Diagnosis Of Latent Tuberculosis Infection Research Articles

Diagnosis and Treatment of Latent Tuberculosis Infection in Healthcare Workers.

Tuberculosis (TB) is one of the most important occupational risks for healthcare workers (HCWs) in South Korea. Many policies regarding the control and prevention of TB in healthcare settings recommend that HCWs are tested for latent tuberculosis infection (LTBI) in addition to active TB. Moreover, the Korean Tuberculosis Prevention Act also recommends that HCWs receive regular testing for LTBI. However, there are no specific or detailed guidelines for dealing with LTBI in HCWs. Herein, we discuss the diagnosis and treatment of LTBI in HCWs and focus particularly on the baseline screening of hired HCWs, routine follow-up, and contact investigation.

Usefulness of interferon-γ release assay for the diagnosis of latent tuberculosis infection in young children.

PurposeLatent tuberculosis infection (LTBI) in young children may progress to severe active tuberculosis (TB) disease and serve as a reservoir for future transmission of TB disease. There are limited data on interferon-γ release assay (IGRA) performance in young children, which our research aims to address by investigating the usefulness of IGRA for the diagnosis of LTBI.MethodsWe performed a tuberculin skin test (TST) and IGRA on children who were younger than 18 years and were admitted to Chung-Ang University Hospital during May 2011–June 2015. Blood samples for IGRA were collected, processed, and interpreted according to manufacturer protocol.ResultsAmong 149 children, 31 (20.8%) and 10 (6.7%) were diagnosed with LTBI and active pulmonary TB, respectively. In subjects lacking contact history with active TB patients, TST and IGRA results were positive in 41.4% (29 of 70) and 12.9% (9 of 70) subjects, respectively. The agreement (kappa) of TST and IGRA was 0.123. The control group, consisting of non-TB-infected subjects, showed no correlation between age and changes in interferon-γ concentration after nil antigen, TB-specific antigen, or mitogen stimulation in IGRAs (P=0.384, P=0.176, and P=0.077, respectively). In serial IGRAs, interferon-γ response to TB antigen increased in IGRA-positive LTBI subjects, but did not change considerably in initially IGRA-negative LTBI or control subjects.ConclusionThe lack of decrease in interferon-γ response in young children indicates that IGRA could be considered for this age group. Serial IGRA tests might accurately diagnose LTBI in children lacking contact history with active TB patients.

Consensus Document on Prevention and Treatment of Tuberculosis in Patients for Biological Treatment

Tuberculosis risk is increased in patients with chronic inflammatory diseases receiving any immunosuppressive treatment, notably tumor necrosis factor (TNF) antagonists therapy. Screening for the presence of latent infection with Mycobacterium tuberculosis and targeted preventive treatment to reduce the risk of progression to tuberculosis disease is mandatory in these patients.This Consensus Document summarizes the current knowledge and expert opinion of biologic therapies, including TNF-blocking treatments. It provides recommendations for the use of interferon-gamma release assays (IGRA) and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in these patients, and for the type and duration of preventive therapy.

Despistaje de tuberculosis latente en el paciente con psoriasis moderada grave candidato a terapia sistémica y/o biológica

Screening to detect latent tuberculosis infection (LTBI) is essential before patients with moderate to severe psoriasis start treatment with biologics and vigilance will continue to be needed during and after such treatment. The most recently analyzed statistics from the BIOBADADERM registry show a 20.5% prevalence of LTBI in psoriasis patients treated with biologics in Spain. Various screening protocols are in effect in different countries according to their levels of endemic TB and bacillus Calmette-Guérin (BCG) vaccination, and there is no consensus on a gold-standard approach to the diagnosis of LTBI. Tuberculin skin testing (TST) continues to be the diagnostic method of choice in spite of its limited sensitivity, mainly in immunocompromised patients. Additional problems include the TST's well-established lack of specificity, errors in application, subjectivity in the interpretation of results (which must be read during a second visit), and lack of privacy; the main advantages of this test are its low cost and ease of application. Most cost-benefit studies are therefore inclined to favor using interferon-γ release assays to detect LTBI because they minimize false positives (especially in BCG-vaccinated individuals), thereby eliminating the extra costs and side effects of unnecessary chemoprophylaxis. We review the methods used for LTBI screening in psoriasis patients who are candidates for biologic therapy. Additionally, given the fact that most guidelines do not currently consider it necessary to screen patients about to start conventional systemic therapy, we discuss the reasons underlying the need for such screening.

A Homogeneous Immunoassay Method for Detecting Interferon-Gamma in Patients with Latent Tuberculosis Infection

IFN-γ release assays (IGRAs) have been developed as viable alternative diagnostic tools for detecting latent tuberculosis infection (LTBI). A customized homogeneous sandwich luminescent oxygen channeling immunoassay (LOCI) was used to quantify IFN-γ levels in IGRAs. Samples were collected from healthy volunteers (n = 40) who were T-Spot-negative and T-Spot-positive patients (n = 32) at rest. Then the amount of IFN-γ in the supernatant of IGRAs was measured by LOCI. The results demonstrated a low background, and high sensitivity, specificity, accuracy, and reproducibility, and a short assay time (only 30 min) with LOCI for IFN-γ. The recovery range was 81.63-102.06%, the coefficients of variation were below 5%, and the limit of detection was 19.0 mIU/ml. Excellent agreement between LOCI IFN-γ and the T-SPOT.TB test was obtained (97.2% agreement, κ = 0.94). The LOCI IFN-γ concentrations were significantly higher in T-Spot-positive patients than in the healthy group (p < 0.001). Moreover, as observed for the comparative LOCI IFN-γ assay, IFN-γ concentrations were related to the numbers of T-SPOT.TB spots. We have established an in vitro blood test for LTBI diagnosis, defined as LOCI IFN-γ. A high level of agreement between the LOCI IFN-γ method and T-SPOT.TB assay was observed in clinical studies that showed the LOCI IFN-γ method could determine LTBI. This study shows acceptable performance characteristics of the LOCI IFN-γ assay to diagnose LTBI.

Knowledge and Perceptions of Latent Tuberculosis Infection among Chinese Immigrants in a Canadian Urban Centre.

Background. Since most tuberculosis (TB) cases in immigrants to British Columbia (BC), Canada, develop from latent TB infection (LTBI), treating immigrants for LTBI can contribute to the eradication of TB. However, adherence to LTBI treatment is a challenge that is influenced by knowledge and perceptions. This research explores Chinese immigrants' knowledge and perceptions towards LTBI in Greater Vancouver. Methods. This mixed methods study included a cross-sectional patient survey at BC's Provincial TB clinics and two focus group discussions (FGDs) with Chinese immigrants. Data from FGDs were coded and analyzed in Simplified Chinese. Codes, themes, and selected quotes were then translated into English. Results. The survey identified a mean basic knowledge score: 40.0% (95% CI: 38.3%, 41.7%). FGDs confirmed that Chinese immigrants' knowledge of LTBI was low, and they confused it with TB disease to the extent of experiencing LTBI associated stigma. Participants also expressed difficulties navigating the health system which impeded testing and treatment of LTBI. Online videos were the preferred format for receiving health information. Conclusion. We identified striking gaps in knowledge surrounding an LTBI diagnosis. Concerns of stigma may influence acceptance and adherence of LTBI treatment in Chinese immigrants. Integrating these findings into routine health care is recommended.

Tuberculose latente em profissionais de saúde: concordância entre 2 testes diagnósticos

The diagnosis of latent tuberculosis infection (LTBI), namely in healthcare workers, has been done by tuberculin skin test (TST). Recently, Interferon‐ʎ Release Assays (IGRA tests) have been introduced. Unlike TST, they do not turn positive after BCG vaccine or after most of non‐tuberculous mycobacteria infections.In the absence of a gold standard for the diagnosis of LTB, the aim of this study was to analyze the correlation between the two LTB diagnostic techniques, by determining Kappa coefficient and concordance rate between TST and IGRA test, in healthcare workers of a Portuguese university hospital.We carried out a cross‐sectional and retrospective study, and we analysed TST and IGRA tests records, that are performed simultaneously (up to 15 days apart) in Occupational Health Department, in 2010 and 2011 (n137).Most of the sample did BCG and 44.5% did two or more inoculations. The average diameter of PT was 17.5mm (SD 4.3). Only two subjects reported TST<10mm, both showing a negative IGRA test. Only 53 (39.3%) of the 135 participants with positive PT had a positive IGRA test too.The level of agreement between TST and the IGRA test was determined by Kappa coefficient. Respectively to a cut off for PT of 10mm, 15mm and 20mm, the degree of agreement was 0.019 (p=0.26), 0,19 (p=0.001) and 0.26 (p=0.003). Concordance rates were respectively 40%, 54% and 65%.It was found that the concordance between the two methods increased as the cut off for TST also increased. Nevertheless, a higher concordance rate would be expected with cut off of 15mm, and particularly of 20mm, since BCG vaccine administered in childhood usually induce smaller reactions. The existence of more than one BCG inoculation in the sample, especially after childhood, can be partly responsible for the low concordance between the two methods. Nevertheless, we cannot also exclude IGRA test's false negatives.In the decision to treat LTB, it is necessary to take into account the limitations of both tests, their level of agreement and weighting individual, occupational and epidemiological factors.

Comparative study of concordance and costs between tuberculin skin test and QuantiFERON®-TB Gold In-Tube in the diagnosis of latent tuberculosis infection among contacts of patients with pulmonary tuberculosis

IntroductionRecently diagnosis of latent tuberculosis infection (LTBI) can be made using the tuberculin skin test (TST) or by techniques known as interferon-γ release assays (IGRAS), being QuantiFERON®-TB Gold In-Tube (QF-G-IT) the most used. The IGRAS avoid some drawbacks of the TST, especially cross-reaction with bacillus Calmette-Guérin (BCG) vaccine, but also present some problems such as those arising from cost and the need of having an adequate infrastructure and experience. There is no clear consensus on which technique should be preferentially used for the diagnosis of LTBI. MethodsThis is a comparative study between the TST and QT-G-IT in a cohort of contacts of patients with pulmonary tuberculosis during the study period. An analysis of global agreement and groups was performed according to whether the contacts were vaccinated with BCG or not. A study of costs of both techniques and diagnostic strategies based on these techniques was performed. ResultsThe agreement between TST and QF-G-IT was acceptable in the whole sample yet it was very good in the unvaccinated group. Few cases of indeterminate values were recorded. The cost study showed that TST was cheaper than QF-G-IT; however when we analysed the cost of the strategies according to each technique, the QF-G-IT showed a better cost-benefit. ConclusionWe suggest considering QF-G-IT as the only preferred technique for the diagnosis of LTBI in household contacts, based on good overall agreement between the 2 techniques (even if we eliminate the effect of the vaccine) and a cost analysis favourable to QF-G-IT.

The diagnosis of latent tuberculosis infection in children in XXI century. Is tuberculin skin test still up to date?

Tuberculosis morbidity rates in Poland have been gradually decreasing. Nevertheless, there are approximately 8 thousand cases being registered annually, which includes almost 3 thousand massively infectious patients. In the last 3 years, around 100 cases/year have been reported among children below 14 years of age. Infection with Mycobacterium tuberculosis should be considered in all patients who present symptoms suggesting tuberculosis, have had recent contact with a person suffering from lung tuberculosis or are planned to undergo an immunosuppressive treatment. HIV infected patients are also supposed to have screening tests for M. tuberculosis infection performed. For over a 100 years tuberculin skin test (TST) was the only test capable of confirming tuberculous infection. TST is based on the assessment of skin reaction to intracutaneous injection of tuberculin. Due to cross-reaction to the injected tuberculin in BCG vaccinated individuals, the correct interpretation of the test is difficult. Since 13 years new immunological assays have been available. They are based on detecting interferon gamma (Interferon Gamma Release Assay - IGRA) concentration in blood serum, which has previously been incubated with Mycobacterium tuberculosis antigens absent in the BCG strain. In infected individuals interferon gamma is intensively produced by memory cells in reaction to the contact with previously met Mycobacterium antigens. Many trials have proved IGRA's high sensitivity and, higher than TST, specificity. Recent guidelines promote the usage of IGRAs, even in children.

Enhanced Tuberculosis Infection Treatment Outcomes after Implementation of QuantiFERON®-Gold Testing.

BackgroundUse of the tuberculin skin test (TST) for diagnosis of latent tuberculosis infection (LTBI) among individuals who received the Bacille Calmette-Guérin (BCG) vaccine is complicated by its potential cross-reaction with TST antigens which may cause false-positive results and lead to patient and physician reluctance to initiate LTBI treatment. QuantiFERON®-TB Gold (QFT-G) lacks this cross-reaction. We sought to study the impact of implementing QFT-G testing in 2006 on LTBI treatment initiation and completion at NYC chest clinics.MethodsQFT-G results from 10/2006–12/2008 in NYC Department of Health and Mental Hygiene chest clinics were obtained from the electronic medical record system. The proportions of patients who initiated and completed treatment among patients tested with QFT-G were compared to those tested with TST from 10/2004–9/2006.ResultsAmong 36,167 patients tested with QFT-G, 2,300 (6%) tested positive, 33,327 (93%) tested negative, and 540 (1%) had an indeterminate result. Among those who had a positive QFT-G test and deemed eligible, 985 (80%) initiated LTBI treatment and 490 (40%) completed treatment. Historically, among patients tested with TST, 7,073 (19%) tested positive (p<0.0001 compared to QFT-G); 3,182 (79%) of those eligible initiated LTBI treatment and 1,210 (30%) completed treatment (p<0.0001 compared to QFT-G).ConclusionsQFT-G implementation increased the proportion of patients completing LTBI treatment. Additional studies are needed in more settings to determine whether using QFT-G leads to a sustained increase in treatment completion.

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

AbstractMost people with latentMycobacterium tuberculosisinfection 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.

T-SPOT.TB Assay Screening for Latent TB Infection Among Healthcare Workers?

Screening for latent tuberculosis infection (LTBI) among healthcare workers (HCWs) is important for long-term control of TB. Diagnosis of LTBI has been augmented by the commercial availability of interferon-γ release assays (IGRAs), which offer advantages in application and interpretation over the tuberculin skin test. However, several recent studies have suggested challenges in using IGRAs for HCW screening programs, including high rates of …

Novel T-cell assays for the discrimination of active and latent tuberculosis infection: the diagnostic value of PPE family.

The diagnosis of active and latent tuberculosis remains a challenge. Although a new approach based on detecting Mycobacterium tuberculosis-specific T-cells has been introduced, it cannot distinguish between latent infection and active disease. The aim of this study was to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarker after specific antigen stimulation with PE35 and PPE68 for the discrimination of active and latent tuberculosis infection (LTBI). The production of IL-2 was measured in the antigen-stimulated whole-blood supernatants following stimulation withrecombinant PE35 and PPE68. The discrimination performance (assessed by the area under ROC curve) for IL-2 following stimulation withrecombinant PE35 and PPE68 between LTBI and patients with active TB were 0.837 [95% confidence interval (CI) 0.72-0.97] for LTBI diagnosis and 0.75 (95% CI 0.63-0.89) for active TB diagnosis, respectively. Applying the 6.4pg/mL cut-off for IL-2 induced by PE35 in the present study population resulted in sensitivity of 78%, specificity of 83%, PPV of 83% and NPV of 78% for the discrimination of active TB and LTBI. In addition, a sensitivity of 81%, specificity of 71%, PPV of 68 and 83% of NPV was reported based on the 4.4pg/mL cut-off for IL-2 induced by PPE68. This study confirms IL-2 induced by PE35 and PPE68 as a sensitive and specific biomarker and highlights IL-2 as new promising adjunct markers for discriminating of LTBI and active TB disease.

Documento de consenso sobre la prevención y el tratamiento de la tuberculosis en pacientes candidatos a tratamiento biológico

Tuberculosis risk is increased in patients with chronic inflammatory diseases receiving any immunosuppressive treatment, notably tumor necrosis factor (TNF) antagonists therapy. Screening for the presence of latent infection with Mycobacterium tuberculosis and targeted preventive treatment to reduce the risk of progression to TB is mandatory in these patients.This Consensus Document summarizes the current knowledge and expert opinion of biologic therapies including TNF-blocking treatments. It provides recommendations for the use of interferon-gamma release assays (IGRA) and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in these patients, and for the type and duration of preventive therapy.

Aplicación y utilidad actual de las técnicas de interferón-γ en el diagnóstico de la tuberculosis

Utility of the in-vitro immunodiagnostic methods, based on the detection of interferon-γ released by T-cells after specific Mycobacterium tuberculosis antigen stimulation (IGRA), has been an improvement in the accuracy of the latent tuberculosis infection diagnosis. IGRA have a well-known higher specificity than the tuberculin skin testing (TST). Moreover, they can obtain a larger number of positive results than the TST in immunocompromised patients. IGRA have shown a high correlation with M. tuberculosis exposure, but their positive and negative predictive value are similar than those obtained by TST. Nevertheless, given their high specificity, they allow reducing number of unnecessary preventive treatments. In addition, these in-vitro techniques are less affected than TST by the different immunosuppressing status. In this review is discussed up-to-date applicability of IGRA in different patient groups: contact studies, pediatric population, immunosuppressed patients, health care workers and active tuberculosis patients. Furthermore, it has been included possible future directions for latent tuberculosis infection and active tuberculosis diagnosis.

Dormancy antigens as biomarkers of latent tuberculosis infection

Mycobacterium tuberculosis (MTB) is a major microbial pathogen that threatens global health. The WHO has estimated about 9 million new tuberculosis (TB) cases and around 1.5 million deaths due to TB in the year 2013 (World Health Organization, 2014). In MTB-infected individuals, bacteria may exist in a dormant state for lengthy periods without causing disease symptoms, or may finally start multiplying and evading immune control, resulting in active TB in 5–10% of infected cases. At present, factors that promote progression from latent tuberculosis infection (LTBI) to disease are not totally understood. Therefore, management of LTBI plays a significant role for TB disease control given that quiescent bacilli are a big reservoir of potential TB cases.

Diagnosis and Management of Latent Tuberculosis Infection.

The post-2015 World Health Organization global tuberculosis strategy recognizes that elimination requires a focus on reducing the pool of latently infected individuals, an estimated 30% of the global population, from which future tuberculosis cases would be generated. Tackling latent tuberculosis infection requires the identification and treatment of asymptomatic individuals to reduce the risk of progression to active disease. Diagnosis of latent tuberculosis infection is based on the detection of an immune response to Mycobacterium tuberculosis antigens using either the tuberculin skin test or interferon-γ release assays. Current treatment requires the use of antibiotics for at least 3 months. In this article, we review the current knowledge of the natural history, immunology, and pathogenesis of latent tuberculosis, describe key population groups for screening and risk assessment, discuss clinical management in terms of diagnosis and preventative treatment, and identify areas for future research.

A scoping review of cost-effectiveness of screening and treatment for latent tubercolosis infection in migrants from high-incidence countries.

BackgroundIn low-incidence countries, most tuberculosis (TB) cases occur among migrants and are caused by reactivation of latent tuberculosis infection (LTBI) acquired in the country of origin. Diagnosis and treatment of LTBI are rarely implemented to reduce the burden of TB in immigrants, partly because the cost-effectiveness profile of this intervention is uncertain.The objective of this research is to perform a review of the literature to assess the cost-effectiveness of LTBI diagnosis and treatment strategies in migrants.MethodsScoping review of economic evaluations on LTBI screening strategies for migrants was carried out in Medline.ResultsNine studies met the inclusion criteria. LTBI screening was cost-effective according to seven studies. Findings of four studies support interferon gamma release assay as the most cost-effective test for LTBI screening in migrants. Two studies found that LTBI screening is cost-effective only if carried out in immigrants who are contacts of active TB cases.Discussion and ConclusionsOur findings support the cost-effectiveness of LTBI diagnostic and treatment strategies in migrants especially if they are focused on young subjects from high incidence countries. These strategies could represent and adjunctive and synergistic tool to achieve the ambitious aim of TB elimination.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-015-1045-3) contains supplementary material, which is available to authorized users.

The diagnostic accuracy of tests for latent tuberculosis infection in hemodialysis patients: a systematic review and meta-analysis.

Reactivation of latent Mycobacterium tuberculosis infection is an important health concern for patients on hemodialysis because of their immunosuppressed state and in kidney transplant patients receiving immunosuppressive therapy to prevent organ rejection. There are several tests available to determine the presence of latent tuberculosis infection: the tuberculin skin test (TST), QuantiFERON-TB Gold (QFT-G), and T-SPOT.TB. The objective of this study is to evaluate the diagnostic accuracy of these tests in determining latent tuberculosis infection in the hemodialysis population. The study design was a systematic review. We selected studies with adequate information to ascertain test sensitivity or specificity of the TST, QFT-G, and TSPOT.TB with regards to determining latent tuberculosis infection in the hemodialysis population. One hundred two articles were selected for full review, and 17 were included in the meta-analysis. The TST had a pooled sensitivity of 31% (26%-36%, 95% confidence interval) and specificity of 63% (60%-65%) across eight studies. The QFT-G test had a pooled sensitivity of 53% (46%-59%) and specificity of 69% (65%-72%) across nine studies. The T-SPOT.TB test had a pooled sensitivity of 50% (42%-59%) and specificity of 67% (61%-73%) across three studies. The QFT-G and the T-SPOT.TB tests were more sensitive than the TST for diagnosis of latent tuberculosis infection in patients on hemodialysis while offering a comparable level of specificity. This systematic review calls into question the practice of using the TST to screen in this population, especially in patients considered for kidney transplantation.

PMD52 - Screening high-risk populations for Latent Tuberculosis: a systematic review of cost-utility analyses

Efforts to reduce the tuberculosis (TB) burden in many countries have recently focused on screening high-risk groups for latent TB infection (LTBI). Clinicians generally use the tuberculin skin test (TST) or interferon-gamma release assay (IGRA) to aid in LTBI diagnosis. We performed a systematic review of cost-utility analyses in this area. Five electronic databases were used to identify studies. Study quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Population, setting, model type, perspective, costs, screening and treatment parameters, and incremental cost-effectiveness ratios (ICERs) were extracted. All costs were adjusted to 2013 US dollars, with ICERs <$20,000 considered highly cost-effective, ICERs between $20,000 and $100,000 moderately cost-effective, and ICERs >$100,000 not cost-effective. Of 415 studies identified, 8 were included in the analysis, with 7 using Markov models and 1 using decision analysis. The decision to screen and how to screen for LTBI was evaluated in 5 studies, while the remaining three only evaluated how to screen. Perspectives used were societal (n=4), healthcare program (n=2), and healthcare system (n=2). Studies evaluating immigrants found adult screening highly cost-effective with a TST (n=1) and moderately cost-effective with an IGRA (n=1). Screening of the foreign-born (n=1) was moderately cost-effective with an IGRA until 44 years of age. Screening for HIV was found to be highly cost-effective with a TST (n=3) and moderately cost-effective with an IGRA (n=1). Screening in those with renal diseases (n=2) and diabetes (n=1) was found to be not cost-effective; screening in other immunocompromised populations was not cost-effective (n=1). Screening of HIV patients with a TST is highly cost-effective and screening of immigrants and foreign-born with an IGRA is moderately cost-effective. Screening of other immunocompromised populations is cost-prohibitive, however with minimal well-designed studies using consistent assumptions and parameters, these Conclusions should be interpreted cautiously.