Suchergebnisse

Abstract Background Healthcare workers are still recognised as a high-risk group for latent TB infection (LTBI). Therefore, the screening of people employed in the healthcare sector for active and LTBI is fundamental to infection control programmes in German hospitals. It was the aim of the study to determine the prevalence and putative risk factors of LTBI. Methods We tested 2028 employees in the healthcare sector with the QuantiFERON-Gold In-tube (QFT-IT) test between December 2005 and May 2009, either in the course of contact tracing or in serial testing of TB high-risk groups following German OSH legislation. Results A positive IGRA was found in 9.9% of the healthcare workers (HCWs). Nurses and physicians showed similar prevalence rates (9.7% to 9.6%). Analysed by occupational group, the highest prevalence was found in administration staff and ancillary nursing staff (17.4% and 16.7%). None of the individuals in the trainee group showed a positive IGRA result. In the different workplaces the observed prevalence was 14.7% in administration, 12.0% in geriatric care, 14.2% in technicians (radiology, laboratory and pathology), 6.5% in admission ward staff and 8.3% in the staff of pulmonary/infectious disease wards. Putative risk factors for LTBI were age (>55 years: OR14.7, 95% CI 5.1-42.1), being foreign-born (OR 1.99, 95% CI 1.4-2.8), TB in the individual's own history (OR 4.96, 95% CI 1.99-12.3) and previous positive TST results (OR 3.5, 95% CI 2.4-4.98). We observed no statistically significant association with gender, BCG vaccination, workplace or profession. Conclusion The prevalence of LTBI in low-incidence countries depends on age. We found no positive IGRA results among trainees in the healthcare sector. Incidence studies are needed to assess the infection risk. Pre-employment screening might be helpful in this endeavour.

ZusammenfassungZiel der Umgebungsuntersuchung bei Tuberkulose ist neben der aktiven Fallfindung
das Aufdecken von Infektionsketten sowie die Verhütung der
Weiterverbreitung der Erkrankung. Dabei ist eine sorgfältige Auswahl der
Kontaktpersonen notwendig, die sich nach Art und Dauer des Kontaktes richtet, um
möglichst frisch Infizierte zu identifizieren und so den Nutzen einer
anschließenden präventiven Therapie zu erhöhen und
unnötige Testungen von Personen ohne Ansteckungsrisiko zu vermeiden.
Seit der letzten Überarbeitung der Empfehlungen zur
Umgebungsuntersuchung hat sich die Datenlage zum Einsatz von Interferon-y
release-Assays (IGRAs) bei Kindern weiterhin verbessert. Diese werden bevorzugt
in der Umgebungsuntersuchung von erwachsenen Kontaktpersonen eingesetzt.
Für Kinder unter 15 Jahren können sowohl IGRAs wie auch
weiterhin der Tuberkulin-Hauttest gleichwertig verwendet werden. Als
präventive Therapie bei nachgewiesener Infektion werden Rifampicin
für 4 Monate, Rifampicin und Isoniazid für 3 Monate oder aber
Isoniazid für 9 Monate empfohlen.Ausführlich wird auf die Durchführung der Umgebungsuntersuchung
in verschiedenen Altersgruppen sowie rechtliche Rahmenbedingungen und
sozialmedizinische Aspekte und Herausforderungen eingegangen. Zusätzlich
werden Sonderfälle, wie die Umgebungsuntersuchung in Kitas, Schulen oder
in anderen Gemeinschaftseinrichtungen, separat dargestellt.

In this study, using the Hain GenoType MTBDRsl assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis result in systematic false-resistance results to fluoroquinolones by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings. ; Funding Agencies|Swedish Heart and Lung Foundation; Marianne and Marcus Wallenberg Foundation; Wellcome Trust [201344/Z/16/Z]; NIHR Oxford Biomedical Research Centre; NIHR Oxford Health Protection Research Unit on Healthcare Associated Infection and Antimicrobial Resistance [HPRU-2012-10041]; Health Innovation Challenge Fund [T5-358, HICF-T5-342, WT098600]; German Center for Infection Research (DZIF); European Union TB-PAN-NET [FP7-223681]; PathoNgenTrace [278864]; UK Department of Health; Pacific Biosciences, Inc.; Illumina, Inc.; Colciencias; Hain Lifescience

A screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to D-cycloserine. ; Funding Agencies|University of Otago; Health Research Council; Maurice Wilkins Centre; European Union [FP7-278864-2]; German Center for Infection Research (DZIF); Fundacao para a Ciencia e a Tecnologia, Portugal [UID/Multi/04413/2013, SFRH/BPD/100688/2014, SFRH/BPD/95406/2013]; Wellcome Trust [201344/Z/16/Z]; Medical Research Council UK [MR/K000551/1, MR/M01360X/1, MR/N010469/1]; Indian Council of Medical Research, New Delhi; L2 Diagnostics LLC, New Haven; Pacific Biosciences, Inc.; Illumina, Inc.; European Society of Mycobacteriology; Hain Lifescience; UK Department of Health [HICF-T5-342, WT098600]; Wellcome Trust

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions. ; SCOPUS: re.j ; info:eu-repo/semantics/published

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

13 Pages, 1 Figure, 4 tables. The authors' affiliations are listed in the Supplementary Appendix, available at NEJM.org. Supplementary Material, available at http://dx.doi.org/10.1056/NEJMoa1800474 ; BACKGROUND: The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHODS: We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance. RESULTS: A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted. CONCLUSIONS: Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.). ; Supported by grants from the Bill and Melinda Gates Foundation (OPP1133541, to CRyPTIC, plus separate support to Dr. Rodwell), a Wellcome Trust/Newton Fund–MRC Collaborative Award (200205/Z/15/Z, to CRyPTIC), the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) and NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford in partnership with Public Health England, the NIHR Biomedical Research Centre at Barts, the NIHR Biomedical Research Centre at Imperial, the NIHR and NHS England (to the 100,000 Genomes Project, which is managed by Genomics England, a wholly owned company of the U.K. Department of Health), the Wellcome Trust, the Medical Research Council, Public Health England, a grant from the National Science and Technology Key Program of China (2014ZX10003002), a grant from the National Basic Research program of China (2014CB744403), a grant from the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29020000), a grant from the European Commission Seventh Framework Program (FP7/2007-2013, to Borstel under grant agreement 278864 in the framework of the Patho-NGen-Trace project), the German Center for Infection Research (to Borstel), Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG), the Belgian Ministry of Social Affairs (to the Belgian Reference Center for Tuberculosis and Mycobacteria from Bacterial Diseases Service through a fund within the Health Insurance System), the French governmental program "Investing for the Future" (to Genoscreen), a grant from the European Commission Seventh Framework Program (FP7/2007-2013, to Genoscreen under grant agreement 278864 in the framework of the Patho-NGen-Trace project), grants from the Drug Resistant Tuberculosis Fund (R015833003, to Dr. Chaiprasert), the Faculty of Medicine, Siriraj Hospital, Mahidol University (to Dr. Chaiprasert), a grant from the Ministry of Economy and Competitiveness (MINECO), Spain (SAF2016-77346-R, to Dr. Comas), a grant from the European Research Council (638553-TB-ACCELERATE, to Dr. Comas), a grant from the BC Centre for Disease Control Foundation for Population and Public Health (to Dr. Gardy), a grant from the British Colombia Lung Association (to Dr. Gardy), grants from the Wellcome Trust and the Royal Society (101237/Z/13/Z and 102541/A/13/Z, to Drs. Wilson and Iqbal [Sir Henry Dale Fellows]), a grant from the National University of Singapore Yong Loo Lin School of Medicine Aspiration Fund (NUHSRO/2014/069/AF-New Idea/04, to Drs. Ong and Teo), a European Commission Seventh Framework Program European Genetic Network (EUROGEN) grant (201483, to Dr. Drobniewski), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health (to Dr. Rodwell). Dr. T. Walker is an NIHR Academic Clinical Lecturer, and Drs. Crook, Peto, and Caulfield are NIHR Senior Investigators. No potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank Stéphanie Duthoy, Carina Hahn, Alamdar Hussain, Yannick Laurent, Mathilde Mairey, Vanessa Mohr, and Mahmood Qadir for technical assistance and George F. Gao, Director of the Chinese Center for Disease Control and Prevention, for directing the Chinese grant and sequencing program ; Peer reviewed