Latent Tuberculosis Testing Research Articles

Acceptability of latent tuberculosis testing of migrants in a college environment in England

ObjectivesThe majority of tuberculosis (TB) cases in England occur from reactivation of latent tuberculosis infection (LTBI) in the settled migrant population. The National Institute for Health and Clinical Excellence recommends that new entrants from high-incidence countries are screened to detect LTBI. This article seeks to describe an outreach programme and testing for LTBI in an innovative setting—ESOL (English for Speakers of Other Languages) classes at a community college (CC) with evaluation of acceptability. Study designPartnership working with mixed methods used for evaluation of acceptability. MethodsA pre-existing network from the local TB partnership designed an outreach intervention and screening for LTBI among students from an ESOL programme at a CC. Screening for LTBI with interferon gamma release assay was the culmination of a programme of health improvement activities across the college. Any student on the ESOL programme younger than the age of 35 years and resident in the UK for less than 5 years was eligible for testing. LTBI testing was carried out on-site, and the experience was evaluated by questionnaires to staff, students and partners. A facilitated debrief among the partners gave further data. ResultsA total of 440 eligible students were tested. One hundred and seventy-two student feedback questionnaires were completed, and 36 partner questionnaires were received with 18 CC staff responding. Students, tutors and healthcare professionals found the setting acceptable with some concerns about insufficient resource for timely follow-up. ConclusionsStudents, tutors, community organisations and health professionals found the exercise worthwhile and the method and setting acceptable. There were resource issues for the clinical team in follow-up of students with positive results for such a large screening event. Unexpected barriers were found by the CC as this kind of activity was not recognised for external quality review purposes. There were concerns about reputational loss and stigma of being involved in a TB project. As current initiatives aim to divert workload from stretched general practice surgeries, this may be an important addition to primary care screening.

Knowledge, experiences, and attitudes toward Mantoux test among medical and health professional students in Italy: a cross-sectional study.

The World Health Organization's Action Framework for tuberculosis elimination in low-tuberculosis incidence countries includes the screening for active and latent tuberculosis in selected high-risk groups, including health care workers. In this context, medical and health profession students, exposed to nosocomial tuberculosis transmission during training and clinical rotations, are target populations for tuberculosis screening. No updated data are available on tuberculosis screening practice and knowledge of medical and health profession students in Italy. Within the activities Italian Study Group on Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine and Public Health, we carried out a multicentre cross-sectional study to assess knowledge, attitude and practices on tuberculosis prevention and control among Medical, Dentistry, Nursing and other health professions' students. Students were enrolled in the study on a voluntary basis and were administered a previously piloted structured questionnaire. Logistic regression models were applied to explore knowledge on tuberculosis prevention by selected socio-demographic variables and University-based tuberculosis prevention practice. Students of seventeen Universities across Italy participated in the study, and 58.2% of them received compulsory tuberculin skin test either at enrollment or while attending clinical practice. A total of 5,209 students filled the questionnaire. 37.7% were medicine and dentistry students (Group 1), 44.9% were nursing students (Group 2) and 17.4% were other health professions' students (Group 3). Age and gender had different distributions by groups, as well as knowledge and practice on tuberculin skin test. 84.4% of the study population (95% CI = 83.3-85.3) was aware of the existence of the tuberculin skin test, 74.4% (95% CI = 73.2-75.6) knew what is the first-level screening test for latent tuberculosis and only 22.5% (95% CI = 21.4-23.6) knew how to proceed after a positive tuberculin skin test result. Overall, knowledge on tuberculosis prevention was higher in Group 2 and lower Group 3, as compared to Group 1. In Italy, the knowledge on tuberculosis screening among University students is generally good. To reduce some of the criticalities found among the different study courses, it would be appropriate to harmonize both the regulations on tuberculosis screening practices for admission to University courses, and the educational activities on the topic of tuberculosis, to be extended to all workers involved in health care setting.

Diagnosis and treatment of latent tuberculosis in patients with multiple sclerosis, expert consensus. On behalf of the Colombian Association of Neurology, Committee of Multiple Sclerosis.

BackgroundMultiple sclerosis is an inflammatory and neurodegenerative demyelinating disease. Current treatment of multiple sclerosis focuses on the use of immunomodulatory, immunosuppressant, and selective immunosuppressant agents. Some of these medications may result in high risk of opportunistic infections including tuberculosis.ObjectiveThe purpose of this study was to obtain consensus from a panel of neurologists, pulmonologists, infectious disease specialists, and epidemiology experts regarding the diagnosis, treatment, and monitoring of latent tuberculosis in patients with multiple sclerosis.MethodsA panel of experts in multiple sclerosis and tuberculosis was established. The methodological process was performed in three phases: definition of questions, answer using Delphi methodology, and the discussion of questions not agreed.ResultsTuberculosis screening is suggested when multiple sclerosis drugs are prescribed. The recommended tests for latent tuberculosis are tuberculin and interferon gamma release test. When an anti-tuberculosis treatment is indicated, monitoring should be performed to determine liver enzyme values with consideration of age as well as comorbid conditions such as a history of alcoholism, age, obesity, concomitant hepatotoxic drugs, and history of liver disease.ConclusionLatent tuberculosis should be considered in patients with multiple sclerosis who are going to be treated with immunomodulatory and immunosuppressant medications. Transaminase level monitoring is required on a periodic basis depending on clinical and laboratory characteristics. In addition to the liver impairment, other side effects should be considered when Isoniazid is prescribed.

National roll-out of latent tuberculosis testing and treatment for new migrants in England: a retrospective evaluation in a high-incidence area.

Latent tuberculosis infection (LTBI) screening is an important intervention for tuberculosis (TB) elimination in low-incidence countries and is, therefore, a key component of England's TB control strategy. This study describes outcomes from a LTBI screening programme in a high-incidence area to inform national LTBI screening in England and other low-incidence countries.We conducted a retrospective cohort study of LTBI screening among eligible migrants (from high-incidence countries and entered the UK within the last 5 years), who were identified at primary-care clinics in Newham, London between August 2014 and August 2015. Multivariable logistic regression was used to identify factors associated with LTBI testing uptake, interferon-γ release assay (IGRA) positivity and treatment uptake.40% of individuals offered LTBI screening received an IGRA test. The majority of individuals tested were 16–35 years old, male and born in India, Bangladesh or Pakistan. Country of birth, smoking status and co-morbidities were associated with LTBI testing uptake. IGRA positivity was 32% among those tested and was significantly associated with country of birth, age, sex and co-morbidities.This study identifies factors associated with screening uptake, IGRA positivity and treatment uptake, and improves understanding of groups that should be supported to increase acceptability of LTBI testing and treatment in the community.

Improved Serodiagnostic Sensitivity of Strip Test for Latent Tuberculosis.

Diagnosis of Latent Tuberculosis Infection (LTBI) is difficult due to no clinical manifestations. Cases of LTBI are mostly sputum negative. The World Health Organization recommends the Tuberculin Skin Test (TST) as the current diagnostic standard for LTBI. Our previously developed serologic strip test for LTBI detection had suboptimal sensitivity. Additional Mycobacteriumtuberculosis (MTB) latency-associated antigens may improve the detection rate of LTBI. The present study aimed to optimize sensitivity of existing strip test. A combination of recombinant latency proteins Rv2029c, Rv2031c, Rv2032, Rv2627c, Rv3133c, and Rv3716c was used to prepare the strips and evaluate the performance with the sera of patients in four well-classified categories: LTBI, active pulmonary TB, healthy TB contacts and other non-TB diseases. A total of 91 serum samples from various clinical categories were screened with the strips. Among clinically diagnosed LTBI patients, strip test yielded a sensitivity of 75.0%. Among clinically diagnosed non-LTBI subjects, strip test yielded 88.1% specificity. The diagnostic positive and negative predictive values for strip test in reference to various clinical contexts were 77.4% and 86.7%, respectively. Addition of the six potential latency proteins could improve the diagnostic performance of existing strip test for LTBI. The use of suitable immunodominant antigens could maximize sensitivity in the diagnosis and differentiate MTB infection status.

Continuing Medical Education Improves Gastroenterologists' Compliance with Inflammatory Bowel Disease Quality Measures.

Low rates of compliance with quality measures for inflammatory bowel disease (IBD) have been reported for US gastroenterologists. We assessed the influence of quality improvement (QI) education on compliance with physician quality reporting system (PQRS) measures for IBD and measures related to National Quality Strategy (NQS) priorities. Forty community-based gastroenterologists participated in the QI study; 20 were assigned to educational intervention and control groups, respectively. At baseline, randomly selected charts of patients with moderate-to-severe ulcerative colitis were retrospectively reviewed for the gastroenterologists' performance of 8 PQRS IBD measures and 4 NQS-related measures. The intervention group participated in a series of accredited continuing medical education (CME) activities focusing on QI. Follow-up chart reviews were conducted 6months after the CME activities. Independent t tests were conducted to compare between-group differences in baseline-to-follow-up rates of documented compliance with each measure. The analysis included 299 baseline charts and 300 follow-up charts. The intervention group had significantly greater magnitudes of improvement than the control group for the following measures: assessment of IBD type, location, and activity (+14%, p=0.009); influenza vaccination (+13%, p=0.025); pneumococcal vaccination (+20%, p=0.003); testing for latent tuberculosis before anti-TNF-α therapy (+10%, p=0.028); assessment of hepatitis B virus status before anti-TNF-α therapy (+9%, p=0.010); assessment of side effects (+17%, p=0.048), and counseling patients about cancer risks (+13%, p=0.013). QI-focused CME improves community-based gastroenterologists' compliance with IBD quality measures and measures aligned with NQS priorities.

An Assessment of the AGA and CCFA Quality Indicators in a Sample of Patients Diagnosed with Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic relapsing disease characterized by activation of the mucosal immune system and inflammation of the gastrointestinal tract. Management of IBD places a significant burden on the health care system because of the complexity of treatment, variability in patient outcomes, and chronic nature of the disease. To investigate the American Gastroenterological Association (AGA) and Crohn's and Colitis Foundation of America's (CCFA) quality measurement sets in a sample of IBD patients. Fourteen quality measures were restated for application to a claims database and calculated using Optum Clinformatics DataMart database. Selected measures were calculated over calendar year 2011. Performance measures ranged from 0.4% for AGA measure 9, prophylaxis for venous thromboembolism, to 66.9% for AGA measure 8, testing for Clostridium difficile. CCFA outcome measures ranged from 0.6% qualifying for CCFA O10, report of fecal incontinence, to 32.9% for CCFA O1, prednisone usage. In addition to Clostridium difficile testing, the use of appropriate corticosteroid-sparing therapy (51.1%) and testing for latent tuberculosis before initiating anti-tumor necrosis factor therapy (45.0%) were the highest achieved measures. This is the first examination of IBD quality measures using administrative claims. Rates of achievement across measures were variable and likely affected by the ability to calculate certain measures with claims data. Future studies should further examine measurement of IBD quality indicators in claims data to assess the validity of claims-based analyses and to ascertain whether measure attainment translates into better overall health or IBD-related outcomes.

O15 IGRA testing for latent tuberculosis in commercial sex workers

Background/introduction Tuberculosis (TB) is a significant public health issue in Birmingham. Targeting ‘hard to reach’ groups, such as commercial sex workers (CSW), is a priority for Public Health England. Additionally, a large proportion of CSW in Birmingham are from Romania, where TB prevalence is high. We undertook a project to look for latent TB amongst CSW attending an outreach sexual health clinic. Aim(s)/objectives To determine the: feasibility of testing and following up this group. prevalence of latent TB in this group. Methods We offered Interferon Gamma Release Assay (IGRA) testing to all CSW attending clinic between 29.04.2014 and 24.11.2014. Results Seventy-one women were screened. Twenty-six were IGRA positive. Of these, eighteen were followed up in TB clinic: Three had results suggesting previous TB and were discharged from clinic without treatment. Eleven were diagnosed with latent TB and treated accordingly. Four were diagnosed with active TB and are on appropriate therapy. Eight were lost to follow up. Discussion/conclusion We demonstrated that testing is acceptable and feasible to this group. Follow-up was challenging but a review of the referral process led to improved attendance rates. To improve adherence, we used weekly rifapentine and isoniazid for latent TB in selected cases. We are the only unit in UK to have used this regimen. The prevalence rate of latent TB was higher than anticipated at 15%. Identifying active TB cases further demonstrated that this is a group worth targeting. These preliminary results led to an extension of this project.

Decreasing cost effectiveness of testing for latent TB in HIV in a low TB incidence area.

Testing for latent tuberculosis infection (LTBI) in HIV-infected persons in low tuberculosis (TB) incidence areas is often recommended. Using contemporary, clinical data, we report the yield and cost-effectiveness of testing all HIV attendees, two current UK strategies and no LTBI testing. Economic modelling was performed utilising 10-year follow up data from a large HIV clinical cohort. Outcomes were numbers of cases of active TB and incremental cost per quality-adjusted life year (QALY) gained. Between 2000 and 2010, 256 people were treated for TB/HIV co-infection. 72 (28%) occurred ≥3 months after HIV diagnosis and may have been prevented by LTBI testing. Between 2000 and 2005, the incremental cost per QALY gained for the British HIV Association (BHIVA) and UK National Institute of Care Excellence (NICE) strategies, and testing all clinic attendees was €6270, €6998 and €33,473, respectively. These rose to €9332, €32,564 and €74,067, respectively, between 2005 and 2010. Probabilistic sensitivity analysis suggested that at a threshold of €24,000 per additional QALY, the most cost-effective strategies would be NICE or testing all in 2000-2005 and BHIVA during 2005-2010. Both UK testing regimens missed cases but are cost-effective compared with no testing. Using recent data, they all became more expensive, suggesting that alternative or more targeted TB testing strategies must be considered.

Acceptability of latent tuberculosis testing among migrant farmworkers along the US-Mexico border

Acceptability of latent tuberculosis testing among migrant farmworkers along the US-Mexico border

Broad adaptive immune responses to M. tuberculosis antigens precede TST conversion in tuberculosis exposed household contacts in a TB-endemic setting.

BackgroundThe identification of Mycobacterium-tuberculosis (Mtb) infected individuals remains a challenge due to an insufficient understanding of immune responses detected with the current diagnostic tests for latent tuberculosis i.e. the tuberculin skin test (TST) or IFN–γ release assays (IGRAs) and an inability to distinguish infection stages with current immunologic assays. Further classification based on markers other than IFN–γ may help to define markers of early Mtb infection.MethodsWe assessed the TST status of Mtb-exposed household contacts at baseline and at 6 months. Contacts were classified into those with initial positive TST (TST+); those with baseline negative TST but TST conversion at 6 months (TST converters, TSTC) and those with persistently negative TST (PTST−). We assessed their short- and long-term immune responses to PPD and ESAT–6/CFP–10 (EC) via IFN–γ ELISPOT and a multiplex cytokine array in relation to TST status and compared them to those of TB cases to identify immune profiles associated with a spectrum of infection stages.ResultsAfter 1 and 6 days stimulation with EC, 12 cytokines (IFN–γ, IL–2, IP–10, TNF–α, IL–13, IL–17, IL–10, GMCSF, MIP–1β, MCP–3, IL–2RA and IL–1A) were not different in TSTC compared to TST+ suggesting that robust adaptive Mtb-specific immune responses precede TST conversion. Stratifying contacts by baseline IFN–γ ELISPOT to EC in combination with TST results revealed that IP–10 and IL–17 were highest in the group of TST converters with positive baseline ELISPOT, suggesting they might be markers for recent infection.ConclusionWe describe a detailed analysis of Mtb-specific biomarker profiles in exposed household contacts in a TB endemic area that provides insights into the dynamic immune responses to Mtb infection and may help to identify biomarkers for ‘at-risk’ populations beyond TST and IGRA.

Targeted Testing for Latent Tuberculosis: How Much Do We Know?

Targeted Testing for Latent Tuberculosis: How Much Do We Know?

FRI0308 Is Tuberculosis Screening Sufficient for Preventing TB Reactivation in Biologic Treated Patients?

BackgroundThe risk of latent tuberculosis (TB) reactivation in patients treated with biologics for rheumatic inflammatory diseases is well-established. This is a great concern especially in countries with high TB burden....

AB0433 Quantiferon-Tb More Useful than Tuberculin Skin Test for Latent Tuberculosis Screening: A Hospital Experience

BackgroundThe use of interferon gamma-release assays (IGRA) has become a very useful tool in the detection of latent tuberculosis (LTB) among patients on biological disease modifying anti-rheumatic drugs (bDMARDs). The...

Efficacy and safety of etanercept in chronic immune-mediated disease

Introduction: TNF-α inhibitors have demonstrated efficacy in large, randomized controlled clinical trials either as monotherapy or in combination with other anti-inflammatory or disease-modifying antirheumatic drugs in the treatment of chronic inflammatory immune-mediated diseases. Etanercept is a fusion protein that acts as a ‘decoy receptor’ for TNF-α.Areas covered: This paper evaluates the efficacy and safety of etanercept in patients with chronic inflammatory immune-mediated diseases.Expert opinion: Etanercept was first approved for the treatment of rheumatoid arthritis (RA) and subsequently of chronic plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and juvenile RA. Etanercept as other TNF-α inhibitors, particularly infliximab, may be administered off-label to treat other chronic inflammatory immune-mediated diseases such as systemic sclerosis, Behcet disease, systemic lupus erythematosus, polymyositis, dermatomyositis and mixed connective tissue disease. Early etanercept treatment prevents joint damage and helps to avoid long-term disability in arthritis. Etanercept administered at a dose of 50 mg once weekly is effective in inducing an earlier remission of RA, and etanercept 50 mg twice weekly may favor a more rapid improvement of psoriasis and psoriatic arthritis. Etanercept and adalimumab may exert beneficial effects on lipid profile and improve endothelial dysfunction. Appropriate screening tests for latent tuberculosis, hepatitis B virus and hepatitis C virus should be performed before starting etanercept. TNF-α inhibitors including etanercept are contraindicated in patients with demyelinating diseases.

IGRA-positive patients and interferon-gamma/interleukin-2 signatures: Can the Fluorospot assay provide further information?

A goal of testing for latent tuberculosis (TB) infection is to identify individuals who are at increased risk for the development of active TB. No laboratory tool is currently available to distinguish between individuals in the process of progressing from latent TB infection towards active disease and those who are not. Determination of the interferon-gamma and interleukin-2 T cell signature might provide an additional and rapid tool to evaluate treatment necessity and clinical management of a patient. Here, we present three cases of interferon-gamma release assay-positive patients with differing interferon-gamma and interleukin-2 signatures when analyzed by the Fluorospot assay.

Screening for Latent TB Infection in a Psoriasis Patient with History of BCG Vaccination and Exposure to TB Prior to Treatment with an Anti-TNF-α Agent

The treatment of psoriasis has undergone a revolution with the introduction of biologic therapies like anti-tumor necrosis factor-α (TNF-α) antibodies. TNF-α not only plays a major role in the pathogenesis of psoriasis, but also is a key cytokine in the body's defenses against microbacterial infection. In patients with latent tuberculosis (TB), treatment with anti-TNF antibodies may result in the development of active TB. Historically, tuberculin skin tests have been used to detect the presence of latent TB infection. More recently, interferon-gamma release assays have been developed. We report a patient who demonstrates pitfalls of some of our testing for latent TB.

P-092 QuantiFERON TB Gold Testing for Latent Tuberculosis is More Frequently Indeterminate in Patients with Inflammatory Bowel Disease

Screening for latent tuberculosis is mandatory prior to the initiation of biologic therapy for inflammatory bowel disease (IBD). Testing has been traditionally performed with the tuberculin skin test (TST) but is often being replaced by the QuantiFERON TB gold test (QFT-G), an interferon-gamma release assay. However, the performance of QFT-G has not been completely validated in patients with inflammatory bowel disease. We aimed to assess the rate of indeterminate QFT-G in patients with IBD and distinguish risk factors that contribute to this result. We performed a retrospective chart review analyzing the Henry Ford Health System clinical database for patients with a diagnosis of IBD who underwent QFT-G testing between January 1, 2005 and July 1, 2013. We obtained demographic and clinical information, including exposure to IBD medications as well as risk factors for tuberculosis, such as homelessness, incarceration, or immigration from an endemic region. A total of 117 IBD patients (mean age = 43.7 ± 16.7, 41.9% male and 49.6% caucasian) were included in the study. The overall rate of indeterminate QFT-G was 19.7% (23 patients). Concomitant medications at the time of testing included: oral or intravenous steroids (n = 37, 31.6%), immunomodulators (n = 32, 27.3%), and biologics (n= 41, 35.1%). In patients with indeterminate QFT-G results, 43.5% were receiving steroids, 21.7% were receiving immunomodulators, and 30.4% were receiving biologics. Steroid use was more likely to result in an indeterminate QFT-G (OR 1.85, (95% CI = 0.72–4.73)) but did not reach statistical significance (P = 0.195). Biologics and immunomodulators did not affect QFT-G results (OR 0.77, P = 0.5; OR 0.69, P = 0.6; respectively). Poor agreement was found between QFT-G and TST results (κ = 0.14). Risk factors for tuberculosis did not affect the rate of indeterminate test results. The rate of indeterminate QFT-G is exceedingly high in patients with IBD. This phenomenon may be due to medication use or the disease itself. Steroid use may increase the likelihood of an indeterminate result.

Latent Tuberculosis in Healthcare Workers: Time to Act

Latent Tuberculosis in Healthcare Workers: Time to Act

Letter: recommendations for the management of latent tuberculosis infection in IBD patients may not be applicable in all settings – author's reply

et al., where the conversion and reversion rates of screening tests for latent tuberculosis (LTB) of patients under antitumour necrosis factor-alpha (TNF-a) therapy were tested. In this context, we present a case report of a Caucasian, 26-year-old woman, with no travelling history to endemic areas for tuberculosis, nor close contact with tuberculosis patients. She had Crohn’s disease diagnosed in 2009, with a nonreactive tuberculin skin test (TST) at the time. In January 2011, azathioprine was started, but interrupted due to acute pancreatitis. Five months later, another TST was performed and repeated 14 days later, according to national standards of care. 3 Both were nonreactive. The chest radiograph remained unchanged. Infliximab was then initiated, but the third infusion was not performed because of fever, dry cough and asthaenia. The TST had a 27-mm induration and the interferon gamma release assay (IGRA) was positive. CT chest, the histology of supraclavicular adenopathy and Ziehl-Neelsen were compatible with disseminated tuberculosis, and polymerase chain reaction was positive for Mycobacterium tuberculosis. The patient began tuberculosis treatment and was afebrile at the 2nd day of therapy. We question the role of the negativity of TST even in the absence of immunosuppression, and support the Austrian guidelines on LTB screening that omit TST as a screening test. According to these recommendations, only 42% of the originally treated patients would have received chemoprophylaxis with isoniazid. 5 Perhaps the patient described in this letter could belong to the remaining 58% and could have been saved from disseminated tuberculosis if IGRA had been performed prior to TNF-a therapy.