Isoniazid use, effectiveness, and safety for treatment of latent tuberculosis infection: a systematic review

ABSTRACT Background: The treatment strategy for latent tuberculosis infection is to reduce the number of tuberculosis cases and consequently reduce the transmission of pathogenic bacteria. This study aimed to determine the safety, effectiveness, and adherence of isoniazid use for latent tuberculosis infection treatment. Methods: To identify studies on isoniazid use for latent tuberculosis infection, five electronic databases were searched. The methods and results are presented in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Most studies (53) used isoniazid for 9 months. The prevalence of use and adherence to treatment varied considerably (18% to 100%), and were evaluated by participant completion of isoniazid treatment for latent tuberculosis infection. The adverse events most frequently reported were hepatotoxicity, gastric intolerance, and neuropathy; the rates of occurrence ranged from < 1% to 48%. In the studies that evaluated the effectiveness of isoniazid for latent tuberculosis infection, the rate varied from 0 to 19.7% for patients who did not have active tuberculosis after the follow-up period. Conclusions: The importance of maintaining follow up for patients using isoniazid should be emphasized due to the risk of developing adverse events. Despite the treatment challenges, the rates of patients who used isoniazid and developed active tuberculosis during the follow-up period were low. We believe that isoniazid continues to contribute to tuberculosis control worldwide, and better care strategies are required.

Novel biomarkers combination in the application of discriminating active tuberculosis and latent tuberculosis infection / 中华传染病杂志

Objective:To evaluate the expressions of three biomarkers combination of CD27, CD38 and human leucocyte antigen (HLA)-DR in the application of discrminating active tuberculosis (ATB) and latent tuberculosis infection (LTBI).Methods:Sixty cases of ATB and 44 cases of LTBI were enrolled from March 2021 to February 2022 in Huashan Hospital, Fudan University and Wuxi Fifth People′s Hospital. Freshly isolated peripheral blood mononuclear cells (PBMC) from patients were stimulated with 6 kDa early secretory antigenic target/culture filtrate protein 10 peptide pools. The expressions of CD27, CD38 and HLA-DR on Mycobacterium tuberculosis-specific CD4 + T lymphocytes were evaluated by polychromatic flow cytometry. Mann-Whitney U test was used for statistical analysis. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the diagnostic value of biomarkers in discriminating ATB and LTBI. Results:The frequencies of CD27 -, CD38 +, HLA-DR +, CD27 -CD38 +, CD27 -HLA-DR + and CD38 + HLA-DR + in ATB group were all higher than those in LTBI group, and the differences were all statistically significant ( U=26.00, 451.00, 384.00, 8.00, 7.00 and 184.00, respectively, all P<0.001). The AUROC of CD27 -CD4 + interferon-γ(IFN-γ) + T lymphocytes was 0.71 with a cut-off value of 52.31%, with the sensitivity of 50.00% and specificity of 87.20%. The AUROC of CD38 + CD4 + IFN-γ + T lymphocytes was 0.82 with a cut-off value of 30.25%, with the sensitivity of 73.40% and specificity of 89.70%. The AUROC of HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.85 with a cut-off value of 36.60%, with the sensitivity of 66.00% and specificity of 94.90%. The AUROC of CD27 -CD38 + CD4 + IFN-γ + T lymphocytes was 0.80 with a cut-off value of 8.82%, with the sensitivity of 90.60% and specificity of 61.50%. The AUROC of CD27 -HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.83 with a cut-off value of 18.62%, with the sensitivity of 75.00% and specificity of 79.50%. The AUROC of CD38 + HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.93 with a cut-off value of 22.35%, with the sensitivity of 79.70% and specificity of 100.00%. Conclusions:The expressions of CD27 -, CD38 + and HLA-DR + in Mycobacterium tuberculosis-specific CD4 + T lymphocytes are higher in ATB group compared to LTBI group. ATB and LTBI could be well discriminated by detecting the expressions of CD27, CD38 and HLA-DR on CD4 + IFN-γ + T lymphocytes with flow cytometry.

Latent tuberculosis infection and screening method among close contacts in schools in Xuhui District，Shanghai from 2020 to 2022 / 上海预防医学

ObjectiveTo investigate the latent tuberculosis infection （LTBI） of close contacts in schools of Xuhui District， and to explore the tuberculin skin test （TST）- interferon-γ release assay （IGRA） two-step method in order to discover the screening strategy of tuberculosis in Xuhui District. MethodsClose contacts of tuberculosis in schools of Xuhui District from 2020 to 2022 were selected as research subjects. Screening was conducted using symptom questionnaire， TST， chest X-rays， IGRA， and the information including the etiological results and grade of the index cases， as well as gender， age， and relationship with the index cases of the research subjects were collected. ResultsTotally 615 close contacts of 32 tuberculosis cases occurred in the schools were finally included. Of the 609 close contacts who completed tuberculosis infection screening and underwent TST testing， 153 TST（+） individuals underwent IGRA testing. The final LTBI rate was 4.6%， and the pulmonary tuberculosis detection rate was 163 per 100 000. The relationship with the index cases was an influencing factor for LTBI. The IGRA positivity rate was higher among close contacts with TST ≥15 mm than among those with 10 mm≤ TST <15 mm （χ2=14.41， P<0.05）. ConclusionThe latent tuberculosis infection among close contacts of school tuberculosis cases in Xuhui District remains serious. TST-IGRA two-step method can assist in the accurate diagnosis of LTBI and pulmonary tuberculosis cases.

Evaluation of screening methods for the students who had close contact with pulmonary tuberculosis patients in Shanghai / 上海预防医学

ObjectiveTo evaluate the current screening methods for the students who were in close contact with tuberculosis patients， that could accurately identify the preventive treatment subjects， and to improve the tuberculosis prevention and control in Shanghai schools. MethodsThe freshman/sophomore who were in close contact with active tuberculosis patients in the colleges in 2019 were recruited. All the subjects underwent both tuberculin skin test （TST） and QuantiFERON-TB gold in-tube （QFT） test at the enrollment. After signed the informed consent， all of the participants filled in a questionnaire and determined their baseline tuberculosis infection status. They were followed up for 2 years to monitor the conversion of infection status and the incidence of tuberculosis. ResultsFour of 9 （44.4%） positive participants had conversion to negative results， and 5 of 300 （1.7%） negative participants had conversion to positive during the 2-year follow-up， one of which was diagnosed with active tuberculosis. We assessed diagnostic agreement between QFT and TST at different cut-off values. The highest coincidence rate was 94.0% when choosing 15 mm as the cut-off value， with Kappa coefficient of 0.45 （95%CI： 0.32‒0.59）. ConclusionAlthough stricter than the national work requirements， the prevention and control of tuberculosis in Shanghai schools still need to be carried out meticulously. It's necessary to strengthen daily prevention and control measures， and improve the ability of management.

Latent tuberculosis infection status and its risk factors among tuberculosis-related health-care workers in Shanghai / 上海预防医学

ObjectiveTo obtain the status of latent tuberculosis infection （LTBI） among tuberculosis （TB）-related health-care workers （HCWs） in Shanghai， and to explore the risk factors related to TB infection. MethodsA multi-center cross-sectional study was conducted by recruiting medical workers from multiple designated TB hospitals， centers for disease control and prevention， and community health service centers in Shanghai. Each subject was required to complete a questionnaire and to provide a blood sample for TB infection test. Univariate and multivariate analysis ware made in order to find risk factors relating to TB infection. ResultsA total of 165 medical workers were recruited， and the proportion of TB infection was 16.36% （95%CI： 11.49%‒22.76%）. Multivariate logistic analysis showed that clinical doctors and nurses （adjusted OR=9.756， 95%CI： 1.790‒53.188）， laboratory staffs （adjusted OR=78.975， 95%CI： 8.749‒712.918）， and nursing and cleaning workers （adjusted OR=89.920， 95%CI： 3.111‒2 598.930） had higher risk of TB infection. ConclusionThe overall LTBI prevalence among TB-related HCWs is low. However， working as doctors， nurses， laboratory staffs， nursing workers and cleaning workers are risk factors of TB infection. TB-related HCWs who work at hospitals are at risk of TB infection comparing to medical staffs who work outside hospitals.

Strengthening management of latent tuberculosis infection and accelerating the elimination of the tuberculosis epidemic / 上海预防医学

Screening and preventive treatment for latent tuberculosis infection （LTBI） are important measures to reduce the incidence of active tuberculosis （TB） and its global burden. This paper discusses the current status of LTBI prevalence and preventive treatment， risk of incidence in high-risk groups， screening methods， and other interventions， emphasizing the importance of prevention and control as early as possible in a scientific strategy， so as to lay a solid foundation for eliminating TB by 2030.

Progress on diagnosis and treatment of latent tuberculosis infection / 浙江大学学报·医学版

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.

To study the prevalence of latent tuberculosis infection among medical students

Background: Risk of developing latent tuberculosis infection increases in medical students with their higher exposure to TB care facilities. Objective: To study the prevalence of latent TB infection among students attending professional degrees MBBS, BDS, MD, MS, MDS at King George’s Medical University, India. Methods: This study was carried out with Tuberculin skin testing among students and active TB cases were excluded. A standard dose of 0.1?mL of purified protein derivative was slowly injected intra dermally into non-dominant forearm. After 48-72 hours, the reaction was estimated by measuring the transverse diameter of the induration. Results: Total 561 students had given consent to get enrolled. Prevalence of latent tuberculosis infection was significant with period of clinical exposure (p-value < 0.05), average size of induration (p-value < 0.001), and history of prior Tuberculin Skin Test (p-value < 0.001). However it was not significant with the age (p-value > 0.05), gender (p-value > 0.05), and history of contact with active cases of TB (p-value > 0.05). Conclusion: The prevalence of latent tuberculosis infection is higher in post graduate students followed by interns and final year students due to more exposure to patients in wards and clinics at King George’s Medical University, India.

Tuberculosis latente: diagnóstico y tratamiento actual / Latent tuberculosis: current diagnosis and treatment

Resumen La infección tuberculosa latente (TL) afecta al 23% de la población y constituye un reservorio de tuberculosis (TBC) ya que 10% progresa hacia una TBC. La TL se reconoce por pruebas como la tuberculina (PPD o TST) y los ensayos de liberación de Interferón gama (IGRAs). La sensibilidad de IGRAs (versión Quantiferon TB Gold plus) es 94% y del PPD 77%. La especificidad del Quantiferon TB Gold Plus es 97% y del PPD 68%. El valor predictivo de progresión a TBC activa de estas pruebas es bajo (PPD: 1,5%, IGRAs: 2,7%) pero mejora en personas de alto riesgo de contraer TBC (PPD: 2,4%, IGRAs: 6,8%). Las personas con pruebas negativas que posteriormente presentan viraje (prueba positiva) tienen mayor riesgo de progresión a TBC activa. Estas pruebas son útiles en el seguimiento de contactos intradomiciliarios, extranjeros de países con altas tasas de TBC, inmunosuprimidos, enfermedad renal crónica, diabetes, silicosis y secuelas pulmonares de TBC no tratada. En la terapia de TL se utiliza isoniazida (H) auto-administrada por plazos de 6 a 12 meses con eficacia protectora de 60% y riesgo de toxicidad hepática de 2% pero con baja adherencia (50-70%). La asociación de H con rifapentina en dosis única semanal durante 12 semanas tiene eficacia de 81%, adherencia de 82% y baja toxicidad hepática (0,4%). Nuevos biomarcadores de TL y vacunas que mejoren la inmunidad en TL se encuentran en estudio. El tratamiento de la TL puede reducir la incidencia de TBC a largo plazo.

Latent tuberculosis infection (LT) affects 23% of the population and constitutes a reservoir of tuberculosis (TB) as 10% progresses to TB. LT is recognized by tests such as tuberculin (PPD or TST) and Interferon gamma release assays (IGRAs). The sensitivity of IGRAs (Quantiferon TB Gold plus version) is 94% and PPD 77%. The specificity of Quantiferon TB Gold Plus is 97% and PPD 68%. The predictive value of progression to active TB of these tests is low (PPD: 1.5%, IGRAs: 2.7%) but improves in people at high risk of contracting TB (PPD: 2.4%, IGRAs: 6.8%). People with negative tests who subsequently turn around (positive) have a higher risk of progression to active TB. These tests are useful in the follow-up of intra-household contacts, foreigners from countries with high rates of TB, immunosuppressed, chronic kidney disease, diabetes, silicosis and pulmonary sequelae of untreated TB. In LT therapy, self-administered isoniazid (H) is used for periods from 6 to 12 months with protective efficacy of 60% and risk of liver toxicity of 2%, but with low adherence (50-70%). The association of H with rifapentine in a single weekly dose for 12 weeks has efficacy of 81%, adherence of 82% and low liver toxicity (0.4%). New LT biomarkers and vaccines that improve immunity in LT are under study. Treatment of LT may reduce the incidence of TB in the long term.

Prevalence of latent tuberculosis infections among residents in Nanchuan District / 预防医学

Objective@#To investigate the current prevalence of latent tuberculosis infection (LTBI) among residents living in Nanchuan District, Chongqing Municipality, so as to provide the evidence for formulating LTBI control measures.@*Methods@#The residents living in one street and one township from Nanchuan District were randomly selected using the multistage cluster sampling method during the period between January and April, 2020, and their demographic information, smoking history, history of alcohol consumption, history of contacts with tuberculosis patients and Bacillus Calmette-Guérin ( BCG ) vaccination scars were collected. The infection of Mycobacterium tuberculosis was detected using interferon gamma release assay ( IGRA ), and a positive IGRA test and exclusion of active tuberculosis was defined as LTBI. The prevalence of LTBI was descriptively analyzed among the study subjects.@*Results@#Totally 1 000 residents were recruited, including 381 males and 619 females, with a male to female ratio of 0.62∶1. The mean age was ( 45.87±18.40 ) years. Among all participants, there were 222 smokers ( 22.20% ), 247 subjects consuming alcohol (24.70%), 62 subjects with a history of contacts with tuberculosis patients ( 6.20% ) and 904 subjects with BCG scars ( 90.40% ). A total of 198 residents were diagnosed with LTBI (19.80% prevalence), and a higher prevalence rate of LTBI was seen in men than in women ( 23.36% vs. 17.61%; χ2=4.911, P=0.027 ). The prevalence of LTBI was significantly higher in married/divorced/widowed residents than in unmarried residents ( 24.22% vs. 2.01%; χ2=49.514, P<0.001 ), and significantly greater prevalence was found in smokers than in non-smokers ( 27.93% vs. 17.48%; χ2=11.871, P=0.001 ). The prevalence of LTBI appeared a tendency towards a rise with age ( χ2trend=59.100, P<0.001 ) and body mass index ( χ2trend=9.479, P=0.002 ).@*Conclusions@#The prevalence of LTBI is high among residents living in Nanchuan District, notably among elder, male smokers with high body mass index. Risk monitoring and timely interventions are required.

Meta-analysis of infection and disease among household contacts of patients with drug-resistant tuberculosis / 中国热带医学

@#Abstract: Objective　To analyze the association between drug resistance and the risk of latent tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis, and to explore whether the compensatory mutation of drug-resistant Mycobacterium tuberculosis will enhance its pathogenicity or transmission ability. Methods　The English and Chinese databases, including PubMed, web of science, EMBASE, Cochrane library database, CNKI and Wanfang database, were searched by computer from the time of establishment of the database to January 2022. Cohort studies on the risk of infection and disease among household contacts of patients with drug-resistant and sensitive pulmonary tuberculosis were searched and screened according to the inclusion and exclusion criteria. The data were extracted and evaluated by NOS scale, using stata16.0 software meta-analysis to calculate the combined effect of tuberculosis infection and disease risk of family contacts, and carry out heterogeneity test, subgroup analysis and sensitivity analysis. Results　A total of 7 cohort studies involving 9653 TB index cases and 29, 734 house contacts were included. The results of meta-analysis showed that compared with drug-sensitive pulmonary tuberculosis patients, the risk of tuberculosis infection in house contacts of drug-resistant pulmonary tuberculosis patients was increased (OR=1.56, 95%CI=1.25-1.96, P<0.001), but there was no difference in the risk of incidence (RR=1.06, 95%CI=0.80-1.41, P=0.67>0.05). Subgroup analysis showed that the risk of latent tuberculosis infection in house contacts was affected by the study area, and the size of family contacts had an impact on the risk of TB . Sensitivity analysis showed that the results of meta-analysis were robust. Conclusion　Compared with drug sensitive TB patients, household contacts with drug-resistant TB patients had a higher risk of tuberculosis, but there was no difference in the risk of TB among the two groups.

Expert consensus on diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases / 中华内科杂志

Rheumatic diseases, a typical kind of autoimmune disease, are often treated with glucocorticoids, immunosuppressants, biological agents, and small-molecule targeted drugs, which often leads to immune dysfunction in patients and increases the risk of activation of latent tuberculosis infection. To regulate the screening, diagnosis, and prophylactic treatment of latent tuberculosis infection in patients with rheumatic diseases, reduce the risk of developing active tuberculosis and improve the prognosis, Peking University Shenzhen Hospital, Shenzhen Third People′s Hospital and Peking Union Medical College Hospital jointly organized domestic experts in the field of rheumatology and tuberculosis to establish the expert consensus on the diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases. This consensus focuses on epidemiology, the importance of screening, screening methods, and prophylactic anti-tuberculosis treatment strategies for latent tuberculosis infection combined with rheumatic diseases.

Polymorphisms of the BCL2 gene associated with susceptibility to tuberculosis

ABSTRACT Although tuberculosis (TB) is a serious public health concern, we still don't understand why only 10% of people infected will develop the disease. Apoptosis plays a role in the interaction of Mycobacterium tuberculosis (Mtb) with the human host and it may be modified by subtle alterations in the B-cell lymphoma 2 (BCL2) gene, an anti-apoptotic regulatory element. Therefore, we investigated whether there is an association between BCL2 polymorphisms and susceptibility to TB by analyzing 130 TB cases, 108 subjects with latent TB infection (LTBI), and 163 healthy controls (HC). Logistic regression was used to calculate odds ratios (ORs) and 95% confidential intervals (95% CIs) for possible associations between single nucleotide polymorphisms (SNPs) in BCL2 and the risk of tuberculosis. We found that the G allele of rs80030866 (OR=0.62, 95%CI:0.42-0.91, P=0.015), and also the G allele of rs9955190 (OR=0.58, 95%CI:0.38-0.88, P=0.011) were less frequent in the TB group compared with the LTBI group. In addition, individuals with rs2551402 CC genotype were more likely to have LTBI than those with AA genotype (OR=2.166, 95%CI:1.046-4.484, P=0.037). Our study suggests that BCL2 gene polymorphisms may be correlated with susceptibility to both TB and LTBI.

Prevalence of latent tuberculosis infection among patients with interstitial lung disease requiring immunosuppression / Prevalência de infecção latente por tuberculose em pacientes com doença pulmonar intersticial com necessidade de imunossupressão

ABSTRACT Objective To characterize the prevalence of latent tuberculosis infection (LTBI) in patients with interstitial lung diseases (ILDs) requiring immunosuppression. Only 5 to 10% of individuals infected with Mycobacterium tuberculosis develop tuberculosis, and certain groups of patients have an increased risk of illness, such as the immunocompromised. Patients with ILDs are frequently treated with immunosuppressants and, therefore, might have a higher risk of developing the disease. Methods Prospective study conducted at the ILD reference center of the Federal University of Paraná from January 2019 to December 2020. The screening of LTBI was performed with the use of the tuberculin skin test (TST). Results The sample consisted of 88 patients, of whom 64.8% were women, with a mean age of 61.4 years. The most frequent diagnoses were autoimmune rheumatic disease ILD (38.6%) and hypersensitivity pneumonitis (35.2%). The most common immunosuppressant in use at the time of the TST was prednisone, either in combination with mycophenolate (19.3%) or alone (17.1%). The majority of participants had fibrotic lung disease, characterized by a reticular interstitial pattern on chest computed tomography (79.5%) and moderate to severe functional impairment (mean FVC 69.2%). A prevalence of LTBI of 9.1% (CI 95%, 2.1%-15.1%) was found, with a TST median of 13. Conclusion Patients with ILD who are treated with immunosuppressants are not commonly screened for LTBI, despite being under a greater risk of progression to active disease. This study suggests the need for a more cautious approach to these patients.

RESUMO Objetivo Caracterizar a prevalência de Infecção Latente por Tuberculose (ILTB) em pacientes com Doenças Pulmonares Intersticiais (DPIs) que necessitam de imunossupressão. Apenas 5 a 10% dos indivíduos infectados pelo Mycobacterium tuberculosis desenvolvem tuberculose, sendo que certos grupos de pacientes apresentam maior risco de doença, tais como os imunocomprometidos. Pacientes com DPIs são frequentemente tratados com imunossupressores, portanto, podem apresentar maior risco de desenvolver a doença. Métodos Estudo prospectivo conduzido no Centro de Referência para DPI da Universidade Federal do Paraná (UFPR), entre Janeiro de 2019 e Dezembro de 2020. O rastreio de ILTB foi realizado por meio da Prova Tuberculínica (PT). Resultados A amostra foi composta por 88 pacientes, dos quais 64,8% eram mulheres, com, em média, 61,4 anos de idade. Os diagnósticos mais frequentes foram DPI associada a doença reumática autoimune (DRAI) (38,6%) e pneumonite de hipersensibilidade (35,2%). Prednisona foi o imunossupressor mais comumente utilizado à época da PT, em combinação com micofenolato (19,3%) ou isoladamente (17,1%). A maioria dos participantes tinha doença pulmonar fibrótica, caracterizada por infiltrado reticular em tomografia computadorizada de tórax (79,5%), bem como comprometimento funcional moderado a grave (Capacidade Vital Forçada (CVF) média de 69,2%). Observou-se uma prevalência de ILTB de 9,1% (Intervalo de Confiança (IC) 95%, 2,1%-15,1%), com mediana da PT de 13. Conclusão Não é comum que pacientes com DPI tratados com imunossupressores sejam avaliados quanto à presença de ILTB, apesar de estarem sob um maior risco de progressão para doença ativa. Este estudo sugeriu a necessidade de uma abordagem mais cuidadosa em relação a esses pacientes.

Spotlight on latent tuberculosis infection screening for juvenile idiopathic arthritis in two countries, comparing high and low risk patients

Abstract Background: Rheumatic diseases are associated with an increase in overall risks of tuberculosis (TB). The aim of this study was to evaluate the frequency of TB and the frequency of latent TB infection (LTBI), in clinical practice, for juvenile idiopathic arthritis (JIA) patients from high and low risk of TB incidence endemic countries. Methods: This is an international, multicenter, cross-sectional, observational study of data collection from Brazil and Registry of Portugal at REUMA.PT. The inclusion criteria were patients with Juvenile Idiopathic Arthritis (JIA) with age ≤ 18 years who underwent screening for Mycobacterium tuberculosis infection [tuberculin skin test (TST) and/or interferon gamma release assay (IGRA)]. Chest X-rays and history of exposure to TB were also assessed. Results: 292 JIA patients were included; mean age 14.3 years, mean disease duration 7.5 years, 194 patients (66.4%) performed only TST, 14 (4.8%) only IGRA and 84 (28.8%) both. The frequency of LTBI (10.6%) and TB was similar between the two countries. The reasons for TB screening were different; in Brazil it was performed more often at JIA onset while in Portugal it was performed when starting Disease Modified Anti-Rheumatic Drugs (DMARD) treatment (p < 0.001). Isoniazid therapy was prescribed in 40 (13.7%) patients (31 with LTBI and 9 with epidemiologic risks and/or due to contact with sick people). Only three patients (1%) developed active TB. Conclusion: We found nearly 10% of patients with LTBI, a small percentage of patients with treatment due to epide-miologic risks and only 1% with active TB. Distinct reasons and screening methods for LTBI were observed between the two countries.

Conversión de prueba cutánea de derivado proteico purificado durante el tratamiento con anti-TNF / Skin test conversion of purified protein derivative during treatment with anti-TNF

Introducción: los anti-TNF-α se asocian con mayor riesgo de desarrollar tuberculosis (TB). La prueba del derivado proteico purificado (purified protein derivative, PPD) se emplea para diagnosticar infección de tuberculosis latente (ITL). Se recomienda el cribado para TB previo al inicio de terapia anti-TNF-α y el seguimiento para evaluar la posible conversión de la PPD durante el tratamiento. El tratamiento de la ITL puede reducir el riesgo de desarrollar enfermedad activa en un 90%. Objetivos: actualmente los resultados de conversión de la PPD y su interpretación durante el tratamiento anti-TNF-α son variables, por tal motivo nos propusimos conocer la frecuencia de conversión de la PPD en este grupo de pacientes de nuestro medio. Materiales y métodos: realizamos un estudio descriptivo, observacional y retrospectivo que incluyó pacientes >18 años, diagnosticados con enfermedad reumática, tratados con anti-TNF-α. Resultados: se incluyeron 54 pacientes (46,7 ± a 12 años), de los cuales 36, presentaron diagnóstico de artritis reumatoidea, seis de artritis idiopática juvenil, cinco de espondilitis anquilosante, tres de artritis psoriásica, tres de uveítis y uno de queratitis intersticial. Los tratamientos fueron: 30 adalimumab, 17 certolizumab, siete etanercept, 44 metotrexato, 19 leflunomida, nueve hidroxicloroquina, dos sulfasalazina, dos azatioprina, uno mofetil micofenolato y glucocorticoides (28 de 54); la conversión de la PPD ocurrió en un solo paciente. Conclusiones: en el presente trabajo la seroconversión fue baja en contraste con otras series. La prueba de PPD es un método accesible, ampliamente disponible, adecuado y sensible para diagnosticar ITL.

Introduction: anti-TNF-α are associated with an increased risk of developing tuberculosis (TB). Purified protein derivative (PPD) is used to demonstrate a latent TB infection (LTBI). Screening is recommended for TB prior to the onset of anti-TNF-α and monitoring evaluating possible conversion of PPD during treatment. Treatment of LTBI can reduce the risk of active disease development by up to 90%. Objectives: currently the results of PPD conversion and its interpretation during anti-TNF-α treatment are variable and that is why we set out to know the frequency of conversion of PPD in this group of patients in our environment. Materials and methods: a descriptive, analytical, observational, retrospective study was conducted. Including patients >18 years old, diagnosed with rheumatic disease, treated with anti-TNF-α. Results: 54 patients were included (46.7 ± to 12 years), of which 36 presented a diagnosis of rheumatoid arthritis, 6 juvenile idiopathic arthritis, 5 ankylosing spondylitis, 3 psoriatic arthritis, 3 uveitis, 1 interstitial keratitis. The treatments were: 30 adalimumab, 17 certolizumab, 7 etanercept, 44 methotrexate, 19 leflunomide, 9 hydroxychloroquine, 2 sulfasalazine, 2 azathioprine, 1 mycophenolate mofetil and glucocorticoids (28/54). PPD conversion took place in 1 patient. Conclusions: in the present study, seroconversion was low in contrast to other series. The PPD test is an accessible, widely available, adequate and sensitive method for diagnosing LTBI, which the rheumatologist should use in his daily practice.

Status quo of exposure to latent tuberculosis infection and progress of prevention among healthcare workers in China / 中华临床感染病杂志

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. The high incidence rate, drug resistance rate and mortality rate of TB infection cause serious social and economic burden in developing countries. Due to high occupational exposure, medical institutions and healthcare workers take the potential risk of TB infection, which have negative impact on the public health and occupational health. As one of the countries with high burden of TB in the world, the occupational exposure of healthcare workers in China is serious, and the infection rate is far higher than that of developed countries. This article reviews the prevalence of latent tuberculosis infection among health care workers and the status quo of occupational protection in medical institutions in China.

Risk of developing tuberculosis in T-cell spot test of tuberculosis infection positive close contacts of tuberculosis patients in Shanghai: a prospective observational study / 中华传染病杂志

Objective:To investigate the risk and temporal characteristics of tuberculosis (TB) in persons with latent tuberculosis infection (LTBI) among close contacts of TB patients in Shanghai.Methods:This was a prospective observational study, the study subjects were the close contacts of TB patients who tested positive for Mycobacterium tuberculosis infection by T-cell spot test of tuberculosis infection (T-SPOT.TB) among the registered population in seven districts of Shanghai from 2009 to 2010. Questionnaire interview was applied to investigate the basic information and contact history.The LTBI cases during nine consecutive years were identified through the TB registration and reporting system.Cumulative incidence rate and incidence density of TB in tuberculosis-infected close contacts were estimated. Chi-square test was used to compare the incidence rate among different sex and age groups. Results:In total, 376 pulmonary TB patients and their 982 close contacts were enrolled in the baseline survey from 2009 to 2010. Of them, 287 close contacts were tested positive for Mycobacterium tuberculosis infection by T-SPOT.TB.The median age of persons with LTBI at the time of survey was 54 years old, and 36.6%(105/287) were male. By the end of December 2019, five new TB cases were detected among the 287 close contacts with LTBI. The two-year and five-year cumulative incidence were 0.35% and 1.05%, respectively. The nine-year cumulative incidence was 1.74%(95% confidence interval 0.57%-4.02%). The median duration for TB occurrence was 3.67 years. The incidence density of TB was 1.875/1 000 person-years with a total of 2 666.75 observation person-years. There were no significant differences in the nine-year cumulative incidence of TB among close contacts with LTBI by age and sex ( χ2=0.600, <0.001, respectively, both P>0.05). Conclusion:The occurrence of TB among close contacts with LTBI is concentrated in the first five years after TB contact.

Infección tuberculosa latente en niños de riesgo / Latent tuberculosis infection in children at risk

Introducción: En países de baja prevalencia la mayoría de los casos de tuberculosis se deben a reactivación de infección tuberculosa latente. Objetivo: Examinar la incidencia de infección tuberculosa latente en niños pertenecientes a grupos vulnerables a la tuberculosis. Métodos: Se realizó un estudio descriptivo, transversal y prospectivo en 85 menores de 19 años asintomáticos, 68 pertenecientes a algunos grupos vulnerables a la tuberculosis atendidos en el Hospital Pediátrico Centro Habana y en el Instituto de Oncología y Radiobiología y un grupo control de 17 adolescentes sanos, provenientes de la Escuela de Enfermería de la Facultad Calixto García, periodo abril-junio 2016. A todos se les realizó examen clínico, evaluación nutricional, radiología torácica y prueba de tuberculina. Resultados: De los 85 estudiados, 41 padecían enfermedades crónicas: 12 diabéticos, 11tenían enfermedad del colágeno, 9 enfermedad renal crónica y 9 enfermedades oncológicas. Todos tenían más de un año de evolución y recibían medicación inmunosupresora (excepto los diabéticos). De los 44 restantes, 27 tuvieron contacto estrecho y frecuente con enfermo de tuberculosis. Predominaron los niños ≥ 10 años (64; 75,3 por ciento), del sexo femenino (49; 57,6 por ciento). Todos estaban vacunados con BCG, con radiografías torácicas normales. Se detectó infección tuberculosa latente en 6 (7,0 por ciento); todos habían estado en contacto con un enfermo. Conclusiones: Existe una baja incidencia de infección tuberculosa latente en los grupos vulnerables estudiados. Los niños en contacto con enfermos son los únicos afectados, lo que puede estar relacionado con la baja tasa de tuberculosis en Cuba y las rápidas acciones de control(AU)

Introduction: Most of the tuberculosis cases in countries with low prevalence of it are due to a reactivation of the latent tuberculosis infection. Objective: To examine the incidence of the latent tuberculosis infection in children of groups vulnerable to tuberculosis. Methods: It was conducted a descriptive, cross-sectional and prospective study in 85 asymptomatic children under 19 years, 68 of them from some groups vulnerable to tuberculosis that were attended in Centro Habana Pediatric Hospital and in the Oncology and Radiobiology Institute; and a control group of 17 healthy adolescents from the Nursing School of Calixto García Faculty, in the period April-June, 2016. All patients underwent a physical examination, nutritional assessment, thoracic radiology and tuberculin test. Results: From the 85 patients studied, 41 suffered chronic diseases: 12 diabetics, 11 had collagen disease, 9 had chronic renal disease and other 9 have oncologic diseases. All patients had an evolution of more than one year and were receiving immunosuppressive medication (except from the diabetics). From the other 44 patients, 27 had close or frequent contact with a tuberculosis patient. There was predominance of children ≥ 10 (64; 75,3 percent) of the female sex (49; 57,6 percent). All of them were vaccinated with BCG and had normal thoracic radiographies. It was detected latent tuberculosis infection in 6 patients (7,0 percent); all of them had had contact with a tuberculosis sufferer. Conclusions: There is low incidence of latent tuberculosis infection in the studied vulnerable groups. Children having contact with tuberculosis sufferers are the only affected, which can be related with the low rate of tuberculosis in Cuba and the fast control actions(AU)

Performance Evaluation of a New Automated Chemiluminescent Immunoanalyzer-Based Interferon-Gamma Releasing Assay AdvanSure I3 in Comparison With the QuantiFERON-TB Gold In-Tube Assay

BACKGROUND: The interferon-gamma (IFN-γ) releasing assay (IGRA) is widely used for latent tuberculosis infection (LTBI) diagnosis. We evaluated the analytical performance of a new automated chemiluminescent immunoanalyzer-based IGRA (CLIA-IGRA), AdvanSure I3 (LG Life Sciences, Seoul, Korea) and compared it with that of the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay. METHODS: Repeatability and reproducibility were evaluated at four levels. Detection capability, including limit of blank (LoB), limit of detection (LoD), and limit of quantification (LoQ), was evaluated using IFN-γ standard material (National Institute for Biological Standards and Control code: 87/586). Agreement between the results of two assays was evaluated using 341 blood samples from healthcare workers and patients at a tertiary care hospital. To determine the cut-off value of CLIA-IGRA for diagnosing LTBI, the ROC curve was analyzed. RESULTS: Repeatability and reproducibility were 4.86–7.00% and 6.36–7.88% CV, respectively. LoB, LoD, and LoQ were 0.022, 0.077, and 0.249 IU/mL, respectively. IFN-γ values between CLIA-IGRA and QFT-GIT showed a strong correlation within the analytical measurable range of both assays, especially when the value was low. Qualitative comparison of the two assays yielded a 99.1% overall agreement (kappa coefficient=0.98). A cut-off value of 0.35 IU/mL was appropriate for diagnosing LTBI. CONCLUSIONS: CLIA-IGRA is a reliable assay for LTBI diagnosis, with performance similar to that of QFT-GIT.