ObjectiveInterferon gamma release assays like Quantiferon Gold In-Tube (QFT) are used to identify individuals infected with Mycobacterium tuberculosis. A dichotomous cut-off (0.35 IU/ml) defines a positive QFT without considering test variability. Our objective was to evaluate the introduction of a borderline range under routine conditions.MethodsResults of routine QFT samples from Sweden (2009–2014) were collected. A borderline range (0.20–0.99 IU/ml) was introduced in 2010 recommending a follow-up sample. The association between borderline results and incident active TB within 3 to 24 months was investigated through linkage with the national TB-register.ResultsUsing the recommended QFT cut-off, 75.1% tests were negative, 21.4% positive and 3.5% indeterminate. In total, 9% (3656/40773) were within the borderline range. In follow-up samples, individuals with initial results between 0.20–0.34 IU/ml and 0.35–0.99 IU/ml displayed negative results below the borderline range (<0.20 IU/ml) in 66.1% (230/348) and 42.5% (285/671) respectively, and none developed incident TB. Among 6712 individuals with a positive initial test >0.99 IU/ml, 65 (0.97%) developed incident TB within 3–24 months.ConclusionsWe recommend retesting of subjects with QFT results in the range 0.20–0.99 IU/ml to enhance reliability and validity of the test. Half of the subjects in the borderline range will be negative at a level <0.20 IU/ml when retested and have a very low risk of developing incident active TB.

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Background: Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and without HIV co-infection has not been reported previously. Thus, our aim was to investigate levels of FeNO in relation to clinical symptoms and urinary NO metabolites (uNO).

The QuantiFERON-TB Gold In-Tube test (QFN) measures interferon-gamma production in response to Mycobacterium tuberculosis antigens. Our aim was to assess the kinetics of the QFN and initial tuberculin skin test (TST) result in relation to severity of disease in a tuberculosis (TB) endemic area. Smear-positive TB patients (n = 71) were recruited at Gondar University Hospital, Ethiopia. The TST, QFN, CD4+ cell count and clinical symptoms (TB score) were assessed and followed up during treatment. From baseline to 7 months after treatment, there was a significant decrease in QFN reactivity (93.8% to 62.5% in HIV-negative/TB; 70.3% to 33.3% in HIV-positive/TB patients) down to a level comparable to a control group of blood donors (51.2%). The agreement between TST and QFN was poor in TB patients compared to healthy controls. A negative TST correlated to more advanced TB in contrast to a negative QFN test. We conclude that the QFN reactivity is significantly reduced at the end of treatment against active TB to the background level of healthy blood donors, and that the agreement between TST and QFN is poor including correlation to the severity of disease.

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Background Tuberculosis (TB) disease has been associated with pregnancy complications. However, the potential impact of TB infection (TBI) on pregnancy outcome is unknown. To investigate this, we conducted a register-based study in immigrant women screened with QuantiFERON assays for TBI in antenatal care in Sweden. Methods Women with history of immigration from TB-endemic countries were eligible for inclusion if national identification numbers and available QuantiFERON results obtained during pregnancy 2014-2018 were available. QuantiFERON results were linked to data on maternal characteristics and pregnancy outcomes from the national Pregnancy and Patient Registers. TBI was defined as nil-corrected QuantiFERON result ≥0.35 IU/ml, in the absence of TB disease. Pregnancies in women with TB disease or HIV infection were excluded, as well as multiplex pregnancies, pregnancies resulting in miscarriage, and pregnancies occurring &gt;10 years after immigration. Odds of defined adverse pregnancy outcomes were compared by maternal TBI status using mixed effects logistic regression with adjustment for maternal age and region of origin. Results In total, 7,408 women with 12,443 pregnancies were included. In multivariable analysis, stillbirth (adjusted Odds ratio [AOR] 1.90, 95% confidence interval [CI] 1.13-3.21, p=0.016), severe preeclampsia (AOR 1.62, 95% CI 1.03-2.56, p=0.036), low birthweight (&lt;2500 grams; AOR 1.38, 95% CI 1.01-1.88, p=0.041) and emergency Caesarean section (AOR 1.28, 95% CI 1.02-1.63, p=0.033) were significantly associated with TBI. Conclusion Among immigrant women seeking antenatal care in Sweden, TBI was independently associated with adverse pregnancy outcomes. Further studies are needed to corroborate these findings and to explore mechanisms involved.