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1.
BMC Infect Dis ; 21(1): 106, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482742

RESUMEN

BACKGROUND: Gene expression signatures have been used as biomarkers of tuberculosis (TB) risk and outcomes. Platforms are needed to simplify access to these signatures and determine their validity in the setting of comorbidities. We developed a computational profiling platform of TB signature gene sets and characterized the diagnostic ability of existing signature gene sets to differentiate active TB from LTBI in the setting of malnutrition. METHODS: We curated 45 existing TB-related signature gene sets and developed our TBSignatureProfiler software toolkit that estimates gene set activity using multiple enrichment methods and allows visualization of single- and multi-pathway results. The TBSignatureProfiler software is available through Bioconductor and on GitHub. For evaluation in malnutrition, we used whole blood gene expression profiling from 23 severely malnourished Indian individuals with TB and 15 severely malnourished household contacts with latent TB infection (LTBI). Severe malnutrition was defined as body mass index (BMI) < 16 kg/m2 in adults and based on weight-for-height Z scores in children < 18 years. Gene expression was measured using RNA-sequencing. RESULTS: The comparison and visualization functions from the TBSignatureProfiler showed that TB gene sets performed well in malnourished individuals; 40 gene sets had statistically significant discriminative power for differentiating TB from LTBI, with area under the curve ranging from 0.662-0.989. Three gene sets were not significantly predictive. CONCLUSION: Our TBSignatureProfiler is a highly effective and user-friendly platform for applying and comparing published TB signature gene sets. Using this platform, we found that existing gene sets for TB function effectively in the setting of malnutrition, although differences in gene set applicability exist. RNA-sequencing gene sets should consider comorbidities and potential effects on diagnostic performance.


Asunto(s)
Perfilación de la Expresión Génica/métodos , Desnutrición/genética , Programas Informáticos , Tuberculosis/genética , Adolescente , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Niño , Comorbilidad , Femenino , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/genética , Masculino , Desnutrición/diagnóstico , Desnutrición/epidemiología , Persona de Mediana Edad , Mycobacterium tuberculosis , Transcriptoma , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Adulto Joven
2.
BMC Infect Dis ; 21(1): 42, 2021 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-33422003

RESUMEN

BACKGROUND: Screening for latent tuberculosis infection (LTBI) among migrant population has become a critical issue for many low tuberculosis (TB) burden countries. Evidence regarding effectiveness of LTBI programs are limited, however, partly because of paucity of national data on treatment outcomes for LTBI. In Japan, notification of LTBI is mandatory, and its treatment outcome is reported as part of Japan's national TB surveillance system. We thus conducted a detailed analysis of LTBI among foreign-born persons, to update the epidemiological trend of newly notified LTBI between 2007 and 2018, and to examine the treatment regimen and outcome of those notified in 2016 and 2017, focusing specifically on the potential risk factors for lost to follow-up. METHODS: We extracted and analyzed the data of newly notified LTBI patients from the Japan Tuberculosis Surveillance System to examine the overall trend of notification and by age groups and modes of detection between 2007 and 2018, and the cohort data for treatment regimen and outcomes of foreign-born persons notified with LTBI in 2016 and 2017. Trends and proportions were summarized descriptively, and logistic regression analysis was conducted to identify potential risk factors for lost to follow-up. Comparisons were made with the Japan-born patients where appropriate, using chi-squared tests. RESULTS: Both the number and proportion of LTBI among foreign-born persons have been constantly increasing, reaching 963 cases in 2018. Cohort analysis of the surveillance data indicated that the proportion of those on shorter regimen was higher among the foreign- than Japan-born patients (5.5% vs. 1.8%, p < 0.001). The proportion of those who have been lost to follow-up and transferred outside of Japan combined was higher among the foreign- than Japan-born patients (12.0% vs, 8.2%, p < 0.001). Risk factors for lost to follow-up were being employed on a temporal basis, and job status unknown (adjusted odds ratios 3.11 and 4.09, 95% confidence intervals 1.34-7.26 and 1.60-10.48, respectively). CONCLUSIONS: Migrant population face greater risk of interrupting LTBI treatment, and interventions to improve adherence are a critical component of programmatic management of LTBI. Further studies are needed to explore the cultural and socioeconomic situation in which foreign-born persons undergo LTBI treatment in Japan.


Asunto(s)
Antituberculosos/uso terapéutico , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/epidemiología , Migrantes/estadística & datos numéricos , Adolescente , Adulto , Niño , Preescolar , Monitoreo Epidemiológico , Femenino , Humanos , Lactante , Japón/epidemiología , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/microbiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
3.
PLoS One ; 15(12): e0243951, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33332458

RESUMEN

In Bangladesh, there is currently no data on the burden of latent TB infection (LTBI) amongst hospital healthcare workers (HCWs). This study aimed to determine the prevalence of LTBI and compare the prevalence among HCWs in two public tertiary care hospitals. Between September 2018 and August 2019, we conducted a cross-sectional study in two public tertiary care general hospitals. Using a survey and tuberculin skin test (TST), we assessed risk factors for LTBI, adjusting for known and plausible confounders. In addition, a facility assessment was undertaken to understand the implementation of relevant IPC measures. The prevalence of LTBI among HCWs was 42%. HCWs spent a median of 6 hours (SD = 1.76, IQR 2.00) per day and attended an average of 1.87 pulmonary TB patients per week. HCWs did not receive any TB IPC training, the wards lacked a symptom checklist to screen patients for TB, and no masks were available for coughing patients. Seventy-seven percent reportedly did not use any facial protection (masks or respirators) while caring for patients. In the multivariable model adjusting for hospital level clustering effect, TST positivity was significantly higher among HCWs aged 35-45 years (aOR1.36, 95% CI: 1.06-1.73) and with >3 years of service (aOR 1.67, 95% CI: 1.62-1.72). HCWs working in the medicine ward had 3.65 (95% CI: 2.20-6.05) times, and HCWs in the gynecology and obstetrics ward had 2.46 (95% CI: 1.42-4.27) times higher odds of TST positivity compared to HCWs working in administrative areas. This study identified high prevalence of LTBI among HCWs. This may be due to the level of exposure to pulmonary TB patients, and/or limited use of personal protective equipment along with poor implementation of TB IPC in the hospitals. Considering the high prevalence of LTBI, we recommend the national TB program consider providing preventative therapy to the HCWs as the high-risk group, and implement TB IPC in the hospitals.


Asunto(s)
Personal de Salud , Tuberculosis Latente/diagnóstico , Tuberculina/aislamiento & purificación , Adolescente , Adulto , Bangladesh/epidemiología , Femenino , Humanos , Tuberculosis Latente/epidemiología , Tuberculosis Latente/microbiología , Masculino , Persona de Mediana Edad , Pruebas Cutáneas/normas , Centros de Atención Terciaria , Adulto Joven
4.
BMC Infect Dis ; 20(1): 746, 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33046016

RESUMEN

BACKGROUND: Effective active case finding (ACF) activities are essential for early identification of new cases of active tuberculosis (TB) and latent TB infection (LTBI). Accurate diagnostics as well as the ability to identify contacts at high risk of infection are essential for ACF, and have not been systematically reported from Central Asia. The objective was to implement a pilot ACF program to determine the prevalence and risk factors for LTBI and active TB among contacts of individuals with TB in Kyrgyz Republic using Quantiferon-TB Gold plus (QuantiFERON). METHODS: An enhanced ACF project in the Kyrgyz Republic was implemented in which close and household (home) contacts of TB patients from the Issyk-Kul Oblast TB Center were visited at home. QuantiFERON and the tuberculin skin test (TST) alongside clinical and bacteriological examination were used to identify LTBI and active TB cases among contacts. The association for QuantiFERON positivity and risk factors were analysed and compared to TST results. RESULTS: Implementation of ACF with QuantiFERON involved close collaboration with the national sanitary and epidemiological services (SES) and laboratories in the Kyrgyz Republic. From 67 index cases, 296 contacts were enrolled of whom 253 had QuantiFERON or TST results; of those 103 contacts had LTBI (positive TST or IGRA), and four (1.4%) active TB cases were detected. Index case smear microscopy (OR 1.76) and high household density (OR 1.97) were significant risk factors for QuantiFERON positivity for all contacts. When stratified by age, association with smear positivity disappeared for children below 15 years. TST was not associated with any risk factor. CONCLUSIONS: This is the first time that ACF activities have been reported for Central Asia, and provide insight for implementation of effective ACF in the region. These ACF activities using QuantiFERON led to increase in the detection of LTBI and active cases, prior to patients seeking treatment. Household density should be taken into consideration as an important risk factor for the stratification of future ACF activities.


Asunto(s)
Trazado de Contacto/métodos , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Pruebas Diagnósticas de Rutina , Composición Familiar , Femenino , Humanos , Lactante , Recién Nacido , Kirguistán/epidemiología , Tuberculosis Latente/microbiología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prevalencia , Factores de Riesgo , Prueba de Tuberculina/métodos , Tuberculosis Pulmonar/microbiología , Adulto Joven
5.
Brasília; CONITEC; out. 2020.
No convencional en Portugués | BRISA/RedTESA | ID: biblio-1141494

RESUMEN

INTRODUÇÃO: A ILTB é definida como um estado de resposta imune persistente à estimulação por antígenos de Mycobacterium tuberculosis sem evidência, sintomas clínicos ou achados radiológicos de doença ativa. Estima-se que um terço da população mundial possua ILTB. A importância de diagnosticar a ILTB reside no potencial de reativação para a doença ativa e transmissível quando o indivíduo estiver imunossuprimido com comorbidades ou em terapia biológica. Quando identificado o potencial de desenvolvimento de doença ativa em um indivíduo com ILTB é recomendada a realização do tratamento preconizado, de forma a impedir que ocorra a reativação. A identificação e tratamento da ILTB constituem estratégias fundamentais para reduzir a carga global de tuberculose, especialmente em países em desenvolvimento. TECNOLOGIA: Teste de liberação de interferon-gama (do inglês interferon gamma release assay - IGRA). PERGUNTAS DE PESQUISA: O uso de IGRA apresenta maior acurácia na detecção de ILTB e capacidade para prever o desenvolvimento de tuberculose ativa, em comparação ao PPD, em pacientes imunocomprometidos? EVIDÊNCIAS CLÍNICAS: Foram analisadas dez revisões sistemáticas que avaliaram o desempenho do IGRA


Asunto(s)
Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/inmunología , Ensayos de Liberación de Interferón gamma/métodos , Evaluación de la Tecnología Biomédica , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio/economía
6.
Medicine (Baltimore) ; 99(36): e22015, 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899054

RESUMEN

INTRODUCTION: Tuberculosis (TB) is a global infectious disease. In low-incidence countries, paediatric TB affects mostly immigrant children and children of immigrants. We hypothesize that these children are at risk of exposure to Mycobacterium tuberculosis when they travel to the country of origin of their parents to visit friends and relatives (VFR). In this study, we aim to estimate the incidence rate and risk factors associated to latent tuberculosis infection (LTBI) and TB in VFR children. METHODS AND ANALYSIS: A prospective study will be carried out in collaboration with 21 primary health care centres (PCC) and 5 hospitals in Catalonia, Spain. The study participants are children under 15 years of age, either immigrant themselves or born to immigrant parents, who travel to countries with high incidence of TB (≥ 40 cases/100,000 inhabitants). A sample size of 492 children was calculated. Participants will be recruited before traveling, either during a visit to a travel clinic or to their PCC, where a questionnaire including sociodemographic, epidemiological and clinical data will be completed, and a tuberculin skin test (TST) will be performed and read after 48 to 72 hours; patients with a positive TST at baseline will be excluded. A visit will be scheduled eight to twelve-weeks after their return to perform a TST and a QuantiFERON-TB Gold Plus test. The incidence rate of LTBI will be estimated per individual/month and person/year per country visited, and also by age-group. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Ethics Committee of the Hospital Universitari Mútua Terrassa (code 02/16) and the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (code P16/094). Articles will be published in indexed scientific journals. TRIAL REGISTRATION: Clinical-Trials.gov: NCT04236765.


Asunto(s)
Tuberculosis Latente/epidemiología , Tuberculosis Latente/transmisión , Mycobacterium tuberculosis/aislamiento & purificación , Adolescente , Niño , Pruebas Diagnósticas de Rutina/métodos , Emigrantes e Inmigrantes , Familia , Femenino , Amigos , Humanos , Incidencia , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis Latente/diagnóstico , Masculino , Mycobacterium tuberculosis/inmunología , Estudios Prospectivos , Factores de Riesgo , España/epidemiología , Viaje/tendencias , Prueba de Tuberculina/métodos
8.
Pediatrics ; 146(4)2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32994177

RESUMEN

BACKGROUND: New guidelines support using interferon-γ release assays (IGRAs) in children ≥2 years for diagnosis of latent tuberculosis infection (LTBI). However, lack of experience in young children and concern that IGRAs are less sensitive than tuberculin skin tests (TSTs) limit their use. Our aim was to identify active tuberculosis (TB) cases among high risk children <5 years and tested for LTBI with an IGRA. METHODS: . Retrospective review of domestic TB screening data from California's Refugee Health Electronic Information System for children <5 years old who resettled in California between October, 2013 and December, 2016. Children were crossmatched with the California TB registry to identify cases of TB disease between October 2013 and December 2018. RESULTS: A total of 3371 children <5 years were identified; the majority were born in countries with high TB incidence (>150 cases per 100 000). Half received IGRAs (n = 1878; 56%), a quarter received TSTs (n = 811; 24%); 1.4% of children were IGRA-positive (n = 26) and 13% were TST-positive (n = 106). Twenty-two IGRA results were indeterminate (1.2%). Sixteen children had both tests; 9 were discrepant (positive TST with negative IGRA). No cases of TB disease were identified during 10 797 person-years of follow-up. CONCLUSIONS: IGRA positivity was less than TST positivity in high risk children <5 years old. Despite fewer LTBI diagnoses in the IGRA-tested population, no cases of TB disease among children who tested negative were identified, suggesting IGRA is valuable tool for identifying LTBI in this population.


Asunto(s)
Ensayos de Liberación de Interferón gamma/estadística & datos numéricos , Tuberculosis Latente/diagnóstico , Refugiados/estadística & datos numéricos , Prueba de Tuberculina/estadística & datos numéricos , California/epidemiología , Preescolar , Femenino , Humanos , Tuberculosis Latente/epidemiología , Masculino , Estudios Retrospectivos
9.
Yonsei Med J ; 61(9): 789-796, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32882763

RESUMEN

PURPOSE: The prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immune responses to M. tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by its strain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immune responses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea. MATERIALS AND METHODS: Pulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection (n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatures were examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination is employed. RESULTS: Statistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-α] of 17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-α also differentiated between active diseases and latent TB infection (p<0.01), and the detection rate of TB was dramatically increased in combination with IL-6 and CXCL10 at the highest levels of specificity (95-100%). CONCLUSION: Our data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information for improved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regions where the M. tb Beijing/K strain is endemic.


Asunto(s)
Tuberculosis Latente/diagnóstico , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Pulmonar/diagnóstico , Adolescente , Adulto , Antígenos Bacterianos/sangre , Antígenos Bacterianos/genética , Antígenos de Superficie/sangre , Antígenos de Superficie/genética , Proteínas Bacterianas , Beijing , Estudios de Casos y Controles , Citocinas/sangre , Femenino , Humanos , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/metabolismo , República de Corea , Sensibilidad y Especificidad
11.
Public Health Rep ; 135(1_suppl): 172S-181S, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32735191

RESUMEN

OBJECTIVE: Targeted testing and treatment of persons with latent tuberculosis infection (LTBI) is a critical component of the US tuberculosis (TB) elimination strategy. In January 2016, the California Department of Public Health issued a tool and user guide for TB risk assessment (California tool) and guidance for LTBI testing, and in September 2016, the US Preventive Services Task Force (USPSTF) issued recommendations for LTBI testing in primary care settings. We estimated the epidemiologic effect of adherence to both recommendations in California. METHODS: We used an individual-based Markov micro-simulation model to estimate the number of cases of TB disease expected through 2026 with baseline LTBI strategies compared with implementation of the USPSTF or California tool guidance. We estimated the risk of LTBI by age and country of origin, the probability of being in a targeted population, and the probability of presenting for primary care based on available data. We assumed 100% adherence to testing guidance but imperfect adherence to treatment. RESULTS: Implementation of USPSTF and California tool guidance would result in nearly identical numbers of tests administered and cases of TB disease prevented. Perfect adherence to either recommendation would result in approximately 7000 cases of TB disease averted (40% reduction compared with baseline) by 2026. Almost all of this decline would be driven by a reduction in the number of cases among non-US-born persons. CONCLUSIONS: By focusing on the non-US-born population, adherence to LTBI testing strategies recommended by the USPSTF and the California tool could substantially reduce the burden of TB disease in California in the next decade.


Asunto(s)
Tuberculosis Latente/diagnóstico , Atención Primaria de Salud/organización & administración , Adulto , Factores de Edad , Antituberculosos/uso terapéutico , California , Emigrantes e Inmigrantes , Adhesión a Directriz , Humanos , Huésped Inmunocomprometido , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/etnología , Cadenas de Markov , Tamizaje Masivo , Guías de Práctica Clínica como Asunto , Atención Primaria de Salud/normas , Instituciones Residenciales , Medición de Riesgo , Tuberculosis/etnología
12.
Aust N Z J Public Health ; 44(5): 353-359, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32776658

RESUMEN

OBJECTIVE: Latent tuberculosis (LTBI) case-finding and treatment are a focus of TB elimination in Australia. We sought the perspectives of migrants from two high-burden countries likely to be targeted by this strategy. METHODS: To understand perceptions of migrant groups in Australia on LTBI screening, 28 in-depth interviews were conducted with Indian and Pakistani community members recruited purposively through local organisations in the Illawarra region, New South Wales. Drawing on local TB policy, data collected qualitatively was analysed using framework methodologies. RESULTS: Australia's immigration system prioritises migrants of higher socioeconomic status. Participants supported elimination but perceived TB as a disease of the poor and not relevant to them. Lack of understanding of LTBI and sensitivity to being 'targeted' are further barriers to screening participation. CONCLUSION: Information provision and targeting rationale are an essential preamble to LTBI screening. Migration appears to modify cultural attitudes to TB, but not significantly. Despite less stigma surrounding TB in Australian contexts, testing privacy and confidentiality, and limiting public identification of specific groups remain important to program acceptability. Implications for public health: Progress towards TB elimination can be enhanced by consulting with targeted communities, using existing networks for communication and service provision; emphasising prevention benefits.


Asunto(s)
Asistencia Sanitaria Culturalmente Competente , Tuberculosis Latente/diagnóstico , Tamizaje Masivo/estadística & datos numéricos , Aceptación de la Atención de Salud/etnología , Vigilancia de la Población/métodos , Migrantes/psicología , Adolescente , Adulto , Anciano , Australia/epidemiología , Femenino , Política de Salud , Humanos , India/etnología , Entrevistas como Asunto , Tuberculosis Latente/etnología , Tuberculosis Latente/psicología , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Pakistán/etnología , Aceptación de la Atención de Salud/psicología , Investigación Cualitativa , Migrantes/estadística & datos numéricos , Adulto Joven
13.
PLoS One ; 15(6): e0235254, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32603343

RESUMEN

OBJECTIVE: An interferon-gamma release assay (IGRA) is used to screen for latent tuberculosis infection (LTBI). Among IGRAs, the QuantiFERON-TB Gold In-Tube (QFT-GIT) results are highly variable, so the borderline zone has been proposed to reduce unnecessary LTBI treatment. The aim of this study was to examine the proportion of the borderline zone of QFT-GIT in healthcare workers' (HCWs) serial IGRA and to retrospectively identify the utility of predicting tuberculosis (TB) in a moderate TB incidence setting. METHODS: The participants were HCWs who had undergone serial LTBI screening between June 2013 and June 2018. IGRA-positive HCWs underwent examinations that included low-dose computed tomography (LDCT) and TB culture, if necessary. Applying the borderline zone (0.2-<0.7 IU/mL), the results were classified as definite negative, borderline negative, borderline positive and definite positive. RESULTS: Through the follow-up of 477 HCWs, 441 (92.5%) invariant, 30 (6.3%) conversion, 2 (0.4%) reversion and 5 (1.0%) indeterminate results were observed with the manufacturer's cutoff. Applying the borderline zone, 419 (87.8%) invariant, 22 (4.6%) conversion, 1 (0.2%) reversion and 36 (7.5%) decision pending, including 5 (1.0%) indeterminate results, were observed. At the time of screening, five TB cases were identified. Chest X-ray (CXR) identified one TB case, and LDCT identified four additional TB cases. After one year, two TB cases were diagnosed, and their screening QFT-GIT results were definite positive and borderline negative. In the Cochran-Armitage trend test, the greater the maximum difference in the QFT-GIT grade with the borderline zone was, the higher the probability of developing TB (P-value <0.001). CONCLUSION: The application of the borderline zone lowered the conversion rate but increased the decision pending rate. Introducing the borderline zone requires a careful approach, and a thorough examination needs to be performed to rule out TB in converters. HCWs with borderline QFT-GIT results also need close observation.


Asunto(s)
Ensayos de Liberación de Interferón gamma , Tuberculosis Latente/diagnóstico , Adulto , Femenino , Personal de Salud , Humanos , Incidencia , Ensayos de Liberación de Interferón gamma/métodos , Ensayos de Liberación de Interferón gamma/estadística & datos numéricos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Tuberculosis/diagnóstico , Adulto Joven
14.
Artículo en Inglés | MEDLINE | ID: mdl-32605191

RESUMEN

Latent tuberculosis infection (LTBI) represents a work-related risk for health workers (HWs). Tuberculosis remains the second most common occupational infectious disease among HWs in Germany. Comparative figures on LTBI prevalence in the general population are missing because testing is only carried out in the context of an outbreak situation. The objective of this study is to investigate whether HWs are at greater risk of LTBI than workers in other sectors. This study is based on two samples. The first sample is a database of HWs who were examined by the German Occupational Physicians Network using an interferon-gamma release assay (IGRA). The second sample consists of general employees (non-health workers, non-HWs) from Hamburg who had no professional contact with the health care system. Propensity score matching (PS matching) was performed to ensure better comparability of the groups. The differences in the prevalence of positive test results from IGRAs were examined using univariate and multivariate analyses. After the PS matching of 1:10, 100 test subjects in the non-HW group and 1000 HWs remained to form the analysis collective. The HWs tended to exhibit higher IGRA values than non-HWs. The univariate analysis showed an odds ratio (OR) of 3.86 for the HWs (95% confidence interval (CI): 0.99 to 32.5; p = 0.056) with respect to a positive test result. The multivariate analysis produced an OR of 4.92, (95% CI: 1.3 to 43.7; p = 0.013) for HWs born in Germany. Despite the declining tuberculosis incidence rates in Germany, a comparison with non-exposed professional groups showed that HWs are at greater risk of LTBI. Preventive medical check-ups still seem to be indicated.


Asunto(s)
Personal de Salud , Tuberculosis Latente , Tuberculosis , Adulto , Femenino , Alemania/epidemiología , Humanos , Ensayos de Liberación de Interferón gamma , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Masculino , Ocupaciones , Prevalencia , Medición de Riesgo , Tuberculosis/epidemiología
15.
PLoS One ; 15(7): e0235261, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32614873

RESUMEN

BACKGROUND: Tuberculosis (TB) is the leading cause of death among people living with HIV (PLWH), and current evidence suggests that heavy alcohol users have an increased risk of developing TB disease compared to non-drinkers. Not known is whether the increased risk for TB disease among alcohol users may reflect higher rates of latent TB infection (LTBI) among this population. We assessed the latent TB infection prevalence based on tuberculin skin testing (TST) and examined association with current alcohol use among HIV-infected persons on antiretroviral therapy (ART) in south-western Uganda. METHODS: We included PLWH at the Mbarara Regional Hospital HIV clinic, who were either current alcohol consumers (prior 3 months) or past year abstainers (2:1 enrolment ratio). Participants were recruited for a study of isoniazid preventive therapy for LTBI. TST was performed using 5 tuberculin units of purified protein derivative. The primary outcome was a positive TST reading (≥5mm induration), reflecting LTBI. We used logistic regression analyses to assess the cross-sectional association between self-reported current alcohol use and a positive TST. RESULTS: Of the 295 of 312 (95%) who returned for TST reading, 63% were females and 63% were current alcohol drinkers. The TST positive prevalence was 27.5% (95% confidence interval [CI]: 22.6% - 32.9%). The odds of a positive TST for current alcohol users compared to abstainers was 0.76 (95% CI: 0.41, 1.41), controlling for gender, age, body mass index, history of smoking, and prior unhealthy alcohol use. CONCLUSIONS: The prevalence of LTBI among PLWH on ART in south-western Uganda was moderate and LTBI poses a risk for future infectious TB. Although alcohol use is common, we did not detect an association between current drinking or prior unhealthy alcohol use and LTBI. Further studies to evaluate the association between LTBI and different levels of current drinking (heavy versus not) are needed.


Asunto(s)
Consumo de Bebidas Alcohólicas , Infecciones por VIH/complicaciones , Tuberculosis Latente/etiología , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Estudios Transversales , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Tuberculosis Latente/diagnóstico , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Prueba de Tuberculina , Uganda/epidemiología
16.
BMC Infect Dis ; 20(1): 469, 2020 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-32615981

RESUMEN

BACKGROUND: Interferon-γ release assays (IGRA) with Resuscitation promoting factor (Rpf) proteins enhanced tuberculosis (TB) screening and diagnosis in adults but have not been evaluated in children. Children often develop paucibacillary TB and their immune response differs from that of adults, which together affect TB disease diagnostics and immunodiagnostics. We assessed the ability of Rpf to identify infection among household TB-exposed children in The Gambia and investigated their ability to discriminate Mycobacterium tuberculosis complex (MTBC) infection from active TB disease in children. METHODS: Detailed clinical investigations were done on 93 household TB-exposed Gambian children and a tuberculin skin test (TST) was administered to asymptomatic children. Venous blood was collected for overnight stimulation with ESAT-6/CFP-10-fusion protein (EC), purified protein derivative and RpfA, B, C, D and E. Interferon gamma (IFN-γ) production was measured by ELISA in supernatants and corrected for the background level. Infection status was defined by IGRA with EC and TB disease by mycobacterial confirmation and/or clinical diagnosis. We compared IFN-γ levels between infected and uninfected children and between infected and TB diseased children using a binomial logistic regression model while correcting for age and sex. A Receiver Operating Characteristics analysis was done to find the best cut-off for IFN-γ level and calculate sensitivity and specificity. RESULTS: Interferon gamma production was significantly higher in infected (IGRA+, n = 45) than in uninfected (IGRA-, n = 20) children after stimulation with RpfA, B, C, and D (P = 0.03; 0.007; 0.03 and 0.003, respectively). Using RpfB and D-specific IFN-γ cut-offs (33.9 pg/mL and 67.0 pg/mL), infection was classified with a sensitivity-specificity combination of 73-92% and 77-72% respectively, which was similar to and better than 65-75% for TST. Moreover, IFN-γ production was higher in infected than in TB diseased children (n = 28, 5 bacteriologically confirmed, 23 clinically diagnosed), following RpfB and D stimulation (P = 0.02 and 0.03, respectively). CONCLUSION: RpfB and RpfD show promising results for childhood MTBC infection screening, and both performed similar to and better than the TST in our study population. Additionally, both antigens appear to discriminate between infection and disease in children and thus warrant further investigation as screening and diagnostic antigens for childhood TB.


Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Citocinas/inmunología , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tamizaje Masivo/métodos , Mycobacterium tuberculosis/inmunología , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Composición Familiar , Femenino , Gambia/epidemiología , Humanos , Interferón gamma/inmunología , Interferón gamma/metabolismo , Tuberculosis Latente/microbiología , Masculino , Sensibilidad y Especificidad , Prueba de Tuberculina
17.
PLoS One ; 15(7): e0235859, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32687494

RESUMEN

In our work, we aim to identify new candidate host biomarkers to discriminate between active TB patients (n = 28), latent infection (LTBI; n = 27) and uninfected (NoTBI; n = 42) individuals. For that, active TB patients and their contacts were recruited that donated serum and saliva samples. A multiplex assay was performed to study the concentration of different cytokines, chemokines and growth factors. Proteins with significant differences between groups were selected and logistic regression and the area under the ROC curve (AUC) was used to assess the diagnostic accuracy. The best marker combinations that discriminate active TB from NoTBI contacts were [IP-10 + IL-7] in serum and [Fractalkine + IP-10 + IL-1α + VEGF] in saliva. Best discrimination between active TB and LTBI was achieved using [IP-10 + BCA-1] in serum (AUC = 0.83) and IP-10 in saliva (p = 0.0007; AUC = 0.78). The levels of TNFα (p = 0.003; AUC = 0.73) in serum and the combination of [Fractalkine+IL-12p40] (AUC = 0.83) in saliva, were able to differentiate between NoTBI and LTBI contacts. In conclusion, different individual and combined protein markers could help to discriminate between active TB and both uninfected and latently-infected contacts. The most promising ones include [IP-10 + IL-7], [IP-10 + BCA-1] and TNFα in serum and [Fractalkine + IP-10 + IL-1α + VEGF], IP-10 and [Fractalkine+IL-12p40] in saliva.


Asunto(s)
Quimiocina CX3CL1/sangre , Quimiocina CXCL10/sangre , Interleucinas/sangre , Tuberculosis Latente/sangre , Tuberculosis Pulmonar/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/metabolismo , Quimiocina CX3CL1/análisis , Quimiocina CXCL10/análisis , Femenino , Humanos , Interleucinas/análisis , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/metabolismo , Masculino , Persona de Mediana Edad , Saliva/química , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/metabolismo , Factor A de Crecimiento Endotelial Vascular/análisis
18.
Med Lav ; 111(3): 170-183, 2020 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-32624559

RESUMEN

INTRODUCTION: Despite great efforts, tuberculosis (TB) is still a major public health threat worldwide. For decades, TB control programs have focused almost exclusively on infectious TB active cases.  However, it is evident that this strategy alone cannot achieve TB elimination. To achieve this objective a comprehensive strategy directed toward integrated latent tuberculosis infection (LTBI) management is needed. Recently it has been recognized that LTBI is not a stable condition but rather a spectrum of infections (e.g., intermittent, transient or progressive) which may lead to incipient, then subclinical, and finally active TB disease. AIM: Provide an overview of current available LTBI diagnostic test including updates, future developments and perspectives. RESULTS: There is currently no test for the direct identification of live MT infection in humans. The diagnosis of LTBI is indirect and relies on the detection of an immune response against MT antigens, assuming that the immune response has developed after a contact with the biological agent. Tuberculin skin test (TST) and interferon gamma release assays (IGRAs) are the main diagnostic tools for LTBI, however, both present strengths and limitations. The most ancient diagnostic test (TST) can be associated with several technical errors, has limited positive predictive value, is being influenced by BCG vaccination and several conditions can reduce the skin reactivity. Notwithstanding these limitations, prompt identification of TST conversion, should orientate indications for preventive therapy of LTBI. IGRAs have superior specificity, are not affected by M. bovis, BCG vaccination and other environmental mycobacteria. However, they present some logistical and organisational constraints and are more expensive. Currently, the WHO guidelines recommend that either a TST or an IGRA can be used to detect LTBI in high-income and upper middle-income countries with estimated TB incidences less than 100 per 100,000 population. Two skin tests (C-TB and Diaskintest), using only two specific M. tuberculosis antigens (ESAT-6 and CFP-10) instead of the tuberculin solution, have recently been developed but, to date, none of these tests is available on the European market. CONCLUSION: Early identification and treatment of individuals with LTBI is an important priority for TB control in specific groups at risk within the population: this is of crucial meaning in recently infected cases both at the community level and in some occupational settings. Currently there is no gold standard test for LTBI: an improved understanding of the available tests is needed to develop better tools for diagnosing LTBI and predicting progression to clinical active disease.


Asunto(s)
Tuberculosis Latente , Tuberculosis , Humanos , Interferón gamma , Tuberculosis Latente/diagnóstico , Sensibilidad y Especificidad , Prueba de Tuberculina
20.
BMC Infect Dis ; 20(1): 403, 2020 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-32517725

RESUMEN

BACKGROUND: Current tools for diagnosing latent TB infection (LTBI) detect immunological memory of past exposure but are unable to determine whether exposure is recent. We sought to identify a whole-blood transcriptome signature of recent TB exposure. METHODS: We studied household contacts of TB patients; healthy volunteers without recent history of TB exposure; and patients with active TB. We performed whole-blood RNA sequencing (in all), an interferon gamma release assay (IGRA; in contacts and healthy controls) and PET/MRI lung scans (in contacts only). We evaluated differentially-expressed genes in household contacts (log2 fold change ≥1 versus healthy controls; false-discovery rate < 0.05); compared these to differentially-expressed genes seen in the active TB group; and assessed the association of a composite gene expression score to independent exposure/treatment/immunological variables. RESULTS: There were 186 differentially-expressed genes in household contacts (n = 26, age 22-66, 46% male) compared with healthy controls (n = 5, age 29-38, 100% male). Of these genes, 141 (76%) were also differentially expressed in active TB (n = 14, age 27-69, 71% male). The exposure signature included genes from inflammatory response, type I interferon signalling and neutrophil-mediated immunity pathways; and genes such as BATF2 and SCARF1 known to be associated with incipient TB. The composite gene-expression score was higher in IGRA-positive contacts (P = 0.04) but not related to time from exposure, isoniazid prophylaxis, or abnormalities on PET/MRI (all P > 0.19). CONCLUSIONS: Transcriptomics can detect TB exposure and, with further development, may be an approach of value for epidemiological research and targeting public health interventions.


Asunto(s)
Tuberculosis Latente/diagnóstico , ARN/sangre , Adulto , Anciano , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Estudios de Casos y Controles , Trazado de Contacto , Femenino , Humanos , Interferón Tipo I/metabolismo , Tuberculosis Latente/microbiología , Tuberculosis Latente/transmisión , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Neutrófilos/metabolismo , Mapas de Interacción de Proteínas/genética , ARN/química , ARN/metabolismo , Receptores Depuradores de Clase F/genética , Proteínas Supresoras de Tumor/genética , Adulto Joven
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