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1.
FP Essent ; 502: 29-40, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33683852

RESUMO

Tuberculosis (TB) is the leading cause of infectious disease-related mortality worldwide, affecting 1.7 billion individuals with 9,000 new cases annually in the United States. Disease burden in the United States is greatest among immigrants from areas with high TB rates (eg, India, China, Philippines, Vietnam). Active TB infection can be recently acquired or latent TB infection (LTBI) that becomes active long after initial infection. LTBI testing is recommended for health care workers at hire, immigrants from high-burden areas, and those in high-risk environments (eg, homeless shelters, correctional facilities, long-term care). Health care workers can be tested with interferon gamma release assays (IGRA) or tuberculin skin tests (TSTs). For others older than 5 years, IGRA is recommended. For children younger than 5 years, TSTs are recommended. If test results are positive, several new therapeutic regimens have replaced the previously standard 9-month isoniazid regimen. For patients suspected of having active TB, testing involves chest x-ray, sputum for microscopy, cultures, and nucleic acid amplification tests. Active TB is managed with 2-months of intensive 4-drug therapy, followed by a 4-month continuation phase with isoniazid and rifampin. If multidrug-resistant TB is diagnosed, consultation with infectious disease subspecialists and the health department is recommended.


Assuntos
Tuberculose Latente , Tuberculose Pulmonar , Tuberculose , Criança , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Teste Tuberculínico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Estados Unidos/epidemiologia
2.
Pan Afr Med J ; 38: 24, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777292

RESUMO

Introduction: Latent Tuberculosis Infection (LTBI) screening is recommended for individuals with a known risk factor for progression to active disease especially in the setting of HIV infection. This will ensure early diagnosis and prompt treatment. The purpose of our study was to compare tuberculin skin test (TST) with Interferon Gamma Release Assay (IGRA) in the diagnosis of LTBI among patients with known HIV infection at University of Ilorin Teaching Hospital (UITH), Ilorin. Methods: this was a hospital based cross-sectional study at the Highly Active Antiretroviral therapy (HAART) Clinic and medical wards of the University of Ilorin Teaching Hospital, Ilorin, Nigeria. A total of 282 consenting patients with HIV infection were recruited. Sociodemographic and clinical information was obtained using a well-structured questionnaire. The screening for LTBI was done using Tuberculin skin test (TST) and Interferon Gamma release assay (IGRA). Results: the prevalence of LTBI among HIV infected patients was 40.6% and 53.1% using TST and QFT-IT respectively, while the overall prevalence considering positivity to either of the test was 66%. There was mild agreement (κ: 0.218) between TST and QFT-IT in the diagnosis of LTBI among patients with HIV infection. The association between CD4 count and TST was not statistically significant (p value = 0.388) but there was strong association between CD4 cell count and QFT results (p = 0.001). Conclusion: the prevalence of LTBI is quite high among patients with HIV infection in our locality. There is a need to encourage screening of at-risk individuals to forestall the morbidity and mortality associated with TB in this population.


Assuntos
Infecções por HIV/complicações , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Teste Tuberculínico/métodos , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose Latente/epidemiologia , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Nigéria , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
3.
Medicine (Baltimore) ; 100(7): e24838, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607853

RESUMO

ABSTRACT: More than 70% of tuberculosis (TB) cases diagnosed in the United States (US) occur in non-US-born persons, and this population has experienced less than half the recent incidence rate declines of US-born persons (1.5% vs 4.2%, respectively). The great majority of TB cases in non-US-born persons are attributable to reactivation of latent tuberculosis infection (LTBI). Strategies to expand LTBI-focused TB prevention may depend on LTBI positive non-US-born persons' access to, and ability to pay for, health care.To examine patterns of health insurance coverage and usual sources of health care among non-US-born persons with LTBI, and to estimate LTBI prevalence by insurance status and usual sources of health care.Self-reported health insurance and usual sources of care for non-US-born persons were analyzed in combination with markers for LTBI using 2011-2012 National Health and Nutrition Examination Survey (NHANES) data for 1793 sampled persons. A positive result on an interferon gamma release assay (IGRA), a blood test which measures immunological reactivity to Mycobacterium tuberculosis infection, was used as a proxy for LTBI. We calculated demographic category percentages by IGRA status, IGRA percentages by demographic category, and 95% confidence intervals for each percentage.Overall, 15.9% [95% confidence interval (CI) = 13.5, 18.7] of non-US-born persons were IGRA-positive. Of IGRA-positive non-US-born persons, 63.0% (95% CI = 55.4, 69.9) had insurance and 74.1% (95% CI = 69.2, 78.5) had a usual source of care. IGRA positivity was highest in persons with Medicare (29.1%; 95% CI: 20.9, 38.9).Our results suggest that targeted LTBI testing and treatment within the US private healthcare sector could reach a large majority of non-US-born individuals with LTBI. With non-US-born Medicare beneficiaries' high prevalence of LTBI and the high proportion of LTBI-positive non-US-born persons with private insurance, future TB prevention initiatives focused on these payer types are warranted.


Assuntos
Assistência à Saúde/economia , Emigrantes e Imigrantes/estatística & dados numéricos , Cobertura do Seguro/estatística & dados numéricos , Tuberculose Latente/epidemiologia , Adolescente , Adulto , Idoso , Criança , Estudos Transversais , Assistência à Saúde/estatística & dados numéricos , Feminino , Acesso aos Serviços de Saúde , Humanos , Incidência , Cobertura do Seguro/tendências , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Tuberculose Latente/prevenção & controle , Masculino , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Inquéritos Nutricionais/métodos , Prevalência , Estados Unidos/epidemiologia , Adulto Jovem
4.
BMC Infect Dis ; 21(1): 42, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422003

RESUMO

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.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Migrantes/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Japão/epidemiologia , Tuberculose Latente/diagnóstico , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
6.
BMC Infect Dis ; 21(1): 106, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482742

RESUMO

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.


Assuntos
Perfilação da Expressão Gênica/métodos , Desnutrição/genética , Software , Tuberculose/genética , Adolescente , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Criança , Comorbidade , Feminino , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Tuberculose Latente/genética , Masculino , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Transcriptoma , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adulto Jovem
7.
Aliment Pharmacol Ther ; 53(3): 390-399, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33314259

RESUMO

BACKGROUND: Anti-tumour necrosis factor (anti-TNF) therapy increases the risk of tuberculosis (TB). Given limitations of screening techniques, it remains uncertain if patients receiving anti-TNF in TB endemic regions should be screened for latent infection with chemoprophylaxis restricted to those with proven infection, or if all patients should receive chemoprophylaxis. AIMS: To compare the incidence of active TB with infliximab (IFX) following targeted and universal TB chemoprophylaxis, and to determine the rates of adverse events (AE) related to TB chemoprophylaxis METHODS: A multi-centre retrospective cohort study was performed at 18 hospitals in China of 1968 adult patients with IBD receiving IFX from 2009 to 2017. TB screening prior to IFX was performed with chest X-ray and/or computed tomography [CT] and immune reactivity testing (interferon-γ release assay and/or tuberculin skin test). Patients were followed-up for a minimum of 3 months after IFX discontinuation, or until last hospital visit if IFX therapy was ongoing. Targeted strategy was defined as TB chemoprophylaxis only for patients with a positive latent TB screen, with universal strategy defined as TB chemoprophylaxis for all patients. RESULTS: Mean follow-up was 1.07 ± 0.87 years with a total follow-up of 2102 patient-years. There were 1433 patients in the targeted and 483 patients in the universal TB chemoprophylaxis groups, with no significant difference in the incidence rates of active TB between groups (673.3 per 100 000 population per year vs 891.5 per 100 000 population per year, P = 0.60). In the targeted group, 55/1433 patients received TB chemoprophylaxis compared with 483/483 in the universal group, with significantly fewer AEs related to TB chemoprophylaxis in the targeted compared to the universal group (0.35% (5/1433) vs 6.8% (33/483), P < 0.05). CONCLUSIONS: In this study of patients receiving IFX in a TB endemic area, universal chemoprophylaxis was not associated with a reduced risk of active TB when compared to a targeted chemoprophylaxis strategy, and AEs were more common. This supports the use of targeted TB chemoprophylaxis when anti-TNF therapy is initiated in TB endemic regions.


Assuntos
Doenças Inflamatórias Intestinais , Tuberculose Latente , Tuberculose , Adulto , Quimioprevenção , China , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Tuberculose Latente/prevenção & controle , Estudos Retrospectivos , Teste Tuberculínico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Fator de Necrose Tumoral alfa/uso terapêutico
8.
PLoS One ; 15(12): e0243951, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33332458

RESUMO

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.


Assuntos
Pessoal de Saúde , Tuberculose Latente/diagnóstico , Tuberculina/isolamento & purificação , Adolescente , Adulto , Bangladesh/epidemiologia , Feminino , Humanos , Tuberculose Latente/epidemiologia , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Testes Cutâneos/normas , Centros de Atenção Terciária , Adulto Jovem
9.
BMC Infect Dis ; 20(1): 746, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046016

RESUMO

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.


Assuntos
Busca de Comunicante/métodos , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Testes Diagnósticos de Rotina , Características da Família , Feminino , Humanos , Lactente , Recém-Nascido , Quirguistão/epidemiologia , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Fatores de Risco , Teste Tuberculínico/métodos , Tuberculose Pulmonar/microbiologia , Adulto Jovem
10.
Brasília; CONITEC; out. 2020.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1141494

RESUMO

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


Assuntos
Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/imunologia , Testes de Liberação de Interferon-gama/métodos , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
11.
Yonsei Med J ; 61(9): 789-796, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882763

RESUMO

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.


Assuntos
Tuberculose Latente/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Antígenos de Bactérias/sangue , Antígenos de Bactérias/genética , Antígenos de Superfície/sangue , Antígenos de Superfície/genética , Proteínas de Bactérias , Pequim , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Humanos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/metabolismo , República da Coreia , Sensibilidade e Especificidade
12.
Medicine (Baltimore) ; 99(36): e22015, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899054

RESUMO

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.


Assuntos
Tuberculose Latente/epidemiologia , Tuberculose Latente/transmissão , Mycobacterium tuberculosis/isolamento & purificação , Adolescente , Criança , Testes Diagnósticos de Rotina/métodos , Emigrantes e Imigrantes , Família , Feminino , Amigos , Humanos , Incidência , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Masculino , Mycobacterium tuberculosis/imunologia , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Viagem/tendências , Teste Tuberculínico/métodos
13.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32994177

RESUMO

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.


Assuntos
Testes de Liberação de Interferon-gama/estatística & dados numéricos , Tuberculose Latente/diagnóstico , Refugiados/estatística & dados numéricos , Teste Tuberculínico/estatística & dados numéricos , California/epidemiologia , Pré-Escolar , Feminino , Humanos , Tuberculose Latente/epidemiologia , Masculino , Estudos Retrospectivos
16.
Public Health Rep ; 135(1_suppl): 172S-181S, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735191

RESUMO

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.


Assuntos
Tuberculose Latente/diagnóstico , Atenção Primária à Saúde/organização & administração , Adulto , Fatores Etários , Antituberculosos/uso terapêutico , California , Emigrantes e Imigrantes , Fidelidade a Diretrizes , Humanos , Hospedeiro Imunocomprometido , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/etnologia , Cadeias de Markov , Programas de Rastreamento , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/normas , Instituições Residenciais , Medição de Risco , Tuberculose/etnologia
17.
Aust N Z J Public Health ; 44(5): 353-359, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32776658

RESUMO

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.


Assuntos
Assistência à Saúde Culturalmente Competente , Tuberculose Latente/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Vigilância da População/métodos , Migrantes/psicologia , Adolescente , Adulto , Idoso , Austrália/epidemiologia , Feminino , Política de Saúde , Humanos , Índia/etnologia , Entrevistas como Assunto , Tuberculose Latente/etnologia , Tuberculose Latente/psicologia , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Paquistão/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Pesquisa Qualitativa , Migrantes/estatística & dados numéricos , Adulto Jovem
18.
PLoS One ; 15(7): e0235859, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687494

RESUMO

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.


Assuntos
Quimiocina CX3CL1/sangue , Quimiocina CXCL10/sangue , Interleucinas/sangue , Tuberculose Latente/sangue , Tuberculose Pulmonar/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Quimiocina CX3CL1/análise , Quimiocina CXCL10/análise , Feminino , Humanos , Interleucinas/análise , Tuberculose Latente/diagnóstico , Tuberculose Latente/metabolismo , Masculino , Pessoa de Meia-Idade , Saliva/química , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/metabolismo , Fator A de Crescimento do Endotélio Vascular/análise
19.
BMC Infect Dis ; 20(1): 469, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615981

RESUMO

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.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Citocinas/imunologia , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Programas de Rastreamento/métodos , Mycobacterium tuberculosis/imunologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Características da Família , Feminino , Gâmbia/epidemiologia , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Tuberculose Latente/microbiologia , Masculino , Sensibilidade e Especificidade , Teste Tuberculínico
20.
Med Lav ; 111(3): 170-183, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32624559

RESUMO

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.


Assuntos
Tuberculose Latente , Tuberculose , Humanos , Interferon gama , Tuberculose Latente/diagnóstico , Sensibilidade e Especificidade , Teste Tuberculínico
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