Yield of chest X-ray tuberculosis screening of immigrants during the European refugee crisis of 2015: a single-centre experience.

OBJECTIVE: Our aim was to determine the prevalence of tuberculosis (TB), the number needed to screen (NNS), and the diagnostic accuracy of chest X-ray (CXR) screening to detect active pulmonary TB during the 2015 European refugee crisis. MATERIALS AND METHODS: We evaluated data of all refugees who underwent CXR screening in a single-centre of one German metropolitan area in 2015. We determined the prevalence of TB, NNS, and accuracy of CXR to detect active pulmonary TB. Reference method for active TB was the database of all definite TB cases registered at the Department of Public Health. RESULTS: A total of 17,487 immigrants underwent single-centre CXR screening in 2015; prevalence of definite pulmonary TB was 0.103%. The NNS for detecting one case of active pulmonary TB was 1749. CXR had a sensitivity of 55.6% [95% confidence interval (CI) 30.8-78.5%) and a specificity 98.3% (CI 98.1-98.5%) to reveal one case of active TB. CONCLUSION: Our single-centre study indicates that chest X-ray screening for TB during the 2015 European refugee crisis was of low yield due the low prevalence of TB and high number needed to screen, thus implicating the need for improved screening algorithms adapted to the overwhelming number of refugees. KEY POINTS: • Prevalence of pulmonary tuberculosis (TB) among refugees in 2015 was low (0.103%). • The number needed to screen to detect one case of active pulmonary TB was 1749. • Tuberculosis X-ray screening resulted in a low sensitivity and high specificity. • Tuberculosis X-ray screening during the European refugee crisis is of low yield. • Improved screening algorithms are needed due to the overwhelming the number of refugees.

Risk of tuberculosis transmission by children in Hamburg, Germany.

BACKGROUND: Data from a prospective molecular-epidemiologic study (1997-2021) in Hamburg, Germany, were evaluated to assess the transmission risk of Mycobacterium tuberculosis complex (Mtbc) by children <15 years in a low-incidence setting. METHODS: Isolates of Mtbc were genotyped whole genome sequencing, applying a core genome multilocus sequence typing scheme. Close contacts of culture-confirmed children were examined for latent Mtbc infections (LTBI) with particular focus on IGRA testing. RESULTS: Out of 3154 culture-confirmed tuberculosis (TB) cases, 79 (2.5%) were children <15 years. Of those, 52 (58%) had pulmonary TB. Genotyping revealed that 35 of the 52 children (67%) were epidemiologically confirmed secondary cluster members; all of their source cases were adults. Six immigrant children presented without a presumed source case; their TB diagnoses came on average 48 weeks (interquartile range [IQR] 71) after their arrival in Germany. Three German-born children were determined to have been infected by adult relatives while visiting their parents' home country. Of the 317 children's close contacts tested with QuantiFERON-TB Gold-In Tube for LTBI, only 21 (6.6%) were positive. Absent a history of prior exposure or immigration from a high-incidence country, none of the contacts of younger (<10 years) TB-afflicted children was latently infected, whereas 2 older children infected 12 of their contacts, children and adults. During a mean observational period of 551 weeks (IQR 735) on average, no secondary TB cases appeared. CONCLUSIONS: Children with pulmonary TB disease, especially those aged below 10 years, rarely transmit Mtbc to their close contacts in a low-incidence setting.

Negative and positive predictive value of a whole-blood interferon-γ release assay for developing active tuberculosis: an update.

RATIONALE: only limited data are available on the predictive value of interferon-γ release assays for progression from latent tuberculosis infection to active tuberculosis (TB). OBJECTIVES: to build on our initial study comparing the QuantiFERON-TB Gold in-tube assay (QFT) with the tuberculin skin test (TST) in close contacts of patients with TB and evaluating progression to active TB for up to 4 years. METHODS: a cohort of close contacts of smear-positive index cases established between May 2005 and April 2008 was tested with QFT and TST. Through April 2010, progressors to active TB were consecutively recorded. MEASUREMENTS AND MAIN RESULTS: of the 1,414 contacts (141 children), 1,033 were still resident in Hamburg at the end of the study period, and results of both tests were available for 954. QFT, but not TST, results were associated with exposure time (P < 0.0001). For QFT, 198 of 954 (20.8%) were positive; 63.3% (604) were TST positive at greater than 5 mm and 25.4% at greater than 10 mm. Nine hundred and three contacts refused chemoprevention and 19 developed active TB. All 19 (100%) had been QFT positive with a progression rate of 12.9% (19 of 147) over the observation period. Corresponding values for the TST were significantly lower: 89.5% (17 of 19) and 3.1% (17 of 555) at greater than 5 mm, and 52.6% (10 of 19) and 4.8% (10 of 207) at greater than 10 mm, respectively. The progression rate of 28.6% (6 of 21) for QFT-positive children was significantly higher than 10.3% (13 of 126) for adults (P = 0.03). CONCLUSIONS: results suggest that QFT is more reliable than the TST for identifying those who will soon progress to active TB, especially in children.

Predictive value of a whole blood IFN-gamma assay for the development of active tuberculosis disease after recent infection with Mycobacterium tuberculosis.

RATIONALE: Numerous studies have been published on the new Mycobacterium tuberculosis (MTB)-specific IFN-gamma release assays. However, their prognostic value for progression from latent tuberculosis infection (LTBI) to active TB has yet to be established. OBJECTIVES: To compare the QuantiFERON-TB Gold In-Tube assay (QFT) with the tuberculin skin test (TST) in recently exposed close contacts of active TB cases with respect to their development of TB disease within 2 years. METHODS: Close contacts (n = 601) of MTB-positive source cases underwent both TST and QFT testing and were subsequently observed for 103 (+/-13.5) weeks. Risk factors for MTB infection were evaluated by multivariate analysis. MEASUREMENTS AND MAIN RESULTS: For the TST, 40.4% (243/601) of contacts were positive at a 5-mm cutoff, whereas only 66 (11%) were QFT positive. QFT positivity, but not TST, was associated with exposure time (P < 0.0001). Six contacts progressed to TB disease within the 2-year follow-up. All were QFT positive and had declined preventive treatment, equating to a progression rate of 14.6% (6/41) among those who were QFT positive. The progression rate for untreated TST-positive subjects was significantly lower (P < 0.003), at 2.3% (5 of 219), and one subject who progressed was TST negative. CONCLUSIONS: Results suggest that QFT is a more accurate indicator of the presence of LTBI than the TST and provides at least the same sensitivity for detecting those who will progress to active TB. The high rate of progression to active TB of those who are QFT positive (14.6%), which is far greater than the 2.3% found for those who are TST positive, has health and economic implications for enhanced TB control, particularly if this higher progression rate is seen in studies of other at-risk populations.

Comparative performance of tuberculin skin test, QuantiFERON-TB-Gold In Tube assay, and T-Spot.TB test in contact investigations for tuberculosis.

RATIONALE: Mycobacterium tuberculosis (MTB)-specific interferon-gamma release assays (IGRAs) are an alternative or adjunct to the tuberculin skin test (TST) in identifying recent contacts with latent tuberculosis infection (LTBI), but there are scarce data directly comparing performance of the tests. OBJECTIVE: To evaluate the agreement between both IGRAs and to determine which contacts were most likely to represent LTBI, the QuantiFERON-TB-Gold In Tube assay (QFT) and the T-Spot.TB test (T-Spot) were compared in TST-positive persons recently exposed to pulmonary tuberculosis cases. METHODS: Prospectively enrolled close contacts (n = 812) of 123 culture-confirmed tuberculosis source cases underwent IGRA testing using standardized collected data. Factors independently influencing the risk of MTB infection and their interactions with each other were evaluated by multivariate analysis. RESULTS: Five variables were found to significantly predict a positive IGRA test result (age, source case acid-fast bacilli positive and/or coughing, cumulative exposure time, foreign origin). There was excellent agreement between the two IGRAs (93.9%, kappa = 0.85), with QFT finding 30.2% of contacts positive and T-Spot finding 28.7%. Assuming positivity to both IGRAs as true infection, sensitivity of the TST at > 10 mm was 72% and at > 15 mm was 39.7%. The use of either IGRA as a replacement for the TST would decrease the number of LTBI suspects to be investigated by approximately 70%. CONCLUSIONS: IGRAs are a more accurate indicator of the presence of LTBI than the TST. Both QFT and T-Spot appear to be valuable public health tools, showing excellent agreement with each other.

Epidemiology of tuberculosis in Hamburg, Germany: long-term population-based analysis applying classical and molecular epidemiological techniques.

To determine a detailed picture of tuberculosis (TB) epidemiology in Hamburg, Germany, 423 Mycobacterium tuberculosis complex isolates from 77.0% of all patients with culture-confirmed TB diagnosed from 1997 to 1999 in Hamburg were analyzed by IS6110 DNA fingerprinting. IS6110 restriction fragment length polymorphism (RFLP) clusters were assumed to have arisen from recent transmission. Results of contact tracing and additional patient interviews were used for further epidemiological analyses. Of the 423 cases, 398 were included in the cluster analysis, of which 135 (33.9%) were classified into 35 clusters ranging from 2 to 23 patients. Epidemiological links verifying recent transmission could be confirmed for 87 of the 135 clustered patients. Risk factors for recent transmission were calculated by a two-step procedure: first, based on patients with clustered isolates; and second, based on patients with clustered isolates and transmission links. In both analyses, alcohol abuse appeared to be the strongest predictor for recent transmission, followed by a history of previous contact tracing and unemployment. Homelessness, foreign ethnicity, sex, drug addiction, and human immunodeficiency virus positivity were not independent risk factors for clustering in multivariate analyses. Classical contact tracing performed prior to IS6110 RFLP analysis identified only 24 of the 135 clustered patient. In conclusion, recent transmission seems to be frequent in Hamburg and was found to be strongly associated with alcohol abuse. Conventional contact tracing appears to be insufficient for the detection of recent transmission chains. The data presented also indicate that improved TB control strategies, including the use of RFLP for the detection of transmission chains, are needed for TB control in the setting of countries with a low incidence of TB.