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Contacts:
Stefan Niemann (sniemann@fz-borstel.de)
Inna Friesen (ifriesen@fz-borstel.de)
Doris Hillemann (dhillemann@fz-borstel.de)
Supranational TB Reference Laboratory in Borstel, Germany
Address:
National Reference Laboratory for Mycobacteria
Research Center Borstel
22946 Borstel, Parkallee 18
Borstel, Germany
Description
The German National Reference Laboratory (NRL) for mycobacteria provides routine and specialized diagnostic services nationally and internationally. The laboratory is located in Northern Germany, 40km from Hamburg. The national reference status is awarded on a 4-yearly basis by the German Department of Health. The NRL also acts as a Supranational Laboratory (SRL) for several countries in Eastern Europe, Central Asia and Africa.
Structure and organization
SRL Borstel encompasses a diagnostic laboratory focused on mycobacteria, along with diagnostic and experimental research groups. The laboratory is situated within the Research Center Borstel, Leibniz Lung Center. Leading the scientific endeavors of the laboratory is Prof. Dr. Stefan Niemann, a biologist with over 25 years of experience, who also serves as the research group leader of Molecular and Experimental Mycobacteriology. Heading the medical aspect are Dr. Inna Friesen and Dr. Martin Kuhns, both MDs specialized in Medical Microbiology, Virology, and Infectious Disease Epidemiology.
Among the other team members are Dr. Susanne Homolka (senior researcher), Dr. Doris Hillemann (senior researcher), and Dr. Sönke Andres (senior researcher). The team also includes approximately 50 scientists, laboratory technologists, students, and administrators.
Services provided by the SRL
In 2021, diagnostic tests were performed on approximately 18,000 samples, including 3,500 susceptibility tests, 3,000 species identifications and 4,500 molecular tests on primary samples. In addition, the SRL sequences a large number of Mycobacterium tuberculosis genomes for genome-based resistance diagnostics and to provide high-resolution genomic data for both nationwide prospective tuberculosis surveillance and several international surveillance and research networks. In addition, SRL Borstel provides twice yearly external quality control samples for approximately 250 national and international mycobacteriology laboratories.
Teaching and capacity building is conducted through lectures and trainings both nationally and internationally. The SRL runs an implementation team to facilitate adoption of state-of-the-art diagnostics including advanced molecular techniques such as genome sequencing in high-incidence settings. A consultation service including a weekly interdisciplinary case conference is available for laboratories, health authorities and physicians managing patients with difficult mycobacterial infections. The SRL offers the Monteillet-Musiolik Tuberculosis Fellowship to foster translational tuberculosis research and capacity building. Fellowships are open to research-driven physicians and scientists from countries with intermediate to high TB incidence (highly suitable candidates from low incidence countries will also be considered) and provide support for training and research on TB and other mycobacterial diseases at Research Center Borstel.
The following techniques are available at the laboratory: fluorescence microscopy, primary culture on solid and liquid media, various commercial and in-house molecular techniques, drug susceptibility testing of first- and second-line drugs by the proportion method on liquid or solid media and by broth microdilution (including the EUCAST reference MIC method), MIRU typing, whole genome sequencing, and deep amplicon sequencing.
Current links and partnerships outside of SRLN
Nationally, the laboratory closely interacts with the German National Public Health Institute (Robert Koch-Institute) and the both state and federal ministries of health. The laboratory is also a founding member of the European Reference Laboratory Network for TB (ERLTB-Net). Both Prof. Maurer and Prof. Niemann are core group members of the European Laboratory Initiative on TB, HIV and viral hepatitis at WHO Europe. Prof. Maurer is a member of the WHO Advisory Group on TB Diagnostics and Laboratory Strengthening and currently acts as the Scientific Secretary of ESGMYC, the mycobacteria study group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Additional partners include the NRL in Freetown/Sierra Leone, Accra/Ghana, Chisinau/Republic of Moldova, Yerevan/Armenia, Baku/Azerbaijan, as well as various members of the WHO SRL network. Further co-operations were established with The Foundation for Innovative New Diagnostics (FIND), Médecins Sans Frontières, the International Committee of Red Cross (ICRC), and various national and international research groups. A large collaborative framework has been established in the SeqMDRTB-Net project to support countries with a high TB incidence such as Moldova in Eastern Europe, Kyrgyzstan in Central Asia and three countries in Southern Africa, Eswatini, Namibia and Mozambique in the application of whole genome sequencing techniques diagnostic and surveillance tools.
Additional information:
Research activities
Research topics include the characterization of molecular correlates of antibiotic resistance in M. tuberculosis, tuberculosis transmission in low and high incidence countries, NGS of mycobacteria for genotyping, and the identification and evaluation of novel antimycobacterial agents. Furthermore, the SRL is the national Center of Excellence for nontuberculous mycobacteria.
Publications
Maurer FP, Shubladze N, Kalmambetova G, Felker I, Kuchukhidze G, Drobniewski F, Yedilbayev A, Ehsani S; European Laboratory Initiative on TB, HIV and Viral Hepatitis. Impact of the COVID-19 pandemic on tuberculosis national reference laboratory services in the WHO European Region, March to November 2020. Euro Surveill. 2021 Jun;26(24):2100426. doi: 10.2807/1560-7917.ES.2021.26.24.2100426.
Homolka S, Paulowski L, Andres S, Hillemann D, Jou R, Günther G, Claassens M, Kuhns M, Niemann S, Maurer FP. Two pandemics, one challenge-leveraging molecular test capacity of tuberculosis laboratories for rapid COVID-19 case-finding. Emerg Infect Dis. 2020 Nov;26(11):2549-2554. doi: 10.3201/eid2611.202602. Epub 2020 Sep 21. PMID: 32956612; PMCID: PMC7588527.
Chesov E, Chesov D, Maurer FP, Andres S, Utpatel C, Barilar I, Donica A, Reimann M, Niemann S, Lange C, Crudu V, Heyckendorf J, Merker M. Emergence of bedaquiline-resistance in a high-burden country of tuberculosis. Eur Respir J. 2021 Sep 9:2100621. doi: 10.1183/13993003.00621-2021. Epub ahead of print. PMID: 34503982.
Sonnenkalb L, Strohe G, Dreyer V, Andres S, Hillemann D, Maurer FP, Niemann S, Merker M. Microevolution of Mycobacterium tuberculosis subpopulations and heteroresistance in a patient receiving 27 years of tuberculosis treatment in Germany. Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0252020. doi: 10.1128/AAC.02520-20. Epub 2021 Jun 17. PMID: 33903103; PMCID: PMC8218629.
Grobbel HP, Merker M, et al. Maurer FP, Lange C, Niemann S. Design of multidrug-resistant tuberculosis treatment regimens based on DNA sequencing. Clin Infect Dis. 2021 26:ciab359.
Nadarajan D, Hillemann D, Kamara R, Foray L, Conteh OS, Merker M, Niemann S, Lau J, Njoya M, Kranzer K, Somoskovi A, Maurer FP. Evaluation of the Roche cobas MTB and MTB-RIF/INH Assays in Samples from Germany and Sierra Leone. J Clin Microbiol. 2021 Apr 20;59(5):e02983-20. doi: 10.1128/JCM.02983-20. PMID: 33658264; PMCID: PMC8091830.
Heyckendorf J, Marwitz S, Reimann M, Avsar K, DiNardo AR, Günther G, Hoelscher M, Ibraim E, Kalsdorf B, Kaufmann SHE, Kontsevaya I, van Leth F, Mandalakas AM, Maurer FP, Müller M, Nitschkowski D, Olaru ID, Popa C, Rachow A, Rolling T, Rybniker J, Salzer HJF, Sanchez-Carballo P, Schuhmann M, Schaub D, Spinu V, Suárez I, Terhalle E, Unnewehr M, Weiner J 3rd, Goldmann T, Lange C. Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model. Eur Respir J. 2021 Sep 2;58(3):2003492. doi: 10.1183/13993003.03492-2020. PMID: 33574078.
Sanchini A, Jandrasits C, Tembrockhaus J, Kohl TA, Utpatel C, Maurer FP, Niemann S, Haas W, Renard BY, Kröger S. Improving tuberculosis surveillance by detecting international transmission using publicly available whole genome sequencing data. Euro Surveill. 2021 Jan;26(2):1900677. doi: 10.2807/1560-7917.ES.2021.26.2.1900677. PMID: 33446303; PMCID: PMC7809720.
Andres S, Merker M, Heyckendorf J, Kalsdorf B, Rumetshofer R, Indra A, Hofmann-Thiel S, Hoffmann H, Lange C, Niemann S, Maurer FP. Bedaquiline-resistant tuberculosis: dark clouds on the horizon. Am J Respir Crit Care Med. 2020 Jun 15;201(12):1564-1568. doi: 10.1164/rccm.201909-1819LE. PMID: 32053752.
Beckert P, Sanchez-Padilla E, Merker M, et al., Maurer FP, Bonnet M, Niemann S. MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era. Genome Med 2020 25;12(1):104.
Schön T, Matuschek E, Mohamed S, Utukuri M, Heysell S, Alffenaar JW, Shin S, Martinez E, Sintchenko V, Maurer FP, Keller PM, Kahlmeter G, Köser CU. Standards for MIC testing that apply to the majority of bacterial pathogens should also be enforced for Mycobacterium tuberculosis complex. Clin Microbiol Infect. 2019 Apr;25(4):403-405. doi: 10.1016/j.cmi.2019.01.019. Epub 2019 Feb 14. PMID: 30771527; PMCID: PMC7903878.
CRyPTIC Consortium and the 100,000 Genomes Project (Niemann S). Prediction of susceptibility to first-line tuberculosis drugs by DNA sequencing. N Engl J Med. 2018 11;379(15):1403-1415.
van Ingen J, Kohl TA, Kranzer K, et al., Nübel U, Bloemberg GV, Böttger EC*, Niemann S*, Wagner D*, Sax H*. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017 17(10):1033-1041. *equal contribution
Sanchez-Padilla E, Merker M, Beckert P, et al., Kahn P, Bonnet M, Niemann S. Detection of drug-resistant tuberculosis by Xpert MTB/RIF in Swaziland. N Engl J Med. 2015 372(12):1181-2.
Merker M, Blin C, et al. Supply P, Niemann S*, Wirth T*. Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat Genet. 2015 47(3):242-9. *equal contribution.
Walker TM, Kohl TA, Omar SV, Hedge J, et al., Ismail N, Niemann S*, Peto TE*, Modernizing Medical Microbiology (MMM) Informatics Group. Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study. Lancet Infect Dis. 2015 15(10):1193-202. *equal contribution.
Roetzer A, Diel R, Kohl TA, et al., Niemann S. Whole genome sequencing versus traditional genotyping for investigation of a Mycobacterium tuberculosis outbreak: a longitudinal molecular epidemiological study. PLoS Med. 2013 10(2):e1001387.
Comas I, Borrell S, Roetzer A, Rose G, Malla B, Kato-Maeda M, Galagan J, Niemann S, Gagneux S. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat Genet. 2011 44(1):106-10.
Trainings
Monteillet-Musiolik Tuberculosis Fellowship:
Annual clinical course on management of tuberculosis
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