Positive Tuberculin Skin Test Research Articles

Multidisciplinary approach to asylum seekers health assessment: a 5-year experience in Modena, Italy

Abstract Background Asylum seekers’ well-being represents a global health issue. They face significant challenges to their physical and mental health due to their migratory path. In the Modena province (Northern Italy), a multidisciplinary approach has been applied to the care of asylum seekers by Department of Public Health (DPH), with a team of specialists in infectious diseases, dermatology, gynaecology, obstetrics, psychology and preventive medicine. Asylum seekers receive a first visit, including medical and psychological assessment and screening for infectious diseases. Ad hoc pathways are also active for asylum seekers who need secondary-level care. This study aims to investigate the health status of asylum seekers referred to Modena Centre. Methods This cohort study enrolled asylum seekers hosted in Modena between November 2018 and May 2023. During the first visit, personal and anamnestic data were collected aided by cultural mediators, along with clinical assessment. Furthermore, Tuberculin-Skin-Test (TST) and blood tests for HBV-HCV-HIV-Syphilis were performed. Results A total of 646 migrants were included, 94% were males with a median age of 26 years (range: 15-50), the majority from Bangladesh (39%). Females were mostly from Ivory Coast (36%), median age of 30 years (range: 17-45). Most conditions were treated at the primary care level and were related to cutaneous disease (22%), only 11% of subjects required second-level diagnostics. Positive TSTs were 41% (N = 265). Of them, 55.5% (N = 147) also tested positive for QuantiFERON-TB. Screening for infectious diseases revealed positivity rates of 4% for HBsAg, 1% for HCVAb, 0.8% for HIV and 1.4% for TPPA+RPR. Conclusions The multidisciplinary approach is the innovative and strength point of this protocol for asylum seekers’ health ensuring prompt management of pathologies after their arrival. Moreover, data collection is useful for improving intake services and implementing public health programs for vulnerable individuals. Key messages • The innovation of this protocol for asylum seekers’ health lies in its multidisciplinary approach. • Clinical data collection will support health policies’ choices to protect vulnerable individuals.

Diagnosis of tuberculosis infection in children with a novel skin test and the traditional tuberculin skin test: An observational study.

A novel skin test-called Diaskintest (DT)-containing specific M. tuberculosis antigens is in clinical use in the Russian Federation (RF). This test may improve diagnosis of tuberculosis (TB) infection. The use and performance of the DT was described and compared to the tuberculin skin test (TST). Data on children <18 years referred to a TB reference centre (Jan/2018- Dec/2019) with ≥1 DT and TST result available were analysed. An immune correlate of TB infection was defined as a positive TST (≥10 mm induration) or a positive DT (any induration). Of 2710 included cases, the median age was 9.0 (IQR 5.7-13.1) years and 97.5% were BCG immunised. Overall, 1976 (79.9%) were TB uninfected, 724 (26.7%) had an immune correlate of TB infection and 10 (0.4%) TB disease. Reasons for referral were: positive or increasing skin test results in routine screening (992, 36.6%), screening before admission to a health care institution (501, 18.5%) and TB contact (457, 16.9%). DT was positive in 11.7% (308/2625) and TST in 63.1% (467/740) (Kappa 0.08, 95% CI:0.013-0.14). A positive DT was associated with older age (OR 1.16 (95% CI: 1.13-1.19) per year). Among TB contacts DT positivity was associated with contagiousness: highest proportion of positivity of 12.0% was observed when the index case was smear positive. In a setting with universal BCG vaccination and regular screening with TST, DT was used to rule out TB infection as TST was commonly positive. We found an association of DT positivity and contagiousness of the index case in children contacts. These observations may suggest improved specificity and sensitivity of DT compared to TST.

Manifestation of ocular tuberculosis in a north Indian tertiary care centre: Case series

Ocular tuberculosis acts as a challenge throughout the world, and its pathophysiology, diagnosis, and treatment are a topic for debate. The present case series represents retrospective study focusing on the variable clinical presentations, the diagnostic and therapeutic characteristics of ocular tuberculosis. We report 12 patients of ocular tuberculosis with variable presentations. : Retrospective analysis of records of patients diagnosed with ocular tuberculosis from August 2022 till March 2023 was done. Diagnosis of ocular tuberculosis was based on detailed ocular and systemic examination including best corrected visual acuity (BCVA), Slit lamp examination, fundus examination, OCT. The patients presenting with features suggestive of ocular tuberculosis were further investigated with complete blood count (CBC), erythrocyte sedimentation rate (ESR), Monteaux test, Chest X-ray, Cartridge Based Nuclear Amplification Test (CBNAAT) and rheumatological work up. Out of 12 of ocular tuberculosis patients, 4 were diagnosed with active retinal vasculitis, 3with choroiditis, 3 had panuveitis, and remaining 2 patients had unilateral nodular episcleritis. The diagnosis was based on compatible clinical picture, highly positive Tuberculin skin test and dramatic response to anti-tuberculous drugs. All 12 cases were strongly Mantaux test positive (2 developed injection site ulceration). All cases were started on ATT immediately with pulmonologist consultation and showed clinical improvement after 1 month. Ocular tuberculosis can have myriad presentations. Positive Mantaux test plays an important role in supporting diagnosis of ocular tuberculosis.

Screening hemodialysis patients for tuberculosis in Sudan

ObjectivesTo estimate the prevalence of latent tuberculosis infection (LTBI) and the need for TB preventive treatment (TPT) among hemodialysis (HD) patients in Sudan. MethodsWe screened patients in a single HD center by two-step tuberculin skin test (TST), symptom survey, physical examination and chest radiography (CXR). ResultsThe survey included 204 patients, five of whom (2.5%) had history of previously treated TB. The proportion of TST positive patients was 12.3% after the first test and increased to 21.1% after the second test. Patients previously treated for TB were more likely to have positive TST (80 vs 20.1%, p = 0.01). We screened 184 patients for TB disease; 16.3% were symptomatic, 15.8% had CXR abnormality and 6.5% were symptomatic with CXR abnormality. Additionally, 13.6% of patients had physical signs consistent with extra-pulmonary TB without symptoms or CXR abnormality. Based on these findings, high probability of pulmonary and extra-pulmonary TB was found in 38.6% and 13.6% of patients respectively and they were referred for bacteriological confirmation. We diagnosed LTBI and prescribed TPT to 9.2% of screened patients. ConclusionIn this cohort of Sudanese HD patients, 21.1% were positive after two-step TST and 52.2% were considered to have high probability of TB disease.

Effectiveness of preventive treatment among different age groups and Mycobacterium tuberculosis infection status: a systematic review and individual-participant data meta-analysis of contact tracing studies.

Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosis infection status while considering tuberculosis burden of the settings. In this systematic review and individual-participant meta-analysis, we investigated the development of incident tuberculosis in people closely exposed to individuals with tuberculosis. We searched for studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase. We restricted our search to cohort studies; case-control studies and outbreak reports were excluded. Two reviewers evaluated titles, abstracts, and full text articles for eligibility. At each stage, two reviewers discussed discrepancies and re-evaluated articles until a consensus was reached. Individual-participant data and a pre-specified list of variables, including characteristics of the exposed contact, the index patient, and environmental characteristics, were requested from authors of all eligible studies; contacts exposed to a drug-resistant tuberculosis index patient were excluded. The primary study outcome was incident tuberculosis. We estimated adjusted hazard ratios (aHRs) for incident tuberculosis with mixed-effects Cox regression models with a study-level random effect. We estimated the number-needed-to-treat (NNT) to prevent one person developing tuberculosis. Propensity score matching procedures were used in all analyses. This study is registered with PROSPERO (CRD42018087022). After screening 25 358 records for eligibility, 439 644 participants from 32 cohort studies were included in the individual-participant data meta-analysis. Participants were followed for 1 396 413 person-years (median of 2·7 years [IQR 1·3-4.4]), during which 2496 people were diagnosed with incident tuberculosis. Overall, effectiveness of preventive treatment was 49% (aHR 0·51 [95% CI 0·44-0·60]). Participants with a positive tuberculin-skin-test (TST) or IFNγ release assay (IGRA) result at baseline benefitted from greater protection, regardless of age (0·09 [0·05-0·17] in children younger than 5 years, 0·20 [0·15-0·28] in individuals aged 5-17 years, and 0·17 [0·13-0·22] in adults aged 18 years and older). The effectiveness of preventive treatment was greater in high-burden (0·31 [0·23-0·40]) versus low-burden (0·58 [0·47-0·72]) settings. The NNT ranged from 9 to 34 depending on age among participants with a positive TST or IGRA in both high-burden and low-burden settings; among all contacts (regardless of TST or IGRA test result), the NNT ranged from 29 to 43 in high-burden settings and 213 to 455 in low-burden settings. Our findings suggest that a risk-targeted strategy prioritising contacts with evidence of M tuberculosis infection might be indicated in low-burden settings, and a broad approach including all contacts should be considered in high-burden settings. Preventive treatment was similarly effective among contacts of all ages. None.

Tuberculin Skin Test Reactivity among Health Care Workers in the Abia State University Teaching Hospital, Aba South-east Nigeria

Background Tuberculosis is one of the infections targeted for eradication and is still under surveillance. Hospital workers in Nigeria take little or no precautions against tuberculosis while attending to patients. Objectives This research aimed to study the prevalence of the reactivity of positive Tuberculin Skin Tests among healthcare workers in a Nigerian University Teaching Hospital. Methods Ethical approval and informed consent were obtained from the participants. Two hundred and ten consented participants were recruited for this study, while 185 contributed till the end. The Tuberculin Skin Test was conducted following the standard operating procedures. The chi-square test was used to compare the variable at a significant level of P &lt; 0.05. Of those who received a BGC vaccine &lt; 3 years, 4.8% were excluded from the analyses. Results Mean ± SD of participants’ age was approximately 30 ± 8 years. Participants comprised 87 (47%) males and 98 (53%) females. The modal age group was 21-25 years. Most participants were clinical medical students, 93(50.3%), while doctors, 7 (3.8%), were second to least. The prevalence of positive reactivity to the Tuberculin Skin Test was 29.9%. There was no significant difference observed regarding sexes and positive reactivity. A significant difference was found in reactivity ≥ 10 mm between those who didn’t receive BCG and those who received BCG vaccine ≥ 10 years before the study. Conclusion Healthcare workers can be potential active TB patients and reservoirs. We recommend highly sensitive and specific periodic TB screening, prophylactic treatment, and re-vaccination of Health Care Workers in Nigeria.

Quantiferon-TB Gold Test in Diagnosis of Tubercular Uveitis

Background: Tuberculosis can occur in eye as a result of an active infection or immunological reaction to the tuberculosis antigen. One of the most accurate tests for suspected ocular tuberculosis is the Quantiferon TB Gold (QFT-G) test, which has a higher specificity than the Tuberculin Skin Test (TST) especially among persons vaccinated with bacillus Calmette-Guérin (BCG) and the fact that most environmental mycobacteria give TST positive results. Methods: We retrospectively reviewed thirty nine presumed ocular tuberculosis cases who had both TST and QFT-G test prior to anti-tuberculosis treatment (ATT) in the National Institute of Ophthalmology and Hospital and Vision Eye Hospital, Dhaka from January, 2019 to December, 2021. Patients who had concomitant pulmonary or other extra pulmonary tuberculosis were excluded from the study. Results: The most common anatomical type of uveitis was posterior uveitis 24(61.5%) and vasculitis retinae 8(20.5%) was the commonest form of specific pattern of uveitis. MT test was positive in 18(46.2%) and QFT-G test was positive in 17 (43.6%) patients. Multifocal choroiditis was commonest form of QFT-G positive uveitis 5(29.5%). There was no significant association of positive QFT-G test with any subset of uveitis (p&gt;0.05). Conclusion: As our study found no significant association of positive QFT-G in patients with any anatomical variety of uveitis or specific variety of uveitis we should advice QFT-G judicially to patients of suspected TBU who have positive TST.

Overlooked, dismissed, and downplayed: reversion of Mycobacterium tuberculosis immunoreactivity.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb). Following infection, immune responses to Mtb antigens can be measured using the tuberculin skin test or an interferon-γ release assay. The gain of Mtb immunoreactivity, a change from a negative to a positive tuberculin skin test or interferon-γ release assay result, is called conversion and has long been used as a measure of Mtb exposure. However, the loss of immunoreactivity (reversion; a positive followed by a negative result) has often been overlooked. Instead, in clinical and epidemiological circles, Mtb immunoreactivity is commonly considered to persist lifelong and confer a lifetime of disease risk. We present a critical review, describing the evidence for reversion from cohort studies, ecological studies and studies of TB progression risk. We outline the inconsistent reasons why reversion has been dismissed from common understanding and present evidence demonstrating that, just as conversion predominantly indicates prior exposure to Mtb antigens, so its opposite, reversion, suggests the reduction or absence of exposure (endogenous or exogenous). Mtb immunoreactivity is dynamic in both individuals and populations and this is why it is useful for stratifying short-term TB progression risk. The neglect of reversion has shaped TB research and policy at all levels, influencing clinical management and skewing Mtb infection risk estimation and transmission modelling, leading to an underestimation of the contribution of re-exposure to the burden of TB, a serious oversight for an infectious disease. More than a century after it was first demonstrated, it is time to incorporate reversion into our understanding of the natural history of TB.

Prevalence and risk factors of latent tuberculosis infection in hemodialysis patients in southwest Iran.

Tuberculosis (TB) is a significant global health concern, particularly in developing countries. Diagnosing latent tuberculosis infection (LTBI) in hemodialysis patients is crucial because of the risk of developing active tuberculosis in this population due to attenuated immune response. Herein, we assessed the prevalence of LTBI in hemodialysis patients. In this cross-sectional study, we included all patients referred to hemodialysis centers in Kohgiluyeh and Boyer-Ahmad Province, southwest Iran, in 2018 through census sampling. Tuberculin skin test (TST) was utilized to screen the patients for LTBI. All steps were done by trained physicians. In total, 183 patients (mean age: 59.3, SD= 16.0) were included in the study of which 76 (41.5%) were females, and 107 (58.5%) were males. Neither the patients nor their family members had a history of tuberculosis. Assuming an above 5-millimeter enduration as a positive TST result, 22 patients (12%) had LTBI. None of the demographic or clinical features differed between TST -negative and -positive groups. Hemodialysis patients are prone to LTBI due to several immunological and environmental factors. Screening for LTBI may be beneficial to prevent active tuberculosis in this population.

A case of solitary choroidal tuberculoma with highly positive tuberculin skin test and negative interferon gamma release assays.

A case of solitary choroidal tuberculoma with highly positive tuberculin skin test and negative interferon gamma release assays.

Predictors of positive tuberculin skin test in neonates exposed to pulmonary tuberculosis.

Neonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Guérin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB. A retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity. Contact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3-3.9, P = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors. Age at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure.

Impact of COVID-19 Pandemic on Tuberculosis and Latent Tuberculosis Infection Diagnosis in Healthcare Workers.

The aim of the study is to compare the prevalence of latent tuberculosis infection and tuberculosis (TB) in the prepandemic period (2017-2019) with the pandemic period (2020-2022), in a group of healthcare workers (HCWs). This is a retrospective study. Data on TB diagnosis was retrieved from the hospital information system database. All HCWs who underwent tuberculin skin test (TST) from January 2017 to December 2022 were included in the study. In the prepandemic period (2017-2019), 163 HCWs out of 710 were TST positive (22.9%), and in the pandemic period (2020-2022), 85 HCWs out of 449 were TST positive (18.9%) ( P = 0.11). There were 10 HCWs diagnosed with TB in the prepandemic period (incidence: 41.7/100,000) and 2 in the pandemic period (incidence: 8.3/100,000) ( P < 0.0001). This study showed that TB incidence was reduced during the pandemic period in HCWs. TST positivity was also reduced, though not statistically significant.

Prevalence and risk factors of latent tuberculosis infection in hemodialysis patients in southwest Iran

INTRODUCTION. Tuberculosis (TB) is a significant global health concern, particularly in developing countries. Diagnosing latent tuberculosis infection (LTBI) in hemodialysis patients is crucial because of the risk of developing active tuberculosis in this population due to attenuated immune response. Herein, we assessed the prevalence of LTBI in hemodialysis patients. METHODS. In this cross-sectional study, we included all patients referred to hemodialysis centers in Kohgiluyeh and Boyer-Ahmad Province, southwest Iran, in 2018 through census sampling. Tuberculin skin test (TST) was utilized to screen the patients for LTBI. All steps were done by trained physicians. RESULTS. In total, 183 patients (mean age: 59.3, SD= 16.0) were included in the study of which 76 (41.5%) were females, and 107 (58.5%) were males. Neither the patients nor their family members had a history of tuberculosis. Assuming an above 5-millimeter enduration as a positive TST result, 22 patients (12%) had LTBI. None of the demographic or clinical features differed between TST -negative and -positive groups. CONCLUSION. Hemodialysis patients are prone to LTBI due to several immunological and environmental factors. Screening for LTBI may be beneficial to prevent active tuberculosis in this population.

Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease

Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.

High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trial

Tuberculosis preventive treatment (TPT) is a key component of tuberculosis elimination. To improve completion and reduce the burden for people and health systems, short, safe, and effective TPT regimens are needed. We aimed to compare safety and treatment completion of various doses and durations of rifampicin in people who were recommended to receive TPT. This partially blinded, parallel-arm, non-inferiority, randomised, controlled, phase 2b trial was done at seven university-affiliated clinics in Canada, Indonesia, and Viet Nam. Participants aged 10 years or older were included if they had an indication for TPT according to WHO guidelines for Indonesia and Viet Nam, or Canadian guidelines for Canadian sites, and a positive tuberculin skin test or interferon-γ release assay. Participants were randomly assigned (1:1:1) to receive oral rifampicin at 10 mg/kg once daily for 4 months (standard-dose group), 20 mg/kg daily for 2 months (20 mg/kg group), or 30 mg/kg daily for 2 months (30 mg/kg group). The randomisation sequence was computer generated with blocks of variable size (three, six, and nine) and stratified by country for Indonesia and Viet Nam, and by city within Canada. Participants and investigators were masked to dose in high-dose groups, but unmasked to duration in all groups. The two co-primary outcomes were safety (in the safety population, in which participants received at least one dose of the study drug) and treatment completion (in the modified intention-to-treat [mITT] population, excluding those ineligible after randomisation). Protocol-defined adverse events were defined as grade 3 or worse, or rash or allergy of any grade, judged by an independent and masked panel as possibly or probably related to the study. A margin of 4% was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03988933 (active). Between Sept 1, 2019, and Sept 30, 2022, 1692 people were assessed for eligibility, 1376 were randomly assigned, and eight were excluded after randomisation. 1368 participants were included in the mITT population (454 in the standard group, 461 in the 20 mg/kg group, and 453 in the 30 mg/kg group). 589 (43%) participants were male and 779 (57%) were female. 372 (82%) in the standard-dose group, 329 (71%) in the 20 mg/kg group, and 293 (65%) in the 30 mg/kg group completed treatment. No participants in the standard-dose group, one (<1%) of 441 participants in the 20 mg/kg group, and four (1%) of 423 in the 30 mg/kg group developed grade 3 hepatotoxicity. Risk of protocol-defined adverse events was higher in the 30 mg/kg group than in the standard-dose group (adjusted risk difference 4·6% [95% CI 1·8 to 7·4]) or the 20 mg/kg group (5·1% [2·3 to 7·8]). There was no difference in the risk of adverse events between the 20 mg/kg and standard-dose groups (-0·5% [95% CI -2·4 to 1·5]; non-inferiority met). Completion was lower in the 20 mg/kg group (-7·8% [95% CI -13·6 to -2·0]) and the 30 mg/kg group (-15·4% [-21·4 to -9·4]) than in the standard-dose group. In this trial, 2 months of 30 mg/kg daily rifampicin had significantly worse safety and completion than 4 months of 10 mg/kg daily and 2 months of 20 mg/kg daily (the latter, a fully blinded comparison); we do not consider 30 mg/kg to be a good option for TPT. Rifampicin at 20 mg/kg daily for 2 months was as safe as standard treatment, but with lower completion. This difference remains unexplained. Canadian Institutes of Health Research.

Management of newborns and healthcare workers exposed to isoniazid-resistant congenital tuberculosis in the neonatal intensive care unit

Management of newborns and healthcare workers (HCWs) exposed to congenital tuberculosis (TB) in the neonatal intensive care unit (NICU) has been reported rarely. To outline a contact investigation process for individuals exposed to congenital TB in the NICU and investigate nosocomial transmission. Additionally, to assess the efficacy and safety of window prophylaxis in exposed newborns. A baby, born at a gestational age of 28+ 1 weeks, was diagnosed with isoniazid-resistant congenital TB on the 39th day of admission to the level IV NICU. Newborns and HCWs exposed cumulatively for ≥8h underwent contact investigation and follow-up for a year. Eighty-two newborns underwent contact investigation. All newborns displayed normal chest X-rays, and 42 hospitalized newborns tested negative for acid-fast bacilli stain and Xpert® MTB/RIF assay in their endotracheal sputum or gastric juices. Eighty received window prophylaxis: six of 75 on rifampin experienced mild adverse events, and none of the five on levofloxacin. After 12 weeks, five (6.1%) had a positive tuberculin skin test, all of whom had already received the Bacillus Calmette-Guérin vaccine and tested negative on TB interferon-gamma releasing assay. Of 119 exposed HCWs, three (2.5%) were diagnosed with latent TB infection and completed a four-month rifampin therapy. There was no active TB disease among exposed newborns and HCWs during a one-year follow-up. Timely diagnosis of congenital TB is crucial for minimizing transmission among exposed neonates and HCWs in the NICU setting. In cases of isoniazid-resistant index patients, even premature newborns may consider the use of rifampin or levofloxacin for window prophylaxis.

Activin A levels are raised during human tuberculosis and blockade of the activin signaling axis influences murine responses to M. tuberculosis infection.

Tuberculosis remains the leading cause of death by a bacterial pathogen. The etiologic agent of tuberculosis, Mycobacterium tuberculosis, can remain dormant in the infected host for years before causing disease. Significant effort has been made to identify biomarkers that can discriminate between latently infected and actively diseased individuals. We found that serum levels of the cytokine activin A were associated with increased lung pathology and could discriminate between active tuberculosis and tuberculin skin-test-positive healthy controls. Activin A signals through the ActRIIB receptor, which can be blocked by administration of the ligand trap ActRIIB-Fc, a soluble activin type IIB receptor fused to human IgG1 Fc. In a murine model of tuberculosis, we found that ActRIIB-Fc treatment reduced mycobacterial loads. Strikingly, ActRIIB-Fc treatment significantly increased the number of tissue-resident memory T cells. These results suggest a role for ActRIIB signaling pathways in host responses to Mycobacterium tuberculosis and activin A as a biomarker of ongoing disease.

Prevalence of Latent Tuberculosis Infection Among Nurses Working in Critical Areas at a Tertiary Care Hospital in Riyadh, Saudi Arabia.

Introduction Tuberculosis is a critical health issue worldwide.Most infected persons are asymptomatic and categorized as having a latent tuberculosis infection (LTBI). Healthcare workers (HCWs) are more prone to being infected with tuberculosis and should be enrolled in a screening program for early detection. Objectives The study aims to estimate the prevalence of LTBI among nurses working in critical areas which include adult intensive care units, pediatric intensive care units, emergency departments, oncology departments, dialysis departments, tuberculosis labs, isolation rooms, and cardiac center intensive care units. Methods A record-based cross-sectional survey measured the prevalence of LTBI among nurses working in critical areas at Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia. We reviewed the occupational health records of all nurses working in critical areas from June 1, 2021, to June 1, 2022. We recorded the data reviewed throughout the year in the Occupational Health Department at PSMMC. We excluded all participants with previously documented positive tuberculin skin test (TST) from the study. We analyzed the sociodemographic data, working years, working location, job title, and TST results. Results We included a total of 771 out of 2025 nurses in this study. Participants were mostly women (88%) and in the 26-35-year age group (67.7%). Most of the participants were originally from the Philippines (66.3%). The overall LTBI prevalence among nurses was 34.5%. The highest prevalence of LTBI was among nurses working in the cardiac intensive care unit (53.5%), and the lowest prevalence was among nurses working in the isolation department (8.9%; p-value <0.0001). Those who worked more in the hospital were significantly more infected with LTBI (p-value <0.04). Conclusion LTBI remains a significant health risk worldwide andin the Middle East as well as among HCWs. This underscores the necessity of comprehensive pre-hiring screening, annual screening, infection control protocols, and active management of HCWs with LTBI.

Diagnostic performance of a novel ESAT6-CFP10 skin test for tuberculosis infection in school tuberculosis outbreak in China.

The ESAT6-CFP10 (EC) skin test is recommended by the World Health Organization for latent tuberculosis infection (LTBI). However, it is still unknown how the EC skin test performs in students during a school tuberculosis outbreak. We conducted an epidemiological investigation to assess the performance of the EC skin test in this high-risk population. A total of 9 active student patients were confirmed in the same class as the index case, with an incidence rate of 18.0% (9/50). Among the 50 close contacts, 14 (28%) were over 15 years old and had a chest X-ray (CXR), and none of them had abnormal CXR findings. The rates of positive tuberculin skin test (TST) ≥ 5 mm and < 10 mm, ≥ 10 mm and < 15 mm, and ≥ 15 mm were 12.0% (6/50), 16.0% (8/50), and 10.0% (5/50), respectively. On the second screening, 44 students with the same class as the index case had the EC skin test, of which 31 (70.5%) had positive EC tests. All patients had negative sputum smear results, of whom 4 (44.4%) had positive Xpert results; three had a TST induration diameter between 5 mm and 10 mm, but all of them had an EC diameter > 15 mm; 5 (55.6%) had abnormal CXR results, but all the confirmed patients had abnormal CT results; Except for four cases that were diagnosed by Xpert, the remaining five were confirmed by CT scan. The novel EC skin test performed well in students during the school tuberculosis outbreak. In some special conditions, such as when the index case is bacteriologically positive for tuberculosis and the rate of LTBI is higher than the average for the local same-age group, secondary screening is recommended 2-3 months after the first screening. Furthermore, we cannot ignore the role of CT in the diagnosis of early student tuberculosis.

Performance of the QuantiFERON- TB gold test in children receiving immunosuppressive therapy for rheumatic diseases

ObjectivesThe mainstay of treatment for pediatric rheumatological disease is disease-modifying anti-rheumatic agents which are immunosuppressive in nature and increase the susceptibility to tuberculosis. The aims and objectives were to evaluate the performance of the QuantiFERON®-TB Gold test (QFT) and Tuberculin skin test (TST) to diagnose latent tuberculosis in children receiving immunosuppressive therapy for rheumatic diseases in a tertiary hospital in South India. MethodsThis was a prospective observational study. 60 consecutive children diagnosed with various rheumatic diseases attending the Paediatric Rheumatology clinic on immunosuppressive therapy were included. The QFT and TST were performed on the same day. Data regarding the demography, diagnosis, treatment received and test results were collected and analysed. ResultsAmong patients included (n = 60), two children had positive QFT and one child had positive TST. The agreement between tests was k = 0.85 and the proportion of latent tuberculosis was 5 %. All the children included were on conventional DMARDs and 3.3 % were on biological DMARDs. There was a significant decrease in the mitogen induced interferon level in children on treatment with hydroxychloroquine (p = 0.022) and a significant increase in the level in children on azathioprine (p = 0.006). Children on steroids had a lower range of mitogen-induced interferon levels. ConclusionQFT may be a more reliable test than TST for the detection of latent tuberculosis in children with rheumatic diseases receiving immunosuppressive treatment. The use of hydroxychloroquine and steroids might influence the mitogen-induced IFN-γ secretion and may interfere with the interpretation of the QFT test.