Incidence Of Active Tuberculosis Research Articles

Drug Persistence and Incidence of Active Tuberculosis of Tumor Necrosis Factor Alpha Inhibitors Versus Tocilizumab as the First-Line Biological Treatment in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Retrospective Cohort Analysis.

Drug persistence may be a surrogate marker that reflects both long-term efficacy and safety in clinical settings, and tuberculosis (TB) is considered as one of the most important opportunistic infections after the biological treatment in rheumatoid arthritis (RA). We aimed to compare drug persistence and incidence of TB between tumor necrosis factor alpha (TNFα) inhibitors and tocilizumab in patients with RA using data from the Korean Health Insurance Review and Assessment Service database. In this analysis, 5449 patients with RA who started TNFα inhibitors, such as adalimumab, etanercept, infliximab, and golimumab or tocilizumab, as the first-line biological therapy between January 2014 and December 2017 were analyzed and followed up until December 2019. Drug persistence was defined as the duration from initiation to first discontinuation, and TB was defined as the prescription of > 2 anti-TB medications after the initiation of biologics. TNFα inhibitors and tocilizumab were prescribed in 4202 (adalimumab, 1413; etanercept, 1100; infliximab, 769; golimumab 920) and 1247 patients with RA, respectively. During the analysis period, 2090 (49.7%) and 477 (38.3%) patients with RA discontinued TNFα inhibitors and tocilizumab, respectively, and 42 patients with RA developed TB (TNFα inhibitors, 33; tocilizumab, 9). After adjustment for confounding factors, TNFα inhibitors were significantly associated with a higher risk of discontinuation compared with tocilizumab (hazard ratio (HR) 1.63, p < 0.001). In subgroup analysis, all types of TNFα inhibitors, except for infliximab, demonstrated a significantly lower persistence rate compared with tocilizumab. There was no significant difference in TB incidence between tocilizumab and TNFα inhibitors. In subgroup analysis, infliximab has a significantly higher risk of TB compared with tocilizumab (HR2.84, p = 0.02). In this analysis, tocilizumab had longer persistence than TNFα inhibitors with a similar incidence of TB. Our analysis has limitations: (1) The HIRA database lacks clinical details like disease activity and joint damage extent, potentially influencing the analysis results. (2) Reasons for discontinuing biological agents were not available. (3) TB diagnoses may be inaccurate because of missing microbiological results. (4) We did not analyze the impact of treating latent TB infection on TB development post-biological treatment, despite mandatory screening in Korea.

Active Tuberculosis Risk Associated with Malignancies: A 4-Year Retrospective Study in a Tertiary Care Hospital

Background Tuberculosis (TB) remains an important public health problem worldwide. Risk of acquiring TB in patients diagnosed with cancers remains high and can result due to reactivation or reinfection. We share the experience in a large tertiary care hospital. Materials and Methods Clinical samples from presumptive TB patients while on cancer therapy were tested by smear Ziehl–Neelsen (ZN) staining, GeneXpert MTB/RIF (Gx), TB polymerase chain reaction (PCR), and liquid culture (MGIT 960) from January 1, 2019, to December 31, 2022. Statistical Analysis Stata 14.0 software was used for statistical analysis. The p-value calculation was done by Pearson's chi-square test. Results Of 906 patients investigated, 42 (4.64%) tested positive for TB. Seven (1.37%) tested positive by ZN staining, 10 patients (6%) had culture positive by MGIT, 20 (10.53%) and 5 (13.51%) samples were positive by Gx and PCR, respectively. Maximum number of TB-positive patients were found to be suffering from carcinoma lung (28%) followed by leukemia (25%), gastrointestinal cancer (13%), and genitourinary cancer (13%), respectively. Seven of the 42 patients succumbed to the disease; the cases belonged to Hodgkin's lymphoma (75% mortality), leukemia (30% mortality), and genitourinary cancer (20% mortality). Conclusion The incidence of active TB is high in cancer patients, especially lung cancer, leukemia, gastrointestinal, and genitourinary cancers. Mortality was high in Hodgkin's lymphoma patients who developed TB. Screening for TB at the time of diagnosis of a high TB risk cancer would help initiate early treatment. We recommend targeted screening for TB in patients with these high-risk cancers, at the time of diagnosis and periodically through cancer treatment.

Active tuberculosis incidence among treatment failure experienced patients in North Wollow Zone: A multicenter historical cohort.

In Ethiopia, tuberculosis (TB) is a significant cause of death among individuals living with HIV, especially in resource-limited areas and those who have experienced treatment failure. However, there is the paucity of data regarding TB among treatment failures experienced people living with HIV. This study aimed to estimate the rate and identify predictors of tuberculosis among patients who received second-line treatment in North Wollo, Northeast Ethiopia. A retrospective follow-up study was conducted on 474 HIV-infected patients who experienced treatment failure. The study period ranged from January 2015 to September 30, 2021. The incidence of TB was assessed using a Cox proportional hazard regression model, after ensuring that all assumptions were met. Factors associated with active TB were determined by analyzing adjusted hazard ratios and 95% confidence intervals. In a study of 474 HIV-positive patients on second-line antiretroviral treatment, we found an incidence rate of 3.6% with 17 new cases of TB observed over 4412.4 persons per year (PPY). The overall incidence density rate was estimated to be 0.39 cases per 100 PPY (95% CI: 0.239-0.618). Regarding the occurrence of active TB in second-line patients, WHO clinical treatment stage (T3 and T4), missed isoniazid preventive therapy had a significantly higher risk (AHR: 13.225, 95% CI: 2.894-60.434, p = 0.001), while being married was associated with a lower risk (AHR: 0.203, 95% CI: 0.045-0.907, p = 0.001). A high incidence of active TB was observed shortly after initiating second-line antiretroviral treatment. Factors such as being in the WHO clinical treatment stage (T3 and T4) and marital status were determinants for active TB. To improve overall survival rates, it is vital to enhance early TB screening and implement effective isoniazid preventive therapy.

Screening and treatment of latent tuberculosis in patients with solid tumors and systemic cancer therapy.

Tuberculosis is one of the infectious diseases with greater morbidity and mortality worldwide. Cancer causes an important immunosuppression with increased risk of infections. There is an enlarged bidirectional incidence between tuberculosis and cancer, mainly due to latent tuberculosis. There is great discrepancy between recommendations for screening and prophylaxis of latent tuberculosis in patients with solid tumors and systemic cancer therapy among different medical societies and guidelines. Most infectious diseases guidelines recommend it, while most oncology guidelines do not. Patients with solid tumours generally have a limited life expectancy and a state of intermittent immunosuppression, resulting in a lower risk of tuberculosis reactivation than other riskypopulations. There is a lack of prospective and retrospective studies analysing the benefit of screening and prophylaxis in this population. The first step is to study the incidence of active tuberculosis in this population to estimate the real magnitude of the problem.

Interleukin-17A Inhibitors in Patients with Psoriasis and Tuberculosis Infection: A 2-Year Prospective Study on Safety Without Preventive Treatment.

The necessity for tuberculosis preventive treatment (TPT) and routine T-SPOT.TB monitoring in patients with psoriasis and tuberculosis infection (TBI) undergoing interleukin (IL)-17A inhibitor therapy remains uncertain. This study aims to evaluate the long-term safety of IL-17A inhibitors administered without TPT and analyze changes in T-SPOT.TB among these patients. It also identifies risk factors for TBI in patients with psoriasis. This single-center prospective study enrolled adult patients with plaque psoriasis and TBI receiving IL-17A inhibitors. TBI was defined as positive T-SPOT.TB results (≥ 6 spots) without symptoms or evidence of active tuberculosis (ATB). TPT administration was based on contraindications, tuberculosis risk factors, and patient preferences. The primary endpoint was the incidence of ATB over 2years. Secondary outcomes included T-SPOT.TB changes and TBI risk factors. Of the 129 patients with psoriasis and TBI enrolled in the study, 97 (75.2%) did not receive TPT, while 32 (24.8%) did. Among them, 109 patients (84.5%) completed the 2-year follow-up. During the 235 person-years of observation, no ATB cases were identified. Median T-SPOT.TB values showed no significant changes from baseline to year2 in both the non-TPT (20 vs. 17 spots, p = 0.975) and TPT groups (55 vs. 58 spots, p = 0.830). T-SPOT.TB reversed in 14 patients (12.8%), mostly in the non-TPT group. Moreover, for TBI risk factor analysis, a cohort of 212 patients with psoriasis with negative baseline T-SPOT.TB was evaluated, revealing a TBI prevalence of 37.8%. Logistic regression analysis highlighted age ≥ 45years (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.50-3.99, p < 0.001) and body mass index (BMI) < 24.0 kg/m2 (OR 2.12, 95%CI 1.27-3.54, p = 0.004) as independent risk factors for TBI. IL-17A inhibitors do not appear to reactivate tuberculosis in patients with psoriasis and TBI, potentially reducing the need for routine TBI screening and preventive treatment. Chinese Clinical Trial Registry, ChiCTR2100045823.

Revisiting the association between vitamin D deficiency and active tuberculosis: A prospective case-control study in Taiwan

BackgroundTo revisit the association between vitamin D deficiency (VDD, defined as serum 25(OH)D < 20 ng/ml) and incident active tuberculosis (TB), after two potentially underpowered randomized trials showed statistically non-significant 13%–22% decrease in TB incidence in vitamin D supplementation groups. MethodsWe prospectively conducted an age/sex-matched case–control study that accounting for body-mass index (BMI), smoking, and other confounding factors to examine the association between VDD and active TB among non-HIV people in Taiwan (latitude 24°N), a high-income society which continues to have moderate TB burden. ResultsWe enrolled 62 people with incident active TB and 248 people in control group. The TB case patients had a significantly higher proportion of VDD compared to the control group (51.6% vs 29.8%, p = 0.001). The 25(OH)D level was also significantly lower in TB patients compared to control group (21.25 ± 8.93 ng/ml vs 24.45 ± 8.36 ng/ml, p = 0.008). In multivariable analysis, VDD (adjusted odds ratio [aOR]: 3.03, p = 0.002), lower BMI (aOR: 0.81, p < 0.001), liver cirrhosis (aOR: 8.99, p = 0.042), and smoking (aOR: 4.52, p = 0.001) were independent risk factors for incident active TB. ConclusionsVDD is an independent risk factor for incident active TB. Future randomized trials examining the effect of vitamin D supplementation on TB incidence should focus on people with a low BMI or other risk factors to maximize the statistical power.

Pulmonary Tuberculosis Incidence among Interferon-Gamma Release Assay-Positive Individuals with Latent Tuberculosis Infection and Fibrotic Lesions in a Vulnerable Urban Population in Osaka City, Japan, 2015-2021.

Latent tuberculosis infection (LTBI) with fibrotic lesions (FL) can progress to active tuberculosis (TB). Most previous studies have used tuberculin skin tests, which have lower specificity than interferon-gamma release assays (IGRAs), for LTBI diagnosis. This study evaluated the incidence of active TB among individuals with LTBI (diagnosed using IGRAs) and FL in Nishinari District, Osaka City. In total, 54 men (mean age: 68.7 years) were enrolled, of whom 10 (18.5%) were homeless, and 36 (66.7%) were welfare recipients. The median observation period was 1,084 days (range: 64-2,907 days). The incidence rate of active TB among individuals with LTBI and FL was 1.18 (95% confidence interval: 0.32-4.29) cases per 100 person-years. Among the 19 participants who had not been treated with anti-TB therapy, one (5.3%) progressed to active TB, and among the 30 participants who had completed anti-TB treatment, one (3.3%) progressed to active TB. The other 5 participants did not have TB. This study revealed the incidence of active TB among individuals with LTBI, diagnosed using IGRAs, and FL in a vulnerable urban population. The higher incidence than that reported in previous studies reinforces the importance of improved LTBI management strategies, including chest radiography screening, and LTBI treatment.

Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease: a randomised strategy trial

Background: Mortality associated with HIV-associated cryptococcal meningitis remains high even in the context of clinical trials (24–45% at 10 weeks); mortality at 12-months is up to 78% in resource limited settings. Co-prevalent tuberculosis (TB) is common and preventable, and likely contributes to poor patient outcomes. Innovative strategies to increase TB preventative therapy (TPT) provision and uptake within this high-risk group are needed. Protocol: The IMPROVE trial is a nested open label, two arm, randomised controlled strategy trial to evaluate the safety (adverse events) and feasibility (adherence and tolerability) of two ultra-short course TPT strategies, in the context of recent diagnosis and treatment for cryptococcal meningitis. We will enrol 205 adults with HIV-associated cryptococcal meningitis from three hospitals in Uganda. Participants will be randomised to either inpatient initiation (early, week 2) or outpatient initiation (standard, week 6) of 1HP (one month of isoniazid and rifapentine). Participant follow-up is to include TB screening, pill counts and tolerability reviews on alternate weeks until week-18. The trial primary endpoint is TB-disease free 1HP treatment completion at 18-weeks, secondary endpoints: 1HP treatment completion, 1HP discontinuation, grade ≥3 adverse events and serious adverse events, drug-induced liver injury, incident active TB, 18-week survival; rifapentine, fluconazole and dolutegravir concentrations will be measured in a drug-drug interaction sub-study of 15 eligible participants. Discussion: The IMPROVE trial will provide preliminary safety and feasibility data to inform 1HP TPT strategies for adults with advanced HIV disease and cryptococcal meningitis. The potential impact of demonstrating that inpatient initiation of 1HP TPT is safe and feasible amongst this high-risk subpopulation with advanced HIV disease, would be to expand the range of clinical encounters in which clinicians can feasibly provide 1HP, and therefore increase the reach of TPT as a preventative intervention. ISRCTN registration: ISRCTN18437550 (05/11/2021)

Incidence, risk factors for active tuberculosis infection and changes of IGRA in patients with Takayasu arteritis: a prospective cohort study

ABSTRACT There is limited evidence to support the association between tuberculosis (TB) and the occurrence of Takayasu arteritis (TAK). To investigate the incidence of active TB (ATB) in TAK and explore the impact of anti-rheumatic therapy on the occurrence of ATB or reactivation of Latent TB infection (LTBI) and their effect on interferon-γ release assay (IGRA) results, we conducted a prospective study based on the Chinese Registry for Systemic Vasculitis cohort. The standard incidence ratio (SIR) was calculated and stratified by age. Kaplan–Meier analysis was used to determine the effect of variables on ATB or LTBI reactivation in patients with TAK. Data from 825 patients with TAK in the registry were analysed. During a median follow-up of 5 years, 5 patients developed ATB with a crude incidence of 154 (95%CI:57–381) person-years/100,000. The SIR was 5.59 (95%CI:1.81–13.04). Glucocorticoids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) did not increase the risk of ATB or LTBI reactivation (P > 0.05). However, the use of tumour necrosis factor inhibitor (TNFi) increased the risk of ATB in patients with LTBI (P < 0.001). Furthermore, the value of the IGRA assay decreased after treatment (P < 0.05). In conclusion, the incidence of TB infection is markedly increased in patients with TAK and patients with TAK are at high risk of developing ATB. Treatment with glucocorticoids and cDMARDs does not significantly increase the risk for ATB in patients with TAK. Moreover, IGRA may have limited effectiveness in monitoring ATB infection or LTBI reactivation in patients with TAK.

Changes in tuberculosis risk after transplantation in the setting of decreased community tuberculosis incidence: a national population-based study, 2008–2020

BackgroundTransplant recipients are immunocompromised and vulnerable to developing tuberculosis. However, active tuberculosis incidence is rapidly declining in South Korea, but the trend of tuberculosis infection among transplant recipients has not been elucidated. This study aimed to evaluate the risk of active tuberculosis after transplantation, including risk factors for tuberculosis and standardized incidence ratios, compared with that in the general population.MethodsThis retrospective study was conducted based on the South Korean health insurance review and assessment database among those who underwent transplantation (62,484 recipients) between 2008 and 2020. Tuberculosis incidence was compared in recipients treated during higher- (2010–2012) and lower-disease burden (2016–2018) periods. Standardized incidence ratios were analyzed using the Korean Tuberculosis Surveillance System. The primary outcome was the number of new tuberculosis cases after transplantation.ResultsOf 57,103 recipients analyzed, the overall cumulative incidence rate 1 year after transplantation was 0.8% (95% confidence interval [CI]: 0.7–0.8), significantly higher in the higher-burden period than in the lower-burden period (1.7% vs. 1.0% 3 years after transplantation, P < 0.001). Individuals who underwent allogeneic hematopoietic stem cell transplantation had the highest tuberculosis incidence, followed by those who underwent solid organ transplantation and autologous hematopoietic stem cell transplantation (P < 0.001). The overall standardized incidence ratio was 3.9 (95% CI 3.7–4.2) and was the highest in children aged 0–19 years, at 9.0 (95% CI 5.7–13.5). Male sex, older age, tuberculosis history, liver transplantation, and allogeneic hematopoietic stem cell transplantation were risk factors for tuberculosis.ConclusionsTransplant recipients are vulnerable to developing tuberculosis, possibly influenced by their immunocompromised status, solid organ transplant type, age, and community prevalence of tuberculosis. Tuberculosis prevalence by country, transplant type, and age should be considered to establish an appropriate tuberculosis prevention strategy for high-risk groups.Graphical

Effect of a Latent Tuberculosis Infection Programme for Healthcare Workers in a Country with an Intermediate Tuberculosis Burden

Management of latent tuberculosis infection (LTBI) among healthcare workers (HCWs) is crucial for the prevention of nosocomial tuberculosis (TB) transmission. We aimed to determine the effect of an LTBI programme for HCWs in a tertiary care hospital in a country with an intermediate TB burden. In 2013, baseline LTBI screening was implemented for newly hired doctors and nurses, along with annual screening of HCWs in high-risk departments. HCWs with LTBI were also provided with treatment. Since 2017, all HCWs without an LTBI test result have been tested for LTBI. We assessed the annual incidence of active TB among HCWs between 2013 and 2020. Additionally, we evaluated the incidence of active TB among HCWs employed at the hospital in 2020, with a specific focus on those who had undergone LTBI tests between 2013 and 2018, considering their LTBI test results and treatment status. The incidence of active TB among HCWs significantly decreased between 2013 and 2020. The average risk reduction for pulmonary TB was 10.2% per year (95% CI, 1.0-19.0; p = 0.034). Among HCWs employed at the hospital in 2020, 4,354 individuals underwent LTBI tests between 2013 and 2018. Out of them, 927 (21.3%) tested positive. Nine (1.5%) out of 588 without LTBI treatment developed active TB. Among the 1,285 HCWs who underwent follow-up testing, 62 (4.8%) converted, and one (4.3%) out of the 23 without treatment developed active TB. None of those who received treatment were diagnosed with active TB. The LTBI programme significantly reduced the incidence of active TB in HCWs. LTBI screening and treatment should be implemented, particularly in countries with a high or intermediate TB burden.

Burden of tuberculosis among vulnerable populations worldwide: an overview of systematic reviews

Tuberculosis is a communicable disease of public health concern that inequitably impacts the most vulnerable populations worldwide. Vulnerable populations are those with a high risk for tuberculosis disease and whose disadvantaged or marginalised socioeconomic position limits their access to the health system. We conducted an overview of reviews that aimed to assess the burden (ie, prevalence and incidence) of tuberculosis disease among 12 vulnerable populations globally. We did an overview of reviews using a systematic search in MEDLINE, Embase, and the Cochrane Database for Systematic Reviews for articles published in English, French, and Chinese, from Jan 1, 2010 to March 8, 2023. We did an initial search on Oct 28, 2021, and updated our search on March 8, 2023. We included systematic and scoping reviews reporting on the prevalence or incidence of active tuberculosis among 12 vulnerable populations. Evidence gaps were supplemented with primary or secondary database studies. Study characteristics and outcome data related to tuberculosis burden were tabulated, including prevalence ratios and incidence rate ratios, and evidence was synthesised narratively. This trial is registered with PROSPERO (CRD42022324421). We screened 13 169 citations and included 44 publications (23 reviews and 21 primary or database studies) in the final synthesis. The comprehensiveness and methodological quality of the evidence differed across population groups. Prevalence of more than 1000 cases per 100 000 were reported in all vulnerable populations. On the basis of pooled estimates, prevalence ratios were often more than 25 among people experiencing homelessness, incarcerated populations, refugees, asylum seekers, and people living with HIV compared with the general population. Incidence was infrequently reported, with the best-available incidence rate ratios documented for people who were incarcerated. There was scarce evidence specific to miners, nomadic populations, sex workers, men who have sex with men, and transgender individuals. The burden of tuberculosis is substantially higher among vulnerable populations than general populations, suggesting a need for improved integration of these groups, including dedicated efforts for their identification, targeted screening and prevention measures, as well as treatment support. WHO.

Alkaloids Lead to Potential Inhibition of the Acyl Carrier Protein Reductase to Attenuate Tuberculosis; an in-silico Analysis

Tuberculosis (TB) is a contagious infection that mostly affects the lungs. Mycobacterium tuberculosis causes tuberculosis infection, leading to granulomatous lesions in affected lung tissue. It is one of the most prevalent and deadly infectious diseases among the under developed countries. This study aims to investigate the possible inhibition of the acyl carrier protein reductase for preventing tuberculosis by well-known alkaloids, thereby reducing Mycobacterium tuberculosis growth in the lungs and thereby reducing the incidence of latent and active TB. About five natural alkaloids were subjected to the molecular docking analysis, which produced favorable findings in terms of best pose and binding energies of these compounds towards the active residues of mycobacterial ACP reductase, with values ranging from -10 kcal/mol to -9.1 kcal/mol. The molecular dynamics simulation produced similar encouraging results. All of the prospective alkaloid compounds were subjected to an in-silico toxicity investigation, which determined that every compound was safe and non-toxic. Further studies may be necessary for effective formulation development employing these compounds as part of the process of drug discovery and development. The findings from this study may be helpful in the development of the novel nanoformulations using natural products for pharmacotherapy of tuberculosis infection.

Screening for Latent Tuberculosis Infection in Solid Organ Transplant Recipients to Predict Active Disease: A Systematic Review and Meta-Analysis of Diagnostic Studies.

This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) for active tuberculosis (TB) among solid organ transplantation (SOT) recipients. Medline, Embase, and the CENTRAL databases were searched from 1946 until June 30, 2022. Two independent assessors extracted data from studies. Sensitivity analyses were performed to investigate the effect of studies with high or low risk of bias. Methodological quality of each publication was assessed using QUADAS-2. A total of 43 studies (36 403 patients) with patients who were screened for latent TB infection (LTBI) and who underwent SOT were included: 18 were comparative and 25 noncomparative (19 TST, 6 QuantiFERON-TB Gold In-Tube [QFT-GIT]). For IGRA tests taken together, positive predictive value (PPV) and negative predictive value (NPV) were 1.2% and 99.6%, respectively. For TST, PPV was 2.13% and NPV was 95.5%. Overall, PPV is higher when TB burden is higher, regardless of test type, although still low in absolute terms. Incidence of active TB was similar between studies using LTBI prophylaxis (mean incidence 1.22%; 95% confidence interval [CI], .2179-2.221) and those not using prophylaxis (mean incidence 1.045%; 95% CI, 0.2731-1.817; P = .7717). Strengths of this study include the large number of studies available from multiple different countries; limitations include absence of gold standard for diagnosis of latent TB and low incidence of active TB. We found both TST and IGRA had a low PPV and high NPV for the development of active TB posttransplant. Further studies are needed to better understand how to prevent active TB in the SOT population.

The dynamics of incidence of active tuberculosis in children in Bukovina, the impact of the COVID-19 pandemic

Ukraine remains one of the leaders in the global ranking of morbidity and mortality from tuberculosis (TB) and, according to WHO, ranks 5th in the world and 2nd in Europe according to these indicators. Objective — to analyze the regional features of the epidemiology of tuberculosis among children in the Chernivtsi region. Materials and methods. The medical records of all pediatric patients with newly diagnosed TB for the period from January 2020 to December 2022 in the Chernivtsi Regional Clinical TB Dispensary were analyzed. Statistical processing of the data obtained during the research was carried out using the IBM SPSS Statistics v. 26.0 program. Results and discussion. An analysis of the dynamics by years, when Ukraine was in lockdown due to COVID-19, revealed an increase in the incidence of TB among children under the age of 14 — by 2.7 times compared to 2021 and almost 8 times compared to 2020. 2 cases (25 %) of extrapulmonary tuberculosis, one of which (meningoencephalitis) had an unfavorable prognosis and resulted in death. Indicators of the tuberculosis situation in the Chernivtsi Region in the age group of 15—17 years showed an increase in TB in the percentage ratio of almost 2 times, with an even gender distribution (50 % each) compared to 2020 and 2021. Conclusions. In Bukovina, for the period from 2020 to 2022, increase in the incidence of tuberculosis among children (almost in 2 times) was registered. In 2022, in 100 % of cases, TB was detected during referral, and in children living in rural areas, the majority were girls (62.5 %). In 87.5 % of cases, the diagnosis was confirmed bacterioscopically, in 50 % of children the presence of contact with a tuberculosis source was determined, in 12.5 % there was no BCG vaccination, in 25 % of children MDR-TB was registered.

Risk factors and prognosis for latent tuberculosis infection in dialysis patients: A retrospective cohort study at a single tertiary care center.

Recent studies report that latent tuberculosis infection (LTBI) may lead to an increased risk of cardiovascular disease (CVD) that led us to hypothesize that LTBI may play an important role in major adverse cardiovascular events (MACE) in dialysis patients. A single-center retrospective cohort study was conducted. A total of 270 patients undergoing hemodialysis or peritoneal dialysis more than 3 months were included. The interferon enzyme-linked immunospot (IFN-γ ELISPOT) assay was used for the diagnosis of LTBI. Primary endpoints were MACE, including all-cause death and acute coronary syndrome (ACS). The association between LTBI and MACE was examined using multivariate Cox proportional hazards regression after adjusting for covariates and Kaplan-Meier survival analysis. In our study, the patients were classified into LTBI (n =47) or non-LTBI (n =223) groups. Independent risk factors for LTBI in dialysis population were prior tuberculosis (TB) history (odds ratio [OR] 4.817 [1.064-22.306]), tobacco use (OR 2.903 [1.155-7.299]), and older age (OR 1.027 [1.002-1.053]). After a median follow-up of 39 months, the incidence of active TB was 6.4% versus 0% in dialysis patients with and without LTBI, respectively (p = 0.005). Multivariate Cox analysis showed that LTBI was significantly associated with MACE (hazardratio[HR] 2.540 [1.490-4.350]) after adjustment for potential confounders. Prior TB history, tobacco use, and the elderly can be used to select cost-effective LTBI screening target groups in dialysis patients. LTBI is not only closely related to active TB but also an independent risk factor for higher incidence of MACE in dialysis population.

A scoping review on the risk of tuberculosis in specific population groups: can we expand the World Health Organization recommendations?

Since 2015, the World Health Organization (WHO) has recommended prioritising testing and treatment of tuberculosis (TB) infection (TBI) in 11 high-risk groups. With new options emerging for TB preventive treatment, we conducted a scoping review, in consultation with the WHO's Global Tuberculosis Programme, to explore the evidence for other population groups at potentially high risk of progression to active TB. We searched six databases for preprints and articles published between 2000 and August 2022. 18 out of 33 668 screened records were included (six meta-analyses and 12 original research studies). Most were observational studies reporting the incidence of active TB in a risk group versus control. Glomerular diseases had the strongest association with active TB (standardised incidence ratio 23.36, 95% CI 16.76-31.68) based on an unpublished study. Other conditions associated with increased risk of active TB included hepatitis C, malignancies, diabetes mellitus, rheumatoid arthritis and vitamin D deficiency. Corticosteroid use was also associated with increased risk in several studies, although heterogeneous definitions of exposure and indications for use challenge interpretation. Despite methodological limitations of the identified studies, expanding the recommendations for TBI screening and treatment to new risk groups such as those reported here should be considered. Further group-specific systematic reviews may provide additional data for decision-making.

Predictive performance of interferon-gamma release assays and the tuberculin skin test for incident tuberculosis: an individual participant data meta-analysis

Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy. We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667. We obtained data from 13 studies out of 40 that were considered eligible (N=32,034 participants: 36% from countries with TB incidence rate ≥100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette-Guérin vaccine (BCG) status (15mm if BCG vaccinated and 5mm if not [TST5/15 mm]) at 2.88 (95% CI 1.69-4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97-8.75). The difference was large in countries with TB incidence rate <100 per 100,000 population (HR 10.38, 95% CI 4.17-25.87 for QFT-GIT VS. HR 5.36, 95% CI 3.82-7.51 for TST5/15 mm) but much of this difference was driven by a single study (HR 5.13, 95% CI 3.58-7.35 for TST5/15 mm VS. 7.18, 95% CI 4.48-11.51 for QFT-GIT, when excluding the study, in which all 19TB cases had positive QFT-GIT results). The comparative performance was similar in the higher burden countries (HR 1.61, 95% CI 1.23-2.10 for QFT-GIT VS. HR 1.72, 95% CI 0.98-3.01 for TST5/15 mm). The predictive performance of both tests was higher in countries with TB incidence rate <100 per 100,000 population. In the lower TB incidence countries, the specificity of TST (76% for TST5/15 mm) and QFT-GIT (74%) for predicting active TB approached the minimum World Health Organization target (≥75%), but the sensitivity was below the target of ≥75% (63% for TST5/15 mm and 65% for QFT-GIT). The absolute differences in positive and negative predictive values between TST15 mm and QFT-GIT were small (positive predictive values 2.74% VS. 2.46%; negative predictive values 99.42% VS. 99.52% in low-incidence countries). Egger's test did not show evidence of publication bias (0.74 for TST15 mm and p=0.68 for QFT-GIT). IGRA appears to have higher predictive performance than the TST in low TB incidence countries, but the difference was driven by a single study. Any advantage in clinical performance may be small, given the numerically similar positive and negative predictive values. Both IGRA and TST had lower performance in countries with high TB incidence. Test choice should be contextual and made considering operational and likely clinical impact of test results. YH, IA, and MXR were supported by the National Institute for Health and Care Research (NIHR), United Kingdom (RP-PG-0217-20009). MQ was supported by the Medical Research Council [MC_UU_00004/07].

Prevalence of pulmonary tuberculosis in post-coronavirus disease patients

Abstract Context Post-coronavirus disease 2019 (COVID-19) disease patients are immunocompromised, especially those who have a history of hospitalization during the COVID time and steroid use during hospitalization. Such patients are very susceptible to opportunistic infections and must be assessed proactively. Patients and methods This was a cross-sectional study on 125 post-COVID-19-positive patients 28 days after being COVID negative confirmed by an RT-PCR test. Sputum/bronchoalveolar lavage samples were taken for analysis. Statistical analysis used SPSS, version 20.0 was used for the analysis. A P value less than 0.05 was considered statistically significant. Results Out of 119 sputum samples assessed, 15 were AFB positive, and Mycobacterium tuberculosis (MTB) was detected in 16 patients by the GeneXpert assay, out of which 15 were sensitive to rifampicin and one was resistant. Bronchoalveolar lavage was performed in nine patients where two were found AFB-positive, and MTB was detected in two patients by the GeneXpert, out of which one was rifampicin sensitive and one was rifampicin resistant. Conclusions A significant portion of the world population has latent tuberculosis (TB) infection, and the COVID-19 disease may have led to an increase in the incidence of active TB. A proactive approach is needed for the diagnosis of TB and to control the spread of TB.

Epidemiological survival pattern, risk factors, and estimated time to develop tuberculosis after test and treat strategies declared for children living with human immune deficiency virus

BackgroundDue to their age category and the immune-suppressing effects of HIV, children were more vulnerable to experience endogenous reactivation of latent bacilli in the lung and increased risk of active tuberculosis incidence. The aim of this study is to assess the survival pattern, risk factors, and estimated time to develop TB after children started ART at selected health facilities of North Wollo, Ethiopia, from November 1, to September 30, 2021. MethodsFacility-based retrospective cohort study was employed from November 1 to September 30, 2021. Cox proportional hazard regression model was used to assess factors associated with incidence of tuberculosis. AHR with 95% CI was used to declare statistical significance for tuberculosis incidence. ResultsDuring follow-up, 54 (10.9%) new cases of tuberculosis was reported. At the end of follow-up period, overall cumulative survival probability was determined as 43.8% (95%CI: 28.2–54.3). WHO clinical stage III&IV (AHR: 2.4 (95% CI: 1.4, 4.7), Hgb≤10 gm/dl (AHR = 2.2: (95%CI: 1.12–5.8), missed isoniazid preventive therapy (AHR = 2.5 (95%CI: 1.56–10.3) and Viral Load (≥400 cell/ml) (AHR = 2.02 (95%CI: 2.03–6.8) were significant risk factors for tuberculosis incidence. ConclusionNearly ten % of HIV-positive children experienced new cases of tuberculosis with median time of 25(IQR = ±12) months. It would be better to give special attention to children who missed isoniazid preventive therapy with WHO stages III&IV Viral load (≥400 cells/ml), and Hgb≤10 gm/dl to prevent tuberculosis incidence and prolonged quality of life.