Latent Tuberculosis Infection Research Articles

Specific human gene expression in response to infection is an effective marker for diagnosis of latent and active tuberculosis.

RNA sequencing and microarray analysis revealed transcriptional markers expressed in whole blood can differentiate active pulmonary TB (ATB) from other respiratory diseases (ORDs), and latent TB infection (LTBI) from healthy controls (HC). Here we describe a streamlined reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assay that could be applied at near point-of-care for diagnosingand distinguishing ATB from ORDs and LTBI from HC. A literature review was undertaken to identify the most plausible host-gene markers (HGM) of TB infection. Primers, and dual labelled hydrolysis probes were designed and analytically evaluated for accuracy in an in-vitro model of infection using a lung fibroblast cell-line. Best performing genes were multiplexed into panels of 2-4 targets and taken forward for clinical evaluation. Mycobacteria Growth Indicator Tube and QuantiFERON-TB Gold Plus were used as reference tests for ATB and LTBI respectively. A total of 16 HGM were selected and incorporated into five multiplex RT-qPCR panels. PCR assay efficiency of all evaluated targets was ≥ 90% with a median analytical sensitivity of 292 copies/µl [IQR: 215.0-358.3 copies/µl], and a median limit of quantification of 61.7 copies/µl [IQR: 29.4-176.3 copies/µl]. Clinically, ATB was characterised by higher gene expression than ORDs, while LTBI was associated with lower gene expression than HC, Kruskal-Wallis p < 0.0001. Crucially, BATF2, CD64, GBP5, C1QB, GBP6, DUSP3, and GAS6 exhibited high differentiative ability for ATB from ORDs, LTBI or HC while KLF2, PTPRC, NEMF, ASUN, and ZNF296 independently discriminated LTBI from HC. Our results show that different HGM maybe required for ATB and LTBI differentiation from ORDs or HC respectively and demonstrate the feasibility of host gene-based RT-qPCR to diagnose ATB and LTBI at near point-of-care.

The Crosstalk Between HIV-TB Co-Infection and Associated Resistance in the Indian Population

Extensive research on tuberculosis (TB) and HIV co-infection reveals the diverse prevalence and co-epidemic patterns across populations, necessitating tailored public health strategies. Co-infection is bidirectional; individuals with HIV are more susceptible to TB, and vice versa. Antiretroviral therapy (ART) and antituberculosis treatment (ATT) are critical for managing these conditions, but pose risks due to drug–pathogen and drug–drug interactions, potentially leading to immune reconstitution inflammatory syndrome (IRIS) in patients with HIV/AIDS. IRIS, often triggered by highly active antiretroviral therapy (HAART), can exacerbate HIV progression, increase drug resistance, and deteriorate patients’ quality of life. Approximately one-third of the global population with HIV is also infected with TB, with extensive drug-resistant (XDR) and multidrug-resistant (MDR) strains posing significant challenges. Latent TB infection (LTBI) further complicates the scenario, as it can progress to active TB, particularly in individuals with both conditions. The global and Indian mortality rates for TB-HIV co-infection remain high, emphasizing the need for new strategies. Additionally, unreported cases and inadequate post-treatment monitoring contribute to the high mortality rate, particularly among patients with LTBI. The complexity of managing HIV-TB co-infection, especially with LTBI, underscores the urgency of addressing these challenges to improve the outcomes for the affected populations.

Novel tuberculosis skin tests for detecting latent tuberculosis infection.

Dear Editor, We are impressed by the article titled "Latent tuberculosis diagnostics: current scenario and review" by Gupta et al. published in your journal. The authors have reviewed the tests used for diagnosis of latent tuberculosis infection and have given a detailed overview of the purified protein derivative-based tuberculin skin test and interferon γ release assays. We would like to draw attention to the fact that in 2022, the World Health Organization has also recommended the use of Mycobacterium tuberculosis antigen-based skin tests for the diagnosis of latent tuberculosis (conditional recommendation, very low certainty of evidence).

Reasons for acceptance or nonparticipation in iAdhere: a trial of latent TB infection treatment.

<sec><title>BACKGROUND</title>Understanding the motivations behind clinical trial participation can help enhance recruitment strategies and determine the generalizability of trial results. This study focuses on the reasons for participating in or declining the Tuberculosis Trials Consortium Study 33 (iAdhere), a clinical trial on the treatment of latent tuberculosis infection (LTBI).</sec><sec><title>METHODS</title>A quantitative evaluation was conducted among screened patients to ascertain their reasons for participating or not in the iAdhere trial. The study gathered data from enrolled participants and those who chose not to enroll.</sec><sec><title>RESULTS</title>Among 1,002 enrolled individuals, 290 participants provided 749 reasons for enrolling. The most common reasons included access to shorter treatment regimens (56%), avoiding progression to TB disease (45%), and improving health (21%). Of the 670 eligible persons who chose not to enroll, 551 individuals provided 800 reasons, with the most common being a preference for standard therapy (17%), disinterest in study medication or TB therapy (both 13%), and the inconvenience of daily observed treatment (12%).</sec><sec><title>CONCLUSION</title>The desire for shorter treatment options and preventing active disease motivates participation in LTBI trials. The diverse reasons for declining enrolment suggest the importance of developing targeted recruitment strategies. These findings support exploring shorter treatment regimens and can guide future recruitment efforts.</sec>.

Isoniazid Prophylaxis Based on Tuberculosis Risk Factors in Living Kidney Transplantation Recipients: A Retrospective Cohort Study

BackgroundTuberculosis (TB) is a major and severe opportunistic infection among solid organ transplant recipients. Chemoprophylaxis is advised for those with latent tuberculosis infection (LTBI). However, the effectiveness of an isoniazid (INH) prophylactic approach based on TB risk factors remains uncertain. MethodsThis study included all living-donor kidney transplant recipients (KTRs) between January 2016 and December 2022. The recipients were categorized into three groups: the risk group with isoniazid (R-INH), the risk group without isoniazid (R-NINH), and the non-risk group (NR), based on the presence of TB risk factors and INH usage. The R-INH group received a 6-month INH prophylactic regimen to prevent post-transplant TB infection. The incidence of active TB among the groups was assessed. ResultsA total of 1348 patients were divided into R-INH (n=108), R-NINH (n=371), and NR (n=869). Forty-seven patients (3.49%) developed TB with an incidence rate of 16.0 per 1000 person-years. Compared to NR, the TB incidence in R-INH was not statistically different (HR, 0.55, 95% CI, 0.07-4.21, P = 0.564), whereas it was significantly higher in R-NINH (HR, 5.04, 95% CI, 2.64-9.62, P < 0.001). The median time from transplantation to TB was 19 months (IQR: 6-39), and 18 patients (38.3%) were diagnosed within one year of transplantation. Ninety-four patients (87.0%) completed INH prophylaxis, with adverse events including two cases of hepatotoxicity (1.85%) and one case of peripheral neuritis (0.93%). ConclusionsA 6-month INH regimen based on TB risk factors is effective and well tolerated for preventing post-transplant TB in KTRs

A modified multiple-criteria decision-making approach based on a protein-protein interaction network to diagnose latent tuberculosis

BackgroundDNA microarrays provide informative data for transcriptional profiling and identifying gene expression signatures to help prevent progression of latent tuberculosis infection (LTBI) to active disease. However, constructing a prognostic model for distinguishing LTBI from active tuberculosis (ATB) is very challenging due to the noisy nature of data and lack of a generally stable analysis approach.MethodsIn the present study, we proposed an accurate predictive model with the help of data fusion at the decision level. In this regard, results of filter feature selection and wrapper feature selection techniques were combined with multiple-criteria decision-making (MCDM) methods to select 10 genes from six microarray datasets that can be the most discriminative genes for diagnosing tuberculosis cases. As the main contribution of this study, the final ranking function was constructed by combining protein-protein interaction (PPI) network with an MCDM method (called Decision-making Trial and Evaluation Laboratory or DEMATEL) to improve the feature ranking approach.ResultsBy applying data fusion at the decision level on the 10 introduced genes in terms of fusion of classifiers of random forests (RF) and k-nearest neighbors (KNN) regarding Yager’s theory, the proposed algorithm reached a sensitivity of 0.97, specificity of 0.90, and accuracy of 0.95. Finally, with the help of cumulative clustering, the genes involved in the diagnosis of latent and activated tuberculosis have been introduced.ConclusionsThe combination of MCDM methods and PPI networks can significantly improve the diagnosis different states of tuberculosis.Clinical trial numberNot applicable.

Role of dormancy survival regulator and resuscitation-promoting factors antigens in differentiating between active and latent tuberculosis: a systematic review and meta-analysis

BackgroundDormancy survival regulator (DosR) and resuscitation-promoting factor (Rpf) antigens of Mycobacterium tuberculosis are activated during dormant phase of tuberculosis (TB). This study evaluates the differential immunogenicity potentials of DosR and Rpf antigens in individuals with latent tuberculosis infection (LTBI) and active TB patients.MethodsAfter a literature search in electronic databases, studies were selected by following precise eligibility criteria. Outcomes were synthesized systematically, and meta-analyses were performed to estimate standardized mean differences (SMDs) in interferon-gamma (IFNγ) levels, and IFNγ positive immune cells between individuals with LTBI and active TB patients.ResultsTwenty-six studies (1278 individuals with LTBI and 1189 active TB patients) were included. DosR antigens Rv0569 (Standardized mean difference; SMD 2.44 [95%CI: 1.21, 3.66]; p < 0.0001), Rv1733c (SMD 0.60 [95%CI: 0.14, 1.07]; p = 0.011), Rv1735c (SMD 1.16 [95%CI: 0.44, 1.88]; p = 0.002), Rv1737c (SMD 1.26 [95%CI: 0.59, 1.92]; p < 0.0001), Rv2029c (SMD 0.89 [95%CI: 0.35, 1.42]; p = 0.002), RV2626c (SMD 1.24 [95%CI: 0.45, 2.02); p = 0.002), and Rv2628 (SMD 0.65 [95%CI: 0.38, 0.91]; p < 0.0001) and Rpf antigens Rv0867c (SMD 1.33 [95%CI: 0.48, 2.18]; p = 0.002), Rv1009 (SMD 0.65 [95%CI: 0.05, 1.25]; p = 0.034), and Rv2450c (SMD 1.54 [95%CI: 0.92, 2.16]; p < 0.0001) elicited higher IFNγ levels in individuals with LTBI in comparison with active TB patients. IFNγ-positive immunoresponsive cells were significantly higher in individuals with LTBI than in active TB patients for antigens Rv1733c (SMD 1.02 [95%CI: 0.15, 1.88]; p = 0.021), Rv2029c (SMD 0.57 [95%CI: 0.05, 1.09]; p = 0.031), and Rv2628 [SMD 0.38 [95%CI: 0.15, 0.61]; p = 0.001).ConclusionDosR antigens Rv0569, Rv1733c, Rv1735c, Rv1737c, RV2626c, Rv2628, and Rv2029c, and Rpf antigens Rv0867c, Rv1009, and Rv2450c are found to elicit immune responses differently in individuals with LTBI and active TB patients.

Study of immune response in a latent tuberculosis infection model

A simple mathematical model describing the immune response during the stage latent tuberculosis infection is established and analyzed. The main purpose of this study is to explore the sustained immune response of the immune system against invaded Mycobacterium tuberculosis in the stage of latent tuberculosis infection. First, the threshold R0 is defined to determine the occurrence of sustained immune response. Then, stability conditions are derived to show that the sustained immune response may converge to a constant or to a stable periodical oscillation, implying that the Mycobacterium tuberculosis, the infected macrophages, the activated uninfected macrophages, and the immune cells coexist to form the tuberculous granuloma structure. This structure may appear calcified if the system solution converges to a constant, or maintains a dynamic balance if the system solution undergoes a periodical oscillation. These findings well demonstrate the process of sustained immune response in the latent tuberculosis infection as the Mycobacterium tuberculosis is changing. Numerical examples are presented to illustrate the theoretical predictions.

Antiviral immune response against HTLV-1 invalidates T-SPOT.TB® results in patients with HTLV-1-positive rheumatic diseases

BackgroundT-SPOT.TB®, one of the screening tests for latent tuberculosis infection (LTBI), yields invalid results in human T-cell leukemia virus type 1 (HTLV-1)-positive patients with rheumatoid arthritis. However, the detailed mechanisms behind this invalidation are unclear. Additionally, it remains unclear whether T-SPOT.TB® or QuantiFERON-TB (QFT) is more useful in HTLV-1-positive patients with rheumatic disease (RD).MethodAmong all of the HTLV-1-positive RD patients who visited our department between August 2012 and December 2022, 44 patients who were screened using T-SPOT.TB® were included in the analysis. QFT testing was performed in 33 of the 44 patients, and the results were compared with that of T-SPOT.TB®. Furthermore, we performed a culture experiment mimicking T-SPOT.TB® using peripheral blood mononuclear cells (PBMCs) obtained from HTLV-1-positive patients with RD. Additionally, T-cell subsets with autonomous product IFN-γ were analyzed using a flow cytometer.ResultsOf the included patients, 13 (29.5%) were invalid for T-SPOT.TB® because of the increased number of negative control spots. The median HTLV-1 proviral load in the invalid group was higher than that in the valid group (2.45 vs. 0.49 copies/100 PBMCs, respectively, p = 0.002). QFT was performed in all 33 patients, including 13 patients who were invalid in T-SPOT.TB®. The main source of IFN-γ production was CD8+ T-cells in the T-SPOT.TB® mimic experiment. Furthermore, Tax-expressing CD4+ T-cells and Tax-specific cytotoxic CD8+ T-cells were more frequently observed in patients with invalid results than in patients with valid results. CD4+ T-cell depletion in the T-SPOT.TB® mimic experiment reduced the population of IFN-γ producing CD8+ T cells.ConclusionT-SPOT.TB® may be invalidated by the interaction between Tax-expressing CD4+ T-cells and cytotoxic CD8+ T-cells. Moreover, HTLV-1-associated immune reactions due to contact between these cells may be unlikely to occur in QFT using whole blood. Therefore, our results reveal the superiority of QFT over T-SPOT.TB® as a screening test for LTBI in HTLV-1-positive patients with RD.

Latent tubercolosis infection in the migrant population: an Italian surveillance experience

Abstract Background The Special Reception Center (“Centro Accoglienza Straordinario” or CAS in Italian) concept was born in Italy in 2014 to receive the large number of migrants arriving in Italy. There are around 3100 centres are in Italy, of which 200+ in Tuscany. Each Center’s objective is to support migrants’ social integration through Italian language and job orientation courses. On arrival at a facility, migrants undergo diagnostic and lab tests to highlight potentially infectious diseases; among these, tuberculosis is one of the most frequently encountered. Therefore, the objective of the study is to estimate the prevalence of Latent Tuberculosis Infections (LTBIs) among migrants hosted in CAS centers. Methods From May-December 2023, Amiata Senese, Val d’Orcia and Valdichiana Senese Public Health Unit staff, according to national and departmental guidelines, implemented a number of health surveillance protocols, with close attention to latent tuberculosis infection. This protocol includes the Mantoux TB skin test at the CAS: in case of positivity, subjects are directed to further exams (chest X-ray, TB-IGRA blood test, infectious disease specialist consultation) in order to implement a therapy. Results From May-December 2023, 259 migrants (241 males and 18 females) received the TB skin tests. Average subject age was 26. Pakistan was the most represented nation of origin with 130 migrants (50%), followed by Bangladesh (9.7%) and Ivory Coast (7.3%). 77 migrants showed a positive TB skin test result (29.7%): of these 56 (i.e. 21.6% of the migrants screened) were also positive to the TB-IGRA blood test and treated for LTBI. Conclusions The high prevalence of LTBIs found in the referenced CAS indicates the need to continue/extend these surveillance protocols. Implementing successfully this procedure requires the involvement of a range of professionals from the socio-health sector within a process necessarily coordinated by the Disease Prevention Department. Key messages • Screening and surveillance of infectious diseases among migrant population represent a major public health issue for European health systems. • Detection and treatment of Latent Tubercolosis Infections require a multiprofessional and integrated approach, coordinated by the Disease Prevention Department.

A prolonged outbreak of tuberculosis associated with an intellectual disability daycentre in Ireland

Abstract One of the factors impeding tuberculosis elimination in low burden countries is its persistence and concentration in vulnerable populations. This is a complex, prolonged Tuberculosis (TB) outbreak in a daycentre for adults with intellectual disability in Ireland. This is a particularly vulnerable population with special considerations for Public Health (PH) management. There are eight cases of active TB, 46 cases of Latent TB Infection (LTBI) and a cumulative total of 116 contacts associated with this outbreak, with diagnosis spanning 15 years. The last three cases were identical on Whole Genome Sequencing. The index case was an Irish-born, Caucasian, social care worker, with smear positive pulmonary TB, who was symptomatic in the facility for three months prior to diagnosis. Case 2 was a household contact of the index case and the other 6 cases were Service Users (SUs) at the facility. At least five of the subsequent seven cases are secondary cases of the index case. Significant to this outbreak was the change in Irish guidance, 2010, relating to the management of contacts of cases. Following the notification of the most recent case, July 2023, the Outbreak Control Team decided a retrospective review be conducted of all SU contacts of the seven cases associated with the facility. The contacts were stratified according to hierarchical risk. A total of six contacts met the criteria for review and offered screening, re-screening or treatment as appropriate. In this outbreak 21.8% of the total contacts and 16.1% of SU contacts completed treatment for LTBI. The significance of this outbreak lies in its duration, infectivity of the index case and particular vulnerabilities of the SUs. There were issues with overcrowding and difficulties in relation to symptom recognition, diagnosis and treatment. The PH team tailored their approach to meet the SU needs, demonstrating the importance of person-centred contact tracing in the disruption of transmission. Key messages • A factor impeding tuberculosis elimination in low burden countries is it’s persistence and concentration in vulnerable populations. • Adapting a patient-centred approach to contact tracing can lead to higher participation rate and the disruption of infection transmission.

European guidelines for the management of tuberculosis screening in migrants: a systematic review

Abstract Background This systematic review assesses the current available evidence across the WHO European region on the effectiveness and cost-effectiveness of the different approaches used for TB screening and also explores the facilitators and barriers that migrants face during screening programs. Methods We conducted an extensive, comprehensive, and systematic literature search across multiple databases, including MEDLINE, Cochrane, Scopus, and ISI Web of Knowledge, without any restrictions on publication date or language. In addition, we reviewed grey literature and reports from WHO. The data were meticulously analyzed using RStudio, with a focus on screening effectiveness indicators, such as infection and disease detection rates, uptake, coverage, and cost-effectiveness economic analyses. Results Our review included 43 studies covering over 8 million migrants from 11 countries. The findings demonstrate that while screening uptake was high, coverage varied, and completion rates for preventive treatments were low. Economic analyses supported the high cost-effectiveness of the screening programs, particularly when integrating both active TB and LTBI screening strategies. Conclusions The implementation of uniform screening protocols could potentially streamline efforts, reduce TB transmission, and offer substantial public health and economic benefits, making this research highly relevant for policymakers and healthcare providers. Key messages • An important strength of this study lies in its pioneering approach of current recommendations regarding screening for latent tuberculosis infection and active TB within the WHO European region. • This is the first study that provides a comprehensive overview of screening interventions across 11 countries and incorporates studies with large sample sizes (n &amp;gt; 8 million migrants).

Changes in TB contact tracing during the COVID-19 pandemic. An Irish single centre experience

Abstract Contact tracing following the diagnosis of tuberculosis (TB) is a crucial process in the identification and treatment of both secondary TB cases and also infected contacts who may require treatment for latent TB infection. During the COVID-19 pandemic, Public Health and Respiratory teams in the St Vincent’s University Hospital (SVUH) TB clinic in Dublin, Ireland, noted anecdotally that there appeared to be fewer contacts screened by public health services per index active TB case identified. To investigate this, we performed a retrospective review of the TB contact tracing service in SVUH, examining and comparing contact tracing of active TB cases in the 3 years prior to the pandemic (2017-2019) and four years thereafter (2020-2023). Results from 2017-2019 calendar years, prior to the COVID-19 pandemic noted an average of 4.77 contacts per index TB case (total 107 index cases and 510 contacts). In comparison, our data from 2020-2022 noted an average of 3.03 contacts per index TB case (total 59 index cases and 179 contacts). As pandemic restrictions were lifted again, we found our 2023 data to be more comparable to that of pre-pandemic times, noting 4.54 contacts per index case (total 22 index cases and 100 contacts). The reduction in TB contacts per index cases noted during the COVID-19 pandemic may reflect work and lifestyle changes over that time, particularly an increase in remote work but also social distancing. It is interesting that as the population emerged from the isolation measures of the pandemic, contact numbers returned quickly to pre-pandemic levels. In line with global concerns, our data highlights the ongoing workload of TB contact tracing locally and the importance of resource allocation for these services. Key messages • Our Irish centre experienced a notable but temporary reduction in contacts requiring screening by public health services, per index active TB case, during the COVID-19 pandemic. • In line with global concerns, our data highlights the ongoing workload of TB contact tracing locally and the importance of resource allocation for these services.

Alterations in purine and pyrimidine metabolism associated with latent tuberculosis infection: insights from gut microbiome and metabolomics analyses.

Individuals with latent tuberculosis infection (LTBI) account for almost 30% of the population worldwide and have the potential to develop active tuberculosis (ATB). Despite this, the current understanding of the pathogenesis of LTBI is limited. The gut microbiome can be altered in tuberculosis patients, and an understanding of the changes associated with the progression from good health to LTBI to ATB can provide novel perspectives for understanding the pathogenesis of LTBI by identifying microbial and molecular biomarkers associated therewith. In this study, fecal samples from healthy controls (HC), individuals with LTBI and ATB patients were collected for gut microbiome and metabolomics analyses. Compared to HC and LTBI subjects, participants with ATB showed a significant decrease in gut bacterial α-diversity. Additionally, there were significant differences in gut microbial communities and metabolism among the HC, LTBI, and ATB groups. PICRUSt2 analysis revealed that microbiota metabolic pathways involving the degradation of purine and pyrimidine metabolites were upregulated in LTBI and ATB individuals relative to HCs. Metabolomic profiling similarly revealed that purine and pyrimidine metabolite levels were decreased in LTBI and ATB samples relative to those from HCs. Further correlation analyses revealed that the levels of purine and pyrimidine metabolites were negatively correlated with those of gut microbial genera represented by Ruminococcus_gnavus_group (R. gnavus), and the levels of R. gnavus were also positively correlated with adenosine nucleotide degradation II, which is a purine degradation pathway. Moreover, a combined signature including hypoxanthine and xanthine was found to effectively distinguish between LTBI and HC samples (area under the curve [AUC] of training set = 0.796; AUC of testing set = 0.924). Therefore, through gut microbiome and metabolomic analyses, these findings provide valuable clues regarding how alterations in gut purine and pyrimidine metabolism are linked to the pathogenesis of LTBI.IMPORTANCEThis study provides valuable insight into alterations in the gut microbiome and metabolomic profiles in a cohort of adults with LTBI and ATB. Perturbed gut purine and pyrimidine metabolism in LTBI was associated with the compositional alterations of gut microbiota, which may be an impetus for developing novel diagnostic strategies and interventions targeting LTBI.

Adverse drug reactions following treatment of latent tuberculosis infection: a linked national tuberculosis surveillance with claims database.

Few real-world studies explored factors associated with latent tuberculosis infection (LTBI) treatment-related adverse drug reactions (ADRs). This study evaluate ADRs that lead to the discontinuation of LTBI treatment and identify the associated factors, including age groups and drug regimens. Using the Korean national tuberculosis registry and HHC investigation database linked to the National Health Insurance Service claims database, we examined treatment discontinuation due to ADRs among HHCs on LTBI treatment from January 2015 to December 2018. Multivariable logistic regression analysis was conducted to examine factors associated with ADRs, including demographics, LTBI treatment, comorbidities, and steroid use. Among 11,913 participants initiated LTBI treatment, 633 participants (5.3%) discontinued treatment due to ADRs. The primary contributors to discontinuation were adverse skin reactions (2.0%) and abnormal liver function (1.9%). Risk associated with ADRs and abnormal liver function showed age-related increase, except for the age group 66-75 (adjusted odds ratio [AOR] 3.82, 95% confidence interval [CI] 2.31-6.31) which reported lower OR to that of age group 36-65 (AOR 4.38, 95% CI 3.09-6.21). Three months isoniazid/rifampin and 4 months rifampin exhibited a lower odds of ADRs and abnormal liver function when compared to 6-9 months isoniazid. We discovered the real-world prevalence of LTBI treatment discontinuation due to ADRs among HHCs. Our findings suggest a notably increased odds of ADRs resulting in discontinuation with age of 76 years or above, emphasizing careful attention when prescribing LTBI treatment in this population. Further studies are warranted to validate these results.

The progress of Mycobacterium tuberculosis drug targets.

Tuberculosis (TB) has been troubling humans for hundreds of years, is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, Mtb can infect almost all organs of the body and is one of the deadly infectious diseases in the world. At present, the first-line treatment regimen has a long treatment cycle and is prone to multiple drug resistance. Anti-tuberculosis drugs and latent tuberculosis infection (LTBI) resistance are increasing year by year, and new targets and new bioactive compounds are urgently needed to treat this disease. This review focuses on the latest reported anti-TB drug targets and related compounds in recent years, reviews the current TB drug regimen and major defects, outlines the key drug targets developed to date in Mtb, and the current situation of newly discovered anti-TB resistant forms of drugs. To provide a reference for the research and development of new anti-TB drugs and bring new treatment strategies for TB patients.

Comparison of the standardized incidence ratio of tuberculosis among workers at medical and educational institutions: a nationwide LTBI observational cohort study

BackgroundThe objective of this study was to determine the incidence of tuberculosis (TB) among workers at medical institutions based on interferon-gamma release assay (IGRA) and compare it with that of workers at educational institutions and the general population. MethodsFrom March 2017 to December 2020, we used a cohort of workers from medical and educational institutions in Korea, who underwent IGRA as part of a national screening program for latent tuberculosis infection (LTBI). After connecting to the National Health Insurance Service (NHIS) database to detect for any actual cases of active TB, we estimated standardized incidence ratio (SIR) and the expected number of cases to compare the incidence of TB with that of the general population. ResultsSignificant disparities in TB incidence were revealed among workers in medical and educational institutions, based on IGRA results, age, and occupation. Individuals positive for IGRA in medical institutions displayed substantially higher SIR for TB, 7.19 (6.15–8.41), compared to counterparts in educational institutions, 3.69 (3.02–4.51). Comparing by age group, we see that the SIRs are higher in younger age groups compared to older ones, with 37.30 (28.11–49.50) and 11.89 (7.28–19.41) for IGRA-positive medical and education workers under 30 years of age, respectively. In the results by occupation within the medical institutions, nurses had the highest SIR at 14.17 (11.14–18.04). ConclusionsHealthcare workers in medical institutions are more likely to develop actual TB after a positive result of LTBI screening in Korea. Intensive management and surveillance programs should be reinforced.

Management implications of latent TB among under-five children at risk: Insights from a community study in Mumbai, India.

Latent tuberculosis infection (LTBI) management is crucial to WHO's End TB Strategy. Indian guidelines recommend treating under-five children with household TB contacts after ruling out active TB, regardless of TBI testing. However, the precise LTBI burden among children in high TB burden settings like India is unknown. A community-based study in Mumbai's urban slums screened and managed under-five children at LTBI risk to understand its epidemiology and inform TB control interventions. Total 369 eligible under-five children were enrolled for the study. LTBI screening was done using Tuberculin skin test and Interferon gamma release assay. Active TB was ruled out before initiation of TB preventive therapy among LTBI positives. Statistical tests like chi-square, logistic regression analysis and Hosmer-Lemeshow test were used. Overall, LTBI prevalence among under-five children was 12.4% by IGRA and 21.4% by TST. Undernourished children had significantly lower LTBI positivity by IGRA (p = 0.027), while those with household contacts, longer contact duration and drug-resistant tuberculosis (DR-TB) exhibited proportionally greater IGRA positivity (p = <0.001). The study found a lower LTBI prevalence among under-five children compared to adults, with key risk factors being HHC, DR-TB contact, and prolonged exposure. These findings suggest the need to revise or revisit the TPT framework for this age group in India, particularly by implementing a test-and-treat approach.

Global cell-free DNA methylation in patients with active tuberculosis and tuberculosis contacts with latent tuberculosis infection

IntroductionTo investigate whether the methylation of circulating cell-free DNA (cfDNA) differentiates active tuberculosis (TB) from latent TB infection (LTBI). MethodsPatients with pulmonary TB, contacts with LTBI, and healthy controls were enrolled (2018–2021). Plasma cfDNA was extracted, and using a 5-methylcytosine (5mC) DNA ELISA kit, the global methylation of cfDNA (5mC-cfDNA) was measured. Results59 TB, 63 LTBI, 39 healthy controls were included. The 5mC-cfDNA level was higher in TB (6.4 %) than LTBI (4.1 %) and healthy controls (4.9 %) (both p<0.05). Independent TB factors were 5mC-cfDNA ≥6.6 % and CRP ≥0.32 mg/dL (adjusted odds ratio (aOR) 4.594 [95 % CI:1.628–12.965], p=0.004 and 5.338 [1.659–17.176], p=0.005). Having one or both factors increased TB odds 8- and 16-fold (aOR 8.688 [3.229–23.378], p <0.001 and 16.080 [3.092–83.632], p =0.001). ConclusionThe global cfDNA methylation level was higher in TB than contacts without TB and helped differentiate patients with TB from contacts with LTBI.

Acceptability and Usability of Mobile Health Application for Enhancing Treatment Adherence in Latent TB Patients

Background: Mobile health interventions showcase effectiveness for improving treatment adherence among Latent TB Infection (LTBI) patients. However, there is a paucity of evidence regarding their acceptability and usability. This study aimed to assess the initial acceptability and usability of a mobile health application that has been designed to ensure treatment adherence in LTBI patients. Methods: A descriptive study was conducted to assess the acceptability and usability of a mobile health application, “My Treatment Friend”. A total of 82 LTBI patients were selected, and access to the application was given to them. This application provides support to LTBI patients in reporting daily medication and side effects. The basic demographic characteristics of the participants were collected through a Google form-based questionnaire. The acceptability and usability of the application were assessed using the Likert scale questionnaire and SUS tool, with samples of n=44 and n=20 participants, respectively. Results: LTBI patients found the mobile application acceptable and feasible, with an SUS score of 73, which comes under Grade B as per the SUS score sheet. The majority believed that the app was very simple to use and easy to understand. However, there is a requirement to add more features that can enhance the acceptability and usability of the application. Conclusion: The study showed the importance and usefulness of mobile applications to assist LTBI patients in finishing their prescribed treatment courses of action. Additionally, it highlights how crucial it is to build future applications using user-centered design. User-centered design may play an important role in designing mobile applications and ensuring effective engagement and satisfaction among users.