Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis: A Key to a Successful Tuberculosis Control Strategy.

As an ancient infectious disease, tuberculosis (TB) is still the leading cause of death from a single infectious agent worldwide. Latent TB infection (LTBI) has been recognized as the largest source of new TB cases and is one of the biggest obstacles to achieving the aim of the End TB Strategy. The latest data indicate that a considerable percentage of the population with LTBI and the lack of differential diagnosis between LTBI and active TB (aTB) may be potential reasons for the high TB morbidity and mortality in countries with high TB burdens. The tuberculin skin test (TST) has been used to diagnose TB for > 100 years, but it fails to distinguish patients with LTBI from those with aTB and people who have received Bacillus Calmette-Guérin vaccination. To overcome the limitations of TST, several new skin tests and interferon-gamma release assays have been developed, such as the Diaskintest, C-Tb skin test, EC-Test, and T-cell spot of the TB assay, QuantiFERON-TB Gold In-Tube, QuantiFERON-TB Gold-Plus, LIAISON QuantiFERON-TB Gold Plus test, and LIOFeron TB/LTBI. However, these methods cannot distinguish LTBI from aTB. To investigate the reasons why all these methods cannot distinguish LTBI from aTB, we have explained the concept and definition of LTBI and expounded on the immunological mechanism of LTBI in this review. In addition, we have outlined the research status, future directions, and challenges of LTBI differential diagnosis, including novel biomarkers derived from Mycobacterium tuberculosis and hosts, new models and algorithms, omics technologies, and microbiota.

Neoteric advancements in TB diagnostics and its future frame.

Tuberculosis (TB) is one of the major infectious disease that causes threat to human health and leads to death in most of the cases. Mycobacterium tuberculosis is the causative agent that can affect both pulmonary and extra pulmonary regions of the body. This infection can be presented either as an active or latent form in the patients. Although this disease has been declared curable and preventable by WHO, it still holds its position as a global emergency. Over the past decade many hurdles such as low immunity, co-infections like HIV, autoimmune disorders, poverty, malnutrition and emerging trends in drug resistance patterns are hindering the eradication of this infection. However, many programmes have been launched by WHO with involvement of governments at various level to put a full stop over the disease. Under the Revised National Tuberculosis Control Programme (RNTCP) which was recently renamed as National Tuberculosis Elimination Programme (NTEP), the major focus is on eliminating tuberculosis by the year 2025. The main aim of the programme is to identify feasible quality testing, evaluate through NIKSHYA poshak yozana, restrict through BCG vaccination and assemble with public awareness to eradicate MTB. Numerous novel diagnostic techniques and molecular tools have been developed to elucidate and differentiate report of various suspected and active tuberculosis patients. However, improvements are still required to cut short the duration of the overall process ranging from screening of patients to their successful treatment.

Latent tuberculosis infection in transplant candidates: a systematic review and meta-analysis on TST and IGRA.

INTRODUCTION: The diagnostic accuracy of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for latent tuberculosis infection (LTBI) in transplant candidates is uncertain. METHODS: Pubmed, Embase and Cochrane library were searched to identify relevant studies. Quality of included studies was assessed with RevMan5 software (via GUADAS2 checklist). Accuracy measures of IGRAs and TST assays (sensitivity, specificity and others) were pooled with random effects model. Data were analyzed by STATA and Meta-DiSc. RESULTS: Twenty-eight studies were selected for full review, and 16 were included in the final analysis. The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) for TST were 46% [95% confidence interval (CI) 38-54%], 86% (95% CI 75-93%), 46.3% (95% CI 40-52), 88.7% (95% CI 87-89), 3.3 (95% CI 1.6-6.4), 0.63 (95% CI 0.52-0.77) and 5 (95% CI 2-12), respectively. For QFT-G, the pooled sensitivity, specificity, PPV, NPV, PLR, NLR, and DOR were 58% (95% CI 41-73%), 89% (95% CI 77-95%), 72.7% (95% CI 68-76), 80.6% (95% CI 78-82), 5.3 (95% CI 2.0-14.0), 0.47 (95% CI 0.30-0.75) and 11 (95% CI 3-46), respectively. Likewise, for T-SPOT.TB, the pooled sensitivity, specificity, PPV, NPV, PLR, NLR, and DOR were 55% (95% CI 40-70%), 92% (95% CI 87-95%), 60.4% (95% CI 47-72), 90.2% (95% CI 86-92), 6.7 (95% CI 4.0-11.1), 0.52 (95% CI 0.31-0.85) and 16 (95% CI 7-37), respectively. CONCLUSIONS: IGRAs were more sensitive and specific than the TST with regard to the diagnosis of LTBI in the transplant candidates. They have added value and can be complementary to TST.

Interferon Gamma Release Assays from T Lymphocytes in Patients with Tuberculosis Infection / 现代检验医学杂志

Objective To explore the application value of interferon gamma release assay (IGRAs)in the clinical detection of tuberculosis infected T lymphocytes.Methods Used IGRAs method to detect the 11 968 outpatients and hospitalized pa-tients from 2013 to 2016 with tuberculosis screening.According to the distribution department analysis,also of positive case detection according to age and gender were analysis and comparison and analysis on the uncertainty of results,different methods were compared.Results Among the 11 968 cases,2 048 cases were positive,the positive rate was 17.11%,and the uncertain result was 107 cases,which accounted for 0.89% of the total number.The positive rates from 2013 to 2016 were 19.65%,21.35%,15.82% and 13.56%,respectively.In the detection and screening of pulmonary and pulmonary tuberculo-sis,the positive rates of the department of respiration,the digestive department,the oncology department,the department of neurology and the department of gynecology were 22.07%,20.27%,23.38%,12.84% and 11.86%,respectively.In the positive screening,men accounted for 62.11%,women accounted for 37.89%,men were significantly higher than women.By age group,was less than or equal to 15,16~25,26~45,46~65,was more than orequal to 66 years old,positive rate were 1.96%,18.51%,16.54%,21.25% and 25.73%,respectively.Analysis of uncertain outcome data,department of respira-tion,rheumatism,department of hematology,accounted for 1.99% and 2.35%,respectively.Compared with other laboratory methods,the IGRAs method had obvious advantages.Conclusion Tuberculosis occurs in various body organs,there were differences in gender and age of Mycobacterium tuberculosis infection.IGRAs is a sensitive and specific method for rapid de-tection of Mycobacterium tuberculosis infection,although it can not be used as a diagnostic indicator,but in patients with suspected tuberculosis IGRAs has a larger clinical application value for the further diagnosis of disease.

Evaluation of IL-2, IL-10, IL-17 and IP-10 as potent discriminative markers for active tuberculosis among pulmonary tuberculosis suspects.

INTRODUCTION: Although interferon gamma release assays (IGRAs) are useful for specifically detecting Mycobacterium tuberculosis, they are limited by their inability to differentiate between active tuberculosis (active TB), latent tuberculosis infection (LTBI), and patients with prior TB infection. The purpose of this study was to rapidly and accurately identify active TB patients among patients with suspected respiratory TB by combining interferon-gamma (IFN-γ) with additional cytokines. MATERIALS AND METHODS: The present study was conducted on patients who required TB screening to discern active TB due to respiratory complaints. Among all patients screened, 80 who tested positive in the QunatiFERON TB GOLD in-tube assay (QFT-GIT) were retrospectively selected and divided into the active TB group (n = 40) and the non-active TB group (n = 40). Supernatants from the Nil tube and TB antigen (Ag)-stimulated tube from the QFT-GIT test were used. Interleukin (IL)-2, IL-10, IL-17, and IP-10 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: In comparing the differences significant differences in TB Ag tube response of IL-17 and IP-10, and 'TB Ag - Nil' response of IL-10 and IP-10 were evident between the active TB and non-active TB groups. From the calculation of diagnostic performance for differentiating active TB patients from QFT-positive patients, among the measured values, the value of IL-17 TB Ag tube with the cut-off value set to ≤0.82 (AUC 0.742) showed sensitivity, specificity, positive predictive value, and negative predictive value of 69.2%, 97.5%, 96.4%, and 76.5%, respectively. DISCUSSION: Among TB suspects, IL-17 TB Ag response had the highest ability to distinguish active TB followed by IP-10 TBAg-Nil response and the IL-17/IFN-γ-TB Ag response combination improved the detection response. Differentiating active TB is best done using IL-17 as a biomarker, with IP-10 and IL-10 being potential useful.

The diagnostic efficiency of QuantiFERONTB®-Gold test in the diagnosis of tuberculous pleurisy.

BACKGROUND: Diagnosis of tuberculous pleurisy is difficult and better diagnostic tools are needed. Interferon gamma release assays (IGRAs) are in vitro immunologic diagnostic tests used to identify Mycobacterium TB infections. They cannot differentiate between latent and active infections. As IGRA tests have recently been approved for the differential diagnosis of active TB, the diagnostic accuracy of the latest generation of IGRA were assessed to detect tuberculous pleurisy in this study. METHODS: The QuantiFERONTB®-Gold (QFT-G) test was used in pleural fluid from 100 immunocompetent patients (23 patients for the tuberculous group and 77 patients for the non-tuberculous group). Clinical data were recorded. Adenosine deaminase activity (ADA) analysis and TB culture were performed on pleural fluid. RESULTS: The QFT-G in pleural fluid was positive in 10 (43.5%) patients and indeterminate in 13(56.5%) patients in the tuberculous pleurisy group. There was not a single patient with a negative test result in the tuberculous pleurisy group. The ADA levels were detected as 46.2±12.6 in patients with tuberculous pleurisy and18.6±39.8 in patients with non-tuberculous pleurisy. The sensitivity, specificity, positive predictive value and negative predictive value of QFT-G in pleural fluid for tuberculous pleurisy were 43.5%, 54.5%, 30.3% and 100%; and of ADA in pleural fluid (>40IU/ml) for tuberculous pleurisy the results were 82.6%, 96.1%, 90.5% and 92.5% respectively. CONCLUSION: While the value of the QFT-G test in exclusion of tuberculous pleurisy was found to be higher in this study, its other diagnostic efficiency values were detected to be low. It is recommended that a new cut-off value be established while diagnosing active TB in prospective clinical studies and that it is also essential to do the same for the studies in various regions with high and low prevalence of TB.