Latent Tuberculosis Infection Cases Research Articles

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.

Retrospective data analysis on the prevalence and demographic risk factors for latent tuberculosis infection (LTBI) cases from a private laboratory in Malaysia.

Tuberculosis (TB) is a critical disease that predominantly affects the lungs. This disease remains a global health threat. Currently, the incidence of TB is estimated to be 92 cases in every 100 000 population. However, latent TB infection (LTBI) cases among Malaysians are another great health concern that requires immediate steps to be taken to detect, diagnose, and treat LTBI as one of the key strategies to end TB. Although individuals with LTBI are unlikely to infect others, the threat of infection is still imminent as these individuals can potentially develop into active TB cases. As such, this study aims to identify the prevalence of LTBI among asymptomatic individuals that underwent QuantiFERON®-TB Gold Plus test from a private laboratory in Malaysia to determine the association between the risk factors and the detected LTBI cases. A retrospective study was conducted by analyzing the archive records of 3 877 samples from January 2021 to March 2022. The cases underwent QuantiFERON®-TB Gold Plus tests for LTBI at Premier Integrated Labs. This study underlines that those who were LTBI positive had a prevalence of 638/3 877 (16.46%) with males contributing to 343/638 cases (53.76%). Furthermore, the majority of the positive cases were between the age of 30-43 years old with 197/638 (30.88%), and Chinese ethnicity with 225/638 (35.27%). The risk factors significantly associated with LTBI cases were age (p = 0.001) and ethnicity (p = 0.001). The prevalence of LTBI determined through this study is considered remarkably low for an intermediate TB burden country. Although LTBI is not contagious, specific clinical and preventative considerations are needed for the diagnosis, treatment, and implementation of appropriate safety measures to curb the spread of TB in Malaysia.

Prevalence of latent tuberculosis infection (LTBI) in healthcare workers in Latin America and the Caribbean: systematic review and meta-analysis.

Tuberculosis remains a significant global health concern, and healthcare workers (HCWs) face a high risk of acquiring latent tuberculosis infection (LTBI) through occupational exposure. In the Latin American and Caribbean (LAC) region, where the burden of tuberculosis is substantial, understanding the prevalence of LTBI among HCWs is crucial for effective infection control measures. Therefore, we conducted a systematic review and meta-analysis to estimate the prevalence of LTBI among HCWs in LAC countries. Our search included MEDLINE, Scopus, EMBASE, Web of Science, and Google Scholar databases, focusing on relevant English-language records. We looked for observational studies from inception until December 2023. Our analysis included 38 studies representing 15,236 HCWs and 6,728 LTBI cases. These studies spanned the period from 1994 to 2023 and were conducted in Brazil, Peru, Cuba, Colombia, Trinidad and Tobago, Mexico, and Chile. The mean prevalence of LTBI among HCWs was 35.32% (range 17.86-56.00%) for interferon-gamma release assay (IGRA) and 43.67% (range 6.68-70.29%) for tuberculin skin test (TST). The pooled prevalence of LTBI among HCWs was 34.5% (95% CI 25.4-44.1%) for IGRA and 43.0% (95% CI 35.5-50.7%) for TST. When considering both IGRA and TST tests, the overall prevalence of LTBI among HCWs was 40.98% (95% CI 34.77-47.33%). LTBI was associated with longer lengths of employment and exposure to patients, family members, or any person with TB. Additionally, older HCWs faced a higher risk of LTBI. Specific professional roles (such as nurses, nurse technicians, or physicians), smoking, and deficient TB infection control measures increased the likelihood of LTBI. However, information regarding gender and BCG vaccination status showed discordance among studies. Our findings underscore a substantial burden of LTBI among HCWs in LAC countries. Implementing adequate infection control measures is essential to prevent and control transmission within healthcare settings.

Evaluating the cost-effectiveness of Cy-Tb for LTBI in India: a comprehensive economic modelling analysis.

Latent tuberculosis infection (LTBI) remains a significant challenge, as there is no gold standard diagnostic test. Current methods used for identifying LTBI are the interferon-γ release assay (IGRA), which is based on a blood test, and the tuberculin skin test (TST), which has low sensitivity. Both these tests are inadequate, primarily because they have limitations with the low bacterial burden characteristic of LTBI. This highlights the need for the development and adoption of more specific and accurate diagnostic tests to effectively identify LTBI. Herein we estimate the cost-effectiveness of the Cy-Tb test as compared with the TST for LTBI diagnosis. An economic modelling study was conducted from a health system perspective using decision tree analysis, which is most widely used for cost-effectiveness analysis using transition probabilities. Our goal was to estimate the incremental cost and number of TB cases prevented from LTBI using the Cy-Tb diagnostic test along with TB preventive therapy (TPT). Secondary data such as demographic characteristics, treatment outcome, diagnostic test results and cost data for the TST and Cy-Tb tests were collected from the published literature. The incremental cost-effectiveness ratio was calculated for the Cy-Tb test as compared with the TST. The uncertainty in the model was evaluated using one-way sensitivity analysis and probability sensitivity analysis. The study findings indicate that for diagnosing an additional LTBI case with the Cy-Tb test and to prevent a TB case by providing TPT prophylaxis, an additional cost of 18658 Indian rupees (US${\$}$223.5) is required. The probabilistic sensitivity analysis indicated that using the Cy-Tb test for diagnosing LTBI was cost-effective as compared with TST testing. If the cost of the Cy-Tb test is reduced, it becomes a cost-saving strategy. The Cy-Tb test for diagnosing LTBI is cost-effective at the current price, and price negotiations could further change it into a cost-saving strategy. This finding emphasizes the need for healthcare providers and policymakers to consider implementing the Cy-Tb test to maximize economic benefits. Bulk procurements can also be considered to further reduce costs and increase savings.

BI44 Latent tuberculosis reactivation in a patient with chronic plaque psoriasis treated with ustekinumab with a review of the literature

Abstract Ustekinumab, a monoclonal antibody against interleukin (IL)-12 and IL-23, is used for the treatment of psoriasis and psoriatic arthritis. The IL-12 pathway also plays an important role in regulating immunity to Mycobacterium tuberculosis. A multicentre, double-blind, randomized clinical trial study of 121 Korean patients with moderate-to-severe psoriasis revealed at least 75% improvement in Psoriasis Area and Severity Index (PASI) score after 12 weeks of ustekinumab treatment. Ten cases of latent tuberculosis infection (LTBI) were reported. Lupea-Chilom et al. [Lupea-Chilom DS, Solovan CS, Farcas SS et al. Latent tuberculosis in psoriasis patients on biologic therapies: real-world data from a care center in Romania. Medicina (Kaunas) 2023; 59: 1015] conducted a retrospective observational study on a total of 97 patients with severe psoriasis who were on different biologics. That study showed that two of seven patients on monotherapy ustekinumab developed LTBI. In this abstract, we present the case of a 49-year-old White woman with resistant moderate-to-severe chronic psoriasis without psoriatic arthritis who developed LTBI while on ustekinumab. She was diagnosed with psoriasis in 2012 with involvement of the scalp, flexural, vulval and gluteal regions as well as the nails. She was started on ustekinumab in October 2013 following a satisfactory prebiologics screen (including a negative QuantiFERON test). Her PASI score was zero at week 12. In 2017, she developed a malar rash and positive antinuclear antibody test, which was not tested prior to starting biologics. As lupus is a potential adverse effect of this medication, the ustekinumab was stopped in April 2017. Further rheumatological investigations ruled out lupus and ustekinumab was restarted in November 2017. As part of the screening process prior to restarting treatment, she had a repeat QuantiFERON test, which was positive. The respiratory team reviewed the patient and issued a 3-month course of rifampicin and isoniazid to treat LTBI. Following a few months of monitoring, it was deemed safe to restart ustekinumab in December 2018 and her PASI improved. In February 2020, due to the COVID pandemic, this medication had to be stopped. She was started on acitretin as an alternative in 2021 with a resulting worsening of her condition. In December 2021, the patient was restarted on ustekinumab. In this abstract, we illustrate that ustekinumab has the potential to reactivate latent tuberculosis, a phenomenon that is infrequently reported and attributed to its impact on the IL-12 pathway. To address this concern, we recommend conducting repeated annual screening during treatment in addition to a comprehensive baseline evaluation, including a chest X-ray and QuantiFERON test. Additionally, it is advisable to consider initiating isoniazid chemoprophylaxis concurrently with ustekinumab treatment as a precautionary measure.

The association of dietary patterns with latent tuberculosis infection among young adults: A case-control study in Shanghai.

In developing and underdeveloped countries, undernutrition plays a major role in subverting the immune system, leading to an increase in TB infections; this study investigated the associations between dietary patterns and latent tuberculosis infection risk among young adults in Shanghai. In a case-control study, 96 cases of latent tuberculosis infection and 192 healthy controls were studied among contacts of students in clusters of tuberculosis epidemics in colleges from January 2021 to March 2023. A standardized questionnaire assessing sociodemographic, lifestyle, and dietary characteristics was applied. Food intake was estimated using a 95-item semiquantitative Food Frequency Questionnaire. Using the principal component analysis to extract dietary patterns from food groups intake. Logistic regression models were applied. Four dietary patterns were identified: "traditional balanced" pattern, "unsaturated fatty acid" pattern, "snack" pattern, and "protein and fruit" pattern. Four components explaining 64.52% of the total variation in consumption were derived. In a conditional logistic regression analysis, three models were created. After adjusting for various confounders, compared to "snack" pattern, the risk of latent TB infection was 91% lower in the "traditional balanced" pattern (OR 0.05, 95% CI 0.01, 0.38, p = 0.004). To prevent TB infection among young adults living in high TB burden areas, a balanced dietary pattern rather than a "snack" pattern should be promoted in school settings. Future research should explore the risk of developing active tuberculosis in Mtb-infected people with different dietary patterns and the prevention of this risk by healthy dietary patterns.

Tuberculose latente entre pessoas vivendo com HIV e contatos num estado hiperendêmico

Abstract Objective To assess latent tuberculosis among people living with HIV and contacts of people with tuberculosis. Methods This is a cross-sectional, quantitative study, carried out in the state of Pará, based on cases of latent tuberculosis infection reported between 2019 and 2020. Data were extracted from the Latent Tuberculosis Infection Information System, at the State Department of Public Health, from November to December 2021. For analysis, descriptive statistics, chi-square test and G test were used, in addition to prevalence ratio, in Bioestat 5.3, with a significance level of 5%. Results A total of 1,116 cases of latent tuberculosis were studied: 653 in 2019 and 463 in 2020. The outcome indicated a low proportion of complete treatments (n=734). Among the records, 371 were of people living with HIV and 416 were of contacts of tuberculosis cases. An association was observed between latent infection in people living with HIV and contacts with the variables sex, age, origin and termination situation (p<0.0001). Conclusion Latent tuberculosis in people living with HIV and contacts presents different patterns when associated with the sociodemographic profile, making it necessary to prioritize the identification of these groups in order to adopt strategic actions that impact disease management.

Risk Factors for Latent Tuberculosis among Health-care Workers in Sri Lanka.

Management of latent tuberculosis infection (LTBI) was introduced as a national policy in Sri Lanka in 2022, targeting high-risk groups, including health-care workers (HCWs). This study aimed to identify the potential risk factors for LTBI among HCWs in government hospitals. A case-control study was conducted. Cases and controls were identified by a screening survey conducted among those tested by the tuberculin skin test (TST). The survey was conducted among HCWs of eight government hospitals in Colombo in 2022. LTBI cases were defined as TST positives (≥10 mm) without a history of pulmonary tuberculosis (TB) and controls were those rated as negative. The cases-to-control ratio was 1:1, with a sample size of 128 cases and 128 controls. Multiple logistic regression analysis was conducted to identify the risk factors. The significant risk factors identified included age ≥40 years (adjusted odds ratio [AOR] - 2.4, 95% confidence interval [CI]: 1.28-4.47) having a service duration of ≥6 years (AOR - 2.92, CI: 1.469-5.82), not maintaining distance (AOR - 2.83, CI: 1.43-5.58) and not wearing face masks when dealing with suspected or diagnosed TB patients (AOR - 3.55, CI: 1.80-7.00), and settings with inadequate TB infection control practices (AOR - 3.47, CI: 1.85-6.47). Improving infection control measures, training HCWs on TB prevention, providing adequate personal protective equipment, and initiating screening for LTBI among HCWs are recommended.

Fructose@histone synergistically improve the performance of DNA-templated Cu NPs: rapid analysis of LAM in tuberculosis urine samples using a handheld fluorometer and a smartphone RGB camera.

This study presented a nanoparticle-enhanced aptamer-recognizing homogeneous detection system combined with a portable instrument (NASPI) to quantify lipoarabinomannan (LAM). This system leveraged the high binding affinity of aptamers, the high sensitivity of nanoparticle cascade amplification, and the stabilization effect of dual stabilizers (fructose and histone), and used probe-Cu2+ to achieve LAM detection at concentrations ranging from 10 ag mL-1 to 100 fg mL-1, with a limit of detection of 3 ag mL-1 using a fluorometer. It can also be detected using an independently developed handheld fluorometer or the red-green-blue (RGB) camera of a smartphone, with a minimum detection concentration of 10 ag mL-1. We validated the clinical utility of the biosensor by testing the LAM in the urine of patients. Forty urine samples were tested, with positive LAM results in the urine of 18/20 tuberculosis (TB) cases and negative results in the urine of 6/10 latent tuberculosis infection cases and 10/10 non-TB cases. The assay results revealed a 100% specificity and a 90% sensitivity, with an area under the curve of 0.9. We believe that the NASPI biosensor can be a promising clinical tool with great potential to convert LAM into clinical indicators for TB patients.

Intention to receive Latent Tuberculosis Infection (LTBI) treatment and its associated factors among healthcare workers in a Malaysian teaching university hospital.

The acceptability of latent tuberculosis infection (LTBI) therapy remains low among healthcare workers (HCWs). Up to 10% of LTBI cases can reactivate into active tuberculosis, posing risks to HCWs and patients. Understanding HCWs' intention to undergo LTBI treatment is crucial for designing effective management policies, especially where no LTBI policy exists. This cross-sectional study investigated the intention to receive LTBI therapy and its associated factors among HCWs in a Malaysian teaching hospital. The study was conducted from 5th to 30th May 2023, in a hospital without an LTBI screening program. Stratified random sampling was used to select HCWs, excluding those undergoing TB or LTBI therapy. Respondents completed a questionnaire measuring intention to receive LTBI treatment, LTBI knowledge, attitude, perceived norm, and perceived behavioral control. Of the 256 respondents, the majority were female (63.7%), under 35 years old (64.45%), had no comorbidities (82.0%), and worked in clinical settings (70.3%). However, 60.5% of respondents had low LTBI knowledge and 60.5% held unfavorable attitudes toward LTBI treatment. Despite this, 53.5% of respondents intended to undergo LTBI therapy if diagnosed. Factors positively associated with this intention included being female [aOR: 2.033, 95% CI: 1.080-3.823], having high LTBI knowledge [aOR 1.926, 95% CI: 1.093-3.397], had favorable attitude [aOR 3.771, 95% CI: 1.759-8.084], and strongly perceiving social norms supportive of LTBI treatment [aOR 4.593, 95% CI: 2.104-10.023]. These findings emphasize the need for an LTBI management policy in the teaching hospital. To boost HCWs' intention and acceptance of LTBI treatment, a focused program improving knowledge, attitude, and perception of social norms could be introduced.

Tuberculosis screening characteristics amongst freshmen in Changping District, Beijing, China

BackgroundScreening for Tuberculosis (TB) is a critical tactic for minimizing the prevalence of illness within schools. Tuberculosis Preventive Therapy (TPT), in turn, effectively staves off the development of TB from latent tuberculosis infection (LTBI). Unfortunately, there is limited research on LTBI and TPT among students. This study aimed to assess LTBI among freshmen in Changping District and advocate for the implementation of TPT.MethodsThe prospective study collected data from 12 educational institutions within the Changping District of Beijing. The Kolmogorov − Smirnov test and other statistical methods were used for statistical analysis, x2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${x}^{2}$$\\end{document} was obtained using the formula x2=\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${x}^{2}=$$\\end{document} nΣA2/nRnC-1, df = (C-1) (R-1). We analyzed potential factors impacting the LTBI rate, and scrutinized the possible causes behind the low application of TPT and its efficacy for LTBI treatment, China.ResultsAmong 19,872 freshmen included in this study, 18 active TB cases (91 per 10,0000) and 2236 LTBI cases (11.6% of 19,223) were identified, respectively. Furthermore, of those with LTBI, 1045 (5.4% of 19,223) showed a strong positive for purified protein derivative (PPD), but only 312 opted for TB preventive treatment. There appeared to be no significant difference in the prevalence of LTBI and TPT rate between male and female students. Concurrently, 11 (71 per 100,000) and 7 (158 per 100,000) cases of active tuberculosis were identified in 6 universities and 6 higher vocational colleges, respectively. Interestingly, almost all freshmen who underwent TPT came from universities, suggesting a statistically significant disparity in TPT rate (χ2 = 139.829, P < 0.001) between these two types of educational institutions. Meanwhile, as for the age-wise distribution of latent infection among 17–20 years old freshmen, the LTBI rate exhibited 10.5%, 11.6%, 12.1% and 13.5%, respectively. Correlation between LTBI rate, the strong positive rate was statistically significant among different ages (χ2 = 34.559, P < 0.001). Over a follow-up period of 2 years, three students were diagnosed with active tuberculosis, one of which was resistant to rifampicin. All three students manifested a strong positive for PPD and declined preventive treatment during TB screening.ConclusionsThe data indicates a high rate of LTBI amongst students in areas with a heavy TB burden, potentially leading to cross-regional TB transmission due to the migration of students. Education level might contribute to the limited uptake of TPT. Therefore, improving the implementation of TB preventive treatments is crucial in controlling and preventing TB across schools.

Latent tuberculosis infection (LTBI) in health-care workers: a cross-sectional study at a northern Peruvian hospital

BackgroundHealthcare workers (HCWs) have a higher risk of latent tuberculosis infection (LTBI) and active tuberculosis than the general population. In HCWs, the risk of tuberculosis infection depends on the local tuberculosis prevalence, HCWs’ characteristics, the healthcare facility, and prevention and control measures. We aimed to estimate the prevalence and risk factors for LTBI in HCWs at a northern Peruvian hospital.MethodsThis study had two phases: (1) a cross-sectional phase involving recruitment, history taking, and sampling for the Interferon-Gamma Release Assays (IGRA test), and (2) a prospective follow-up of IGRA-positive participants. We enrolled direct and non-direct patient caregivers among HCWs. We defined an LTBI case if the IGRA test was positive and clinical, laboratory, and radiological evaluations for active tuberculosis were negative.ResultsWe recruited 308 participants between November 2022 and May 2023. The mean age was 38.6 ± 8.3 years. Over 75% of the participants were female. The most common job category was technicians (30.5%), physicians (22.7%), nurses (20.5%), and other HCWs groups (17.5%). Most participants worked in hospital wards (28.2%), diagnostics departments (16.9%), and critical care departments (15.6%). The LTBI prevalence among HCWs was 17.86% (95% CI 13.84–22.70). In multivariate analysis, after adjusting for age, time working in our hospital, and family history of tuberculosis, males had a higher risk of LTBI (aPR 1.69, 95% CI 1.01–2.77) than females. Working for more than 10 years increased the risk of LBTI (aPR 2.4, 95% CI 1.44–3.97) compared to working for ≤10 years. Even further, participants who had worked for more than 20 years had an aPR of 4.31 (95% CI 1.09–13.65) compared to those with ≤10 years. Similarly, occupational exposure increased the risk of LTBI (aPR 2.21, 95% CI 1.27–4.08) compared to those HCWs not occupationally exposed.ConclusionThe LTBI prevalence in HCWs at a northern Peruvian hospital was lower compared to other Peruvian cities. Males, more experienced, and occupational exposed HCWs are at higher risk of LTBI. LTBI prevalence in Peruvian HCWs is still high. More studies are needed to address some aspects this study has not examined.

Screening for tuberculosis infection and effectiveness of preventive treatment among people with HIV in low-incidence settings.

To determine the yield of screening for latent tuberculosis infection (LTBI) among people with HIV (PWH) in low tuberculosis (TB) incidence countries (<10 TB cases per 100 000 persons). A systematic review and meta-analysis were performed to assess prevalence and predictive factors of LTBI, rate of TB progression, effect of TB preventive treatment (TPT), and numbers needed to screen (NNS). PubMed and Cochrane Library were searched for studies reporting primary data, excluding studies on active or paediatric TB. We extracted LTBI cases, odds ratios, and TB incidences; pooled estimates using a random-effects model; and used the Newcastle-Ottawa scale for bias. In 51 studies with 65 930 PWH, 12% [95% confidence interval (CI) 10-14] had a positive LTBI test, which was strongly associated with origin from a TB-endemic country [odds ratio (OR) 4.7] and exposure to TB (OR 2.9). Without TPT (10 629 PWH), TB incidence was 28/1000 person-years (PY; 95% CI 12-45) for LTBI-test positive versus 4/1000 PY (95% CI 0-7) for LTBI-test-negative individuals. Among 625 PWH (1644 PY) receiving TPT, 15 developed TB (6/1000 PY). An estimated 20 LTBI-positive individuals would need TPT to prevent one case of TB, and numbers NNS to detect LTBI or prevent active TB varied according to a-priori risk of LTBI. The relatively high prevalence of LTBI among PWH and the strong correlation with origin from a TB-endemic country support risk-stratified LTBI screening strategies for PWH in low-incidence countries and treating those who test positive.

Backward bifurcation and optimal control problem for a tuberculosis model incorporating LTBI detectivity and exogenous reinfection

The detection of latent tuberculosis infection (LTBI) is one of the vital means in controlling the spread of TB. The dynamical properties of a mathematical model with LTBI detectivity and exogenous reinfection are analyzed and their impacts on TB control are explored. By applying the center manifold theory, it is revealed that the model may exhibit the phenomenon of backward bifurcation caused by exogenous reinfection. Furthermore, sensitivity analysis for the basic reproduction number R0 is performed and an optimal control problem is further formulated by incorporating TB prevention and education propaganda, timely treatment and enhancing therapy efficacy. Finally, our analysis and numerical results show that an increase in detection rate of LTBI cases reduces the value of R0 as well as the possibility that backward bifurcation occurs and the joint implementation of all three strategies effectively contains TB transmission.

Epidemiology of latent tuberculosis infection in Japan-born and foreign-born children in Japan.

This study aims to compare the epidemiology of notifications of latent tuberculosis infection (LTBI) among Japan-born and foreign-born children in Japan between 2010 and 2020, and to assess the language used during LTBI case interviews with parents or caregivers of foreign-born children with LTBI during 2019. Our study consisted of two parts: (1) an analysis of national data from the Japan Tuberculosis Surveillance (JTBS) system on the epidemiology of LTBI among Japan-born and foreign-born children in Japan, and (2) a survey of staff at public health centres that had registered at least one foreign-born child aged ≤14 years with LTBI. Data were extracted from the JTBS system for all children aged ≤14 years who were newly notified as having LTBI between 2010 and 2020, and analysed to determine trends, characteristics and treatment outcomes. Staff at relevant public health centres completed a self-administered survey. A total of 7160 Japan-born and 320 foreign-born children were notified as having LTBI between 2010 and 2020. Compared with Japan-born children, foreign-born children notified as having LTBI were more likely to be older, have their mother or sibling as their source of infection and have LTBI detected via a routine school health check. At case interviews, the use of language interpretation services was limited, even when both parents were non-Japanese. No interview was directly conducted with children themselves, not even with school-aged children. Foreign-born children and their parents may be unfamiliar with the system of testing for TB infection and the diagnosis of LTBI in Japan in school settings. Public health centres are required to provide education to patients and their families and care that takes into account cultural and linguistic differences. However, the provision of language support during case interviews may need strengthening.

A novel chemokine biomarker to distinguish active tuberculosis from latent tuberculosis: a cohort study.

Interferon-γ release assays (IGRAs), which are widely used to diagnose tuberculosis (TB), cannot effectively discriminate latent TB infection (LTBI) from active TB (ATB). This study aimed to identify potential antigen-specific biomarkers for differentiating LTBI cases from ATB cases. Ongoing recruitment was conducted of individuals meeting study inclusion criteria at Beijing Chest Hospital from May 2020 to April 2022; 208 participants were enrolled and assigned to three groups: HC (60 healthy controls), LTBI (52 subjects with LTBI) and ATB (96 ATB patients). After participants were assigned to the discovery cohort (20 or 21 subjects/group), all others were assigned to the verification cohort. Discovery cohort blood levels of 40 chemokines were measured using Luminex assays to identify chemokines that could be used to discriminate LTBI cases from ATB cases; candidate biomarkers were verified using enzyme-linked immunosorbent assay-based testing of validation cohort samples. Luminex results revealed highest ATB group levels of numerous cytokines, growth factors and chemokines. Receiving operating characteristic curve-based analysis of 40 biomarkers revealed CCL8 (AUC = 0.890) and CXCL9 (AUC = 0.883) effectively discriminated between LTBI and TB cases; greatest diagnostic efficiency was obtained using both markers together (AUC = 0.929). Interpretation of CCL8 and CXCL9 levels for validation cohort IGRA-positive subjects (based on a 0.658-ng/ml cutoff) revealed ATB group CCL8-based sensitivity and specificity rates approaching 90.79% and 100.00%, respectively. TB-specific chemokines hold promise as ATB diagnostic biomarkers. Additional laboratory confirmation is needed to establish whether CCL8-based assays can differentiate between ATB and LTBI cases, especially for bacteriologically unconfirmed TB cases.

Features of detection of latent tuberculosis infection and tuberculosis in children from household contacts within a household (clinical case)

Aim: to demonstrate the features of detection and diagnosis of latent tuberculosis infection and pulmonary tuberculosis in children from household contacts based on own clinical observation.&#x0D; Materials and methods. A clinical case of own observation of pulmonary tuberculosis and latent tuberculosis infection in children from household contacts who were treated in the paediatric department of the clinical base of the Phthysiatry and Pulmonology Department of Zaporizhzhia State Medical and Pharmaceutical University on Public Non-Profit Enterprise of the “Zaporizhzhia Regional Clinical and Diagnostic Center of Phthysiatry and Pulmonology” of Zaporizhzhia Regional Council.&#x0D; Results. Children from household contacts were examined at ages: 8 months, 2, 3, 5 and 7 years, after their mother was diagnosed with tuberculosis (TB). All children showed an increase in tuberculin skin test, at the X-ray of the thoracic cavity organs (TCO) no changes were detected in any child. Taking into account the age of the children and their constant residence with the index patient, a decision was made to conduct an additional examination using CT scan of the TCO. Thus, three children were diagnosed with pulmonary tuberculosis – primary tuberculosis complex, and two were infected. After receiving the results of the culture test in the gastric lavage, the youngest child was found MBT, which was resistant to first-line drugs, namely isoniazid and rifampicin, which required a treatment regimen adjustment. It should be noted that the youngest girl, who was not vaccinated, had the most widespread process in the lungs compared to other children.&#x0D; Conclusions. Monitoring and screening of children who have been in contact with the index patient within the household maximises the detection of additional cases of latent tuberculosis infection and pulmonary TB. The most at-risk groups are those who not vaccinated with BCG vaccine and children under 5 years of age. Early detection and timely prescription of anti-TB therapy is the key not only to effective treatment, but also to preventing the transmission of TB infection.

The Risk of Latent Tuberculosis Infection Among Healthcare Workers at a General Hospital in Bisha, the Kingdom of Saudi Arabia.

Background and objective Tuberculosis (TB) is a global health issue, often preceded by a latent tuberculosis infection (LTBI) in individuals. Significant global and local efforts have recently beendirected toward this infection, focusing on TB control and eradication. This study aimedto assessthe magnitude of LTBI among healthcare workers (HCWs) in the Kingdom of Saudi Arabia, by evaluating its prevalence and associated risk factors. Methods An analytical cross-sectional study was conducted among HCWs at the King Abdullah Hospital (KAH), from January to August 2018, by using two surveys: the first one involved data related to HCW demographics and the tuberculin skin test (TST) readings, and the second involved a questionnaire that assessed LTBI risk factors. Results Out of the total 561 HCWs who participated in the study, 66 had an induration reading of more than 10 mm in TST.Many factors were associated with LTBI cases,but multivariate analysis showed that age, gender, and nationality were statistically significant risk factors. Conclusion Given the nature of their work, HCWs are at a greater risk of TB and LTBI. At the same time, HCWs are uniquely positioned to play a crucial role in halting the spread of TB. Gaps in preventive measures may result in the increased spread of TB. Our study assessedrisk factors associated with the increased risk of LTBI and proposed possible ways of addressing them.

The Adjusted Cut-Off Value of Interferon-Γ Release Assays (IGRA) to Diagnose LTBI in Indonesia

Latent Tuberculosis Infection (LTBI) is as a condition when Mycobacterium tuberculosis (MTB) persists in the body without causing symptoms while maintaining viability with the possibility to become active tuberculosis in the future. The detection of LTBI is an important strategy from WHO to end the chain of tuberculosis. LTBI can be diagnosed by using the IGRA test. IGRA uses specific antigens of MTB, early antigenic target-6 (ESAT-6), to induce interferon-gamma production by antigen-specific T cells. In the IGRA test, the cut-off value is explicitly needed to distinguish healthy people from LTBI patients. This study aimed to find IGRA's adjusted cut-off value in Indonesia. The subjects were 150 people, which were 50 healthy people, 50 subjects with active TB, and 50 with suspected LTBI. Isolated Lymphocytes derived from PBMC sand were cultured in a complete RPMI medium and induced by Esat-6 for six days. IFN-g levels were assayed from supernatants by the sandwich Elisa technique. Statistical analysis was used to determine cut-off values for IFN-g derived from healthy and diseased patients. The highest aptitude index (κ value) that could discriminate between healthy and LTBI groups was 0.925 at a concentration of 0.792 ng/ml of IFN-g, hence the cut-off value to diagnose LTBI was 0.792 ng/ml of IFN-g. Based on this value, out of 40 suspected cases of LTBI, up to 17 (42.5%) and 23 without LTBI (57.5%) were found. So, the conclusion was that the adjusted cut-off value for IFN-g to diagnose LTBI in Indonesia was 0.792 ng/ml.

Immune Biomarker Combinations for Diagnosis Monitoring of Latent Tuberculosis Infection

Objective: Global Tuberculosis (TB) eradication efforts must also focus on detecting and treating cases of Latent TB Infection (LTBI); persons with LTBI can progress to active TB at any time, often many years or even decades after the initial infection, thereby serving as a source of new infections. Methods: The aim was evaluated the diagnostic accuracy of the combination of serological host biomarkers that may support the differentiation between LTBI and Non-Infected (NI) individuals. A total of 182 adult Warao Amerindians were included; cases with LTBI (n=103) and Non-Infected (NI) individuals (n=79). The Real-time quantitative PCR (qPCR) was performed on all peripheral blood samples from Warao Amerindians and analyzed transcriptional immune biomarkers (i.e., IFN-γ, CD14, MMP-9, CCR5, CCL11, CXCL9/MIG, and uPAR/PLAUR proteins) under stimulation condition with ESAT-6, CFP10, and TB7.7 Mycobacterium Tuberculosis (Mtb)-antigens. Additionally, Enzyme-Linked Immunosorbent Assays (ELISA) were performed for evaluating host biomarker anti-synthetic peptides (5 ESAT-6 and 17 Ag85A synthetic peptides) covering Mtb antigen sequences. Results: The approach’s diagnostic information was compared using Receiver Operating Characteristic (ROC) curves. The ROC analysis revealed high biosignature discriminative ability for the relative gene expression of MMP-9 high levels (AUC=0.799 ± 0.071: 0.640 - 0.917, 95% CI), p &lt; 0.002) between LTBI and NI; additionally IgG anti-synthetic peptide; ESAT-6 P-12037 (AUC=0.640; 0.545-0.735 95% CI, p&lt;0.007) allowed differentiation between LTBI and NI or healthy ones. Conclusion: The accuracy of the MMP-9/IgG anti-P-12037 combination could have a high discriminative ability for diagnosing LTBI; such an approach holds promise for further validation.