Is the new tuberculous antigen-based skin test ready for use as an alternative to tuberculin skin test/interferon-gamma release assay for tuberculous diagnosis? A narrative review.

In recent years, novel specific Mycobacteria tuberculous (TB) antigen-based skin test (TBST) has become available for clinical use. The mechanism of TBST is similar to the interferon-gamma release assay (IGRA), making it a potential alternative for identifying latent tuberculous infection (LTBI), especially in subjects with history of bacille Calmette-Guérin vaccination. Three different commercial brands have been developed in Denmark, Russia, and China. Clinical studies in the respective countries have shown promising sensitivity, specificity, and safety profile. Some studies attempted to address the applicability of TBST in specific subject groups but the discrepancy in defining LTBI and problematic methodologies undermine the generalisation of the results to other communities across the world. Limited cost-effectiveness studies for TBST have been conducted without exploring the health economics for preventing development of LTBI into active TB. Unlike IGRA, no clinical studies have addressed the correlation of TBST results (magnitude of induration) with the likelihood of development of active TB. Moreover, the different TBSTs are not widely available for clinical use. While TBST is a promising test to overcome the shortcomings of tuberculin skin tests, more clinical data are needed to support its general application globally for the diagnosis of LTBI.

[Lung pathology in post-covid syndrome]. / Patologiya legkikh pri postkovidnom sindrome.

The clinic and pathological anatomy of the infection caused by the SARS-CoV-2 virus (coronavirus infection - CI) with the development of Post-Covid syndrome (PS) have not been studied enough. This also applies to morphofunctional changes in the lungs, one of the most important components of PS. We conducted a histological and bacterioscopic study of lung biopsy specimens in 20 patients of both sexes aged 22-75 years. In many patients, PS developed relatively late - not earlier than 1 year - 1 year 4 months after the onset of acute clinical symptoms of CI. Structural changes in the lungs in PS appear as an inflammatory reaction such as interstitial pneumonia. Most patients had nonspecific interstitial pneumonia with elements of organizing interstitial pneumonia, in some cases complicated by the presence of a specific granulomatous reaction, characteristic of pulmonary tuberculosis. Despite this, according to the results of traditional bacterioscopic and bacteriological studies, the tuberculous etiology of pulmonary fibrosis has not yet been confirmed. Perhaps this is due to the fact that we are talking about an inapparent tuberculosis infection, the causative agent of which is the L-form of Mycobacterium tuberculosis. Patients with PS who have pulmonary fibrosis on x-ray should be under the special supervision of a phthisiatrician or pulmonologist.

Necesidad de la determinación inmunológica del Quantiferon (Interferón-gamma Relase-Assay) para el diagnóstico de la Infección Tuberculosa latente / Need for immunological determination of Quantiferon (Interferon-gamma Relase-Assay) for the diagnosis of latent tuberculous infection

Introducción: La tuberculosis es un importante problema de salud pública, primera causa de muerte en adultos contagiados de un solo agente infeccioso. Diferenciaremos enfermedad tuberculosa activa de Infección Tuberculosa Latente. El control biológico del examen inicial de salud establece si el trabajador es portador de ITL para diferenciarlo de un posible contagio posterior con motivo del trabajo. Objetivos: Objetivo general estimar la validez del Mantoux/Booster y Quantiferon como pruebas diagnósticas de la ITL. Objetivo específico definir los casos diagnosticados como ITL. Material y Métodos: Recogida de datos de las historias clínico-laborales del personal de nueva incorporación, del Área de Salud de Zamora, años 2018-2021, se importan a una base de datos, se realiza estudio descriptivo cualitativo/cuantitativo. Resultados: De los trabajadores estudiados son tuberculina positivos el 29’1%; siendo Quantiferón positivos el 10’3%. Diagnosticamos 159 casos de ITL. Conclusión: La técnica más precisa para diagnosticar la ITL es la determinación del Quantiferón. (AU)

Introduction: Tuberculosis is a major public health problem, first cause of death in adults infected with a single infectious agent. We will differentiate active tuberculosis disease from latent tuberculosis infection. The biological control of the initial health examination establishes whether the worker is a carrier of LTTI to differentiate him/her from a possible subsequent contagion at work. Objectives: General objective to estimate the validity of Mantoux/Booster and Quantiferon as diagnostic tests for LTTI. Specific objective: To define the cases diagnosed as ITL. Material and Methods: Collection of data from the clinical-work histories of newly hired personnel, from the Zamora Health Area, years 2018-2021, imported into a database, qualitative/quantitative descriptive study is performed. Results: 29.1% of the workers studied were tuberculin positive; 10.3% were Quantiferon positive. We diagnosed 159 cases of ITL. Conclusion: The most accurate technique to diagnose ITL is the determination of Quantiferon. (AU)

A change in the timing of the Bacillus Calmette-Guérin vaccination in 2013 was associated with an increase in the incidence rate of infants with latent tuberculosis infection.

BACKGROUND: A change in the timing of the Bacillus Calmette-Guérin (BCG) vaccination among infants in Japan appears to be associated with an increase in the incidence rate of latent tuberculosis infection (LTBI). METHODS: Data on both active and latent tuberculosis (TB) infections from 2007 to 2019, which were reported by the Japan Anti-Tuberculosis Association, were statistically analyzed by comparing TB incidence rates in 2007-2012 and 2013-2019. RESULTS: Although the incidence rate for active TB disease did not statistically increase nor decrease in the infant age group for either sex (and in fact decreased for some of the other age groups), the incidence rates of LTBI for both sexes were increased in the infant age group, while the incidence rates decreased in the other age groups. Between 2007 and 2012, the incidence rate of LTBI in females was statistically greater than those of males in the 1-4-year-old age group. From 2013 to 2019, the incidence rates of females were greater than those of males in both the infant and 1-4-year-old age groups, suggesting a growing preponderance of infections among female children in the youngest age groups. CONCLUSION: It may be that the change of BCG vaccination timing in Japan which took place in 2013 affected the infant incidence rate of LTBI, with a more prominent effect on females than males. In order to control TB infection, the ramifications of a change in vaccination timing therefore need careful exploration, as one such change appears associated with increased numbers of infants with LTBI, with disproportionate effects on females.

Diagnóstico de la infección tuberculosa en pacientes inmunodeprimidos y/o candidatos a terapias biológicas mediante el uso combinado de dos pruebas IGRA: T-SPOT.TB/QuantiFERON TB Gold In-Tube vs. T-SPOT.TB/QuantiFERON TB Gold Plus / Diagnosis of Tuberculous Infection in Immunosuppressed Patients and/or Candidates for Biologics Using a Combination of 2 IGRA Tests: T-SPOT.TB/QuantiFERON TB Gold In-Tube vs. T-SPOT.TB/QuantiFERON TB Gold Plus

Introducción: El diagnóstico de la infección tuberculosa latente (ITL) mediante IGRA sigue generando debate. La experiencia empleando dos pruebas IGRA de manera simultánea es escasa. El objetivo de este estudio es comparar los resultados de dos versiones de QuantiFERON-TB Gold (In-Tube/Plus) con los de T-SPOT.TB y analizar la eficacia de esta estrategia dual (T-SPOT.TB + QTF) para el diagnóstico de la ITL en población con alguna condición inmunosupresora.Métodos: Estudio prospectivo (mayo 2015-junio 2017) que incluye 2.999 pacientes inmunodeprimidos y/o candidatos a terapias biológicas, a los que se les realizó de manera simultánea dos IGRA: grupo-1 (1.535 pacientes): T-SPOT.TB + QuantiFERON-TB Gold-In-Tube (QTF-GIT); grupo-2 (1.464 pacientes): T-SPOT.TB + QuantiFERON-TB Gold Plus (QTF-Plus).Resultados: La concordancia entre QTF-GIT y T-SPOT.TB fue del 83,19% (κ = 0,532). Las proporciones de resultados positivos, negativos e indeterminados fueron, respectivamente: 14,33 vs. 17,06%; 82,41 vs. 74,46%; y 3,25 vs. 8,46%. La concordancia entre QTF-Plus y T-SPOT.TB fue del 87,56% (κ=0,609). Las proporciones de resultados positivos, negativos e indeterminados fueron, respectivamente: 15,02 vs. 15,36%; 82,92 vs. 79,37%; y 2,04 vs. 5,25%. Las discordancias entre T-SPOT.TB y QTF-Plus fueron del 12,43%, que implicaban que había 103 pacientes positivos y otros 79 pacientes negativos a expensas exclusivamente de uno de los dos IGRA.Conclusiones: Se evidenció una mayor concordancia entre QTF-Plus y T-SPOT.TB que entre QTF-GIT y T-SPOT.TB. Sin embargo, creemos que la proporción de resultados discordantes entre T-SPOT.TB y QTF-Plus es lo suficientemente relevante clínicamente como para justificar el empleo simultáneo de dos IGRA en este grupo específico de pacientes. (AU)

Introduction: The diagnosis of latent tuberculous infection (LTI) by IGRA continues to generate debate. Experience in the simultaneous use of 2 IGRA tests is scant. The aim of this study was to compare the results of 2 versions of QuantiFERON-TB Gold (In-Tube/Plus) with those of T-SPOT.TB, and to analyse the effectiveness of a dual strategy (T-SPOT.TB + QTF) for the diagnosis of LTI in an immunosuppressed population.Methods: We conducted a prospective study (May 2015-June 2017) that included 2,999 immunosuppressed patients and/or candidates for biologics, in whom 2 simultaneous IGRA tests were performed: Group 1 (1535 patients): T-SPOT.TB + QuantiFERON-TB Gold-In-Tube (QTF-GIT); Group 2 (1464 patients): T-SPOT.TB + QuantiFERON-TB Gold Plus (QTF-Plus).Results: The concordance between QTF-GIT and T-SPOT.TB was 83.19% (κ=0.532). The percentage of positive, negative, and indeterminate results were, respectively: 14.33% vs. 17.06%; 82.41% vs. 74.46%; and 3.25% vs. 8.46%. The concordance between QTF-Plus and T-SPOT.TB was 87.56% (κ=0.609). The percentage of positive, negative, and indeterminate results were, respectively: 15.02% vs. 15.36%; 82.92% vs. 79.37%; and 2.04% vs. 5.25%. Discrepancies between T-SPOT.TB and QTF-Plus were 12.43%, suggesting that 103 patients were positive and another 79 were negative due exclusively to 1 of the 2 IGRAs.Conclusions: Greater concordance was found between QTF-Plus and T-SPOT.TB than between QTF-GIT and T-SPOT.TB. However, we believe that the proportion of discrepancies between T-SPOT.TB and QTF-Plus is sufficiently important from a clinical point of view to justify the simultaneous use of 2 IGRA in this specific patient group. (AU)

[Translated article] Diagnosis of tuberculous infection in immunosuppressed patients and/or candidates for biologics using a combination of 2 IGRA tests: T-SPOT.TB/QuantiFERON TB Gold In-Tube vs. T-SPOT.TB/QuantiFERON TB Gold Plus / Diagnóstico de la infección tuberculosa en pacientes inmunodeprimidos y/o candidatos a terapias biológicas mediante el uso combinado de dos pruebas IGRA: T-SPOT.TB/QuantiFERON TB Gold In-Tube vs. T-SPOT.TB/QuantiFERON TB Gold Plus

Introduction: The diagnosis of latent tuberculous infection (LTI) by IGRA continues to generate debate. Experience in the simultaneous use of 2 IGRA tests is scant. The aim of this study was to compare the results of 2 versions of QuantiFERON-TB Gold (In-Tube/Plus) with those of T-SPOT.TB, and to analyse the effectiveness of a dual strategy (T-SPOT.TB + QTF) for the diagnosis of LTI in an immunosuppressed population.Methods: We conducted a prospective study (May 2015-June 2017) that included 2,999 immunosuppressed patients and/or candidates for biologics, in whom 2 simultaneous IGRA tests were performed: Group 1 (1535 patients): T-SPOT.TB + QuantiFERON-TB Gold-In-Tube (QTF-GIT); Group 2 (1464 patients): T-SPOT.TB + QuantiFERON-TB Gold Plus (QTF-Plus).Results: The concordance between QTF-GIT and T-SPOT.TB was 83.19% (κ=0.532). The percentage of positive, negative, and indeterminate results were, respectively: 14.33% vs. 17.06%; 82.41% vs. 74.46%; and 3.25% vs. 8.46%. The concordance between QTF-Plus and T-SPOT.TB was 87.56% (κ=0.609). The percentage of positive, negative, and indeterminate results were, respectively: 15.02% vs. 15.36%; 82.92% vs. 79.37%; and 2.04% vs. 5.25%. Discrepancies between T-SPOT.TB and QTF-Plus were 12.43%, suggesting that 103 patients were positive and another 79 were negative due exclusively to 1 of the 2 IGRAs.Conclusions: Greater concordance was found between QTF-Plus and T-SPOT.TB than between QTF-GIT and T-SPOT.TB. However, we believe that the proportion of discrepancies between T-SPOT.TB and QTF-Plus is sufficiently important from a clinical point of view to justify the simultaneous use of 2 IGRA in this specific patient group. (AU)

Introducción: El diagnóstico de la infección tuberculosa latente (ITL) mediante IGRA sigue generando debate. La experiencia empleando dos pruebas IGRA de manera simultánea es escasa. El objetivo de este estudio es comparar los resultados de dos versiones de QuantiFERON-TB Gold (In-Tube/Plus) con los de T-SPOT.TB y analizar la eficacia de esta estrategia dual (T-SPOT.TB + QTF) para el diagnóstico de la ITL en población con alguna condición inmunosupresora.Métodos: Estudio prospectivo (mayo 2015-junio 2017) que incluye 2.999 pacientes inmunodeprimidos y/o candidatos a terapias biológicas, a los que se les realizó de manera simultánea dos IGRA: grupo-1 (1.535 pacientes): T-SPOT.TB + QuantiFERON-TB Gold-In-Tube (QTF-GIT); grupo-2 (1.464 pacientes): T-SPOT.TB + QuantiFERON-TB Gold Plus (QTF-Plus).Resultados: La concordancia entre QTF-GIT y T-SPOT.TB fue del 83,19% (κ = 0,532). Las proporciones de resultados positivos, negativos e indeterminados fueron, respectivamente: 14,33 vs. 17,06%; 82,41 vs. 74,46%; y 3,25 vs. 8,46%. La concordancia entre QTF-Plus y T-SPOT.TB fue del 87,56% (κ=0,609). Las proporciones de resultados positivos, negativos e indeterminados fueron, respectivamente: 15,02 vs. 15,36%; 82,92 vs. 79,37%; y 2,04 vs. 5,25%. Las discordancias entre T-SPOT.TB y QTF-Plus fueron del 12,43%, que implicaban que había 103 pacientes positivos y otros 79 pacientes negativos a expensas exclusivamente de uno de los dos IGRA.Conclusiones: Se evidenció una mayor concordancia entre QTF-Plus y T-SPOT.TB que entre QTF-GIT y T-SPOT.TB. Sin embargo, creemos que la proporción de resultados discordantes entre T-SPOT.TB y QTF-Plus es lo suficientemente relevante clínicamente como para justificar el empleo simultáneo de dos IGRA en este grupo específico de pacientes. (AU)

Diagnosis of Tuberculous Infection in Immunosuppressed Patients and/or Candidates for Biologics Using a Combination of 2 IGRA Tests: T-SPOT.TB/QuantiFERON TB Gold In-Tube vs. T-SPOT.TB/QuantiFERON TB Gold Plus. / Diagnóstico de la infección tuberculosa en pacientes inmunodeprimidos y/o candidatos a terapias biológicas mediante el uso combinado de dos pruebas IGRA: T-SPOT.TB/QuantiFERON TB Gold In-Tube vs. T-SPOT.TB/QuantiFERON TB Gold Plus.

INTRODUCTION: The diagnosis of latent tuberculous infection (LTI) by IGRA continues to generate debate. Experience in the simultaneous use of 2 IGRA tests is scant. The aim of this study was to compare the results of 2 versions of QuantiFERON-TB Gold (In-Tube/Plus) with those of T-SPOT.TB, and to analyse the effectiveness of a dual strategy (T-SPOT.TB + QTF) for the diagnosis of LTI in an immunosuppressed population. METHODS: We conducted a prospective study (May 2015-June 2017) that included 2,999 immunosuppressed patients and/or candidates for biologics, in whom 2 simultaneous IGRA tests were performed: Group 1 (1535 patients): T-SPOT.TB + QuantiFERON-TB Gold-In-Tube (QTF-GIT); Group 2 (1464 patients): T-SPOT.TB + QuantiFERON-TB Gold Plus (QTF-Plus). RESULTS: The concordance between QTF-GIT and T-SPOT.TB was 83.19% (κ=0.532). The percentage of positive, negative, and indeterminate results were, respectively: 14.33% vs. 17.06%; 82.41% vs. 74.46%; and 3.25% vs. 8.46%. The concordance between QTF-Plus and T-SPOT.TB was 87.56% (κ=0.609). The percentage of positive, negative, and indeterminate results were, respectively: 15.02% vs. 15.36%; 82.92% vs. 79.37%; and 2.04% vs. 5.25%. Discrepancies between T-SPOT.TB and QTF-Plus were 12.43%, suggesting that 103 patients were positive and another 79 were negative due exclusively to 1 of the 2 IGRAs. CONCLUSIONS: Greater concordance was found between QTF-Plus and T-SPOT.TB than between QTF-GIT and T-SPOT.TB. However, we believe that the proportion of discrepancies between T-SPOT.TB and QTF-Plus is sufficiently important from a clinical point of view to justify the simultaneous use of 2 IGRA in this specific patient group.

Screening of Latent Tuberculous Infection (LTBI) before Starting Anti-Tumor Necrosis Factor Therapy in Patients with Psoriasis: A Primer for Clinical Dermatologist.

Anti-tumor necrosis agents are being increasingly used in the management of moderate to severe psoriasis. Therapy with antitumor necrosis factor alpha (TNF-α) agents is being fraught with reactivation of latent tuberculosis infection (LTBI). This paper addresses the intricate relation between LTBI and anti-TNF-α agents and provides working guidelines for screening of LTBI and its management before prescribing anti-TNF-α therapy in patients with psoriasis.

To start or to complete? - Challenges in implementing tuberculosis preventive therapy among people living with HIV: a mixed-methods study from Karnataka, India.

Background: Isoniazid preventive therapy (IPT) has been shown to reduce the risk of tuberculosis (TB) among people living with HIV (PLHIV). In 2017, India began a nationwide roll-out of IPT, but there is a lack of evidence on the implementation and the challenges.Objectives: Among PLHIV newly initiated on antiretroviral therapy (ART) from January 2017 to June 2018, to: (i) assess the proportion who started and completed IPT and (ii) explore reasons for non-initiation and non-completion from health-care providers' and patients' perspectives.Methods: An explanatory mixed-methods study was conducted in two selected districts of Karnataka, South India. A quantitative phase (cohort analysis of routinely collected program data) was followed by a qualitative phase involving thematic analysis of in-depth interviews with providers (n = 22) and patients (n = 8).Results: Of the 4020 included PLHIV, 3780 (94%) were eligible for IPT, of whom, 1496 (40%, 95% CI: 38%-41%) were initiated on IPT. Among those initiated, 423 (28.3%) were still on IPT at the time of analysis. Among 1073 patients with declared IPT outcomes 870 (81%, 95% CI: 79%-83%) had completed the six-month course of IPT. The main reason for IPT non-initiation and non-completion was frequent drug stock-outs. This required health-care providers to restrict IPT initiation in selected patient subgroups and earmark six-monthly courses for each patient to ensure that, once started, treatment was not interrupted. The other reasons for non-completion were adverse drug effects and loss to follow-up.Conclusion: The combined picture of 'low IPT initiation and high completion' seen in our study mirrors findings from other countries. Drug stock-out was the key challenge, which obliged health-care providers to prioritize 'IPT completion' over 'IPT initiation'. There is an urgent need to improve the procurement and supply chain management of isoniazid.

Low prioritization of latent tuberculosis infection-A systemic barrier to tuberculosis control: A qualitative study in Ontario, Canada.

BACKGROUND: Eliminating tuberculosis (TB) in low-incidence countries is an important global health priority, and Canada has committed to achieve this goal. The elimination of TB in low-incidence countries requires effective management and treatment of latent tuberculosis infection (LTBI). This study aimed to understand and describe the system-level barriers to LTBI treatment for immigrant populations in the Greater Toronto and Hamilton Area, Ontario, Canada. METHODS: A qualitative study that used purposive sampling to recruit and interview health system advisors and planners (n = 10), providers (n = 13), and clients of LTBI health services (n = 9). Data were recorded, transcribed verbatim, and analyzed using content analysis. RESULTS: Low prioritization of LTBI was an overarching theme that impacted four dimensions of LTBI care: management, service delivery, health literacy, and health care access. These factors explained, in part, inequities in the system that were linked to variations in health care quality and health care access. While some planners and providers at the local level were attempting to prioritize LTBI care, there was no clear pathway for information sharing. CONCLUSIONS: This multiperspective study identified barriers beyond the typical socioeconomic determinants and highlighted important upstream factors that hinder treatment initiation and adherence. Addressing these factors is critical if Canada is to meet the WHO's global call to eradicate TB in all low incidence settings.

The usefulness of routine chest radiograph examinations in patients treated with TNF inhibitors for inflammatory arthritis in South Korea.

OBJECTIVES: We aimed to investigate the usefulness of routine chest radiograph (CXR) examinations for patients with inflammatory arthritis treated with a tumor necrosis factor (TNF) inhibitor in terms of (i) the role of CXR in baseline latent tuberculosis infection (LTBI) screening and (ii) detecting asymptomatic active tuberculosis after TNF inhibitor initiation. METHODS: From January 2011 to June 2017, 469 patients with inflammatory arthritis were enrolled in the study at a tertiary referral center in South Korea. At our institution, CXR was performed for all patients undergoing a tuberculin skin test (TST) and/or an interferon-gamma release assay (IGRA) at the LTBI screening visit. LTBI treatment was determined by (i) positive TST or IGRA or (ii) CXR findings suggestive of spontaneously healed tuberculosis. After TNF inhibitor initiation, patients were recommended to undergo CXR at a specified interval. RESULTS: Of 469 patients, 187 were treated for LTBI. Among them, 181 patients were treated for LTBI because of a positive TST or IGRA result. TST was considered positive if induration size was ≥10 mm. The remaining six patients were considered positive on the basis of CXR findings compatible with spontaneously healed tuberculosis, such as noncalcified nodules with distinct margins and fibrotic linear opacity, despite demonstrating negative results for TST and IGRA. Thus, CXR had a diagnostic value as a baseline LTBI test in 6 (1.3%) patients. After TNF inhibitor initiation, 2 patients who had respiratory symptoms were diagnosed with active tuberculosis. For asymptomatic patients, routine CXR follow-up could not detect any case of active pulmonary tuberculosis within 1 year (n = 219) or after 1 year (n = 217). CONCLUSIONS: CXR should be performed as one of the LTBI screening tests for patients with inflammatory arthritis in a tuberculosis-prevalent country. However, after TNF inhibitor treatment, routine CXR follow-up was not advantageous.

Epidemiologic Evidence of and Potential Mechanisms by Which Second-Hand Smoke Causes Predisposition to Latent and Active Tuberculosis.

Many studies have linked cigarette smoke (CS) exposure and tuberculosis (TB) infection and disease although much fewer have studied second-hand smoke (SHS) exposure. Our goal is to review the epidemiologic link between SHS and TB as well as to summarize the effects SHS and direct CS on various immune cells relevant for TB. PubMed searches were performed using the key words "tuberculosis" with "cigarette," "tobacco," or "second-hand smoke." The bibliography of relevant papers were examined for additional relevant publications. Relatively few studies associate SHS exposure with TB infection and active disease. Both SHS and direct CS can alter various components of host immunity resulting in increased vulnerability to TB. While the epidemiologic link of these 2 health maladies is robust, more definitive, mechanistic studies are required to prove that SHS and direct CS actually cause increased susceptibility to TB.

Epidemiologic Evidence of and Potential Mechanisms by Which Second-Hand Smoke Causes Predisposition to Latent and Active Tuberculosis

Many studies have linked cigarette smoke (CS) exposure and tuberculosis (TB) infection and disease although much fewer have studied second-hand smoke (SHS) exposure. Our goal is to review the epidemiologic link between SHS and TB as well as to summarize the effects SHS and direct CS on various immune cells relevant for TB. PubMed searches were performed using the key words “tuberculosis” with “cigarette,”“tobacco,” or “second-hand smoke.” The bibliography of relevant papers were examined for additional relevant publications. Relatively few studies associate SHS exposure with TB infection and active disease. Both SHS and direct CS can alter various components of host immunity resulting in increased vulnerability to TB. While the epidemiologic link of these 2 health maladies is robust, more definitive, mechanistic studies are required to prove that SHS and direct CS actually cause increased susceptibility to TB.

Increasing isoniazid preventive therapy uptake in an HIV program in rural Papua New Guinea.

Setting: Tuberculosis (TB) is the leading cause of death among people living with the human immunodeficiency virus (PLHIV) in Papua New Guinea. Despite a policy for isoniazid preventive therapy (IPT) among PLHIV, implementation has been slow. Objective: We prospectively evaluated a standardized guided screening process, including TB diagnostic support, to increase IPT initiation in adult PLHIV on antiretro-viral treatment. Design: The guided process included a paper-based IPT screening tool that prompted review of patient history and TB symptoms and sputum analysis by smear microscopy and Xpert® MTB/RIF. Chest X-ray was performed at the provider's discretion. We quantified the yield of this guided process on IPT initiation and detection of TB and rifampicin resistance, and examined the contributions of each diagnostic modality. Results: Among 532 patients, TB was ruled out and IPT initiated in 450 (84%). TB was diagnosed and treatment was started in 82 (15%) patients. Xpert detected rifampicin resistance in one of 21 patients (5%, 95%CI 0.24-21.3) with a positive Xpert result. All TB cases were diagnosed by chest X-ray and/or Xpert. No cases were diagnosed by sputum smear alone. Conclusion: A standardized guided process, including TB diagnostic support, successfully enabled IPT initiation and identified a large burden of undetected TB.

Contexte : La tuberculose (TB) est la première cause de décès parmi les personnes vivant avec le VIH (PVVIH) en Papouasie Nouvelle Guinée. En dépit d'une politique en faveur du traitement préventif par isoniazide (TPI) parmi les PVVIH, la mise en oeuvre a été lente.Objectif : Nous avons prospectivement évalué un processus de dépistage standardisé guidé, incluant le soutien au diagnostic de la TB, pour augmenter la mise en route du TPI chez les adultes PVVIH sous traitement antirétroviral.Schéma : Le processus guidé a inclus un outil de dépistage sur support papier du TPI qui a suscité la revue des antécédents des patients, les symptômes de TB et l'analyse des crachats par microscopie de frottis et Xpert® MTB/RIF. Une radiographie pulmonaire a été réalisée à la discrétion du prestataire de soins. Nous avons quantifié le rendement de ce processus guidé relatif à la mise en route du TPI et à la détection de la TB et de la résistance à la rifampicine et examiné les contributions de chaque modalité de diagnostic.Résultats : Parmi 532 patients, la TB a été éliminée et le TPI a été initié chez 450 (84%) patients. Une TB a été diagnostiquée et le traitement a été mis en œuvre chez 82 (15%) patients. L'Xpert a détecté la résistance à la rifampicine chez un des 21 patients (5% ; IC95% 0,24­21,3) avec un résultat d'Xpert positif. Tous les cas de TB ont été diagnostiqués par radiographie pulmonaire et/ou Xpert. Aucun cas n'a été diagnostiqué par frottis de crachats seul.Conclusion : Un processus guidé standardisé, incluant la soutien au diagnostic de la TB, a permis la mise en route du TPI et identifié une large charge de TB non détectée.

Marco de referencia: La tuberculosis (TB) es la principal causa de muerte en las personas infectadas por el virus de la inmunodeficiencia humana (VIH) en Papua Nueva Guinea. Pese a las políticas vigentes en materia de tratamiento preventivo con isoniazida (TPI) en las personas afectadas por el VIH, su aplicación ha sido lenta.Objetivo: Se evaluó de manera prospectiva un procedimiento normalizado dirigido de detección sistemática, que comprendía el apoyo al diagnóstico de la TB, con el objeto de aumentar la tasa de iniciación del TPI en los adultos aquejados de infección por el VIH que recibían tratamiento antirretrovírico.Método: El procedimiento dirigido comportaba un instrumento impreso de detección para el TPI, que incitaba la evaluación de los antecedentes del paciente, los síntomas de TB y un análisis del esputo mediante la baciloscopia y la prueba Xpert® MTB/RIF. La radiografía de tórax se practicó según el criterio del profesional de salud. Se cuantificó el efecto de este método dirigido sobre la iniciación del TPI, la detección de la TB y la resistencia a rifampicina y se examinaron además las contribuciones de cada modalidad diagnóstica.Resultados: De los 532 pacientes, en 450 se descartó el diagnóstico de TB y se inició el TPI (84%). Se diagnosticó la TB y se inició el tratamiento a 82 personas (15%). Mediante la prueba Xpert se detectó la resistencia a rifampicina en uno de los 21 pacientes con resultado positivo a esta prueba (5%; intervalo de confianza del 95% de 0,24 a 21,3). Todos los casos de TB se diagnosticaron mediante la radiografía de tórax, la prueba Xpert o ambas. La baciloscopia por sí sola no permitió el diagnostico de ningún caso.Conclusión: Un procedimiento normalizado dirigido, que comportaba apoyo al diagnóstico de la TB, hizo posible la iniciación del TPI y favoreció el reconocimiento de una gran carga de morbilidad por TB no detectada.

Evaluation of tuberculin skin testing in tuberculosis contacts in Victoria, Australia, 2005-2013.

AIM: To review the programmatic use of the tuberculin skin test (TST) following tuberculosis (TB) exposure in Victoria, Australia. METHODS: A retrospective review of data collected for public health surveillance was performed to identify contact demographic factors, including bacille Calmette-Guérin (BCG) status and age and outcomes of TST. RESULTS: Contact tracing was performed for 15 094 people, of whom 13 427 (89.0%) had a TST performed. The TST was positive in 31.4% (95%CI 30.6-32.2) of all contacts, and 48.8% of contacts born outside of Australia. Amongst contacts who were TST-negative at baseline, the conversion rate following exposure was 14.8%. Conversion was most common in those aged 45-54 years, with <12% positivity in both the youngest (<5 years) and oldest (⩾65 years) age groups. Active TB developed in 1.1% of all contacts. Contacts aged <5 years had the highest risk of developing active TB following exposure (3.8%), while low risk was seen in those aged ⩾65 years (0.3%). CONCLUSION: Overall, contact tracing and TST in this setting appear to yield a high proportion of people at risk for the development of active TB. The yield of testing in some groups, particularly those aged ⩾65 years, was low, and investigation of alternative strategies should be considered.

Objectif : Revoir l'utilisation par les programmes du test cutané à la tuberculine (TST) après exposition à la tuberculose (TB) dans l'état de Victoria, en Australie.Méthode : Une revue rétrospective des données recueillies pour la surveillance en matière de santé publique a été réalisée afin d'identifier les caractéristiques démographiques des contacts, notamment le statut en matière du vaccin bacille Calmette-Guérin et l'âge et le résultat du TST.Résultats : La recherche des contacts a été réalisée auprès de 15 094 personnes dont 13 427 (89.0%) ont eu un TST. Le TST a été positif chez 31,4% (95%IC 30,6­32,2) de tous les contacts et chez 48,8% des contacts nés hors d'Australie. Parmi les contacts qui ont été TST négatifs au départ, le taux de conversion après exposition a été de 14,8%. La conversion a été plus fréquente chez les personnes âgées de 45­54 ans, avec <12% de positivité à la fois dans les tranches d'âge les plus jeunes (<5 ans) et les plus âgées (⩾65 ans). Une TB active s'est développée chez 1,1% de tous les contacts. Cependant, les contacts âgés de <5 ans ont eu le risque le plus élevé de développer une TB active après exposition (3,8%), tandis que le risque a été le plus faible chez les personnes âgées de ⩾65 ans (0,3%).Conclusion : Dans l'ensemble, la recherche de contacts et le TST réalisés dans ce contexte semblent aboutir à une proportion élevée de personnes à risque de développer une TB active. Le rendement du dépistage dans certains groupes, en particulier ceux âgés de ⩾65 ans, a été faible, et il faudrait envisager des stratégies alternatives d'investigation.

Objetivo: Analizar el uso programático de la prueba cutánea de la tuberculina (TST) tras la exposición a la tuberculosis (TB) en el estado de Victoria en Australia.Método: Fue este un estudio retrospectivo de los datos recogidos en la vigilancia de salud pública, con el propósito de determinar los factores demográficos incluidos el antecedente de vacunación antituberculosa y la edad y evaluar los resultados de la TST.Resultados: Se investigaron 15 094 contactos y en 13 427 de ellos se había practicado la TST (89,0%). La reacción TST fue positiva en el 31,4% de todos los contactos (IC95% 30,6­32,2) y en el 48,8% de los contactos nacidos en el extranjero. De los contactos con una TST inicial negativa, la tasa de conversión después de la exposición fue 14,8%. La conversión fue más frecuente en el grupo de edad de 45­54 años y los grupos extremos, es decir, de <5 años y de ⩾65 años de edad, obtuvieron una positividad de <12%. Se observó evolución hacia la enfermedad tuberculosa activa en el 1,1% de todos los contactos. Sin embargo, los contactos de edad <5 años presentaron una mayor probabilidad de sufrir TB activa tras la exposición (3,8%) y a partir de los 65 años el riesgo fue bajo (0,3%).Conclusión: En general, la investigación de los contactos y la práctica de la TST en este entorno pusieron de manifiesto una alta proporción de personas vulnerables a la enfermedad activa. El rendimiento diagnóstico de la prueba en algunos grupos, en especial a partir de los 65 años de edad, fue bajo y es preciso considerar la posibilidad de usar otras estrategias diagnósticas.

[Longitudinal follow-up of contact subjects of cases of tuberculosis in Paris]. / Suivi longitudinal des sujets contacts de cas de tuberculose à Paris.

AIM: To our knowledge, the proportion of active tuberculosis diagnosed after 12-18 months during a screening tuberculosis process in a specialized centre (centre de lutte antituberculeuse [CLAT]) has not been described in France. The majority of other countries do not have any recommendation to screen at this time. METHODS: We evaluated the number of treated or not treated latent tuberculosis infections (LTI) identified during tuberculosis screening. We identified the causes of ITL non-treatment, the number of active disease cases and the proportion of subjects lost to follow-up after 12-18 months. RESULTS: Among the 1066 contact subjects, 159 (15 %) had a positive QuantiFERON-TB-Gold In-Tube(®) test. A prophylactic treatment with Rifinah(®) was given to 97 (61 %) subjects, 7 (7.3 %) having developed side effects that led to treatment interruption. A high proportion (56 %) of contact subjects were lost of follow-up and the main reason for no prophylactic treatment (20/52, 38 %) was due to these losses. No active disease cases were identified among the 474 (44 %) contact subjects who had a chest X-ray after 12-18 months follow-up by the CLAT. The low level of positive QuantiFERON-TB-Gold In-Tube(®) tests (15 %) could be explained by the high specificity of this test and the strong proportion of occupational contacts, of whom a probably significant number were not exposed to active disease. CONCLUSION: The absence of active disease at 12-18 months and a majority (56 %) of contact subjects lost from follow-up at this period let us propose not to recall contact subjects at 12-18 months with the exception of those living under the same roof as the index case and/or those having a cumulative contact time of greater than 100 hours during the theoretical infectious period. This proposal remains to be confirmed by other studies, particularly including possible secondary cases diagnosed outside the screening periods by the CLAT.

Prevalence and evolution of Mycobacterium tuberculosis infection in tuberculosis case contacts

INTRODUCTION : The tuberculin test is a diagnostic method for detecting latent tuberculosis (TB) infection, especially among disease contact cases. The objective of this study was to analyze the prevalence and evolution of Mycobacterium tuberculosis infection among TB contact cases. METHODS : A retrospective cohort study was performed in a reference center for TB. The study population consisted of 2,425 patients who underwent a tuberculin test from 2003 to 2010 and whose results indicated contact with individuals with TB. The data were collected from the registry book of the tuberculin tests, patient files and the Information System Records of Notification Grievance. To verify the evolution of TB, case records through September 2014 were consulted. Data were analyzed using the Statistical Package for the Social Sciences (SPSS). In all hypothesis tests, a significance level of 0.05 was used. RESULTS : From the studied sample, 435 (17.9%) contacts did not return for reading. Among the 1,990 contacts that completed the test, the prevalence of latent TB infection was 35.4%. Of these positive cases, 50.6% were referred to treatment; the dropout rate was 42.5%. Among all of the contacts, the TB prevalence was 1.8%, from which 13.2% abandoned treatment. CONCLUSIONS : The collected data indicate the need for more effective public policies to improve TB control, including administering tests that do not require a return visit for reading, enhancing contact tracing and encouraging actions that reinforce full treatment adherence. .

Inactive fibrotic lesions versus pulmonary tuberculosis with negative bacteriology.

This article analyzes the concept of inactive fibrotic lesions of presumed tuberculous origin (old healed tuberculosis), defined by radiological characteristics and a positive tuberculin skin test (TST), and we examine the evidence-based foundation for the indication of treatment of latent tuberculosis infection in these cases. We explore the risk of reactivation in older and recent literature, and the problems raised by the differential diagnosis with active tuberculosis with negative bacteriology. We also analyze data on the prevalence of fibrotic lesions in the recent literature. We examine the possible role of Interferon Gamma Release Assays (IGRAs) versus TST and other molecular antigen detection techniques in sputum that can aid in establishing the diagnosis and we discuss the current indications for chemoprophylaxis and the different options available. We propose diagnostic guidelines and therapeutic algorithms based on risk stratification by age and other factors in the management of radiological lesions that raise a differential diagnosis between fibrotic lesions and active pulmonary tuberculosis with negative bacteriology.

Tuberculosis in haemodialysis patients: A single centre experience.

We prospectively followed-up new patients of tuberculosis while on maintenance hemodialysis at a State Government-run tertiary care institute. Between 2000 and 2010, 1237 new patients were initiated on maintainence hemodialysis. The number of patients diagnosed with tuberculosis after initiation of hemodialysis was 131 (10.5% of 1237). The age was 46.4 ± 10.4 (range 8-85) years and there were 90 (68.7%) males. The number of patients diagnosed with tuberculosis on the basis of organ involvement were: Pulmonary-60, pleural effusion-31, lymph node-21, meningitis-8, pericardial effusion-7, peritoneum-2, latent tuberculosis-2. The incidence of tuberculosis in hemodialysis was found to be 105.9 per 1000 patient years. Male gender, diabetes mellitus, past history of tuberculosis, mining as an occupation, low serum albumin, and duration of hemodialysis more than 24 months, and unemployment were found to be significant risk-factors on univariate analysis.

It's hard work, but it's worth it: the task of keeping children adherent to isoniazid preventive therapy.

SETTING: Isoniazid preventive therapy (IPT) offers children protection against tuberculosis (TB), but it has been difficult to implement, particularly in developing countries. OBJECTIVE: To understand what encourages or inhibits children from adhering to IPT. DESIGN: In-depth interviews were conducted with two parents of children adherent to IPT and two staff members from three primary health care clinics in high TB prevalence communities. Themes explored were knowledge and attitudes towards IPT, problems in accessing and adhering to treatment, and community responses. RESULTS: Parents administering treatment valued it positively, realised their children's risk of TB, and were positive about the clinic. Nurses acknowledged that resistance to treatment remained, with some parents not wanting to acknowledge risk nor willing to make the effort for their children; there was also considerable misinformation about IPT. Clinic nurses acknowledged problems of staff shortages, lengthy waiting times and conflict between staff and community members. Adherence was affected by social problems, stigma about TB and its link to the human immunodeficiency virus, and the extended treatment period. CONCLUSION: Parents who maintained adherence to the IPT regimen showed that it was possible even in very difficult circumstances. Further effort is required to improve some of the clinic services, correct misinformation, reduce stigma and provide support to parents.