scholarly journals Evaluating latent tuberculosis infection diagnostics using latent class analysis

Thorax ◽  
2018 ◽  
Vol 73 (11) ◽  
pp. 1062-1070 ◽  
Author(s):  
Jason E Stout ◽  
Yanjue Wu ◽  
Christine S Ho ◽  
April C Pettit ◽  
Pei-Jean Feng ◽  
...  

BackgroundLack of a gold standard for latent TB infection has precluded direct measurement of test characteristics of the tuberculin skin test and interferon-γ release assays (QuantiFERON Gold In-Tube and T-SPOT.TB).ObjectiveWe estimated test sensitivity/specificity and latent TB infection prevalence in a prospective, US-based cohort of 10 740 participants at high risk for latent infection.MethodsBayesian latent class analysis was used to estimate test sensitivity/specificity and latent TB infection prevalence among subgroups based on age, foreign birth outside the USA and HIV infection.ResultsLatent TB infection prevalence varied from 4.0% among foreign-born, HIV-seronegative persons aged <5 years to 34.0% among foreign-born, HIV-seronegative persons aged ≥5 years. Test sensitivity ranged from 45.8% for the T-SPOT.TB among foreign-born, HIV-seropositive persons aged ≥5 years to 80.7% for the tuberculin skin test among foreign-born, HIV-seronegative persons aged ≥5 years. The skin test was less specific than either interferon-γ release assay, particularly among foreign-born populations (eg, the skin test had 70.0% specificity among foreign-born, HIV-seronegative persons aged ≥5 years vs 98.5% and 99.3% specificity for the QuantiFERON and T-SPOT.TB, respectively). The tuberculin skin test’s positive predictive value ranged from 10.0% among foreign-born children aged <5 years to 69.2% among foreign-born, HIV-seropositive persons aged ≥5 years; the positive predictive values of the QuantiFERON (41.4%) and T-SPOT.TB (77.5%) were also low among US-born, HIV-seropositive persons aged ≥5 years.ConclusionsThese data reinforce guidelines preferring interferon-γ release assays for foreign-born populations and recommending against screening populations at low risk for latent TB infection.Trial registration numberNCT01622140.

2016 ◽  
Vol 48 (5) ◽  
pp. 1411-1419 ◽  
Author(s):  
Lucia Barcellini ◽  
Emanuele Borroni ◽  
James Brown ◽  
Enrico Brunetti ◽  
Daniela Campisi ◽  
...  

Identifying latently infected individuals is crucial for the elimination of tuberculosis (TB). We evaluated for the first time the performance of a new type of interferon-γ release assay, QuantiFERON-TB Plus (QFT-Plus), which includes an additional antigen tube (TB2), stimulating both CD4+ and CD8+ T-cells in contacts of TB patients.Contacts were screened for latent TB infection by tuberculin skin test, QFT-Plus and QuantiFERON-TB Gold in Tube (QFT-GIT).In 119 TB contacts, the overall agreement between QFT-Plus and QFT-GIT was high, with a Cohen's κ of 0.8. Discordant results were found in 12 subjects with negative QFT-GIT and positive QFT-Plus results. In analyses of markers of TB exposure and test results, the average time spent with the index case was the strongest risk factor for positivity in each of these tests. The difference in interferon-γ production between the two antigen tubes (TB2−TB1) was used as an estimate of CD8+ stimulation provided by the TB2. TB2−TB1 values >0.6 IU·mL−1 were significantly associated with proximity to the index case and European origin.QFT-Plus has a stronger association with surrogate measures of TB exposure than QFT-GIT in adults screened for latent TB infection. Interferon-γ response in the new antigen tube used an indirect estimate of specific CD8+ response correlates with increased Mycobacterium tuberculosis exposure, suggesting a possible role in identifying individuals with recent infection.


2014 ◽  
Vol 45 (2) ◽  
pp. 473-482 ◽  
Author(s):  
Martha Torres ◽  
Lourdes García-García ◽  
Pablo Cruz-Hervert ◽  
Heinner Guio ◽  
Claudia Carranza ◽  
...  

Treatment of persons with latent tuberculosis (TB) infection at greatest risk of reactivation is an important component of TB control and elimination strategies. Biomarkers evaluating the effectiveness of treatment of latent TB infection have not yet been identified. This information would enhance control efforts and assist the evaluation of new treatment regimes.We designed a two-group, two-arm, randomised clinical study of tuberculin skin test-positive participants: 26 with documented contact with TB patients and 34 with non-documented contact. Participants in each group were randomly assigned to the immediate- or deferred-isoniazid treatment arms. Assays ofin vitrointerferon (IFN)-γ secretion in response to recombinant Rv1737 and overlapping synthetic peptide pools from various groups of immunodominant proteins were performed.During isoniazid therapy, a significant increase from baseline in the proportion of IFN-γ responders to the 10-kDa culture filtrate protein, Rv2031, Rv0849, Rv1986, Rv2659c, Rv2693c and the recombinant Rv1737 protein was observed (p⩽0.05). The peptide pool of Rv0849 and Rv1737 recombinant proteins induced the highest percentage of IFN-γ responders after isoniazid therapy.Thein vitroIFN-γ responses to these proteins might represent useful markers to evaluate changes associated with treatment of latent TB infection.


2017 ◽  
Author(s):  
Marissa M. Barron ◽  
Kate M. Shaw ◽  
Kai McKeever Bullard ◽  
Mohammed K. Ali ◽  
Matthew J. Magee

ABSTRACTAimsWe aimed to determine the association between prediabetes and diabetes with latent TB using National Health and Nutrition Examination Survey data.MethodsWe performed a cross-sectional analysis of 2011-2012 National Health and Nutrition Examination Survey data. Participants ≥20 years were eligible. Diabetes was defined by glycated hemoglobin (HbA1c) as no diabetes (≤5.6% [38 mmol/mol]), prediabetes (5.7-6.4% [3946mmol/mol]), and diabetes (≥6.5% [48 mmol/mol]) combined with self-reported diabetes. Latent TB infection was defined by the QuantiFERON®-TB Gold In Tube (QFT-GIT) test. Adjusted odds ratios (aOR) of latent TB infection by diabetes status were calculated using logistic regression and accounted for the stratified probability sample.ResultsDiabetes and QFT-GIT measurements were available for 4,958 (89.2%) included participants. Prevalence of diabetes was 11.4% (95%CI 9.8-13.0%) and 22.1% (95%CI 20.523.8%) had prediabetes. Prevalence of latent TB infection was 5.9% (95%CI 4.9-7.0%). After adjusting for age, sex, smoking status, history of active TB, and foreign born status, the odds of latent TB infection were greater among adults with diabetes (aOR 1.90, 95%CI 1.15-3.14) compared to those without diabetes. The odds of latent TB in adults with prediabetes (aOR 1.15, 95%CI 0.90-1.47) was similar to those without diabetes.ConclusionsDiabetes is associated with latent TB infection among adults in the United States, even after adjusting for confounding factors. Given diabetes increases the risk of active TB, patients with co-prevalent diabetes and latent TB may be targeted for latent TB treatment.


2019 ◽  
Vol 70 (8) ◽  
pp. 1562-1572 ◽  
Author(s):  
Mary R Reichler ◽  
Awal Khan ◽  
Timothy R Sterling ◽  
Hui Zhao ◽  
Bin Chen ◽  
...  

Abstract Background Close contacts of persons with pulmonary tuberculosis (TB) have high rates of TB disease. Methods We prospectively enrolled TB patients and their close contacts at 9 US/Canadian sites. TB patients and contacts were interviewed to identify index patient, contact, and exposure risk factors for TB. Contacts were evaluated for latent TB infection (LTBI) and TB, and the effectiveness of LTBI treatment for preventing contact TB was examined. Results Among 4490 close contacts, multivariable risk factors for TB were age ≤5 years, US/Canadian birth, human immunodeficiency virus infection, skin test induration ≥10 mm, shared bedroom with an index patient, exposure to more than 1 index patient, and index patient weight loss (P &lt; .05 for each). Of 1406 skin test–positive contacts, TB developed in 49 (9.8%) of 446 who did not initiate treatment, 8 (1.8%) of 443 who received partial treatment, and 1 (0.2%) of 517 who completed treatment (1951, 290, and 31 cases/100 000 person-years, respectively; P &lt; .001). TB was diagnosed in 4.2% of US/Canadian-born compared with 2.3% of foreign-born contacts (P = .002), and TB rates for US/Canadian-born and foreign-born contacts who did not initiate treatment were 3592 and 811 per 100 000 person-years, respectively (P &lt; .001). Conclusions Treatment for LTBI was highly effective in preventing TB among close contacts of infectious TB patients. Several index patient, contact, and exposure characteristics associated with increased risk of contact TB were identified. These findings help inform contact investigation, LTBI treatment, and other public health prevention efforts.


2015 ◽  
Vol 4 (3) ◽  
pp. 69-74
Author(s):  
Ling Zhou

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.


2016 ◽  
Vol 48 (3) ◽  
pp. 808-817 ◽  
Author(s):  
Masoud Dara ◽  
Ivan Solovic ◽  
Giovanni Sotgiu ◽  
Lia D'Ambrosio ◽  
Rosella Centis ◽  
...  

No evidence exists on tuberculosis (TB) and latent TB infection (LTBI) management policies among refugees in European countries.A questionnaire investigating screening and management practices among refugees was sent to 38 national TB programme representatives of low and intermediate TB incidence European countries/territories of the WHO European Region.Out of 36 responding countries, 31 (86.1%) reported screening for active TB, 19 for LTBI, and eight (22.2%) reporting outcomes of LTBI treatment. Screening for TB is based on algorithms including different combinations of symptom-based questionnaires, bacteriology and chest radiography and LTBI screening on different combinations of tuberculin skin test and interferon-γ release assays. In 22 (61.1%) countries, TB and LTBI screening are performed in refugee centres. In 22 (61.1%) countries, TB services are organised in collaboration with the private sector. 27 (75%) countries answered that screening for TB is performed as per national and international guidelines, while 19 (52.7%) gave the same answer with regards to LTBI screening. Infection control measures are inadequate in several of the countries surveyed.There is need for improved coordination of TB screening in Europe to implement the End TB Strategy and achieve TB elimination.


2018 ◽  
Vol 52 (1) ◽  
pp. 1800591 ◽  
Author(s):  
Claudia C. Dobler ◽  
Greg J. Fox ◽  
Paul Douglas ◽  
Kerri A. Viney ◽  
Faiz Ahmad Khan ◽  
...  

In most settings with a low incidence of tuberculosis (TB), foreign-born people make up the majority of TB cases, but the distribution of the TB risk among different migrant populations is often poorly quantified. In addition, screening practices for TB disease and latent TB infection (LTBI) vary widely. Addressing the risk of TB in international migrants is an essential component of TB prevention and care efforts in low-incidence countries, and strategies to systematically screen for, diagnose, treat and prevent TB among this group contribute to national and global TB elimination goals.This review provides an overview and critical assessment of TB screening practices that are focused on migrants and visitors from high to low TB incidence countries, including pre-migration screening and post-migration follow-up of those deemed to be at an increased risk of developing TB. We focus mainly on migrants who enter the destination countryviaapplication for a long-stay visa, as well as asylum seekers and refugees, but briefly consider issues related to short-term visitors and those with long-duration multiple-entry visas. Issues related to the screening of children and screening for LTBI are also explored.


2009 ◽  
Vol 137 (9) ◽  
pp. 1342-1347 ◽  
Author(s):  
I. RIVAS ◽  
I. LATORRE ◽  
A. SANVISENS ◽  
J. DOMÍNGUEZ ◽  
J. TOR ◽  
...  

SUMMARYIn vitro tests have been developed for the diagnosis of tuberculosis (TB) infection. The objective was to analyse latent TB infection in drug and alcohol abusers through two interferon-γ techniques. One hundred and thirty-nine patients were admitted between February 2006 and May 2007. Mean age was 39·8 years [31% HIV positive]. The enzyme immunoassay (EIA) and enzyme-linked immunospot (ELISPOT) interferon-γ assays were positive in 34% of patients with an agreement of 83% (κ=0·63). Tuberculin skin test (TST) was positive in 29% of patients and the agreement of TST with EIA and ELISPOT interferon-γ assays was 85% (κ=0·62) and 83% (κ=0·57), respectively. Almost 50% of patients with history of TB had a positive in vitro test. In conclusion, we observed a high prevalence of latent TB and good agreement between the new in vitro tests that otherwise may continue to be positive long after developing TB disease.


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