Developing a diagnostic method for latent tuberculosis infection using circulating miRNA

Abstract Background Mycobacterium tuberculosis is known to cause latent tuberculosis infection (LTBI) in 25–50% of the cases, of whom 10–20% develop active tuberculosis (TB). Notably, no marker currently exists for judging the therapeutic effect of TB; it is currently judged by chest X-ray and clinical symptoms. We attempted to establish a marker for distinguishing LTBI from active TB and to identify the probability of recurrence after TB treatment, using information on circulating miRNA expression. Methods In total, 32 patients were enrolled in this study: 16 with an onset or recurrence of active TB, and 16 with LTBI showing positive interferon-gamma release assays (IGRA) test and chest X-ray. Total RNA from serum in an exosome-rich fraction was first extracted, followed by miRNA expression analysis using a next-generation sequencer, then, this data were analyzed using miRDeep2. Results Using the expression information of eight miRNAs, LTBI and TB could be diagnosed with an accuracy of 71.8% (odds ratio: 6.16, p value = 3.20e-02). Conclusions A novel method for efficiently differentiating between LTBI and active TB was established. This method appears to be promising for evaluating the therapeutic effect of TB, as it can be performed in a minimally invasive manner.

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RISK FACTORS OF LATENT TUBERCULOSIS INFECTION IN HEALTHCARE WORKERS AT HOSPITALS IN JEMBER CITY INDONESIA

African Journal of Infectious Diseases ◽

10.21010/ajid.v15i1.4 ◽

2020 ◽

Vol 15 (1) ◽

pp. 34-40

Author(s):

Hamidah Retno Wardani ◽

Ni Made Mertaniasih ◽

Soedarsono Soedarsono

Keyword(s):

Risk Factors ◽

Tuberculin Skin Test ◽

Skin Test ◽

Healthcare Workers ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Tuberculosis Infection ◽

P Value ◽

X Ray ◽

Chest X Ray

Background: Healthcare workers in Tuberculosis (TB) and non-TB units in hospitals have a high risk of experiencing Latent Tuberculosis Infection (LTBI), because of exposure to droplets containing Mycobacterium tuberculosis. This study aims to prove LTBI incidence and risk factors to healthcare workers at the hospital in Jember City. Material and Methods: a cross-sectional study, from January to March 2020 in two hospitals in Jember City. Healthcare workers in the TB care and non-TB care unit were examined using Tuberculin skin test (TST) with a cut off ≥ 10 mm for positive LTBI. Chest x-ray and clinical examination to rule out active TB and a standardized questionnaire were also used. Results: 128 healthcare workers completed the questionnaires, clinical, tuberculin skin test (TST), and chest x-ray data. LTBI incidence of positive results 61.7% (n = 79). Contacts TB in the workplace (p value = 0.219; OR = 1.643; CI = 0.742-3.641) and a unit of work (p value = 0.102; OR = 0.760; CI = 0.559-1.031) has no relationship with LTBI. The profession (p value = 0.020; OR = 1.112; CI = 0.896-1.403), the duration of the work (p value = 0.039; OR = 2.984; CI = 1.067-8.342), and BCG immunization (p value =0.000; OR = 0.151; CI = 0.052-0.438) have important relationships with LTBI. Conclusion: TB infection with a high incidence, a risk of transmission to healthcare workers, and a relationship between occupational risk factors and LTBI among healthcare workers in Jember City, Indonesia have been established in this study.

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Latent tuberculosis infection and tuberculosis in children and adolescents

Einstein (São Paulo) ◽

10.1590/s1679-45082018ao4090 ◽

2018 ◽

Vol 16 (3) ◽

Author(s):

Cassia Satsuki Ishikawa ◽

Olivia Mari Matsuo ◽

Flavio Sarno

Keyword(s):

Computed Tomography ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Tuberculin Test ◽

Tuberculosis Infection ◽

Gastric Aspirate ◽

X Ray ◽

Qualitative Variables ◽

Chest X Ray ◽

Tuberculosis In Children

ABSTRACT Objective: To describe the characteristics of patients diagnosed with tuberculosis and latent tuberculosis infection. Methods: A retrospective study, between 2012 and 2015, with data from patients of Programa Einstein na Comunidade de Paraisópolis. To evaluate possible factors associated with patient's sex and diagnoses of tuberculosis and latent tuberculosis infection, χ2 or Fisher's exact tests were used for qualitative variables, and Mann-Whitney test for quantitative or ordinal qualitative variables. Results: A total of 77 patients were evaluated. Age ranged from 6 months to 13.4 years, with a majority of males (54.5%), aged zero to 4 years (54.5%), diagnosed with latent tuberculosis infection (64.9%), and classified as eutrophic (71.2%). The tuberculin test was positive in 92% and in most cases the values were above 10mm (68.0%). Approximately three-quarters of chest X-ray tests were normal (72.7%). After chest X-ray, computed tomography of thorax was the most ordered exam (29.9%), followed by smear and culture for Mycobacterium tuberculosis in the gastric aspirate (28.6%). The frequencies of altered chest X-ray (70.4% versus 4.0%), computed tomography of thorax requests (55.6% versus 16.0%) and other tests requested (81.5% versus 38.0%) were significantly higher in patients with a diagnosis of tuberculosis, relative to those with latent tuberculosis infection, respectively. Conclusion: In our sample, proportions of altered chest X-ray, and performing computed tomography of thorax and other tests in patients diagnosed with tuberculosis were higher than in those with latent tuberculosis infection.

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Diagnosis and treatment of latent tuberculosis infection in patients undergoing treatment with immunobiologic agents: a four-year experience in an endemic area

Jornal Brasileiro de Pneumologia ◽

10.1590/1806-3713/e20180225 ◽

2019 ◽

Vol 45 (6) ◽

Cited By ~ 1

Author(s):

Diana Maria de Almeida Lopes ◽

Valéria Goes Ferreira Pinheiro ◽

Helena Serra Azul Monteiro

Keyword(s):

Endemic Area ◽

Prophylactic Treatment ◽

Latent Tuberculosis Infection ◽

Immunosuppressive Agents ◽

Latent Tuberculosis ◽

Preventive Therapy ◽

Active Tuberculosis ◽

Tuberculosis Infection ◽

X Ray ◽

Chest X Ray

ABSTRACT Objective: To describe the incidence of active tuberculosis and the occurrence of adverse events after isoniazid treatment in patients with latent tuberculosis infection (LTBI) who also had chronic inflammatory diseases and were treated with immunobiologic agents in an endemic area in Brazil. Methods: The diagnosis of LTBI was based on anamnesis, clinical examination, chest X-ray, and a tuberculin skin test (TST). Patients received prophylactic treatment (isoniazid for six months) in accordance with the Brazilian guidelines. Results: A total of 101 patients were evaluated between July of 2011 and July of 2015. Of those, 55 (54.46%) were women (mean age, 53.16 ± 1.76 years) and 46 (45.54%) were men (mean age, 45.39 ± 2.13 years). A total of 79 patients (78.22%) were being treated with immunobiologic agents and 22 (21.78%) were being treated with immunomodulatory or immunosuppressive agents. In the screening for LTBI, 53 patients (52.48%) had a TST induration ≥ 10 mm. Chest X-ray findings consistent with LTBI were observed in 36 patients (35.64%). Isoniazid preventive therapy was effective in 96 (95.05%) of the 101 patients evaluated. It is of note that 84 (83.17%) of the patients experienced no adverse effects from the use of isoniazid and that 83 (98.81%) of those patients completed the prophylactic treatment (p = 0.002). Active tuberculosis was diagnosed in 5 (6.33%) of the 79 patients treated with immunobiologic agents and in 1 (4.55%) of the 22 patients treated with other immunomodulators/immunosuppressants. Conclusions: A six-month course of isoniazid proved to be safe and effective in the treatment of LTBI, which is essential to reducing the risk of developing active tuberculosis.

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Factors Associated with Latent Tuberculosis Infection among the Hospital Employees in a Tertiary Hospital of Northeastern Thailand

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17186876 ◽

2020 ◽

Vol 17 (18) ◽

pp. 6876

Author(s):

Patimaporn Chanpho ◽

Naesinee Chaiear ◽

Supot Kamsa-ard

Keyword(s):

High Risk ◽

Latent Tuberculosis Infection ◽

Conditional Logistic Regression ◽

Critical Role ◽

Latent Tuberculosis ◽

Tertiary Hospital ◽

Tuberculosis Infection ◽

P Value ◽

Factors Associated ◽

Northeastern Thailand

Latent tuberculosis infection (LTBI) can develop into tuberculosis (TB). The WHO requires the discovery and management of LTBI among high-risk groups. Health care workers (HCWs) constitute a high-risk group. Factors associated with LTBI among HCWs in Thailand need further study. The current study aimed to explore the factors related to LTBI among Thai HCWs. A hospital-based, matched case-control study was conducted. All cases and controls were HCWs at a tertiary hospital in northeastern Thailand. Between 2017 and 2019, a total of 85 cases of interferon-γ release assays (IGRAs)-proven LTBI, and 170 control subjects were selected from a hospital (two controls per case). The two recruited controls were individually matched with LTBI cases by sex and age (±5 years). Secondary data were obtained from the occupational health and safety office. Case HCWs had a higher proportion of significant factors than control HCWs (i.e., working closely with pulmonary TB—94.1% vs. 88.8%, and working in the area of aerosol-generating procedures (AGPs) 81.2% vs. 69.4%). The bivariate conditional logistic regression showed that the occurrence of LTBI in HCWs was statistically significant (p-value < 0.05), particularly with respect to: workplaces of AGPs (crude OR = 1.90, 95% CI: 1.01–3.58, p = 0.041); among HCWs performing AGPs (crude OR = 2.04, 95% CI: 1.20, 3.48, p = 0.007); and, absent Bacille Calmette-Guérin (BCG) scar (crude OR = 2.59, 95% CI: 1.50–4.47, p = 0.001). Based on the multivariable conditional logistics analysis, HCWs who performed AGPs while contacting TB cases had a statistically significant association with LTBI (adjusted OR = 1.82, 95% CI: 1.04–3.20, p = 0.035). HCWs who reported the absence of a BCG scar had a statistically significant association with LTBI (adjusted OR = 2.49, 95% CI: 1.65–5.36, p = 0.001), whereas other factors including close contact with TB (adjusted OR = 2.44, 95% CI: 0.74, 8.09, p = 0.123) were not significantly associated with LTBI. In conclusion, HCWs who performed AGPs and were absent a BCG scar had a significant association with LTBI, while other factors played a less critical role.

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Impact of latent tuberculosis infection on health and wellbeing: a systematic review and meta-analysis

European Respiratory Review ◽

10.1183/16000617.0260-2020 ◽

2021 ◽

Vol 30 (159) ◽

pp. 200260

Author(s):

Yen Jun Wong ◽

Noorliza Mohd Noordin ◽

Salmaan Keshavjee ◽

Shaun Wen Huey Lee

Keyword(s):

Quality Of Life ◽

Latent Tuberculosis Infection ◽

Clinical Symptoms ◽

Meta Analysis ◽

Latent Tuberculosis ◽

Tuberculosis Infection ◽

Health And Wellbeing ◽

Patient Reported ◽

The Impact

The impact of latent tuberculosis infection (LTBI) on health and wellbeing is not well understood. This review aims to evaluate the health and wellbeing of individuals with LTBI. A systematic literature search was performed to assess studies reporting patient-reported outcomes in LTBI management including health-related quality of life (HRQoL), health utilities, disease burden and experience of individuals with LTBI. A pooled analysis was performed to estimate the effect of LTBI on HRQoL.A total of 4464 studies were screened, of which 13 eligible articles describing nine unique studies were included for review. The HRQoL of individuals with LTBI and without tuberculosis (TB) infection were comparable, and better than patients with active TB disease. However, individuals with LTBI reported poorer mental health compared with individuals without TB infection (mean difference −4.16, 95% CI −7.45– −0.87; p=0.01). Qualitative studies suggest the presence of fear, anxiety and stigma in individuals with LTBI.This review highlights potential psychosocial challenges in individuals with LTBI despite the absence of clinical symptoms. While their quality of life was marginally affected, this could be evidence to support LTBI management in preventing TB re-activation and the severe consequences of active TB disease that affect all domains of HRQoL.

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Performance of 4 methods for screening of latent tuberculosis infection in patients with chronic inflammatory arthritis under TNFα inhibitors: a 24-month prospective study

Advances in Rheumatology ◽

10.1186/s42358-021-00226-z ◽

2021 ◽

Vol 61 (1) ◽

Author(s):

Carina M. F. Gomes ◽

Maria Teresa Terreri ◽

Maria Isabel Moraes-Pinto ◽

Marcelo M. Pinheiro

Keyword(s):

Inflammatory Arthritis ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Tuberculosis Infection ◽

Chronic Inflammatory Arthritis ◽

Interferon Gamma Release Assays ◽

Tnfα Inhibitors ◽

Chest X Ray ◽

Incident Cases

Abstract Background The reactivation rate of tuberculosis in patients with chronic inflammatory arthritis (CIA) on TNFα inhibitors (TNFi) and baseline negative screening for latent tuberculosis infection (LTBI) is higher than in the general population. Aim To compare the performance of tuberculin skin test (TST), TST-Booster, ELISPOT (T-SPOT.TB) and QuantiFERON-TB Gold in tube (QFT-IT) to detect LTBI in patients with CIA on TNFi. Patients and methods A total of 102 patients with CIA [rheumatoid arthritis (RA), n = 40; ankylosing spondylitis (AS), n = 35; psoriatic arthritis (PsA), n = 7; and juvenile idiopathic arthritis (JIA), n = 20] were prospectively followed-up for 24 months to identify incident LTBI cases. Epidemiologic data, TST, T-SPOT.TB, QFT-IT and a chest X-ray were performed at baseline and after 6 months of LTBI treatment. Results Thirty six percent (37/102) of patients had positive TST or Interferon Gamma Release Assays (IGRAs) tests. Agreement among TST and IGRAs was moderate (k = 0.475; p = 0.001), but high between T-SPOT.TB and QFT-IT (k = 0.785; p < 0.001). During the 24-Month follow-up, 15 (18.5%) incident cases of LTBI were identified. In comparison to TST, the IGRAs increased the LTBI diagnosis power in 8.5% (95% CI 3.16–17.49). TST-Booster did not add any value in patients with negative TST at baseline. After 6-Month isoniazid therapy, IGRAs results did not change significantly. Conclusions Almost 20% of CIA patients had some evidence of LTBI, suggesting higher conversion rate after exposition to TNFi. TST was effective in identifying new cases of LTBI, but IGRAs added diagnostic power in this scenario. Our findings did not support the repetition of IGRAs after 6-Month isoniazid therapy and this approach was effective to mitigate active TB in 2 years of follow-up.

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