Prognostic value of interferon-γ release assays, a population-based study from a TB low-incidence country.

BACKGROUND: The ability of interferon-γ release assays to predict the development of TB has been investigated in many studies, but few cases develop TB during follow-up limiting the generalisation of results. METHODS: We assessed QuantiFERON-TB Gold In-Tube test (QFT) results from 15 980 Danish individuals and data on all TB cases in Denmark from 2005 to 2012 and determined the predictive value of the QFT for coprevalent TB (0-90 days after testing) and incident TB (>90 days). RESULTS: Coprevalent TB was diagnosed in 10.7% (183/1703) and 0.3% (38/13 463) cases with a positive and negative QFT, respectively. For the QFT-positive cases, coprevalent TB was more frequent among persons <35 years compared with those >35  years (19.3% vs 7.2%, p<0.001). The cohort was followed-up for 52 807 person-years, median follow-up time was 3.36 years. For incident TB, the positive and negative predictive values (PPV and NPV) were 1.32% and 99.85%, respectively. Incidence rates (IR) for incident TB among QFT-positives and QFT-negatives were 383 per 10(5) and 45 per 10(5) person-years, respectively. Among cases with a positive QFT, IR for incident TB was associated with time interval since QFT (<2 years, p<0.001), but not with age (<35 years, p=0.087). CONCLUSIONS: We confirmed a high NPV of the QFT and found positive QFT associated with a higher risk of subsequent incident TB. Overall, the PPV for incident cases was 1.32%, and development of incident TB was associated with time interval after the QFT, but not with age.

Incidence and clinical significance of non-tuberculous mycobacteria among migrants in Denmark: A nationwide register-based cohort study from 1991 through 2021.

BACKGROUND: There is limited knowledge about non-tuberculous mycobacteria (NTM) infections in migrants. We aimed to assess the incidence and clinical significance of NTM among migrants in Denmark. METHOD: Nationwide register-based cohort study of migrants with a positive NTM culture in Denmark from 1991 through 2021, stratified by patient demographics, disease localisation, species, and clinical significance. RESULTS: 433 migrants had a positive NTM culture, resulting in an overall incidence rate (IR) of 3.7 (95%CI 3.3-4.0) per 100,000 migrants. Overall NTM IRs for definite disease were 1.0 (95%CI 0.9-1.2), possible disease 1.0 (95%CI 0.8-1.2), and isolation 1.7 (95%CI 1.4-1.9) per 100,000 migrants. Migrants had considerably higher age- and sex-adjusted NTM IRs of positive cultures (incidence rate ratio [IRR] = 2.1, 95%CI 1.9-2.3, p < 0.001), possible disease (IRR = 2.4, 95%CI 2.0-3.0, p < 0.001), and isolation (IRR = 4.6, 95%CI 3.9-5.4, p < 0.001) compared to Danish-born, but not of definite disease (IRR = 1.1, 95%CI 0.9-1.3, p = 0.562). IRs of migrants with positive NTM cultures did not increase over time (-0.8 %/year, p = 0.133). CONCLUSIONS: Migrants have a higher, but stable, burden of NTM compared with Danish-born. The higher rates likely reflect that more specimens are examined for Mycobacterium tuberculosis. Microbiologically classified definite NTM disease is not substantially more common among migrants.

Negative effect of smoking on the performance of the QuantiFERON TB gold in tube test.

BACKGROUND: False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively. METHODS: Patients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results. RESULTS: Smokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and more false negative (45 vs. 0%, p < 0.01 and 26 vs. 11%, p = 0.04) QFT results. In Tanzanian patients, logistic regression analysis adjusted for sex, age, HIV and alcohol consumption showed an association of smoking with false negative (OR 17.1, CI: 3.0-99.1, p < 0.01) and indeterminate QFT results (OR 5.1, CI: 1.2-21.3, p = 0.02). CONCLUSIONS: Cigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status.

[Pulmonary infections with non-tuberculous mycobacteria].

In recent decades, an increasing incidence of pulmonary infections with non-tuberculous mycobacteria has been reported, primarily affecting patients with structural lung diseases and/or immunosuppression. In Denmark, approximately 100 new cases of infection with non-tuberculous mycobacteria occur yearly, most commonly with Mycobac-terium avium complex. Diagnosis is based on clinical, radiological and microbiological criteria. Treatment is difficult, and outcomes are often poor. Antibiotic treatment should be performed by specialists with reference to international guidelines.

Non-tuberculous mycobacteria and the performance of interferon gamma release assays in Denmark.

BACKGROUND: The QuantiFERON-TB-Gold Test (QFT) is more specific than the Mantoux skin-test to discriminate between Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterial (NTM) infections. Here we study the performance of the QFT in patients with NTM disease. METHODS: From 2005 to 2011, nationwide patient data on positive NTM cultures (n = 925) were combined with nationwide data on QFT results (n = 16,133), both retrieved from the International Reference Laboratory of Mycobacteriology, Denmark. A total of 112 patients with NTM infections had a QFT performed, 53 patients had definite NTM disease, 10 had possible disease and 49 had NTM colonization. RESULTS: QFT was positive in 8% (4/53) of patients with definite disease, 40% (4/10) with possible disease and 31% (15/49) with colonization. Positivity rate was lowest among patients with definite disease infected with NTM without the RD1 region 4% (2/50). None of the 15 children with MAC lymphadenitis had a positive QFT. CONCLUSION: This study is one of the largest assessing IGRAs in patients with NTM disease in a TB low-incidence setting. Our study showed that the QFT holds potential to discriminate between NTM and MTB infections. We found no positive IGRA test results among children with NTM not sharing the RD1-region of MTB resulting in a 100% specificity and we suggest that a QFT in a child presenting with cervical lymphadenitis may be helpful in distinguishing NTM from TB lymphadenitis.