QuantiFERON-TB Gold In-Tube Conversion Research Articles

Prevalence and incidence of tuberculosis infection among healthcare workers in chest diseases hospitals, Bangladesh: Putting infection control into context.

Healthcare workers (HCWs) are at increased risk of tuberculosis infection (TBI). We estimated the prevalence and incidence of TBI and risk factors among HCWs in Bangladeshi hospitals to target TB infection prevention and control (IPC) interventions. During 2013-2016, we conducted a longitudinal study among HCWs in four chest disease hospitals. At baseline, we administered a questionnaire on sociodemographic and occupational factors for TB, tuberculin skin tests (TST) in all hospitals, and QuantiFERON ®-TB Gold in-Tube (QFT-GIT) tests in one hospital. We assessed factors associated with baseline TST positivity (induration ≥10mm), TST conversion (induration increase ≥10mm from baseline), baseline QFT-GIT positivity (interferon-gamma ≥0.35 IU/mL), and QFT-GIT conversion (interferon-gamma <0.35 IU/mL to ≥0.35 IU/mL). We included factors with a biologically plausible relationship with TBI identified in prior studies or having an association (p = <0.20) in the bivariate analyses with TST positivity or QFT-GIT positivity in multivariable generalized linear models. The Kaplan-Meier was used to estimate the cumulative TBI incidence rate per 100 person-years. Of the 758 HCWs invited, 732 (97%) consented to participate and 731 completed the one-step TST, 40% had a positive TST result, and 48% had a positive QFT-GIT result. In multivariable models, HCWs years of service 11-20 years had 2.1 (95% CI: 1.5-3.0) times higher odds of being TST-positive and 1.6 (95% CI 1.1-2.5) times higher odds of QFT-GIT-positivity at baseline compared with those working ≤10 years. HCWs working 11-20 years in pulmonary TB ward had 2.0 (95% CI: 1.4-2.9) times higher odds of TST positivity, and those >20 years had 2.5 (95% CI: 1.3-4.9) times higher odds of QFT-GIT-positivity at baseline compared with those working <10 years. TBI incidence was 4.8/100 person-years by TST and 4.2/100 person-years by QFT-GIT. Females had 8.5 (95% CI: 1.5-49.5) times higher odds of TST conversion than males. Prevalent TST and QFT-GIT positivity was associated with an increased number of years working as a healthcare worker and in pulmonary TB wards. The incidence of TBI among HCWs suggests ongoing TB exposure in these facilities and an urgent need for improved TB IPC in chest disease hospitals in Bangladesh.

Interpretation of serial interferon-gamma test results to measure new tuberculosis infection among household contacts in Zambia and South Africa

BackgroundA more stringent QuantiFERON-TB Gold In-Tube (QFT) conversion (from negative to positive) definition has been proposed to allow more definite detection of recent tuberculosis (TB) infection. We explored alternative conversion definitions to assist the interpretation of serial QFT results and estimate incidence of TB infection in a large cohort study.MethodsWe used QFT serial results from TB household contacts aged ≥15 years, collected at baseline and during two follow-up visits (2006–2011) as part of a cohort study in 24 communities in Zambia and South Africa (SA). Conversion rates using the manufacturers’ definition (interferon-gamma (IFN-g) < 0.35 to ≥0.35, ‘def1’) were compared with stricter definitions (IFN-g < 0.2 to ≥0.7 IU/ml, ‘def2’; IFN-g < 0.2 to ≥1.05 IU/ml, ‘def3’; IFN-g < 0.2 to ≥1.4 IU/ml, ‘def4’). Poisson regression was used for analysis.ResultsOne thousand three hundred sixty-five individuals in Zambia and 822 in SA had QFT results available. Among HIV-negative individuals, the QFT conversion rate was 27.4 per 100 person-years (CI:22.9–32.6) using def1, 19.0 using def2 (CI:15.2–23.7), 14.7 using def3 (CI:11.5–18.8), and 12.0 using def4 (CI:9.2–15.7). Relative differences across def1-def4 were similar in Zambia and SA. Using def1, conversion was less likely if HIV positive not on antiretroviral treatment compared to HIV negative (aRR = 0.7, 95%CI = 0.4–0.9), in analysis including both countries. The same direction of associations were found using def 2–4.ConclusionHigh conversion rates were found even with the strictest definition, indicating high incidence of TB infection among household contacts of TB patients in these communities. The trade-off between sensitivity and specificity using different thresholds of QFT conversion remains unknown due to the absence of a reference standard. However, we identified boundaries within which an appropriate definition might fall, and our strictest definition plausibly has high specificity.

Latent Tuberculosis Infection Increases in Kidney Transplantation Recipients Compared With Transplantation Candidates: A Neglected Perspective in Tuberculosis Control.

BackgroundThe prevalence and incidence of latent tuberculosis infection (LTBI) in patients with kidney transplantation remain unclear.MethodsIn this prospective study, we enrolled kidney transplantation candidates (KTCs) and recipients (KTRs) from 2014 to 2018. We defined LTBI as a positive result of QuantiFERON-TB Gold In-tube (QFT). We analyzed the predictors for LTBI acquisition and followed up on QFT assay test for 2 years among those initially without LTBI.ResultsOf 425 patients enrolled, 305 (71.8%) patients belonged to the KTC group and 120 (28.2%) to the KTR group. The initial QFT showed positive results in 32 (10.5%) and 24 (20.0%) patients in the KTC and KTR groups, respectively (P = .009). The QFT response value in patients with LTBI was higher in the KTR group than in the KTC group (1.85 vs 1.06 IU/mL, P = .046). Multivariate logistic regression showed that old age, absence of bacillus Calmette–Guérin (BCG) scar, presence of donor-specific antibody, and KTR group were independent factors for positive LTBI. For participants with initial negative QFT, positive QFT conversion within a 2-year follow-up was higher after kidney transplantation (20%) than in KTCs (5.5%) (P = .034).ConclusionsThis study is the first cohort to follow up LTBI status in patients with kidney transplantation and shows its higher prevalence and incidence in KTRs. It indicates that surveillance of LTBI after renal transplantation is important. In addition to status of kidney transplantation, old age, no BCG vaccination, and positive donor-specific antibody are also positive predictors for LTBI.

Serum level of IL-8 is associated with reversion of QuantiFERON-TB gold in-tube tests

Frequent reversion has been commonly observed in serial QuantiFERON-TB Gold In-Tube (QFT) tests, which limited its accuracy in defining the status of Mycobacterium tuberculosis (MTB) infection. Serum cytokine profiles might provide additional information to clarify the infection status. Based on a population-based cohort study aiming to track MTB infection acquisition and disease development, serum profiles of 12 cytokines were determined by bead-based multiplex assays in parallel with QFT and tuberculin skin tests (TST) to explore potential relation between serum cytokines and MTB infection status. Totally, 309 subjects got QFT conversion in one year (2013-2014) and 46.92% (145/309) of them got reversion in 2015. The study subjects were classified into three groups according to their QFT and TST results in 2015 (QFT persistence positive, QFT-/TST + and QFT-/TST-). The serum levels of MCP-1 and IL-8 were significantly different among the three groups. Furthermore, level of IL-8 was dramatically lower in QFT-/TST- group as compared to the other two groups, and no significant difference was observed for QFT-/TST + group as comparing with persistent positive group. Our results suggested that the decreased serum level of IL-8 might be potential biomarker to identify QFT reversion caused by infection clearance.

2300 Association between source case cavitation on chest radiograph and QuantiFERON-TB Gold In-Tube conversion among close contacts of active tuberculosis cases in Brazil

OBJECTIVES/SPECIFIC AIMS: QuantiFERON-TB Gold In-Tube (QFT) conversion from negative to positive, is regarded as a marker of recent latent tuberculosis infection and may be predictive of incident active tuberculosis (TB) disease. However, it remains unclear how conversion is influenced by individual and environmental factors, including the infectiousness of the source case to whom the contact was exposed. We aimed to examine the effect of infectiousness of TB in the source case, as measured by presence of cavitation on chest X-ray, on the incidence of QFT conversion among close contacts of the pulmonary TB index case, after adjusting for potential confounding by contact and source case characteristics. METHODS/STUDY POPULATION: The Regional Prospective Observational Research for Tuberculosis (RePORT)-Brazil is an ongoing prospective cohort study that enrolls close contacts of culture-confirmed pulmonary TB patients and follows them for 24 months for development of active TB. Demographic, clinical, and diagnostic information are obtained at baseline and during follow-up at clinical visits and by telephone. QFT testing is performed at baseline and repeated after 6 months if the baseline QFT is negative. A positive IFN-γ value is defined as &gt;0.35 IU/mL, as recommended by the manufacturer and the CDC, and QFT conversion is defined as a negative QFT at baseline followed by a positive QFT at 6 months. RESULTS/ANTICIPATED RESULTS: Among 260 enrolled contacts with nonpositive baseline QFT results and 6 months of follow-up, 198 (76%) were retested with QFT 6 months after enrollment. Of those retested, 26 (13%) converted to positive. Presence of any cavitation in the source case, based on chest radiography, was significantly associated with QFT-conversion (ORunadjusted=2.4, 95% CI: 1.0–5.7). Additional univariate analyses revealed that QFT conversion was associated with black and brown race (compared with white race) of the contact, current smoking and current alcohol use in the source case. After adjusting for potential confounders (age, sex, and race of the contact and current smoking of the source case), the association between source case cavitation and QFT conversion remained (ORadjusted=2.5 95% CI: 1.0–6.2). As of December 6, 2017, none of the QFT-retested contacts had developed active TB, with a median follow-up of 12.3 months (IQR: 7.1–13.1). We anticipate that ongoing enrollment and follow-up may yield cases of active TB; future analyses will provide greater precision for examining predictors of QFT-conversion and its association with incident TB. DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary results agree with published literature suggesting the infectiousness of TB in the index case is a predictor of incident LTBI. Along with recent LTBI, immune suppression, HIV co-infection, and type 2 diabetes are considered risk factors for progression to active TB disease. Because only a small proportion of persons progress from LTBI to active TB disease, it is not appropriate to treat all persons with LTBI. Thus, more research is needed to identify groups at highest risk for QFT-conversion and incident TB disease, so these groups can be targeted for TB prevention, interventions, and facilitate a decline in TB incidence and mortality.

Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study

The value of quantitative interferon-γ release assay results for predicting progression from Mycobacterium tuberculosis infection to active disease is unknown. We aimed to investigate the relation between QuantiFERON-TB Gold In-Tube (QFT) conversion interferon-γ values and risk of subsequent active tuberculosis disease and of QFT reversion. We analysed data from a reported vaccine efficacy trial of the tuberculosis vaccine MVA85A in South Africa. QFT negative, HIV uninfected young children aged 18-24 weeks were enrolled. We stratified participants by quantitative QFT result (interferon-γ <0·35 IU/mL, 0·35-4·00 IU/mL, and >4·00 IU/mL) at the intermediate study visit (day 336) and determined risk of progression to active tuberculosis disease over the subsequent 6-24 months. No QFT differences were observed between placebo and MVA85A groups at day 336 or end of study; therefore, both groups were included in analyses. Study clinicians were not masked to QFT values, but strict case definitions were used that excluded QFT results. We used generalised additive models to evaluate the quantitative relation between day 336 QFT value and subsequent disease risk, and we compared disease rates between QFT strata using a two-sample Poisson test. Among 2512 young children with QFT tests done at day 336, 172 (7%) were positive; 87 (7%) of 1267 in placebo group and 85 (7%) of 1245 in the MVA85A group (p=1·00). Compared with QFT non-converters (tuberculosis disease incidence 0·7 per 100 person-years [95% CI 0·4-1·1]), children with QFT conversion at interferon-γ values between 0·35-4·00 IU/mL did not have significantly increased risk of disease (2·5 per 100 person-years [95% CI 0·4-9·4]; incidence rate ratio (IRR) 3·7 (95% CI 0·4-15·8; p=0·23). However, QFT conversion at interferon-γ values higher than 4·00 IU/mL was associated with substantially increased disease incidence (28·0 per 100 person-years [95% CI 14·9-45·7]) compared with non-converters (IRR 42·5 [95% CI 17·2-99·7]; p<0·0001), and compared with children with interferon-γ values between 0·35-4·00 IU/mL (IRR 11·4 [95% CI 2·4-107·2]; p=0·00047). Among 91 QFT converters who were given a repeat test, 53 (58%) reverted from positive to negative. QFT reversion risk was inversely associated with interferon-γ value at QFT conversion and was highest with interferon-γ values less than 4·00 IU/mL (47 [77%] of 61). In young children, tuberculosis disease risk was not significantly increased, and QFT reversion was common, following QFT conversion at interferon-γ values up to 10 times the recommended test threshold (0·35 IU/mL). By contrast, QFT conversion at very high interferon-γ values (>4·00 IU/mL) warrants intensified diagnostic and preventive intervention because of the extremely high risk of tuberculosis disease in these young children. Aeras, Wellcome Trust, and Oxford-Emergent Tuberculosis Consortium (OETC) were the funders of the MVA85A 020 Trial. National Institute of Allergy and Infectious Diseases supported this analysis.

Annual risk of tuberculosis infection in rural China: a population-based prospective study.

Prospective population data on the incidence of tuberculosis (TB) infection has been sparsely reported in the global literature.A population-based prospective study was conducted in rural China to investigate the annual risk of TB infection, and its persistence using serial tuberculin skin tests (TSTs) and an interferon-γ release assay. In total, 13 580 eligible participants from four rural sites, identified as TST negative (<10 mm) or QuantiFERON-TB Gold In-Tube (QFT) (an interferon-γ release assay) negative from a baseline survey, were included in the first year's follow-up examination.The annual conversion rate of QFT among the study sites ranged between 2.1% and 4.9% (average 3.1%), and the incidence of TST conversion ranged between 6.0% and 31.1% (average 14.5%). During the second year's follow-up, infection persistence was investigated using 390 subjects with QFT conversions. Among them, 49.7% (164 out of 330) were found to be consistently QFT positive. Both the conversion and the persistence of QFT positivity were found to be significantly increased with increasing age.In conclusion, the annual TB infection rate was suggested to be ∼1.5% based on persistent positive results after QFT conversion in rural China. Therefore, infection control among those high-risk populations, including the elderly, should be prioritised for TB control in China.

The dynamics of QuantiFERON-TB Gold In-Tube conversion and reversion in a cohort of South African adolescents

The dynamics of QuantiFERON-TB Gold In-Tube conversion and reversion in a cohort of South African adolescents

Serial QuantiFERON-TB Gold In-Tube testing for psoriatic patients receiving antitumor necrosis factor-alpha therapy

Tumor necrosis factor-α (TNF-α) antagonists have become increasingly popular in the treatment of psoriasis. However, the increased risk of latent tuberculosis infection (LTBI) reactivation has also become an important issue in clinical practice. The aim of this study was to evaluate serial QuantiFERON-TB Gold In-Tube (QFT-GIT) testing for detecting LTBI among a cohort of psoriatic patients vaccinated with bacille Calmette-Guérin in a country with an intermediate burden of TB during long-term treatment with TNF-α antagonists. We enrolled psoriatic patients treated with TNF-α antagonists who also accepted yearly serial QFT-GIT testing and regular chest X-ray examinations before and during the anti-TNF-α treatment from January 2010 to August 2014. Patients diagnosed with LTBI received chemoprophylaxis, and QFT-GIT testing was performed in these patients after completion of chemoprophylaxis. In this retrospective study, 101 patients had completed baseline and at least 1 year of follow-up. Among these patients, 60 had continued TNF-α antagonists therapy and received examinations in the 2 nd year, whereas 18 had continued the therapy until the 3 rd year. The conversion rate among these patients was 14.29% (13/91). In this study, 23 patients were diagnosed with LTBI according to the positive results obtained in the QFT-GIT test, with 19 of them having completed chemoprophylactic therapy. Follow-up QFT-GIT testing revealed reversion in 11 patients (57.89%) and decreased interferon-γ (IFN-γ) levels (68.42%) in 13 patients. Patients over 45 years of age tended to have a persistent positive result. This study demonstrated that 14.29% of psoriatic patients undergoing long-term TNF-α antagonist therapy had a QFT-GIT conversion. Although a decreased IFN-γ level and QFT-GIT reversion were observed in most cases following prophylactic therapy, the value of QFT-GIT for evaluating the effect of LTBI prophylaxis remains controversial.

Challenges with QuantiFERON-TB Gold Assay for Large-Scale, Routine Screening of U.S. Healthcare Workers

North American occupational health programs that switched from the tuberculin skin test (TST) to IFN-γ release assays for latent tuberculosis screening are reporting challenges with interpretation of serial testing results in healthcare workers (HCWs). However, limited data exist on the reproducibility of serial IFN-γ release assay results in low-risk HCWs. To evaluate the short-term reproducibility of QuantiFERON-TB Gold In-Tube (QFT) in a large cohort of HCWs and to define a QFT cutoff yielding a conversion rate equivalent to historical TST rates. We retrospectively evaluated the QFT results from HCWs with two or more QFT tests performed between June 2008 and July 2010 at an academic institution. Outcome measures were proportions of reproducibility, quantitative results, and conversion rates with alternate QFT cutoffs. A total of 9,153 HCWs with two or more QFT tests were included in the analysis. Of 8,227 individuals with a negative result, 4.4% (n = 361) converted their QFT result over 2 years. A total of 261 (72.3%) of the HCWs with conversions underwent repeat short-term testing after the first positive result with 64.8% reverting (n = 169). An IFN-γ cutoff of 5.3 IU/ml or higher (manufacturer's cutoff is ≥0.35 IU/ml) yielded a conversion rate of 0.4%, equal to our institution's historical TST conversion rate. The manufacturer's definition of QFT conversion results in an inflated conversion rate that is incompatible with our low-risk setting. A significantly higher QFT cutoff value is needed to match the historical TST conversion rate. Nonreproducible conversions in most converters suggested false-positive results.

Changes in QuantiFERON®-TB Gold In-Tube results during treatment for tuberculous infection

Randomised trial comparing 9 months of isoniazid with 4 months of rifampicin for the treatment of high-risk tuberculin skin test positive subjects in Rio de Janeiro, Brazil. To compare QuantiFERON®-TB Gold In-Tube (QFT-GIT) responses before and 1, 4 and 9 months after starting treatment for latent tuberculous infection (LTBI) according to adherence to one of the two regimens. Participants in the trial were invited to undergo serial QFT-GIT. Within-subject differences at different time points were analysed as quantitative responses and categorised as positive or negative using different cut-off points. Of 215 participants, 118 completed treatment, of whom 58 underwent all three tests; and 97 did not complete treatment, of whom 10 underwent all tests. After 1 month of treatment, there was no significant difference in QFT-GIT response between the groups. After 4 and 9 months, reversions were more frequent in non-adherent subjects. Marked within-subject fluctuations were observed. No cut-off point could be established at which QFT-GIT responses were consistently positive or associated with adherence or type of treatment. Frequent within-subject variability in QFT-GIT responses, not associated with LTBI treatment, makes it difficult for clinicians to interpret QFT-GIT conversions and reversions.

Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial

SummaryBackgroundBCG vaccination provides incomplete protection against tuberculosis in infants. A new vaccine, modified Vaccinia Ankara virus expressing antigen 85A (MVA85A), was designed to enhance the protective efficacy of BCG. We aimed to assess safety, immunogenicity, and efficacy of MVA85A against tuberculosis and Mycobacterium tuberculosis infection in infants.MethodsIn our double-blind, randomised, placebo-controlled phase 2b trial, we enrolled healthy infants (aged 4–6 months) without HIV infection who had previously received BCG vaccination. We randomly allocated infants (1:1), according to an independently generated sequence with block sizes of four, to receive one intradermal dose of MVA85A or an equal volume of Candida skin test antigen as placebo at a clinical facility in a rural region near Cape Town, South Africa. We actively followed up infants every 3 months for up to 37 months. The primary study outcome was safety (incidence of adverse and serious adverse events) in all vaccinated participants, but we also assessed efficacy in a protocol-defined group of participants who received at least one dose of allocated vaccine. The primary efficacy endpoint was incident tuberculosis incorporating microbiological, radiological, and clinical criteria, and the secondary efficacy endpoint was M tuberculosis infection according to QuantiFERON TB Gold In-tube conversion (Cellestis, Australia). This trial was registered with the South African National Clinical Trials Register (DOH-27-0109-2654) and with ClinicalTrials.gov on July 31, 2009, number NCT00953927FindingsBetween July 15, 2009, and May 4, 2011, we enrolled 2797 infants (1399 allocated MVA85A and 1398 allocated placebo). Median follow-up in the per-protocol population was 24·6 months (IQR 19·2–28·1), and did not differ between groups. More infants who received MVA85A than controls had at least one local adverse event (1251 [89%] of 1399 MVA85A recipients and 628 [45%] of 1396 controls who received the allocated intervention) but the numbers of infants with systemic adverse events (1120 [80%] and 1059 [76%]) or serious adverse events (257 [18%] and 258 (18%) did not differ between groups. None of the 648 serious adverse events in these 515 infants was related to MVA85A. 32 (2%) of 1399 MVA85A recipients met the primary efficacy endpoint (tuberculosis incidence of 1·15 per 100 person-years [95% CI 0·79 to 1·62]; with conversion in 178 [13%] of 1398 infants [95% CI 11·0 to 14·6]) as did 39 (3%) of 1395 controls (1·39 per 100 person-years [1·00 to 1·91]; with conversion in 171 [12%] of 1394 infants [10·6 to 14·1]). Efficacy against tuberculosis was 17·3% (95% CI −31·9 to 48·2) and against M tuberculosis infection was −3·8% (–28·1 to 15·9).InterpretationMVA85A was well tolerated and induced modest cell-mediated immune responses. Reasons for the absence of MVA85A efficacy against tuberculosis or M tuberculosis infection in infants need exploration.FundingAeras, Wellcome Trust, and Oxford-Emergent Tuberculosis Consortium (OETC).

Repeat IGRA testing in Canadian health workers: conversions or unexplained variability?

BackgroundAlthough North American hospitals are switching from tuberculin testing (TST) to interferon-gamma release assays (IGRAs), data are limited on the association between occupational exposure and serial QuantiFERON-TB Gold In-Tube (QFT) results in healthcare workers (HCWs).MethodsIn a cohort of Canadian HCWs, TST and QFT were performed at study enrolment (TST1 and QFT1) and 1 year later (TST2 and QFT2). Conversion and reversion rates were estimated, and correlation with TB exposure was assessed.ResultsAmong 258 HCWs, median age was 36.8 years, 188/258 (73%) were female and 183/258 (71%) were Canadian-born. In 245 subjects with a negative QFT1 we found a QFT conversion rate of 5.3% (13/245, 95% CI 2.9–8.9%). Using more stringent definitions, QFT conversion rates ranged from 2.0 to 5.3%. No TST conversions were found among the 241 HCWs with negative TST1, and no measure of recent TB exposure was associated with QFT conversions. In the 13 HCWs with a positive QFT1, 62% reverted.ConclusionUsing the conventional QFT conversion definition, we found a higher than expected rate of conversion. Recent occupational exposures were not associated with QFT conversions, and no TST conversions occurred in this cohort, suggesting the ‘conversions’ may not reflect new TB infection.

The effects of rituximab therapy on released interferon- levels in the QuantiFERON assay among RA patients with different status of Mycobacterium tuberculosis infection

To investigate the influence of rituximab therapy on released IFN-γ levels in the QuantiFERON-TB-Gold In-Tube (QFT-GIT) assay among RA patients of different Mycobacterium tuberculosis infection status. Change in levels of released IFN-γ in the QFT-GIT assay was evaluated in RA patients who had received 1 year of rituximab treatment. A tuberculin skin test was performed using the Mantoux method and the QFT-GIT assay was performed by measuring IFN-γ levels in whole blood treated with tuberculosis (TB)-specific antigens. Among 56 patients, 43 patients were presumed to be without latent TB infection (LTBI), 7 patients had LTBI and 6 patients had anti-TNF-associated TB. During the 1-year period of rituximab therapy, no patient developed active TB or had QFT-GIT conversion. No significant change in released IFN-γ levels on QFT-GIT assay after 1-year rituximab therapy was observed in patients with LTBI [3.39 (1.21) vs 2.47 (0.82) IU/ml] or in those with anti-TNF-associated TB [1.06 (0.22) vs 0.87 (0.39) IU/ml]. Rituximab did not inhibit TB antigen-stimulated IFN-γ production ex vivo. The frequency of circulating CD19(+) B cells was significantly decreased [8.56 (0.84) vs 1.52 (0.44)%, P < 0.001], paralleling the decrease in RF titre [318.5 (76.0) vs 115.1 (32.1) IU/ml, P < 0.001] and DAS28 [6.49 (0.13) vs 4.59 (0.14), P < 0.001] after 1 year of rituximab therapy. However, there was no significant change in the frequency of CD3(+) T cells after rituximab therapy. No occurrence of active TB or QFT-GIT conversion was observed in patients receiving 1 year of rituximab therapy. No significant effect of rituximab therapy on IFN-γ release levels was observed in patients with LTBI and with anti-TNF-α-associated TB. Rituximab may be an alternative therapeutic agent for these patients.

Conversion rates of an interferon-γ release assay and the tuberculin skin test in the serial monitoring of healthcare workers

Regular monitoring of latent tuberculosis (TB) infection in healthcare workers (HCWs) is recommended, but the view about the effective method and performance of serial monitoring is controversial. The aim of this study was to determine differences in conversion rates according to TB exposure risk using the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT), and to evaluate the reproducibility and within-subject variability of the QFT-GIT in South Korea. Fifty-three HCWs were grouped according to their risk for TB exposure: group 1, high risk (n = 21); group 2, low risk (n = 32). Baseline and follow-up TSTs and QFT-GITs were performed from June 2009 to July 2011. Enzyme-linked immunosorbent assays (ELISAs) were repeated for the second QFT-GIT and a third QFT-GIT was performed after 8 weeks when discordant results of the second TST and QFT-GIT or a conversion or reversion were observed. No difference in the QFT-GIT conversion rate was evident between the two groups (15.4 vs. 6.5 %, p = 0.57), and no TST conversion was observed. The rate of QFT-GIT positivity was higher in the high-risk group (first QFT-GIT: 38.1 vs. 3.1 %, p = 0.002; second QFT-GIT: 33.3 vs. 9.4 %, p = 0.039). The re-test reproducibility of QFT-GIT results was high (100 %), and the within-subject results of repetitive QFT-GITs were variable. Stricter prevention strategies remain necessary in HCWs at high risk of TB exposure, and serial interferon-γ release assays (IGRAs) should be interpreted with caution in HCWs.

Serial interferon-γ release assays for screening and monitoring of tuberculosis infection during treatment with biologic agents

Screening for latent tuberculosis infection (LTBI) prior to the prescribing of anti-TNF agents and monitoring for infection during treatment are recommended. The feasibility of novel screening tools, including QuantiFERON-TB Gold In-Tube (QFT-GIT), remains unclear in the setting of immunosuppression. The aim of this study was to evaluate the usefulness of serial QFT-GIT during biologic therapy to assess whether dynamic changes in IFN-γ levels may be helpful in identifying reactivation of LTBI or newly acquired TB. We conducted a prospective study on patient candidates to TNF inhibitors. QFT-GIT was performed at baseline and after 3 and 6 months since biologic onset. A further follow-up period of 6 months was observed. Among patients enrolled (n = 119; F = 69 %; median age = 47 years, range 18-80), 24 had at least 1 risk factor for LTBI. Ninety-six were taking immunosuppressants at the time of TB testing. At baseline, 5 patients displayed positive, 93 negative, and 21 indeterminate QFT-GIT results. We observed QFT-GIT conversions and reversions in 12 patients with LTBI and in 73 without LTBI. QFT-GIT results changed of 28 % at month 3 and of 21 % at month 6; the greatest change was observed in patients with indeterminate results that became negative (15 %; p < 0.02). No TB cases were detected. In conclusion, the routine use of both QFT-GIT and TST at screening seems not to give any advantage in the setting of patients awaiting biologics. In addition, the feasibility of serial QFT-GIT during biologic therapy needs definition since changes in IFN-γ levels may occur without a pathologic connotation.

Challenges of Interferon-γ Release Assay Conversions in Serial Testing of Health-care Workers in a TB Control Program

Clinical data with use of serial interferon-γ release assay (IGRA) testing in US health-care workers (HCWs) are limited. A single-center, retrospective chart review was done from 2007 to 2010 of HCWs who underwent preemployment QuantiFERON-TB Gold In-Tube testing. Demographic data, bacille Calmette-Guérin history, prior tuberculin skin test result if done, and baseline and serial IGRA values were obtained. The number of IGRA converters and reverters and their subsequent management by infectious disease physicians were reviewed. Quantitative IGRA-negative values were not available. A total of 7,374 IGRAs were performed on newly hired HCWs. Of these tests, 486 (6.6%) were positive at baseline, 305 (4.1%) were indeterminate, and 6,583 (89.3%) were negative. From 2007 to 2010, 52 of 1,857 HCWs (2.8%) with serial IGRA tests were identified as converters, with a serial IGRA median value of 0.63 IU/mL. Seventy-one percent of HCWs with IGRA conversion had values ≤ 1 IU/mL. None of the converters had active TB or were part of an outbreak investigation. Clinical significance of most QuantiFERON-TB Gold In-Tube conversions in serial testing remains a challenging task for clinicians. The use of a single cutoff point criterion for IGRA may lead to overdiagnosis of new TB infections. Clinical assessment and evaluation may help to prevent unnecessary therapy in these cases. The criteria for defining conversions and reversions by establishing new cutoffs needs to be evaluated further, especially in HCWs.

Cigarette-Smoking Intensity and Interferon-Gamma Release Assay Conversion among Persons Who Inject Drugs: A Cohort Study.

We analyzed data from a longitudinal cohort study of persons who inject drugs (PWID) in Tijuana, Mexico, to explore whether cigarette smoking increases the risk of interferon gamma release assay (IGRA) conversion. PWID were recruited using respondent driven sampling (RDS). QuantiFERON-TB Gold In-Tube (QFT) assay conversion was defined as interferon-gamma concentrations <0.35 IU/mL at baseline and ≥0.7 IU/mL at 18 months. We used multivariable Poisson regression adjusted for RDS weights to estimate risk ratios (RRs). Of 129 eligible participants, 125 (96.9%) smoked at least one cigarette during followup with a median of 11 cigarettes smoked daily, and 52 (40.3%) had QFT conversion. In bivariate analysis, QFT conversion was not associated with the number of cigarettes smoked daily (P = 0.716). Controlling for age, gender, education, and alcohol use, the RRs of QFT conversion for smoking 6–10, 11–15, and ≥16 cigarettes daily compared to smoking 0–5 cigarettes daily were 0.9 (95% confidence interval (CI), 0.5–1.6), 0.5 (95% CI, 0.3–1.2), and 0.7 (95% CI, 0.3–1.6), respectively. Although this study did not find an association between self-reported smoking intensity and QFT conversion, it was not powered sufficiently to negate such an association. Larger longitudinal studies are needed to fully explore this relationship.

Longitudinal Analysis of QuantiFERON-TB Gold In-Tube in Children with Adult Household Tuberculosis Contact in South Africa: A Prospective Cohort Study

BackgroundQuantiFERON-TB Gold In Tube (QFT-GIT) is a tool for detecting M. tuberculosis infection. However, interpretation and utility of serial QFT-GIT testing of pediatric tuberculosis (TB) contacts is not well understood. We compared TB prevalence between baseline and 6 months follow-up using QFT-GIT and tuberculin skin testing (TST) in children who were household contacts of adults with pulmonary TB in South Africa, and explored factors associated with QFT-GIT conversions and reversions.MethodProspective study with six month longitudinal follow-up.ResultsAmong 270 enrolled pediatric contacts, 196 (73%) underwent 6-month follow-up testing. The 6-month prevalence estimate of MTB infection in pediatric contacts increased significantly from a baseline of 29% (79/270, 95%CI [24–35]) to 38% (103/270, 95% CI [32–44], p<0.001) using QFT-GIT; prevalence increased from a baseline of 28% (71/254, 95%CI [23–34]) to 33% (88/263, 95%CI [21–32], p = 0.002) using TST. Prevalence estimates were influenced by thresholds for positivity for TST, but not for QFT-GIT. Among 134 children with a negative or indeterminate baseline QFT-GIT, 24 (18%) converted to positive at follow-up; conversion rates did not differ significantly when using more stringent thresholds to define QFT-GIT conversion. Older age >10 years (AOR 8.9 95%CI [1.1–72]) and baseline TST positivity ≥5 mm (AOR 5.2 95%CI [1.2–23]) were associated with QFT-GIT conversion. Among 62 children with a positive baseline QFT-GIT, 9 (15%) reverted to negative; female gender (AOR 18.5 95%CI [1.1–321]; p = 0.04] was associated with reversion, while children with baseline positive TST were less likely to have QFT-GIT reversion (AOR 0.01 95%CI [0.001–0.24]).ConclusionAmong pediatric contacts of adult household TB cases in South Africa, prevalence estimates of TB infection increased significantly from baseline to 6 months. Conversions and reversions occurred among pediatric TB contacts using QFT-GIT, but QFT-GIT conversion rates were less influenced by thresholds used for conversions than were TST conversion rates.

Clinical applicability of Quantiferon‐TB‐Gold testing in psoriasis patients during long‐term anti‐TNF‐alpha treatment: a prospective, observational study

Psoriasis patients who are treated with tumour necrosis factor (TNF)-alpha antagonists are at increased risk of reactivation of latent tuberculosis infection (LTBI) and should be adequately screened and monitored during active treatment. To evaluate in a prospective study, the performance of Quantiferon-TB-Gold in tube (QFT) in vitro assay compared to the conventional tuberculin skin test (TST) in detecting LTBI among a cohort of non-BCG-vaccinated patients with moderate-to-severe psoriasis during long-term treatment (12 months) with TNF-alpha antagonists. A total of 50 patients underwent QFT and TST testing at baseline and after 6 and 12 months of continuous anti-TNF-alpha treatment. Diagnosis of LTBI was made on the basis of a positive QFT result and negative chest-radiographic and microbiological assays. Patients with LTBI were subjected to standard isoniazid chemoprophylaxis and after 1 month, they resumed anti-TNF-alpha treatment with subsequent QFT and TST testing after 6 months. In all the cases, a follow-up period of 12 months was observed. During the 12-month-study period, 14% of patients presented a QFT conversion. During active anti-TNF-alpha treatment, a QFT conversion was observed in 10% of patients (five cases). Agreement between QFT and TST was moderate (κ=0.408) at screening, good (κ=0.734) after 6 months and fair (κ=0.328) after 12 months of treatment. A total of 18% of patients presented a positive, discordant TST during the study period. A single-test QFT-based screening strategy for LTBI in psoriasis patients receiving long-term anti-TNF-alpha treatment could reduce the incidence of false-positive LTBI cases, preventing unnecessary TB chemoprophylaxis.