Tuberculin Skin Test Research Articles

Prevalence, Risk Factors, and Result Features in the Detection of Latent Tuberculosis Infection in Thai Healthcare Workers Using QuantiFERON-TB Gold Plus.

Introduction Latent tuberculosis infection (LTBI) is an enormous reservoir for tuberculosis (TB), and healthcare workers (HCWs) are at high risk for TB infection. QuantiFERON-TB Gold Plus (QFT-Plus) is an alternative to the tuberculin skin test for LTBI detection, but data on its application and LTBI detected by QFT-Plus in high TB burden countries are limited. This study aimed to determine the prevalence of LTBI and its risk factors, and to investigate the QFT-Plus results in Thai HCWs. Methods A cross-sectional analytical study was conducted among HCWs at a secondary care hospital in Health Region 5, Thailand. Eligible HCWs were enrolled and underwent QFT-Plus testing. Interferon-gamma (IFN-γ) values in tubes were analysed. The prevalence and associated risk factors for LTBI were assessed based on laboratory and sociodemographic data. Logistic regression analyses were applied to calculate odds ratios (OR, aOR) reported with 95% confidence intervals (CI). Results Of the 269 participants enrolled, their median age was 42 years and 93.31% (n = 251/269) were female. The majority (n = 178/269, 66.17%) were nurses or nurse assistants and 42.75% (n = 115/269) worked in the inpatient medical wards. Overall, the QFT-Plus results showed 110 (40.89%) positive with good agreement (93.68%; κ 0.87) and high correlation (Spearman's ρ 0.91) of IFN-γ concentrations in the two antigen tubes. A true difference inIFN-γ values for predicting a recent infection was found about 7.81% (n = 21/269). By univariate and multivariate analyses, the participants' age > 40 years (OR = 3.21, 95% CI: 1.84-5.64%; aOR = 2.05, 95% CI: 1.07-3.96%), and employment duration > 10 years (OR = 3.19, 95% CI: 1.66-6.37%; aOR = 2.34, 95% CI: 1.05-5.21%) were significantly associated with the increased risk of LTBI (p-value < 0.05). Conclusions The prevalence of LTBI among these HCWs was high, and the increased risk factors for LTBI according to QFT-Plus positivity were age over 40 years and working time in the hospital for more than 10 years. It is important to screen HCWs in this setting for LTBI, particularly those with long employment durations and older ages. The high prevalence of LTBI suggests that LTBI management, such as regular screening and treatment, should be considered together with strengthening preventive measures, especially in high-risk groups.

Latent Tuberculosis Infection Is Associated with an Enrichment of Short-Chain Fatty Acid-Producing Bacteria in the Stool of Women Living with HIV.

Latent tuberculosis infection (LTBI) is common in people living with HIV (PLHIV) in high-TB-burden settings. Active TB is associated with specific stool taxa; however, little is known about the stool microbiota and LTBI in PLHIV. We characterised the stool microbiota of PLHIV with [interferon-γ release assay (IGRA)- and tuberculin skin test (TST)-positive] or without (IGRA- and TST-negative) LTBI (n = 25 per group). The 16S rRNA DNA sequences were analysed using QIIME2, Dirichlet-Multinomial Mixtures, DESeq2, and PICRUSt2. No α- or β-diversity differences occurred by LTBI status; however, LTBI-positive people were Faecalibacterium-, Blautia-, Gemmiger-, and Bacteroides-enriched and Moryella-, Atopobium-, Corynebacterium-, and Streptococcus-depleted. Inferred metagenome data showed that LTBI-negative-enriched pathways included several metabolite degradation pathways. Stool from LTBI-positive people demonstrated differential taxa abundance based on a quantitative response to antigen stimulation. In LTBI-positive people, older people had different β-diversities than younger people, whereas in LTBI-negative people, no differences occurred across age groups. Amongst female PLHIV, those with LTBI were, vs. those without LTBI, Faecalibacterium-, Blautia-, Gemmiger-, and Bacteriodes-enriched, which are producers of short-chain fatty acids. Taxonomic differences amongst people with LTBI occurred according to quantitative response to antigen stimulation and age. These data enhance our understanding of the microbiome's potential role in LTBI.

Limited usefulness of the IS6110 touchdown-PCR in blood for tuberculin skin test false-negative cattle with serological response to Mycobacterium bovis.

Ante-mortem diagnosis of bovine tuberculosis (bTB) is based mainly on the tuberculin skin test (TST) and the ɣ-IFN release assay (IGRA). Some infected animals escape screening tests, thus, limit herd sanitation. Previous reports have suggested a predominant pattern of multi-organ lesions attributable to Mycobacterium bovis (the causative agent of bTB) bacteraemia. A case-control study was conducted to investigate blood PCR as an alternative tool for improving ante-mortem detection of TST false-negative bovines. Cases comprised 70 TST false-negative bovines (cases), which were serology positive, and controls included 81 TST positive bovines; all of them confirmed as infected with M. bovis. Detection of the IS6110 target through touchdown blood-PCR (IS6110 TD-PCR) was performed. The positivity of the blood-PCR was 27.2% in the control group. This performance was similar to the 15% obtained among cases (p = 0.134). Most cases identified by the IS6110 TD-PCR exhibited focalized lesions (p = 0.002). Results demonstrated that blood-PCR could detect TST false-negative cattle, even if they are negative for IGRA. Considering that cases exhibited humoral response to M. bovis, further studies conducted in a pre-serological stage could provide evidence about the real contribution of the technique in herds.

Evaluating Treatment Outcomes and Tuberculosis Infection Risks: A Comparative Study of Centralized Hospitalization vs. Home-Based Treatment.

Background: Guizhou Province in Southwest China has experimented with a centralized hospitalization (CH) treatment for active and severe cases of pulmonary tuberculosis (PTB). The objective of this study was to compare treatment outcomes of patients with tuberculosis (TB) receiving care in a CH setting with those receiving home-based (HB) care. In addition, this study aimed to assess the probability of their household contacts contracting tuberculosis infection. Method: A retrospective review of medical records was undertaken for patients with TB who completed their treatment in four counties in Guizhou, China, spanning from January 2022 to August 2023. In addition, a cross-sectional survey was conducted on the tuberculin skin test (TST) among household contacts of new patients with TB who had completed their treatment. Results: In the retrospective study, 94.8% had successful CH treatment, and 93.1% had successful HB treatment (p value = 0.70). In the prospective study, 559 and 448 household contacts of patients receiving CH treatment had 16 positive and 89 negative TST results, whereas those with HB treatment showed 26 positive and 74 negative TST results. Regarding a logistic regression analysis, the CH group was nearly two times more likely to test negative on the TST, 1.95 (95% CI: 0.98, 3.92). After adjusting for confounding variables, the odds ratio increased significantly to 4.42 (95% CI: 1.22, 16.04). Conclusions: CH for treatment of TB did not show superior success rates, but it may reduce the risk of transmitting tuberculosis infection to household contacts compared to home treatment.

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.

Feature fusion method for pulmonary tuberculosis patient detection based on cough sound.

Since the COVID-19, cough sounds have been widely used for screening purposes. Intelligent analysis techniques have proven to be effective in detecting respiratory diseases. In 2021, there were up to 10 million TB-infected patients worldwide, with an annual growth rate of 4.5%. Most of the patients were from economically underdeveloped regions and countries. The PPD test, a common screening method in the community, has a sensitivity of as low as 77%. Although IGRA and Xpert MTB/RIF offer high specificity and sensitivity, their cost makes them less accessible. In this study, we proposed a feature fusion model-based cough sound classification method for primary TB screening in communities. Data were collected from hospitals using smart phones, including 230 cough sounds from 70 patients with TB and 226 cough sounds from 74 healthy subjects. We employed Bi-LSTM and Bi-GRU recurrent neural networks to analyze five traditional feature sets including the Mel frequency cepstrum coefficient (MFCC), zero-crossing rate (ZCR), short-time energy, root mean square, and chroma_cens. The incorporation of features extracted from the speech spectrogram by 2D convolution training into the Bi-LSTM model enhanced the classification results. With traditional futures, the best TB patient detection result was achieved with the Bi-LSTM model, with 93.99% accuracy, 93.93% specificity, and 92.39% sensitivity. When combined with a speech spectrogram, the classification results showed 96.33% accuracy, 94.99% specificity, and 98.13% sensitivity. Our findings underscore that traditional features and deep features have good complementarity when fused using Bi LSTM modelling, which outperforms existing PPD detection methods in terms of both efficiency and accuracy.

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.

Attenuated tuberculin skin test responses associated with Mycobacterium intracellulare sputum colonization in an adolescent TB prevalence survey in Western Kenya

IntroductionExposure to Non-tuberculous Mycobacteria (NTM) varies regionally and may partly explain the disparate outcomes of BCG vaccination and tuberculosis (TB) susceptibility. MethodsWe examined NTM sputum colonization, associations with clinical characteristics, and tuberculin skin test (TST) responses in an adolescent TB prevalence survey. ResultsAmong 5004 adolescents screened, 2281 (45.5 %) were evaluated further. TB and NTM prevalence rates were 0.3 % and 8.0 %, respectively. Among 418 NTM isolates, 103 were unidentifiable, and 315 (75 %) comprised 15 species, the most frequent being M. intracellulare (MAC) (108, 26 %), M. scrofulaceum (96, 23 %) and M. fortuitum (51, 12 %). “NTM colonized” adolescents had less frequent chronic cough and night sweats (adjusted odds ratio [aOR] 0.62, 95 % confidence interval [CI] 0.44-0.87and aOR 0.61, CI 0.42–0.89 respectively), and lower TST induration (median 11 mm (interquartile range [IQR] 0–16) vs 13 mm (IQR 6–17; p = 0.006)) when compared to “NTM not colonized” participants. MAC, but not M. scrofulaceum or M. fortuitum, was associated with decreased TST induration (median 7.5 mm (IQR 0–15) vs 13 mm (IQR 6–17) among “MAC colonized” vs “not colonized”, p = 0.001). ConclusionWe observed high NTM prevalence rates with species-specific associations with TST induration, consistent with a model of species-dependent heterologous immunity among mycobacteria.

Latent tuberculosis diagnostics: current scenario and review.

This review presents a comprehensive examination of the contemporary landscape pertaining to latent tuberculosis infection (LTBI) diagnostics, with a particular emphasis on the global ramifications and the intricacies surrounding LTBI diagnosis and treatment. It accentuates the imperative of bolstering diagnostic, preventive, and treatment modalities for tuberculosis (TB) to fulfill the ambitious targets set forth by the World Health Organization aimed at reducing TB-related mortalities and the incidence of new TB cases. The document underscores the significance of addressing LTBI as a means of averting the progression to active TB, particularly in regions burdened with high TB prevalence, such as India. An in-depth analysis of the spectrum delineating latent and active TB disease is provided, elucidating the risk factors predisposing individuals with LTBI to progress towards active TB, including compromised immune functionality, concurrent HIV infection, and other immunosuppressive states. Furthermore, the challenges associated with LTBI diagnosis are elucidated, encompassing the absence of a definitive diagnostic assay, and the merits and demerits of tuberculin skin testing (TST) and interferon-γ release assays (IGRAs) are expounded upon. The document underscores the necessity of confronting these challenges and furnishes a meticulous examination of the advantages and limitations of TST and IGRAs, along with the intricacies involved in interpreting their outcomes across diverse demographics and settings. Additionally, attention is drawn towards the heritability of the interferon-γ response to mycobacterial antigens and the potential utility of antibodies in LTBI diagnosis.

Latent Tuberculosis Infection Management in Solid Organ Transplantation Recipients: A National Snapshot.

Latent tuberculosis infection (LTBI) screening is strongly recommended in the pre-transplant evaluation of solid organ transplant (SOT) recipients, although it remains inadequate in many transplant centers. We decided to investigate pre-transplant TB risk assessment, LTBI treatment, and registry rates in Turkey. Adult SOT recipients who underwent tuberculin skin test (TST) and/or interferon-gamma release test (IGRA) from 14 centers between 2015 and 2019 were included in the study. An induration of ≥5 mm on TST and/or probable/positive IGRA (QuantiFERON-TB) was considered positive for LTBI. Demographic features, LTBI screening and treatment, and pre-/post-transplant TB history were recorded from the electronic database of transplantation units across the country and pooled at a single center for a unified database. TST and/or IGRA were performed in 766 (33.8%) of 2266 screened patients most of whom were kidney transplant recipients (n= 485, 63.4%). LTBI screening test was positive in 359 (46.9%) patients, and isoniazid was given to 203 (56.5%) patients. Of the patients treated for LTBI, 112 (55.2%) were registered in the national registry, and 82 (73.2%) completed the treatment. Tuberculosis developed in 6 (1.06%) of 563 patients who were not offered LTBI treatment. We determined that overall, only one-third of SOT recipients in our country were evaluated in terms of TB risk, only 1 of the 2 SOT recipients with LTBI received treatment, and half were registered. Therefore, we want to emphasize the critical importance of pretransplant TB risk stratification and registration, guided by revised national guidelines.

Diagnostic accuracy of the Enferplex Bovine TB antibody test using individual milk samples from cattle.

Bovine tuberculosis is usually diagnosed using tuberculin skin tests or at post-mortem. Recently, we have developed a serological test for bovine tuberculosis in cattle which shows a high degree of accuracy using serum samples. Here, we have assessed the performance of the test using individual bovine milk samples. The diagnostic specificity estimate using the high sensitivity setting of the test was 99.7% (95% CI: 99.2-99.9). This estimate was not altered significantly by tuberculin boosting. The relative sensitivity estimates of the test using the high sensitivity setting in milk samples from comparative skin test positive animals was 90.8% (95% CI: 87.1-93.6) with boosting. In animals with lesions, the relative sensitivity was 96.0% (95% CI: 89.6-98.7). Analysis of paired serum and milk samples from skin test positive animals showed correlation coefficients ranging from 0.756-0.955 for individual antigens used in the test. Kappa analysis indicated almost perfect agreement between serum and milk results, while McNemar marginal homogeneity analysis showed no statistically significant differences between the two media. The positive and negative likelihood ratio were 347.8 (95% CI: 112.3-1077.5) and 0.092 (95% CI: 0.07-0.13) respectively for boosted samples from skin test positive animals. The results show that the test has high sensitivity and specificity in individual milk samples and thus milk samples could be used for the diagnosis of bovine tuberculosis.

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.

The role of phenotypic factors in predicting the effectiveness of chemoprophylaxis in children

Background. The purpose was to study the prognostic role of some phenotypic factors in the effectiveness of tuberculosis chemoprophylaxis in children at present stage. Materials and methods. To study the role of phenotypic factors in predic­ting the effectiveness of tuberculosis chemoprophylaxis, an analysis was performed of dermatoglyphic indicators, gender, and the inactivation phenotype of isonicotinic acid hydrazide (IAH) in 76 children with tuberculin skin test conversion who underwent a 3-month course of preventive therapy with isoniazid. Dermatoglyphics of fingers and palms was determined according to the standard method [5]. The dynamics of skin sensitivity to tuberculin PPD-L according to the Mantoux test with 2 tuberculin units was used as a criterion for the effectiveness of chemoprophylaxis. According to the latter, the examinees were divided into two groups: the first one consisted of 52 children in whom the size of a wheal decreased by 4 mm or more after the end of a course (effective chemoprevention); the second one included 24 patients in whom skin sensitivity to tuberculin increased or remained at the previous level or decreased by a wheal size for 3 mm or less (ineffective chemoprevention). Results. The conducted statistical analysis revealed a significant difference in 7 indicators between the groups (p &lt; 0.05). Determination of their prognostic informativeness made it possible to rank the prognostic significance of phenotypic signs, namely: the size of the atd angle on the left palm (J = 1.7), the number of ulnar loops on the right hand (J = 1.4), the type of IAH inactivation (J = 1.3), the number of whorls on the right hand (J = 1.2), the total number of whorls (J = 1.1), the atd angle on the right palm (J = 0.7), the number of whorls on the left hand (J = 0.5). The correlation analysis between the dermatoglyphic indicators and the type of IAH inactivation showed that there are reliable connections between them (p &lt; 0.05), but their number differs significantly in groups. In patients with ineffective chemoprophylaxis, the number of correlations (n = 13) exceeded that of the alternative group (n = 2) by more than 6 times, which indicates significant structural phenotypic differences. Conclusions. There were significant correlations between the type of IAH inactivation and dermatoglyphic indicators, but the number of such connections was 6 times higher in children with ineffective chemoprophylaxis than in the alternative group. This indicates that a more pronounced integration of dermatoglyphic genes and the ability to neutralize IAH is a favorable moment in general, but negative in relation to the effectiveness of tuberculosis prevention.

Navigating the complexities: a case report on the varied presentation of lupus vulgaris

A 16-year-old female presented with an asymptomatic lesion in the right axilla, evolving over six months into a scaly, erythematous to brownish-colored plaque with associated axillary lymphadenopathy. Routine investigations revealed mild anemia, elevated erythrocyte sedimentation rate (ESR), and a positive Mantoux test. Histopathological examination confirmed lupus vulgaris, characterized by tuberculoid granulomas within the superficial dermis. Treatment with anti-tubercular therapy led to significant lesion improvement. Lupus vulgaris, a form of cutaneous tuberculosis, presents varied clinical features and poses diagnostic challenges. Early recognition and prompt treatment are essential to prevent morbidity and scarring. This case highlights the importance of considering lupus vulgaris in differential diagnosis of atypical cutaneous lesions, contributing to better disease management and reduced morbidity.

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.

Pott’s disease and scrofuloderma as presentation of clinically extrapulmonary tuberculosis in 15 years old girl: a case report

Backgrounds: Extrapulmonary tuberculosis (TB) accounts for 15–20% of all tuberculosis cases, with the lymph node being the most commonly affected organ. Spinal tuberculosis and scrofuloderma are rare manifestations of extrapulmonary TB and constitute less than 5% of the cases. Establishing the diagnosis is a challenge. Eradication and prevention of sequelae complicate further management of the disease. This study aims to describe the clinical manifestation and the management of spondylitis tuberculosis and scrofuloderma in a child. Case presentation: A 15-year-old girl came with a chief complaint of lower extremities weakness for a week following monthly chronic low back pain. She also reported a painless lesion on her back with no sign of acute inflammation. She also complained of intermittent fever with night sweats and lost 3 kilos of body weight in the last two months. From physical examination, we found a kyphotic posture and severe malnutrition. Skin examination revealed an open wound on her right lower back, size 4x3 cm, with no sign of inflammation. The tuberculin skin test was positive with 15 mm induration. The spinal magnetic resonance imaging revealed destruction of the vertebral corpus thoracal segment, hyperintense sacrum, and right ileum bone with a cold abscess, suggesting spondylitis TB. A wound biopsy with hematoxylin-eosin stain concluded chronic granulomatous inflammation and showed multinucleated giant cell Langhans-type, suggestive of cutaneous tuberculosis. Microbiology examination (PCR GeneXpert) from wound biopsy and ziehl neelsen stain failed to detect Mycobacterium tuberculosis. The patient was diagnosed with Pott’s disease and scrofuloderma. Anti-tuberculous therapy commenced, and the patient responded well after several months of treatment. Conclusions: The diagnosis of extrapulmonary TB manifests as spinal tuberculosis, and scrofuloderma could be made from clinical manifestation and imaging.

A Rare Presentation - Case Report on Tubercular Cold Abscess

Tuberculosis is a chronic granulomatous infection that is quite common and a threat to many developing countries. However, extrapulmonary cases involving tubercular skin and soft tissue abscess formation are rare, accounting for 1 or 2% of cases of Mycobacterium TB infections with skin and soft tissue involvement. The typical extrapulmonary tuberculosis symptoms and indications are nonspecific, making diagnosis difficult and time-consuming. We present a case of right arm tubercular cold abscess in a child related to mycobacterium tuberculosis, which was diagnosed by Ziehl- Neelson stain FNAC (Fine needle Aspiration cytology) and Mantoux test (18mm) induration. Due to its rare manifestation, it often gets misdiagnosed or overlooked. A proper diagnosis will ensure a proper treatment plan. Our case further depicts the collaborative effort of healthcare professionals. The patient came back complaining about the increased swelling in his right arm.&#x0D; Keywords: Tubercular Cold Abscess, Ziehl- Neelson, Fine needle Aspiration cytology, Mantoux test, Mycobacterium Tuberculosis

Capturing Recent Mycobacterium tuberculosis Infection by Tuberculin Skin Test vs. Interferon-Gamma Release Assay.

Reductions in tuberculosis (TB) incidence require identification of individuals at high risk of developing active disease, such as those with recent Mycobacterium tuberculosis (Mtb) infection. Using a prospective household contact (HHC) study in Kampala, Uganda, we diagnosed new Mtb infection using both the tuberculin skin test (TST) and interferon-gamma release assay (IGRA). Our study aimed to determine if the TST adds additional value to the characterization of IGRA converters. We identified 13 HHCs who only converted the IGRA (QFT-only converters), 39 HHCs who only converted their TST (TST-only converters), and 24 HHCs who converted both tests (QFT/TST converters). Univariate analysis revealed that TST-only converters were older. Additionally, increased odds of TST-only conversion were associated with older age (p = 0.02) and crowdedness (p = 0.025). QFT/TST converters had higher QFT quantitative values at conversion than QFT-only converters and a bigger change in TST quantitative values at conversion than TST-only converters. Collectively, these data indicate that TST conversion alone likely overestimates Mtb infection. Its correlation to older age suggests an "environmental" boosting response due to prolonged exposure to environmental mycobacteria. This result also suggests that QFT/TST conversion may be associated with a more robust immune response, which should be considered when planning vaccine studies.

Incipient tuberculosis: a comprehensive overview.

In the context of the evolving global health landscape shaped by the COVID-19 pandemic, tuberculosis (TB) is gaining renewed attention as a reemerging threat even in low-endemic countries. Immunological tests such as the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) are pivotal in identifying tuberculosis infection (TBI). However, their inability to distinguish between past and ongoing infection poses a diagnostic challenge, possibly leading to the unnecessary treatment of a significant portion of the population with potential side effects. This review delves into the concept of incipient tuberculosis (ITB), a dynamic, presymptomatic stage characterized by heightened Mycobacterium tuberculosis complex (MTC) metabolic activity and replication that result in minimal radiological changes, signifying a transitional state between TBI and TB. Key focus areas include epidemiological factors, underlying pathogenesis, imaging findings, and the ongoing challenges in the identification of individuals with ITB through the development of new biomarkers and the use of whole-genome sequencing-based analyses to implement early treatment strategies.

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.