Risk for latent and active tuberculosis in Germany

Infection (2017) 45:283–290 DOI 10.1007/s15010-016-0963-2 ORIGINAL PAPER Risk for latent and active tuberculosis in Germany Christian Herzmann1,2 · Giovanni Sotgiu3 · Oswald Bellinger4 · Roland Diel5,6 · Silke Gerdes7 · Udo Goetsch8 · Helga Heykes‑Uden7 · Tom Schaberg9 · Christoph Lange1,10,11,12 · For the TB or not TB consortium Received: 22 June 2016 / Accepted: 7 November 2016 / Published online: 19 November 2016 © The Author(s) 2016. This article is published with open access at Springerlink.com Abstract Purpose Few individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany. Methods Healthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-γ release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs. Results From 2008–2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p = 0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio Electronic supplementary material The online version of this article (doi:10.1007/s15010-016-0963-2) contains supplementary material, which is available to authorized users. * Christoph Lange clange@fz‑borstel.de 1 Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up. Conclusions Positive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis. Keywords LTBI · Incidence · Diabetes mellitus · IGRA · Health care workers · Household contacts Abbreviation AFB Acid fast bacilli BCG  M. bovis Bacillus Calmette-Guérin BMBF Bundesministerium für Bildung und Forschung BMI Body mass index EEA European Economic Area EU European Union HCW Healthcare worker 6 LungenClinic Grosshansdorf, Airway Research Center North, Großhansdorf, Germany 7 Municipal Health Authority Hannover, Hanover, Germany 8 Municipal Health Authority Frankfurt, Frankfurt, Germany Center of Pneumology, Agaplesion Deaconess Hospital Rotenburg, Rotenburg, Germany 2 Center for Clinical Studies, Research Center Borstel, Borstel, Germany 9 3 Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari, Sassari, Italy 10 German Center for Infection Research (DZIF), Clinical Tuberculosis Unit, Borstel, Germany 4 DAHW German Leprosy and Tuberculosis Relief Association, Würzburg, Germany 11 International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany 5 Institute of Epidemiology, University Medical Hospital Schleswig–Holstein, Campus Kiel, Germany 12 Department of Medicine, Karolinska Institute, Stockholm, Sweden 13 284 HHC Household contact IGRA Interferon-gamma release assay IPT Isoniazid preventive therapy IQR Interquartile range IVDU Intravenous drug use LTBI Latent tuberculosis infection OR Odds ratio PTB Pulmonary tuberculosis SD Standard deviation TB Tuberculosis TST Tuberculin skin test UK United Kingdom WHO World Health Organisation Introduction Tuberculosis incidence has declined in Western Europe [1]. In 2014, the notified incidence in the European Union and European Economic Area (EU/EEA) was 14.2 cases per 100,000 population [1], in some countries only 5 cases per 100,000 [1]. Aiming at further reduction, the WHO advocated a target tuberculosis incidence of <1 cases per 1,000,000 in low incidence countries, i.e. the consensual tuberculosis elimination threshold [2]. Tuberculosis prevention relies on early case finding and on the identification of persons latently infected with Mycobacterium tuberculosis (LTBI) [3]. LTBI is defined by a positive response to the tuberculin skin test (TST) or an interferon-release assay (IGRA) without tuberculosis associated symptoms or signs. It is unclear whether the test results reflect viable bacilli in the human host. False positive results can be found, especially in populations of low prevalence. Approximately 9% of healthy persons in Western Europe have a positive TST or IGRA test result [4]. If the whole population was screened with subsequent preventive chemotherapy for all who tested positive, the number needed to treat to prevent one case would not be cost effective. LTBI screening and treatment is, therefore, only performed in populations with an a priori higher risk for the disease [5], e.g. house hold contacts. Contact tracing identifies 16–44% of close household contacts of contagious patients with LTBI [6, 7]. Nevertheless, only a small fraction develops active tuberculosis despite the absence of preventive chemotherapy [8]. Predictive markers of progression to active tuberculosis are lacking. The number of latently infected contacts requiring preventive chemotherapy to prevent a single case of tuberculosis is >1:30 in Western Europe [8]. Adherence to recommendations for preventive chemotherapy is poor in Germany [9]. 13 C. Herzmann et al. To improve prevention and to target individuals for preventive chemotherapy more precisely, additional knowledge of risk factors for of LTBI and tuberculosis is needed. Therefore, our consortium collected epidemiological and clinical data from pulmonary tuberculosis (PTB) patients and close contacts. Methods This observational, multicentre, prospective study was conducted by the German research consortium on “pulmonary tuberculosis—host and pathogen determinants of resistance and disease progression—(TB or not TB)”. It was approved by the ethics committee of the University of Lübeck (reference 07–125) and adopted by the ethics committees of all 18 participating centres. Household contacts (HHCs) were recruited at three municipal healthcare centres (Frankfurt, Hamburg, Hannover). They were suitable for enrolment if they were asymptomatic with no signs of tuberculosis on chest X-ray, were exposed >8 h to patients with acid-fast bacilli (AFB) in the sputum or >40 h in AFB negative, culture-confirmed PTB. Their last unprotected exposure was ≥8 weeks prior to enrolment. Healthcare workers (HCWs) with ongoing professional contact to patients with AFB sputum smear-positive tuberculosis, a cumulative exposure of ≥2 years, and no signs or symptoms of tuberculosis were recruited a (...truncated)