Development Of Active Tuberculosis Research Articles

Incidence and risk factors of active tuberculosis among older individuals with latent tuberculosis infection: a cohort study in two high-epidemic sites in eastern China.

The influencing factors of the process from latent tuberculosis infection (LTBI) to the onset of active tuberculosis (TB) remain unknown among different population groups, especially among older individuals in high-incidence areas. This study aimed to investigate the development of active TB among older adults with LTBI and identify groups in greatest need of improved prevention and control strategies for TB. In 2021, we implemented an investigation among older individuals (≥ 65 years old) in two towns in Zhejiang Province with the highest incidence of TB. All participants underwent assessment using standardized questionnaires, physical examinations, interferon-gamma release assays, and chest radiography. All the participants with suspected TB based on the clinical symptoms or abnormal chest radiography results, as well as those with LTBI, were referred for diagnostic investigation in accordance with the national guidelines. Those with an initial diagnosis of TB were then excluded, whereas those with LTBI were included in a follow-up at baseline. Incident patients with active TB were identified from the Chinese Tuberculosis Management Information System, and a multivariate Cox regression model was used to estimate the incidence and risk of TB among those with LTBI. In total, 667 participants with LTBI were followed up for 1,315.3 person-years, revealing a disease density of 1,292.5 individuals/100,000 person-years (17/1,315.3). For those with LTBI, chest radiograph abnormalities had adjusted hazard ratios for active TB of 4.9 (1.6-15.3). The presence of abnormal chest radiography findings increased the risk of active TB among older individuals with LTBI in high-epidemic sites in eastern China.

Comparison of active tuberculosis occurrence associated with Janus kinase inhibitors and biological DMARDs in rheumatoid arthritis

ObjectivesThis study aimed to evaluate the risk of tuberculosis associated with the use of Janus kinase (JAK) inhibitors or biological disease-modifying antirheumatic drugs (bDMARDs) in patients diagnosed with rheumatoid arthritis...

Incidence and Risk Factors of Active Tuberculosis Among Hospitalized Patients with Latent Tuberculosis Infection in China: A Cohort Study.

The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB. Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis. A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61-93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584-644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430-1570], and the incidence density was 240 per 100,000 person-years[95% CI:144-375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273-49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122-7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 -33.070), anemia (aHR=2.565, 95% CI:1.015-6.479) and T-SPOT.TB level≥300SFCs/106 PBMCs (aHR=4.195, 95% CI:1.365-12.892) were independent risk factors for ATB development in LTBI patients. The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥300SFCs/106PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT.

IGRA-based INH regimen for prevention of active tuberculosis after kidney transplantation: A single-centre retrospective study

ObjectivesTo evaluate the effectiveness and safety of Interferon-gamma release Assay (IGRA)-based isoniazid (INH) prophylaxis strategy to prevent tuberculosis (TB) infection in kidney transplantation (KT) with a risk of TB occurrence. MethodsAdult KT recipients (KTRs) between June 2014 and July 2021 were retrospectively enrolled. The development of active TB after KT was evaluated. ResultsOf 925 KTRs, 111 (12.0%) developed active TB. Among the 501 KTRs at a risk of TB occurrence, 70 (14.0%) patients developed active TB, while 41 (9.7%) of 424 patients without risk factors developed active TB (P = 0.05). Two hundred thirty-nine KTRs received IGRA test with 62 (25.9%) were positive. None of IGRA positive patients (0/40) receiving INH prophylaxis developed active TB, whereas 8 out of 22 patients who had positive IGRA results without INH prophylaxis developed active TB (0 vs. 36.4%, P < 0.01). Of note, for those in risk group but with negative IGRA result, no active TB was found even without INH prophylaxis. Although alanine aminotransferase and aspartate aminotransferase in INH prevention group were higher than those before treatment, they did not exceed three-fold of limit of reference range. ConclusionsIGRA-based INH treatment is an effective and safe protocol to prevent the development of active TB in KTRs.

Latent and active tuberculosis development in patients with rheumatoid arthritis receiving biologic disease-modifying antirheumatic drugs: A single-center prospective study.

Biologics have revolutionized the treatment of rheumatoid arthritis (RA) in recent years. However, data from clinical trials and actual clinical practice have shown that biologics currently in use may constitute a risk factor for reactivation of tuberculosis (TB) in patients with latent TB infection. Therefore, screening for latent and active TB infection is mandatory before initiating biologic therapy in patients with RA. This prospective study aimed to analyze the clinical characteristics of patients with RA receiving biologic disease-modifying antirheumatic drugs at Bach Mai Hospital, Vietnam, between 2017 and 2022, and to identify factors affecting the occurrence of active and latent TB infection among these patients. Over a 12-month follow-up period, latent TB infection was confirmed in 20% of the total 180 included patients, while 3 (1.7%) patients developed active TB (one case of pulmonary, pleural, and gluteal TB each). History of TB risk factor exposure and lack of education were significantly associated with the occurrence of active and latent TB infection, with odds ratios (95% confidence intervals [CIs]) of 1.98 (1.78; 2.2) and 1.45 (1.31; 1.6), respectively. Follow-up duration and number of X-ray, computed tomography, bronchoscopy, and sputum acid-fast bacteria examinations were identified as factors that can aid in the early diagnosis of latent TB, with odds ratios (95% CIs) of 1.00 (1; 1.01), 1.02 (1; 1.05), 1.12 (1.11; 1.2), 1.11 (1.09; 1.2), and 1.13 (1.09; 1.17), respectively. Our study showed that, in countries with high TB burden like Vietnam, latent TB infection has high prevalence among patients with RA. We also provide useful information for the screening, monitoring, and treatment of latent and active TB infection in patients with RA.

Impact of fine particulate matter on latent tuberculosis infection and active tuberculosis in older adults: a population-based multicentre cohort study

ABSTRACT Evidence showed that air pollution was associated with an increased risk of tuberculosis (TB). This study aimed to study the impact of long-term exposure to ambient particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) on the acquisition of LTBI and on the risk of subsequent active disease development among rural older adults from a multicentre cohort, which have not yet been investigated to date. A total of 4790 older adults were included in a population-based, multicentre, prospective cohort study (LATENTTB-NSTM) from 2013 to 2018. The level of long-term exposure to PM2.5 for each participant was assessed by aggregating satellite-based estimates. Logistic regression and time-varying Cox proportional hazards models with province-level random intercepts were employed to assess associations of long-term exposures to PM2.5 with the risk of LTBI and subsequent development of active TB, respectively. Out of 4790 participants, 3284 were LTBI-free at baseline, among whom 2806 completed the one-year follow-up and 127 developed newly identified LTBI. No significant associations were identified between PM2.5 and the risk of LTBI. And among 1506 participants with LTBI at baseline, 30 active TB cases were recorded during the 5-year follow-up. Particularly, an increment of 5 μg/m3 in 2-year moving averaged PM2.5 was associated with a 50.6% increased risk of active TB (HR = 1.506, 95% CI: 1.161-1.955). Long-term air pollution might be a neglected risk factor for active TB development from LTBI, especially for those living in developing or less-developed areas where the air quality is poor.

Features of detection of latent tuberculosis infection in patients with inflammatory intestinal diseases

A quarter of the world’s population has latent tuberculosis infection (LTBI). Systemic immunosuppression is a risk factor for the reactivation of LTBI and the development of active tuberculosis, and such reactivation is associated with a substantial risk of morbidity and mortality. Despite the growing global prevalence of inflammatory bowel diseases (IBD) and the use of immunosuppressive therapies, current recommendations for LTBI testing and treatment in IBD patients lack a systematic approach due to a lack of evidence. Currently, the main challenge in accurately diagnosing inflammatory bowel diseases (IBD) is the high prevalence of conditions that lead to intestinal lesions mimicking IBD.

Psoriasis'te Biyolojik Tedavi Öncesi Latent Tüberküloz Enfeksiyonunun Değerlendirilmesi: Web Tabanlı Yorumlayıcı ile Yeni Bir Tanı Yaklaşımı

Purpose: The use of biological agents, particularly anti-TNF-alpha treatments, is associated with an elevated risk of tuberculosis (TB). Hence, a comprehensive assessment of latent tuberculosis infection (LTBI) before biologic therapies is imperative. The objective of this study was to evaluate the utility of an online tuberculin skin test (TST)/ interferon-γ release assay (IGRA) interpreter (OI-TST/IGRA) in assessing the risk of LTBI prior to initiating biological therapies in psoriasis patients.&#x0D; Materials and methods: 116 psoriasis patients who were previously evaluated for TB by a pulmonologist before being treated with a biologic agent were re-evaluated retrospectively with OI-TST/IGRA (tstin3d.com). Mean positive predictive value (PPV), mean annual risk of development of active tuberculosis (ARDATB), and mean cumulative risk of active tuberculosis (CRATB) values were calculated with OI-TST/IGRA and compared with previous results. Chi-square, Fisher-Freeman-Halton exact tests, Cohen's Kappa, and Mann-Whitney U-test were used in comparisons of groups. &#x0D; Results: The PPV of the LTBI-positive group was significantly higher than the LTBI-negative group. The PPV, ARDATB and CRATB values of the TST size of &gt;15 mm group were significantly higher than the TST size of 5-9 mm and TST size of 10-15 mm groups. The PPV, ARDATB, and CRATB values of the QuantiFERON-TB Gold In-tube test (QFT-GIT)-positive group were significantly higher than the QFT-GIT-negative group. And the same values of the chest X-ray (CXR)-positive group were significantly higher than the CXR-negative group. The PPV, ARDATB, and CRATB values were positively correlated with QFT-GIT and CXR results. In addition, the PPV was positively correlated with previous LTBI decisions and TSTs.&#x0D; Conclusion: OI-TST/IGRA in which many factors are questioned and PPV, ARDATB, and CRATB values are evaluated together, may be a valuable tool for assessing the risk of active TB in psoriasis patients and preventing overdiagnosis and unnecessary prophylaxis.

Sequence of COVID-19 Vaccination and COVID-19 Infection and Their Association With the Development of Active Tuberculosis: A Case-Control Study.

Introduction Information regarding the cross-risk of coronavirus disease 2019 (COVID-19) and tuberculosis (TB) is still sparse. This study aimed to identify the patterns of sequence of COVID-19 vaccination and COVID-19 infection and to explore the association between COVID-19 vaccination, COVID-19 infection, and the development of active TB. Methods It was a case-control study conducted in RSUD Dr. Iskak Hospital, Tulungagung, between October 2022 and April 2023. Active cases of TB patients were compared with non-TB controls in the same hospital, with the same age and sex. Their pattern of sequence of COVID-19 vaccination and infection was investigated. Logistic regression was used to assess the association between these key variables. Results Of 296 case-control sets, 64.2% were female. The mean ± standard deviation of age was 46 ± 15.6 years. 5.7% of the cases and 6.4% of the controls had a history of COVID-19 infection, whereas 58.8% and 68.4% had been vaccinated (mostly after infection). The adjusted odds ratio (95% confidence interval) of COVID-19 infection on risk to the development of active TB was 1.45 (0.58, 3.65). Those of COVID-19 vaccination of one to four doses were 0.42 (0.17, 1), 0.98 (0.58, 1.66), 0.48 (0.25, 0.93), and 0.09 (0.01, 0.81), respectively. Conclusion It was found that there were five patterns of sequence of COVID-19 infection and COVID-19 vaccination, with the most frequent being having COVID-19 infection before COVID-19 vaccination. Our data did not support the association between COVID-19 infection and the subsequent development of active TB. On the other hand, COVID-19 vaccination has been demonstrated to increase some protection against the development of active TB.

Molecular Markers of Early Immune Response in Tuberculosis: Prospects of Application in Predictive Medicine.

Tuberculosis (TB) remains an important public health problem and one of the leading causes of death. Individuals with latent tuberculosis infection (LTBI) have an increased risk of developing active TB. The problem of the diagnosis of the various stages of TB and the identification of infected patients in the early stages has not yet been solved. The existing tests (the tuberculin skin test and the interferon-gamma release assay) are useful to distinguish between active and latent infections. But these tests cannot be used to predict the development of active TB in individuals with LTBI. The purpose of this review was to analyze the extant data of the interaction of M. tuberculosis with immune cells and identify molecular predictive markers and markers of the early stages of TB. An analysis of more than 90 sources from the literature allowed us to determine various subpopulations of immune cells involved in the pathogenesis of TB, namely, macrophages, dendritic cells, B lymphocytes, T helper cells, cytotoxic T lymphocytes, and NK cells. The key molecular markers of the immune response to M. tuberculosis are cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12, IL-17, IL-22b, IFNɣ, TNFa, and TGFß), matrix metalloproteinases (MMP-1, MMP-3, and MMP-9), and their inhibitors (TIMP-1, TIMP-2, TIMP-3, and TIMP-4). It is supposed that these molecules could be used as biomarkers to characterize different stages of TB infection, to evaluate the effectiveness of its treatment, and as targets of pharmacotherapy.

Tuberculosis screening practices and outcomes in an australian dialysis unit

BackgroundThe World Health Organisation (WHO) recommends all dialysis patients undertake routine screening for latent tuberculosis infection (LTBI) in high income countries such as Australia. However, we employ a targeted screening approach in our Australian dialysis unit in line with local and some international guidelines. We analysed our practices to assess the validity of our approach.MethodsA retrospective review of new dialysis patients during the period 2012–2018 was undertaken. Patient records were reviewed for basic demographic data, comorbidities, LTBI screening using Quantiferon Gold (QFG), and outcomes, including episodes of active TB, to June 2020.Results472 patients were included. WHO high risk country of origin patients accounted for 22% (n = 103). 229 patients (48.5%) were screened using QFG. The single main indication for screening was transplantation waitlisting. 34 patients had a positive QFG result. Active tuberculosis developed in two patients during the observation period. Both occurred in the screened cohort, the cases having previously tested negative via QFG at 11 and 16 months, prior to the development of active tuberculosis. No patients in the unscreened cohort developed active tuberculosis during the observation period. WHO high risk country of origin was associated with positive QFG status, odds ratio 10.4 (95% CI 3.3–31.2).ConclusionThe data failed to show a benefit from widening of the screening program within our dialysis unit. However, a much larger sample size will be required to confidently assess the impact of the current approach on patient outcomes. Analysis of current screening practices and outcomes across all Australian dialysis services is warranted to assess the risks and benefits of widening the screening practices to include all dialysis patients as recommended by the WHO.

Tuberculosis and COVID-19 Dually Affect Human Th17 Cell Immune Response.

We analyzed the features of immune response in tuberculosis and COVID-19 patients. For this, we analyzed publications released from December 2019 to March 2023; those which were published in accessible international databases ("Medline", "PubMed", "Scopus") and with keywords such as "COVID-19", "SARS-CoV-2", "tuberculosis", "pulmonary tuberculosis", "latent tuberculosis infection", "Treg", "follicular Treg", and "Treg subsets", we considered. Through our analysis, we found that tuberculosis patients who had been infected with COVID-19 previously and elevated Th1 and Th2 cell levels. High levels of Th1 and Th2 cells may serve as a positive marker, characterizing activated immune response during TB infection. COVID-19 or post-COVID-19 subjects showed decreased Th17 levels, indicating a lack of tuberculosis development. Moreover, the typical course of tuberculosis is associated with an increase in Treg level, but COVID-19 contributes to a hyperinflammatory response. According to the data obtained, the course of tuberculosis proceeds in a dissimilar way due to the distinct immune response, elicited by SARS-CoV-2. Importantly, the development of active tuberculosis with a severe course is associated with a decline in Treg levels. Both pathogens lead to disturbed immune responses, increasing the risk of developing severe TB. The insights and findings of this paper may be used to improve the future management of individuals with latent and active tuberculosis.

Frequency of latent tuberculosis in patients receiving Anti-TNF-Alpha therapy.

In this study, it was aimed to reveal the incidence of tuberculosis development in patients receiving tumor necrosis factor-alpha (TNF-α) blocker therapy, despite tuberculosis chemoprophylaxis. 520 patients who were receiving anti TNF-α treatment in the last 3 years were evaluated retrospectively. Radiological imaging tuberculin skin test (TST), history of tuberculosis, BCG vaccine, chemoprophylaxis administration, used anti TNF-α drugs were recorded. There were 265(51.0%) of the patients with ankylosing spondylitis (AS), 175(33.7%) with rheumatoid arthritis, 35(6.7%) with Crohn's, 10(1.9%) with ulcerative colitis (UC), 21(4.0%) with psoriatic arthritis, 14(2.7%) with psoriasis vulgaris. In total, 455 (79.6%) patients were given INH prophylaxis. Active tuberculosis development was observed in five patients (4: pulmonary,1: extrapulmonary; 3: UC, 2:AS) who all received anti TNF-α treatment (0.96%), infliximab. Three patients had tuberculosis disease in the 6th month, and the other 2 patients in the 5th and 24th month of their anti TNF-α treatments, and two had 9-month, and 1 had 6-month chemoprophylaxis history. The incidence of tuberculosis development in patients treated with anti TNF-α was found to be higher than the general population. In our country, where tuberculosis is still prevalent, patients receiving Anti TNF-α treatment (especially infliximab) should be carefully questioned and examined about tuberculosis.

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.

Isoniazid preventive therapy among HIV infected patients on antiretroviral therapy diagnosed with latent tuberculosis: A retrospective assessment of the outcome in Tanzania

BackgroundPeople infected with HIV are at a higher risk up to 20-folds of developing active TB than those not infected with HIV. Isoniazid Preventive Therapy (IPT) is employed in HIV eligible individuals to prevent progression of active tuberculosis (TB) disease. However, there is limited data on the efficacy of IPT in clinical settings in Tanzania and other parts of the world. This study was carried to assess the real-time IPT effectiveness in preventing TB incidences among HIV infected individuals on antiretroviral therapy. MethodsA retrospective cohort study was carried employing secondary data of 1000 HIV infected individuals receiving anti-retroviral therapy. TB incidence and associated factors were determined after a four years follow-up. ResultsA total of 1000 people were enrolled in the study. The mean age was 44.87 years. The incidence rate was 7.37/1000 person-years (PY) [95% confidence interval (CI) 3.96-13.71]. One percent (1%) of patients developed active tuberculosis within four years of follow up after receiving isoniazid tablets as part of IPT. ConclusionIPT has a high efficacy in preventing active TB development among HIV infected individuals on ART in clinical settings thus warranting the scale up of IPT services in the country.

Miliary Tuberculosis in a Patient With Ulcerative Colitis Treated With Tofacitinib

ABSTRACT Immunosuppression with tumor necrosis factor-alpha inhibitors and tofacitinib is a risk factor for reactivation of latent tuberculosis (TB) and the development of active TB. We report a case of miliary TB in a patient on treatment with tofacitinib for active ulcerative colitis. By week 4 of therapy, a clinical response was achieved. Subsequently, although being on treatment, the patient started having fever with night sweats and myalgias. The investigative workup revealed pulmonary miliary TB. Tofacitinib was withdrawn, and antitubercular therapy was initiated. The patient responded, both clinically and radiologically, to the antitubercular therapy. This case report highlights the importance of screening for latent TB in patients receiving tofacitinib.

Progress in research of prophylactic therapy in contacts of rifampicin-resistant tuberculosis patients

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.

Activation of tuberculosis in recovered COVID-19 patients: a case report.

In these two cases, the authors observed the development of active TB after a period of COVID recovery. Two patients who were admitted to the hospital complained mainly, among other symptoms, of fever and a continuous cough after a period of COVID-19 recovery. Radiological examination revealed a caving density in the two cases, and the Gene-Xpert test proved the presence of Mycobacterium tuberculosis bacteria despite the negative result of the Ziehl-Neelsen stain. The two patients were improved after standard TB treatment. Patients with post-COVID-19 chronic respiratory symptoms should be screened for TB, especially in TB-endemic areas, even though the result of the Ziehl-Neelsen stain was negative.

Protective Role of Vitamin D Against Development of Active Tuberculosis in Close Household Contacts of Pulmonary Tuberculosis Patients: A Prospective Cohort Study.

Vitamin-D is known to promote innate immune responses by acting as a cofactor of VDR for induction of antimicrobial peptides like cathelicidin. Close household contacts of pulmonary tuberculosis patients are at high risk of active infection, Therefore, possible role of vitamin-D in TB prevention through cathelicidin production was studied in high-risk household contacts (HHCs) of pulmonary tuberculosis (PTB) patients. 20 HHCs of PTB patients were recruited and followed up for one year. Levels of vitamin-D (25(OH)D) and its associated molecules were evaluated at 3-months intervals for one year or until the development of active TB. 25(OH)D was measured using chemiluminescence method. Serum VDR and cathelicidin levels were measured by ELISA and VDR mRNA expression by qPCR. Throughout the study period mean range of serum 25(OH)D levels was 20.51 ± 5.12 ng/ml. VDR and cathelicidin levels however showed significant decline after six months suggesting decrease in bacterial exposure. None of the HHCs developed active infection even with high exposure to 2 + to 3 + AFB positive index cases. Mantoux positive household contacts had high levels of VDR and cathelicidin, suggestive of an early or latent phase of infection, did not develop active TB plausibly due to maintenance of adequate serum levels of vitamin-D. Optimal levels of 25(OH)D and its associated molecules during early stages of infection may serve as protective factor against development of active TB. Cohort of HHCs with severely deficient vitamin-D levels (10 ng/ml) could be followed up for a better risk assessment.

Active tuberculosis in inflammatory bowel disease patients: a case–control study

Background/Aims: Anti-tumor necrosis factor (anti-TNF) drugs have been the mainstay therapy for moderate to severe inflammatory bowel disease (IBD) over the past 25 years. Nevertheless, these drugs are associated with serious opportunistic infections like tuberculosis (TB). Brazil is ranked among the 30 countries with the highest incidence of TB in the world. This study aimed at identifying risk factors for the development of active TB and describing clinical characteristics and outcomes in IBD patients followed at a tertiary referral center in Brazil. Methods: We conducted a retrospective, case–control study between January 2010 and December 2021. Active TB cases in IBD patients were randomly matched 1:3 to controls (IBD patients with no previous history of active TB) according to gender, age, and type of IBD. Design: This was a retrospective, case–control study. Results: A total of 38 (2.2%) cases of TB were identified from 1760 patients under regular follow-up at our outpatient clinics. Of the 152 patients included in the analysis (cases and controls), 96 (63.2%) were male, and 124 (81.6%) had Crohn’s disease. Median age at TB diagnosis was 39.5 [interquartile range (IQR) 30.8–56.3]. Half of the active TB cases were disseminated (50%). Overall, 36 patients with TB (94.7%) were being treated with immunosuppressive medications. Of those, 31 (86.1%) were under anti-TNF drugs. Diagnosis of TB occurred at a median of 32 months after the first dose of anti-TNF (IQR 7–84). In multivariate analysis, IBD diagnosis older than 17 years and anti-TNF therapy were significantly associated with the development of TB ( p &lt; 0.05). After the TB treatment, 20 (52.7%) patients received anti-TNF therapy, and only one developed ‘de novo’ TB 10 years after the first infection. Conclusions: TB remains a significant health problem in IBD patients from endemic regions, especially those treated with anti-TNFs. In addition, age at IBD diagnosis (&gt;17 years old) was also a risk factor for active TB. Most cases occur after long-term therapy, suggesting a new infection. The reintroduction of anti-TNFs agents after the anti-TB treatment seems safe. These data highlight the importance of TB screening and monitoring in IBD patients living in endemic areas.