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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(5): e23207, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592820

RESUMO

ABSTRACT: Tuberculosis (TB) is one of the leading causes of childhood morbidity and death globally. Lack of rapid, effective non-sputum diagnosis and prediction methods for TB in children are some of the challenges currently faced. In recent years, blood transcriptional profiling has provided a fresh perspective on the diagnosis and predicting the progression of tuberculosis. Meanwhile, combined with bioinformatics analysis can help to identify the differentially expressed genes (DEGs) and functional pathways involved in the different clinical stages of TB. Therefore, this study investigated potential diagnostic markers for use in distinguishing between latent tuberculosis infection (LTBI) and active TB using children's blood transcriptome data.From the Gene Expression Omnibus database, we downloaded two gene expression profile datasets (GSE39939 and GSE39940) of whole blood-derived RNA sequencing samples, reflecting transcriptional signatures between latent and active tuberculosis in children. GEO2R tool was used to screen for DEGs in LTBI and active TB in children. Database for Annotation, Visualization and Integrated Discovery tools were used to perform Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis. STRING and Cytoscape analyzed the protein-protein interaction network and the top 15 hub genes respectively. Receiver operating characteristics curve was used to estimate the diagnostic value of the hub genes.A total of 265 DEGs were identified, including 79 upregulated and 186 downregulated DEGs. Further, 15 core genes were picked and enrichment analysis revealed that they were highly correlated with neutrophil activation and degranulation, neutrophil-mediated immunity and in defense response. Among them TLR2, FPR2, MMP9, MPO, CEACAM8, ELANE, FCGR1A, SELP, ARG1, GNG10, HP, LCN2, LTF, ADCY3 had significant discriminatory power between LTBI and active TB, with area under the curves of 0.84, 0.84, 0.84, 0.80, 0.87, 0.78, 0.88, 0.84, 0.86, 0.82, 0.85, 0.85, 0.79, and 0.88 respectively.Our research provided several genes with high potential to be candidate gene markers for developing non-sputum diagnostic tools for childhood Tuberculosis.


Assuntos
Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Tuberculose/epidemiologia , Tuberculose/genética , Adolescente , Biomarcadores , Criança , Pré-Escolar , Bases de Dados Genéticas , Feminino , Regulação da Expressão Gênica , Humanos , Tuberculose Latente/epidemiologia , Tuberculose Latente/genética , Masculino , Neutrófilos/metabolismo , Mapas de Interação de Proteínas , Curva ROC
4.
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
5.
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.
Artigo em Inglês | MEDLINE | ID: mdl-33406582

RESUMO

Type 2 diabetes mellitus (T2DM) and tuberculosis (TB) together impose a high disease burden in terms of both mortality and health economics worldwide. The objective of this study was to estimate the prevalence and risk factors of latent TB infection (LTBI) in patients with T2DM in Malaysia. A cross-sectional study was performed, and adult T2DM patients (n = 299) were included. Simple and multiple logistic regression analyses were performed to identify the LTBI-associated risk factors in patients with T2DM. Multiple logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) between T2DM and LTBI and was adjusted for potential confounders. The prevalence of LTBI in patients with T2DM was 11.4% (95% CI: 8.0-15.0%). There was no significant difference in the socio-demographic characteristics between LTBI and non-LTBI subjects. No significant difference in the smoking status, the duration of smoking, and the duration of T2DM, HbA1c, or treatments was observed. Interestingly, a higher level of education was observed to be associated with a lower prevalence of LTBI in T2DM patients (aOR: 0.08, 95% CI: 0.01-0.70, p = 0.02). Although the prevalence of LTBI in T2DM was low, it is important to screen for it in T2DM patients due to the risk of developing severe active TB.


Assuntos
Diabetes Mellitus Tipo 2 , Tuberculose Latente , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Tuberculose Latente/epidemiologia , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Teste Tuberculínico
7.
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
8.
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
9.
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
10.
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
11.
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
12.
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
13.
Am J Trop Med Hyg ; 103(4): 1466-1472, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32876010

RESUMO

In many low- and middle-income countries, tuberculosis (TB) incidence in prisons is high, exposing incarcerated populations to an elevated risk of TB infection. We conducted a randomized, double-blind, placebo-controlled trial among HIV-negative male inmates of a high TB burden prison to determine whether isoniazid given twice weekly (900 mg) for 12 months prevents TB infection. The primary outcome was QuantiFERON-TB Gold in Plus (QFT) conversion to ≥ 0.35 international units per milliliter (IU/mL) at 6 months; secondary outcomes included alternative QFT thresholds (≥ 0.7, ≥ 2.0, and ≥ 4.0 IU/mL). In total, 467 participants were randomly assigned to intervention (N = 258) or control (N = 209). In an interim analysis of participants who had completed 6 months of follow-up (N = 170), QFT conversion occurred in 20.8% (19/91) and 21.5% (17/79) of participants in intervention and control arms (efficacy: 2.9%, P = 0.91), respectively. The trial was then stopped according to the trial protocol, and the remaining participants prematurely discontinued. In an analysis of secondary outcomes, the intervention arm had significantly lower rates of conversion at a cutoff of ≥ 2.0 IU/mL (efficacy: 82.6%, P < 0.01). In conclusion, 900 mg of isoniazid, administered twice a week, did not effectively prevent QFT conversion at a cutoff point ≥ 0.35 IU/mL in a trial of QFT-negative inmates. Higher QFT cutoffs are associated with sustained conversion and greater protection. Future clinical trials that evaluate protection for latent infection should use the highest cutoff than that recommended by the manufacturer.


Assuntos
Isoniazida , Tuberculose Latente/tratamento farmacológico , Prevenção Primária , Prisioneiros , Tuberculose/prevenção & controle , Adulto , Método Duplo-Cego , Humanos , Incidência , Testes de Liberação de Interferon-gama/métodos , Isoniazida/administração & dosagem , Isoniazida/uso terapêutico , Tuberculose Latente/epidemiologia , Mycobacterium tuberculosis/isolamento & purificação , Prisões/estatística & dados numéricos , Teste Tuberculínico/métodos , Adulto Jovem
14.
Epidemiol Infect ; 148: e181, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32741390

RESUMO

Despite considerable efforts to control tuberculosis (TB) among Ethiopian immigrants in Israel, an outbreak of TB among second-generation Ethiopian immigrants that involved native Israelis occurred between January 2011 and December 2019. The aim of this article is to report on this outbreak and discuss the patient and health system barriers that led to its propagation. Overall, 13 culture-positive TB patients were diagnosed in this outbreak. An additional 36 cases with identical mycobacterium tuberculosis genotypes were identified through cross-checking with the National TB Laboratory Registry. Among the 32 close contacts of the index case, 18 (56.3%) reported for screening and treatment of latent TB infection (LTBI) was recommended for 11 (61.1%) of them. However, none completed treatment and eight eventually developed TB. Of the 385 close contacts identified in this outbreak, 286 (74.3%) underwent contact investigation, 154 (53.8%) were recommended LTBI treatment, but only 26 (16.9%) completed the treatment. Routine contact investigation and treatment practice measures failed to contain the cascade of infection and disease, leading to the spread of the infecting strain of TB. This report highlights the challenges to identify the high-risk group and address barriers to care among such a vulnerable population.


Assuntos
Busca de Comunicante , Emigrantes e Imigrantes , Tuberculose/epidemiologia , Tuberculose/transmissão , Adolescente , Adulto , Surtos de Doenças , Etiópia/epidemiologia , Feminino , Humanos , Israel/epidemiologia , Tuberculose Latente/epidemiologia , Masculino , Mycobacterium tuberculosis , Estudos Retrospectivos , Tuberculose/prevenção & controle , Adulto Jovem
15.
N Engl J Med ; 383(4): 359-368, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32706534

RESUMO

BACKGROUND: Vitamin D metabolites support innate immune responses to Mycobacterium tuberculosis. Data from phase 3, randomized, controlled trials of vitamin D supplementation to prevent tuberculosis infection are lacking. METHODS: We randomly assigned children who had negative results for M. tuberculosis infection according to the QuantiFERON-TB Gold In-Tube assay (QFT) to receive a weekly oral dose of either 14,000 IU of vitamin D3 or placebo for 3 years. The primary outcome was a positive QFT result at the 3-year follow-up, expressed as a proportion of children. Secondary outcomes included the serum 25-hydroxyvitamin D (25[OH]D) level at the end of the trial and the incidence of tuberculosis disease, acute respiratory infection, and adverse events. RESULTS: A total of 8851 children underwent randomization: 4418 were assigned to the vitamin D group, and 4433 to the placebo group; 95.6% of children had a baseline serum 25(OH)D level of less than 20 ng per milliliter. Among children with a valid QFT result at the end of the trial, the percentage with a positive result was 3.6% (147 of 4074 children) in the vitamin D group and 3.3% (134 of 4043) in the placebo group (adjusted risk ratio, 1.10; 95% confidence interval [CI], 0.87 to 1.38; P = 0.42). The mean 25(OH)D level at the end of the trial was 31.0 ng per milliliter in the vitamin D group and 10.7 ng per milliliter in the placebo group (mean between-group difference, 20.3 ng per milliliter; 95% CI, 19.9 to 20.6). Tuberculosis disease was diagnosed in 21 children in the vitamin D group and in 25 children in the placebo group (adjusted risk ratio, 0.87; 95% CI, 0.49 to 1.55). A total of 29 children in the vitamin D group and 34 in the placebo group were hospitalized for treatment of acute respiratory infection (adjusted risk ratio, 0.86; 95% CI, 0.52 to 1.40). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS: Vitamin D supplementation did not result in a lower risk of tuberculosis infection, tuberculosis disease, or acute respiratory infection than placebo among vitamin D-deficient schoolchildren in Mongolia. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02276755.).


Assuntos
Colecalciferol/uso terapêutico , Suplementos Nutricionais , Tuberculose Latente/prevenção & controle , Mycobacterium tuberculosis , Vitaminas/uso terapêutico , Criança , Colecalciferol/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Incidência , Tuberculose Latente/epidemiologia , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Falha de Tratamento , Teste Tuberculínico , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitaminas/efeitos adversos
16.
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
17.
MMWR Recomm Rep ; 69(7): 1-27, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32730235

RESUMO

This report provides an introduction and reference tool for tuberculosis (TB) controllers regarding the essential components of a public health program to prevent, control, and eliminate TB. The Advisory Council for the Elimination of Tuberculosis and the National Tuberculosis Controllers Association recommendations in this report update those previously published (Advisory Council for the Elimination of Tuberculosis. Essential components of a tuberculosis prevention and control program. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR Recomm Rep 1995;44[No. RR-11]). The report has been written collaboratively on the basis of experience and expert opinion on approaches to organizing programs engaged in diagnosis, treatment, prevention, and surveillance for TB at state and local levels.This report reemphasizes the importance of well-established priority strategies for TB prevention and control: identification of and completion of treatment for persons with active TB disease; finding and screening persons who have had contact with TB patients; and screening, testing, and treatment of other selected persons and populations at high risk for latent TB infection (LTBI) and subsequent active TB disease.Health departments are responsible for public safety and population health. To meet their responsibilities, TB control programs should institute or ensure completion of numerous responsibilities and activities described in this report: preparing and maintaining an overall plan and policy for TB control; maintaining a surveillance system; collecting and analyzing data; participating in program evaluation and research; prioritizing TB control efforts; ensuring access to recommended laboratory and radiology tests; identifying, managing, and treating contacts and other persons at high risk for Mycobacterium tuberculosis infection; managing persons who have TB disease or who are being evaluated for TB disease; providing TB training and education; and collaborating in the coordination of patient care and other TB control activities. Descriptions of CDC-funded resources, tests for evaluation of persons with TB or LTBI, and treatment regimens for LTBI are provided (Supplementary Appendices; https://stacks.cdc.gov/view/cdc/90289).


Assuntos
Erradicação de Doenças/organização & administração , Saúde Pública , Tuberculose/prevenção & controle , Comitês Consultivos , Humanos , Tuberculose Latente/epidemiologia , Tuberculose Latente/prevenção & controle , Programas de Rastreamento , Desenvolvimento de Programas , Tuberculose/epidemiologia , Estados Unidos/epidemiologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-32605191

RESUMO

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.


Assuntos
Pessoal de Saúde , Tuberculose Latente , Tuberculose , Adulto , Feminino , Alemanha/epidemiologia , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Masculino , Ocupações , Prevalência , Medição de Risco , Tuberculose/epidemiologia
19.
Ann Hematol ; 99(9): 2201-2203, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32699943
20.
BMC Public Health ; 20(1): 838, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493327

RESUMO

BACKGROUND: In 2018, there were 70.8 million refugees, asylum seekers and persons displaced by wars and conflicts worldwide. Many of these individuals face a high risk for tuberculosis in their country of origin, which may be accentuated by adverse conditions endured during their journey. We summarised the prevalence of active and latent tuberculosis infection in refugees and asylum seekers through a systematic literature review and meta-analyses by country of origin and host continent. METHODS: Articles published in Medline, EMBASE, Web of Science and LILACS from January 2000 to August 2017 were searched for, without language restriction. Two independent authors performed the study selection, data extraction and quality assessment. Random effect models were used to estimate average measures of active and latent tuberculosis prevalence. Sub-group meta-analyses were performed according to country of origin and host continent. RESULTS: Sixty-seven out of 767 identified articles were included, of which 16 entered the meta-analyses. Average prevalence of active and latent tuberculosis was 1331 per 100 thousand inhabitants [95% confidence interval (CI) = 542-2384] and 37% (95% CI = 23-52%), respectively, both with high level of heterogeneity (variation in estimative attributable to heterogeneity [I2] = 98.2 and 99.8%). Prevalence varied more according to countries of origin than host continent. Ninety-one per cent of studies reported routine screening of recently arrived immigrants in the host country; two-thirds confirmed tuberculosis bacteriologically. Many studies failed to provide relevant information. CONCLUSION: Tuberculosis is a major health problem among refugees and asylum seekers and should be given special attention in any host continent. To protect this vulnerable population, ensuring access to healthcare for early detection for prevention and treatment of the disease is essential.


Assuntos
Tuberculose Latente/epidemiologia , Refugiados/estatística & dados numéricos , Tuberculose/epidemiologia , Feminino , Humanos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Prevalência
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