Evaluation of Interferon-Gamma Release Assay Testing and Tuberculin Skin Test for Early Diagnosis of Tuberculosis in Children and Adolescents

Background: This study aimed to evaluate the diagnostic value of interferon-γ release assay (IGRA), a sensitive microbiological diagnostic method, in children and adolescents with suspected tuberculosis in a country with a high burden of tuberculosis. Method: This study included 581 children and adolescents aged 4 - 19 years who were suspected of having tuberculosis, were latently infected with Mycobacterium tuberculosis, and had received at least one dose of BCG vaccine between April 17, 2019, and February 24, 2021. The study evaluated the TST results of 106 patients who had a positive Quantiferon test and were suspected of having tuberculosis. Results: The study included 581 patients aged between 4 and 19 years. Of these, 106 patients tested positive for the Quantiferon test, while 19 were indeterminate and 456 were negative. The Quantiferon test positivity rate was 18.24%. Among the 106 QFT-Plus-positive cases, 23 patients also tested positive for TST. The difference in distribution was found to be statistically significant. Conclusion: The QFT-Plus test is considered an alternative to TST and other microbiological diagnostic methods for early tuberculosis diagnosis, particularly in children and adolescents.

Interferon-gamma release assays in tuberculous uveitis:a comprehensive review

·Tuberculous uveitis(TBU)comprises a broad clinical spectrum of ocular manifestations,making its diagnosis challenging.Ophthalmologists usually require evidence from investigations to confirm or support a clinical diagnosis of TBU.Since direct isolation of the causative organism from ocular specimens has limitations owing to the small volume of the ocular specimens,resultant test positivities are low in yield.Immunodiagnostic tests,including the tuberculin skin test and interferon-gamma release assays(IGRAs),can help support a clinical diagnosis of TBU.Unlike the tuberculin skin test,IGRAs are in vitro tests that require a single visit and are not affected by prior Bacillus Calmette-Guerin vaccination.Currently,available IGRAs consist of different techniques and interpretation methods.Moreover,newer generations have been developed to improve the sensitivity and ability to detect active tuberculosis.This narrative review collates salient practice points as a reference for general ophthalmologists,such as evidence for the utilization of IGRAs in patients with suspected TBU,and summarizes basic knowledge and details of clinical applications of these tests in a clinical setting.

Interferon-Gamma Release Assay is Not Appropriate for the Diagnosis of Active Tuberculosis in High-Burden Tuberculosis Settings： A Retrospective Multicenter Investigation

Background：Interferon-gamma release assay （IGRA） has been used in latent tuberculosis （TB） infection and TB diagnosis,but the results from different high TB-endemic countries are different.The aim of this study was to investigate the value of IGRA in the diagnosis of active pulmonary TB （PTB） in China.Methods：We conducted a large-scale retrospective multicenter investigation to further evaluate the role of IGRA in the diagnosis of active PTB in high TB-epidemic populations and the factors affecting the performance of the assay.All patients who underwent valid T-SPOT.TB assays from December 2012 to November 2015 in six large-scale specialized TB hospitals in China and met the study criteria were retrospectively evaluated.Patients were divided into three groups：Group 1,sputum culture-positive PTB patients,confirmed by positive Mycobacterium tuberculosis sputum culture;Group 2,sputum culture-negative PTB patients;and Group 3,non-TB respiratory diseases.The medical records of all patients were collected.Chi-square tests and Fisher＇s exact test were used to compare categorical data.Multivariable logistic analyses were performed to evaluate the relationship between the results of T-SPOT in TB patients and other factors.Results：A total of 3082 patients for whom complete information was available were included in the investigation,including 905 sputum culture-positive PTB cases,914 sputum cultmre-negative PTB cases,and 1263 non-TB respiratory disease cases.The positive rate of T-SPOT.TB was 93.3% in the culture-positive PTB group and 86.1% in the culture-negative PTB group.In the non-PTB group,the positive rate of T-SPOT.TB was 43.6%.The positive rate of T-SPOT.TB in the culture-positive PTB group was significantly higher than that in the culture-negative PTB group （x2 =25.118,P 〈 0.01）,which in turn was significantly higher than that in the non-TB group （x2 =566.l 16,P 〈 0.01）.The overall results were as follows：sensitivity,89.7%;specificity,56.37%;positive predictive value,74.75%;negative predictive value,79.11%;and accuracy,76.02%.Conclusions：High false-positive rates of T-SPOT.TB assays in the non-TB group limit the usefulness as a single test to diagnose active TB in China.We highly recommend that IGRAs not be used for the diagnosis of active TB in high-burden TB settings.

In vitro antihistamine-releasing activity of a peptide derived from wasp venom of Vespa orientalis

Objective: To investigate the antihistamine-releasing effect of a peptide isolated from wasp venom of Vespa orientalis.Methods: This peptide was separated from crude venom by chromatography methods and mass spectrometry. Then various concentrations(2, 4, 8, 16, 32, 64, 128 and256 mmol/L) of the peptide were incubated with mast cells and lactate dehydrogenase assay was performed.Results: No significant effect was observed in lactate dehydrogenase absorbance under128 mmol/L concentration. This implied that the peptide did not cause cell death in mast cells and consequently, histamine release did not happen. Moreover, the results showed the IC50 of mast cells degranulation at 126 mmol/L, which was approximately high implying that this peptide had high selectivity for normal cells and did not cause histamine release from these cells.Conclusions: This would be a great aim in new drug development, in which an agent acts potentially on its target tissue without activating the immune system.

Usefulness of interferon-γrelease assay for the diagnosis of sputum smear-negative pulmonary and extra-pulmonary TB in Zhejiang Province,China

Background:Quick diagnosis of smear-negative pulmonary tuberculosis(TB)and extra-pulmonary TB are urgently needed in clinical diagnosis.Our research aims to investigate the usefulness of the interferon-γrelease assay(IGRA)for the diagnosis of smear-negative pulmonary and extra-pulmonary TB.Methods:We performed TB antibody and TB-IGRA tests on 389 pulmonary TB patients(including 120 smear-positive pulmonary TB patients and 269 smear-negative pulmonary TB patients),113 extra-pulmonary TB patients,81 patients with other pulmonary diseases and 100 healthy controls.Blood samples for the TB-Ab test and the TB-IGRA were collected,processed,and interpreted according to the manufacturer’s protocol.Results:The detection ratio of smear-positive pulmonary TB patients and smear-negative pulmonary TB patients were 90.8%(109 of 120)and 89.6%(241 of 269),respectively.There was no statistically significant difference of its performance between these two sample sets(P>0.05).The detection ratio of positive TB patients and extra-pulmonary TB patients were 90.0%(350 of 389)and 87.6%(99 of 113),respectively,which was not significantly different(P>0.05).Conclusions:In this work,the total detection ratio using TB-IGRA was 89.4%,therefore TB-IGRA has diagnostic values in smear-negative pulmonary TB and extra-pulmonary TB diagnosis.

Prevalence of Latent Tuberculosis (LTB) among Household Contacts of Newly Diagnosed Omani Pulmonary Tuberculosis Patients

Background: Oman is a high-income, low prevalent country for tuberculosis disease. Although the rates have remained static over the last decade, the country is aiming for Tuberculosis (TB) elimination. Household contacts of pulmonary TB (PTB) patients form a high-risk group of susceptible individuals who could remain reservoirs of active disease. Objective: A retrospective study was conducted to estimate the prevalence of latent TB infection by Tuberculin Skin Test (TST) or Interferon-Gamma Release Assay (IGRA) screening tests among the household contacts of Omani patients with pulmonary tuberculosis. Design: A cross-sectional survey conducted between 2017 and 2018 of TB cases and their contacts in Muscat Governorate, Oman. Results: Out of the 278 contacts identified, 188 contacts fulfilled the inclusion criteria and were enrolled into the study. The prevalence of Latent Tuberculosis Infection (LTBI) was 22.8% (95% CI: 17.0 - 29.5) among household contacts. We found higher proportions of LTBI among females than males (28.7% vs. 15%, p = 0.027). Those who were exposed to Acid Fast Bacilli (AFB) smear positive cases were more likely to be LTBI (28.7% versus 15% in smear negative cases;p = 0.047). We also found an increasing trend of infection (32.3%) in the oldest age group (46 - 80 years). Conclusion: Besides children, female household contacts and older age contacts should be prioritized for screening as they are more likely to be infected and develop active disease.

Latent tuberculosis infection among medical students in Malaysia

Objective: This study aimed to determine prevalence of latent tuberculosis infection among medical students and tuberculosis exposure at the health facilities. Methods: A cross-section of study year 1(n=68) and year 5(n=75) medical students in a local university were recruited for latent tuberculosis infection testing using QuantiFERON-TB Gold Plus and a questionnaire analyzed for multivariate risk. Results: The majority of the study were vaccinated with BCG. None of year 1 medical students were positive for latent tuberculosis infection, however, six(8.0%) year 5 students were tested positive for latent tuberculosis infection. A higher incidence of year 5 medical students claimed to be exposed to tuberculosis at health facility(65.3% vs. 4.4%) and a higher percentage reported contact with tuberculosis case over the preceding year compared to year 1 students(30.7% vs. 8.8%). Conclusion: We observed a higher incidence of latent tuberculosis infection and higher exposure to tuberculosis in health facilities among year 5 medical students. Baseline screening and monitoring for progression to tuberculosis infection may benefit tuberculosis management programs.

Recent Progress in Diagnosis Methods for Latent Tuberculosis Infection and Its Clinical Applications

Most people with latent Mycobacterium tuberculosis infection can partly develop active tuberculosis (TB). Therefore, diagnosis of this condition bears significance in early TB prevention. To date, the main methods for diagnosis of latent TB infection (LTBI) include tuberculin skin test and interferon γ release test. These two methods feature their own advantages and disadvantages. Although new diagnostic markers continually emerge, no uniform diagnostic criteria are available for TB detection. This study summarizes several methods for diagnosis of LTBI and new related markers and their application value in clinical practice.

Performance of QuantiFERON(R)-TB Gold In-Tube assay in children receiving disease modifying anti-rheumatic drugs

Background:To evaluate the performance of theQuantiferon(R)-TB Gold In-Tube (QFT-IT) interferon (IFN)-7 assay for the detection of latent tuberculosis infection (LTBI)in children receiving anti-rheumatic treatment in a tertiary referral hospital of Northern Greece.Methods:A total of 79 consecutive children receiving anti-rheumatic treatment [of which 18 screened prior to antitumor necrosis factor (TNF)-α treatment] were tested using Mantoux tuberculin skin test (TST) and QFT-IT.Association of both tests with risk factors for latent tuberculosis and Bacillus Calmette-Guerin immunization was determined.Influence of age,TNF-α inhibitors,systemic corticosteroids,conventional disease modifying anti-rheumatic drugs (DMARDs) and total duration of therapy on the QFT-IT mitogen-induced response was evaluated.Results:Agreement between TST and QFT-IT results was moderate (k=0.38).Frequency of QFT-IT indeterminate results was low (2.5%).In patients with risk factors for LTBI,the odds of a positive IFN-7 assay was increased by a factor of 27.6 (P=0.002),whereas there was no positive TST.There was a significant difference in the mitogeninduced IFN-7 secretion among various treatments (P=0.038).TNF-α inhibitors were associated with increased mitogen-induced IFN-7 secretion compared to monotherapy with conventional DMARDs (P=0.008).All children screened prior to anti-TNF-a treatment exhibited a negative QFT-IT and no active TB disease was detected during a 2-year follow-up.Conclusions:QFT-IT may be a more reliable test than TST for detection of LTBI in children with rheumatic diseases receiving anti-rheumatic treatment.Drug regimen might influence the mitogen-induced IFN-γ secretion and the effect of TNF-α inhibitors might vary according to the specific agent administered.