO level, suggesting its role in greater expression of the NOS2A gene.

Unraveling the Link between Obesity and Tuberculosis: A Systematic Review of the Underlying Mechanisms

Background: Tuberculosis (TB) and obesity are significant global health concerns with potentially complex interactions. Obesity, through its effects on metabolism, inflammation, and the immune system, may influence TB susceptibility, progression, and treatment outcomes. This systematic review aims to analyze the published literature on the relationship between obesity and TB, focusing on the underlying mechanisms. Methods: A systematic search of PubMed, Science Direct, and Google Scholar was conducted for articles published in the last 10 years. The search strategy included keywords such as "tuberculosis," "TB," "obesity," and "BMI." Articles were selected using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) method. Results: The review identified 11 studies that met the inclusion criteria. The studies revealed a complex relationship between obesity and TB, with nutritional status, immunity, and diabetes mellitus (DM) playing key roles. Obesity can alter the immune response to TB, potentially increasing the risk of disease and affecting treatment efficacy. Conclusion: The relationship between obesity and TB is multifaceted, with obesity potentially influencing both disease susceptibility and outcomes. Further research is needed to fully elucidate the underlying mechanisms and to develop targeted interventions for individuals with both obesity and TB.

Beyond Infection: The Role of Stunting in Tuberculosis Susceptibility and Treatment Outcomes

Background: Tuberculosis (TB) remains a major global health concern, particularly in developing countries. Stunting, a manifestation of chronic malnutrition, is prevalent in these regions and is increasingly recognized as a significant risk factor for TB. This systematic review aims to comprehensively analyze the impact of stunting on TB susceptibility and treatment outcomes. Methods: A systematic search of PubMed and ScienceDirect databases was conducted for studies published in the last 10 years, focusing on the relationship between stunting and TB. The PRISMA guidelines were followed for article selection and data extraction. Results: The review identified a significant association between stunting and increased TB risk. Stunted individuals exhibit impaired immune responses, making them more susceptible to TB infection. Moreover, stunting negatively affects TB treatment outcomes, including increased treatment duration, higher relapse rates, and greater mortality risk. Conclusion: Stunting is a critical determinant of TB susceptibility and treatment outcomes. Addressing stunting through comprehensive nutritional interventions is crucial not only for reducing the burden of malnutrition but also for enhancing TB prevention and control efforts.

Immunological mechanisms of tuberculosis susceptibility in TB-infected individuals with type 2 diabetes mellitus: insights from mycobacterial growth inhibition assay and cytokine analysis.

This study is important because it sheds light on the impaired immune response in individuals with type 2 diabetes mellitus (T2DM) who are infected with Mycobacterium tuberculosis (M.tb), offering critical insights into why they are at higher risk of developing active tuberculosis (TB). By demonstrating that T2DM individuals exhibit a weakened ability to control M.tb growth and a compromised cytokine profile, the research underscores the need for better diagnostic tools, such as the mycobacterial growth inhibition assay (MGIA), to identify those at greater risk of progression to active TB. The findings also highlight the importance of integrated care strategies for managing both T2DM and TB, particularly in TB-endemic regions, and point to the need for further research to develop more effective interventions tailored to this vulnerable population.

Evolution of Hematobiochemical Profiles in Newly Diagnosed HIV Patients and HIV-TB Co-Infected Patients: Correlation with Immunological and Virological Status.

CD4+ cells, HIV-1 plasma viral load (PVL), and IFN-γ have been observed to enhance susceptibility in TB infection/reactivation among HIV-1 infected people, leading to unusual clinical manifestations. HIV-TB co-infection is significant for immunological and virological response, making it a great clinical challenge for patient management. The objective of this study was to explore the correlation among various hematological and biochemical profiles with CD4+ count and PVL in order to decipher mechanisms of TB development or reactivation in HIV-infected patients. In this cross-sectional study, we included 200 newly diagnosed treatment naïve HIV-1 infected patients, of which 118 were HIV-TB co-infected and 82 were HIV-alone. The CD4+ T count was determined using the BD FACS Count System, and the plasma HIV-1 viral load was estimated using the Abbott m2000 real-time platform. The hematobiochemical testing was performed on fully-automated analyzer ADVIA® 560 and Cobas® 501 Roche Diagnostics. Statistical software SPSS-2, Spearman correlation analysis was used for data analysis and a P-value less than 0.05 was considered statistically significant. Declined hemoglobulin level positively correlated with CD4 counts (r = 0.229; p = 0.001), and a negative correlation was observed with HIV-1 plasma viral load (r = -0.171; p = 0.016). Moreover, the CD4+ count and HIV-1 plasma viral load (PVL) were also correlated to anomalies such as thrombocytopenia, leucopenia, eosinophils, neutrophils, ESR, potassium, Albumin, globulin, SGOT, uric acid. Studies also found significantly higher absolute neutrophil count, ESR, and serum fasting blood sugar, creatine, uric acid, total bilirubin, globulin, and alkaline phosphatase in HIV-TB co-infected patients. The initial value of Hb, ESR, absolute neutrophil counts, serum calcium, uric acid, and potassium can be used as an early indicator for active tuberculosis (TB) and as a substitute marker for the course of HIV disease, especially in areas with low resources.

Survival analysis shows tuberculosis patients with silicosis experience earlier mortality and need employer-led care models in occupational settings in India

India’s high tuberculosis (TB) burden is exacerbated by concurrent silicosis, which increases TB susceptibility and worsens treatment outcomes. Limited studies on TB patients with silicosis highlight the need to address this vulnerable group’s specific challenges, particularly to improve diagnosis and management. This retrospective cohort study analyzed survival data from 137 silico-tuberculosis and 2,605 TB-only patients in Khambhat, India, using Kaplan-Meier curves, log-rank tests, and comparisons between Cox proportional hazards and accelerated failure time (AFT) models. The lognormal AFT model, selected for its lowest Akaike Information Criterion (AIC), estimated survival times based on age, gender, HIV status, and prior TB treatment. Among the 2,742 patients, 309 (11%) died within 27 months. Median time from diagnosis to outcome was shorter for deceased patients (1.7 months) than for censored patients (5.6 months, p < 0.001, median test). Kaplan-Meier analysis showed a significantly steeper survival decline for silico-tuberculosis patients (p < 0.001, log-rank test). Silico-tuberculosis was associated with a two-fold increased mortality risk (HR = 2.0, 95% CI: 1.4-3.0, p < 0.001, Cox-proportional hazards regression). The lognormal AFT model indicated silico-tuberculosis patients had 36% of the median survival time compared to TB-only patients (16 vs. 44 months). These findings highlight significantly earlier mortality in silico-tuberculosis patients, underscoring the need for targeted, employer-led care models and TB-silicosis collaborative screening within India’s TB program for high-risk occupational groups.

Meta-analysis of interleukin-10gene polymorphisms and tuberculosis susceptibility: Insights from recent studies.

Tuberculosis (TB) remains a universal health problem with significant morbidity and mortality. Understanding the genetic factors affecting TB susceptibility is crucial for effective prevention and treatment. Interleukin-10 (IL-10), a regulatory cytokine, may influence TB pathogenesis through genetic variations. The PubMed, Embase, and Google Scholar databases were searched to find studies on the relationship between IL-10gene variants and tuberculosis. Relevant studies from 2016 to 2024 were identified through database searches. The selected case-control studies met the inclusion criteria. Software such as Review Manager was used to analyze quantitative data, with statistical significance set at p< 0.05. We calculated odds ratios and their respective confidence intervals to evaluate the associations. Nine studies examined IL-10 gene polymorphisms (rs1800871 and rs1800872) in TB susceptibility. The present study did not show a notable association between IL-10 gene polymorphisms and TB among all genetic models (allelic, homozygote, heterozygote, dominant, and recessive). The obtained p-value > 0.05 indicates an insignificant association between both gene polymorphisms of IL-10. An OR-1.13; 95% CI-0.85, 1.50 was obtained for the SNP rs1800871, whereas an OR-1.02; 95% CI-0.75, 1.40 was obtained for the SNP rs1800872. Our meta-analysis revealed no significant association between IL-10 gene polymorphisms and TB susceptibility, suggesting that these variations may not significantly contribute to TB susceptibility. Further research with a larger sample size and diverse ethnicities is needed to explore additional genetic variations and their implications in TB pathogenesis.

Analysis of genetic characteristics associated with reduced bedaquiline susceptibility in multidrug-resistant Mycobacterium tuberculosis

Bedaquiline (BDQ) has shown efficacy in shortening treatment duration and enhancing treatment success rates for multidrug-resistant tuberculosis (MDR-TB), thereby prompting widespread adoption. However, resistance to BDQ has emerged. This study aimed to identify genetic characteristics associated with decreased susceptibility to BDQ, using a public database to aid in the detection of resistant strains. Seventy-one BDQ-resistant and 929 BDQ-susceptible isolates from the open-source CRyPTIC database were selected for analysis. Variant calling was conducted via the clockwork pipeline. Univariate logistic regression was performed for each gene mutation, followed by LASSO regression for further variant selection. Ultimately, a multiple linear regression model was developed using log2-transformed Minimum Inhibitory Concentration values as the dependent variable, with variant selection refined through stepwise regression based on the Akaike Information Criterion. Ten gene mutations were significantly associated with reduced BDQ susceptibility, including two key gene mutations: Rv0678_141_ins_1 and Rv1979c_D249E, with effect estimates of 1.76 (95 % CI: 0.67–2.84) and 1.69 (95 % CI: 0.22–3.17), respectively. Other implicated genes included Rv2699c_-84_del_1, hsaB_I179T, mmpL9_T241A, pncA_C14R, Rv0373c_G621S, Rv0893c_L27F, Rv1770_A4D, and Rv3428c_S327C. This study identified ten gene mutations linked to decreased susceptibility to BDQ, providing a reference for developing a comprehensive catalog of BDQ-resistant genes.

Exploring the association between SLC11A1 and CARD15 gene polymorphisms and tuberculosis susceptibility in Holstein cattle

Abstract. Bovine tuberculosis (bTB) is a contagious disease that has a socio-economic impact on familial and industrial farms. Genetic selection can improve resistance against bTB. This study aimed to characterize the links between SLC11A1 and CARD15 gene polymorphisms and tuberculosis (TB) susceptibility. In total 200 animals were used (50 cases and 150 controls). Polymorphisms in the SLC11A1 and CARD15 genes were identified and analyzed with the restriction fragment length polymorphism (PCR-RFLP) method. Our results report the PstI PCR-RFLP marker for the SLC11A1-SNP1 site and the StyI PCR-RFLP marker for the CARD51-SNP1 site in Tunisian Holstein cows. Statistical analysis showed a significant association between SLC11A1-SNP1, CARD15-SNP1 and susceptibility/resistance to TB (P &lt; 0.05). Two SLC11A1-SNP1 genotypes were susceptible to tuberculosis, i.e., the heterozygote CG and the homozygote CC, while one SLC11A1-SNP1 genotype, i.e., the GG mutated homozygote, was less susceptible to infection. Concerning the CARD15 gene, two genotypes are highly sensitive to the incidence of bovine tuberculosis, i.e., AA and AG, while the GG genotype is more beneficial and more tolerant of Mycobacterium bovis. SLC11A1 and CARD15 are two useful candidate genes associated with tuberculosis, and this information can be used to improve the health status of domestic cattle and humans.

Use of Dispersible Fixed-Dose Combinations in Chemotherapy of Drug Susceptible Tuberculosis: Results of the Observational Study

The objective: to assess effectiveness, safety and pharmacoeconomic feasibility of using a dispersible fixed-dose combination (isoniazid 150 mg, rifampicin 150 mg, pyrazinamide 375 mg) in patients with respiratory tuberculosis and preserved susceptibility of Mycobacterium tuberculosis (MTB) to anti-tuberculosis drugs.Subjects and Methods. A post-registration observational study was conducted to assess treatment effectiveness of pulmonary tuberculosis in 60 adult patients with drug susceptible tuberculosis. In Main Group, patients received the fixed-dose combination (isoniazid 150 mg, rifampicin 150 mg, pyrazinamide 375 mg), while in Control Group, patients were treated with the regimen consisting of single anti-tuberculosis drugs.Results. Sputum conversion rate made 76.7% by the end of the intensive phase (60 doses) when replacing isoniazid, rifampicin and pyrazinamide with the dispersible fixed-dose combination, while with the standard choice of drugs, it was 66.7%. The incidence of adverse reactions was 7-fold lower when using the investigational drug which contributed to a high level of adherence and high effectiveness of therapy. Pharmacoeconomic analysis convincingly demonstrated advantages and economic benefits of the dispersible fixed-dose combination (isoniazid 150 mg, rifampicin 150 mg, pyrazinamide 375 mg), which was more costly than the combination of single drugs.

Lipid Peroxidation and Type I Interferon Coupling Fuels Pathogenic Macrophage Activation Causing Tuberculosis Susceptibility.

A quarter of human population is infected with Mycobacterium tuberculosis, but less than 10% of those infected develop pulmonary TB. We developed a genetically defined sst1-susceptible mouse model that uniquely reproduces a defining feature of human TB: the development of necrotic lung granulomas and determined that the sst1-susceptible phenotype was driven by the aberrant macrophage activation. This study demonstrates that the aberrant response of the sst1-susceptible macrophages to prolonged stimulation with TNF is primarily driven by conflicting Myc and antioxidant response pathways leading to a coordinated failure 1) to properly sequester intracellular iron and 2) to activate ferroptosis inhibitor enzymes. Consequently, iron-mediated lipid peroxidation fueled IFNβ superinduction and sustained the Type I Interferon (IFN-I) pathway hyperactivity that locked the sst1-susceptible macrophages in a state of unresolving stress and compromised their resistance to Mtb. The accumulation of the aberrantly activated, stressed, macrophages within granuloma microenvironment led to the local failure of anti-tuberculosis immunity and tissue necrosis. The upregulation of Myc pathway in peripheral blood cells of human TB patients was significantly associated with poor outcomes of TB treatment. Thus, Myc dysregulation in activated macrophages results in an aberrant macrophage activation and represents a novel target for host-directed TB therapies.

Mast cells promote pathology and susceptibility in tuberculosis.

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), infects approximately one-fourth of the world's population. While most infected individuals are asymptomatic, latent TB infection (LTBI) can progress to cause pulmonary TB (PTB). We recently reported an increased accumulation of mast cells (MCs) in lungs of macaques with PTB, compared with LTBI in macaques. MCs respond in vitro to Mtb exposure via degranulation and by inducing proinflammatory cytokines. In the current study, we show the dominant production of chymase by MCs in granulomas of humans and macaques with PTB. Using scRNA seq analysis, we show that MCs found in LTBI and healthy lungs in macaques are enriched in genes involved in tumor necrosis factor alpha, cholesterol and transforming growth factor beta signaling. In contrast, MCs clusters found in PTB express transcriptional signatures associated with interferon gamma, oxidative phosphorylation, and MYC signaling. Additionally, MC deficiency in the mouse model showed improved control of Mtb infection that coincided with reduced accumulation of lung myeloid cells and diminished inflammation at chronic stages. Thus, these collective results provide novel evidence for the pathological contribution of MCs during Mtb infection and may represent a novel target for host directive therapy for TB.

Diagnostic accuracy of LiquidArray MTB-XDR VER1.0 for the detection of Mycobacterium tuberculosis complex, fluoroquinolone, amikacin, ethambutol, and linezolid susceptibility.

Drug susceptibility testing (DST) is essential for effectively starting people on effective tuberculosis (TB) regimens. No accuracy data exists for the new high-throughput LiquidArray MTB-XDR (LA-XDR) test, which detects Mycobacterium tuberculosis complex (MTBC) and susceptibility to the fluoroquinolones, amikacin, ethambutol, and linezolid (the latter two drugs have no rapid molecular DSTs available). We enrolled (n=720) people with presumptive TB who provided two sputa for Xpert MTB/RIF Ultra and culture (MTBC reference standard). Phenotypic DST and Sanger sequencing served as a composite reference standard. Manual FluoroLyse and automated GenoXtract-fleXT (fleXT) DNA extraction methods were compared. For MTBC, LA-XDR using fleXT-extracted or FluoroLyse-extracted DNA had similar sensitivities (85-87%; which improved upon eluate retesting) and specificities (99%). Drug susceptibility sensitivities varied: 94% (86, 98) for fluoroquinolones, 64% (45, 80) for amikacin, and 88% (79, 93) for ethambutol (specificities 97-100%). LA-XDR detected 86% (6/7) phenotypically resistant linezolid isolates. LA-XDR with fleXT had indeterminate proportions of 8% (21/251) for fluoroquinolones, 1% (2/251) for ethambutol, 25% (63/251) for amikacin, and 37% (93/251) for linezolid. In a hypothetical population of 100 smear-negative fluoroquinolones-resistant cases, 24% (24/100) could be missed due to an unsuccessful result (1 fleXT error and, for LA-XDR, 2 invalid results, 15 MTBC-negative, 6 fluoroquinolone-indeterminate, 1 false-susceptible). LA-XDR met the minimum WHO target product profile for a next-generation sputum-based moderate complexity DST with high sensitivity for fluoroquinolones and ethambutol resistance, moderate sensitivity for amikacin resistance, and promise for linezolid resistance, for which more data are needed. Improved MTBC detection would reduce missed resistance.

Association between vitamin D receptor gene polymorphisms and susceptibility to tuberculosis: a systematic review and meta-analysis.

Tuberculosis (TB) is the leading cause of mortality worldwide. Previous studies have reported that TB susceptibility can be caused by vitamin D deficiency, which is affected by polymorphisms in the vitamin D receptor (VDR) gene. However, these results have been inconsistent. Therefore, we performed a meta-analysis to investigate the association between VDR polymorphisms and TB susceptibility. We systematically searched for relevant literature in PubMed, Embase, and Medline databases through December 31st, 2022. Inclusion and exclusion criteria were made to ensure that HIV-negative population is the targeted subjects. The pooled odds ratio (OR) and 95% confidence interval (CI) were then used to assess the strength of the association, and the quality of the included articles was evaluated using the Newcastle-Ottawa Scale. Potential sources of heterogeneity were evaluated based on subgroup and meta-regression analyses. In our meta-analysis, we found that the FokI polymorphism in the VDR gene was associated with increased TB susceptibility in the allele and recessive genotype models (OR f vs. F = 1.235, 95%CI: 1.035-1.475; OR ff vs. Ff + FF = 1.317, 95%CI: 1.005-1.727. Further subgroup analysis based on ethnicity demonstrated the association with the risk of TB in all genotype models of the FokI polymorphism for Han population. Meta-regression analysis also indicated that ethnicity could be a potential source of heterogeneity in the FokI and BsmI polymorphisms in the VDR gene. However, publication year was another source of heterogeneity for the TaqI polymorphism. In summary, the FokI polymorphism in the VDR gene was found to increase the risk of TB in the HIV-negative population, both overall and in Asian populations. The findings presented in this paper could provide clues for preventing TB from the perspective of vitamin D supplementation, which is a controversial topic in the field of medicine and health.

Tuberculosis susceptibility in genetically diverse mice reveals functional diversity of neutrophils.

Tuberculosis (TB) is a heterogenous disease in humans with individuals exhibiting a wide range of susceptibility. This heterogeneity is not captured by standard laboratory mouse lines. We used a new collection of 19 wild-derived inbred mouse lines collected from diverse geographic sites to identify novel phenotypes during Mycobacterium tuberculosis ( Mtb ) infection. Wild derived mice have heterogenous immune responses to infection that result in differential ability to control disease at early timepoints. Correlation analysis with multiple parameters including sex, weight, and cellular immune responses in the lungs revealed that enhanced control of infection is associated with increased numbers of CD4 T cells, CD8 T cells and B cells. Surprisingly, we did not observe strong correlations between IFN-γ production and control of infection. Although in most lines high neutrophils were associated with susceptibility, we identified a mouse line that harbors high neutrophils numbers yet controls infection. Using single-cell RNA sequencing, we identified a novel neutrophil signature associated with failure to control infection.

The course of tuberculosis infection in hyper-susceptible mice carrying the &lt;i&gt;H2&lt;/i&gt;ᵛ haplotype

Genetic regulation of the host susceptibility to Mycobacterium tuberculosis (Mtb) and severity of tuberculosis (TB) infection remain incompletely investigated. Identification of particular genes and involved in TB control and immune reactions regulated by these genes is essential for our understanding of pathogenesis of the disease, discovery of drug targets and rational vaccine development. We have shown that mice of the B10.SM (H2ᵛ) strain are extremely TB susceptible; meanwhile, the general genome structure of this mouse strain and the H2ᵛ haplotype itself are poorly characterized. We selected a pool of Mit genetic markers differentiating B10.SM mice from Chr. 17-congenic mice of the B10 strain by the PCR products motility in the electrophoresis setting. TB susceptibility of B10 mice is much lower than that of B10.SM. In the model of infection triggered by two different dosed of Mtb (100 and 600 CFU per mouse) administered via respiratory tract we demonstrated that B10.SM mice have significantly shorter survival time and significantly higher lung mycobacterial multiplication compared to B10 mice. We demonstrated (intracellular staining and ELISA) that IFNγ production in the lungs of infected mice of the two strains corresponds well to their disease phenotypes. Thus, more resistant B10 mice possess significantly more lung IFNγ-positive CD4⁺ T cells and a higher level of IFNγ secretion. We have established (B10х B10.SM) F1 hybrids and demonstrated that the post-infection phenotypes of survival time, lung mycobacterial multiplication and IFNγ production in these mice are intermediate compared to parental mice. Thus, we deal with the genetic trait with incomplete dominance expression. These data were confirmed in F2 hybrids by segregation genetic analysis. To characterize the phenotype of B10.SM mice in more detail, we vaccinated these mice with the BCG vaccine before TB challenge. Vaccination significantly prolonged survival time, diminished mycobacterial multiplication in the lungs and the degree of lung tissue pathology. Thus, a high level of susceptibility to primary infection did not interfere with BCG vaccination efficacy. We intend to continue genetic and immunologic analyses of TB-hyper-susceptible B10.SM mice. Experimental data regarding the cause of extreme disturbances in protection against infection are prerequisite for our better understanding causality of the wide spectrum of TB manifestations in human populations, as well as for rational search for novel vaccines and medications against TB infection.

Strong effect of demographic changes on Tuberculosis susceptibility in South Africa.

South Africa is among the world's top eight tuberculosis (TB) burden countries, and despite a focus on HIV-TB co-infection, most of the population living with TB are not HIV co-infected. The disease is endemic across the country, with 80-90% exposure by adulthood. We investigated epidemiological risk factors for (TB) in the Northern Cape Province, South Africa: an understudied TB endemic region with extreme TB incidence (926/100,000). We leveraged the population's high TB incidence and community transmission to design a case-control study with similar mechanisms of exposure between the groups. We recruited 1,126 participants with suspected TB from 12 community health clinics and generated a cohort of 774 individuals (cases = 374, controls = 400) after implementing our enrollment criteria. All participants were GeneXpert Ultra tested for active TB by a local clinic. We assessed important risk factors for active TB using logistic regression and random forest modeling. We find that factors commonly identified in other global populations tend to replicate in our study, e.g. male gender and residence in a town had significant effects on TB risk (OR: 3.02 [95% CI: 2.30-4.71]; OR: 3.20 [95% CI: 2.26-4.55]). We also tested for demographic factors that may uniquely reflect historical changes in health conditions in South Africa. We find that socioeconomic status (SES) significantly interacts with an individual's age (p = 0.0005) indicating that protective effect of higher SES changed across age cohorts. We further find that being born in a rural area and moving to a town strongly increases TB risk, while town birthplace and current rural residence is protective. These interaction effects reflect rapid demographic changes, specifically SES over recent generations and mobility, in South Africa. Our models show that such risk factors combined explain 19-21% of the variance (r2) in TB case/control status.

Psychological manifestations in patients with tuberculosis: prevalence and contributing factors

Tuberculosis (TB) continues to be a major global health concern impacting millions of people each year. Beyond its outward symptoms TB can have a significant negative influence on psychological health and cause psychological anguish in those who are afflicted. The purpose of this review is to recapitulate the frequency and contributing variables of psychological discomfort in TB patients. Previous studies show varying prevalence rates of psychological distress which frequently manifests as stress, worry, and depression. Numerous factors such as sociodemographic characteristics the severity of the disease the treatment plan, stigma, and social support. these factors can alter gene expression patterns, epigenetic modifications, and immune responses linked to higher psychological distress. Psychological factors like stress, anxiety, and depression can influence gene metabolism in TB patients through various mechanisms. These factors impacting TB susceptibility, disease progression, and treatment outcomes. To effectively address the mental health needs of TB patients, it is imperative to comprehend the prevalence and factors of psychological distress in tb population. Promote the holistic well-being of TB patients, it is imperative that mental health treatments be integrated into TB care in conjunction with initiatives to lessen stigma and enhance social support.

Drug Susceptibility and Mutation Profiles in Mycobacterium tuberculosis Isolates from a Tertiary Care Hospital in Kerala, India.

The rising prevalence of drug-resistant Mycobacterium tuberculosis (MTB) strains poses a significant challenge to global tuberculosis (TB) control efforts. This study aimed to analyze drug resistance patterns and investigate the molecular characteristics of 193 MTB clinical isolates to shed light on the mechanisms of drug resistance. Of the 193 MTB clinical isolates, 28.5% (n = 53) exhibited mono-drug or multidrug resistance. Pyrazinamide mono-drug resistance (PZAr) was the most prevalent (17%, n = 33), followed by isoniazid mono-drug resistance (3.6%, n = 7). Rifampicin resistance was associated with mutations in the rpoB gene (D435Y, D435V, S450L, L452P). Isoniazid resistance mutations were found in the katG (S315T), inhA (C[-15] T), and ndh (R268H) genes, whereas ethambutol resistance mutations were observed in the embB gene (M306V, M306I, M306L, G406S, Q497R). Surprisingly, 94% of PZAr isolates (n = 31) showed no mutations in the pncA or rpsA genes. The presence of the R268H mutation in the ndh gene, not previously linked to PZAr, was detected in 15% of PZAr isolates (n = 5), suggesting its potential contribution to PZAr in specific cases but not as a predominant mechanism. The specific molecular mechanisms underlying PZAr in the majority of the isolates remain unknown, emphasizing the need for further research to uncover the contributing factors. These findings contribute to the understanding of drug resistance patterns and can guide future efforts in TB control and management.

Association of CYP27B1 gene polymorphisms with pulmonary tuberculosis and vitamin D levels

Background and ObjectivesGenetic factors are reported to be connected with tuberculosis (TB) infection. Studies have shown that genetic variations in genes involved in the vitamin D pathway influence the levels of vitamin D found in the bloodstream (serum). Cyp27b1 (1α-hydroxylase) is an enzyme that activates the synthesis of bioactive vitamin D3 by hydroxylation of 25(OH)D3.The in vitro studies reported rare gene variants of Cyp27b1 such as rs118204011 and rs118204012, associated with loss of Cyp27b1 function and lower serum vitamin D levels. Globally, a critical gap exists in understanding the link between these gene variants with TB and vitamin D levels. Hence, the study objective is to comprehend the association of Cyp27b1 rs118204009 (G/A), rs118204011 (C/T), and rs118204012 (A/G) with tuberculosis susceptibility/protection and to assess the influence of gene variants on vitamin D levels in both healthy controls (HCs) and those with pulmonary tuberculosis (PTB) in South India. MethodsGenomic DNA extraction was performed by salting-out procedure and subsequently genotyped through polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Vitamin D level was measured by Enzyme-Linked Immunosorbent Assay (ELISA). ResultsIn rs118204012 (A/G), a substantial association was found with PTB susceptibility in allele ‘A’ [Odds Ratio (OR): 1.52 (1.02–2.26); p = 0.044] and ‘AA’ genotype [OR: 1.69 (1.02–2.81); p = 0.040] through the dominant model. Allele ‘G’ [OR: 0.66 (0.44–0.98); p = 0.044) was found to be associated with protection against TB. Males were associated with increased susceptibility towards TB compared to females in the rs118204011 “CC” [OR: 3.94 (1.94–7.98); p = 0.002] and rs118204012 ‘AA’ [OR: 4.57 (2.13–9.79); p = 0.0001] genotypes. Vitamin D insufficiency (<30 ng/ml) was more prevalent in PTB patients (66.67 %) with the rs118201012 ‘AA’ genotype compared with healthy controls (57.14 %). This genotype was associated with disease susceptible odds ratio of 1.5. ConclusionCyp27b1 rs118204012 ‘AA’ genotype was found to have association with vitamin D insufficiency and TB susceptibility. In terms of gender, our findings suggest that male individuals are correlated with a higher TB risk. This suggest that the gene variants may be involved in the downstream processing of serum Vitamin D levels and its association with the disease.